FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Suwara, MI
Borthwick, LA
Mahida, R
Green, NJ
Mayer-Barber, K
Gardner, A
Mann, J
Wynn, TA
Corris, PA
Farrow, SN
Mann, DA
Fisher, AJ
AF Suwara, M. I.
Borthwick, L. A.
Mahida, R.
Green, N. J.
Mayer-Barber, K.
Gardner, A.
Mann, J.
Wynn, T. A.
Corris, P. A.
Farrow, S. N.
Mann, D. A.
Fisher, A. J.
TI INTERLEUKIN-1 ALPHA (IL-1 alpha) RELEASED FROM INJURED LUNG EPITHELIUM
IS A CRITICAL ALARMIN DRIVING ACTIVATION OF A POTENT INFLAMMATORY
PHENOTYPE IN LUNG FIBROBLASTS
SO THORAX
LA English
DT Meeting Abstract
CT Winter Meeting of the British-Thoracic-Society 2012
CY DEC 05-07, 2012
CL London, ENGLAND
SP British Thorac Soc
C1 [Suwara, M. I.; Borthwick, L. A.; Mahida, R.; Green, N. J.; Gardner, A.; Mann, J.; Corris, P. A.; Mann, D. A.; Fisher, A. J.] Newcastle Univ, Tissue Fibrosis & Repair Grp, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Mayer-Barber, K.; Wynn, T. A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Farrow, S. N.] GlaxoSmithKline, Resp Therapy Area, Stevenage, Herts, England.
RI Gardner, Aaron/H-1511-2012
OI Gardner, Aaron/0000-0001-8729-9823
NR 0
TC 0
Z9 0
U1 0
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0040-6376
J9 THORAX
JI Thorax
PD DEC
PY 2012
VL 67
SU 2
BP A60
EP A61
DI 10.1136/thoraxjnl-2012-202678.131
PG 4
WC Respiratory System
SC Respiratory System
GA 056PK
UT WOS:000312503000133
ER
PT J
AU Hesselbach, RA
Petering, DH
Berg, CA
Tomasiewicz, H
Weber, D
AF Hesselbach, Renee A.
Petering, David H.
Berg, Craig A.
Tomasiewicz, Henry
Weber, Daniel
TI A Guide to Writing a Scientific Paper: A Focus on High School Through
Graduate Level Student Research
SO ZEBRAFISH
LA English
DT Article
AB This article presents a detailed guide for high school through graduate level instructors that leads students to write effective and well-organized scientific papers. Interesting research emerges from the ability to ask questions, define problems, design experiments, analyze and interpret data, and make critical connections. This process is incomplete, unless new results are communicated to others because science fundamentally requires peer review and criticism to validate or discard proposed new knowledge. Thus, a concise and clearly written research paper is a critical step in the scientific process and is important for young researchers as they are mastering how to express scientific concepts and understanding. Moreover, learning to write a research paper provides a tool to improve science literacy as indicated in the National Research Council's National Science Education Standards (1996), and A Framework for K-12 Science Education (2011), the underlying foundation for the Next Generation Science Standards currently being developed. Background information explains the importance of peer review and communicating results, along with details of each critical component, the Abstract, Introduction, Methods, Results, and Discussion. Specific steps essential to helping students write clear and coherent research papers that follow a logical format, use effective communication, and develop scientific inquiry are described.
C1 [Hesselbach, Renee A.; Tomasiewicz, Henry; Weber, Daniel] Univ Wisconsin, NIEHS Childrens Environm Hlth Sci Core Ctr, Milwaukee, WI 53201 USA.
[Petering, David H.] Univ Wisconsin, Dept Chem & Biochem, Milwaukee, WI 53201 USA.
RP Hesselbach, RA (reprint author), Univ Wisconsin, NIEHS Childrens Environm Hlth Sci Core Ctr, POB 413, Milwaukee, WI 53201 USA.
EM hesselba@uwm.edu
FU Science Education Partnership Award (SEPA) grant [R25RR026299]; National
Institute of Environmental Health Sciences of the National Institutes of
Health; National Institute of Environmental Health Sciences
[P30ES004184]
FX This article was supported by a Science Education Partnership Award
(SEPA) grant (Award Number R25RR026299) from the National Institute of
Environmental Health Sciences of the National Institutes of Health. The
SEPA program at the University of Wisconsin-Milwaukee is part of the
Children's Environmental Health Sciences Core Center, Community Outreach
and Education Core, funded by the National Institute of Environmental
Health Sciences (Award Number P30ES004184). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health or the National
Institute of Environmental Health Sciences.
NR 8
TC 2
Z9 2
U1 5
U2 61
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1545-8547
J9 ZEBRAFISH
JI Zebrafish
PD DEC
PY 2012
VL 9
IS 4
BP 246
EP 249
DI 10.1089/zeb.2012.0743
PG 4
WC Developmental Biology; Zoology
SC Developmental Biology; Zoology
GA 057RQ
UT WOS:000312582100013
PM 23094692
ER
PT J
AU Weng, TJ
Yi, LX
Huang, JL
Luo, FT
Wen, X
Du, XL
Chen, Q
Deng, CX
Chen, D
Chen, L
AF Weng, Tujun
Yi, Lingxian
Huang, Junlan
Luo, Fengtao
Wen, Xuan
Du, Xiaolan
Chen, Qian
Deng, Chuxia
Chen, Di
Chen, Lin
TI Genetic Inhibition of Fibroblast Growth Factor Receptor 1 in Knee
Cartilage Attenuates the Degeneration of Articular Cartilage in Adult
Mice
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID MATRIX METALLOPROTEINASE-13; MOUSE MODEL; OSTEOARTHRITIS; CHONDROCYTES;
AGGRECANASE; EXPRESSION; ARTHRITIS; ADAMTS5; CHONDROGENESIS; DEGRADATION
AB Objective. Fibroblast growth factor (FGF) family members are involved in the regulation of articular cartilage homeostasis. The aim of this study was to investigate the function of FGF receptor 1 (FGFR-1) in the development of osteoarthritis (OA) and its underlying mechanisms.
Methods. FGFR-1 was deleted from the articular chondrocytes of adult mice in a cartilage-specific and tamoxifen-inducible manner. Two OA models (aging-associated spontaneous OA, and destabilization-induced OA), as well as an antigen-induced arthritis (AIA) model, were established and tested in Fgfr1-deficient and wild-type (WT) mice. Alterations in cartilage structure and the loss of proteoglycan were assessed in the knee joints of mice of either genotype, using these 3 arthritis models. Primary chondrocytes were isolated and the expression of key regulatory molecules was assessed quantitatively. In addition, the effect of an FGFR-1 inhibitor on human articular chondrocytes was examined.
Results. The gross morphologic features of Fgfr1-deficient mice were comparable with those of WT mice at both the postnatal and adult stages. The articular cartilage of 12-month-old Fgfr1-deficient mice displayed greater aggrecan staining compared to 12-month-old WT mice. Fgfr1 deficiency conferred resistance to the proteoglycan loss induced by AIA and attenuated the development of cartilage destruction after surgically induced destabilization of the knee joint. The chondro-protective effect of FGFR-1 inhibition was largely associated with decreased expression of matrix metalloproteinase 13 (MMP-13) and up-regulation of FGFR-3 in mouse and human articular chondrocytes.
Conclusion. Disruption of FGFR-1 in adult mouse articular chondrocytes inhibits the progression of cartilage degeneration. Down-regulation of MMP-13 expression and up-regulation of FGFR-3 levels may contribute to the phenotypic changes observed in Fgfr1-deficient mice.
C1 [Chen, Lin] Third Mil Med Univ, Ctr Bone Metab & Repair, State Key Lab Trauma Burns & Combined Injury, Trauma Ctr,Daping Hosp, Chongqing 400042, Peoples R China.
[Weng, Tujun; Yi, Lingxian; Huang, Junlan; Luo, Fengtao; Wen, Xuan; Du, Xiaolan; Chen, Lin] Third Mil Med Univ, Inst Surg Res, Chongqing 400042, Peoples R China.
[Chen, Qian] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Chen, Qian] Rhode Isl Hosp, Providence, RI USA.
[Deng, Chuxia] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Chen, Di] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
RP Chen, L (reprint author), Third Mil Med Univ, Ctr Bone Metab & Repair, State Key Lab Trauma Burns & Combined Injury, Trauma Ctr,Daping Hosp, Chongqing 400042, Peoples R China.
EM linchen70@tmmu.edu.cn
RI deng, chuxia/N-6713-2016
FU Special Funds for Major State Basic Research Program of China (973
Program) [2011CB964701, 2012CB518106]; National Natural Science
Foundation of China [81000422, 81030036]; State Key Laboratory of
Trauma, Burns, and Combined Injury, China [SKLZZ200902]; NIH [AG-017021,
GM-104937]
FX Supported by the Special Funds for Major State Basic Research Program of
China (973 Program grants 2011CB964701 and 2012CB518106), the National
Natural Science Foundation of China (grants 81000422 and 81030036), the
State Key Laboratory of Trauma, Burns, and Combined Injury, China (grant
SKLZZ200902), and the NIH (grants AG-017021 and GM-104937).
NR 44
TC 26
Z9 28
U1 2
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD DEC
PY 2012
VL 64
IS 12
BP 3982
EP 3992
DI 10.1002/art.34645
PG 11
WC Rheumatology
SC Rheumatology
GA 045ON
UT WOS:000311706300019
PM 22833219
ER
PT J
AU Lukacik, P
Barnard, TJ
Buchanan, SK
AF Lukacik, Petra
Barnard, Travis J.
Buchanan, Susan K.
TI Using a bacteriocin structure to engineer a phage lysin that targets
Yersinia pestis
SO BIOCHEMICAL SOCIETY TRANSACTIONS
LA English
DT Article
DE C-terminal domain; lysin; peptidoglycan; pesticin; yersiniabactin
ID ESCHERICHIA-COLI STRAINS; HIGH-PATHOGENICITY ISLAND; PREVALENCE;
UROSEPSIS; LYSOZYMES; BACILLUS; RECEPTOR
AB Purified phage lysins present an alternative to traditional antibiotics and work by hydrolysing peptidoglycan. Phage lysins have been developed against Gram-positive pathogens such as Bacillus anthracis and Streptococcus pneumoniae, where the peptidoglycan layer is exposed on the cell surface. Addition of the lysin to a bacterial culture results in rapid death of the organism. Gram-negative bacteria are resistant to phage lysins because they contain an outer membrane that protects the peptidoglycan from degradation. We solved crystal structures of a Yersinia pestis outer-membrane protein and the bacteriocin that targets it, which informed engineering of a bacterial-phage hybrid lysin that can be transported across the outer membrane to kill specific Gram-negative bacteria. This work provides a template for engineering phage lysins against a wide variety of bacterial pathogens.
C1 [Lukacik, Petra; Barnard, Travis J.; Buchanan, Susan K.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Buchanan, SK (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA.
EM skbuchan@helix.nih.gov
FU Intramural Program of the National Institute of Diabetes and Digestive
and Kidney Diseases of the National Institutes of Health
FX P.L., N.N. and S.K.B. are supported by the Intramural Program of the
National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health.
NR 27
TC 9
Z9 11
U1 0
U2 7
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0300-5127
J9 BIOCHEM SOC T
JI Biochem. Soc. Trans.
PD DEC
PY 2012
VL 40
BP 1503
EP 1506
DI 10.1042/BST20120209
PN 6
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 051AR
UT WOS:000312096800059
PM 23176506
ER
PT J
AU Kim, JA
Nunez, M
Briggs, DB
Laskowski, BL
Chhun, JJ
Eleid, JK
Quon, MJ
Tsao, TS
AF Kim, Jeong-a
Nunez, Martha
Briggs, David B.
Laskowski, Bethany L.
Chhun, Jimmy J.
Eleid, Joseph K.
Quon, Michael J.
Tsao, Tsu-Shuen
TI Extracellular conversion of adiponectin hexamers into trimers
SO BIOSCIENCE REPORTS
LA English
DT Article
DE adipocyte; adiponectin; oligomerization; oxidation-reduction; redox;
thiol
ID MOLECULAR-WEIGHT ADIPONECTIN; METABOLIC SYNDROME; INSULIN SENSITIVITY;
COLLAGENOUS DOMAIN; HUMAN PLASMA; POSTTRANSLATIONAL MODIFICATIONS;
THIOREDOXIN REDUCTASE; RAT ADIPOCYTES; PROTEIN-KINASE; GLUTATHIONE
AB Adiponectin is an adipocyte-secreted hormone that exists as trimers, hexamers and larger species collectively referred to as HMW (high-molecular-weight) adiponectin. Whether hexamers or HMW adiponectin serve as precursors for trimers outside the circulation is currently unknown. Here, we demonstrate that adiponectin trimers can be generated from larger oligomers secreted from primary rat adipose cells or differentiated 3T3-L1 adipocytes. Purified hexameric, but not HMW, adiponectin converted into trimers in conditioned media separated from 3T3-L1 adipocytes or, more efficiently, when enclosed in the dialysis membrane in the presence of adipocytes. Several lines of evidence indicate that the conversion is mediated by an extracellular redox system. First, N-terminal epitope-tagged hexamers converted into trimers without proteolytic removal of the tag. Secondly, appearance of trimers was associated with conversion of disulfide-bonded dimers into monomers. Thirdly, thiol-reactive agents inhibited conversion into trimers. Consistent with a redox-based mechanism, purified hexamers reductively converted into trimers in defined glutathione redox buffer with reduction potential typically found in the extracellular environment while the HMW adiponectin remained stable. In addition, conversion of hexamers into trimers was enhanced by NADPH, but not by NADP+. Collectively, these data strongly suggest the presence of an extracellular redox system capable of converting adiponectin oligomers.
C1 [Nunez, Martha; Briggs, David B.; Laskowski, Bethany L.; Chhun, Jimmy J.; Eleid, Joseph K.; Tsao, Tsu-Shuen] Univ Arizona, Dept Chem & Biochem, Tucson, AZ 85724 USA.
[Kim, Jeong-a] Univ Alabama Birmingham, Dept Med, Div Endocrinol Diabet & Metab, Birmingham, AL 35294 USA.
[Kim, Jeong-a] Univ Alabama Birmingham, Dept Cell Biol, Birmingham, AL 35294 USA.
[Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
RP Tsao, TS (reprint author), Univ Arizona, Dept Chem & Biochem, Tucson, AZ 85724 USA.
EM tsushuen@email.arizona.edu
OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707
FU American Diabetes Association [1-08-JF-54, 1-09-JK-33, 1-12-BS-99];
Arizona Biomedical Research Commission; UAB Diabetes Research Training
Center Pilot and Feasibility Fund [P-60 DK-079626]; Intramural Research
Programme, National Center for Complementary and Alternative Medicine,
National Institutes of Health
FX This work was supported by the American Diabetes Association [grant
number 1-08-JF-54 (to T.-S. T.), and grant numbers 1-09-JK-33 and
1-12-BS-99 (to J.-a. K.)], the Arizona Biomedical Research Commission
(to T.-S. T.), the UAB Diabetes Research Training Center Pilot and
Feasibility Fund [grant number P-60 DK-079626 (to J.-a. K.)] and the
Intramural Research Programme, National Center for Complementary and
Alternative Medicine, National Institutes of Health (to M.J.Q.).
NR 52
TC 6
Z9 6
U1 0
U2 2
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0144-8463
J9 BIOSCIENCE REP
JI Biosci. Rep.
PD DEC
PY 2012
VL 32
IS 6
BP 641
EP 652
DI 10.1042/BSR20120067
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 053OD
UT WOS:000312281400014
PM 22973892
ER
PT J
AU Turkbey, B
Huang, R
Vourganti, S
Trivedi, H
Bernardo, M
Yan, P
Benjamin, C
Pinto, PA
Choyke, PL
AF Turkbey, Baris
Huang, Robert
Vourganti, Srinivas
Trivedi, Hari
Bernardo, Marcelino
Yan, Pingkun
Benjamin, Compton
Pinto, Peter A.
Choyke, Peter L.
TI Age-related changes in prostate zonal volumes as measured by
high-resolution magnetic resonance imaging (MRI): a cross-sectional
study in over 500 patients
SO BJU INTERNATIONAL
LA English
DT Article
DE BPH; MRI; prostate zonal volumes; age-related changes
ID URINARY FLOW-RATES; LONGITUDINAL CHANGES; NATURAL-HISTORY; HYPERPLASIA;
ANTIGEN; MEN; ADENOCARCINOMA; POPULATION; SYMPTOMS; COHORT
AB OBJECTIVE
To use ability of magnetic resonance imaging (MRI) to investigate age-related changes in zonal prostate volumes.
PATIENTS AND METHODS
This Institutional Review Board approved, Health Insurance Portability and Accountability Act-compliant study consisted of 503 patients who underwent 3 T prostate MRI before any treatment for prostate cancer.
Whole prostate (WP) and central gland (CG) volumes were manually contoured on T2-weighted MRI using a semi-automated segmentation tool. WP, CG, peripheral zone (PZ) volumes were measured for each patient.
WP, CG, PZ volumes were correlated with age, serum prostate-specific antigen (PSA) level, International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM) scores.
RESULTS
Linear regression analysis showed positive correlations between WP, CG volumes and patient age (P < 0.001); there was no correlation between age and PZ volume (P= 0.173).
There was a positive correlation between WP, CG volumes and serum PSA level (P < 0.001), as well as between PZ volume and serum PSA level (P= 0.002).
At logistic regression analysis, IPSS positively correlated with WP, CG volumes (P < 0.001).
SHIM positively correlated with WP (P= 0.015) and CG (P= 0.023) volumes.
As expected, the IPSS of patients with prostate volumes (WP, CG) in first decile for age were significantly lower than those in tenth decile.
CONCLUSIONS
Prostate MRI is able to document age-related changes in prostate zonal volumes.
Changes in WP and CG volumes correlated inversely with changes in lower urinary tract symptoms.
These findings suggest a role for MRI in measuring accurate prostate zonal volumes; have interesting implications for study of age-related changes in the prostate.
C1 [Turkbey, Baris; Huang, Robert; Bernardo, Marcelino; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Vourganti, Srinivas; Trivedi, Hari; Benjamin, Compton; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Yan, Pingkun] Chinese Acad Sci, Ctr OPT IMagery Anal & Learning OPTIMAL, State Key Lab Transient Opt & Photon, Xian Inst Opt & Precis Mech, Xian, Shaanxi, Peoples R China.
RP Choyke, PL (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Room B69, Bethesda, MD 20892 USA.
EM pchoyke@mail.nih.gov
FU Intramural NIH HHS [ZID BC011089-05, ZIE BC011023-05, ZIA BC011081-05]
NR 21
TC 10
Z9 10
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD DEC
PY 2012
VL 110
IS 11
BP 1642
EP 1647
DI 10.1111/j.1464-410X.2012.11469.x
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 053BY
UT WOS:000312245900018
PM 22973825
ER
PT J
AU Pratt, E
Sissung, TM
Figg, WD
AF Pratt, Elias
Sissung, Tristan M.
Figg, William D.
TI Loss of oatp1b3 function causes rotor syndrome Implications for
potential use of inhibitors in cancer
SO CANCER BIOLOGY & THERAPY
LA English
DT Editorial Material
DE OATP; prostate; cancer; therapy; Rotor syndrome; inhibition; DDI
ID PROSTATE-CANCER; TESTOSTERONE; SLCO1B3
AB There has been increasing recognition that organic anion transporter proteins (OATPs) play an important role in the biology of various cancers. De novo expression of OATPs has been identified in breast, colon, pancreatic, gastric and prostate cancer cells, among others.(1) In patients with prostate cancer, polymorphisms encoding decreased functioning OATP1B3 were associated with a longer time to progression on androgen deprivation therapy and a longer overall survival which is likely caused by reduced tumoral testosterone uptake.(2-4) Because of these findings, therapeutic inhibition targeting OATP1B3 has been proposed. However, any enthusiasm for inhibiting OATP1Bs therapeutically has been tempered by reservations about potential consequences. For instance, inhibitors could interfere with several normal physiological processes mediated by OATP1B3 (i.e., bile acid reuptake, bilirubin uptake, etc.) or cause potential, as-yet unknown, drug interactions by barring hepatic uptake, subsequent metabolism and elimination.
C1 [Pratt, Elias; Sissung, Tristan M.; Figg, William D.] NCI, Clin Pharmacol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
EM figgw@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU Intramural NIH HHS
NR 7
TC 1
Z9 1
U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD DEC
PY 2012
VL 13
IS 14
BP 1374
EP 1375
DI 10.4161/cbt.22010
PG 2
WC Oncology
SC Oncology
GA 052QD
UT WOS:000312212200003
PM 22954695
ER
PT J
AU Pinsky, PF
Black, A
Parnes, HL
Grubb, R
Crawford, ED
Miller, A
Reding, D
Andriole, G
AF Pinsky, Paul F.
Black, Amanda
Parnes, Howard L.
Grubb, Robert
Crawford, E. David
Miller, Anthony
Reding, Douglas
Andriole, Gerald
TI Prostate cancer specific survival in the Prostate, Lung, Colorectal, and
Ovarian (PLCO) Cancer Screening Trial
SO CANCER EPIDEMIOLOGY
LA English
DT Article
DE Prostate cancer; Screening; PSA; Survival; Gleason grade
ID FOLLOW-UP; MORTALITY; DESIGN; GRADE
AB Background: The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized screening trial demonstrated no mortality effect of screening. Here we analyze prostate cancer specific survival in PLCO and its relation to screening. Methods: 76,693 men aged 55-74 were randomized to usual care (n = 38,350) or intervention (n = 38,343). Intervention arm men received annual prostate-specific antigen (6 years) and digital rectal exam (4 years). Men were followed for cancer diagnosis and mortality through 13 years. Medical record abstractors confirmed prostate cancer diagnoses, stage and grade. Prostate-specific survival in PLCO cases was analyzed using Kaplan-Meier analysis and proportional hazards modeling. We utilized data from the Surveillance, Epidemiology and End Results (SEER) program to compute expected survival in PLCO and compared this to observed. Results: There was no significant difference in prostate-specific survival rates between arms; 10 year survival rates were 94.7% (intervention, n = 4250 cases) versus 93.5% (usual care, n = 3815 cases). Within the intervention arm, cases never screened in PLCO had lower 10 year survival rates (82%) than screen detected or interval (following a negative screen) cases, both around 95.5%. The ratio of observed to expected 10 year prostate-specific death (1-survival) rates was 0.59 (95% CI: 0.51-0.68) for all PLCO cases, 0.66 (95% CI: 0.51-0.81) for Gleason 5-7 cases and 1.07 (95% CI: 0.87-1.3) for Gleason 8-10 cases. Conclusion: Prostate cancer specific survival in PLCO was comparable across arms and significantly better than expected based on nationwide population data. How much of the better survival is due to a healthy volunteer effect and to lead-time and overdiagnosis biases is not readily determinable. Published by Elsevier Ltd.
C1 [Pinsky, Paul F.; Parnes, Howard L.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Black, Amanda] NCI, Div Canc Epidemiol, NIH, Bethesda, MD 20892 USA.
[Grubb, Robert; Andriole, Gerald] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Crawford, E. David] Univ Colorado, Denver, CO 80202 USA.
[Miller, Anthony] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Reding, Douglas] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA.
RP Pinsky, PF (reprint author), NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
EM pp4f@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 15
TC 6
Z9 6
U1 1
U2 10
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1877-7821
J9 CANCER EPIDEMIOL
JI Cancer Epidemiol.
PD DEC
PY 2012
VL 36
IS 6
BP E401
EP E406
DI 10.1016/j.canep.2012.08.008
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 053HB
UT WOS:000312260900011
PM 23000116
ER
PT J
AU Clarke, MA
Wentzensen, N
Mirabello, L
Ghosh, A
Wacholder, S
Harari, A
Lorincz, A
Schiffman, M
Burk, RD
AF Clarke, Megan A.
Wentzensen, Nicolas
Mirabello, Lisa
Ghosh, Arpita
Wacholder, Sholom
Harari, Ariana
Lorincz, Attila
Schiffman, Mark
Burk, Robert D.
TI Human Papillomavirus DNA Methylation as a Potential Biomarker for
Cervical Cancer
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Review
ID LONG CONTROL REGION; 16 E6 GENE; INTRAEPITHELIAL NEOPLASIA; CPG
METHYLATION; CARCINOGENIC PROGRESSION; NATURAL-HISTORY; INVASIVE CANCER;
SQUAMOUS-CELLS; BINDING-SITE; PAP CYTOLOGY
AB Sexually transmitted carcinogenic human papillomavirus (HPV) infections are extraordinarily prevalent worldwide. However, most incident HPV infections clear within a few years, whereas a small minority persists to invasive cancer. Recent studies indicate that detection of methylated viral DNA may distinguish women with cervical intraepithelial neoplasia grade 2+ (CIN2+) from those with a carcinogenic HPV-type infection that shows no evidence of CIN2+. Several studies have reported a positive association between methylation of CpG sites in the L1 gene and CIN2+, although there are inconclusive results about methylation of CpG sites in the upstream regulatory region (URR). In this review, we summarize the current state of knowledge on HPV DNA methylation in cervical carcinogenesis, and discuss the merits of different methods used to measure HPV DNA methylation. To follow the promising leads, we suggest future studies to validate the use of methylated carcinogenic HPV DNA as a predictive and/or diagnostic biomarker for risk of cervical cancer among HPV-positive women. Cancer Epidemiol Biomarkers Prev; 21(12); 2125-37. (C)2012 AACR.
C1 [Harari, Ariana; Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Microbiol & Immunol, Bronx, NY 10461 USA.
[Clarke, Megan A.; Wentzensen, Nicolas; Mirabello, Lisa; Ghosh, Arpita; Wacholder, Sholom; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Pediat, Bronx, NY 10461 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10461 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
[Lorincz, Attila] Univ London, Wolfson Inst Prevent Med, Ctr Canc Prevent, London, England.
RP Burk, RD (reprint author), Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Microbiol & Immunol, 1300 Morris Pk Ave,Ullman Bldg,Room 515, Bronx, NY 10461 USA.
EM robert.burk@einstein.yu.edu
FU NIH; National Cancer Institute [5U01CA078527]
FX This research was supported (in part) by the Intramural Research Program
of the NIH and the National Cancer Institute (5U01CA078527 to R.D.
Burk).
NR 74
TC 44
Z9 46
U1 0
U2 19
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 DEC
PY 2012
VL 21
IS 12
BP 2125
EP 2137
DI 10.1158/1055-9965.EPI-12-0905
PG 13
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 053NX
UT WOS:000312280800001
PM 23035178
ER
PT J
AU Rosenberg, PS
Wilson, KL
Anderson, WF
AF Rosenberg, Philip S.
Wilson, Katherine L.
Anderson, William F.
TI Are Incidence Rates of Adult Leukemia in the United States Significantly
Associated with Birth Cohort?
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; BODY-MASS INDEX; ACUTE LYMPHOBLASTIC-LEUKEMIA;
CHRONIC LYMPHOCYTIC-LEUKEMIA; BREAST-CANCER INCIDENCE; AGE-SPECIFIC
INCIDENCE; EUROPEAN COUNTRIES; TESTICULAR CANCER; TEMPORAL TRENDS; RISK
AB Background: Leukemia is a common cancer among U.S. adults but there are few established risk factors. If leukemia risks are substantially influenced by exposures that vary in prevalence across generations, then population incidence rates should vary significantly by birth cohort. However, prior studies have not examined leukemia birth cohort effects using contemporary data and methods.
Methods: We used incidence data from the National Cancer Institute's Surveillance, Epidemiology and End Results Program from 1992 through 2009 for adults 25-84 years old and age period cohort models to estimate incidence rate ratios according to birth cohort for acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphoid leukemia (CLL).
Results: Leukemia incidence varied significantly between birth cohorts for each major leukemia type in men and women except female AMLs; changes on the order of 1% per birth year or 20% per generation were observed. The most significant birth cohort signatures were observed for CLLs and AMLs in men, which were decreasing and increasing, respectively, in cohorts born since 1946.
Conclusions: Our results support the hypothesis that adult leukemia risks are significantly modulated by environmental and lifestyle exposures.
Impact: A number of well-established (smoking, certain chemicals, radiation) and newly recognized (obesity) leukemia risk factors are modifiable; ultimately, efforts to promote healthy lifestyles might also help reduce incidence rates of adult leukemia. Cancer Epidemiol Biomarkers Prev; 21(12); 2159-66. (C)2012 AACR.
C1 [Rosenberg, Philip S.; Wilson, Katherine L.; Anderson, William F.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
RP Rosenberg, PS (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Execut Plaza S,Room 8022, Rockville, MD 20852 USA.
EM rosenbep@mail.nih.gov
FU NIH, National Cancer Institute, Division of Cancer Epidemiology and
Genetics
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Cancer Institute, Division of Cancer Epidemiology
and Genetics.
NR 63
TC 4
Z9 4
U1 1
U2 13
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 DEC
PY 2012
VL 21
IS 12
BP 2159
EP 2166
DI 10.1158/1055-9965.EPI-12-0910
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 053NX
UT WOS:000312280800004
PM 23064005
ER
PT J
AU Lam, TK
Shao, S
Zhao, Y
Marincola, F
Pesatori, A
Bertazzi, PA
Caporaso, NE
Wang, E
Landi, MT
AF Lam, Tram K.
Shao, Stephanie
Zhao, Yingdong
Marincola, Francesco
Pesatori, Angela
Bertazzi, Pier Alberto
Caporaso, Neil E.
Wang, Ena
Landi, Maria Teresa
TI Influence of Quercetin-Rich Food Intake on microRNA Expression in Lung
Cancer Tissues
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID PANCREATIC-CANCER; FLAVONOID INTAKE; GENE-EXPRESSION; LET-7; FAMILY;
RISK; PREVENTION; MIR-17-92; CELLS; TUMORIGENESIS
AB Background: Epidemiologic studies have reported that frequent consumption of quercetin-rich foods is inversely associated with lung cancer incidence. A quercetin-rich diet might modulate microRNA (miR) expression; however, this mechanism has not been fully examined.
Methods: miR expression data were measured by a custom-made array in formalin-fixed paraffin-embedded tissue samples from 264 lung cancer cases (144 adenocarcinomas and 120 squamous cell carcinomas). Intake of quercetin-rich foods was derived from a food-frequency questionnaire. In individual-miR based analyses, we compared the expression of miRs (n = 198) between lung cancer cases consuming high versus low quercetin-rich food intake using multivariate ANOVA tests. In family-miR based analyses, we used Functional Class Scoring (FCS) to assess differential effect on biologically functional miR families. We accounted for multiple testing using 10,000 global permutations (significance at P-global <0.10). All multivariate analyses were conducted separately by histology and by smoking status (former and current smokers).
Results: Family-based analyses showed that a quercetin-rich diet differentiated miR expression profiles of the tumor suppressor let-7 family among adenocarcinomas (P-FCS < 0.001). Other significantly differentiated miR families included carcinogenesis-related miR-146, miR-26, and miR-17 (P (FCS) < 0.05). In individual-based analyses, we found that among former and current smokers with adenocarcinoma, 33 miRs were observed to be differentiated between highest and lowest quercetin-rich food consumers (23 expected by chance; P-global = 0.047).
Conclusions: We observed differential expression of key biologically functional miRs between high versus low consumers of quercetin-rich foods in adenocarcinoma cases.
Impact: Our findings provide preliminary evidence on the mechanism underlying quercetin-related lung carcinogenesis. Cancer Epidemiol Biomarkers Prev; 21(12); 2176-84. (C)2012 AACR.
C1 [Landi, Maria Teresa] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Zhao, Yingdong] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Marincola, Francesco] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Marincola, Francesco] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA.
[Shao, Stephanie] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Pesatori, Angela; Bertazzi, Pier Alberto] Univ Milan, Osped Maggiore Policlin, Fdn IRCCS, Epidemiol Unit, Milan, Italy.
[Pesatori, Angela; Bertazzi, Pier Alberto] Univ Milan, Dept Occupat & Environm Hlth, Milan, Italy.
RP Landi, MT (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM landim@mail.nih.gov
RI bertazzi, pietro alberto/D-5039-2017;
OI bertazzi, pietro alberto/0000-0003-3475-2449; pesatori,
angela/0000-0002-0261-3252
FU Intramural NIH HHS [ZIA CP005804-15]
NR 42
TC 19
Z9 22
U1 0
U2 8
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 DEC
PY 2012
VL 21
IS 12
BP 2176
EP 2184
DI 10.1158/1055-9965.EPI-12-0745
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 053NX
UT WOS:000312280800006
PM 23035181
ER
PT J
AU Kitahara, CM
Neta, G
Pfeiffer, RM
Kwon, D
Xu, L
Freedman, ND
Hutchinson, AA
Chanock, SJ
Sturgis, EM
Sigurdson, AJ
Brenner, AV
AF Kitahara, Cari M.
Neta, Gila
Pfeiffer, Ruth M.
Kwon, Deukwoo
Xu, Li
Freedman, Neal D.
Hutchinson, Amy A.
Chanock, Stephen J.
Sturgis, Erich M.
Sigurdson, Alice J.
Brenner, Alina V.
TI Common Obesity-Related Genetic Variants and Papillary Thyroid Cancer
Risk
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID BODY-MASS INDEX
AB Background: Epidemiologic studies have shown consistent associations between obesity and increased thyroid cancer risk, but, to date, no studies have investigated the relationship between thyroid cancer risk and obesity-related single-nucleotide polymorphisms (SNP).
Methods: We evaluated 575 tag SNPs in 23 obesity-related gene regions in a case-control study of 341 incident papillary thyroid cancer (PTC) cases and 444 controls of European ancestry. Logistic regression models, adjusted for attained age, year of birth, and sex were used to calculate ORs and 95% confidence intervals (CI) with SNP genotypes, coded as 0, 1, and 2 and modeled continuously to calculate P-trend.
Results: Nine of 10 top-ranking SNPs (P-trend <0.01) were located in the FTO (fat mass and obesity associated) gene region, whereas the other was located in INSR (insulin receptor). None of the associations were significant after correcting for multiple testing.
Conclusions: Our data do not support an important role of obesity-related genetic polymorphisms in determining the risk of PTC.
Impact: Factors other than selected genetic polymorphisms may be responsible for the observed associations between obesity and increased PTC risk. Cancer Epidemiol Biomarkers Prev; 27(72); 2268-77. (C)2012 AACR.
C1 [Kitahara, Cari M.; Neta, Gila; Pfeiffer, Ruth M.; Freedman, Neal D.; Chanock, Stephen J.; Sigurdson, Alice J.; Brenner, Alina V.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Hutchinson, Amy A.] SAIC Frederick Inc, Natl Canc Inst Frederick, Core Genotyping Facil, Frederick, MD USA.
[Kwon, Deukwoo] Univ Miami, Sylvester Comprehens Canc Ctr, Biostat & Bioinformat Core, Miami, FL USA.
[Xu, Li; Sturgis, Erich M.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA.
RP Kitahara, CM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, EPS 7056,6120 Execut Blvd, Rockville, MD 20852 USA.
EM kitaharac@mail.nih.gov
RI Xu, Li/B-9535-2012; Freedman, Neal/B-9741-2015; Kitahara,
Cari/R-8267-2016
OI Freedman, Neal/0000-0003-0074-1098;
FU NCI, NIH [HHSN261200800001E]
FX This research was supported in part by the Intramural Research Program
of the NCI, NIH. This project has been funded in whole or in part with
federal funds from the NCI, NIH, under contract no. HHSN261200800001E.
NR 8
TC 11
Z9 11
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD DEC
PY 2012
VL 21
IS 12
BP 2268
EP 2271
DI 10.1158/1055-9965.EPI-12-0790
PG 4
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 053NX
UT WOS:000312280800016
PM 23064004
ER
PT J
AU Holland, RJ
Maciag, AE
Kumar, V
Shi, L
Saavedra, JE
Prud'homme, RK
Chakrapani, H
Keefer, LK
AF Holland, Ryan J.
Maciag, Anna E.
Kumar, Varun
Shi, Lei
Saavedra, Joseph E.
Prud'homme, Robert K.
Chakrapani, Harinath
Keefer, Larry K.
TI Cross-Linking Protein Glutathionylation Mediated by O-2-Arylated
Bis-Diazeniumdiolate "Double JS-K"
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID NITRIC-OXIDE DONOR; S-GLUTATHIONYLATION; IN-VITRO; ANTINEOPLASTIC
ACTIVITY; CANCER-CELLS; VIVO; DAMAGE; ACTIN; DNA
AB Attachment of glutathione (GSH) to cysteine residues in proteins (S-glutathionylation) is a reversible post-translational modification that can profoundly alter protein structure and function. Often serving in a protective role, for example, by temporarily saving protein thiols from irreversible oxidation and inactivation, glutathionylation can be identified and semiquantitatively assessed using anti-GSH antibodies, thought to be specific for recognition of the S-glutathionylation modification. Here, we describe an alternate mechanism of protein glutathionylation in which the sulfur atoms of the GSH and the protein's thiol group are covalently bound via a cross-linking agent, rather than through a disulfide bond. This form of thiol cross-linking has been shown to occur and has been confirmed by mass spectrometry at the solution chemistry level, as well as in experiments documenting the potent antiproliferative activity of the bis-diazeniumdiolate Double JS-K in H1703 cells in vitro and in vivo. The modification is recognized by the anti-GSH antibody as if it were authentic S-glutathionylation, requiring mass spectrometry to distinguish between them.
C1 [Holland, Ryan J.; Keefer, Larry K.] Frederick Natl Lab Canc Res, Biol Chem Lab, Frederick, MD 21702 USA.
[Maciag, Anna E.; Saavedra, Joseph E.] Frederick Natl Lab Canc Res, SAIC Frederick, Basic Sci Program, Frederick, MD 21702 USA.
[Kumar, Varun; Shi, Lei; Prud'homme, Robert K.] Princeton Univ, Dept Chem & Biol Engn, Princeton, NJ 08544 USA.
[Chakrapani, Harinath] Indian Inst Sci Educ & Res, Pune 411008, Maharashtra, India.
RP Holland, RJ (reprint author), Frederick Natl Lab Canc Res, Biol Chem Lab, Frederick, MD 21702 USA.
EM hollandrj@mail.nih.gov
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute; National Cancer Institute
[HHSN261200800001E]; NIH [R01 CA155061-01]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, with Federal
funds from the National Cancer Institute under Contract
HHSN261200800001E, and through NIH grant R01 CA155061-01.
NR 22
TC 6
Z9 7
U1 0
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD DEC
PY 2012
VL 25
IS 12
BP 2670
EP 2677
DI 10.1021/tx3003142
PG 8
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA 054RI
UT WOS:000312360500007
PM 23106594
ER
PT J
AU Kamakura, N
Yamamoto, J
Brooks, PJ
Iwai, S
Kuraoka, I
AF Kamakura, Naoto
Yamamoto, Junpei
Brooks, Philip J.
Iwai, Shigenori
Kuraoka, Isao
TI Effects of 5 ',8-Cyclodeoxyadenosine Triphosphates on DNA Synthesis
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID NUCLEOTIDE EXCISION-REPAIR; RADICAL-INDUCED FORMATION; RADIATION-INDUCED
DAMAGE; HUMAN-CELLS; MAMMALIAN-CELLS; POLYMERASE-ETA; GEMCITABINE;
PATHWAY; CANCER; ACID
AB Hydroxyl radicals generate a broad range of DNA lesions in living cells. Cyclopurine deoxynucleosides (CPUs) are a biologically significant class of oxidative DNA lesions due to their helical distortion and chemically stability. The CPUs on DNA are substrates for the nucleotide excision repair (NER) but not for base excision repair or direct damage reversal. Moreover, these lesions block DNA and RNA polymerases, resulting in cell death. Here, we describe the chemical synthesis of 5'S and 5'R isomers of 5',8-cyclodeoxyadenosine triphosphate (cdATP) and demonstrate their ability to be incorporated into DNA by replicative DNA polymerases. DNA synthesis assays revealed that the incorporation of the stereoisomeric cdATPs strongly inhibits DNA polymerase reactions. Surprisingly, the two stereoisomers had different mutagenic profiles, since the S isomer of cdATP could be inserted opposite to the dTMP, but the R isomer of cdATP could be inserted opposite to the dCMP. Kinetic analysis revealed that the S isomer of cdATP could be incorporated more efficiently (25.6 mu M-1 min(-1)) than the R isomer (1.13 mu M-1 min(-1)) during DNA synthesis. Previous data showed that the S isomer in DNA blocked DNA synthesis and the exonuclease activity of DNA polymerase and is less efficiently repaired by NER This indicates that the S isomer has a tendency to accumulate on the genome DNA, and as such, the S isomer of cdATP may be a candidate cytotoxic drug.
C1 [Kamakura, Naoto; Yamamoto, Junpei; Iwai, Shigenori; Kuraoka, Isao] Osaka Univ, Grad Sch Engn Sci, Grad Sch Engn Sci, Toyonaka, Osaka 5608531, Japan.
[Brooks, Philip J.] NIAAA, Neurogenet Lab, Mol Neurobiol Sect, Bethesda, MD 20892 USA.
RP Kuraoka, I (reprint author), Osaka Univ, Grad Sch Engn Sci, Grad Sch Engn Sci, 1-3 Machikaneyama, Toyonaka, Osaka 5608531, Japan.
EM Kuraoka@chem.es.osaka-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) of
Japan
FX This work was supported by a Grant-in-aid for Scientific Research from
the Ministry of Education, Culture, Sports, Science and Technology
(MEXT) of Japan.
NR 38
TC 6
Z9 6
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD DEC
PY 2012
VL 25
IS 12
BP 2718
EP 2724
DI 10.1021/tx300351p
PG 7
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA 054RI
UT WOS:000312360500012
PM 23146066
ER
PT J
AU Chary, P
Beard, WA
Wilson, SH
Lloyd, RS
AF Chary, Parvathi
Beard, William A.
Wilson, Samuel H.
Lloyd, R. Stephen
TI DNA Polymerase beta Gap-Filling Translesion DNA Synthesis
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID NUCLEOTIDE INCORPORATION; REVERSE-TRANSCRIPTASE; MINOR-GROOVE; ADDUCTS;
REPLICATION; REPAIR; EXCISION; BYPASS; LESION; SITES
AB Although the primary function of DNA polymerase (pol) beta is associated with gap-filling DNA synthesis as part of the DNA base excision repair pathway, translesion synthesis activity has also been described. To further understand the potential role of pol beta-catalyzed translesion DNA synthesis (TLS) and the structure-function relationships of specific residues in pol beta, wild-type and selected mutants of pol beta were used in TLS assays with DNA substrates containing bulky polycyclic aromatic hydrocarbon-adducted oligonucleotides. Stereospecific (+) and (-)-anti-trans-(C10S and C10R) benzo[a]pyrene-7,8- dihydrodiol-9-10-epoxide (BPDE) adducts were covalently attached to both the N-6-adenine and N-2-guanine in the major and minor grooves, respectively. For all substrates tested, the presence of the BPDE adducts greatly decreased the efficiency of nucleotide incorporation opposite the lesion, and the stereochemistry of the adducts also further modulated the efficiency of the insertion step, such that lesions which were oriented in the 3' direction relative to the approaching polymerase were considerably more blocking than those oriented in the 5' direction. In the absence of a downstream DNA strand, the extension step beyond the adduct was extremely inefficient, relative to a dinucleotide gap-filling reaction, such that in the presence of the downstream DNA, dinucleotide incorporation was strongly favored. In general, analyses of the TLS activities of four pol beta mutants revealed similar overall properties, but wild-type pol beta exhibited more than 50-fold greater extension and bypass of the C10S-dA adducts as compared to a low fidelity mutant R283K expected to interact with the templating base. Replication bypass investigations were further extended to include analyses of HIV-1 reverse transcriptase, and these studies revealed patterns of inhibition very similar to that observed for pol beta.
C1 [Chary, Parvathi; Lloyd, R. Stephen] Oregon Hlth & Sci Univ, CROET, Portland, OR 97239 USA.
[Beard, William A.; Wilson, Samuel H.] Natl Inst Environm Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Lloyd, RS (reprint author), Oregon Hlth & Sci Univ, CROET, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM lloydst@ohsu.edu
FU NIH, National Institute of Environmental Health Sciences [Z01-ES050158,
Z01-ES050161]; National Institutes of Health [P01 ES05355, P01 CA160032,
1U19CA105010, P41 RR-01081]
FX This research was supported by NIH Grants P01 ES05355 and P01 CA160032
(to R.S.L.) and research project numbers Z01-ES050158 and Z01-ES050161
in the intramural research program of the NIH, National Institute of
Environmental Health Sciences (to S.H.W.), and was in association with
the National Institutes of Health Grant 1U19CA105010. Molecular graphics
images were produced using the Chimera package34 from the
Resource for Biocomputing, Visualization, and Informatics at the
University of California, San Francisco (supported by NIH P41 RR-01081).
NR 34
TC 10
Z9 10
U1 0
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD DEC
PY 2012
VL 25
IS 12
BP 2744
EP 2754
DI 10.1021/tx300368f
PG 11
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA 054RI
UT WOS:000312360500015
PM 23121263
ER
PT J
AU Robertson, JWF
Kasianowicz, JJ
Banerjee, S
AF Robertson, Joseph W. F.
Kasianowicz, John J.
Banerjee, Soojay
TI Analytical Approaches for Studying Transporters, Channels and Porins
SO CHEMICAL REVIEWS
LA English
DT Review
ID ATOMIC-FORCE MICROSCOPY; SOLID-STATE NMR; BILAYER-LIPID MEMBRANES;
PROTEIN-STRUCTURE DETERMINATION; NUCLEAR-MAGNETIC-RESONANCE; ANTHRAX
PROTECTIVE ANTIGEN; MOLECULAR-WEIGHT PROTEINS; LANGMUIR-BLODGETT-FILMS;
CYTOCHROME-C-OXIDASE; DEPENDENT K+ CHANNEL
C1 [Robertson, Joseph W. F.; Kasianowicz, John J.] NIST, Phys Measurement Lab, Gaithersburg, MD 20899 USA.
[Banerjee, Soojay] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20824 USA.
RP Robertson, JWF (reprint author), NIST, Phys Measurement Lab, Gaithersburg, MD 20899 USA.
EM joseph.robertson@nist.gov
NR 412
TC 23
Z9 26
U1 4
U2 61
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
EI 1520-6890
J9 CHEM REV
JI Chem. Rev.
PD DEC
PY 2012
VL 112
IS 12
BP 6227
EP 6249
DI 10.1021/cr300317z
PG 23
WC Chemistry, Multidisciplinary
SC Chemistry
GA 051JG
UT WOS:000312121900003
PM 23153067
ER
PT J
AU Nestorovich, EM
Bezrukov, SM
AF Nestorovich, Ekaterina M.
Bezrukov, Sergey M.
TI Obstructing Toxin Pathways by Targeted Pore Blockage
SO CHEMICAL REVIEWS
LA English
DT Review
ID PLANAR LIPID-BILAYERS; PERFRINGENS EPSILON-TOXIN; BOTULINUM C2 TOXIN;
CHOLESTEROL-DEPENDENT CYTOLYSIN; UNION-OF-PHARMACOLOGY; STAPHYLOCOCCAL
ALPHA-TOXIN; ANTHRAX PROTECTIVE ANTIGEN; INFLUENZA-A VIRUS;
VIBRIO-CHOLERAE CYTOLYSIN; CHANNEL-FORMING DOMAIN
C1 [Nestorovich, Ekaterina M.] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA.
[Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
RP Bezrukov, SM (reprint author), NICHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
EM NESTOROVICH@cua.edu; BEZRUKOS@mail.nih.gov
FU Catholic University of America; NIH, Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX E.M.N.'s research is supported by startup funds from The Catholic
University of America. S.M.B.'s research is supported by the Intramural
Research Program of the NIH, Eunice Kennedy Shriver National Institute
of Child Health and Human Development.
NR 595
TC 17
Z9 17
U1 1
U2 41
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
EI 1520-6890
J9 CHEM REV
JI Chem. Rev.
PD DEC
PY 2012
VL 112
IS 12
BP 6388
EP 6430
DI 10.1021/cr300141q
PG 43
WC Chemistry, Multidisciplinary
SC Chemistry
GA 051JG
UT WOS:000312121900010
PM 23057504
ER
PT J
AU Reiner, JE
Balijepalli, A
Robertson, JWF
Campbell, J
Suehle, J
Kasianowicz, JJ
AF Reiner, Joseph E.
Balijepalli, Arvind
Robertson, Joseph W. F.
Campbell, Jason
Suehle, John
Kasianowicz, John J.
TI Disease Detection and Management via Single Nanopore-Based Sensors
SO CHEMICAL REVIEWS
LA English
DT Review
ID SOLID-STATE NANOPORES; MOLECULE FORCE-SPECTROSCOPY; OPTICAL-ROTATORY
DISPERSION; AUREUS ALPHA-HEMOLYSIN; ANTHRACIS LETHAL TOXIN; DNA HAIRPIN
MOLECULES; NANOMETER-SCALE PORE; ION CHANNELS; POLYMER TRANSLOCATION;
CIRCULAR-DICHROISM
C1 [Reiner, Joseph E.] Virginia Commonwealth Univ, Dept Phys, Richmond, VA 23284 USA.
[Balijepalli, Arvind; Robertson, Joseph W. F.; Campbell, Jason; Suehle, John; Kasianowicz, John J.] NIST, Phys Measurement Lab, Gaithersburg, MD 20899 USA.
[Balijepalli, Arvind] NHLBI, Lab Computat Biol, Rockville, MD 20852 USA.
RP Reiner, JE (reprint author), Virginia Commonwealth Univ, Dept Phys, 701 W Grace St, Richmond, VA 23284 USA.
EM jereiner@vcu.edu
RI Reiner, Joseph/B-7893-2013;
OI Reiner, Joseph/0000-0002-1056-8703
NR 274
TC 84
Z9 84
U1 13
U2 155
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
EI 1520-6890
J9 CHEM REV
JI Chem. Rev.
PD DEC
PY 2012
VL 112
IS 12
BP 6431
EP 6451
DI 10.1021/cr300381m
PG 21
WC Chemistry, Multidisciplinary
SC Chemistry
GA 051JG
UT WOS:000312121900011
PM 23157510
ER
PT J
AU Dibble, CT
Shimbo, D
Barr, G
Bagiella, E
Chahal, H
Ventetuolo, CE
Herrington, DM
Lima, JAC
Bluemke, DA
Kawut, SM
AF Dibble, Christopher T.
Shimbo, Daichi
Barr, Graham
Bagiella, Emilia
Chahal, Harjit
Ventetuolo, Corey E.
Herrington, David M.
Lima, Joao A. C.
Bluemke, David A.
Kawut, Steven M.
TI Brachial Artery Diameter and the Right Ventricle The Multi-Ethnic Study
of Atherosclerosis-Right Ventricle Study
SO CHEST
LA English
DT Article
ID FLOW-MEDIATED DILATION; ENDOTHELIUM-DEPENDENT VASODILATION; INCIDENT
CARDIOVASCULAR EVENTS; MESA-RIGHT VENTRICLE; CORONARY-ARTERIES;
OLDER-ADULTS; DYSFUNCTION; HYPERTENSION; RISK; DISEASE
AB Background: Endothelial dysfunction is associated with left ventricular morphology and long-term cardiovascular outcomes. The purpose of this study was to assess the relationship between both baseline brachial artery diameter and peripheral endothelial function (assessed by brachial artery ultrasonography) and right ventricular (RV) mass, RV end-diastolic volume (RVEDV), and RV ejection fraction (RVEF).
Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI and brachial artery ultrasonography on participants without clinical cardiovascular disease. Baseline brachial artery diameter and flow-mediated dilation were assessed.
Results: The mean age was 60.9 years, and 49.4% of subjects were men (n = 2,425). In adjusted models, larger brachial artery diameter was strongly associated with greater RV mass (beta = 0.55 g, P < .001), larger RVEDV (beta = 3.99 mL, P < .001), and decreased RVEF (beta = -0.46%, P = .03). These relationships persisted after further adjustment for the respective left ventricular parameters. Flow-mediated dilation was not associated with RV mass or RVEF and was only weakly associated with RVEDV.
Conclusions: Brachial artery diameter is associated with greater RV mass and RVEDV, as well as lower RVEF. Changes in the systemic arterial circulation may have pathophysiologic links to pulmonary vascular dysfunction or abnormalities in RV perfusion. CHEST 2012; 142(6):1399-1405
C1 [Dibble, Christopher T.; Kawut, Steven M.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Dibble, Christopher T.; Kawut, Steven M.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Kawut, Steven M.] Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Shimbo, Daichi; Barr, Graham] Columbia Univ, Mailman Sch Publ Hlth, Dept Med, New York, NY USA.
[Barr, Graham] Columbia Univ, Coll Phys & Surg, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Bagiella, Emilia] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA.
[Chahal, Harjit; Lima, Joao A. C.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD USA.
[Ventetuolo, Corey E.] Brown Univ, Alpert Med Sch, Dept Med, Providence, RI 02912 USA.
[Herrington, David M.] Wake Forest Univ Hlth Sci, Dept Med, Winston Salem, NC USA.
RP Kawut, SM (reprint author), Univ Penn, Perelman Sch Med, Dept Med, 423 Guardian Dr,Room 718, Philadelphia, PA 19104 USA.
EM kawut@upenn.edu
OI Ventetuolo, Corey /0000-0002-4223-4775; Bluemke,
David/0000-0002-8323-8086
FU National Institutes of Health [HL086719, HL103844, HL077612,
N01-HC95159, HC95165, HL007891]; Intramural Research Program of the
National Institutes of Health (National Institute of Biomedical Imaging
and Bioengineering); Pfizer, Inc
FX This work was supported by the National Institutes of Health [Grants and
Contracts HL086719, HL103844, HL077612, N01-HC95159 through HC95165, and
HL007891]. This research was also supported (in part) by the Intramural
Research Program of the National Institutes of Health (National
Institute of Biomedical Imaging and Bioengineering).; The authors have
reported to CHEST the following conflicts of interest: Dr Ventetuolo has
received grant funding from Pfizer, Inc and has served on advisory
boards for Actelion Pharmaceuticals Ltd, Gilead, and United Therapeutics
Corp. Drs Dibble, Shimbo, Barr, Bagiella, Chahal, Herrington, Lima,
Bluemke, and Kawut have reported that no potential conflicts of interest
exist with any companies/organizations whose products or services may be
discussed in this article.
NR 46
TC 4
Z9 4
U1 0
U2 5
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD DEC
PY 2012
VL 142
IS 6
BP 1399
EP 1405
DI 10.1378/chest.12-0028
PG 7
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 053PA
UT WOS:000312283800012
PM 22661452
ER
PT J
AU Gupta, J
Mitra, N
Kanetsky, PA
Devaney, J
Wing, MR
Reilly, M
Shah, VO
Balakrishnan, VS
Guzman, NJ
Girndt, M
Periera, BG
Feldman, HI
Kusek, JW
Joffe, MM
Raj, DS
AF Gupta, Jayanta
Mitra, Nandita
Kanetsky, Peter A.
Devaney, Joe
Wing, Maria R.
Reilly, Muredach
Shah, Vallabh O.
Balakrishnan, Vaidyanathapura S.
Guzman, Nicolas J.
Girndt, Matthias
Periera, Brian G.
Feldman, Harold I.
Kusek, John W.
Joffe, Marshall M.
Raj, Dominic S.
CA CRIC Study Investigators
TI Association between Albuminuria, Kidney Function, and Inflammatory
Biomarker Profile in CKD in CRIC
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CHRONIC-RENAL-FAILURE; C-REACTIVE PROTEIN; HEMODIALYSIS-PATIENTS;
CARDIOVASCULAR EVENTS; DIALYSIS PATIENTS; SERUM-ALBUMIN; CYSTATIN-C;
TNF-ALPHA; DISEASE; RISK
AB Background and objectives Increased risk of mortality in patients with CKD has been attributed to inflammation. However, the association between kidney function, albuminuria, and biomarkers of inflammation has not been examined in a large cohort of CKD patients.
Design, setting, participants, & measurements This study measured the plasma levels of IL-1 beta, IL-1 receptor antagonist (IL-1RA), IL-6, TNF-alpha, TGF-beta, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and serum albumin in 3939 participants enrolled in the Chronic Renal Insufficiency Cohort study between June 2003 and September 2008. An inflammation score was established based on plasma levels of IL-1 beta, IL-6, TNF-alpha, hs-CRP, and fibrinogen. Estimated GFR (eGFR) and serum cystatin C were used as measures of kidney function. Albuminuria was quantitated by urine albumin to creatinine ratio (UACR).
Results Plasma levels of IL-1 beta, IL-IRA, IL-6, TNF-alpha, hs-CRP, and fibrinogen were higher among participants with lower levels of eGFR. Inflammation score was higher among those with lower eGFR and higher UACR. In regression analysis adjusted for multiple covariates, eGFR, cystatin C, and UACR were strongly associated with fibrinogen, serum albumin, IL-6, and TNF-alpha. Each unit increase in eGFR, cystatin C, and UACR was associated with a -1.2% (95% confidence interval, -1.4, -1), 64.9% (56.8, 73.3) and 0.6% (0.4, 0.8) change in IL-6, respectively (P<0.001).
Conclusions Biomarkers of inflammation were inversely associated with measures of kidney function and positively with albuminuria. Clin J Am Soc Nephrol 7: 1938-1946, 2012. doi: 10.2215/CJN.03500412
C1 [Raj, Dominic S.] George Washington Univ, Sch Med, Med Fac Associates, Div Renal Dis & Hypertens, Washington, DC 20037 USA.
[Gupta, Jayanta; Mitra, Nandita; Kanetsky, Peter A.; Reilly, Muredach; Feldman, Harold I.; Joffe, Marshall M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Shah, Vallabh O.] Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA.
[Balakrishnan, Vaidyanathapura S.; Periera, Brian G.] Tufts New England Sch Med, Boston, MA USA.
[Girndt, Matthias] Univ Halle Wittenberg, Dept Med 2, Halle, Germany.
[Kusek, John W.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Raj, DS (reprint author), George Washington Univ, Sch Med, Med Fac Associates, Div Renal Dis & Hypertens, 2150 Penn Ave NW, Washington, DC 20037 USA.
EM draj@mfa.gwu.edu
OI Girndt, Matthias/0000-0003-2823-0847
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[R01 DK073665-01A1, R01-DK071224, U01DK060990, U01DK060984, U01DK061022,
U01DK061021, U01DK061028, U01DK060980, U01DK060963, U01DK060902];
University of Pennsylvania CTRC CTSA [UL1 RR-024134]; Johns Hopkins
University [UL1 RR-025005]; University of Maryland GCRC [M01 RR-16500];
National Center for Advancing Translational Sciences component of the
National Institutes of Health and NIH road map for Medical Research
[UL1TR000439]; Michigan Institute for Clinical and Health Research
[UL1RR024986]; University of Illinois at Chicago CTSA [UL1RR029879];
Clinical and Translational Research, Education, and Commercialization
Project; Kaiser NIH/NCRR UCSF-CTSI [UL1RR-024131]
FX This study is supported in part by grants from the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) awarded to D.R. (R01
DK073665-01A1) and M.R. (R01-DK071224). Funding for the CRIC study was
obtained under a cooperative agreement from the NIDDK (U01DK060990,
U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980,
U01DK060963, and U01DK060902). In addition, this work was supported in
part by the University of Pennsylvania CTRC CTSA (UL1 RR-024134), Johns
Hopkins University (UL1 RR-025005), University of Maryland GCRC (M01
RR-16500), Clinical and Translational Science Collaborative of Cleveland
(UL1TR000439 from the National Center for Advancing Translational
Sciences component of the National Institutes of Health and NIH road map
for Medical Research), Michigan Institute for Clinical and Health
Research (UL1RR024986), University of Illinois at Chicago CTSA
(UL1RR029879), The Clinical and Translational Research, Education, and
Commercialization Project, and Kaiser NIH/NCRR UCSF-CTSI (UL1RR-024131).
NR 53
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Z9 55
U1 0
U2 11
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD DEC
PY 2012
VL 7
IS 12
BP 1938
EP 1946
DI 10.2215/CJN.03500412
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 051FK
UT WOS:000312111400006
PM 23024164
ER
PT J
AU Atkinson, EC
Hadigan, C
AF Atkinson, Emily C.
Hadigan, Colleen
TI Management of dyslipidemia in HIV infection
SO CLINICAL LIPIDOLOGY
LA English
DT Editorial Material
DE antiretroviral therapy; drug interaction; dyslipidemia; HIV; HMG-CoA
reductase; inhibitor; treatment
ID COMBINATION ANTIRETROVIRAL THERAPY; MYOCARDIAL-INFARCTION; RISK;
CHOLESTEROL; FENOFIBRATE; TRIALS; LIPIDS
C1 [Atkinson, Emily C.; Hadigan, Colleen] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Hadigan, C (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM hadiganc@niaid.nih.gov
NR 20
TC 0
Z9 0
U1 0
U2 1
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1758-4299
J9 CLIN LIPIDOL
JI Clin. Lipidol.
PD DEC
PY 2012
VL 7
IS 6
BP 603
EP 606
DI 10.2217/CLP.12.63
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 052YT
UT WOS:000312237300002
ER
PT J
AU Regard, JB
Zhong, ZD
Williams, BO
Yang, YZ
AF Regard, Jean B.
Zhong, Zhendong
Williams, Bart O.
Yang, Yingzi
TI Wnt Signaling in Bone Development and Disease: Making Stronger Bone with
Wnts
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID RECEPTOR-RELATED PROTEIN-5; MESENCHYMAL STEM-CELLS; FRIZZLED-RELATED
PROTEIN-1; SYNOVIAL JOINT FORMATION; BETA-CATENIN; IN-VIVO;
MULTIPLE-MYELOMA; CHONDROCYTE DIFFERENTIATION; OSTEOGENIC
DIFFERENTIATION; SHEAR-STRESS
AB The skeleton as an organ is widely distributed throughout the entire vertebrate body. Wnt signaling has emerged to play major roles in almost all aspects of skeletal development and homeostasis. Because abnormal Wnt signaling causes various human skeletal diseases, Wnt signaling has become a focal point of intensive studies in skeletal development and disease. As a result, promising effective therapeutic agents for bone diseases are being developed by targeting the Wnt signaling pathway. Understanding the functional mechanisms of Wnt signaling in skeletal biology and diseases highlights how basic and clinical studies can stimulate each other to push a quick and productive advancement of the entire field. Here we review the current understanding of Wnt signaling in critical aspects of skeletal biology such as bone development, remodeling, mechanotransduction, and fracture healing. We took special efforts to place fundamentally important discoveries in the context of human skeletal diseases.
C1 [Regard, Jean B.; Yang, Yingzi] NHGRI, NIH, Bethesda, MD 20892 USA.
[Zhong, Zhendong; Williams, Bart O.] Van Andel Res Inst, Ctr Skeletal Dis Res, Grand Rapids, MI 49503 USA.
RP Yang, YZ (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM yingzi@mail.nih.gov
RI Williams, Bart/A-3539-2013; Zhong, Zhendong/K-5223-2013
OI Williams, Bart/0000-0002-5261-5301;
FU Division of Intramural Research of the National Institutes of Health,
DHHS; NIH [R01AR053293]
FX We thank Darryl Leja and Julia Fekecs for preparing the figures. This
work is supported by the Division of Intramural Research of the National
Institutes of Health, DHHS, to J.B.R. and Y.Y. and NIH R01AR053293 to
B.O.W. and Z.Z.
NR 125
TC 29
Z9 29
U1 0
U2 20
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 DEC
PY 2012
VL 4
IS 12
AR a007997
DI 10.1101/cshperspect.a007997
PG 17
WC Cell Biology
SC Cell Biology
GA 054SL
UT WOS:000312363400003
ER
PT J
AU Sack, MN
Finkel, T
AF Sack, Michael N.
Finkel, Toren
TI Mitochondrial Metabolism, Sirtuins, and Aging
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID REGULATES INSULIN-SECRETION; FATTY-ACID OXIDATION; PANCREATIC
BETA-CELLS; PERMEABILITY TRANSITION; LYSINE ACETYLATION; SIRT3-MEDIATED
DEACETYLATION; PROTEIN HYPERACETYLATION; SIRT3 DEACETYLATES; MAMMALIAN
SIR2; UREA CYCLE
AB The sirtuins are a family of proteins that act predominantly as nicotinamide adenine dinucleotide (NAD)-dependent deacetylases. In mammals seven sirtuin family members exist, including three members, Sirt3, Sirt4, and Sirt5, that localize exclusively within the mitochondria. Although originally linked to life-span regulation in simple organisms, this family of proteins appears to have various and diverse functions in higher organisms. One particular property that is reviewed here is the regulation of mitochondrial number, turnover, and activity by various mitochondrial and nonmitochondrial sirtuins. An emerging consensus from these recent studies is that sirtuins may act as metabolic sensors, using intracellular metabolites such as NAD and short-chain carbon fragments such as acetyl coenzyme A to modulate mitochondrial function to match nutrient supply.
C1 [Sack, Michael N.; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM finkelt@nih.gov
NR 64
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Z9 38
U1 1
U2 25
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 DEC
PY 2012
VL 4
IS 12
AR a013102
DI 10.1101/cshperspect.a013102
PG 10
WC Cell Biology
SC Cell Biology
GA 054SL
UT WOS:000312363400016
ER
PT J
AU Cherkaoui-Malki, M
Surapureddi, S
El Hajj, HI
Vamecq, J
Andreoletti, P
AF Cherkaoui-Malki, Mustapha
Surapureddi, Sailesh
El Hajj, Hammam I.
Vamecq, Joseph
Andreoletti, Pierre
TI Hepatic Steatosis and Peroxisomal Fatty Acid Beta-oxidation
SO CURRENT DRUG METABOLISM
LA English
DT Review
DE ACOX1; Coactivators; hepatic Steatosis; hepatocarcinogenesis; MED1;
NASH; beta-oxidation; Peroxisome; Peroxisomes proliferation; PPARalpha
ID PROLIFERATOR-ACTIVATED-RECEPTOR; ACYL-COA OXIDASE; RAT-LIVER
PEROXISOMES; TUMOR-NECROSIS-FACTOR; PALMITOYLTRANSFERASE I GENE; CARRIER
PROTEIN-X; THIOLASE-B GENE; PPAR-ALPHA; BINDING-PROTEIN; ENOYL-COA
AB Three subhepatocellular compartments concur for fatty acids degradation including omega-oxidation in endoplasmic reticulum and beta-oxidation in both mitochondria and peroxisomes. Deficits affecting the peroxisomal physiology may be associated with multiple metabolic disturbances. Nowadays, a growing body of evidence underlines the key role of peroxisomal beta-oxidation in the sensing of lipid metabolism through the production/degradation of some essential metabolites. Lessons from several mice models strengthen the link between fatty acid beta-oxidation in peroxisomes and the nuclear hormone receptor Peroxisome Proliferator-Activated Receptor (PPAR)-alpha with an additional level of coregualtor complexity, which couples regulation of body energetic balance and hepatic caloric flux to functional peroxisome status. Here, we review key determinants of disrupted peroxisomal beta-oxidation pathway, which in liver promotes hepatic steatosis and hepatocarcinogenesis.
C1 [Cherkaoui-Malki, Mustapha; El Hajj, Hammam I.; Andreoletti, Pierre] Univ Bourgogne, EA 7270, BioperoxIL, Lab Biochim Peroxysome Inflammat & Metab Lipid, F-21000 Dijon, France.
[Surapureddi, Sailesh] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Vamecq, Joseph] CHRU Lille, Dept Biochem & Mol Biol, Lab Hormonol Metab Nutr & Oncol, Ctr Biol & Pathol Pierre Marie Degand, F-59037 Lille, France.
RP Cherkaoui-Malki, M (reprint author), Univ Bourgogne, EA 7270, BioperoxIL, Lab Biochim Peroxysome Inflammat & Metab Lipid, 6 Bd Gabriel, F-21000 Dijon, France.
EM malki@u-bourgogne.fr
OI Andreoletti, Pierre/0000-0003-2118-7858
FU Institut national de la sante et de la recherche medicale; Regional
Council of Burgundy; Ministere de l'enseignement superieur et de la
recherche; Centre National de la Recherche Scientifique; Intramural
Research Program of NIH, National Institute of Environmental Health
Sciences, NIH intramural project [Z01ES02124]
FX Financial Supports by a grants from the Institut national de la sante et
de la recherche medicale, the Regional Council of Burgundy, the
Ministere de l'enseignement superieur et de la recherche, The Centre
National de la Recherche Scientifique and the Intramural Research
Program of NIH, National Institute of Environmental Health Sciences, NIH
intramural project number Z01ES02124.
NR 155
TC 17
Z9 18
U1 1
U2 19
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-2002
J9 CURR DRUG METAB
JI Curr. Drug Metab.
PD DEC
PY 2012
VL 13
IS 10
BP 1412
EP 1421
PG 10
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 052NC
UT WOS:000312203600006
PM 22978396
ER
PT J
AU Thompson, MD
Thompson, HJ
AF Thompson, Matthew D.
Thompson, Henry J.
TI A Systems Pharmacokinetic and Pharmacodynamic Approach to Identify
Opportunities and Pitfalls in Energy Stress-Mediated Chemoprevention:
The Use of Metformin and Other Biguanides
SO CURRENT DRUG TARGETS
LA English
DT Review
DE Biguanides; cancer prevention; pharmacokinetics; pharmacodynamics;
metformin
ID ORGANIC CATION TRANSPORTERS; ACTIVATED PROTEIN-KINASE; PREVENTION TRIAL
SELECT; CANCER PREVENTION; BREAST-CANCER; IN-VITRO; GENETIC-VARIATION;
DRUG DEVELOPMENT; VITAMIN-E; TISSUE DISTRIBUTION
AB Metformin, a widely used anti-hyperglycemic drug in the biguanide class, is currently under investigation for the prevention of cancer. Surprisingly however, considering the time and cost of clinical chemoprevention trials and the current scrutiny of cancer chemoprevention, limited attention has been given to integrating available data, identifying the subpopulations most likely to benefit, or to quantitatively understanding the potential pitfalls of biguanide chemoprevention. Herein, a physiologically-based pharmacokinetic (PBPK) and pharmacodynamic framework is proposed for integrating information on physicochemical, cell-based, animal, and human studies of various biguanides to identify gaps in knowledge and to build a systems model that may facilitate the planning of randomized cancer chemoprevention trials of metformin.
C1 [Thompson, Henry J.] Colorado State Univ, Canc Prevent Lab, Ft Collins, CO 80523 USA.
[Thompson, Matthew D.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
RP Thompson, HJ (reprint author), Colorado State Univ, Canc Prevent Lab, 1173 Campus Delivery, Ft Collins, CO 80523 USA.
EM henry.thompson@colostate.edu
FU National Cancer Institute [CA52626]
FX This work was supported by PHS grant CA52626 from the National Cancer
Institute (HJT). MDT is a Cancer Prevention Fellow in the Cancer
Prevention Fellowship Program, National Cancer Institute, Bethesda, MD.
NR 87
TC 2
Z9 2
U1 0
U2 13
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-4501
J9 CURR DRUG TARGETS
JI Curr. Drug Targets
PD DEC
PY 2012
VL 13
IS 14
BP 1876
EP 1884
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 052MC
UT WOS:000312200900018
PM 23140331
ER
PT J
AU Arana, ME
Kerns, RT
Wharey, L
Gerrish, KE
Bushel, PR
Kunkel, TA
AF Arana, Mercedes E.
Kerns, Robnet T.
Wharey, Laura
Gerrish, Kevin E.
Bushel, Pierre R.
Kunkel, Thomas A.
TI Transcriptional responses to loss of RNase H2 in Saccharomyces
cerevisiae
SO DNA REPAIR
LA English
DT Article
DE RNase H2; Ribonucleotides; Genome instability; R-loops; Stress response
ID AICARDI-GOUTIERES-SYNDROME; REPEAT-CONTAINING RNA; R-LOOP FORMATION;
YEAST REPLICATIVE POLYMERASES; OKAZAKI FRAGMENT MATURATION; DNA
TOPOISOMERASE-I; RIBONUCLEOTIDE INCORPORATION; SUBSTRATE-SPECIFICITY;
EXCISION-REPAIR; INSTABILITY
AB We report here the transcriptional responses in Saccharomyces cerevisiae to deletion of the RNH201 gene encoding the catalytic subunit of RNase H2. Deleting RNH201 alters RNA expression of 349 genes by >= 1.5-fold (q-value <0.01), of which 123 are upregulated and 226 are downregulated. Differentially expressed genes (DEGs) include those involved in stress responses and genome maintenance, consistent with a role for RNase H2 in removing ribonucleotides incorporated into DNA during replication. Upregulated genes include several that encode subunits of RNA polymerases land Ill, and genes involved in ribosomal RNA processing, ribosomal biogenesis and tRNA modification and processing, supporting a role for RNase H2 in resolving R-loops formed during transcription of rRNA and tRNA genes. A role in R-loop resolution is further suggested by a higher average GC-content proximal to the transcription start site of downregulated as compared to upregulated genes. Several DEGs are involved in telomere maintenance, supporting a role for RNase H2 in resolving RNA-DNA hybrids formed at telomeres. A large number of DEGs encode nucleases, helicases and genes involved in response to dsRNA viruses, observations that could be relevant to the nucleic acid species that elicit an innate immune response in RNase H2-defective humans. Published by Elsevier B.V.
C1 [Arana, Mercedes E.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Arana, Mercedes E.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Kerns, Robnet T.; Bushel, Pierre R.] NIEHS, Microarray & Genome Informat Grp, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Kerns, Robnet T.] NIEHS, SRA Int, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Wharey, Laura; Gerrish, Kevin E.] NIEHS, Microarray Core Facil, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Bushel, Pierre R.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
FU Division of Intramural Research of the NIH, NIEHS [Z01 ES065070, Z01
ES102345-04]
FX We thank Keith Shockley and Jessica Williams for helpful comments on the
manuscript. This work was supported by Projects Z01 ES065070 (to T.A.K.)
and Z01 ES102345-04 (to P.R.B.) from the Division of Intramural Research
of the NIH, NIEHS.
NR 61
TC 14
Z9 14
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD DEC 1
PY 2012
VL 11
IS 12
BP 933
EP 941
DI 10.1016/j.dnarep.2012.09.006
PG 9
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 052YO
UT WOS:000312236800002
PM 23079308
ER
PT J
AU So, R
Sasai, H
Matsuo, T
Tsujimoto, T
Eto, M
Saotome, K
Tanaka, K
AF So, R.
Sasai, H.
Matsuo, T.
Tsujimoto, T.
Eto, M.
Saotome, K.
Tanaka, K.
TI Multiple-slice magnetic resonance imaging can detect visceral adipose
tissue reduction more accurately than single-slice imaging
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE multiple-slice image; single-slice image; weight-loss detecting; MRI
ID COMPUTED-TOMOGRAPHY; MEASUREMENT SITE; JAPANESE MEN; OBESE WOMEN;
WEIGHT-LOSS; FAT; VOLUMES; DISEASE
AB BACKGROUND/OBJECTIVE: Imaging methods by magnetic resonance imaging are being increasingly used to quantify visceral adipose tissue (VAT), but there is no clear consensus as to a standardized protocol. We compared the ability of two commonly used imaging protocols (multiple slice versus single slice) to detect changes in VAT with diet or exercise.
SUBJECTS/METHODS: We utilized data from the participants who completed our diet (n=22) or exercise (n=35) based weight-loss interventions. The intervention mainly comprised of weekly dietary modification sessions or aerobic exercise sessions over 12 weeks. Multiple-slice images obtained from T9 to S1 and a single-slice image at L4-L5 were compared using the effect size of the VAT change. In addition, we calculated the sample size needed to compare the two imaging protocols' ability to detect significant changes in VAT.
RESULTS: VAT and subcutaneous adipose tissue volumes and areas, and other anthropometry decreased significantly after both the diet and exercise interventions. For VAT, a single-slice image had a lower effect size (diet: 1.23; exercise: 0.49) than the multiple-slice images (diet: 1.81; exercise: 0.90). The sample size required for multiple slice was substantially lower than for the single-slice with both weight-loss interventions.
CONCLUSIONS: The different image protocols may lead to different results in relative VAT changes. Furthermore, single-slice imaging required a substantially larger sample size than multiple-slice imaging, and for researchers to detect smaller changes in VAT with single-slice imaging, a larger sample size would be needed. Thus, multiple-slice imaging has advantages for assessing VAT change in future clinical research. European Journal of Clinical Nutrition (2012) 66, 1351-1355; doi:10.1038/ejcn.2012.147; published online 24 October 2012
C1 [So, R.; Matsuo, T.; Tsujimoto, T.] Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058577, Japan.
[So, R.] Japan Soc Promot Sci, Tokyo, Japan.
[Sasai, H.] NIH, JSPS, Bethesda, MD 20892 USA.
[Eto, M.; Tanaka, K.] Univ Tsukuba, Fac Hlth & Sport Sci, Tsukuba, Ibaraki 3058577, Japan.
[Saotome, K.] Univ Tsukuba, Ctr Cybern Res, Tsukuba, Ibaraki 3058577, Japan.
RP So, R (reprint author), Univ Tsukuba, Grad Sch Comprehens Human Sci, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058577, Japan.
EM rina@stat.taiiku.tsukuba.ac.jp
OI Sasai, Hiroyuki/0000-0001-8120-6163
FU 'Center for Cybernics Research-World Leading Human-Assistive Technology
Supporting a Long-Lived and Healthy Society' through the 'Funding
Program for World-Leading Innovative R&D on Science and Technology
(FIRST Program)'; Council for Science and Technology Policy; Japan
Society for the Promotion of Science [23650429]
FX This study was supported in part by the 'Center for Cybernics
Research-World Leading Human-Assistive Technology Supporting a
Long-Lived and Healthy Society' granted through the 'Funding Program for
World-Leading Innovative R&D on Science and Technology (FIRST Program)'
initiated by the Council for Science and Technology Policy and by a
Grant-in-Aid for Exploratory Research (no. 23650429) from the Japan
Society for the Promotion of Science.
NR 20
TC 13
Z9 13
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0954-3007
J9 EUR J CLIN NUTR
JI Eur. J. Clin. Nutr.
PD DEC
PY 2012
VL 66
IS 12
BP 1351
EP 1355
DI 10.1038/ejcn.2012.147
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 050VX
UT WOS:000312083600013
PM 23093345
ER
PT J
AU Sambataro, F
Safrin, M
Lemaitre, HS
Steele, SU
Das, SB
Callicott, JH
Weinberger, DR
Mattay, VS
AF Sambataro, Fabio
Safrin, Martin
Lemaitre, Herve S.
Steele, Sonya U.
Das, Saumitra B.
Callicott, Joseph H.
Weinberger, Daniel R.
Mattay, Venkata S.
TI Normal aging modulates prefrontoparietal networks underlying multiple
memory processes
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE aging; episodic memory; functional magnetic resonance imaging; human;
working memory
ID AGE-RELATED-CHANGES; SPATIAL WORKING-MEMORY; ADULT LIFE-SPAN;
DECLARATIVE MEMORY; PREFRONTAL CORTEX; EPISODIC MEMORY;
HEMISPHERIC-ASYMMETRY; NEURAL MECHANISMS; BRAIN ACTIVATION; PARIETAL
CORTEX
AB A functional decline of brain regions underlying memory processing represents a hallmark of cognitive aging. Although a rich literature documents age-related differences in several memory domains, the effect of aging on networks that underlie multiple memory processes has been relatively unexplored. Here we used functional magnetic resonance imaging during working memory and incidental episodic encoding memory to investigate patterns of age-related differences in activity and functional covariance patterns common across multiple memory domains. Relative to younger subjects, older subjects showed increased activation in left dorso-lateral prefrontal cortex along with decreased deactivation in the posterior cingulate. Older subjects showed greater functional covariance during both memory tasks in a set of regions that included a positive prefronto-parietal-occipital network as well as a negative network that spanned the default mode regions. These findings suggest that the memory process-invariant recruitment of brain regions within prefronto-parietal-occipital network increases with aging. Our results are in line with the dedifferentiation hypothesis of neurocognitive aging, thereby suggesting a decreased specialization of the brain networks supporting different memory networks.
C1 [Sambataro, Fabio] Ist Italiano Tecnol, Brain Ctr Motor & Social Cognit, I-43100 Parma, Italy.
[Sambataro, Fabio; Safrin, Martin; Lemaitre, Herve S.; Steele, Sonya U.; Das, Saumitra B.; Callicott, Joseph H.; Weinberger, Daniel R.; Mattay, Venkata S.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Weinberger, Daniel R.; Mattay, Venkata S.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
RP Sambataro, F (reprint author), Ist Italiano Tecnol, Brain Ctr Motor & Social Cognit, I-43100 Parma, Italy.
EM fabio.sambataro@iit.it; anand.mattay@libd.org
RI Sambataro, Fabio/E-3426-2010; Callicott, Joseph/C-9102-2009;
OI Sambataro, Fabio/0000-0003-2102-416X; Callicott,
Joseph/0000-0003-1298-3334; Lemaitre, Herve/0000-0002-5952-076X
FU National Institute of Mental Health, NIH, Bethesda, MD, USA
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, NIH, Bethesda, MD 20892, USA. None
of the authors has any actual or potential conflicts of interest.
NR 76
TC 16
Z9 17
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD DEC
PY 2012
VL 36
IS 11
BP 3559
EP 3567
DI 10.1111/j.1460-9568.2012.08254.x
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 051VT
UT WOS:000312156700012
PM 22909094
ER
PT J
AU Almeida, LO
Goto, RN
Pestana, CR
Uyemura, SA
Gutkind, S
Curti, C
Leopoldino, AM
AF Almeida, Luciana O.
Goto, Renata N.
Pestana, Cezar R.
Uyemura, Sergio A.
Gutkind, Silvio
Curti, Carlos
Leopoldino, Andreia M.
TI SET overexpression decreases cell detoxification efficiency: ALDH2 and
GSTP1 are downregulated, DDR is impaired and DNA damage accumulates
SO FEBS JOURNAL
LA English
DT Article
DE ALDH2; BRCA2; cisplatin; ethanol; GSTP1
ID PROTEIN PHOSPHATASE 2A; GENETIC POLYMORPHISMS; CANCER-CELLS; HEAD;
EXPRESSION; CARCINOMA; TUMOR; PHOSPHORYLATION; SET/TAF-1-BETA;
TRANSCRIPTION
AB Alcohol and tobacco consumption are risk factors for head and neck squamous cell carcinoma (HNSCC). Aldehyde dehydrogenase 2 (ALDH2) and glutathione Stransferase pi 1 (GSTP1) are important enzymes for cellular detoxification and low efficiencies are implicated in cancer. We assessed the potential role of SET protein overexpression, a histone acetylation modulator accumulated in HNSCC, in gene regulation and protein activity of ALDH2 and GSTP1. SET was knocked down in HN13, HN12 and Cal27, and overexpressed in HEK293 cells; ethanol and cisplatin were the chemical agents. Cells with SET overexpression (HEK293/SET, HN13 and HN12) showed lower ALDH2 and GSTP1 mRNA levels and trichostatin A increased them (real-time PCR). Ethanol upregulated GSTP1 and ALDH2 mRNAs, whereas cisplatin upregulated GSTP1 in HEK293 cells. SET-chromatin binding revealed SET interaction with ALDH2 and GSTP1 promoters, specifically via SET NAP domain; ethanol and cisplatin abolished SET binding. ALDH2 and GSTP1 efficiency was assessed by enzymatic and comet assay. A lower ALDH2 activity was associated with greater DNA damage (tail intensity) in HEK293/SET compared with HEK293 cells, whereas HN13/siSET showed ALDH2 activity higher than HN13 cells. HN13/siSET cells showed increased tail intensity. Cisplatin-induced DNA damage response showed negative relationship between SET overexpression and BRCA2 recruitment. SET downregulated repair genes ATM, BRCA1 and CHEK2 and upregulated TP53. Cisplatin-induced cell-cycle arrest occurred in G0/G1 and S in HEK293 cells, whereas HEK293/SET showed G2/M stalling. Overall, cisplatin was more cytotoxic for HN13 than HN13/siSET cells. Our data suggest a role for SET in cellular detoxification, DNA damage response and genome integrity.
C1 [Almeida, Luciana O.; Goto, Renata N.; Uyemura, Sergio A.; Leopoldino, Andreia M.] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP, Brazil.
[Pestana, Cezar R.; Curti, Carlos] Univ Sao Paulo, Dept Quim & Fis, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP, Brazil.
[Gutkind, Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RP Leopoldino, AM (reprint author), Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP, Brazil.
EM andreiaml@usp.br
RI Uyemura, Sergio/B-4656-2011; Inov Farmaceutica, Inct/K-2313-2013;
Pestana, Cezar/K-6250-2012; Leopoldino, Andreia/E-9926-2012; Curti,
Carlos/H-6982-2016;
OI Uyemura, Sergio/0000-0001-5505-9817; Leopoldino,
Andreia/0000-0002-8313-4754; Curti, Carlos/0000-0001-8154-5595; Oliveira
de Almeida, Luciana/0000-0002-5342-0434
FU FAPESP [2010/20384-0, 2009/52228-0, 2009/10783-7, 2010/20536-4,
2010/08328-7]; CNPq
FX This work was supported by FAPESP (research grants: 2010/20384-0 and
2009/52228-0; fellowships: 2009/10783-7, 2010/20536-4 and 2010/08328-7)
and CNPq. The authors thank Cristiana Bernadelli Garcia for her
excellent technical assistance.
NR 38
TC 4
Z9 6
U1 0
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD DEC
PY 2012
VL 279
IS 24
BP 4615
EP 4628
DI 10.1111/febs.12047
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 052US
UT WOS:000312224600016
PM 23106910
ER
PT J
AU Lee, SY
Yoon, YH
Kim, SH
Lee, SR
Chu, JM
Kim, SI
Kang, TH
Chung, JW
Larionov, V
Leem, SH
AF Lee, Sang-Yeop
Yoon, Young-Ho
Kim, Si-Hoon
Lee, Se-Ra
Chu, Jeong-Min
Kim, Seung Il
Kang, Tae-Hong
Chung, Jin Woong
Larionov, Vladimir
Leem, Sun-Hee
TI Characterization of the hamster genomic fragment cloned by TAR cloning
technology with interspecific sequence information
SO GENES & GENOMICS
LA English
DT Article
DE Hamster genome; TAR cloning; c14orf4; B1-B2 repeats
ID TRANSFORMATION-ASSOCIATED RECOMBINATION; HUMAN GENE; CLUSTAL-X; YEAST;
DNA; EVOLUTION; ALIGNMENT; SOFTWARE; C14ORF4; REPEAT
AB CHO (Chinese Hamster ovary) cells are widely used for biotechnology and biomedical purposes, and now the EST library database of CHO cells is built. Based on this, the construction of the hamster genome library is under exertion. Though the transformation-associated recombination (TAR) cloning method is accounted as an innovative cloning technology without the construction of the genome library in human and mouse, there has been no trial to isolate the genomic fragment from hamster genome by TAR cloning. In this study, approximately 31 kb of hamster genomic fragment was isolated from the normal human/hamster mono-chromosomal somatic cell line (UV5HL9-5B) using universal hooks of rodent repeats sequence of B1 and B2 by TAR cloning. This fragment was analyzed by bioinformatics tools related to the genome alignment for the similarity analysis among rodent and primate, and was classified into rodents by phylogenetic analysis. One putative gene was found in this region which has homology with the human c14orf4 gene. A zinc finger protein domain was found in the translated hamster ORF. Therefore, we suggest that TAR cloning technique can be applied in CHO cells using mouse genomic information, and it can lead to the establishment of the hamster genome database.
C1 [Lee, Sang-Yeop; Yoon, Young-Ho; Kim, Si-Hoon; Lee, Se-Ra; Kang, Tae-Hong; Chung, Jin Woong; Leem, Sun-Hee] Dong A Univ, Dept Biol Sci, Pusan 604714, South Korea.
[Chu, Jeong-Min] Univ Texas Austin, Dept Biol, Austin, TX 78712 USA.
[Larionov, Vladimir] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
[Kim, Seung Il] Korea Basic Sci Inst, Div Life Sci, Taejon 305806, South Korea.
RP Leem, SH (reprint author), Dong A Univ, Dept Biol Sci, Pusan 604714, South Korea.
EM shleem@dau.ac.kr
FU Basic Science Research Program, through the National Research Foundation
of Korea (NRF); Ministry of Education, Science and Technology (MEST)
[2012-0000481]; Korea Basic Science Institute Program [T32414]
FX This work was supported by the Basic Science Research Program, through
the National Research Foundation of Korea (NRF) funded by the Ministry
of Education, Science and Technology (MEST) (2012-0000481) and was
partially supported by a grant from the Korea Basic Science Institute
Program (grant T32414).
NR 27
TC 0
Z9 0
U1 1
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1976-9571
J9 GENES GENOM
JI Genes Genom.
PD DEC
PY 2012
VL 34
IS 6
BP 647
EP 652
DI 10.1007/s13258-012-0084-y
PG 6
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 055GC
UT WOS:000312402300008
ER
PT J
AU Szanton, SL
Rifkind, JM
Mohanty, JG
Miller, ER
Thorpe, RJ
Nagababu, E
Epel, ES
Zonderman, AB
Evans, MK
AF Szanton, Sarah L.
Rifkind, Joseph M.
Mohanty, Joy G.
Miller, Edgar R., III
Thorpe, Roland J.
Nagababu, Eneka
Epel, Elissa S.
Zonderman, Alan B.
Evans, Michele K.
TI Racial Discrimination Is Associated with a Measure of Red Blood Cell
Oxidative Stress: A Potential Pathway for Racial Health Disparities
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Health disparities; Racial discrimination; Oxidative stress; Accelerated
aging
ID HEME DEGRADATION; PERCEIVED DISCRIMINATION; HEMOGLOBIN; DISEASE; DAMAGE;
PRESSURE; EXPOSURE; STUDENTS; ADULTS
AB There are racial health disparities in many conditions for which oxidative stress is hypothesized to be a precursor. These include cardiovascular disease, diabetes, and premature aging. Small clinical studies suggest that psychological stress may increase oxidative stress. However, confirmation of this association in epidemiological studies has been limited by homogenous populations and unmeasured potential confounders.
We tested the cross-sectional association between self-reported racial discrimination and red blood cell (RBC) oxidative stress in a biracial, socioeconomically heterogeneous population with well-measured confounders.
We performed a cross-sectional analysis of a consecutive series of 629 participants enrolled in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Conducted by the National Institute on Aging Intramural Research Program, HANDLS is a prospective epidemiological study of a socioeconomically diverse cohort of 3,721 Whites and African Americans aged 30-64 years. Racial discrimination was based on self-report. RBC oxidative stress was measured by fluorescent heme degradation products. Potential confounders were age, smoking status, obesity, and C-reactive protein.
Participants had a mean age of 49 years (SD = 9.27). In multivariable linear regression models, racial discrimination was significantly associated with RBC oxidative stress (Beta = 0.55, P < 0.05) after adjustment for age, smoking, C-reactive protein level, and obesity. When stratified by race, discrimination was not associated with RBC oxidative stress in Whites but was associated significantly for African Americans (Beta = 0.36, P < 0.05).
These findings suggest that there may be identifiable cellular pathways by which racial discrimination amplifies cardiovascular and other age-related disease risks.
C1 [Szanton, Sarah L.; Miller, Edgar R., III; Thorpe, Roland J.] Johns Hopkins Univ, Baltimore, MD 21205 USA.
[Rifkind, Joseph M.; Mohanty, Joy G.; Nagababu, Eneka; Zonderman, Alan B.; Evans, Michele K.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Epel, Elissa S.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Szanton, SL (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA.
EM sszanton@son.jhmi.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU Intramural NIH HHS [ZIA AG000513-09]; NCRR NIH HHS [1KL2RR025006-01, KL2
RR025006]; NICHD NIH HHS [R24 HD042854]
NR 42
TC 19
Z9 19
U1 1
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1070-5503
J9 INT J BEHAV MED
JI Int. J. Behav. Med.
PD DEC
PY 2012
VL 19
IS 4
BP 489
EP 495
DI 10.1007/s12529-011-9188-z
PG 7
WC Psychology, Clinical
SC Psychology
GA 054LU
UT WOS:000312345900002
PM 21913047
ER
PT J
AU Gabay, O
Sanchez, C
AF Gabay, Odile
Sanchez, Christelle
TI Epigenetics, sirtuins and osteoarthritis
SO JOINT BONE SPINE
LA English
DT Review
DE Chromatin-modifying enzymes; Sirt1; OA; Cartilage; Sirtuins
ID SMALL-MOLECULE ACTIVATORS; SIRT1-NULL MICE DEVELOP; HUMAN CHONDROCYTES;
SACCHAROMYCES-CEREVISIAE; RHEUMATOID-ARTHRITIS; ENDOTHELIAL-CELLS;
GENE-EXPRESSION; DEACETYLASE; RESVERATROL; CARTILAGE
AB Epigenetics, modifications of the DNA other than changes on the DNA sequences, is frequently studied in cancer research and aging. DNA methylation, mi-RNA, and histones deacetylation are investigated in different pathologies, including inflammatory diseases and age-related diseases such as osteoarthritis (OA). In this review, we focus on the chromatin-modifying enzymes in arthritic pathologies, and more particularly on Sirtuins. We also review the role of Sirt1 in OA, which has been highlighted in recent publications, and examine the possible protective role Sirt1 could play in this disease. Moreover, we discuss the possible therapeutic target of such a protein, reviewing the potential inhibitors/activators of this enzyme and their properties. (C) 2012 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
C1 [Gabay, Odile] NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Bethesda, MD 20892 USA.
[Sanchez, Christelle] Univ Liege, Bone & Cartilage Res Unit, Inst Pathol B23, Liege, Belgium.
RP Gabay, O (reprint author), NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Bldg 50, Bethesda, MD 20892 USA.
EM gabayo@mail.nih.gov
FU National Institutes of Arthritis; National Institutes of Arthritis and
Musculoskeletal and Skin Diseases of the National Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Arthritis and Musculoskeletal and Skin
Diseases of the National Institutes of Health. The authors want to thank
Drs Michael Ward and David Engel for their valuable reading and editing
of the manuscript.
NR 60
TC 19
Z9 22
U1 1
U2 24
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 1297-319X
J9 JOINT BONE SPINE
JI Joint Bone Spine
PD DEC
PY 2012
VL 79
IS 6
BP 570
EP 573
DI 10.1016/j.jbspin.2012.04.005
PG 4
WC Rheumatology
SC Rheumatology
GA 052MB
UT WOS:000312200800012
PM 22738809
ER
PT J
AU Mukherjee, K
Gitlin, JM
Loftin, CD
AF Mukherjee, Kamalika
Gitlin, Jonathan M.
Loftin, Charles D.
TI Effectiveness of Cyclooxygenase-2 Inhibition in Limiting Abdominal
Aortic Aneurysm Progression in Mice Correlates With a Differentiated
Smooth Muscle Cell Phenotype
SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
LA English
DT Article
DE abdominal aortic aneurysm; cyclooxygenase-2; cyclooxygenase-2 inhibitor;
angiotensin II; smooth muscle cell phenotype
ID E-DEFICIENT MICE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN E-2
SYNTHESIS; ANGIOTENSIN-II; MYOCARDIAL-INFARCTION; HYALURONAN; RISK;
MUTATIONS; EXPANSION; ATHEROSCLEROSIS
AB Abdominal aortic aneurysms (AAAs) are a chronic condition that often progress over years to produce a weakened aorta with increased susceptibility for rupture, and currently, there are no pharmacological treatments available to slow disease progression. AAA development has been characterized by increased expression of cyclooxygenase-2 (COX-2), and inactivation of COX-2 before disease initiation reduces AAA incidence in a mouse model of the disease. The current study determined the effectiveness of COX-2 inhibition on AAA progression when treatment was begun after initiation of the disease. COX-2 inhibitor treatment with celecoxib was initiated after angiotensin II-induced AAA formation in a strain of nonhyperlipidemic mice that we have previously identified as highly susceptible to AAA development. When analyzed at different time points during progression of the disease, celecoxib treatment significantly reduced the incidence and severity of AAAs. The celecoxib treatment also protected the mice from aortic rupture and death. The aneurysmal lesion displayed an altered smooth muscle cell (SMC) phenotype, whereas celecoxib treatment was associated with increased expression of differentiated SMC markers and reduced dedifferentiation marker expression during AAA progression. Maintenance of a differentiated SMC phenotype is associated with the effectiveness of COX-2 inhibition for limiting AAA progression in nonhyperlipidemic mice.
C1 [Loftin, Charles D.] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA.
[Mukherjee, Kamalika] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON, Canada.
[Gitlin, Jonathan M.] NHGRI, Policy & Program Anal Branch, Off Director, NIH, Bethesda, MD 20892 USA.
RP Loftin, CD (reprint author), Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Bio Pharm Complex,Rm 347,789 S Limestone St, Lexington, KY 40536 USA.
EM cdloft2@email.uky.edu
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[HL083122]
FX Supported by the National Heart, Lung, and Blood Institute, National
Institutes of Health (HL083122).
NR 36
TC 4
Z9 5
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0160-2446
J9 J CARDIOVASC PHARM
JI J. Cardiovasc. Pharmacol.
PD DEC
PY 2012
VL 60
IS 6
BP 520
EP 529
DI 10.1097/FJC.0b013e318270b968
PG 10
WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy
SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy
GA 052UP
UT WOS:000312224300005
PM 22967986
ER
PT J
AU Tao, P
Hodoscek, M
Larkin, JD
Shao, YH
Brooks, BR
AF Tao, Peng
Hodoscek, Milan
Larkin, Joseph D.
Shao, Yihan
Brooks, Bernard R.
TI Comparison of Three Chain-of-States Methods: Nudged Elastic Band and
Replica Path with Restraints or Constraints
SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION
LA English
DT Article
ID MATRIX-METALLOPROTEINASE 2; GROWING STRING METHOD; MINIMUM-ENERGY PATHS;
TRANSITION-STATE; CONFORMATIONAL TRANSITIONS; QUANTUM-MECHANICS; HELIX
FORMATION; SADDLE-POINTS; FORCE-FIELDS; DYNAMICS
AB Chain-of-state methods are becoming important tools in studying the chemical reaction mechanisms, especially for biomacromolecules. In this article, three chain-of-state methods, the nudged elastic band (NEB) method and the replica path method with restraints or constraints, were tested and compared using three model systems with various sizes and at different levels of theory: alanine dipeptide isomerization, beta-alanine intramolecular condensation, and the matrix metalloproteinase 2 inhibition mechanism. The levels of theory used to describe the three model systems include molecular mechanics (MM), quantum mechanics (QM), and combined quantum mechanics and molecular mechanics (QM/MM). All three methods could correctly determine a reaction path with reasonable estimation of reaction barriers in most cases. The RMSD measurement with additional weighting schemes provides practically infinite choices of reaction coordinates to describe the reaction progress. These findings demonstrate that the chain-of-state methods are powerful tools when being used carefully to generate a plausible reaction mechanism with full pathway for complex systems at an affordable computational cost.
C1 [Tao, Peng; Larkin, Joseph D.; Shao, Yihan; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Hodoscek, Milan] Natl Inst Chem, Ctr Mol Modeling, SI-1000 Ljubljana, Slovenia.
[Shao, Yihan] Q Chem Inc, Pittsburgh, PA 15213 USA.
RP Tao, P (reprint author), NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
EM peng.tao@nih.gov
OI Tao, Peng/0000-0002-2488-0239
FU NIH, NHLBI
FX The research was supported by the Intramural Research Program of the
NIH, NHLBI. Computational resources and services used in this work were
provided by the LoBoS cluster of the National Institutes of Health.
NR 83
TC 9
Z9 9
U1 2
U2 30
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9618
J9 J CHEM THEORY COMPUT
JI J. Chem. Theory Comput.
PD DEC
PY 2012
VL 8
IS 12
BP 5035
EP 5051
DI 10.1021/ct3006248
PG 17
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 051JJ
UT WOS:000312122200019
PM 23526888
ER
PT J
AU Jacobson, S
AF Jacobson, Steve
TI Common Sense Paths Follow Brain Injuries
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Editorial Material
DE Brain injury; HIV associated neurocognitive disorder; Alzheimer's
disease; Multiple sclerosis
ID DISEASES
C1 NINDS, NIH, Bethesda, MD 20892 USA.
RP Jacobson, S (reprint author), NINDS, NIH, Bldg 10,Room 5C103,10 Ctr Dr,MSC 1400, Bethesda, MD 20892 USA.
EM jacobsons@ninds.nih.gov
FU Intramural NIH HHS [ZIA NS002817-23]
NR 5
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1890
J9 J NEUROIMMUNE PHARM
JI J. Neuroimmune Pharm.
PD DEC
PY 2012
VL 7
IS 4
BP 717
EP 718
DI 10.1007/s11481-012-9413-9
PG 2
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 054SM
UT WOS:000312363500002
PM 23138697
ER
PT J
AU Chen, SL
Lee, SY
Tao, PL
Chang, YH
Chen, SH
Chu, CH
Chen, PS
Lee, IH
Yeh, TL
Yang, YK
Hong, JS
Lu, RB
AF Chen, Shiou-Lan
Lee, Sheng-Yu
Tao, Pao-Luh
Chang, Yun-Hsuan
Chen, Shih-Heng
Chu, Chun-Hsien
Chen, Po See
Lee, I. Hui
Yeh, Tzung Lieh
Yang, Yen Kuang
Hong, Jau-Shyong
Lu, Ru-Band
TI Dextromethorphan Attenuated Inflammation and Combined Opioid Use in
Humans Undergoing Methadone Maintenance Treatment
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Article
DE Cytokines; Dextromethorphan; Methadone maintenance therapy; Opioid;
Plasma
ID DOPAMINERGIC-NEURONS; NUCLEUS-ACCUMBENS; SIGMA-RECEPTORS; MICROGLIAL
ACTIVATION; INDUCED NEUROTOXICITY; TNF-ALPHA; MORPHINE; RATS; BRAIN;
3-HYDROXYMORPHINAN
AB Recent studies show that proinflammatory cytokines might be related to the development of opioid dependence (physiological, psychological, or both). In a double-blind, randomly stratified clinical trial investigating whether add-on dextromethorphan (60-120 mg/day) attenuated inflammation and the combined use of opioids in heroin-dependent patients undergoing methadone maintenance treatment, we evaluated whether inflammation is related to the progression of opioid dependence. All participants (107 heroin-dependent patients and 84 nondependent healthy controls) were recruited from National Cheng Kung University Hospital. Their plasma cytokine levels were measured to evaluate the effect of add-on dextromethorphan. Plasma TNF-alpha and IL-8 levels were significantly higher in long-term heroin-dependent patients than in healthy controls (p < 0.001). Chronic heroin-use-induced TNF-alpha and IL-8 levels were significantly (p < 0.05) attenuated in patients treated for 12 weeks with add-on dextromethorphan. Moreover, both tolerance to methadone and the combined use of opioids were significantly (p < 0.05) attenuated in patients taking dextromethorphan. We conclude that dextromethorphan might be a feasible adjuvant therapeutic for attenuating inflammation and inhibiting methadone tolerance and combined opioid use in heroin-dependent patients.
C1 [Chen, Shiou-Lan; Lee, Sheng-Yu; Chen, Po See; Lee, I. Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Dept Psychiat, Coll Med & Hosp, Tainan 70428, Taiwan.
[Chen, Shiou-Lan; Lu, Ru-Band] Natl Cheng Kung Univ, Inst Behav Med, Coll Med, Tainan 70428, Taiwan.
[Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsien] Natl Cheng Kung Univ, Dept Psychiat, Coll Med, Tainan 70428, Taiwan.
[Chang, Yun-Hsuan; Lu, Ru-Band] Natl Cheng Kung Univ, Inst Allied Hlth Sci, Coll Med, Tainan 70428, Taiwan.
[Chen, Shiou-Lan; Lee, Sheng-Yu; Chen, Po See; Lee, I. Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Addict Res Ctr, Tainan 70428, Taiwan.
[Tao, Pao-Luh] Natl Hlth Res Inst, Div Mental Hlth & Addict Med, Inst Populat Hlth Sci, Zhunan, Taiwan.
[Chen, Shih-Heng; Chu, Chun-Hsien; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
RP Lu, RB (reprint author), Natl Cheng Kung Univ, Dept Psychiat, Coll Med & Hosp, 138 Sheng Li Rd, Tainan 70428, Taiwan.
EM rblu@mail.ncku.edu.tw
RI Tao, Pao-Luh/F-6085-2010
FU Taiwan Ministry of Health [DOH98-TD-I-111-DD004]; Taiwan National Health
Research Institutes [NHRI-EX97-9401NP, NHRI-99A1-PDCO-0809111]; National
Cheng Kung University
FX This study was supported in part by grant DOH98-TD-I-111-DD004 from the
Taiwan Ministry of Health (to R-BL); grants NHRI-EX97-9401NP (to P-LT)
and NHRI-99A1-PDCO-0809111 (to P-LT) from the Taiwan National Health
Research Institutes; and a grant from the National Cheng Kung University
Project to Promote Academic Excellence & Develop World Class Research
Centers (to R-BL). We thank Ms. Yi-Syuan Wu and Ms. Yu-Shan Wang for
their assistance in preparing this manuscript. R-B Lu had full access to
all the data in the study and takes responsibility for the integrity of
the data and the accuracy of the data analysis.
NR 54
TC 6
Z9 6
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1890
J9 J NEUROIMMUNE PHARM
JI J. Neuroimmune Pharm.
PD DEC
PY 2012
VL 7
IS 4
BP 1025
EP 1033
DI 10.1007/s11481-012-9400-1
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 054SM
UT WOS:000312363500030
PM 22990619
ER
PT J
AU Chen, SL
Lee, SY
Chang, YH
Chen, SH
Chu, CH
Tzeng, NS
Lee, IH
Chen, PS
Yeh, TL
Huang, SY
Yang, YK
Lu, RB
Hong, JS
AF Chen, Shiou-Lan
Lee, Sheng-Yu
Chang, Yun-Hsuan
Chen, Shih-Heng
Chu, Chun-Hsieh
Tzeng, Nian-Sheng
Lee, I-Hui
Chen, Po-See
Yeh, Tzung Lieh
Huang, San-Yuan
Yang, Yen-Kuang
Lu, Ru-Band
Hong, Jau-Shyong
TI Inflammation in Patients with Schizophrenia: The Therapeutic Benefits of
Risperidone Plus Add-On Dextromethorphan (vol 7, pg 656, 2012)
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Correction
C1 [Lu, Ru-Band] Natl Cheng Kung Univ, Dept Psychiat, Coll Med & Hosp, Tainan 70428, Taiwan.
[Chen, Shiou-Lan; Chang, Yun-Hsuan; Lu, Ru-Band] Inst Behav Med, Tainan, Taiwan.
[Chen, Shiou-Lan; Lee, Sheng-Yu; Chen, Shih-Heng; Chu, Chun-Hsieh; Lee, I-Hui; Chen, Po-See; Yeh, Tzung Lieh; Yang, Yen-Kuang; Lu, Ru-Band] Natl Cheng Kung Univ Hosp, Dept Psychiat, Tainan 70428, Taiwan.
[Chang, Yun-Hsuan; Lu, Ru-Band] Natl Cheng Kung Univ, Inst Allied Hlth Sci, Coll Med, Tainan 70428, Taiwan.
[Chen, Shiou-Lan; Lee, Sheng-Yu; Chen, Shih-Heng; Chu, Chun-Hsieh; Lee, I-Hui; Chen, Po-See; Yeh, Tzung Lieh; Yang, Yen-Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Addict Res Ctr, Tainan 70428, Taiwan.
[Tzeng, Nian-Sheng; Huang, San-Yuan] Tri Serv Gen Hosp, Dept Psychiat, Natl Def Med Ctr, Taipei, Taiwan.
[Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Lu, RB (reprint author), Natl Cheng Kung Univ, Dept Psychiat, Coll Med & Hosp, 138 Sheng Li Rd, Tainan 70428, Taiwan.
EM rblu@mail.ncku.edu.tw
NR 1
TC 0
Z9 0
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1890
J9 J NEUROIMMUNE PHARM
JI J. Neuroimmune Pharm.
PD DEC
PY 2012
VL 7
IS 4
BP 1034
EP 1034
DI 10.1007/s11481-012-9389-5
PG 1
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 054SM
UT WOS:000312363500031
ER
PT J
AU Remy, KE
Elder, RW
Tsankova, NM
Conroy, RM
AF Remy, Kenneth E.
Elder, Robert W.
Tsankova, Nadejda M.
Conroy, Rushika M.
TI Cerebellar metastatic papillary thyroid carcinoma in a pediatric patient
with complex congenital heart disease
SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
LA English
DT Article
DE cancer; cerebellar mass; congenital heart disease; metastatic;
papillary; pediatrics; radiation exposure; thyroid; thyroid carcinoma
ID RADIATION-EXPOSURE; CHARGE-SYNDROME; CARDIAC-CATHETERIZATION; CHILDREN;
MUTATIONS
AB This case describes the first pediatric case of metastatic papillary thyroid carcinoma (PTC) to the cerebellum as the presenting sign of cancer in a child with CHARGE syndrome and complex congenital heart disease. Diagnostic radiation exposure as a strong risk factor for PTC is discussed.
C1 [Remy, Kenneth E.] Columbia Univ Coll Phys & Surg, Dept Pediat, Div Pediat Crit Care Med, New York, NY 10032 USA.
[Elder, Robert W.] Columbia Univ Coll Phys & Surg, Dept Pediat, Div Cardiol, New York, NY 10032 USA.
[Tsankova, Nadejda M.] Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA.
[Conroy, Rushika M.] Columbia Univ Coll Phys & Surg, Div Endocrine Diabet & Metab, Dept Pediat, New York, NY 10032 USA.
RP Remy, KE (reprint author), NIH, Room 2C145,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kenneth.remy@nih.gov
OI Remy, Kenneth/0000-0001-5222-9884; Elder, Robert/0000-0002-4956-8604
NR 22
TC 0
Z9 0
U1 0
U2 0
PU WALTER DE GRUYTER & CO
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0334-018X
J9 J PEDIATR ENDOCR MET
JI J. Pediatr. Endocrinol. Metab.
PD DEC
PY 2012
VL 25
IS 11-12
BP 1195
EP 1199
DI 10.1515/jpem-2012-0162
PG 5
WC Endocrinology & Metabolism; Pediatrics
SC Endocrinology & Metabolism; Pediatrics
GA 051WW
UT WOS:000312159700027
PM 23329771
ER
PT J
AU Weiss, PF
Beukelman, T
Schanberg, LE
Kimura, Y
Colbert, RA
AF Weiss, Pamela F.
Beukelman, Timothy
Schanberg, Laura E.
Kimura, Yukiko
Colbert, Robert A.
CA CARRA Registry Investigators
TI Enthesitis-related Arthritis Is Associated with Higher Pain Intensity
and Poorer Health Status in Comparison with Other Categories of Juvenile
Idiopathic Arthritis: The Childhood Arthritis and Rheumatology Research
Alliance Registry
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Article
DE JUVENILE IDIOPATHIC ARTHRITIS; PEDIATRIC RHEUMATIC DISEASES; PAIN;
HEALTH STATUS; EPIDEMIOLOGY
ID QUALITY-OF-LIFE; ASSESSMENT QUESTIONNAIRE; DISEASE-ACTIVITY; VISUAL
ANALOG; CHILDREN; ADOLESCENTS; VALIDATION; POPULATION; VALIDITY; ASTHMA
AB Objective. To assess the relative effect of clinical factors and medications on pain intensity, physical function, and health status in juvenile idiopathic arthritis (JIA).
Methods. We conducted a retrospective cross-sectional study of data from children with JIA enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. We tested whether clinical characteristics of JIA were associated with pain intensity, physical function, and health status using multivariable linear and ordinal logistic regression.
Results. During the study period, 2571 subjects with JIA enrolled in the CARRA Registry. Ratings of pain intensity, physical function, and health status differed significantly between JIA categories. In comparison to other categories of JIA, subjects with enthesitis-related arthritis (ERA) reported worse pain and function. In multivariable analyses, higher active joint count and current use of nonsteroidal anti inflammatory drugs (NSAID), biologics, or corticosteroids were associated with worse scores on all patient-reported measures. ERA and older age were significantly associated with higher pain intensity and poorer health status. Systemic JIA and uveitis were significantly associated with worse health status. Enthesitis, sacroiliac tenderness, and NSAID use were independently associated with increased pain intensity in ERA. The correlation was low between physician global assessment of disease activity and patient-reported pain intensity, physical function, and health status.
Conclusion. Significant differences in pain intensity, physical function, and health status exist among JIA categories. These results suggest that current treatments may not be equally effective for particular disease characteristics more common in specific JIA categories, such as enthesitis or sacroiliac tenderness in ERA. (First Release Oct 15 2012: J Rheumatol 2012;39:2341-51; doi:10.3899/jrheum.120642)
C1 [Weiss, Pamela F.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA.
[Beukelman, Timothy] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Schanberg, Laura E.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA.
[Kimura, Yukiko] Hackensack Univ, Med Ctr, Dept Pediat, Hackensack, NJ USA.
US Natl Inst Arthrit & Musculoskeletal & Skin Dis, NIH, Bethesda, MD USA.
RP Weiss, PF (reprint author), Childrens Hosp Philadelphia, 3535 Market St,Room 1526, Philadelphia, PA 19104 USA.
EM weisspa@email.chop.edu
FU NIH [RC2AR058934, RO1 AR053845]; Arthritis Foundation; Friends of CARRA;
NIAMS NIH [1-K23-AR059749-01A1]; NIH NIAMS Intramural Research Program
[ZO1-AR041184]
FX The CARRA Registry is supported by NIH grant RC2AR058934. CARRA is
supported by grants from the Arthritis Foundation and Friends of CARRA.
Dr. Weiss is supported by NIAMS NIH grant 1-K23-AR059749-01A1. Dr.
Schanberg is supported by NIH grants RC2AR058934 and RO1 AR053845. Dr.
Colbert is supported by the NIH NIAMS Intramural Research Program,
ZO1-AR041184
NR 39
TC 15
Z9 16
U1 1
U2 6
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA
SN 0315-162X
J9 J RHEUMATOL
JI J. Rheumatol.
PD DEC
PY 2012
VL 39
IS 12
BP 2341
EP 2351
DI 10.3899/jrheum.120642
PG 11
WC Rheumatology
SC Rheumatology
GA 054PJ
UT WOS:000312355400017
PM 23070991
ER
PT J
AU Puthanakit, T
Saphonn, V
Ananworanich, J
Kosalaraksa, P
Hansudewechakul, R
Vibol, U
Kerr, SJ
Kanjanavanit, S
Ngampiyaskul, C
Wongsawat, J
Luesomboon, W
Ngo-Giang-Huong, N
Chettra, K
Cheunyam, T
Suwarnlerk, T
Ubolyam, S
Shearer, WT
Paul, R
Mofenson, LM
Fox, L
Law, MG
Cooper, DA
Phanuphak, P
Vun, MC
Ruxrungtham, K
AF Puthanakit, Thanyawee
Saphonn, Vonthanak
Ananworanich, Jintanat
Kosalaraksa, Pope
Hansudewechakul, Rawiwan
Vibol, Ung
Kerr, Stephen J.
Kanjanavanit, Suparat
Ngampiyaskul, Chaiwat
Wongsawat, Jurai
Luesomboon, Wicham
Ngo-Giang-Huong, Nicole
Chettra, Kea
Cheunyam, Theshinee
Suwarnlerk, Tulathip
Ubolyam, Sasiwimol
Shearer, William T.
Paul, Robert
Mofenson, Lynne M.
Fox, Lawrence
Law, Matthew G.
Cooper, David A.
Phanuphak, Praphan
Vun, Mean Chhi
Ruxrungtham, Kiat
CA PREDICT Study Grp
TI Early versus deferred antiretroviral therapy for children older than 1
year infected with HIV (PREDICT): a multicentre, randomised, open-label
trial
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID VISUAL-MOTOR INTEGRATION; DISEASE PROGRESSION; DEVELOPMENTAL TEST;
UGANDAN CHILDREN; MORTALITY; THAILAND; CD4; SURVIVAL; OUTCOMES; INFANTS
AB Background The optimum time to start antiretroviral therapy for children diagnosed with HIV infection after 1 year of age is unknown. We assessed whether antiretroviral therapy could be deferred until CD4 percentages declined to less than 15% without affecting AIDS-free survival.
Methods In our multicentre, randomised, open-label trial at nine research sites in Thailand and Cambodia, we enrolled children aged 1-12 years who were infected with HIV and had CD4 percentages of 15-24%. Participants were randomly assigned (1:1) by a minimisation scheme to start antiretroviral therapy at study entry (early treatment group) or antiretroviral therapy to start when CD4 percentages declined to less than 15% (deferred treatment group). The primary endpoint was AIDS-free survival (based on US Centers for Disease Control and Prevention category C events) at week 144, assessed with the Kaplan-Meier analysis and the log-rank approach. This study is registered with ClinicalTrials.gov, number NCT00234091.
Findings Between March 28,2006, and Sept 10,2008, we enrolled 300 Thai and Cambodian children infected with HIV, with a median age of 6.4 years (IQR 3.9-8.4). 150 children were randomly allocated early antiretroviral therapy (one participant was excluded from analyses after withdrawing before week 0) and 150 children were randomly allocated deferred antiretroviral therapy. Median baseline CD4 percentage was 19% (16-22%). 69 children (46%) in the deferred treatment group started antiretroviral therapy during the study. AIDS-free survival at week 144 in the deferred treatment group was 98.7% (95% CI 94.7-99.7; 148 of 150 patients) compared with 97.9% (93.7-99.3; 146 of 149 patients) in the early treatment group (p=0.6).
Interpretation AIDS-free survival in both treatment groups was high. This low event rate meant that our study was underpowered to detect differences between treatment start times and thus additional follow-up of study participants or future studies are needed to answer this clinical question.
C1 [Puthanakit, Thanyawee; Ananworanich, Jintanat; Kerr, Stephen J.; Cheunyam, Theshinee; Suwarnlerk, Tulathip; Ubolyam, Sasiwimol; Phanuphak, Praphan; Ruxrungtham, Kiat] Thai Red Cross AIDS Res Ctr, HIV Netherlands Australia Thailand Res Collaborat, Bangkok 10330, Thailand.
[Ananworanich, Jintanat; Phanuphak, Praphan] Thai Red Cross AIDS Res Ctr, SEARCH, Bangkok 10330, Thailand.
[Puthanakit, Thanyawee] Chulalongkorn Univ, Fac Med, Dept Pediat, Bangkok 10330, Thailand.
[Ananworanich, Jintanat; Phanuphak, Praphan; Ruxrungtham, Kiat] Chulalongkorn Univ, Fac Med, Dept Med, Bangkok 10330, Thailand.
[Saphonn, Vonthanak; Chettra, Kea; Vun, Mean Chhi] Natl Ctr HIV AIDS Dermatol & STDs, Phnom Penh, Cambodia.
[Kosalaraksa, Pope] Khon Kaen Univ, Dept Pediat, Fac Med, Khon Kaen, Thailand.
[Hansudewechakul, Rawiwan] Chiangrai Prachanukroh Hosp, Chiang Rai, Thailand.
[Vibol, Ung] Natl Pediat Hosp, Phnom Penh, Cambodia.
[Kanjanavanit, Suparat] Nakornping Hosp, Chiang Mai, Thailand.
[Ngampiyaskul, Chaiwat] Prapokklao Hosp, Chanthaburi, Thailand.
[Wongsawat, Jurai] Bamrasnaradura Infect Dis Inst, Nonthaburi, Thailand.
[Luesomboon, Wicham] Queen Savang Vadhana Mem Hosp, Chon Buri, Thailand.
[Ngo-Giang-Huong, Nicole] Inst Rech Dev IRD U174, Program HIV Prevent & Treatment, Chiang Mai, Thailand.
[Shearer, William T.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA.
[Paul, Robert] Univ Missouri, Dept Psychol, St Louis, MO 63121 USA.
[Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Fox, Lawrence] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Ananworanich, Jintanat; Kerr, Stephen J.; Law, Matthew G.; Cooper, David A.] Univ New S Wales, Kirby Inst Infect & Immun Soc, Sydney, NSW, Australia.
RP Ruxrungtham, K (reprint author), Thai Red Cross AIDS Res Ctr, HIV Netherlands Australia Thailand Res Collaborat, Bangkok 10330, Thailand.
EM kiat.r@chula.ac.th
OI Mofenson, Lynne/0000-0002-2818-9808; Kerr, Stephen/0000-0002-1919-4525;
Ngo-Giang-Huong, Nicole/0000-0001-8950-3234
FU US National Institutes of Health, Division of AIDS; National Institute
of Allergy and Infectious Diseases; National Institute of Child Health
and Human Development; National Institute of Mental Health; ViiV
Healthcare; Abbott; Gilead; Thai National Research University Project of
the Commission for Higher Education [HR1161A]; Ratchadaphiseksomphot
Endowment Fund, Thailand [HR1161A]; National Science and Technology
Development Agency, BIOTEC; Thai Research Fund; National Institute of
Allergy and Infectious Diseases of the US National Institutes of Health
through the Comprehensive International Program of Research on AIDS
Network [U19 AI53741]; Eunice Shriver Kennedy National Institute of
Child Health and Human Development; National Research Council of
Thailand; National Health Security Office, Thailand
FX Funding US National Institutes of Health, Division of AIDS; National
Institute of Allergy and Infectious Diseases; National Institute of
Child Health and Human Development; and National Institute of Mental
Health.; JA has received consulting fees or speaker's honoraria from
ViiV Healthcare, Abbott, and Gilead. KR has received consulting fees or
speaker's honoraria from ViiV Healthcare and Abbott, and support through
grants HR1161A from the Thai National Research University Project of the
Commission for Higher Education and the Ratchadaphiseksomphot Endowment
Fund, Thailand; the Professional Researcher Strengthen Grant from the
National Science and Technology Development Agency, BIOTEC; and Senior
researcher scholar from the Thai Research Fund. All other authors
declare that they have no conflicts of interest.; The trial was
supported by a grant from the National Institute of Allergy and
Infectious Diseases of the US National Institutes of Health through the
Comprehensive International Program of Research on AIDS Network (U19
AI53741), and was co-funded by the Eunice Shriver Kennedy National
Institute of Child Health and Human Development and the National
Institute of Mental Health, the National Research Council of Thailand,
and National Health Security Office, Thailand. Antiretroviral drugs were
provided by ViiV Healthcare, GlaxoSmithKline, Boehringer Ingelheim,
Merck, Abbott, and Roche. The views in this report do not necessarily
reflect the views of the National Institutes of Health or US Department
of Health and Human Services. We thank the families and children who
participated in the trial, and June Piraporn Ohata for her help with
preparation of the report for submission.
NR 29
TC 37
Z9 37
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD DEC
PY 2012
VL 12
IS 12
BP 933
EP 941
DI 10.1016/S1473-3099(12)70242-6
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA 052EH
UT WOS:000312180000022
PM 23059199
ER
PT J
AU Anders, KL
Hay, SI
AF Anders, Katherine L.
Hay, Simon I.
TI Lessons from malaria control to help meet the rising challenge of dengue
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID PLASMODIUM-FALCIPARUM TRANSMISSION; DOMINANT ANOPHELES VECTORS;
PRIMARY-SCHOOL CHILDREN; WATER CONTAINER COVERS; AEDES-AEGYPTI DIPTERA;
GLOBAL DISTRIBUTION; VIRUS TRANSMISSION; DISTRIBUTION MAPS; BIONOMIC
PRECIS; COMMUNITY INVOLVEMENT
AB Achievements in malaria control could inform efforts to control the increasing global burden of dengue. Better methods for quantifying dengue endemicity- equivalent to parasite prevalence surveys and endemicity mapping used for malaria-would help target resources, monitor progress, and advocate for investment in dengue prevention. Success in controlling malaria has been attributed to widespread implementation of interventions with proven efficacy. An improved evidence base is needed for large-scale delivery of existing and novel interventions for vector control, alongside continued investment in dengue drug and vaccine development. Control of dengue is unlikely to be achieved without coordinated international financial and technical support for national programmes, which has proven effective in reducing the global burden of malaria.
C1 [Anders, Katherine L.] Hosp Trop Dis, OUCRU, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
[Anders, Katherine L.] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England.
[Anders, Katherine L.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia.
[Hay, Simon I.] Univ Oxford, Spatial Ecol & Epidemiol Grp, Dept Zool, Oxford OX1 2JD, England.
[Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Anders, KL (reprint author), Hosp Trop Dis, OUCRU, Wellcome Trust Major Overseas Programme, 764 Vo Van Kiet,Dist 5, Ho Chi Minh City, Vietnam.
EM kanders@oucru.org
RI Hay, Simon/F-8967-2015
OI Hay, Simon/0000-0002-0611-7272
FU Wellcome Trust; Li Ka Shing Foundation; Science and Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health; European Commission [281803]
FX KLA is supported by the Wellcome Trust and the Li Ka Shing Foundation.
SIH is funded by a Senior Research Fellowship from the Wellcome Trust
and is supported by the Li Ka Shing Foundation, the RAPIDD program of
the Science and Technology Directorate, Department of Homeland Security,
and the Fogarty International Center, National Institutes of Health.
This research was also supported partly by the IDAMS Project (grant no
281803) within the 7th Framework Programme of the European Commission.
The sponsors had no role in preparation of the manuscript or the
decision to publish. We thank Cameron Simmons, Oliver Brady, Peter
Gething, Thomas Scott, Philip McCall, and Jeremy Farrar for valuable
comments and suggestions during the preparation of this manuscript; and
Katherine Battle for proofreading.
NR 123
TC 16
Z9 16
U1 2
U2 27
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD DEC
PY 2012
VL 12
IS 12
BP 977
EP 984
PG 8
WC Infectious Diseases
SC Infectious Diseases
GA 052EH
UT WOS:000312180000026
PM 23174383
ER
PT J
AU Zhang, Y
Hong, H
Niu, G
Valdovinos, HF
Orbay, HK
Nayak, TR
Chen, XY
Barnhart, TE
Cai, WB
AF Zhang, Yin
Hong, Hao
Niu, Gang
Valdovinos, Hector F.
Orbay, Hakan
Nayak, Tapas R.
Chen, Xiaoyuan
Barnhart, Todd E.
Cai, Weibo
TI Positron Emission Tomography Imaging of Vascular Endothelial Growth
Factor Receptor Expression with Cu-61-Labeled Lysine-Tagged VEGF(121)
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE Vascular endothelial growth factor (VEGF); VEGF receptor (VEGFR); Cu-61;
positron emission tomography (PET); tumor angiogenesis; molecular
imaging
ID TUMOR ANGIOGENESIS; MONOCLONAL-ANTIBODY; VEGF RECEPTORS; SITE;
INHIBITOR; CARCINOMA; VASCULAR-ENDOTHELIAL-GROWTH-FACTOR-RECEPTOR-2;
MICROBUBBLES; BIOMARKERS; DOSIMETRY
AB Overexpression of vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) indicates poor prognosis for cancer patients in a variety of clinical studies. Our goal is to develop a tracer for positron emission tomography (PET) imaging of VEGFR expression using recombinant human VEGF(121) with three lysine residues fused to the N-terminus (denoted as K-3-VEGF(121)), which can facilitate radiolabeling without affecting its VEGFR binding affinity. K-3-VEGF(121) was conjugated with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and labeled with Cu-61 (t(1/2): 3.3 h; 62% beta(+)). The IC50 value of NOTA-K-3-VEGF(121) for VEGFR-2 was comparable to that of K-3-VEGF(121) (1.50 and 0.65 nM, respectively) based on a cell binding assay. Cu-61 labeling was achieved with good yield (55 +/- 10%) and specific activity (4.2 GBq/mg). Serial PET imaging showed that the 4T1 tumor uptake of Cu-61-NOTA-K-3-VEGF(121) was 3.4 +/- 0.5, 4.9 +/- 1.0, 5.2 +/- 1.0, and 4.8 +/- 0.8%ID/g (n = 4) at 0.5, 2, 4, and 8 h postinjection, respectively, which was consistent with biodistribution data measured by gamma counting. Blocking experiments and ex vivo histology confirmed the VEGFR specificity of Cu-61-NOTA-K-3-VEGF(121). Extrapolated human dosimetry calculation showed that liver was the organ with the highest radiation dose. The use of Cu-61 as the radiolabel is desirable for small proteins such as K-3-VEGF(121), which has a much higher beta(+) branching ratio than the commonly used Cu-64 (62% vs 17%), thereby offering stronger signal intensity and lower tracer dose for PET imaging.
C1 [Hong, Hao; Orbay, Hakan; Nayak, Tapas R.; Cai, Weibo] Univ Wisconsin, Dept Radiol, Madison, WI 53705 USA.
[Zhang, Yin; Valdovinos, Hector F.; Barnhart, Todd E.; Cai, Weibo] Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USA.
[Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
[Cai, Weibo] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53705 USA.
RP Cai, WB (reprint author), Univ Wisconsin, Dept Radiol, Room 7137,1111 Highland Ave, Madison, WI 53705 USA.
EM wcai@uwhealth.org
RI Nayak, Tapas /A-2574-2013; Cai, Weibo/B-9174-2008; Zhang,
Yin/E-6547-2015;
OI Nayak, Tapas /0000-0001-6770-6524; Cai, Weibo/0000-0003-4641-0833;
Barnhart, Todd/0000-0002-9981-2150
FU University of Wisconsin Carbone Cancer Center; Department of Defense
[W81XWH-11-1-0644]; Elsa U. Pardee Foundation
FX The authors acknowledge financial support from the University of
Wisconsin Carbone Cancer Center, the Department of Defense
(W81XWH-11-1-0644), and the Elsa U. Pardee Foundation.
NR 49
TC 7
Z9 7
U1 1
U2 15
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD DEC
PY 2012
VL 9
IS 12
BP 3586
EP 3594
DI 10.1021/mp3005269
PG 9
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 046OI
UT WOS:000311773900019
PM 23137334
ER
PT J
AU Shepard, K
Ito, T
Griffith, AJ
AF Shepard, Kenneth
Ito, Taku
Griffith, Andrew J.
TI Extracting energy from the inner ear
SO NATURE BIOTECHNOLOGY
LA English
DT Editorial Material
C1 [Shepard, Kenneth] Columbia Univ, Dept Elect Engn & Biomed Engn, New York, NY USA.
[Ito, Taku; Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, US Natl Inst Hlth, Rockville, MD USA.
RP Shepard, K (reprint author), Columbia Univ, Dept Elect Engn & Biomed Engn, New York, NY USA.
EM shepard@ee.columbia.edu; griffita@nidcd.nih.gov
NR 10
TC 2
Z9 2
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD DEC
PY 2012
VL 30
IS 12
BP 1204
EP 1205
DI 10.1038/nbt.2448
PG 3
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 050ZA
UT WOS:000312092400021
PM 23222789
ER
PT J
AU Tatem, AJ
Huang, Z
Das, A
Qi, Q
Roth, J
Qiu, Y
AF Tatem, A. J.
Huang, Z.
Das, A.
Qi, Q.
Roth, J.
Qiu, Y.
TI Air travel and vector-borne disease movement
SO PARASITOLOGY
LA English
DT Article
DE Air transport network; imported disease; malaria; chikungunya; Aedes
albopictus
ID DOMINANT ANOPHELES VECTORS; AIRLINE TRANSPORTATION NETWORK;
INFECTIOUS-DISEASES; FALCIPARUM-MALARIA; DISTRIBUTION MAPS;
AEDES-ALBOPICTUS; BIONOMIC PRECIS; GLOBAL SPREAD; YELLOW-FEVER;
CHIKUNGUNYA
AB Recent decades have seen substantial expansions in the global air travel network and rapid increases in traffic volumes. The effects of this are well studied in terms of the spread of directly transmitted infections, but the role of air travel in the movement of vector-borne diseases is less well understood. Increasingly however, wider reaching surveillance for vector-borne diseases and our improving abilities to map the distributions of vectors and the diseases they carry, are providing opportunities to better our understanding of the impact of increasing air travel. Here we examine global trends in the continued expansion of air transport and its impact upon epidemiology. Novel malaria and chikungunya examples are presented, detailing how geospatial data in combination with information on air traffic can be used to predict the risks of vector-borne disease importation and establishment. Finally, we describe the development of an online tool, the Vector-Borne Disease Airline Importation Risk (VBD-Air) tool, which brings together spatial data on air traffic and vector-borne disease distributions to quantify the seasonally changing risks for importation to non-endemic regions. Such a framework provides the first steps towards an ultimate goal of adaptive management based on near real time flight data and vector-borne disease surveillance.
C1 [Tatem, A. J.; Huang, Z.; Das, A.; Qiu, Y.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32610 USA.
[Tatem, A. J.; Huang, Z.; Qi, Q.; Qiu, Y.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Tatem, A. J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Roth, J.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
RP Tatem, AJ (reprint author), Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32610 USA.
EM Andy.Tatem@gmail.com
FU Transportation Research Board of the National Academy of Sciences
[ACRP02-20]; RAPIDD program of the Science & Technology Directorate,
Department of Homeland Security; Fogarty International Center, National
Institutes of Health; Bill and Melinda Gates Foundation [49446, 1032350]
FX AJT, ZH, AD and YQ acknowledge support from the Transportation Research
Board of the National Academy of Sciences, through contract #ACRP02-20.
AJT also acknowledges funding support from the RAPIDD program of the
Science & Technology Directorate, Department of Homeland Security, and
the Fogarty International Center, National Institutes of Health, and is
also supported by grants from the Bill and Melinda Gates Foundation
(#49446 and #1032350).
NR 106
TC 35
Z9 36
U1 3
U2 41
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0031-1820
J9 PARASITOLOGY
JI Parasitology
PD DEC
PY 2012
VL 139
IS 14
BP 1816
EP 1830
DI 10.1017/S0031182012000352
PG 15
WC Parasitology
SC Parasitology
GA 048IP
UT WOS:000311904900002
PM 22444826
ER
PT J
AU Blackwood, JC
Cummings, DAT
Broutin, H
Iamsirithaworn, S
Rohani, P
AF Blackwood, J. C.
Cummings, D. A. T.
Broutin, H.
Iamsirithaworn, S.
Rohani, P.
TI The population ecology of infectious diseases: pertussis in Thailand as
a case study
SO PARASITOLOGY
LA English
DT Article
DE Population ecology; spatio-temporal dynamics; persistence; pertussis
ID SPATIAL HIERARCHIES; SEASONAL-VARIATION; MEASLES EPIDEMICS;
TRAVELING-WAVES; DYNAMICS; VACCINATION; IMPACT; PERIODICITY;
PERSISTENCE; SYNCHRONY
AB Many of the fundamental concepts in studying infectious diseases are rooted in population ecology. We describe the importance of population ecology in exploring central issues in infectious disease research including identifying the drivers and dynamics of host-pathogen interactions and pathogen persistence, and evaluating the success of public health policies. The use of ecological concepts in infectious disease research is demonstrated with simple theoretical examples in addition to an analysis of case notification data of pertussis, a childhood respiratory disease, in Thailand as a case study. We stress that further integration of these fields will have significant impacts in infectious diseases research.
C1 [Blackwood, J. C.; Rohani, P.] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Blackwood, J. C.; Rohani, P.] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[Cummings, D. A. T.] Johns Hopkins Bloomberg Sch Publ Hlth Baltimore, Baltimore, MD 21205 USA.
[Cummings, D. A. T.; Rohani, P.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Broutin, H.] UMR CNRS 5290 IRD 224 UM1 UM2 Ctr Rech IRD, MIVEGEC, F-34394 Montpellier 5, France.
[Iamsirithaworn, S.] Minist Publ Hlth Nonthaburi, Bur Epidemiol, Nonthaburi, Thailand.
RP Blackwood, JC (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
EM juliecb@umich.edu
FU RAPIDD program of the Science and Technology Directorate, Department of
Homeland Security; Fogarty International Center, National Institutes of
Health; Bill and Melinda Gates Vaccine Modeling Initiative; Scientific
Interface from the Burroughs Welcome Fund
FX PR and DATC were supported by the RAPIDD program of the Science and
Technology Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health as well as the Bill
and Melinda Gates Vaccine Modeling Initiative. HB was funded by the
Intramural Research Group of Fogarty International Center, National
Institutes of Health. DATC holds a Career Award at the Scientific
Interface from the Burroughs Welcome Fund.
NR 61
TC 4
Z9 4
U1 0
U2 15
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0031-1820
J9 PARASITOLOGY
JI Parasitology
PD DEC
PY 2012
VL 139
IS 14
BP 1888
EP 1898
DI 10.1017/S0031182012000431
PG 11
WC Parasitology
SC Parasitology
GA 048IP
UT WOS:000311904900007
PM 22717183
ER
PT J
AU Eblen, M
Fabsitz, RR
Olson, JL
Pearson, K
Pool, LR
Puggal, M
Wu, C
Wagner, RM
AF Eblen, Matthew
Fabsitz, Richard R.
Olson, Jean L.
Pearson, Katrina
Pool, Lindsay R.
Puggal, Mona
Wu, Charles
Wagner, Robin M.
TI Social network analysis comparing researcher collaborations in two
cardiovascular cohort studies
SO RESEARCH EVALUATION
LA English
DT Article
DE social network analysis; co-authorship networks; researcher
collaboration; cohort studies; cardiovascular disease; American Indian
population
ID AMERICAN-INDIANS; PATTERNS; DISEASE
AB The development of social network analysis techniques and comprehensive online bibliographic databases has led to studies of scientific co-authorship networks. This study compares collaboration among researchers associated with two epidemiological cohort studies, the Cardiovascular Health Study (CHS) and the Strong Heart Study (SHS), using journal article citations published from 1990 through 30 June 2011. Descriptive analyses of their publications and authors were computed, network graphs were produced, and network statistics were calculated. While similar in scientific methodology, these studies differed in ways that influenced researcher collaboration and entry into the networks. As a result, the number of unique authors for the CHS was three times greater than for the SHS (1,749 versus 571, respectively), driven by the CHS' larger number of research institutions and the higher influx of non-formally affiliated authors into its network. The CHS network had more ports of entry and also had more components, or collections of authors collaborating independently from the main network. In contrast, even at similar sizes, the SHS network was denser, indicating a greater cohesiveness than the CHS. The SHS had higher network centralization scores, suggesting the network contained relatively more authors that acted as gatekeepers. Indeed, the SHS had the majority of authors with the highest individual centrality scores, a measure of their collaborative prominence in the network. Differences in the studies' designs, populations, and organizations; funding mechanisms and policies; and awardee institutions likely explain these findings.This work provides a preliminary glimpse into understanding the mechanisms of collaboration among research studies.
C1 [Eblen, Matthew; Pearson, Katrina; Pool, Lindsay R.; Wu, Charles; Wagner, Robin M.] NIH, Off Stat Anal & Reporting, Off Extramural Res, Off Director,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Fabsitz, Richard R.; Olson, Jean L.; Puggal, Mona] NHLBI, Epidemiol Branch, Div Cardiovasc Sci, US Natl Inst Hlth,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Wagner, RM (reprint author), NIH, Off Stat Anal & Reporting, Off Extramural Res, Off Director,US Dept Hlth & Human Serv, 6705 Rockledge Dr,Suite 4090, Bethesda, MD 20892 USA.
EM wagnerr2@mail.nih.gov
NR 25
TC 4
Z9 4
U1 0
U2 27
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0958-2029
J9 RES EVALUAT
JI Res. Evaluat.
PD DEC
PY 2012
VL 21
IS 5
SI SI
BP 392
EP 405
DI 10.1093/reseval/rvs030
PG 14
WC Information Science & Library Science
SC Information Science & Library Science
GA 053AF
UT WOS:000312241100007
ER
PT J
AU Mejia, R
Booth, GS
Fedorko, DP
Hsieh, MM
Khuu, HM
Klein, HG
Mu, JB
Fahle, G
Nutman, TB
Su, XZ
Williams, EC
Flegel, WA
Klion, A
AF Mejia, Rojelio
Booth, Garrett S.
Fedorko, Daniel P.
Hsieh, Matthew M.
Khuu, Hanh M.
Klein, Harvey G.
Mu, Jianbing
Fahle, Gary
Nutman, Thomas B.
Su, Xin-Zhuan
Williams, Esther C.
Flegel, Willy A.
Klion, Amy
TI Peripheral blood stem cell transplant-related Plasmodium falciparum
infection in a patient with sickle cell disease
SO TRANSFUSION
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; TRANSFUSION-TRANSMITTED MALARIA;
HISTIDINE-RICH PROTEIN-2; DONOR; TRANSMISSION; TESTS; VIVAX; ASSAY
AB BACKGROUND: Although transmission of Plasmodium falciparum (Pf) infection during red blood cell (RBC) transfusion from an infected donor has been well documented, malaria parasites are not known to infect hematopoietic stem cells. We report a case of Pf infection in a patient 11 days after peripheral blood stem cell transplant for sickle cell disease.
STUDY DESIGN AND METHODS: Malaria parasites were detected in thick blood smears by Giemsa staining. Pf HRP2 antigen was measured by enzyme-linked immunosorbent assay on whole blood and plasma. Pf DNA was detected in whole blood and stem cell retention samples by real-time polymerase chain reaction using Pf speciesspecific primers and probes. Genotyping of eight Pf microsatellites was performed on genomic DNA extracted from whole blood.
RESULTS: Pf was not detected by molecular, serologic, or parasitologic means in samples from the recipient until Day 11 posttransplant, coincident with the onset of symptoms. In contrast, Pf antigen was retrospectively detected in stored plasma collected 3 months before transplant from the asymptomatic donor. Pf DNA was detected in whole blood from both the donor and the recipient after transplant, and genotyping confirmed shared markers between donor and recipient Pf strains. Lookback analysis of RBC donors was negative for Pf infection.
CONCLUSIONS: These findings are consistent with transmission by the stem cell product and have profound implications with respect to the screening of potential stem cell donors and recipients from malaria-endemic regions.
C1 NIAID, Dept Transfus Med, Bethesda, MD 20892 USA.
Microbiol Serv, Dept Lab Med, Bethesda, MD USA.
NHLBI, NIH, Bethesda, MD 20892 USA.
RP Klion, A (reprint author), Parasit Dis Lab, Eosinophil Pathol Unit, Bldg 50,Room 6351, Bethesda, MD 20892 USA.
EM aklion@niaid.nih.gov
OI Klion, Amy/0000-0002-4986-5326; Su, Xinzhuan/0000-0003-3246-3248
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 26
TC 3
Z9 3
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD DEC
PY 2012
VL 52
IS 12
BP 2677
EP 2682
DI 10.1111/j.1537-2995.2012.03673.x
PG 6
WC Hematology
SC Hematology
GA 056BI
UT WOS:000312461500024
PM 22536941
ER
PT J
AU Wang, D
Sun, JF
Solomon, SB
Klein, HG
Natanson, C
AF Wang, Dong
Sun, Junfeng
Solomon, Steven B.
Klein, Harvey G.
Natanson, Charles
TI In reply to "Transfusion of older blood and risk of death: unanswered
questions"
SO TRANSFUSION
LA English
DT Letter
ID METAANALYSIS
C1 [Wang, Dong; Sun, Junfeng; Solomon, Steven B.; Klein, Harvey G.; Natanson, Charles] NIH, Dept Crit Care Med, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Wang, D (reprint author), NIH, Dept Crit Care Med, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
EM CNatanson@cc.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD DEC
PY 2012
VL 52
IS 12
BP 2724
EP 2725
DI 10.1111/j.1537-2995.2012.03913.x
PG 2
WC Hematology
SC Hematology
GA 056BI
UT WOS:000312461500031
PM 23231676
ER
PT J
AU Kourrich, S
Su, TP
Fujimoto, M
Bonci, A
AF Kourrich, Said
Su, Tsung-Ping
Fujimoto, Michiko
Bonci, Antonello
TI The sigma-1 receptor: roles in neuronal plasticity and disease
SO TRENDS IN NEUROSCIENCES
LA English
DT Review
DE neuronal excitability; voltage-gated ion channels; glutamate receptors;
GABA receptors; mitochondrion-associated ER membrane; binding
immunoglobulin protein
ID METHYL-D-ASPARTATE; IMPROVED COGNITIVE IMPAIRMENTS; GATED POTASSIUM
CHANNELS; SIGNAL-REGULATED KINASE; CENTRAL-NERVOUS-SYSTEM; NMDA-INDUCED
PAIN; BINDING-SITES; RAT-BRAIN; CALCIUM-CHANNELS; ION CHANNELS
AB Sigma-1 receptors (Sig-1Rs) have been implicated in many neurological and psychiatric conditions. Sig-1Rs are intracellular chaperones that reside specifically at the endoplasmic reticulum (ER)-mitochondrion interface, referred to as the mitochondrion-associated ER membrane (MAM). Here, Sig-1Rs regulate ER-mitochondrion Ca2+ signaling. In this review, we discuss the current understanding of Sig-1R functions. Based on this, we suggest that the key cellular mechanisms linking Sig-1Rs to neurological disorders involve the translocation of Sig-1Rs from the MAM to other parts of the cell, whereby Sig-1Rs bind and modulate the activities of various ion channels, receptors, or kinases. Thus, Sig-1Rs and their associated ligands may represent new avenues for treating aspects of neurological and psychiatric diseases.
C1 [Su, Tsung-Ping; Fujimoto, Michiko] NIDA, Cellular Pathobiol Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD USA.
[Kourrich, Said; Bonci, Antonello] NIDA, Synapt Plast Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD USA.
[Bonci, Antonello] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Bonci, Antonello] Johns Hopkins Univ, Sch Med, Solomon H Snyder Neurosci Inst, Baltimore, CA USA.
RP Su, TP (reprint author), NIDA, Cellular Pathobiol Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD USA.
EM TSU@intra.nida.nih.gov; antonello.bonci@nih.gov
RI kourrich, said/M-3916-2014
FU NIDA, NIH/DHHS
FX This work is supported by the intramural Research Program of NIDA,
NIH/DHHS.
NR 99
TC 69
Z9 73
U1 3
U2 31
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0166-2236
J9 TRENDS NEUROSCI
JI Trends Neurosci.
PD DEC
PY 2012
VL 35
IS 12
BP 762
EP 771
DI 10.1016/j.tins.2012.09.007
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 054PI
UT WOS:000312355300007
PM 23102998
ER
PT J
AU Jones, RB
Kovacs, C
Chun, TW
Ostrowski, MA
AF Jones, R. Brad
Kovacs, Colin
Chun, Tae-Wook
Ostrowski, Mario A.
TI Short Communication HIV Type 1 Accumulates in Influenza-Specific T Cells
in Subjects Receiving Seasonal Vaccination in the Context of Effective
Antiretroviral Therapy
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RALTEGRAVIR INTENSIFICATION; IMMUNE
ACTIVATION; PERIPHERAL-BLOOD; LATENT RESERVOIR; PLASMA VIREMIA;
REPLICATION; INDIVIDUALS; PERSISTENCE; INFECTION
AB Whether or not HIV-1 continues to infect cells in individuals treated with effective antiretroviral therapy (ART) remains controversial. Here, we determined whether the redistribution of the HIV-1 proviral burden with respect to antigen specificity of CD4(+) cells would provide evidence for ongoing infection cycles in vivo. HIV-1 preferentially infects antigen-stimulated CD4(+) T cells. In the setting of prolonged effective ART, we postulated that if infection cycles were occurring, influenza-specific CD4(+) T cells, activated by influenza vaccination, would preferentially accumulate proviral burden. Peripheral blood mononuclear cells (PBMCs) were collected from HIV-1-infected subjects who had been treated with effective ART for >5 years, before and after influenza vaccination. CD4(+) T cells were sorted by antigen specificity and HIV-1 proviral burdens were determined. Levels of HIV-1 production upon in vitro antigenic stimulation were also measured. At baseline, influenza-specific CD4(+) T cells carried higher HIV-1 proviral loads than HIV-1-p55-specific CD4(+) T cells. Upon influenza vaccination we observed trends toward elevated levels of HIV-1 proviral DNA in influenza and HIV-1-p55-specific, but not tetanus toxoid or cytomegalovirus (CMV)-specific CD4(+) T cells. Higher levels of HIV-1 virions were produced upon influenza stimulation in postvaccination as compared to baseline samples. While the trends toward increased proviral burdens in influenza-specific cells failed to reach statistical significance, our observation of disproportionately high levels of provirus in influenza-specific cells at baseline indicates that this may represent a real increase that is cumulative over multiple annual vaccinations. This has implications for the eradication of HIV-1 by adding to the evidence that the resting CD4(+) T cell viral reservoir is continually replenished in ART-treated subjects.
C1 [Jones, R. Brad; Ostrowski, Mario A.] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada.
[Kovacs, Colin] Maple Leaf Med Clin, Toronto, ON, Canada.
[Chun, Tae-Wook] NIAID, NIH, Bethesda, MD 20892 USA.
[Ostrowski, Mario A.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada.
RP Jones, RB (reprint author), Univ Toronto, Dept Immunol, Med Sci Bldg,Room 6271,1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada.
EM brad.jones@utoronto.ca
FU Canadian Institutes of Health Research; Ontario HIV Treatment Network
(OHTN)
FX Funding for this work was obtained from the Canadian Institutes of
Health Research. The following reagents were obtained from the NIH AIDS
Research and Reference Reagent Program, Division of AIDS, NIAID, NIH:
nevirapine and 3TC. R.B.J. gratefully acknowledges salary support from
the Ontario HIV Treatment Network (OHTN). Biosafety level 3 laboratory
space was provided by the Canadian Foundation for HIV Research (CANFAR)
in partnership with the Ontario Innovation Trust and the Canadian
Foundation for Innovation.
NR 38
TC 0
Z9 0
U1 0
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD DEC
PY 2012
VL 28
IS 12
BP 1687
EP 1692
DI 10.1089/aid.2012.0115
PG 6
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 047FW
UT WOS:000311825000023
PM 22734882
ER
PT J
AU Neumeister, A
Normandin, MD
Murrough, JW
Henry, S
Bailey, CR
Luckenbaugh, DA
Tuit, K
Zheng, MQ
Galatzer-Levy, IR
Sinha, R
Carson, RE
Potenza, MN
Huang, YY
AF Neumeister, Alexander
Normandin, Marc D.
Murrough, James W.
Henry, Shannan
Bailey, Christopher R.
Luckenbaugh, David A.
Tuit, Keri
Zheng, Ming-Qiang
Galatzer-Levy, Isaac R.
Sinha, Rajita
Carson, Richard E.
Potenza, Marc N.
Huang, Yiyun
TI Positron Emission Tomography Shows Elevated Cannabinoid CB 1 Receptor
Binding in Men with Alcohol Dependence
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol Dependence; Brain Imaging; Positron Emission Tomography;
Endogenous Cannabinoids; CB 1 Receptor
ID KNOCKOUT MICE; ENDOCANNABINOID SYSTEM; GENDER-DIFFERENCES;
NUCLEUS-ACCUMBENS; ETHANOL INTAKE; HUMAN BRAIN; DRUG-ABUSE; PET TRACER;
RATS; STRESS
AB Background Several lines of evidence link cannabinoid (CB) type 1 (CB 1) receptor-mediated endogenous CB (eCB) signaling to the etiology of alcohol dependence (AD). However, to date, only peripheral measures of eCB function have been collected in living humans with AD and no human in vivo data on the potentially critical role of the brain CB 1 receptor in AD have been published. This is an important gap in the literature, because recent therapeutic developments suggest that these receptors could be targeted for the treatment for AD. Methods Medication-free participants were scanned during early abstinence 4 weeks after their last drink. Using positron emission tomography (PET) with a high-resolution research tomograph and the CB 1 receptor selective radiotracer [11 C]OMAR, we determined [11 C]OMAR volume of distribution ( V T) values, a measure of CB 1 receptor density, in a priori selected brain regions in men with AD (n = 8, age 37.4 +/- 7.9 years; 5 smokers) and healthy control (HC) men (n = 8, age 32.5 +/- 6.9 years; all nonsmokers). PET images reconstructed using the MOLAR algorithm with hardware motion correction were rigidly aligned to the subject-specific magnetic resonance (MR) image, which in turn was warped to an MR template. Timeactivity curves (TACs) were extracted from the dynamic PET data using a priori selected regions of interest delineated in the MR template space. Results In AD relative to HC, [11 C]OMAR V T values were elevated by approximately 20% (p = 0.023) in a circuit, including the amygdala, hippocampus, putamen, insula, anterior and posterior cingulate cortices, and orbitofrontal cortex. Age, body mass index, or smoking status did not influence the outcome. Conclusions These findings agree with preclinical evidence and provide the first, albeit still preliminary in vivo evidence suggesting a role for brain CB 1 receptors in AD. The current study design does not answer the important question of whether elevated CB 1 receptors are a preexisting vulnerability factor for AD or whether elevations develop as a consequence of AD.
C1 [Neumeister, Alexander; Galatzer-Levy, Isaac R.] NYU, Dept Psychiat & Radiol, Sch Med, Mol Imaging Program, New York, NY 10016 USA.
[Neumeister, Alexander; Murrough, James W.; Bailey, Christopher R.] Mt Sinai Sch Med, Mood & Anxiety Disorders Program, Dept Psychiat, New York, NY USA.
[Normandin, Marc D.; Henry, Shannan; Zheng, Ming-Qiang; Carson, Richard E.; Huang, Yiyun] Yale Univ, Sch Med, Dept Diagnost Radiol, Positron Emiss Tomog Ctr, New Haven, CT 06510 USA.
[Luckenbaugh, David A.] NIMH, Expt Therapeut Mood & Anxiety Disorders Program, Div Intramural Res Programs, Bethesda, MD 20892 USA.
[Tuit, Keri; Sinha, Rajita; Potenza, Marc N.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Potenza, Marc N.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA.
[Potenza, Marc N.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA.
RP Neumeister, A (reprint author), NYU, Dept Psychiat & Radiol, Sch Med, Mol Imaging Program, 1 Pk Ave,8th Floor,Room 225, New York, NY 10016 USA.
EM alexander.neumeister@nyumc.org
RI Zheng, MingQiang/A-2181-2013; Carson, Richard/H-3250-2011; Murrough,
James/J-7129-2013; Normandin, Marc/C-6728-2015;
OI Carson, Richard/0000-0002-9338-7966; Murrough,
James/0000-0001-6286-1242; Normandin, Marc/0000-0003-1645-523X;
Galatzer-Levy, Isaac/0000-0003-1864-064X
FU National Institutes of Health (NIH) Roadmap for Medical Research Common
Fund [UL1-DE019586, PL1-DA024859]; National Institute on Alcohol Abuse
and Alcoholism (NIAAA) [RAA017540B, RAA017540Y, RAA018329B]
FX The authors acknowledge the excellent work of the staff of the Yale PET
Center and the nursing support from Michelle San Pedro, RN, and Brenda
Breault, RN, BSN, for their contributions with patient care during the
PET scans. The project described was supported by the National
Institutes of Health (NIH) Roadmap for Medical Research Common Fund,
through the following grants: UL1-DE019586 and the PL1-DA024859, the
National Institute on Alcohol Abuse and Alcoholism (NIAAA) through the
following awards: RAA017540B and RAA017540Y (American Reinvestment and
Recovery Act of 2009), and RAA018329B.
NR 52
TC 15
Z9 15
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD DEC
PY 2012
VL 36
IS 12
BP 2104
EP 2109
DI 10.1111/j.1530-0277.2012.01815.x
PG 6
WC Substance Abuse
SC Substance Abuse
GA 051MN
UT WOS:000312131400010
PM 22551199
ER
PT J
AU Lee, PP
West, SK
Block, SS
Clayton, J
Cotch, MF
Flynn, C
Geiss, LS
Klein, R
Olsen, TW
Owsley, C
Primo, SA
Rubin, GS
Ryskulova, A
Sharma, S
Friedman, DS
Zhang, X
Crews, JE
Saaddine, JB
AF Lee, Paul P.
West, Sheila K.
Block, Sandra S.
Clayton, Janine
Cotch, Mary Frances
Flynn, Colin
Geiss, Linda S.
Klein, Ronald
Olsen, Timothy W.
Owsley, Cynthia
Primo, Susan A.
Rubin, Gary S.
Ryskulova, Asel
Sharma, Sanjay
Friedman, David S.
Zhang, Xinzhi
Crews, John E.
Saaddine, Jinan B.
TI Surveillance of Disparities in Vision and Eye Health in the United
States: An Expert Panel's Opinions
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID VISUAL IMPAIRMENT; DIABETIC-RETINOPATHY; PREVALENCE; ADULTS; CARE;
ACCESS
AB PURPOSE: To define surveillance approaches and metrics to capture the burden of vision health disparities and to identify properties of a surveillance system to guide public health interventions.
DESIGN: Expert panel.
METHODS: Analysis of relevant literature and deliberations of expert panel.
RESULTS: The panel identified that the purpose of vision surveillance was to link data to public health interventions. Panel members noted the importance of assessing vision through self-reported and performance-based measures. Defined populations should be included in a surveillance system to assess disparities in utilization of eye care and vision loss. The panel suggested that ophthalmic/vision measures should be sustained in national surveys and suggested that a vision surveillance system should be forged among federal agencies.
CONCLUSIONS: Employing the 6 outlined strategies would improve vision surveillance and help reach the vision-related objectives of Healthy People 2020. (Am J Ophthalmol 2012;154:S3-S7. (c) 2012 by Elsevier Inc. All rights reserved.)
C1 [Lee, Paul P.] Univ Michigan, Sch Med, Ann Arbor, MI 48105 USA.
[West, Sheila K.; Friedman, David S.] Johns Hopkins Univ Hosp, Dana Ctr Prevent Ophthalmol, Wilmer Eye Inst, Baltimore, MD 21287 USA.
[Block, Sandra S.] Illinois Coll Optometry, Chicago, IL USA.
[Cotch, Mary Frances] NEI, NIH, Bethesda, MD 20892 USA.
[Flynn, Colin] Maryland Dept Hlth & Mental Hyg, Baltimore, MD USA.
[Geiss, Linda S.; Zhang, Xinzhi; Crews, John E.; Saaddine, Jinan B.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA.
[Klein, Ronald] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[Olsen, Timothy W.; Primo, Susan A.] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA.
[Owsley, Cynthia] Univ Alabama Birmingham, Dept Ophthalmol, Sch Med, Birmingham, AL 35294 USA.
[Rubin, Gary S.] UCL Inst Ophthalmol, Biomed Res Ctr Ophthalmol, London, England.
[Ryskulova, Asel] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD USA.
[Sharma, Sanjay] Queens Univ, Dept Ophthalmol, Kingston, ON, Canada.
[Sharma, Sanjay] Queens Univ, Dept Epidemiol, Kingston, ON, Canada.
RP Lee, PP (reprint author), Univ Michigan, Sch Med, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM pleemd@umich.edu
RI Rubin, Gary/A-4928-2009;
OI Rubin, Gary/0000-0002-2547-4953; Cotch, Mary
Frances/0000-0002-2046-4350; Klein, Ronald/0000-0002-4428-6237; Lee,
Paul/0000-0002-3338-136X
FU Intramural NIH HHS [ZIA EY000402-12, Z01 EY000402-06, Z01 EY000402-07,
Z99 EY999999, ZIA EY000402-08, ZIA EY000402-09, ZIA EY000402-10, ZIA
EY000402-11, ZIA EY000402-13]
NR 18
TC 10
Z9 10
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD DEC
PY 2012
VL 154
IS 6
SU S
BP S3
EP S7
DI 10.1016/j.ajo.2012.09.006
PG 5
WC Ophthalmology
SC Ophthalmology
GA 047ZC
UT WOS:000311879000002
PM 23158221
ER
PT J
AU Zhang, XZ
Cotch, MF
Ryskulova, A
Primo, SA
Nair, P
Chou, CF
Geiss, LS
Barker, LE
Elliott, AF
Crews, JE
Saaddine, JB
AF Zhang, Xinzhi
Cotch, Mary Frances
Ryskulova, Asel
Primo, Susan A.
Nair, Parvathy
Chou, Chiu-Fang
Geiss, Linda S.
Barker, Lawrence E.
Elliott, Amanda F.
Crews, John E.
Saaddine, Jinan B.
TI Vision Health Disparities in the United States by Race/Ethnicity,
Education, and Economic Status: Findings From Two Nationally
Representative Surveys
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID BLUE MOUNTAINS EYE; OPEN-ANGLE GLAUCOMA; VISUAL IMPAIRMENT;
DIABETIC-RETINOPATHY; OLDER-ADULTS; MACULAR DEGENERATION; SEE PROJECT;
US POPULATION; PREVALENCE; CARE
AB PURPOSE: To assess vision health disparities in the United States by race/ethnicity, education, and economic status.
DESIGN: Cross-sectional, nationally representative samples.
METHODS: We used national survey data from the National Health and Nutrition Examination Survey (NHANES) and the National Health Interview Survey (NHIS). Main outcome measures included, from NHANES, age-related eye diseases (ie, age-related macular degeneration [AMD], cataract, diabetic retinopathy [DR], glaucoma) and from NHIS, eye care use (ie, eye doctor visits and cannot afford eyeglasses when needed) among those with self-reported visual impairment. The estimates were age- and sex-standardized to the 2000 US Census population. Linear trends in the estimates were assessed by weighted least squares regression.
RESULTS: Non-Hispanic whites had a higher prevalence of AMD and cataract surgery than non-Hispanic blacks, but a lower prevalence of DR and glaucoma (all P < .001 in NHANES 2005-2008). From 1999 to 2008, individuals with less education (ie, high school) and lower income (poverty income ratio [PM] <1.00 vs >= 4.00) were consistently less likely to have had an eye care visit in the past 12 months compared with their counterparts (all P <.05). During this period, inability to afford needed eyeglasses increased among non-Hispanic whites and Hispanics (trend P = .004 and P = .007; respectively), those with high school education (trend P = .036), and those with PIR 1.00-1.99 (trend P < .001).
CONCLUSIONS: Observed vision health disparities suggest a need for educational and innovative interventions among socioeconomically disadvantaged groups. (Am J Ophthalmol 2012;154:S53-S62. (c) 2012 Published by Elsevier Inc.)
C1 [Zhang, Xinzhi] Ctr Dis Control & Prevent, Vis Hlth Initiat, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Ryskulova, Asel] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Primo, Susan A.] Emory Univ, Sch Med, Emory Eye Ctr, Atlanta, GA USA.
RP Zhang, X (reprint author), Ctr Dis Control & Prevent, Vis Hlth Initiat, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Hwy NE,K-10, Atlanta, GA 30341 USA.
EM XZhang4@cdc.gov
OI Cotch, Mary Frances/0000-0002-2046-4350
FU National Center for Health Statistics (NCHS); Centers for Disease
Control and Prevention (Atlanta, Georgia); Intra Agency from the
Division of Diabetes Translation [05FED47304]; Centers for Disease
Control and Prevention; National Eye Institute, National Institutes of
Health, Intramural Research Program grant (Bethesda, Maryland)
[ZIAEY000402]
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
OF POTENTIAL CONFLICTS OF INTEREST and none were reported. Publication
of this article was supported by the National Center for Health
Statistics (NCHS), Centers for Disease Control and Prevention (Atlanta,
Georgia). Funding for the National Health and Nutrition Examination
Survey (NHANES) ophthalmology component was provided by the Intra Agency
Agreement 05FED47304 from the Division of Diabetes Translation, the
Centers for Disease Control and Prevention. Funding for the vision
component was provided by the National Eye Institute, National
Institutes of Health, Intramural Research Program grant ZIAEY000402
(Bethesda, Maryland). The NCHS was involved in the design and conduct of
the NHANES and NHIS study and in data collection. The Division of
Diabetes Translation provided funding support for the ophthalmology
component and was involved in the design and conduct of the study, in
the collection, analysis, and interpretation of the data, and in the
preparation, review, and approval of this article before submission.
Involved in design (X.Z., M.F.C., A.R., J.B.S.) and conduct of the study
(X.Z., M.F.C., A.R., S.A.P., J.B.S.); collection, management, analysis
(X.Z., P.N., C.F.C.), and interpretation of the data (X.Z., M.F.C.,
A.R., S.A.P., P.N., C.F.C., L.S.G., L.E.B., A.F.E., J.E.C., J.B.S.); and
preparation, review, or approval of the manuscript (X.Z., M.F.C., A.R.,
S.A.P., P.N., C.F.C., L.S.G., L.E.B., A.F.E., J.E.C., J.B.S.). Drs
Zhang, Chou, and Nair had full access to all the data in the study and
take responsibility for the integrity of the data and the accuracy of
the data analysis. The NHANES and NHIS surveys are publicly available
data and their protocols were approved by a human subjects review board,
and written informed consent was obtained from all participants. The
authors thank the NHANES and NHIS participants, without whom this study
Would not be possible. The findings and conclusions in this paper are
those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
NR 43
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Z9 26
U1 1
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD DEC
PY 2012
VL 154
IS 6
SU S
BP S53
EP S62
DI 10.1016/j.ajo.2011.08.045
PG 10
WC Ophthalmology
SC Ophthalmology
GA 047ZC
UT WOS:000311879000007
PM 23158224
ER
PT J
AU Knepper, MA
AF Knepper, Mark A.
TI Systems biology in physiology: the vasopressin signaling network in
kidney
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Review
DE aquaporin-2; signaling networks; collecting duct; phosphoproteomics;
mass spectrometry; Nedd4-2
ID MEDULLARY COLLECTING DUCT; RAT-KIDNEY; UREA TRANSPORTER; WATER CHANNEL;
PHOSPHOPROTEOMIC ANALYSIS; QUANTITATIVE PROTEOMICS; CONCENTRATING
MECHANISM; TRANSDUCTION NETWORKS; MASS-SPECTROMETRY; PLASMA-MEMBRANE
AB Knepper MA. Systems biology in physiology: the vasopressin signaling network in kidney. Am J Physiol Cell Physiol 303: C1115-C1124, 2012. First published August 29, 2012; doi:10.1152/ajpcell.00270.2012.-Over the past 80 years, physiological research has moved progressively in a reductionist direction, providing mechanistic information on a smaller and smaller scale. This trend has culminated in the present focus on "molecular physiology," which deals with the function of single molecules responsible for cellular function. There is a need to assemble the information from the molecular level into models that explain physiological function at cellular, tissue, organ, and whole organism levels. Such integration is the major focus of an approach called "systems biology." The genome sequencing projects provide a basis for a new kind of systems biology called "data-rich" systems biology that is based on large-scale data acquisition methods including protein mass spectrometry, DNA microarrays, and deep sequencing of nucleic acids. These techniques allow investigators to measure thousands of variables simultaneously in response to an external stimulus. My laboratory is applying such an approach to the question: " How does the peptide hormone vasopressin regulate water permeability in the renal collecting duct?" We are using protein mass spectrometry to identify and quantify the phosphoproteome of collecting duct cells. The response to vasopressin, presented in the form of a network model, includes a general downregulation of proline-directed kinases (MAP kinases and cyclin-dependent kinases) and upregulation of basophilic kinases (ACG kinases and calmodulin-dependent kinases). Further progress depends on characterization and localization of candidate protein kinases in these families. The ultimate goal is to use multivariate statistical techniques and differential equations to obtain predictive models describing vasopressin signaling in the renal collecting duct.
C1 NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Knepper, MA (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 6N260, Bethesda, MD 20892 USA.
EM knep@helix.nih.gov
FU Division of Intramural Research of the National Heart, Lung, and Blood
Institute [ZO1-HL001285]
FX This work was funded by the Division of Intramural Research of the
National Heart, Lung, and Blood Institute (Project ZO1-HL001285 to M. A.
Knepper).
NR 78
TC 15
Z9 15
U1 0
U2 24
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD DEC
PY 2012
VL 303
IS 11
BP C1115
EP C1124
DI 10.1152/ajpcell.00270.2012
PG 10
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 051KU
UT WOS:000312126200001
PM 22932685
ER
PT J
AU Zhang, JL
Qiu, SO
Zhang, YJ
Merino, M
Fetsch, P
Avital, I
Filie, A
Pastan, I
Hassan, R
AF Zhang, Jingli
Qiu, Shuo
Zhang, Yujian
Merino, Maria
Fetsch, Patricia
Avital, Itzhak
Filie, Armando
Pastan, Ira
Hassan, Raffit
TI Loss of Mesothelin Expression by Mesothelioma Cells Grown In Vitro
Determines Sensitivity to Anti-Mesothelin Immunotoxin SS1P
SO ANTICANCER RESEARCH
LA English
DT Article
DE Mesothelin; MPF; SS1P; pleural mesothelioma; peritoneal mesothelioma
ID MEGAKARYOCYTE POTENTIATING FACTOR; MALIGNANT PLEURAL MESOTHELIOMA;
OVARIAN-CANCER; RECOMBINANT IMMUNOTOXIN; TUMOR-MARKER; DIAGNOSIS;
IMMUNOTHERAPY; BINDING
AB Background/Aim: To determine if early passage tumor cells obtained from patients with mesothelioma continue to express the tumor differentiation antigen mesothelin and their sensitivity to the anti-mesothelin immunotoxin SS1P. Materials and Methods: Cell cultures were established from ascites or pleural effusion of 6 peritoneal and 3 pleural mesothelioma patients, respectively. These cells were evaluated for mesothelin expression by immunohistochemistry and flow cytometry. Results: Although mesothelin was highly expressed in tumor biopsies of all patients, only 3 out of 9 malignant effusions from these patients when grown in short-term culture showed strong mesothelin positivity by IHC. By flow cytometry, the number of mesothelin sites per cell was variable ranging from 580 to 210,000 sites/cell. Cells with strong mesothelin expression by IHC and increased number of mesothelin sites/cell were sensitive to SS1P. Conclusions: Most mesothelioma tumors loose mesothelin when grown in vitro and the sensitivity of these cells to SS1P is dependent on the number of mesothelin sites/cell.
C1 [Zhang, Jingli; Qiu, Shuo; Zhang, Yujian; Pastan, Ira; Hassan, Raffit] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Merino, Maria; Fetsch, Patricia; Filie, Armando] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Avital, Itzhak] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hassan, R (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5116, Bethesda, MD 20892 USA.
EM hassanr@mail.nih.gov
FU Intramural Research Program of the 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 28
TC 10
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U1 0
U2 0
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD DEC
PY 2012
VL 32
IS 12
BP 5151
EP 5158
PG 8
WC Oncology
SC Oncology
GA 050GA
UT WOS:000312040000002
PM 23225411
ER
PT J
AU Baskaran, S
Ragusa, MJ
Hurley, JH
AF Baskaran, Sulochanadevi
Ragusa, Michael J.
Hurley, James H.
TI How Atg18 and the WIPIs sense phosphatidylinositol 3-phosphate
SO AUTOPHAGY
LA English
DT Editorial Material
DE Atg18; Atg21; WIPI; membrane binding; autophagy
AB The key autophagic lipid sensors are Atg18 in yeast and the WIPI proteins in mammals. Atg18 and the WIPIs belong to the PROPPIN family of proteins. PROPPINs are seven-bladed beta-propellers that bind to phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2]. In order to understand how PROPPINs bind phosphoinositides, we have determined the crystal structure of a representative, biochemically tractable PROPPIN, Hsv2 of Kluveromyces lactis. The structure revealed that PROPPINs contain two phosphoinositide binding sites which cooperate with a hydrophobic anchoring loop in membrane binding. These three binding elements cooperate in function, as demonstrated by the incremental loss of function in Atg18 mutants impaired in combinations of the two phosphoinositide binding sites and the hydrophobic loop.
C1 [Baskaran, Sulochanadevi; Ragusa, Michael J.; Hurley, James H.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM james.hurley@nih.gov
FU Intramural NIH HHS
NR 0
TC 6
Z9 6
U1 0
U2 6
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8627
J9 AUTOPHAGY
JI Autophagy
PD DEC
PY 2012
VL 8
IS 12
BP 1851
EP 1852
DI 10.4161/auto.22077
PG 2
WC Cell Biology
SC Cell Biology
GA 049AD
UT WOS:000311953500024
PM 22996041
ER
PT J
AU Floisand, Y
Brinch, L
Gedde-Dahl, T
Tjonnfjord, GE
Dybedal, I
Holte, H
Heldal, D
Torfoss, D
Aurlien, E
Lauritzsen, GF
Fossa, A
Lehne, G
Baggerod, E
Kvalheim, G
Egeland, T
Bishop, MR
Fowler, DH
Kolstad, A
AF Floisand, Y.
Brinch, L.
Gedde-Dahl, T.
Tjonnfjord, G. E.
Dybedal, I.
Holte, H.
Heldal, D.
Torfoss, D.
Aurlien, E.
Lauritzsen, G. F.
Fossa, A.
Lehne, G.
Baggerod, E.
Kvalheim, G.
Egeland, T.
Bishop, M. R.
Fowler, D. H.
Kolstad, A.
TI Ultra-short course sirolimus contributes to effective GVHD prophylaxis
after reduced-intensity allogeneic hematopoietic cell transplantation
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE reduced-intensity conditioning; lymphoma; sirolimus; GVHD
ID BONE-MARROW-TRANSPLANTATION; SINGLE-CENTER EXPERIENCE;
VERSUS-HOST-DISEASE; FOLLICULAR LYMPHOMA; MULTIPLE-MYELOMA;
HODGKIN-LYMPHOMA; EUROPEAN GROUP; FOLLOW-UP; BLOOD; RISK
AB Reduced-intensity conditioning (RIC) allo-SCT is a potentially curative treatment approach for patients with relapsed Hodgkin's or non-Hodgkin's lymphoma. In the present study, 37 patients underwent RIC allo-SCT after induction treatment with EPOCH-F(R) using a novel form of dual-agent immunosuppression for GVHD prophylaxis with CsA and sirolimus. With a median follow-up of 28 months among survivors, the probability for OS at 3 and 5 years was 56%. Treatment-related mortality was 16% at day +100 and 30% after 1 year of transplant. Acute GVHD grades II-IV developed in 38% of patients, suggesting that the regimen consisting of CsA and an ultra-short course of sirolimus is effective in the prevention of acute GVHD. Bone Marrow Transplantation (2012) 47, 1552-1557; doi:10.1038/bmt.2012.63; published online 23 April 2012
C1 [Floisand, Y.; Brinch, L.; Gedde-Dahl, T.; Tjonnfjord, G. E.; Dybedal, I.; Heldal, D.] Natl Hosp Norway, Oslo Univ Hosp, Dept Hematol, NO-0424 Oslo, Norway.
[Tjonnfjord, G. E.] Univ Oslo, Inst Clin Med, Oslo, Norway.
[Holte, H.; Torfoss, D.; Aurlien, E.; Lauritzsen, G. F.; Fossa, A.; Lehne, G.; Baggerod, E.; Kolstad, A.] Oslo Univ Hosp, Dept Oncol, Oslo, Norway.
[Kvalheim, G.] Oslo Univ Hosp, Dept Cellular Therapy, Oslo, Norway.
[Egeland, T.] Oslo Univ Hosp, Inst Immunol, Oslo, Norway.
[Bishop, M. R.; Fowler, D. H.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Floisand, Y (reprint author), Natl Hosp Norway, Oslo Univ Hosp, Dept Hematol, Sognsvannsveien 20,POB 4950, NO-0424 Oslo, Norway.
EM yngvar.floisand@oslo-universitetssykehus.no
NR 31
TC 4
Z9 4
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD DEC
PY 2012
VL 47
IS 12
BP 1552
EP 1557
DI 10.1038/bmt.2012.63
PG 6
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 050VO
UT WOS:000312082600011
PM 22522568
ER
PT J
AU Montrose, DC
Zhou, XK
Kopelovich, L
Yantiss, RK
Karoly, ED
Subbaramaiah, K
Dannenberg, AJ
AF Montrose, David C.
Zhou, Xi Kathy
Kopelovich, Levy
Yantiss, Rhonda K.
Karoly, Edward D.
Subbaramaiah, Kotha
Dannenberg, Andrew J.
TI Metabolic Profiling, a Noninvasive Approach for the Detection of
Experimental Colorectal Neoplasia
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID MASS-SPECTROMETRY; COLON TUMORS; BETA-CATENIN; MOUSE COLON; KI-RAS;
CANCER; AZOXYMETHANE; MUTATIONS; GENE; DNA
AB Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Although noninvasive stool-based screening tests are used for the early detection of colorectal neoplasia, concerns have been raised about their sensitivity and specificity. A metabolomics-based approach provides a potential noninvasive strategy to identify biomarkers of colorectal carcinogenesis including premalignant adenomas. Our primary objective was to determine whether a distinct metabolic profile could be found in both feces and plasma during experimental colorectal carcinogenesis. Feces, plasma as well as tumor tissue and normal colorectal mucosa were obtained from A/J mice at several time points following administration of azoxymethane or saline. Ultra-performance liquid chromatography tandem mass spectroscopy and gas chromatography mass spectroscopy were used to quantify metabolites in each of these matrices. Here, we show that colorectal carcinogenesis was associated with significant metabolic alterations in both the feces and plasma, some of which overlap with metabolic changes in the tumor tissue. These consisted of 33 shared changes between feces and tumor, 14 shared changes between plasma and tumor, and 3 shared changes across all 3 matrices. For example, elevated levels of sarcosine were found in both tumor and feces whereas increased levels of 2-hydroxyglutarate were found in both tumor and plasma. Collectively, these results provide evidence that metabolomics can be used to detect changes in feces and plasma during azoxymethane-induced colorectal carcinogenesis and thus provide a strong rationale for future studies in humans. Cancer Prev Res; 5(12); 1358-67. (c) 2012 AACR.
C1 [Montrose, David C.; Subbaramaiah, Kotha; Dannenberg, Andrew J.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
[Zhou, Xi Kathy] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10065 USA.
[Yantiss, Rhonda K.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Karoly, Edward D.] Metabolon Inc, Durham, NC USA.
RP Dannenberg, AJ (reprint author), Weill Cornell Med Coll, Dept Med, 525 E 68th St,Room F-206, New York, NY 10065 USA.
EM ajdannen@med.cornell.edu
FU NCI [N01-CN-43302]; NIH [T32 CA062948]; NIH CTSC [UL-RR024996]; New York
Crohn's Foundation
FX The project was supported by NCI N01-CN-43302, NIH T32 CA062948, NIH
CTSC UL-RR024996, and the New York Crohn's Foundation.
NR 36
TC 22
Z9 22
U1 0
U2 28
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD DEC
PY 2012
VL 5
IS 12
BP 1358
EP 1367
DI 10.1158/1940-6207.CAPR-12-0160
PG 10
WC Oncology
SC Oncology
GA 049VL
UT WOS:000312011400004
PM 22961778
ER
PT J
AU Menendez, D
Resnick, MA
Haran, TE
AF Menendez, Daniel
Resnick, Michael A.
Haran, Tali E.
TI Transactivation by low and high levels of human p53 reveals new physical
rules of engagement and novel super-transactivation sequences
SO CELL CYCLE
LA English
DT Editorial Material
C1 [Menendez, Daniel; Resnick, Michael A.] NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Haran, Tali E.] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel.
RP Resnick, MA (reprint author), NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM resnick@niehs.nih.gov; bitali@tx.technion.ac.il
OI Haran, Tali E./0000-0002-9700-3392
NR 9
TC 3
Z9 3
U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD DEC 1
PY 2012
VL 11
IS 23
BP 4287
EP 4288
DI 10.4161/cc.22467
PG 2
WC Cell Biology
SC Cell Biology
GA 048ZJ
UT WOS:000311951500002
PM 23095671
ER
PT J
AU Zhang, YW
Ghosh, AK
Pommier, Y
AF Zhang, Yong-Wei
Ghosh, Arun K.
Pommier, Yves
TI Lasonolide A, a potent and reversible inducer of chromosome condensation
SO CELL CYCLE
LA English
DT Article
DE histone H3 phosphorylation; histone H3 deacetylation; chromosome
condensation; maturation promoting factor; topoisomerase II; Aurora
kinase
ID DNA TOPOISOMERASE-II; HISTONE H3 PHOSPHORYLATION; AURORA-B; MITOTIC
CHROMOSOMES; PREMATURE MITOSIS; MAMMALIAN-CELLS; KINASE-ACTIVITY;
PROTEIN-KINASE; OKADAIC ACID; INHIBITOR
AB Lasonolide A (LSA) is a natural product with high and selective cytotoxicity against mesenchymal cancer cells, including leukemia, melanomas and glioblastomas. Here, we reveal that LSA induces rapid and reversible premature chromosome condensation (PCC) associated with cell detachment, plasma membrane smoothening and actin reorganization. PCC is induced at all phases of the cell cycle in proliferative cells as well as in circulating human lymphocytes in G(0). It is independent of Cdk1 signaling, associated with cyclin B downregulation and induced in cells at LSA concentrations that are three orders of magnitude lower than those required to block phosphatases 1 and 2A in vitro. At the epigenetic level, LSA-induced PCC is coupled with histone H3 and H1 hyperphosphorylation and deacetylation. Treatment with SAHA reduced LSA-induced PCC, implicating histone deacetylation as one of the PCC effector mechanisms. In addition, PCC is coupled with topoisomerase II (Top2) and Aurora A hyperphosphorylation and activation. Inhibition of Top2 or Aurora A partially blocked LSA-induced PCC. Our findings demonstrate the profound epigenetic alterations induced by LSA and the potential of LSA as a new cytogenetic tool. Based on the unique cellular effects of LSA, further studies are warranted to uncover the cellular target of lasonolide A ("TOL").
C1 [Zhang, Yong-Wei; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU Center for Cancer Research, National Cancer Institute Intramural Program
FX Our studies are supported by the Center for Cancer Research, National
Cancer Institute Intramural Program. We wish to thank Ernest Hamel,
Toxicology and Pharmacology Branch, Developmental Therapeutics Program,
National Cancer Institute, Frederick, MD for bringing LSA to our
attention and providing initial drug samples. We also wish to thank
Kiyung S. Lee, Laboratory of Metabolism, CCR-NCI, Bethesda for
discussions and for suggesting or providing the Aurora and Plk
inhibitors.
NR 48
TC 6
Z9 6
U1 2
U2 12
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD DEC 1
PY 2012
VL 11
IS 23
BP 4424
EP 4435
DI 10.4161/cc.22768
PG 12
WC Cell Biology
SC Cell Biology
GA 048ZJ
UT WOS:000311951500026
PM 23159859
ER
PT J
AU Gavin, PG
Colangelo, LH
Fumagalli, D
Tanaka, N
Remillard, MY
Yothers, G
Kim, C
Taniyama, Y
Kim, SI
Choi, HJ
Blackmon, NL
Lipchik, C
Petrelli, NJ
O'Connell, MJ
Wolmark, N
Paik, S
Pogue-Geile, KL
AF Gavin, Patrick G.
Colangelo, Linda H.
Fumagalli, Debora
Tanaka, Noriko
Remillard, Matthew Y.
Yothers, Greg
Kim, Chungyeul
Taniyama, Yusuke
Kim, Seung Il
Choi, Hyun Joo
Blackmon, Nicole L.
Lipchik, Corey
Petrelli, Nicholas J.
O'Connell, Michael J.
Wolmark, Norman
Paik, Soonmyung
Pogue-Geile, Kay L.
TI Mutation Profiling and Microsatellite Instability in Stage II and III
Colon Cancer: An Assessment of Their Prognostic and Oxaliplatin
Predictive Value
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ISLAND METHYLATOR PHENOTYPE; POPULATION-BASED SERIES; COLORECTAL-CANCER;
PIK3CA MUTATION; BRAF MUTATIONS; POOR SURVIVAL; ADJUVANT TREATMENT;
MISMATCH-REPAIR; KRAS MUTATIONS; GENE-MUTATIONS
AB Purpose: The purpose of this study was to examine the prognostic and oxaliplatin predictive value of mismatch repair (MMR) status and common hot spot mutations, which we previously identified in stage II and III colon cancer.
Experimental Design: Mutations in BRAF, KRAS, NRAS, MET, and PIK3CA were profiled in 2,299 stage II and III colon tumors from National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials C-07 (n = 1,836) and C-08 (n = 463) with Type Plex chemistry and mass spectrometry. C-07 tested the worth of adding oxaliplatin to 5-fluorouracil plus leucovorin, and C-08 tested the worth of adding bevacizumab to FOLFOX. Cox proportional hazard models were used to assess prognostic or oxaliplatin predictive value of mutations for tumor recurrence, overall survival (OS), and survival after recurrence (SAR).
Results: BRAF mutations were associated with MMR-deficient tumors (P < 0.0001), poor OS [HR, 1.46; 95% confidence interval (CI), 1.20-1.79; P <= 0.0002], and poor SAR (HR, 2.31; 95% CI, 1.83-2.95; P < 0.0001). Mutations in KRAS, NRAS, MET, and PIK3CA were not associated with recurrence, OS, or SAR. MMR-deficient tumors were associated with an improved prognosis based on recurrence (HR, 0.48; 95% CI, 0.33-0.70; P < 0.0001). Mutations and MMR status were not predictive for oxaliplatin benefit.
Conclusions: This study shows that BRAF mutations profiled from stage II and III colon cancer tumors were associated with poor SAR and validates and explains, at least in part, previous observations associating it with poor OS. Profiling of all of these mutations is warranted for future clinical trials testing new targeted therapies that block relevant signaling pathways. Such clinical trials are under development at NSABP. Clin Cancer Res; 18(23); 6531-41. (C) 2012 AACR.
C1 [Gavin, Patrick G.; Colangelo, Linda H.; Fumagalli, Debora; Tanaka, Noriko; Remillard, Matthew Y.; Yothers, Greg; Kim, Chungyeul; Taniyama, Yusuke; Kim, Seung Il; Choi, Hyun Joo; Blackmon, Nicole L.; Lipchik, Corey; Petrelli, Nicholas J.; O'Connell, Michael J.; Wolmark, Norman; Paik, Soonmyung; Pogue-Geile, Kay L.] Univ Pittsburgh, Natl Surg Adjuvant Breast & Bowel Project NSABP, Pittsburgh, PA USA.
[Colangelo, Linda H.; Tanaka, Noriko; Yothers, Greg] Univ Pittsburgh, NSABP Biostat Ctr, Pittsburgh, PA USA.
[Colangelo, Linda H.; Tanaka, Noriko; Yothers, Greg] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Wolmark, Norman] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
[Petrelli, Nicholas J.] Christiana Care, Helen F Graham Canc Ctr, Newark, DE USA.
RP Pogue-Geile, KL (reprint author), NSABP, Div Pathol, 1307 Fed St,Ste 303, Pittsburgh, PA 15212 USA.
EM kay.pogue@nsabp.org
OI kim, chungyeul/0000-0002-9636-5228; Yothers, Greg/0000-0002-7965-7333
FU National Cancer Institute, Department of Health and Human Services
[U10-CA-37377, U10-CA-69974, U10-CA-12027, U10-CA-69651, U24-CA-114732];
Sanofi-Synthelabo, Inc.; Genentech, Inc.; Pennsylvania Department of
Health
FX The study was supported by Public Health Service Grants U10-CA-37377,
U10-CA-69974, U10-CA-12027, U10-CA-69651, and U24-CA-114732 from the
National Cancer Institute, Department of Health and Human Services; by
Sanofi-Synthelabo, Inc.; Genentech, Inc.; and funded in part under a
grant from the Pennsylvania Department of Health.
NR 46
TC 87
Z9 90
U1 1
U2 9
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 DEC 1
PY 2012
VL 18
IS 23
BP 6531
EP 6541
DI 10.1158/1078-0432.CCR-12-0605
PG 11
WC Oncology
SC Oncology
GA 050AU
UT WOS:000312025600016
PM 23045248
ER
PT J
AU Cohen, RM
Sacks, DB
AF Cohen, Robert M.
Sacks, David B.
TI Comparing Multiple Measures of Glycemia: How to Transition from
Biomarker to Diagnostic Test?
SO CLINICAL CHEMISTRY
LA English
DT Editorial Material
ID GLUCOSE; HBA1C; A1C; COMPLICATIONS; FRUCTOSAMINE; MARKER
C1 [Cohen, Robert M.] Univ Cincinnati, Med Ctr, Dept Med, Div Endocrinol Diabet & Metab,Coll Med, Cincinnati, OH 45267 USA.
[Cohen, Robert M.] Cincinnati VA Med Ctr, Cincinnati, OH USA.
[Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
RP Cohen, RM (reprint author), Univ Cincinnati, Med Ctr, Dept Med, Div Endocrinol Diabet & Metab,Coll Med, POB 670547, Cincinnati, OH 45267 USA.
EM Robert.cohen@uc.edu
OI Sacks, David/0000-0003-3100-0735
FU Intramural NIH HHS; NCRR NIH HHS [5UL1RR026314]; NIDDK NIH HHS [R01
DK63088]
NR 17
TC 8
Z9 8
U1 0
U2 11
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD DEC
PY 2012
VL 58
IS 12
BP 1615
EP 1617
DI 10.1373/clinchem.2012.196139
PG 3
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 049KJ
UT WOS:000311981600001
PM 23115055
ER
PT J
AU Coglianese, EE
Larson, MG
Vasan, RS
Ho, JE
Ghorbani, A
McCabe, EL
Cheng, S
Fradley, MG
Kretschman, D
Gao, W
O'Connor, G
Wang, TJ
Januzzi, JL
AF Coglianese, Erin E.
Larson, Martin G.
Vasan, Ramachandran S.
Ho, Jennifer E.
Ghorbani, Anahita
McCabe, Elizabeth L.
Cheng, Susan
Fradley, Michael G.
Kretschman, Dana
Gao, Wei
O'Connor, George
Wang, Thomas J.
Januzzi, James L.
TI Distribution and Clinical Correlates of the Interleukin Receptor Family
Member Soluble ST2 in the Framingham Heart Study
SO CLINICAL CHEMISTRY
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; NATRIURETIC PEPTIDE; ACUTE EXACERBATION;
FAILURE; MORTALITY; PROTEIN; DISEASE; PLASMA; RISK; INDIVIDUALS
AB BACKGROUND: Soluble ST2 (sST2) is a cardiac biomarker whose concentration rises in response to myocardial strain. Increased sST2 concentrations may predict adverse outcomes in patients with heart failure and myocardial infarction. Because sST2 was largely undetectable with first-generation assays in ambulatory individuals, there are few data regarding its distribution and correlates in community-based populations.
METHODS: We measured sST2 using a highly sensitive ELISA in 3450 Framingham Heart Study participants who attended a routine examination. We used multivariable linear regression models to identify covariates associated with sST2 in the general sample. We obtained a reference sample (n = 1136) by excluding individuals with prevalent coronary disease, heart failure, atrial fibrillation, diabetes, hypertension, obesity, valvular disease, left ventricular systolic dysfunction, and pulmonary and renal dysfunction. We used empiric and quantile regression techniques to estimate the 2.5th, 50th, 97.5th, and 99th quantiles.
RESULTS: In the general sample (mean age 59 years, 55% women), systolic blood pressure (P = 0.006), antihypertensive medication use (P = 0.03), and diabetes (P < 0.001) were associated with sST2 concentrations. In the reference sample (mean age 55, 59% women), male sex (P < 0.0001) and older age (P = 0.004) were predictive of higher sST2 concentrations. Quantile and empirical methods were used to define the reference intervals. Using the empirical approach, upper 99% percentile values in different age groups ranged from 46.6 to 64.4 mu g/L in men and 36.7 to 53.0 mu g/L in women.
CONCLUSIONS: In a well-characterized, community-based cohort, values for sST2 differ between men and women, increase with age, and are associated with diabetes and hypertension. (C) 2012 American Association for Clinical Chemistry
C1 [Ho, Jennifer E.; Ghorbani, Anahita; Fradley, Michael G.; Wang, Thomas J.; Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Coglianese, Erin E.] Loyola Univ Hlth Syst, Div Cardiol, Maywood, IL USA.
[Larson, Martin G.; Vasan, Ramachandran S.; Cheng, Susan; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Larson, Martin G.; McCabe, Elizabeth L.; Gao, Wei] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Prevent Med & Epidemiol Sect, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Cardiol Sect, Boston, MA 02215 USA.
[Cheng, Susan] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
[Kretschman, Dana; O'Connor, George] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA.
RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA.
EM jjanuzzi@partners.org
OI Larson, Martin/0000-0002-9631-1254; Ho, Jennifer/0000-0002-7987-4768;
O'Connor, George/0000-0002-6476-3926; Ramachandran,
Vasan/0000-0001-7357-5970
FU Ellison Foundation; Roman W. DeSanctis Clinical Scholar Fund;
[N01-HC-25195]; [K99HL107642]; [R01-HL-086875]
FX N01-HC-25195, a contract to the Framingham Heart Study. S. Cheng, grant
K99HL107642 and the Ellison Foundation; T.J. Wang, R01-HL-086875; J.L.
Januzzi, endowment from the Roman W. DeSanctis Clinical Scholar Fund.
NR 36
TC 36
Z9 41
U1 0
U2 9
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD DEC
PY 2012
VL 58
IS 12
BP 1673
EP 1681
DI 10.1373/clinchem.2012.192153
PG 9
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 049KJ
UT WOS:000311981600014
PM 23065477
ER
PT J
AU Hoffmann, W
Singh, SR
AF Hoffmann, Werner
Singh, Shree Ram
TI Stem Cells in Regenerative Medicine and Cancer
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Editorial Material
C1 [Hoffmann, Werner] Univ Magdeburg, Inst Mol Biol & Med Chem, D-39120 Magdeburg, Germany.
[Singh, Shree Ram] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
RP Hoffmann, W (reprint author), Univ Magdeburg, Inst Mol Biol & Med Chem, Leipziger Str 44, D-39120 Magdeburg, Germany.
EM werner.hoffmann@med.ovgu.de; singhshr@mail.nih.gov
RI Singh, Shree Ram/B-7614-2008
OI Singh, Shree Ram/0000-0001-6545-583X
NR 0
TC 1
Z9 1
U1 0
U2 0
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 0929-8673
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD DEC
PY 2012
VL 19
IS 35
BP 5964
EP 5964
PG 1
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 049CM
UT WOS:000311959600006
PM 22963574
ER
PT J
AU Singh, SR
AF Singh, Shree Ram
TI Stem Cell Niche in Tissue Homeostasis, Aging and Cancer
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE Stem cell; stem cell niche; tissue homeostasis; aging; cancer
ID BONE-MARROW NICHE; HEMATOPOIETIC STEM; SELF-RENEWAL; DROSOPHILA TESTIS;
C-ELEGANS; GERM-LINE; JAK-STAT; IN-VIVO; REGENERATIVE MEDICINE;
SIGNALING PATHWAYS
AB Stem cells have an essential role in tissue homeostasis, repair, and regeneration of a tissue or an organ. Stem cells are immature cells having unlimited ability of self-renewal and capacity to differentiate into specialized cell types. Proper regulation of these dual properties is critical in animal development, growth control, and reproduction. Accumulating evidences suggest that stem cell behavior is regulated by both extracellular signals from the niche cells and intrinsic signal within stem cells. Using diverse model systems, tremendous work has been done to understand how niche control the stem cell self-renewal and differentiation. This review presents the progress made in stem cell niche field in germline and somatic stem cells in lower organism and mammals. The knowledge gained by studying the stem cells and its niches in diverse model organisms and the molecular mechanisms regulate their behavior are vital in understanding tissue homeostasis, regeneration, aging and cancer in humans.
C1 NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
RP Singh, SR (reprint author), NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
EM singhshr@mail.nih.gov
RI Singh, Shree Ram/B-7614-2008
OI Singh, Shree Ram/0000-0001-6545-583X
FU Intramural NIH HHS [Z99 CA999999]
NR 181
TC 17
Z9 17
U1 0
U2 35
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 0929-8673
EI 1875-533X
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD DEC
PY 2012
VL 19
IS 35
BP 5965
EP 5974
PG 10
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 049CM
UT WOS:000311959600007
PM 22963571
ER
PT J
AU Nitert, MD
Dayeh, T
Volkov, P
Elgzyri, T
Hall, E
Nilsson, E
Yang, BT
Lang, S
Parikh, H
Wessman, Y
Weishaupt, H
Attema, J
Abels, M
Wierup, N
Almgren, P
Jansson, PA
Ronn, T
Hansson, O
Eriksson, KF
Groop, L
Ling, C
AF Nitert, Marloes Dekker
Dayeh, Tasnim
Volkov, Peter
Elgzyri, Targ
Hall, Elin
Nilsson, Emma
Yang, Beatrice T.
Lang, Stefan
Parikh, Hemang
Wessman, Ylva
Weishaupt, Holger
Attema, Joanne
Abels, Mia
Wierup, Nils
Almgren, Peter
Jansson, Per-Anders
Ronn, Tina
Hansson, Ola
Eriksson, Karl-Fredrik
Groop, Leif
Ling, Charlotte
TI Impact of an Exercise Intervention on DNA Methylation in Skeletal Muscle
From First-Degree Relatives of Patients With Type 2 Diabetes
SO DIABETES
LA English
DT Article
ID GENE-EXPRESSION; LIFE-STYLE; INSULIN-SECRETION; CAMK ACTIVATION; CPG
METHYLATION; IN-VIVO; PROMOTER; MELLITUS; BINDING; DIET
AB To identify epigenetic patterns, which may predispose to type 2 diabetes (T2D) due to a family history (FH) of the disease, we analyzed DNA methylation genome-wide in skeletal muscle from individuals with (FH+) or without (FH-) an FH of T2D. We found differential DNA methylation of genes in biological pathways including mitogen-activated protein kinase (MAPK), insulin, and calcium signaling (P <= 0.007) and of individual genes with known function in muscle, including MAPK1, MYO18B, HOXC6, and the AMP-activated protein kinase subunit PRKAB1 in skeletal muscle of FH+ compared with FH- men. We further validated our findings from Fir men in monozygotic twin pairs discordant for T2D, and 40% of 65 analyzed genes exhibited differential DNA methylation in muscle of both FH+ men and diabetic twins. We further examined if a 6-month exercise intervention modifies the genome-wide DNA methylation pattern in skeletal muscle of the FH+ and FH- individuals. DNA methylation of genes in retinol metabolism and calcium signaling pathways (P < 3 x 10(-6)) and with known functions in muscle and T2D including MEF2A, RUNX1, NDUFC2, and THADA decreased after exercise. Methylation of these human promoter regions suppressed reporter gene expression in vitro. In addition, both expression and methylation of several genes, i.e., ADIPOR1, BDKRB2, and TRIM, changed after exercise. These findings provide new insights into how genetic background and environment can alter the human epigenome. Diabetes 61:3322-3332, 2012
C1 [Nitert, Marloes Dekker; Dayeh, Tasnim; Volkov, Peter; Elgzyri, Targ; Hall, Elin; Nilsson, Emma; Yang, Beatrice T.; Lang, Stefan; Wessman, Ylva; Abels, Mia; Wierup, Nils; Almgren, Peter; Ronn, Tina; Hansson, Ola; Eriksson, Karl-Fredrik; Groop, Leif; Ling, Charlotte] Lund Univ, Dept Clin Sci, Ctr Diabet, CRC,Scania Univ Hosp, Malmo, Sweden.
[Parikh, Hemang] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Weishaupt, Holger; Attema, Joanne] Lund Univ, Inst Expt Med Sci, Immunol Unit, Malmo, Sweden.
[Jansson, Per-Anders] Sahlgrens Univ Hosp, Wallenberg Lab, Gothenburg, Sweden.
RP Ling, C (reprint author), Lund Univ, Dept Clin Sci, Ctr Diabet, CRC,Scania Univ Hosp, Malmo, Sweden.
EM charlotte.ling@med.lu.se
RI Hansson, Ola/F-1793-2011; Ling, Charlotte/Q-2432-2015; Dekker Nitert,
Marloes/A-8822-2011
OI Hansson, Ola/0000-0002-7394-7639; Ling, Charlotte/0000-0003-0587-7154;
Dekker Nitert, Marloes/0000-0002-1909-8920
FU Swedish Research Council [349-2008-6589]; strategic research area grant
(Excellence of Diabetes Research in Sweden) [2009-1039]; Knut and Alice
Wallenberg Foundation [2009-0243]; Lundberg Foundation [359]; Avtal om
Lakarutbildning och Forskning; Novo Nordisk Foundation;
Universitetssjukhuset Malmo Allmana Sjukhus Fonder; Tore Nilsson;
Syskonen Svenssons Fond; Diabetes Foundation; Kungliga Fysiografiska
Sallskapet in Lund; European Foundation for the Study of Diabetes-Lilly
Foundation; Svenska stiftelsen for medicinsk forskning; Pahlsson
FX This work was supported by grants from the Swedish Research Council,
including a Linnaeus grant (Lund University Diabetes Center,
349-2008-6589) and a strategic research area grant (Excellence of
Diabetes Research in Sweden, 2009-1039), as well as equipment grants
from the Knut and Alice Wallenberg Foundation (2009-0243), the Lundberg
Foundation (Grant 359), Avtal om Lakarutbildning och Forskning, the Novo
Nordisk Foundation, Universitetssjukhuset Malmo Allmana Sjukhus Fonder,
Tore Nilsson, Syskonen Svenssons Fond, Diabetes Foundation, Kungliga
Fysiografiska Sallskapet in Lund, European Foundation for the Study of
Diabetes-Lilly Foundation, Svenska stiftelsen for medicinsk forskning,
and Pahlsson. The group of Swedish twins was recruited from the Swedish
Twin Registry, which is supported by grants from the Swedish Department
of Higher Education and the Swedish Research Council. No other potential
conflicts of interest relevant to this article were reported.
NR 50
TC 103
Z9 109
U1 1
U2 42
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD DEC
PY 2012
VL 61
IS 12
BP 3322
EP 3332
DI 10.2337/db11-1653
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 050GR
UT WOS:000312041700040
PM 23028138
ER
PT J
AU Hu, G
Tian, HG
Zhang, FX
Liu, HK
Zhang, CP
Zhang, S
Wang, LS
Liu, GS
Yu, ZJ
Yang, XL
Qi, L
Zhang, CL
Wang, H
Li, M
Leng, JH
Li, Y
Dong, L
Tuomilehto, J
AF Hu, Gang
Tian, Huiguang
Zhang, Fuxia
Liu, Huikun
Zhang, Cuiping
Zhang, Shuang
Wang, Leishen
Liu, Gongshu
Yu, Zhijie
Yang, Xilin
Qi, Lu
Zhang, Cuilin
Wang, Hua
Li, Min
Leng, Junhong
Li, Yi
Dong, Ling
Tuomilehto, Jaakko
TI Tianjin Gestational Diabetes Mellitus Prevention Program Study design,
methods, and 1-year interim report on the feasibility of lifestyle
intervention program
SO DIABETES RESEARCH AND CLINICAL PRACTICE
LA English
DT Article
DE Gestational diabetes mellitus; Type 2 diabetes; Diet; Physical activity;
Primary intervention; Weight loss
ID IMPAIRED GLUCOSE-TOLERANCE; PHYSICAL-ACTIVITY; RISK-FACTORS;
WEIGHT-LOSS; FOLLOW-UP; INCREASING PREVALENCE; METABOLIC SYNDROME;
GRAVES-DISEASE; WOMEN; CHINA
AB Objective: To assess whether lifestyle intervention can reduce type 2 diabetes risk in women with prior GDM in the Tianjin Gestational Diabetes Mellitus (GDM) Prevention Program.
Methods: 1180 women who were diagnosed with GDM from 2005 to 2009 were randomly assigned to either a lifestyle intervention (n = 586) or a control group (n = 594). Major elements of the intervention include six face-to-face meetings with study dietitians in the first year, and two additional sessions and two telephone calls in second year.
Results: During the first year, average body weight loss in the first 404 subjects was 1.40 kg (2.1%) in the intervention group vs 0.21 kg (0.3%) in the control group (P = 0.001), and the decrease was more significant among baseline overweight women (body bass index [BMI] >= 24 kg/m(2)) in the intervention (2.91 kg/4.2%) compared with that in the control group (0.51 kg/0.7%) (P < 0.001). In addition, women in the intervention group, compared with those in the control group, have decreased BMI, body fat, waist circumference, and plasma insulin levels, and have improved behaviors including increased leisure time activity and dietary fiber intake and decreased sedentary time and fat consumptions.
Conclusion: The interim results support the efficacy and feasibility of the lifestyle intervention program. Crown Copyright (C) 2012 Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Hu, Gang] Pennington Biomed Res Ctr, Chron Dis Epidemiol Lab, Baton Rouge, LA 70808 USA.
[Tian, Huiguang; Zhang, Fuxia; Liu, Huikun; Zhang, Cuiping; Zhang, Shuang; Wang, Leishen; Liu, Gongshu; Wang, Hua; Li, Min; Leng, Junhong; Li, Yi; Dong, Ling] Tianjin Womens & Childrens Hlth Ctr, Tianjin, Peoples R China.
[Yu, Zhijie] Dalhousie Univ, Populat Canc Res Program, Halifax, NS, Canada.
[Yang, Xilin] Tianjin Med Univ, Sch Publ Hlth, Dept Epidemiol, Tianjin, Peoples R China.
[Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.
[Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland.
RP Hu, G (reprint author), Pennington Biomed Res Ctr, Chron Dis Epidemiol Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA.
EM gang.hu@pbrc.edu
FU European Foundation for the Study of Diabetes (EFSD)/Chinese Diabetes
Society (CDS); Tianjin Public Health Bureau; Eunice Kennedy Shriver
National Institute of Child Health & Human Development, National
Institutes of Health
FX This study was supported by grants from the European Foundation for the
Study of Diabetes (EFSD)/Chinese Diabetes Society (CDS)/Lilly Programme
for Collaborative Research between China and Europe, and Tianjin Public
Health Bureau. Dr. Zhang was supported by the Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
& Human Development, National Institutes of Health.
NR 39
TC 30
Z9 32
U1 2
U2 20
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0168-8227
J9 DIABETES RES CLIN PR
JI Diabetes Res. Clin. Pract.
PD DEC
PY 2012
VL 98
IS 3
BP 508
EP 517
DI 10.1016/j.diabres.2012.09.015
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 051NI
UT WOS:000312133700026
PM 23010556
ER
PT J
AU Dawson, DA
Smith, SM
Saha, TD
Rubinsky, AD
Grant, BF
AF Dawson, Deborah A.
Smith, Sharon M.
Saha, Tulshi D.
Rubinsky, Anna D.
Grant, Bridget F.
TI Comparative performance of the AUDIT-C in screening for DSM-IV and DSM-5
alcohol use disorders
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE AUDIT-C; Screening; Alcohol use disorder; DSM-IV; DSM-5
ID IDENTIFICATION TEST AUDIT; RISK DRINKING; GENERAL-POPULATION;
QUESTIONNAIRES; CONSUMPTION; DEPENDENCE; DIAGNOSIS; SAMPLE; MISUSE;
TESTS
AB Objective: Under the proposed DSM-5 revision to the criteria for alcohol use disorder (AUD), a substantial proportion of DSM-IV AUD cases will be lost or shifted in terms of severity, with some new cases added. 'Accordingly, the performance of the AUDIT-C in screening for DSM-IV AUD cannot be assumed to extend to DSM-5 AUD. The objective of this paper is to compare the AUDIT-C in screening for DSM-IV and DSM-5 AUD.
Methods: Using a broad range of performance metrics, the AUDIT-C was tested and contrasted as a screener for DSM-IV AUD (any AUD, abuse and dependence) and DSM-5 AUD (any AUD, moderate AUD and severe AUD) in a representative sample of U.S. adults aged 21 and older and among past-year drinkers.
Results: Optimal AUDIT-C cutpoints were identical for DSM-IV and DSM-5 AUD: >= 4 for any AUD, >= 3 or >= 4 for abuse/moderate AUD and >= 4 or >= 5 for dependence/severe AUD. Screening performance was slightly better for DSM-5 severe AUD than DSM-IV dependence but did not differ for other diagnoses. At optimal screening cutpoints, positive predictive values were slightly higher for DSM-5 overall AUD and moderate AUD than for their DSM-IV counterparts. Sensitivities were slightly higher for DSM-5 severe AUD than DSM-IV dependence. Optimal screening cutpoints shifted upwards for past-year drinkers but continued to be identical for DSM-IV and DSM-5 disorders.
Conclusions: Clinicians should not face any major overhaul of their current screening procedures as a result of the DSM-5 revision and should benefit from fewer false positive screening results. Published by Elsevier Ireland Ltd.
C1 [Dawson, Deborah A.; Smith, Sharon M.; Saha, Tulshi D.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Clin & Biol Res, NIH, Bethesda, MD USA.
[Dawson, Deborah A.] Kelly Govt Serv Inc, Bethesda, MD USA.
[Rubinsky, Anna D.] Dept Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA.
[Rubinsky, Anna D.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA.
RP Dawson, DA (reprint author), 5111 Duvall Dr, Bethesda, MD 20816 USA.
EM deborah.anne.dawson@gmail.com
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health, U.S. Department of Health and Human Services; National
Institutes of Health, National Institute on Alcohol Abuse and Alcoholism
FX The study on which this paper is based, the Wave 2 National
Epidemiologic Survey on Alcohol and Related Conditions (NESARC), is
sponsored by the National Institute on Alcohol Abuse and Alcoholism,
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, National Institute on Alcohol Abuse
and Alcoholism.
NR 28
TC 25
Z9 25
U1 2
U2 17
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD DEC 1
PY 2012
VL 126
IS 3
BP 384
EP 388
DI 10.1016/j.drugalcdep.2012.05.029
PG 5
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 050JM
UT WOS:000312049600015
PM 22728044
ER
PT J
AU Johnson, EO
Calogero, AE
Konstandi, M
Kamilaris, TC
La Vignera, S
Chrousos, GP
AF Johnson, Elizabeth O.
Calogero, Aldo E.
Konstandi, Mary
Kamilaris, Themis C.
La Vignera, Sandro
Chrousos, George P.
TI Effects of short- and long-duration hypothyroidism on
hypothalamic-pituitary-adrenal axis function in rats: In vitro and in
situ studies
SO ENDOCRINE
LA English
DT Article
DE Thyroid hormone; CRH; ACTH; Corticosterone; Corticotrophs;
Hypothalamic-pituitary-adrenal axis; Stress
ID CORTICOTROPIN-RELEASING HORMONE; MELANOCYTE-STIMULATING HORMONE; BINDING
GLOBULIN; RESPONSES; VASOPRESSIN; PROOPIOMELANOCORTIN; CORTICOSTERONE;
STRESS; HYPERTHYROIDISM; ACTIVATION
AB The purpose of this study is to assess the effects of hypothyroidism on the hypothalamic-pituitary-adrenal (HPA) axis; the functional integrity of each component of the HPA axis was examined in short-term and long-term hypothyroidism. Neuropeptide synthesis, release, and content were evaluated in vitro both in the hypothalamus and anterior pituitary, and corticosterone release was assessed in primary adrenal cell cultures at 7 (short-term) and 60 days (long-term hypothyroidism) after thyroidectomy in male rats. Hypothyroid rats showed adrenal insufficiency in several parameters, which were associated with the duration of hypothyroidism. Cerebrospinal (CSF) ACTH was decreased in all hypothyroid animals, while CSF corticosterone levels were significantly decreased only in long-term hypothyroidism. Long-term hypothyroid animals showed decreased corticotropin-releasing hormone (CRH) mRNA expression in the hypothalamic paraventricular nucleus under both basal and stress conditions, decreased CRH release from hypothalamic organ cultures after KCL and arginine vasopressin stimulation, as well as an increased number of anterior pituitary CRH receptors. In contrast, short-term hypothyroid rats showed changes in anterior pituitary function with an increased responsiveness to CRH that was associated with an increase in CRH receptors. Although both short- and long-term hypothyroidism was associated with significant decreases in adrenal weights, only long-term hypothyroid rats showed changes in adrenal function with a significant decrease of ACTH-induced corticosterone release from cultured adrenal cells. The data suggest that long-term hypothyroidism is associated with adrenal insufficiency with abnormalities in all three components of the HPA axis. Short-term hypothyroidism, on the other hand, is associated with increased pituitary corticotroph responsiveness to CRH.
C1 [Johnson, Elizabeth O.] Univ Athens, Sch Med, Dept Anat, GR-11527 Athens, Greece.
[Calogero, Aldo E.] Univ Catania, Osped Garibaldi, Dept Biomed Sci, Sect Endocrinol Androl & Internal Med, Catania, Italy.
[Konstandi, Mary] Univ Ioannina, Sch Med, Dept Pharmacol, GR-45110 Ioannina, Greece.
[Kamilaris, Themis C.] Natl Inst Child Hlth & Human Dev, Dev Endocrinol Branch, Bethesda, MD 20892 USA.
[La Vignera, Sandro] Univ Catania, Dept Internal Med & Syst Dis, Sect Endocrinol Androl & Internal Med, Catania, Italy.
[Chrousos, George P.] Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece.
RP Johnson, EO (reprint author), Univ Athens, Sch Med, Dept Anat, 75 Mikras Asias Str, GR-11527 Athens, Greece.
EM elizabethojohnson@gmail.com
NR 36
TC 7
Z9 7
U1 1
U2 15
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-008X
EI 1559-0100
J9 ENDOCRINE
JI Endocrine
PD DEC
PY 2012
VL 42
IS 3
BP 684
EP 693
DI 10.1007/s12020-012-9714-z
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 050SE
UT WOS:000312073500033
PM 22695985
ER
PT J
AU Novak, RL
Harper, DP
Caudell, D
Slape, C
Beachy, SH
Aplan, PD
AF Novak, Rachel L.
Harper, David P.
Caudell, David
Slape, Christopher
Beachy, Sarah H.
Aplan, Peter D.
TI Gene expression profiling and candidate gene resequencing identifies
pathways and mutations important for malignant transformation caused by
leukemogenic fusion genes
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; HEMATOPOIETIC
STEM-CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; MYELODYSPLASTIC SYNDROME;
NUP98-HOXD13 FUSION; BETHESDA PROPOSALS; TRANSGENIC MICE; HOX
EXPRESSION; UP-REGULATION
AB NUP98-HOXD13 (NHD13) and CALM-AF10 (CA10) are oncogenic fusion proteins produced by recurrent chromosomal translocations in patients with acute myeloid leukemia (AML). Transgenic mice that express these fusions develop AML with a long latency and incomplete penetrance, suggesting that collaborating genetic events are required for leukemic transformation. We employed genetic techniques to identify both preleukemic abnormalities in healthy transgenic mice as well as collaborating events leading to leukemic transformation. Candidate gene resequencing revealed that 6 of 27(22%) CA10 AMLs spontaneously acquired a Ras pathway mutation and 8 of 27 (30%) acquired an Flt3 mutation. Two CA10 AMLs acquired an Flt3 internal-tandem duplication, demonstrating that these mutations can be acquired in murine as well as human AML. Gene expression profiles revealed a marked up-regulation of Hox genes, particularly Hoxa5, Hoxa9, and Hoxa10 in both NHD13 and CA 10 mice. Furthermore, mir196b, which is embedded within the Hoxa locus, was overexpressed in both CA10 and NHD13 samples. In contrast, the Hox cofactors Meisl and Pbx3 were differentially expressed; Meisl was increased in CA10 AMLs but not NHD13 AMLs, whereas Pbx3 was consistently increased in NHD13 but not CA10 AMLs. Silencing of Pbx3 in NHD13 cells led to decreased proliferation, increased apoptosis, and decreased colony formation in vitro, suggesting a previously unexpected role for Pbx3 in leukemic transformation. Published by Elsevier Inc. on behalf of ISEH - Society for Hematology and Stem Cells.
C1 [Novak, Rachel L.; Caudell, David; Slape, Christopher; Beachy, Sarah H.; Aplan, Peter D.] NCI, Leukemia Biol Sect, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Harper, David P.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA.
RP Aplan, PD (reprint author), NCI, Leukemia Biol Sect, Genet Branch, Ctr Canc Res,NIH, 41 Ctr Dr, Bethesda, MD 20892 USA.
EM aplanp@mail.nih.gov
RI Slape, Christopher/H-8586-2016; Aplan, Peter/K-9064-2016
OI Slape, Christopher/0000-0002-8407-3092;
FU National Institutes of Health, National Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute.
NR 49
TC 10
Z9 11
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD DEC
PY 2012
VL 40
IS 12
BP 1016
EP 1027
DI 10.1016/j.exphem.2012.08.001
PG 12
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 049KP
UT WOS:000311982200006
PM 22885519
ER
PT J
AU Teixeira, PF
Pinho, CM
Branca, RM
Lehtio, J
Levine, RL
Glaser, E
AF Teixeira, Pedro Filipe
Pinho, Catarina Moreira
Branca, Rui M.
Lehtio, Janne
Levine, Rodney L.
Glaser, Elzbieta
TI In vitro oxidative inactivation of human presequence protease (hPreP)
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Mitochondria; Presequence protease; Peptide degradation; Oxidation;
Methionine; Free radicals
ID METHIONINE SULFOXIDE REDUCTASE; AMYLOID-BETA-PEPTIDE;
ALZHEIMERS-DISEASE; ORGANELLAR PEPTIDASOME; A-BETA; MITOCHONDRIAL
PRESEQUENCES; ARABIDOPSIS-THALIANA; ANTIOXIDANT DEFENSE; PREP; PROTEINS
AB The mitochondrial peptidasome called presequence protease (Prep) is responsible for the degradation of presequences and other unstructured peptides including the amyloid-beta, peptide, whose accumulation may have deleterious effects on mitochondrial function. Recent studies showed that PreP activity is reduced in Alzheimer disease (AD) patients and AD mouse models compared to controls, which correlated with an enhanced reactive oxygen species production in mitochondria. In this study, we have investigated the effects of a biologically relevant oxidant, hydrogen peroxide (H2O2), on the activity of recombinant human PreP (hPreP). H2O2 inhibited hPreP activity in a concentration-dependent manner, resulting in oxidation of amino acid residues (detected by carbonylation) and lowered protein stability. Substitution of the evolutionarily conserved methionine 206 for leucine resulted in increased sensitivity of hPreP to oxidation, indicating a possible protective role of M2O6 as internal antioxidant. The activity of hPreP oxidized at low concentrations of H2O2 could be restored by methionine sulfoxide reductase A (MsrA), an enzyme that localizes to the mitochondrial matrix, suggesting that hPreP constitutes a substrate for MsrA. In summary, our in vitro results suggest a possible redox control of hPreP in the mitochondrial matrix and support the protective role of the conserved methionine 206 residue as an internal antioxidant. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Teixeira, Pedro Filipe; Pinho, Catarina Moreira; Glaser, Elzbieta] Stockholm Univ, Dept Biochem & Biophys, Arrhenius Labs Nat Sci, SE-10691 Stockholm, Sweden.
[Branca, Rui M.; Lehtio, Janne] Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.
[Branca, Rui M.; Lehtio, Janne] Karolinska Inst, Stockholm, Sweden.
[Levine, Rodney L.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Teixeira, PF (reprint author), Stockholm Univ, Dept Biochem & Biophys, Arrhenius Labs Nat Sci, SE-10691 Stockholm, Sweden.
EM pedro@dbb.su.se
RI Levine, Rodney/D-9885-2011;
OI Lehtio, Janne/0000-0002-8100-9562; Branca, Rui/0000-0003-3890-6476
FU Swedish Research Council; Alzheimerfonden; Fundacao para a Ciencia e a
Tecnologia (Portugal); Stohnes Foundation; Sigurd och Elsa Goljes Minne
Foundation; Swedish Cancer Society; National Heart, Lung, and Blood
Institute
FX This work was supported by research grants from the Swedish Research
Council and Alzheimerfonden to E.G.; a doctoral grant from Fundacao para
a Ciencia e a Tecnologia (Portugal) to C.M.P.; a postdoctoral grant from
Fundacao para a Ciencia e a Tecnologia (Portugal) and research grants
from the Stohnes and the Sigurd och Elsa Goljes Minne Foundations to
P.F.T.; research grants from the Swedish Cancer Society and the Swedish
Research Council to J.L.; and the Intramural Research Program of the
National Heart, Lung, and Blood Institute to R.L.L. The authors also
thank Dr. Therese Eneqvist for the hPreP structural model.
NR 51
TC 8
Z9 8
U1 0
U2 1
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 DEC 1
PY 2012
VL 53
IS 11
BP 2188
EP 2195
DI 10.1016/j.freeradbiomed.2012.09.039
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 050MV
UT WOS:000312058300020
PM 23041349
ER
PT J
AU Ranguelova, K
Ganini, D
Bonini, MG
London, RE
Mason, RP
AF Ranguelova, Kalina
Ganini, Douglas
Bonini, Marcelo G.
London, Robert E.
Mason, Ronald P.
TI Kinetics of the oxidation of reduced Cu,Zn-superoxide dismutase by
peroxymonocarbonate (vol 53, pg 589, 2012)
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Correction
C1 [Ranguelova, Kalina; Ganini, Douglas; Mason, Ronald P.] NIEHS, Lab Pharmacol & Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
[London, Robert E.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Bonini, Marcelo G.] Univ Illinois, Dept Med, Cardiol Sect, Chicago, IL USA.
[Bonini, Marcelo G.] Univ Illinois, Dept Pharmacol, Chicago, IL USA.
RP Mason, RP (reprint author), NIEHS, Lab Pharmacol & Toxicol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM mason4@niehs.nih.gov
NR 1
TC 0
Z9 0
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD DEC 1
PY 2012
VL 53
IS 11
BP 2196
EP 2196
DI 10.1016/j.freeradbiomed.2012.10.526
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 050MV
UT WOS:000312058300021
ER
PT J
AU Ndlebe, T
Neumann, RD
Panyutin, IG
AF Ndlebe, Thabisile
Neumann, Ronald D.
Panyutin, Igor G.
TI Study of charge transport mechanisms in I-125-induced DNA damage at
various temperatures
SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
LA English
DT Article
DE DNA; charge transport; Auger electron emitters
ID SYNTHETIC OLIGODEOXYNUCLEOTIDE; ELECTRON-TRANSFER; I-125 DECAY;
CRYSTALLINE DNA; HOLE TRANSFER; RADIATION; MIGRATION; RANGE; BREAKAGE;
GEOMETRY
AB Purpose: Iodine-125 decay induces localized DNA damage by three major mechanisms: (1) Direct damage by the emitted Auger electrons, (2) indirect damage by diffusible free radicals, and (3) charge neutralization of the residual, highly positively charged, tellurium daughter atom by stripping electrons from neighboring residues. The charge neutralization mechanism of I-125-induced DNA damage is poorly understood. Charge transport along a DNA molecules can occur by either a hopping mechanism initiated by charge injection into DNA and propagated by charge migration through DNA bases along the DNA length, or by a tunneling mechanism in which charge transfers directly from a donor to an acceptor residue. In the first case additional damage in DNA nucleotides can be inflicted by the traveling charge; therefore, it is important to learn if charge hopping plays a role in I-125-decay-induced DNA damage. In our previous work, we determined that at 193K the charge hopping mechanism was not an appreciable component of the mechanism of I-125-induced DNA damage. However, the question whether this is also the case at higher temperatures remained open.
Methods : In the current study we used a well-known chemical barrier for charge hopping, 8-oxo-7,8,-dihydroguanine (8-oxo-G), to assess the role of this mechanism in I-125-decay-induced DNA damage at the following temperatures: 198, 253, 277 and 298 K.
Results : We found that varying the temperature had little effect on the distribution of I-125-induced DNA breaks, as well as on the breaks found at the 8-oxo-G probe both with and without piperidine treatment.
Conclusions : We thus conclude that charge transport by the hopping mechanism is not a major factor in I-125-decay-induced DNA damage at biologically relevant temperatures.
C1 [Ndlebe, Thabisile; Neumann, Ronald D.; Panyutin, Igor G.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Panyutin, IG (reprint author), NIH, Ctr Clin, Bldg 10,Rm 1C401, Bethesda, MD 20892 USA.
EM ipanyuting@mail.nih.gov
FU National Institutes of Health, Clinical Center
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, Clinical Center.
NR 29
TC 1
Z9 1
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0955-3002
J9 INT J RADIAT BIOL
JI Int. J. Radiat. Biol.
PD DEC
PY 2012
VL 88
IS 12
BP 941
EP 947
DI 10.3109/09553002.2012.697645
PG 7
WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Nuclear Science &
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 047JS
UT WOS:000311837000014
PM 22631602
ER
PT J
AU Panyutin, IV
Eniafe, R
Panyutin, IG
Neumann, RD
AF Panyutin, Irina V.
Eniafe, Rhoda
Panyutin, Igor G.
Neumann, Ronald D.
TI Effect of 5-[I-125]iodo-2 '-deoxyuridine uptake on the proliferation and
pluripotency of human embryonic stem cells
SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
LA English
DT Article
DE Auger emitters; stem cells; cell biology
ID IONIZING-RADIATION; MAMMALIAN-CELLS; RADIOTOXICITY; TOXICITY; I-125
AB Purpose: Human embryonic stem cells (hESC) hold a great potential for regenerative medicine because, in principle, they can differentiate into any cell type found in the human body. In addition, studying the effect of ionizing radiation (IR) on hESC may provide valuable information about the response of human cells to IR exposure in their most naive state, as well as the consequences of IR exposure on the development of organisms. However, the effect of IR, in particular radionuclide uptake, on the pluripotency, proliferation and survival of hESC has not been extensively studied.
Methods: In this study we treated cultured hESC with 5-[I-125]-iodo-2'-deoxyuridine ((125)IdU), a precursor of DNA synthesis. Then we measured the expansion of colonies and expression of pluripotency markers in hESC.
Results: We found that uptake of (125)IdU was similar in both hESC and HT1080 human fibrosarcoma cells. However, treatment with 0.1 mu Ci/ml (125)IdU for 24 hours resulted in complete death of the hESC population; whereas HT1080 cancer cells continued to grow. Treatment with a 10-fold lower dose (125)IdU (0.01 mu Ci/ml) resulted in colonies of hESC becoming less defined with numerous cells growing in monolayer outside of the colonies showing signs of differentiation. Then we analyzed the expression of pluripotency markers (octamer-binding transcription factor 4 [Oct-4] and stage-specific embryonic antigen-4 [SSEA4]) in the surviving hESC. We found that hESC in the surviving colonies expressed pluripotency markers at levels comparable with those in the non-treated controls.
Conclusions: Our results provide important initial insights into the sensitivity of hESC to IR, and especially that produced by the decay of an internalized radionuclide.
C1 [Panyutin, Irina V.; Eniafe, Rhoda; Panyutin, Igor G.; Neumann, Ronald D.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Panyutin, IG (reprint author), NIH, Ctr Clin, Bldg 10,Room 1C401, Bethesda, MD 20892 USA.
EM ipanyuting@mail.nih.gov
FU NIH Clinical Center
FX This work was supported by the Intramural Research Program of the NIH
Clinical Center.
NR 17
TC 2
Z9 2
U1 1
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0955-3002
J9 INT J RADIAT BIOL
JI Int. J. Radiat. Biol.
PD DEC
PY 2012
VL 88
IS 12
BP 954
EP 960
DI 10.3109/09553002.2012.700435
PG 7
WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Nuclear Science &
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 047JS
UT WOS:000311837000016
PM 22676300
ER
PT J
AU Karamychev, VN
Wang, DF
Mazur, SJ
Appella, E
Neumann, RD
Zhurkin, VB
Panyutin, IG
AF Karamychev, Valeri N.
Wang, Difei
Mazur, Sharlyn J.
Appella, Ettore
Neumann, Ronald D.
Zhurkin, Victor B.
Panyutin, Igor G.
TI Radioprobing the conformation of DNA in a p53-DNA complex
SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
LA English
DT Article
DE Radioprobing; iodine-125; p53; DNA structure
ID P53 TUMOR-SUPPRESSOR; CRYSTAL-STRUCTURE; NUCLEOSOME CORE; DOMAIN;
RECOGNITION; TETRAMER; MUTATIONS; SITE
AB Purpose: The frequency of DNA strand breaks produced by the decay of Auger electron-emitting radionuclides is inversely proportional to the distance of DNA nucleotides from the decay site; and thus is very sensitive to changes in the local conformation of the DNA. Analysis of the frequency of DNA breaks, or radioprobing, gives valuable information about the local DNA structure. More than 10 years ago, we demonstrated the feasibility of radioprobing using a DNA-repressor complex with a known structure. Herein, we used radioprobing to study the conformation of DNA in complex with the tumor suppressor protein 53 (p53). Several structures of p53-DNA complexes have been solved by X-ray crystallography. These structures, obtained with the p53 DNA binding domain, a truncated form, laid the groundwork for understanding p53-DNA interactions and their relation to p53 functions. However, whether all observed stereochemical details are relevant to the native p53-DNA complex remains unclear. A common theme of the crystallographic structures is the lack of significant bending in the central part of the DNA response element. In contrast, gel electrophoresis and electron microscopy data showed strong DNA bending and overtwisting upon binding to the native p53 tetramer.
Methods: To analyze DNA in complex with p53, we incorporated 125 I-dCTP in two different positions of synthetic duplexes containing the consensus p53-binding site.
Results: The most significant changes in the break frequency distributions were detected close to the center of the binding site, which is consistent with an increase in DNA twisting in this region and local DNA bending and sliding.
Conclusions: Our data confirm the main results of the studies made in solution and lay a foundation for systematic examination of interactions between DNA and native p53 using 125 I radioprobing.
C1 [Karamychev, Valeri N.; Neumann, Ronald D.; Panyutin, Igor G.] NCI, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Wang, Difei; Mazur, Sharlyn J.; Appella, Ettore; Zhurkin, Victor B.] NCI, Cell Biol Lab, CCR, NIH, Bethesda, MD 20892 USA.
RP Panyutin, IG (reprint author), NCI, Ctr Clin, NIH, 10 Ctr Dr,Room 1C401, Bethesda, MD 20892 USA.
EM igorp@helix.nih.gov
RI Wang, Difei/E-7066-2010
FU NIH Clinical Center; National Cancer Institute
FX This work was supported by the Intramural Research Program of the NIH
Clinical Center and National Cancer Institute.
NR 29
TC 1
Z9 1
U1 1
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0955-3002
J9 INT J RADIAT BIOL
JI Int. J. Radiat. Biol.
PD DEC
PY 2012
VL 88
IS 12
BP 1039
EP 1045
DI 10.3109/09553002.2012.698030
PG 7
WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Nuclear Science &
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 047JS
UT WOS:000311837000025
PM 22640875
ER
PT J
AU Sahasrabuddhe, VV
Gunja, MZ
Graubard, BI
Trabert, B
Schwartz, LM
Park, Y
Hollenbeck, AR
Freedman, ND
McGlynn, KA
AF Sahasrabuddhe, Vikrant V.
Gunja, Munira Z.
Graubard, Barry I.
Trabert, Britton
Schwartz, Lauren M.
Park, Yikyung
Hollenbeck, Albert R.
Freedman, Neal D.
McGlynn, Katherine A.
TI Nonsteroidal Anti-inflammatory Drug Use, Chronic Liver Disease, and
Hepatocellular Carcinoma
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID CANCER-RISK; CELL-GROWTH; ASPIRIN; CYCLOOXYGENASE-2; CHEMOPREVENTION;
EPIDEMIOLOGY; INHIBITION; APOPTOSIS; DECADE
AB Background Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce chronic inflammation and risk of many cancers, but their effect on risk of hepatocellular carcinoma (HCC) and death due to chronic liver disease (CLD) has not been investigated.
Methods We analyzed prospective data on 300504 men and women aged 50 to 71 years in the National Institutes of HealthAARP Diet and Health Study cohort and linked self-reported aspirin and nonaspirin NSAID use with registry-confirmed diagnoses of HCC (n250) and death due to CLD (n428, excluding HCC). We calculated hazard rate ratios (RRs) and their two-sided 95% confidence intervals (CIs) using Cox proportional hazard regression models with adjustment for age, sex, race/ethnicity, cigarette smoking, alcohol consumption, diabetes, and body mass index. All tests of statistical significance were two-sided.
Results Aspirin users had statistically significant reduced risks of incidence of HCC (RR 0.59; 95% CI 0.45 to 0.77) and mortality due to CLD (RR 0.55; 95% CI 0.45 to 0.67) compared to those who did not use aspirin. In contrast, users of nonaspirin NSAIDs had a reduced risk of mortality due to CLD (RR 0.74; 95% CI 0.61 to 0.90) but did not have lower risk of incidence of HCC (RR 1.08; 95% CI 0.84 to 1.39) compared to those who did not use nonaspirin NSAIDs. The risk estimates did not vary in statistical significance by frequency (monthly, weekly, daily) of aspirin use, but the reduced risk of mortality due to CLD was statistically significant only among monthly users of nonaspirin NSAIDs compared to non-users.
Conclusions Aspirin use was associated with reduced risk of developing HCC and of death due to CLD whereas nonaspirin NSAID use was only associated with reduced risk of death due to CLD. J Natl Cancer Inst 2012:104;1808-1814
C1 [Sahasrabuddhe, Vikrant V.; Gunja, Munira Z.; Graubard, Barry I.; Trabert, Britton; Schwartz, Lauren M.; Park, Yikyung; Freedman, Neal D.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Sahasrabuddhe, VV (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 5032, Rockville, MD 20852 USA.
EM vikrant.sahasrabuddhe@nih.gov
RI Freedman, Neal/B-9741-2015; Trabert, Britton/F-8051-2015;
OI Freedman, Neal/0000-0003-0074-1098; Park, Yikyung/0000-0002-6281-489X
FU National Institutes of Health, Division of Cancer Epidemiology and
Genetics, National Cancer Institute, Department of Health and Human
Services
FX This work was funded by the Intramural Research Program of the National
Institutes of Health, Division of Cancer Epidemiology and Genetics,
National Cancer Institute, Department of Health and Human Services.
NR 32
TC 60
Z9 61
U1 1
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD DEC
PY 2012
VL 104
IS 23
BP 1808
EP 1814
DI 10.1093/jnci/djs452
PG 7
WC Oncology
SC Oncology
GA 051EZ
UT WOS:000312109500010
PM 23197492
ER
PT J
AU Kim, W
Yeganova, L
Comeau, DC
Wilbur, WJ
AF Kim, Won
Yeganova, Lana
Comeau, Donald C.
Wilbur, W. John
TI Identifying well-formed biomedical phrases in MEDLINE (R) text
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Machine learning; Imbalanced data; Biomedical phrases; Statistical
phrase identification; Unified medical language system; Abbreviation
full forms
ID IDENTIFICATION
AB In the modern world people frequently interact with retrieval systems to satisfy their information needs. Humanly understandable well-formed phrases represent a crucial interface between humans and the web, and the ability to index and search with such phrases is beneficial for human-web interactions. In this paper we consider the problem of identifying humanly understandable, well formed, and high quality biomedical phrases in MEDLINE documents. The main approaches used previously for detecting such phrases are syntactic, statistical, and a hybrid approach combining these two. In this paper we propose a supervised learning approach for identifying high quality phrases. First we obtain a set of known well-formed useful phrases from an existing source and label these phrases as positive. We then extract from MEDLINE a large set of multiword strings that do not contain stop words or punctuation. We believe this unlabeled set contains many well-formed phrases. Our goal is to identify these additional high quality phrases. We examine various feature combinations and several machine learning strategies designed to solve this problem. A proper choice of machine learning methods and features identifies in the large collection strings that are likely to be high quality phrases. We evaluate our approach by making human judgments on multiword strings extracted from MEDLINE using our methods. We find that over 85% of such extracted phrase candidates are humanly judged to be of high quality. Published by Elsevier Inc.
C1 [Kim, Won; Yeganova, Lana; Comeau, Donald C.; Wilbur, W. John] Natl Lib Med, CBB, NCBI, NIH, Bethesda, MD 20894 USA.
RP Kim, W (reprint author), Natl Lib Med, CBB, NCBI, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM wonkim@mail.nih.gov
FU Intramural Research Program of the NIH, National Library of Medicine
FX This research was supported by the Intramural Research Program of the
NIH, National Library of Medicine.
NR 25
TC 1
Z9 1
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 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD DEC
PY 2012
VL 45
IS 6
BP 1035
EP 1041
DI 10.1016/j.jbi.2012.05.005
PG 7
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 050KE
UT WOS:000312051400002
PM 22683889
ER
PT J
AU Gu, HY
Elhanan, G
Perl, Y
Hripcsak, G
Cimino, JJ
Xu, JL
Chen, Y
Geller, J
Morrey, CP
AF Gu, Huanying (Helen)
Elhanan, Gai
Perl, Yehoshua
Hripcsak, George
Cimino, James J.
Xu, Julia
Chen, Yan
Geller, James
Morrey, C. Paul
TI A study of terminology auditors' performance for UMLS semantic type
assignments
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Auditing of terminologies; UMLS auditing; Semantic type assignments;
Auditor performance; Auditor reliability; Quality Assurance
ID MEDICAL LANGUAGE SYSTEM; DIFFERENT VIEWS; METATHESAURUS; NETWORK
AB Auditing healthcare terminologies for errors requires human experts. In this paper, we present a study of the performance of auditors looking for errors in the semantic type assignments of complex UMLS concepts. In this study, concepts are considered complex whenever they are assigned combinations of semantic types. Past research has shown that complex concepts have a higher likelihood of errors. The results of this study indicate that individual auditors are not reliable when auditing such concepts and their performance is low, according to various metrics. These results confirm the outcomes of an earlier pilot study. They imply that to achieve an acceptable level of reliability and performance, when auditing such concepts of the UMLS, several auditors need to be assigned the same task. A mechanism is then needed to combine the possibly differing opinions of the different auditors into a final determination. In the current study, in contrast to our previous work, we used a majority mechanism for this purpose. For a sample of 232 complex UMLS concepts, the majority opinion was found reliable and its performance for accuracy, recall, precision and the F-measure was found statistically significantly higher than the average performance of individual auditors. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Gu, Huanying (Helen)] New York Inst Technol, Dept Comp Sci, New York, NY 10023 USA.
[Elhanan, Gai; Perl, Yehoshua; Geller, James] New Jersey Inst Technol, Newark, NJ 07102 USA.
[Hripcsak, George] Columbia Univ, New York, NY USA.
[Cimino, James J.; Xu, Julia] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Chen, Yan] CUNY, BMCC, New York, NY 10021 USA.
[Morrey, C. Paul] Utah Valley Univ, Orem, UT USA.
RP Gu, HY (reprint author), New York Inst Technol, Dept Comp Sci, 1855 Broadway, New York, NY 10023 USA.
EM hgu03@nyit.du
OI Cimino, James/0000-0003-4101-1622
FU United States National Library of Medicine [R01LM008445-01A2]
FX This work was partially supported by the United States National Library
of Medicine under Grant R01LM008445-01A2.
NR 31
TC 7
Z9 7
U1 1
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD DEC
PY 2012
VL 45
IS 6
BP 1042
EP 1048
DI 10.1016/j.jbi.2012.05.006
PG 7
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 050KE
UT WOS:000312051400003
PM 22687822
ER
PT J
AU Cohen, T
Widdows, D
Schvaneveldt, RW
Davies, P
Rindflesch, TC
AF Cohen, Trevor
Widdows, Dominic
Schvaneveldt, Roger W.
Davies, Peter
Rindflesch, Thomas C.
TI Discovering discovery patterns with predication-based Semantic Indexing
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Distributional semantics; Literature-based discovery; Predication-based
Semantic Indexing; Vector symbolic architectures
ID MULTIPLE-MYELOMA CELLS; KNOWLEDGE DISCOVERY; IN-VITRO; FISH-OIL; SYSTEM;
REPRESENTATIONS; DEXAMETHASONE; INTERFERON; INHIBITOR; APOPTOSIS
AB In this paper we utilize methods of hyperdimensional computing to mediate the identification of therapeutically useful connections for the purpose of literature-based discovery. Our approach, named Predication-based Semantic Indexing, is utilized to identify empirically sequences of relationships known as "discovery patterns", such as "drug x INHIBITS substance y, substance y CAUSES disease z" that link pharmaceutical substances to diseases they are known to treat. These sequences are derived from semantic predications extracted from the biomedical literature by the SemRep system, and subsequently utilized to direct the search for known treatments for a held out set of diseases. Rapid and efficient inference is accomplished through the application of geometric operators in PSI space, allowing for both the derivation of discovery patterns from a large set of known TREATS relationships, and the application of these discovered patterns to constrain search for therapeutic relationships at scale. Our results include the rediscovery of discovery patterns that have been constructed manually by other authors in previous research, as well as the discovery of a set of previously unrecognized patterns. The application of these patterns to direct search through PSI space results in better recovery of therapeutic relationships than is accomplished with models based on distributional statistics alone. These results demonstrate the utility of efficient approximate inference in geometric space as a means to identify therapeutic relationships, suggesting a role of these methods in drug repurposing efforts. In addition, the results provide strong support for the utility of the discovery pattern approach pioneered by Hristovski and his colleagues. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Cohen, Trevor] Univ Texas Hlth Sci Ctr, Houston, TX USA.
[Widdows, Dominic] Microsoft Bing, Redmond, WA USA.
[Schvaneveldt, Roger W.] Arizona State Univ, Mesa, AZ USA.
[Davies, Peter] Texas A&M Hlth Sci Ctr, Ctr Translat Canc Res, Inst Biosci & Technol, Houston, TX USA.
[Rindflesch, Thomas C.] Natl Lib Med, Bethesda, MD USA.
RP Cohen, T (reprint author), Univ Texas Houston, Sch Biomed Informat, 7000 Fannin St,Suite 600, Houston, TX 77004 USA.
EM Trevor.cohen@uth.tmc.edu
OI Schvaneveldt, Roger/0000-0003-3470-9141
FU US National Library of Medicine [R21LM010826]; Encoding Semantic
Knowledge in Vector Space for Biomedical Information Retrieval;
Intramural Research Program of the National Institutes of Health,
National Library of Medicine
FX This research was supported by the US National Library of Medicine Grant
(R21LM010826), Encoding Semantic Knowledge in Vector Space for
Biomedical Information Retrieval and the Intramural Research Program of
the National Institutes of Health, National Library of Medicine.
NR 69
TC 12
Z9 12
U1 1
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD DEC
PY 2012
VL 45
IS 6
BP 1049
EP 1065
DI 10.1016/j.jbi.2012.07.003
PG 17
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 050KE
UT WOS:000312051400004
PM 22841748
ER
PT J
AU Keselman, A
Smith, CA
AF Keselman, Alla
Smith, Catherine Arnott
TI A classification of errors in lay comprehension of medical documents
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Information literacy; Clinical documentation; Consumer health; Patients;
Classification; Content analysis
ID PERSONAL HEALTH RECORDS; SELF-REPORTED HISTORY; INFORMED-CONSENT;
INFORMATION; PHYSICIANS; CARE; TAXONOMY; CANCER; EXPERIENCES;
READABILITY
AB Emphasis on participatory medicine requires that patients and consumers participate in tasks traditionally reserved for healthcare providers. This includes reading and comprehending medical documents, often but not necessarily in the context of interacting with Personal Health Records (PHRs). Research suggests that while giving patients access to medical documents has many benefits (e.g., improved patient-provider communication), lay people often have difficulty understanding medical information. Informatics can address the problem by developing tools that support comprehension: this requires in-depth understanding of the nature and causes of errors that lay people make when comprehending clinical documents. The objective of this study was to develop a classification scheme of comprehension errors, based on lay individuals' retellings of two documents containing clinical text: a description of a clinical trial and a typical office visit note. While not comprehensive, the scheme can serve as a foundation of further development of a taxonomy of patients' comprehension errors. Eighty participants, all healthy volunteers, read and retold two medical documents. A data-driven content analysis procedure was used to extract and classify retelling errors. The resulting hierarchical classification scheme contains nine categories and 23 subcategories. The most common error made by the participants involved incorrectly recalling brand names of medications. Other common errors included misunderstanding clinical concepts, misreporting the objective of a clinical research study and physician's findings during a patient's visit, and confusing and misspelling clinical terms. A combination of informatics support and health education is likely to improve the accuracy of lay comprehension of medical documents. Published by Elsevier Inc.
C1 [Keselman, Alla] Natl Lib Med, Div Specialized Informat Serv, Bethesda, MD 20892 USA.
[Smith, Catherine Arnott] Univ Wisconsin, Sch Lib & Informat Studies, Madison, WI 53706 USA.
RP Keselman, A (reprint author), Natl Lib Med, Div Specialized Informat Serv, 6707 Democracy Blvd,Suite 510, Bethesda, MD 20892 USA.
EM keselmana@mail.nih.gov
FU NIDDK [7R01DK075837]; Intramural Research Program of the National
Library of Medicine
FX The authors gratefully acknowledge Marsha Naydich, MD for her assistance
with the data coding. Funding support by NIDDK 7R01DK075837; and the
Intramural Research Program of the National Library of Medicine.
NR 75
TC 11
Z9 11
U1 2
U2 14
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD DEC
PY 2012
VL 45
IS 6
BP 1151
EP 1163
DI 10.1016/j.jbi.2012.07.012
PG 13
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 050KE
UT WOS:000312051400011
PM 22925723
ER
PT J
AU Gershengorn, MC
Neumann, S
AF Gershengorn, Marvin C.
Neumann, Susanne
TI Update in TSH Receptor Agonists and Antagonists
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID RECOMBINANT HUMAN TSH; GLYCOPROTEIN HORMONE-RECEPTORS; DIFFERENTIATED
THYROID-CANCER; SMALL-MOLECULE AGONISTS; THYROTROPIN RECEPTOR;
GRAVES-DISEASE; ORBITAL FIBROBLASTS; INVERSE AGONIST; CAMP PRODUCTION;
BINDING
AB The physiological role of the TSH receptor (TSHR) as a major regulator of thyroid function is well understood, but TSHRs are also expressed in multiple normal extrathyroidal tissues, and the physiological roles of TSHRs in these tissues are unclear. Moreover, TSHRs play a major role in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Small molecule, "drug-like" TSHR agonists, neutral antagonists, and inverse agonists may be useful as probes of TSHR function in extrathyroidal tissues and as leads to develop drugs for several diseases of the thyroid. In this Update, we review the most recent findings regarding the development and use of these small molecule TSHR ligands. (J Clin Endocrinol Metab 97: 4287-4292, 2012)
C1 [Gershengorn, Marvin C.; Neumann, Susanne] NIDDKD, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
RP Gershengorn, MC (reprint author), Bldg 50,Room 4134,50 South Dr,MSC 8029, Bethesda, MD 20892 USA.
EM marving@intra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health [Z01 DK011006, Z01 DK047044]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health (Z01 DK011006, Z01 DK047044.
NR 33
TC 20
Z9 21
U1 0
U2 8
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD DEC
PY 2012
VL 97
IS 12
BP 4287
EP 4292
DI 10.1210/jc.2012-3080
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 049SO
UT WOS:000312003900019
PM 23019348
ER
PT J
AU Finkielstain, GP
Kim, MS
Sinaii, N
Nishitani, M
Van Ryzin, C
Hill, SC
Reynolds, JC
Hanna, RM
Merke, DP
AF Finkielstain, Gabriela P.
Kim, Mimi S.
Sinaii, Ninet
Nishitani, Miki
Van Ryzin, Carol
Hill, Suvimol C.
Reynolds, James C.
Hanna, Reem M.
Merke, Deborah P.
TI Clinical Characteristics of a Cohort of 244 Patients with Congenital
Adrenal Hyperplasia
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID STEROID 21-HYDROXYLASE DEFICIENCY; NUTRITION EXAMINATION SURVEY;
BONE-MINERAL DENSITY; ENDOCRINE-SOCIETY; BLOOD-PRESSURE; REST TUMORS;
ADULT WOMEN; INSULIN SENSITIVITY; PRACTICE GUIDELINE; METABOLIC SYNDROME
AB Context: Patients with congenital adrenal hyperplasia (CAH) often suffer from long-term complications secondary to chronic glucocorticoid therapy and suboptimal treatment regimens.
Objective: The aim of the study was to describe clinical characteristics of a large cohort of pediatric and adult CAH patients.
Design and Setting: We conducted a cross-sectional study of 244 CAH patients [183 classic, 61 nonclassic (NC)] included in a Natural History Study at the National Institutes of Health.
Main Outcome Measure(s): Outcome variables of interest were height SD score, obesity, hypertensive blood pressure (BP), insulin resistance, metabolic syndrome, bone mineral density, hirsutism (females), and testicular adrenal rest (TART).
Results: The majority had elevated or suppressed androgens, with varied treatment regimens. Mean adult height SD score was -1.0 +/- 1.1 for classic vs. -0.4 +/- 0.9 for NC patients (P = 0.015). Obesity was present in approximately one third of patients, across phenotypes. Elevated BP was more common in classic than NC patients (P <= 0.01); pediatric hypertensive BP was associated with suppressed plasma renin activity (P = 0.001). Insulin resistance was common in classic children (27%) and adults (38% classic, 20% NC); 18% of adults had metabolic syndrome. The majority (61%) had low vitamin D; 37% of adults had low bone mineral density. Hirsutism was common (32% classic; 59% NC women). TART was found in classic males (33% boys; 44% men).
Conclusions: Poor hormonal control and adverse outcomes are common in CAH, necessitating new treatments. Routine monitoring of classic children should include measuring BP and plasma renin activity. Osteoporosis prophylaxis and TART screening should begin during childhood. A longitudinal study is under way. (J Clin Endocrinol Metab 97: 4429-4438, 2012)
C1 [Merke, Deborah P.] NIH, Ctr Clin, Clin Res Ctr, Bethesda, MD 20892 USA.
[Finkielstain, Gabriela P.; Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Finkielstain, Gabriela P.] Hosp Ninos Dr Ricardo Gutierrez, Ctr Invest Endocrinol, Div Endocrinol, Buenos Aires, DF, Argentina.
[Kim, Mimi S.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
RP Merke, DP (reprint author), NIH, Ctr Clin, Clin Res Ctr, Bldg 10,Room 1-2740,10 Ctr Dr,Mail Stop Code 1932, Bethesda, MD 20892 USA.
EM dmerke@nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD); National Institutes of Health Clinical Center;
Congenital Adrenal Hyperplasia Research, Education and Support
Foundation
FX This work was supported by the Intramural Research Programs of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) and the National Institutes of Health Clinical
Center; and by The Congenital Adrenal Hyperplasia Research, Education
and Support Foundation.
NR 42
TC 57
Z9 58
U1 0
U2 12
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD DEC
PY 2012
VL 97
IS 12
BP 4429
EP 4438
DI 10.1210/jc.2012-2102
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 049SO
UT WOS:000312003900042
PM 22990093
ER
PT J
AU Korn, EL
Freidlin, B
AF Korn, Edward L.
Freidlin, Boris
TI Methodology for Comparative Effectiveness Research: Potential and
Limitations
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID EVALUATING STATISTICAL ADJUSTMENTS; HIGH-DOSE CHEMOTHERAPY; METASTATIC
COLORECTAL-CANCER; RANDOMIZED CONTROLLED-TRIALS; RE COMPARATIVE
EFFECTIVENESS; CISPLATIN PLUS GEMCITABINE; CELL LUNG-CANCER;
CLINICAL-TRIALS; PROSTATE-CANCER; OBSERVATIONAL DATA
C1 [Korn, Edward L.; Freidlin, Boris] NCI, Bethesda, MD 20892 USA.
RP Korn, EL (reprint author), NCI, Bethesda, MD 20892 USA.
NR 41
TC 19
Z9 19
U1 0
U2 12
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 DEC 1
PY 2012
VL 30
IS 34
BP 4185
EP 4187
DI 10.1200/JCO.2012.44.8233
PG 3
WC Oncology
SC Oncology
GA 048DA
UT WOS:000311889200002
PM 23071226
ER
PT J
AU McShane, LM
Hayes, DF
AF McShane, Lisa M.
Hayes, Daniel F.
TI Publication of Tumor Marker Research Results: The Necessity for Complete
and Transparent Reporting
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID GROUP RANDOMIZED-TRIALS; B-CELL LYMPHOMA; METASTATIC BREAST-CANCER;
CONSORT STATEMENT; AMERICAN-SOCIETY; CLINICAL-TRIALS; REVISED
RECOMMENDATIONS; ADJUVANT CHEMOTHERAPY; PROGNOSTIC MARKERS; QUALITY
BRISQ
AB Clinical management decisions for patients with cancer are increasingly being guided by prognostic and predictive markers. Use of these markers should be based on a sufficiently comprehensive body of unbiased evidence to establish that benefits to patients outweigh harms and to justify expenditure of health care dollars. Careful assessments of the clinical utility of markers by using comparative effectiveness research methods are urgently needed to more rigorously summarize and evaluate the evidence, but multiple factors have made such assessments difficult. The literature on tumor markers is plagued by nonpublication bias, selective reporting, and incomplete reporting. Several measures to address these problems are discussed, including development of a tumor marker study registry, greater attention to assay analytic performance and specimen quality, use of more rigorous study designs and analysis plans to establish clinical utility, and adherence to higher standards for reporting tumor marker studies. More complete and transparent reporting by adhering to criteria such as BRISQ [Biospecimen Reporting for Improved Study Quality] criteria for reporting details about specimens and REMARK [Reporting Recommendations for Tumor Marker Prognostic Studies] criteria for reporting a multitude of aspects relating to study design, analysis, and results, is essential for reliable assessment of study quality, detection of potential biases, and proper interpretation of study findings. Adopting these measures will improve the quality of the body of evidence available for comparative effectiveness research and enhance the ability to establish the clinical utility of prognostic and predictive tumor markers. J Clin Oncol 30:4223-4232. (C) 2012 by American Society of Clinical Oncology
C1 [McShane, Lisa M.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
[McShane, Lisa M.] NCI, Canc Diag Program, Bethesda, MD 20892 USA.
[Hayes, Daniel F.] Univ Michigan, Breast Oncol Program, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
RP McShane, LM (reprint author), NCI, Biometr Res Branch, Room 8126,Execut Plaza N,MSC 7434,6130 Execut Blv, Bethesda, MD 20892 USA.
EM lm5h@nih.gov
FU Fashion Footwear Charitable Foundation of New York/QVC Presents Shoes on
Sale; Pfizer; Novartis; Veridex; Janssen Pharmaceutica
FX Supported by a grant from Fashion Footwear Charitable Foundation of New
York/QVC Presents Shoes on Sale (D.F.H.).; Research Funding: Daniel F.
Hayes, Pfizer, Novartis, Veridex, Janssen Pharmaceutica
NR 81
TC 80
Z9 81
U1 0
U2 16
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 DEC 1
PY 2012
VL 30
IS 34
BP 4223
EP 4232
DI 10.1200/JCO.2012.42.6858
PG 10
WC Oncology
SC Oncology
GA 048DA
UT WOS:000311889200009
PM 23071235
ER
PT J
AU Pearson, SD
AF Pearson, Steven D.
TI Cost, Coverage, and Comparative Effectiveness Research: The Critical
Issues for Oncology
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID EFFECTIVENESS INFORMATION; REIMBURSEMENT SCHEMES; CANCER DRUGS; CARE;
COUNTRIES; OUTCOMES
AB A new national initiative in comparative effectiveness research (CER) is part of a broad and long-term evolution toward greater reliance on scientific evidence in clinical practice and medical policy. But CER has been controversial because of its high profile in the health care reform effort, its instantiation in a prominent new national research institute, and lingering concerns that the ultimate goal of CER is to empower the government and private insurers to reduce health care costs by restricting access to expensive new medical tests and treatments. This article presents an analysis of the policy development behind CER and focuses on its potential impact on insurance coverage and payment for oncology services. By itself, CER will not solve the tension that exists between the goal of innovative, personalized care and the eroding affordability of cancer treatment in the United States. But CER does offer an important opportunity for progress. Oncologists have taken important first steps in acknowledging their responsibility for addressing cost issues; as a professional society, they should now move forward to assume leadership in the effort to integrate clinical evidence with considerations of cost effectiveness to guide clinical practice and insurer policies. J Clin Oncol 30:4275-4281. (C) 2012 by American Society of Clinical Oncology
C1 [Pearson, Steven D.] NIH, Bethesda, MD 20892 USA.
[Pearson, Steven D.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Inst Technol Assessment, Boston, MA 02114 USA.
RP Pearson, SD (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM pearsonsd@cc.nih.gov
FU Merck; Johnson Johnson
FX Research Funding: Steven D. Pearson, Merck, Johnson & Johnson
NR 34
TC 15
Z9 15
U1 1
U2 4
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 DEC 1
PY 2012
VL 30
IS 34
BP 4275
EP 4281
DI 10.1200/JCO.2012.42.6601
PG 7
WC Oncology
SC Oncology
GA 048DA
UT WOS:000311889200016
PM 23071229
ER
PT J
AU Scott, A
Petrykowska, HM
Hefferon, T
Gotea, V
Elnitski, L
AF Scott, Alexandra
Petrykowska, Hanna M.
Hefferon, Timothy
Gotea, Valer
Elnitski, Laura
TI Functional analysis of synonymous substitutions predicted to affect
splicing of the CFTR gene
SO JOURNAL OF CYSTIC FIBROSIS
LA English
DT Article
DE Synonymous substitution; Exon skipping; Minigene assay; SplicePort
predictions; Ectopic splice sites
ID CYSTIC-FIBROSIS; REGULATORY ELEMENTS; MUTATIONS; SEQUENCE; NONSENSE;
DELTA-F508; MISSENSE; EXON-12; TOOL
AB Background: Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Over 1800 CFTR mutations have been reported, and about 12% of mutations are believed to impair pre-mRNA splicing. Given that several synthetic, non-splice-junction synonymous substitutions have been reported to alter splicing in CFTR, we predicted that naturally occurring synonymous substitutions may be erroneously classified as functionally neutral.
Methods: Computational tools were used to predict the effect of synonymous substitutions on CFTR pre-mRNA splicing. The functional consequences of selected substitutions were evaluated using a minigene splicing assay.
Results: Two synonymous mutations were shown to have a dramatic effect on CFTR pre-mRNA splicing, and consequently could alter protein integrity and phenotypic outcome.
Conclusions: Traditional methods of mutation analysis overlook splicing defects that occur at internal positions in coding exons, especially synonymous substitutions. We show that bioinformatics tools and minigene splicing assays arc a potent combination to prioritize and identify mutations that cause aberrant CFTR pre-mRNA splicing. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.
C1 [Scott, Alexandra; Petrykowska, Hanna M.; Gotea, Valer; Elnitski, Laura] NHGRI, DIR GTB Genom Funct Anal Sect, NIH, Rockville, MD 20852 USA.
[Hefferon, Timothy] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Elnitski, L (reprint author), 5625 Fishers Lane, Rockville, MD 20852 USA.
OI Scott, Alexandra/0000-0002-1930-9265; Gotea, Valer/0000-0001-7857-3309
FU National Human Genome Research Institute, National Institutes of Health
FX We thank Ursula Harper of the NHGRI Genomics Core for performing the
fluorescent quantitation. This work was supported by the Intramural
program of the National Human Genome Research Institute, National
Institutes of Health. Edward Edkins and Marie des Georges provided
historical information on variants 2 and 5.
NR 29
TC 7
Z9 7
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1569-1993
J9 J CYST FIBROS
JI J. Cyst. Fibros
PD DEC
PY 2012
VL 11
IS 6
BP 511
EP 517
DI 10.1016/j.jcf.2012.04.009
PG 7
WC Respiratory System
SC Respiratory System
GA 051HC
UT WOS:000312115900005
PM 22591852
ER
PT J
AU Bennett, CL
Starko, KM
Thomsen, HS
Cowper, S
Sartor, O
Macdougall, IC
Qureshi, ZP
Bookstaver, PB
Miller, AD
Norris, LB
Xirasagar, S
Trenery, A
Lopez, I
Kahn, A
Murday, A
Luminari, S
Cournoyer, D
Locatelli, F
Ray, P
Mattison, DR
AF Bennett, Charles L.
Starko, Karen M.
Thomsen, Henrik S.
Cowper, Shawn
Sartor, Oliver
Macdougall, Iain C.
Qureshi, Zaina P.
Bookstaver, P. Brandon
Miller, April D.
Norris, LeAnn B.
Xirasagar, Sudha
Trenery, Alyssa
Lopez, Isaac
Kahn, Adam
Murday, Alanna
Luminari, Stefano
Cournoyer, Denis
Locatelli, Francesco
Ray, Paul
Mattison, Donald R.
TI Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia,
Nephrogenic Systemic Fibrosis, and Reye's Syndrome. A Report From the
Southern Network on Adverse Reactions (SONAR)
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE pure red cell aplasia; nephrogenic systemic fibrosis; Reye's syndrome
ID PUBLIC-HEALTH-SERVICE; SALICYLATE INTOXICATION; FATTY DEGENERATION;
ANTIERYTHROPOIETIN ANTIBODIES; RECOMBINANT ERYTHROPOIETIN; DIALYSIS
PATIENTS; UNITED-STATES; ASPIRIN; EPOETIN; ENCEPHALOPATHY
AB Identification of serious adverse drug reactions (sADRS) associated with commonly used drugs can elude detection for years. Reye's syndrome (RS), nephrogenic systemic fibrosis (NSF), and pure red cell aplasia (PRCA) among chronic kidney disease (CKD) patients were recognized in 1951, 2000, and 1998, respectively. Reports associating these syndromes with aspirin, gadodiamide, and epoetin, were published 29, 6, and 4 years later, respectively. We obtained primary information from clinicians who identified causes of these sADRs and reviewed factors contributing to delayed identification of these toxicities. Overall, 3,500 aspirin-associated RS cases in the United States, 1,605 gadolinium-associated NSF cases, and 181 epoetin-associated PRCA cases were reported. Delays in FDA regulation of over-the- counter medications and administration of aspirin to children contributed to development of RS. For NSF, in 1996, the Danish Medicine Agency approved high-dose gadodiamide administration to chronic kidney disease (CKD) patients undergoing MR scans. Overall, 88 % of Danish NSF cases were from two hospitals and 97 % of United States' NSF cases were from 60 hospitals. These hospitals frequently administered high-doses of gadodiamide to CKD patients. Another factor was the decision to administer linear chelated contrast agents versus lower risk macrocyclic chelated agents. For PRCA, increased use of subcutaneous epoetin formulations to CKD patients, in part due to convenience and cost-savings considerations, and a European regulatory requirement requiring removal of albumin as a stabilizer, led to toxicity. Overall, 81, 13, and 17 years elapsed between drug introduction into practice and identification of a causal relationship for aspirin, erythropoietin, and gadodiamide, respectively. A substantial decline in new cases of these sADRs occurred within two years of identification of the offending drug. Clinicians should be vigilant for sADRs, even for frequently-prescribed pharmaceuticals, particularly in settings where formulation or regulatory changes have occurred, or when over-the-counter, off-label, or pediatric use is common.
C1 [Bennett, Charles L.; Qureshi, Zaina P.; Bookstaver, P. Brandon; Miller, April D.; Norris, LeAnn B.; Trenery, Alyssa; Lopez, Isaac; Kahn, Adam; Murday, Alanna; Ray, Paul] S Carolina Coll Pharm, Columbia, SC 29208 USA.
[Bennett, Charles L.; Qureshi, Zaina P.; Xirasagar, Sudha] Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC 29208 USA.
[Bennett, Charles L.] Hollings Canc Ctr, Charleston, SC USA.
[Thomsen, Henrik S.] Univ Copenhagen, Dept Diagnost Sci, Copenhagen, Denmark.
[Cowper, Shawn] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA.
[Sartor, Oliver] Tulane Coll Med, Dept Med, New Orleans, LA USA.
[Sartor, Oliver] Tulane Coll Med, Dept Urol, New Orleans, LA USA.
[Sartor, Oliver] Tulane Canc Ctr, New Orleans, LA USA.
[Macdougall, Iain C.] Kings Coll Hosp, Renal Unit, London, England.
[Luminari, Stefano] Univ Modena & Reggio Emilia, Dept Hematol & Oncol, Modena, Italy.
[Cournoyer, Denis] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
[Locatelli, Francesco] Alessandro Manzoni Hosp, Dept Nephrol, Lecce, Italy.
[Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
[Mattison, Donald R.] Risk Sci Int, Ottawa, ON, Canada.
RP Bennett, CL (reprint author), S Carolina Coll Pharm, 715 Sumter St,Suite 311, Columbia, SC 29208 USA.
EM bennettc@sccp.sc.edu
RI luminari, stefano/J-5916-2014; Mattison, Donald/L-4661-2013;
OI luminari, stefano/0000-0001-8446-2285; Mattison,
Donald/0000-0001-5623-0874; Norris, LeAnn/0000-0001-7656-1259
FU National Cancer Institute, South Carolina Center of Economic Excellence
Center for Medication Safety initiative [1R01CA 102713-01]; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institute of Health
FX Funding was provided by grants from the National Cancer Institute
(1R01CA 102713-01) (CLB) the South Carolina Center of Economic
Excellence Center for Medication Safety initiative (CLB), and the
intramural program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institute of Health (DRM).
This paper was prepared in part by DRM as an employee of the US
Government making this a "work of the US Government" and therefore the
copyright is non-transferable. The opinions stated in this paper are
those of the authors and do not necessarily represent views of the
Department of Health and Human Services, the National Institutes of
Health or the Eunice Kennedy Shriver National Institute of Child Health
and Human Development.
NR 59
TC 4
Z9 5
U1 2
U2 25
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD DEC
PY 2012
VL 27
IS 12
BP 1697
EP 1703
DI 10.1007/s11606-012-2098-1
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 050RR
UT WOS:000312072200020
PM 22692632
ER
PT J
AU Phillips, KA
Hirsch, GA
Epstein, DH
Preston, KL
AF Phillips, Karran A.
Hirsch, Glenn A.
Epstein, David H.
Preston, Kenzie L.
TI Cardiac Complications of Unwitting Co-injection of Quinine/Quinidine
with Heroin in an Intravenous Drug User
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE arrhythmias; heroin; cocaine; adulterants
ID METHADONE-MAINTENANCE; FALCIPARUM-MALARIA; QUINIDINE; LEVAMISOLE;
QUININE; SCOPOLAMINE; EPIDEMIC
AB Adulterants "cut into" street heroin are common and often not detected by standard urine toxicology screening; however, their unwitting co-injection may have clinical consequences. We report a case of accelerated atrioventricular junctional arrhythmia that we determined to have been caused by quinine/quinidine cut into heroin. While identification and discontinuation of the offending agent helps confirm the diagnosis and is the treatment of choice, this is often complicated by the individual's dependence on the street drug in which the adulterant is mixed. This case highlights the need for clinicians to be aware of common adulterants, to know how to test for them, and to consider them as possible causes of medical complications in individuals who use drugs.
C1 [Phillips, Karran A.; Epstein, David H.; Preston, Kenzie L.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Hirsch, Glenn A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
RP Phillips, KA (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd,Bldg BRC,Suite 200, Baltimore, MD 21224 USA.
EM phillipsk@nida.nih.gov
RI Preston, Kenzie/J-5830-2013
OI Preston, Kenzie/0000-0003-0603-2479
FU National Institute on Drug Abuse, Intramural Research Program, National
Institutes of Health
FX Thanks to Mr. (Arnold) Keith Adkins and Ms. Sini Panicker, DEA Special
Testing and Research Lab, for providing the detailed information on
confiscated heroin in Baltimore. This research was supported by the
National Institute on Drug Abuse, Intramural Research Program, National
Institutes of Health. This research was presented at the SGIM
Mid-Atlantic Meeting in March 2011.
NR 23
TC 4
Z9 4
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD DEC
PY 2012
VL 27
IS 12
BP 1722
EP 1725
DI 10.1007/s11606-012-2089-2
PG 4
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 050RR
UT WOS:000312072200025
PM 22592353
ER
PT J
AU Peters, M
Trembovler, V
Alexandrovich, A
Parnas, M
Birnbaumer, L
Minke, B
Shohami, E
AF Peters, Maximilian
Trembovler, Victoria
Alexandrovich, Alexander
Parnas, Moshe
Birnbaumer, Lutz
Minke, Baruch
Shohami, Esther
TI Carvacrol Together with TRPC1 Elimination Improve Functional Recovery
after Traumatic Brain Injury in Mice
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE head trauma; neuronal cell death; TBI
ID NF-KAPPA-B; CB1 CANNABINOID RECEPTORS; INDUCED CELL-DEATH; NEURONAL
DEATH; CHANNELS; NEUROPROTECTION; OVEREXPRESSION; ACTIVATION; APOPTOSIS;
ISCHEMIA
AB Death of Central Nervous System (CNS) neurons following traumatic brain injury (TBI) is a complex process arising from a combination of factors, many of which are still unknown. It has been found that inhibition of transient receptor potential (TRP) channels constitutes an effective strategy for preventing death of CNS neurons following TBI. TRP channels are classified into seven related subfamilies, most of which are Ca2+ permeable and involved in many cellular functions, including neuronal cell death. We hypothesized that TRP channels of the TRPC subfamily may be involved in post-TBI pathophysiology and that the compound 5-isopropyl-2-methylphenol (carvacrol), by inhibition of TRP channels, may exert neuroprotective effect after TBI. To test these suppositions, carvacrol was given to mice after TBI and its effect on their functional recovery was followed for several weeks. Our results show that neurological recovery after TBI was significantly enhanced by application of carvacrol. To better define the type of the specific channel involved, the effect of carvacrol on the extent and speed of recovery after TBI was compared among mice lacking TRPC1, TRPC3, or TRPC5, relative to wild type controls. We found that neurological recovery after TBI was significantly enhanced by combining carvacrol with TRPC1 elimination, but not by the absence of TRPC3 or TRPC5, showing a synergistic effect between carvacrol application and TRPC1 elimination. We conclude that TRPC1-sensitive mechanisms are involved in TBI pathology, and that inhibition of this channel by carvacrol enhances recovery and should be considered for further studies in animal models and humans.
C1 [Trembovler, Victoria; Alexandrovich, Alexander; Shohami, Esther] Hebrew Univ Jerusalem, Fac Med, Dept Pharmacol, Inst Drug Res,Sch Pharm, IL-91120 Jerusalem, Israel.
[Peters, Maximilian; Parnas, Moshe; Minke, Baruch] IMRIC, Dept Med Neurobiol, Jerusalem, Israel.
[Peters, Maximilian; Parnas, Moshe; Minke, Baruch] Edmond & Lily Safra Ctr Brain Sci ELSC, Jerusalem, Israel.
[Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Shohami, E (reprint author), Hebrew Univ Jerusalem, Fac Med, Dept Pharmacol, Inst Drug Res,Sch Pharm, IL-91120 Jerusalem, Israel.
EM esty.shohami@mail.huji.ac.il
RI Peters, Maximilian/B-7406-2008
FU Rosetrees Trust; National Institutes of Health (NIH) [Z01-ES-101684]
FX This study was approved by the Institutional Animal Care Committee of
the Hebrew University. We thank Ben Katz for critical reading of the
manuscript. This research was supported by grants from the Rosetrees
Trust (to Dr. Minke) and by the Intramural Research Program of the
National Institutes of Health (NIH) (project Z01-ES-101684 to Dr. Lutz
Birnbaumer).
NR 33
TC 9
Z9 10
U1 1
U2 7
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD DEC
PY 2012
VL 29
IS 18
BP 2831
EP 2834
DI 10.1089/neu.2012.2575
PG 4
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 050ZE
UT WOS:000312092800013
PM 22994850
ER
PT J
AU Nath, S
Bachani, M
Harshavardhana, D
Steiner, JP
AF Nath, Samir
Bachani, Muznabanu
Harshavardhana, Deepti
Steiner, Joseph P.
TI Catechins protect neurons against mitochondrial toxins and HIV proteins
via activation of the BDNF pathway
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Article
DE Catechins; Neurons; Mitochondrial toxins; BDNF pathway
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELL-DEATH; OXIDATIVE STRESS; DEMENTIA;
ACID; EPIGALLOCATECHIN-3-GALLATE; PROLIFERATION; TOXICITY; CAPACITY;
EXTRACT
AB Currently, there is no effective treatment for neurological complications of infection with the human immunodeficiency virus that persists despite the use of combination antiretroviral therapy. A medium throughput assay was developed for screening neuroprotective compounds using primary mixed neuronal cells and mitochondrial toxin 3-nitropropionic acid. Using this assay, a library of 2,000 compounds was screened. Out of 256 compounds that showed variable degrees of neuroprotection, nine were related to epicatechin, a monomeric flavonoid found in cocoa and green tea leaves that readily crosses the blood-brain barrier. Hence, catechin, epicatechin, and the related compound, epigallocatechin gallate (EGCG) were further screened for their neuroprotective properties against HIV proteins Tat and gp120, and compared to those of resveratrol. Epicatechin and EGCG targets the brain-derived neurotrophic factor (BDNF) and its precursor proBDNF signaling pathways, normalizing both Tat-mediated increases in proapoptotic proBDNF and concomitant Tat-mediated decreases in the mature BDNF protein in hippocampal neurons. Epicatechin and epigallocatechin gallate were more potent than catechin or resveratrol as neuroprotectants. Due to its simpler structure and more efficient blood-brain barrier penetration properties, epicatechin might be the best therapeutic candidate for neurodegenerative diseases including HIV-associated neurocognitive disorders where oxidative stress is an important pathophysiological mechanism.
C1 [Nath, Samir; Bachani, Muznabanu; Harshavardhana, Deepti; Steiner, Joseph P.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA.
RP Steiner, JP (reprint author), NINDS, Neurotherapeut Dev Unit, Translat Neurosci Ctr, 10 Ctr Dr,Bldg 10-7C105, Bethesda, MD 20892 USA.
EM joe.steiner@nih.gov
NR 40
TC 20
Z9 22
U1 1
U2 18
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD DEC
PY 2012
VL 18
IS 6
BP 445
EP 455
DI 10.1007/s13365-012-0122-1
PG 11
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 051MB
UT WOS:000312130200002
PM 22886603
ER
PT J
AU Gao, HK
Kiesewetter, DO
Zhang, XX
Huang, XL
Guo, N
Lang, LX
Hida, N
Wang, H
Wang, HC
Cao, F
Niu, G
Chen, XY
AF Gao, Haokao
Kiesewetter, Dale O.
Zhang, Xiaoxiang
Huang, Xinglu
Guo, Ning
Lang, Lixin
Hida, Naoki
Wang, Hui
Wang, Haichang
Cao, Feng
Niu, Gang
Chen, Xiaoyuan
TI PET of Glucagonlike Peptide Receptor Upregulation After Myocardial
Ischemia or Reperfusion Injury
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE PET imaging; GLP-1R; myocardial infarction; exendin 4
ID IN-VIVO; HEME OXYGENASE-1; GLP-1; INFARCTION; EXPRESSION; HEART;
EXENDIN-4; DEGRADATION; TOMOGRAPHY; INSULINOMA
AB Glucagonlike peptide (GLP-1) and its receptor (GLP-1R) exhibit cardioprotective effects after myocardial ischemia and reperfusion (MI/R) in both animal studies and clinical trials. However, the kinetics of GLP-1R expression in the infarcted/ischemic myocardium has not yet been explored. The purpose of this study was to monitor the presence and time course of regional myocardial GLP-1R expression after MI/R with noninvasive PET. Methods: Male Sprague-Dawley rats underwent a 45-min transient left coronary artery occlusion, followed by reperfusion. The myocardial infarction was confirmed by electrocardiogram and cardiac ultrasound. In vivo PET was performed to determine myocardial uptake of F-18-FBEM-Cys(40)-exendin-4 at different time points after reperfusion. The localization of F-18-FBEM-Cys(40)-exendin-4 accumulation was determined by coregistering F-18-FDG PET and CT images. Ex vivo autoradiography, GLP-1R immunohistochemical staining, and Western blot analysis were performed to confirm the PET results. Results: Myocardial origin and infarcted/ischemic area localization of F-18-FBEM-Cys(40)-exendin-4 accumulation was confirmed by coregistration of small-animal CT and 18F-FDG images. At 8 h after MI/R, tracer uptake in the infarcted/ischemic region was 0.37 +/- 0.05 percentage injected dose per gram, significantly higher than that in the control group (P < 0.01). The localized tracer uptake decreased, relative to the 8-h time point, but was still significantly higher than the control group on days 1 and 3 after MI/R. At 2 wk after MI/R, the tracer uptake in the affected area showed no significant difference, compared with that in the healthy myocardium. Autoradiography showed the same trend of F-18-FBEM-Cys(40)-exendin-4 uptake in the myocardial infarcted/ischemic area. The specificity of tracer uptake into ischemic myocardium was supported by decreased tracer uptake after the rats were pretreated with an excess amount of unlabeled exendin-4. Immunohistochemical staining and Western blotting of GLP-1R protein of excised cardiac sections confirmed that the change in uptake observed by PET corresponded to a change in GLP-1R expression. Conclusion: Noninvasive PET using F-18-FBEM-Cys(40)-exendin-4 revealed a dynamic pattern of GLP-1R upregulation in the infarcted/ischemic area after MI/R. The imaging results will deepen our understanding of the mechanism of the cardioprotective effect of GLP-1 and its analogs and potentially provide guidance for optimization of the time frame of therapeutic intervention.
C1 [Gao, Haokao; Wang, Haichang; Cao, Feng] Fourth Mil Med Univ, Dept Cardiol, Xijing Hosp, Xian 710032, Peoples R China.
[Gao, Haokao; Kiesewetter, Dale O.; Zhang, Xiaoxiang; Huang, Xinglu; Guo, Ning; Lang, Lixin; Hida, Naoki; Wang, Hui; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD USA.
[Guo, Ning] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen, Peoples R China.
RP Cao, F (reprint author), Fourth Mil Med Univ, Dept Cardiol, Xijing Hosp, Xian 710032, Peoples R China.
EM wind8828@gmail.com; niug@mail.nih.gov
FU National Basic Research Program of China (973 program) [2013CB733802];
National Science Foundation of China (NSFC) [81028009, 81100234];
Chinese Academy of Sciences [2011T2J06]; National Institute of
Biomedical Imaging and Bioengineering (NIBIB), the National Institutes
of Health (NIH)
FX This project was supported, in part, by the National Basic Research
Program of China (973 program, 2013CB733802), the National Science
Foundation of China (NSFC) (81028009, 81100234), the Chinese Academy of
Sciences professorship for Senior International Scientists (2011T2J06),
and the Intramural Research Program of the National Institute of
Biomedical Imaging and Bioengineering (NIBIB), the National Institutes
of Health (NIH). No other potential conflict of interest relevant to
this article was reported.
NR 41
TC 5
Z9 5
U1 3
U2 13
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD DEC
PY 2012
VL 53
IS 12
BP 1960
EP 1968
DI 10.2967/jnumed.112.109413
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 051GX
UT WOS:000312115400022
PM 23139087
ER
PT J
AU Calzone, KA
Jenkins, J
Yates, J
Cusack, G
Wallen, GR
Liewehr, DJ
Steinberg, SM
McBride, C
AF Calzone, Kathleen A.
Jenkins, Jean
Yates, Jan
Cusack, Georgie
Wallen, Gwenyth R.
Liewehr, David J.
Steinberg, Seth M.
McBride, Colleen
TI Survey of Nursing Integration of Genomics Into Nursing Practice
SO JOURNAL OF NURSING SCHOLARSHIP
LA English
DT Article
DE Nurses; nursing; genetics; genomics; survey; nursing practice
ID GENETICS; MEDICINE; HEALTH
AB Purpose: Translating clinically valid genomic discoveries into practice is hinged not only on technologic advances, but also on nursesthe largest global contingent of health providersacquiring requisite competencies to apply these discoveries in clinical care. The study aim was to assess practicing nurse attitudes, practices, receptivity, confidence, and competency of integrating genomics into nursing practice.
Design: A convenience sample of practicing nurses was recruited to complete an online survey that assessed domains from Roger's Diffusion of Innovations Theory and used family history utilization as the basis for competency assessment.
Methods: Results were tabulated and analyzed using descriptive statistical techniques.
Findings: Two-hundred-thirty-nine licensed registered nurses, 22 to 72 years of age, with a median of 20 years in practice, responded, for an overall response rate of 28%. Most were White (83%), female (92%), and held baccalaureate degrees (56%). Seventy-one percent considered genetics to be very important to nursing practice; however, 81% rated their understanding of the genetics of common diseases as poor or fair. Per-question response rates varied widely. Instrument assessment indicated that modifications were necessary to decrease respondent burden.
Conclusions: Respondents perceived genomic competency was inadequate, family history was not routinely utilized in care delivery, and the extent of family history varied widely. However, most nurses indicated interest in pursuing continuing genomic education.
C1 [Calzone, Kathleen A.] NCI, NIH, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA.
[McBride, Colleen] NHGRI, Social & Behav Res Branch, Head Publ Hlth Genom Sect, NIH, Bethesda, MD 20892 USA.
[Yates, Jan; Cusack, Georgie; Wallen, Gwenyth R.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Liewehr, David J.; Steinberg, Seth M.] Biostat & Data Management Sect, Bethesda, MD USA.
RP Calzone, KA (reprint author), NCI, NIH, Ctr Canc Res, Genet Branch, 41 Medlars Dr,Bldg 41,RM B622,MSC 5055, Bethesda, MD 20892 USA.
EM calzonek@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health United
States; National Cancer Institute; National Human Genome Research
Institute; National Institute of Nursing Research; National Institutes
of Health Clinical Center
FX This research was supported by the Intramural Research Program of the
National Institutes of Health United States, including support from the
National Cancer Institute, National Human Genome Research Institute, and
the National Institute of Nursing Research, as well as the National
Institutes of Health Clinical Center.
NR 18
TC 18
Z9 18
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1527-6546
J9 J NURS SCHOLARSHIP
JI J. Nurs. Scholarsh.
PD DEC
PY 2012
VL 44
IS 4
BP 428
EP 436
DI 10.1111/j.1547-5069.2012.01475.x
PG 9
WC Nursing
SC Nursing
GA 048QW
UT WOS:000311928600016
PM 23205780
ER
PT J
AU Cheng, J
Groninger, H
AF Cheng, Jennifer
Groninger, Hunter
TI Modafinil #259
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Editorial Material
ID DOUBLE-BLIND; FATIGUE; CANCER; TRIAL
C1 [Groninger, Hunter] NIH, Pain & Palliat Care Serv, Ctr Clin, Bethesda, MD 20829 USA.
RP Groninger, H (reprint author), NIH, Pain & Palliat Care Serv, Ctr Clin, Room 2-1733, Bethesda, MD 20829 USA.
EM hunter.groninger@nih.gov
NR 16
TC 1
Z9 1
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
J9 J PALLIAT MED
JI J. Palliat. Med.
PD DEC
PY 2012
VL 15
IS 12
BP 1388
EP 1389
DI 10.1089/jpm.2012.9542
PG 2
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 048UB
UT WOS:000311937500017
PM 23206152
ER
PT J
AU de Sousa, RT
Busnello, JV
Forlenza, OV
Zanetti, MV
Soeiro-de-Souza, MG
van de Bilt, MT
Moreno, RA
Zarate, CA
Gattaz, WF
Machado-Vieira, R
AF de Sousa, Rafael T.
Busnello, Joao V.
Forlenza, Orestes V.
Zanetti, Marcus V.
Soeiro-de-Souza, Marcio G.
van de Bilt, Martinus T.
Moreno, Ricardo A.
Zarate, Carlos A., Jr.
Gattaz, Wagner F.
Machado-Vieira, Rodrigo
TI Early improvement of psychotic symptoms with lithium monotherapy as a
predictor of later response in mania
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Psychosis; Mania; Bipolar disorder; Lithium; Early improvement;
Monotherapy
ID BIPOLAR DISORDER; DOUBLE-BLIND; PLACEBO; EFFICACY; RECOMMENDATIONS;
ANTIPSYCHOTICS; SCHIZOPHRENIA; SPECIFICITY; GUIDELINES; ILLNESS
AB Although lithium has been the first line agent in the treatment of bipolar disorder (BD), few studies have evaluated lithium's efficacy in mania with psychosis and its association with later response. Furthermore, given the widespread concern about antipsychotic side effects, answering a question about whether lithium alone can manage to treat both psychotic and non-psychotic mania seems a very relevant one. The present study addresses the antipsychotic efficacy of lithium monotherapy in acute mania and early improvement of psychotic symptoms as a predictor of later response of manic symptoms. Forty-six patients presenting a manic episode (32 with psychotic features and 14 subjects without psychotic features) were treated for 4 weeks with lithium monotherapy and evaluated weekly using the Young Mania Rating Scale (YMRS). Subjects with rapid cycling, substance abuse/dependence, or mixed episodes were excluded. The overall antimanic efficacy of lithium in psychosis vs. non-psychosis groups was evaluated. In addition, early improvement of psychotic symptoms and its prediction of subsequent response (>50% decrease in total YMRS scores) or remission were evaluated. Lithium showed a similar efficacy in both psychosis and non-psychosis mania. Early improvement of psychotic symptoms was associated with clinical response and remission at endpoint. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [de Sousa, Rafael T.; Forlenza, Orestes V.; Zanetti, Marcus V.; van de Bilt, Martinus T.; Gattaz, Wagner F.; Machado-Vieira, Rodrigo] Univ Sao Paulo HC FMUSP, Sch Med, Dept & Inst Psychiat, Lab Neurosci LIM 27, BR-05403010 Sao Paulo, Brazil.
[Busnello, Joao V.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
[Soeiro-de-Souza, Marcio G.; Moreno, Ricardo A.] Univ Sao Paulo HC FMUSP, Sch Med, Dept & Inst Psychiat, Mood Disorders Unit GRUDA, BR-05403010 Sao Paulo, Brazil.
[Zarate, Carlos A., Jr.] NIMH, Sect Neurobiol & Treatment Mood Disorders, Intramural Res Program, Bethesda, MD 20892 USA.
[Forlenza, Orestes V.; Zanetti, Marcus V.; Gattaz, Wagner F.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-05508 Sao Paulo, Brazil.
RP Machado-Vieira, R (reprint author), Univ Sao Paulo HC FMUSP, Sch Med, Dept & Inst Psychiat, Lab Neurosci LIM 27, Rua Dr Ovidio Pires de Campos 785,3rd Floor N, BR-05403010 Sao Paulo, Brazil.
EM machadovieirar@gmail.com
RI Gattaz, Wagner/C-4456-2012; Soeiro-de-Souza, Marcio/J-9430-2012;
MACHADO-VIEIRA, RODRIGO/D-8293-2012; Zanetti, Marcus/A-9013-2008;
Forlenza, Orestes/B-8848-2013
OI Soeiro-de-Souza, Marcio/0000-0002-9293-3128; MACHADO-VIEIRA,
RODRIGO/0000-0002-4830-1190;
FU Stanley Medical Research Institute [03T-356]
FX This work was supported by a grant from the Stanley Medical Research
Institute (03T-356 to RMV), which had no role in study design or data
analysis.
NR 25
TC 0
Z9 0
U1 0
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD DEC
PY 2012
VL 46
IS 12
BP 1564
EP 1568
DI 10.1016/j.jpsychires.2012.08.011
PG 5
WC Psychiatry
SC Psychiatry
GA 049KY
UT WOS:000311983100005
PM 23000368
ER
PT J
AU Ayres, EJ
Greer-Carney, JL
McShane, PEF
Miller, A
Turner, P
AF Ayres, Elaine J.
Greer-Carney, Janet Lea
McShane, Phyllis E. Fatzinger
Miller, Amy
Turner, Peggy
TI Nutrition Informatics Competencies across All Levels of Practice: A
National Delphi Study
SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
LA English
DT Editorial Material
ID NURSING-EDUCATION; MEMBER SURVEY; NURSES; WORKFORCE
C1 [Ayres, Elaine J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA.
[Greer-Carney, Janet Lea] Concord Hosp, Concord, NH USA.
[McShane, Phyllis E. Fatzinger] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
[Miller, Amy] UHS, Johnson City, NY USA.
[Turner, Peggy] Univ Oklahoma, Hlth Sci Ctr, Didact Program Nutr & Dietet, Oklahoma City, OK USA.
RP Ayres, EJ (reprint author), NIH, Lab Informat Dev, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM eayres@nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 33
TC 5
Z9 5
U1 2
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-2672
J9 J ACAD NUTR DIET
JI J. Acad. Nutr. Diet.
PD DEC
PY 2012
VL 112
IS 12
BP 2042
EP 2053
DI 10.1016/j.jand.2012.09.025
PG 12
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 050HY
UT WOS:000312045600017
PM 23174690
ER
PT J
AU Silverman, DT
Attfield, MD
AF Silverman, Debra T.
Attfield, Michael D.
TI Re: The Diesel Exhaust in Miners Study: A Nested Case-Control Study of
Lung Cancer and Diesel Exhaust and a Cohort Mortality Study with
Emphasis on Lung Cancer Response
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
C1 [Silverman, Debra T.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Attfield, Michael D.] NIOSH, Surveillance Branch, Div Resp Dis Studies, Morgantown, WV USA.
RP Silverman, DT (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rm 8012,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM silvermd@mail.nih.gov
NR 11
TC 1
Z9 1
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD DEC
PY 2012
VL 104
IS 23
BP 1848
EP 1849
DI 10.1093/jnci/djs417
PG 2
WC Oncology
SC Oncology
GA 051EZ
UT WOS:000312109500021
ER
PT J
AU McCabe, MS
AF McCabe, Mary S.
TI Cancer Survivorship: We've Only Just Begun
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Editorial Material
ID CARE
C1 [McCabe, Mary S.] Mem Sloan Kettering Canc Ctr, Canc Survivorship Program, New York, NY 10021 USA.
[McCabe, Mary S.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP McCabe, MS (reprint author), Mem Sloan Kettering Canc Ctr, Canc Survivorship Program, New York, NY 10021 USA.
NR 10
TC 0
Z9 0
U1 0
U2 1
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD DEC
PY 2012
VL 10
IS 12
BP 1468
EP 1470
PG 3
WC Oncology
SC Oncology
GA 051GM
UT WOS:000312114200003
PM 23221785
ER
PT J
AU Madan, RA
Schwaab, T
Gulley, JL
AF Madan, Ravi A.
Schwaab, Thomas
Gulley, James L.
TI Strategies for Optimizing the Clinical Impact of Immunotherapeutic
Agents Such as Sipuleucel-T in Prostate Cancer
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Article
ID TUMOR-INFILTRATING LYMPHOCYTES; DOSE-ESCALATION TRIAL; COMBINATION
THERAPY; PHASE-II; CELLULAR IMMUNOTHERAPY; METASTATIC MELANOMA;
RECOMBINANT VACCINE; DENDRITIC CELLS; IMMUNE-SYSTEM; DOCETAXEL
AB Sipuleucel-T is a therapeutic cancer vaccine that has shown improved survival in men with metastatic castration-resistant prostate cancer. As a first-in-class agent, it has been met with both fan-fare and controversy. A broad review of immune-based therapies may reveal the delayed clinical impact of sipuleucel-T to be a class effect. As new strategies of immune-based therapy are developed, their effects can be optimized through better understanding of how they affect disease differently from more standard therapeutics. Furthermore, combination therapy with agents that can either work synergistically with immune-activating therapies or deplete immune-regulating cells may result in more vigorous immune responses and improved clinical outcomes. In addition, therapeutic vaccines may be ideal candidates to safely combine with standard-of-care therapies because of their nonoverlapping toxicity profile. The ultimate role of immunotherapy may not be to supplant standard therapies, but rather to work in concert with them to maximize clinical benefit for patients. (JNCCN 2012;10:1505-1512)
C1 [Gulley, James L.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Schwaab, Thomas] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
RP Gulley, JL (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,8B09 MSC 1750, Bethesda, MD 20892 USA.
EM gulleyj@mail.nih.gov
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 63
TC 9
Z9 9
U1 0
U2 4
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD DEC
PY 2012
VL 10
IS 12
BP 1505
EP 1512
PG 8
WC Oncology
SC Oncology
GA 051GM
UT WOS:000312114200006
PM 23221788
ER
PT J
AU Chung, JY
Bae, YA
Yun, DH
Yang, HJ
Kong, Y
AF Chung, Joon-Yong
Bae, Young-An
Yun, Doo-Hee
Yang, Hyun-Jong
Kong, Yoon
TI Experimental Murine Fascioliasis Derives Early Immune Suppression with
Increased Levels of TGF-beta and IL-4
SO KOREAN JOURNAL OF PARASITOLOGY
LA English
DT Article
DE Fasciola hepatica; murine fascioliasis; Mac 1(+) cell; T-lymphocyte;
IL-4; TGF-beta
ID GROWTH-FACTOR-BETA; T-CELL; HEPATICA INFECTION; RESPONSES; MICE;
SCHISTOSOMIASIS; GIGANTICA; PATHOGEN; ANTIGENS; DISEASES
AB In fascioliasis, T-helper 2 (Th2) responses predominate, while little is known regarding early immune phenomenon. We herein analyzed early immunophenotype changes of BALB/c, C57BL/6, and C3H/He mice experimentally infected with 5 Fasciola hepatica metacercariae. A remarkable expansion of CD19(+) B cells was observed as early as week 1 post-infection while CD4(+)/CD8(+) T cells were down-regulated. Accumulation of Mac1(+) cells with time after infection correlated well with splenomegaly of all mice strains tested. The expression of tumor necrosis factor (TNF)-alpha mRNA in splenocytes significantly decreased while that of IL-4 up-regulated. IL-1 beta expression was down-modulated in BALB/c and C57BL/6 mice, but not in C3H/He. Serum levels of transforming growth factor (TGF)-beta were considerably elevated in all mice during 3 weeks of infection period. These collective results suggest that experimental murine fascioliasis might derive immune suppression with elevated levels of TGF-beta and IL-4 during the early stages of infection.
C1 [Chung, Joon-Yong; Bae, Young-An; Yun, Doo-Hee; Kong, Yoon] Sungkyunkwan Univ, Sch Med, Dept Mol Parasitol, Suwon 440746, South Korea.
[Chung, Joon-Yong; Bae, Young-An; Yun, Doo-Hee; Kong, Yoon] Samsung Biomed Res Inst, Ctr Mol Med, Suwon 440746, South Korea.
[Chung, Joon-Yong] NCI, Tissue Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Yang, Hyun-Jong] Ewha Womans Univ, Sch Med, Dept Parasitol, Seoul 158710, South Korea.
RP Kong, Y (reprint author), Sungkyunkwan Univ, Sch Med, Dept Mol Parasitol, Suwon 440746, South Korea.
EM kongy@skku.edu
OI Chung, Joon-Yong/0000-0001-5041-5982
FU Korea Science and Engineering Foundation [KOSEF R01-2003-000-10305-0]
FX This work was supported by a grant from Korea Science and Engineering
Foundation (KOSEF R01-2003-000-10305-0).
NR 30
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U1 1
U2 3
PU KOREAN SOC PARASITOLOGY, SEOUL NATL UNIV COLL MEDI
PI SEOUL
PA DEPT PARASITOLOGY, SEOUL, 00000, SOUTH KOREA
SN 0023-4001
J9 KOREAN J PARASITOL
JI Korean J. Parasitol.
PD DEC
PY 2012
VL 50
IS 4
BP 301
EP 308
DI 10.3347/kjp.2012.50.4.301
PG 8
WC Parasitology
SC Parasitology
GA 050MC
UT WOS:000312056400004
PM 23230327
ER
PT J
AU Hoopes, BC
Rimbault, M
Liebers, D
Ostrander, EA
Sutter, NB
AF Hoopes, Barbara C.
Rimbault, Maud
Liebers, David
Ostrander, Elaine A.
Sutter, Nathan B.
TI The insulin-like growth factor 1 receptor (IGF1R) contributes to reduced
size in dogs
SO MAMMALIAN GENOME
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; PRIMARY LENS LUXATION; HUMAN HEIGHT; DOMESTIC
DOG; POSTNATAL-GROWTH; ADULT HEIGHT; HAPLOTYPE; VARIANTS; LOCI;
POPULATION
AB Domestic dog breeds have undergone intense selection for a variety of morphologic features, including size. Among small-dog breeds, defined as those averaging less than similar to 15 in. at the withers, there remains still considerable variation in body size. Yet essentially all such dogs are fixed for the same allele at the insulin-like growth factor 1 gene, which we and others previously found to be a size locus of large effect. In this study we sought to identify additional genes that contribute to tiny size in dogs using an association scan with the single nucleotide polymorphism (SNP) dataset CanMap, in which 915 purebred dogs were genotyped at 60,968 SNP markers. Our strongest association for tiny size (defined as breed-average height not more than 10 in. at the withers) was on canine chromosome 3 (p = 1.9 x 10(-70)). Fine mapping revealed a nonsynonymous SNP at chr3:44,706,389 that changes a highly conserved arginine at amino acid 204 to histidine in the insulin-like growth factor 1 receptor (IGF1R). This mutation is predicted to prevent formation of several hydrogen bonds within the cysteine-rich domain of the receptor's ligand-binding extracellular subunit. Nine of 13 tiny dog breeds carry the mutation and many dogs are homozygous for it. This work underscores the central importance of the IGF1 pathway in controlling the tremendous size diversity of dogs.
C1 [Sutter, Nathan B.] Cornell Univ, Ctr Vet Med C3 179, Ithaca, NY 14850 USA.
[Hoopes, Barbara C.] Colgate Univ, Dept Biol, Hamilton, NY 13346 USA.
[Rimbault, Maud; Liebers, David; Ostrander, Elaine A.] Natl Human Genome Res Inst, Bethesda, MD 20892 USA.
[Sutter, Nathan B.] Cornell Univ, Dept Clin Sci, Coll Vet Med, Ithaca, NY 14853 USA.
RP Sutter, NB (reprint author), Cornell Univ, Ctr Vet Med C3 179, Ithaca, NY 14850 USA.
EM nbs39@cornell.edu
OI Ostrander, Elaine/0000-0001-6075-9738
FU NHGRI/NIH; Cornell University
FX We thank members of the Ostrander and Sutter laboratories and the
students of BCH. We thank Jeffrey Schoenebeck for helpful discussion and
Roger Rowlett for assistance with IGF1R structure analysis. This
research would not be possible without the generous support of dog
owners who provided access to their animals. BCH carried out a majority
of her portion of this work while on sabbatical in the Ostrander lab
with support from the Colgate Research Council. This work was funded by
the intramural program at NHGRI/NIH (EAO, MR, DL) and Cornell University
internal funds (NBS).
NR 52
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U1 4
U2 51
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-8990
J9 MAMM GENOME
JI Mamm. Genome
PD DEC
PY 2012
VL 23
IS 11-12
BP 780
EP 790
DI 10.1007/s00335-012-9417-z
PG 11
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 050QR
UT WOS:000312069600007
PM 22903739
ER
PT J
AU Rhodes, KV
Miller, FG
AF Rhodes, Karin V.
Miller, Franklin G.
TI Simulated Patient Studies: An Ethical Analysis
SO MILBANK QUARTERLY
LA English
DT Article
DE research ethics; simulated patient studies; audit methodology; deceptive
design; exceptions to consent; access to care; public health; health
services
ID PSYCHIATRIC-SERVICES; ACCESS; CARE; COMMUNICATION; INSURANCE; MYSTERY
AB Context: In connection with health care reform, the U.S. Department of Health and Human Services commissioned a mystery shopper, or simulated patient study, to measure access to primary care. But the study was shelved because of public controversy over government spying on doctors. Opponents of the study also raised ethical concerns about the use of deception with human subjects without soliciting their informed consent. Methods: We undertook an ethical analysis of the use of simulated patient techniques in health services research, with a particular focus on research measuring access to care. Using a case study, we explored relevant methodological considerations and ethical principles relating to deceptive research without informed consent, as well as U.S. federal regulations permitting exceptions to consent. Findings: Several relevant considerations both favor and oppose soliciting consent for simulated patient studies. Making research participation conditional on informed consent protects the autonomy of research subjects and shields them from unreasonable exposure to research risks. However, scientific validity is also an important ethical principle of human subjects research, as the net risks to subjects must be justified by the value to society of the knowledge to be gained. The use of simulated patients to monitor access is a naturalistic and scientifically sound experimental design that can answer important policy-relevant questions, with minimal risks to human subjects. As interaction between researchers and subjects increases, however, so does the need for consent. Conclusions: As long as adequate protections of confidentiality of research data are in place, minimally intrusive simulated patient research that gathers policy-relevant data on the health system without the consent of individuals working in that system can be ethically justified when the risks and burdens to research subjects are minimal and the research has the potential to generate socially valuable knowledge.
C1 [Rhodes, Karin V.] Univ Penn, Perelman Sch Med, UPHS, Dept Emergency Med, Philadelphia, PA 19104 USA.
[Rhodes, Karin V.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA.
[Miller, Franklin G.] NIH, Clin Ctr, Bethesda, MD USA.
[Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD USA.
[Rhodes, Karin V.] Univ Penn, Dept Emergency Med, Ctr Emergency Care Policy Res, Philadelphia, PA 19104 USA.
RP Rhodes, KV (reprint author), Univ Penn, Perelman Sch Med, UPHS, Dept Emergency Med, 3400 Spruce St,1 Ravdin, Philadelphia, PA 19104 USA.
EM Karin.rhodes@uphs.upenn.edu
NR 26
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Z9 7
U1 3
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-378X
J9 MILBANK Q
JI Milbank Q.
PD DEC
PY 2012
VL 90
IS 4
BP 706
EP 724
DI 10.1111/j.1468-0009.2012.00680.x
PG 19
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 051ON
UT WOS:000312137000004
PM 23216428
ER
PT J
AU Patwardhan, A
Carazo, JM
Carragher, B
Henderson, R
Heymann, JB
Hill, E
Jensen, GJ
Lagerstedt, I
Lawson, CL
Ludtke, SJ
Mastronarde, D
Moore, WJ
Roseman, A
Rosenthal, P
Sorzano, COS
Sanz-Garcia, E
Scheres, SHW
Subramaniam, S
Westbrook, J
Winn, M
Swedlow, JR
Kleywegt, GJ
AF Patwardhan, Ardan
Carazo, Jose-Maria
Carragher, Bridget
Henderson, Richard
Heymann, J. Bernard
Hill, Emma
Jensen, Grant J.
Lagerstedt, Ingvar
Lawson, Catherine L.
Ludtke, Steven J.
Mastronarde, David
Moore, William J.
Roseman, Alan
Rosenthal, Peter
Sorzano, Carlos-Oscar S.
Sanz-Garcia, Eduardo
Scheres, Sjors H. W.
Subramaniam, Sriram
Westbrook, John
Winn, Martyn
Swedlow, Jason R.
Kleywegt, Gerard J.
TI Data management challenges in three-dimensional EM
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID PARTICLE ELECTRON CRYOMICROSCOPY; PROTEIN DATA-BANK; IMAGE DATA;
MICROSCOPY; VALIDATION; DEPOSITION; SYSTEM; MODEL; SUITE
AB This report describes the outcomes of the Data Management Challenges in 3D Electron Microscopy workshop. Key topics discussed include data models, validation and raw-data archiving. The meeting participants agreed that the EMDataBank should take the lead in addressing these issues, and concrete action points were agreed upon that will have a substantial impact on the accessibility of three-dimensional EM data in biology and medicine.
C1 [Patwardhan, Ardan; Lagerstedt, Ingvar; Sanz-Garcia, Eduardo; Kleywegt, Gerard J.] European Bioinformat Inst, European Mol Biol Lab, Prot Data Bank Europe, Hinxton, England.
[Carazo, Jose-Maria; Sorzano, Carlos-Oscar S.] Natl Biotechnol Ctr, Biocomp Unit, Madrid, Spain.
[Carazo, Jose-Maria; Sorzano, Carlos-Oscar S.] Natl Biotechnol Ctr, Instruct Image Proc Ctr, Madrid, Spain.
[Carragher, Bridget] Scripps Res Inst, La Jolla, CA 92037 USA.
[Henderson, Richard; Scheres, Sjors H. W.] MRC, Mol Biol Lab, Cambridge CB2 2QH, England.
[Heymann, J. Bernard] NIAMSD, Struct Biol Res Lab, Bethesda, MD 20892 USA.
[Hill, Emma; Moore, William J.; Swedlow, Jason R.] Univ Dundee, Wellcome Trust Ctr Gene Regulat & Express, Dundee, Scotland.
[Jensen, Grant J.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
[Jensen, Grant J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
[Lawson, Catherine L.; Westbrook, John] Rutgers State Univ, Piscataway, NJ USA.
[Ludtke, Steven J.] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA.
[Ludtke, Steven J.] Baylor Coll Med, Natl Ctr Macromol Imaging, Houston, TX 77030 USA.
[Mastronarde, David] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA.
[Roseman, Alan] Univ Manchester, Fac Life Sci, Manchester, Lancs, England.
[Rosenthal, Peter] Natl Inst Med Res, MRC, Div Phys Biochem, London NW7 1AA, England.
[Subramaniam, Sriram] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Winn, Martyn] Sci & Technol Facil Council, Daresbury Lab, Dept Comp Sci, Warrington, Cheshire, England.
RP Kleywegt, GJ (reprint author), European Bioinformat Inst, European Mol Biol Lab, Prot Data Bank Europe, Hinxton, England.
EM j.swedlow@dundee.ac.uk; gerard@ebi.ac.uk
RI S. Sorzano, Carlos Oscar/F-2639-2016;
OI S. Sorzano, Carlos Oscar/0000-0002-9473-283X; Westbrook,
John/0000-0002-6686-5475; Lagerstedt, Ingvar/0000-0002-3346-4528;
Sanz-Garcia, Eduardo/0000-0002-7166-191X; Heymann,
Bernard/0000-0002-8872-5326; Carragher, Bridget/0000-0002-0624-5020;
Swedlow, Jason/0000-0002-2198-1958; Kleywegt, Gerard
J./0000-0002-4670-0331; Patwardhan, Ardan/0000-0001-7663-9028; Scheres,
Sjors/0000-0002-0462-6540
FU BBSRC [BB/G022577]; US National Institutes of Health National Institute
of General Medical Sciences [R01GM079429]; European Molecular Biology
Laboratory-EBI; Wellcome Trust [088944]
FX We thank P. Haslam for help with the manuscript. This workshop and the
OMERO-EMDB project are supported by the BBSRC (BB/G022577). The
EMDataBank is funded by the US National Institutes of Health National
Institute of General Medical Sciences (R01GM079429). The work on the
EMDB at the PDBe also profits from funding by European Molecular Biology
Laboratory-EBI and the Wellcome Trust (088944).
NR 24
TC 19
Z9 19
U1 0
U2 21
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD DEC
PY 2012
VL 19
IS 12
BP 1203
EP 1207
DI 10.1038/nsmb.2426
PG 5
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 049OC
UT WOS:000311991700001
PM 23211764
ER
PT J
AU Shi, K
Kurahashi, K
Gao, R
Tsutakawa, SE
Tainer, JA
Pommier, Y
Aihara, H
AF Shi, Ke
Kurahashi, Kayo
Gao, Rui
Tsutakawa, Susan E.
Tainer, John A.
Pommier, Yves
Aihara, Hideki
TI Structural basis for recognition of 5 '-phosphotyrosine adducts by Tdp2
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID TYROSYL-DNA PHOSPHODIESTERASE; CANCER DEVELOPMENT; TOPOISOMERASE-II;
SCATTERING SAXS; SOFTWARE; REPAIR; CRYSTALLOGRAPHY; TDP2/TTRAP;
ANTICANCER; ACTIVATION
AB The DNA-repair enzyme Tdp2 resolves 5'-phosphotyrosyl DNA adducts and mediates resistance to anticancer drugs that target covalent topoisomerase-DNA complexes. Tdp2 also participates in key signaling pathways during development and tumorigenesis and cleaves a protein-RNA linkage during picornavirus replication. The crystal structure of zebrafish Tdp2 bound to DNA reveals a deep, narrow basic groove that selectively accommodates the 5' end of single-stranded DNA in a stretched conformation. The crystal structure of the full-length Caenorhabditis elegans Tdp2 shows that this groove can also accommodate an acidic peptide stretch in vitro, with glutamate and aspartate side chains occupying the DNA backbone phosphate-binding sites. This extensive molecular mimicry suggests a potential mechanism for autoregulation and interaction of Tdp2 with phosphorylated proteins in signaling. Our study provides a framework to interrogate functions of Tdp2 and develop inhibitors for chemotherapeutic and antiviral applications.
C1 [Shi, Ke; Kurahashi, Kayo; Aihara, Hideki] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
[Gao, Rui; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Tsutakawa, Susan E.; Tainer, John A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA.
[Tainer, John A.] Scripps Res Inst, Dept Mol Biol, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
RP Aihara, H (reprint author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
EM aihar001@umn.edu
FU National Center for Research Resources at the US National Institutes of
Health (NIH) [RR15301]; US DOE [DE-AC02-06CH11357]; NIH [GM095558,
AI087098, R01GM105404]; Center for Cancer Research [Z01 BC 006150-19];
Intramural Program of the US National Cancer Institute; NCI [P01
CA092584, GM046312]; IDAT DOE program [DE-AC02-05CH11231]
FX We thank the beamline staff at Sector-24 of the Advanced Photon Source
(APS) and J. Nix of the Molecular Biology Consortium at the Advanced
Light Source (ALS) for help in data collection and H. Hiasa, D.
Grandgenett and J. Lee for comments on the manuscript. Computer
resources were provided by the Basic Sciences Computing Laboratory of
the University of Minnesota Supercomputing Institute. The work conducted
at the APS NE-CAT beamlines was supported by award RR15301 from the
National Center for Research Resources at the US National Institutes of
Health (NIH). Use of the APS, an Office of Science User Facility
operated for the US Department of Energy (DOE) Office of Science by
Argonne National Laboratory, was supported by the US DOE under contract
no. DE-AC02-06CH11357. This work was supported by NIH grants GM095558
and AI087098 (H.A.), the Center for Cancer Research (Z01 BC 006150-19),
the Intramural Program of the US National Cancer Institute (R.G. and
Y.P.) and NCI P01 CA092584 and GM046312 (J.A.T.). SAXS data were
collected at the ALS SIBYLS beamline 12.3.1 supported by the IDAT DOE
program DE-AC02-05CH11231 and by NIH R01GM105404.
NR 38
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Z9 28
U1 0
U2 25
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD DEC
PY 2012
VL 19
IS 12
BP 1372
EP +
DI 10.1038/nsmb.2423
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 049OC
UT WOS:000311991700027
PM 23104058
ER
PT J
AU van Landingham, SW
Willis, JR
Vitale, S
Ramulu, PY
AF van Landingham, Suzanne W.
Willis, Jeffrey R.
Vitale, Susan
Ramulu, Pradeep Y.
TI Visual Field Loss and Accelerometer-Measured Physical Activity in the
United States
SO OPHTHALMOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; OLDER-ADULTS; MACULAR DEGENERATION; RISK-FACTORS;
GLAUCOMA; IMPAIRMENT; VISION; PEOPLE; FALLS; FEAR
AB Objective: To determine whether visual field (VF) loss is associated with lower levels of accelerometer-defined walking or physical activity in a nationally representative sample of American adults.
Design: Cross-sectional study.
Participants: A total of 2934 adults aged 40 years or older who participated in the examination component of the 2005-2006 National Health and Nutritional Examination Survey.
Methods: Frequency-doubling technology (FDT) testing was performed in both eyes and used to categorize subjects as having no VF loss, unilateral VF loss, or bilateral VF loss. Accelerometer data were collected over 7 days of normal activity.
Main Outcome Measures: Steps per day and daily minutes of moderate or vigorous physical activity (MVPA).
Results: A total of 1468 participants (50.0%) had complete FDT and accelerometer data. Individuals without VF loss averaged 9751 steps/day and 20.8 minutes/day of MVPA, compared with 8023 steps/day and 14.5 minutes/day for subjects with unilateral VF loss (age-adjusted P = 0.11 and P = 0.51) and 6840 steps/day and 10.1 minutes/day for subjects with bilateral VF loss (age-adjusted P = 0.02 and 0.09, respectively). In multivariable models adjusted for age, sex, race/ethnicity, education, and several comorbid illnesses, individuals with bilateral VF loss took 17% fewer steps per day (P < 0.01) and engaged in 30% less MVPA (P = 0.02) than individuals without VF loss. No significant difference in steps per day or MVPA was observed between individuals with unilateral VF loss and no VF loss (P > 0.05). In addition to VF loss, older age, female sex, arthritis, diabetes, congestive heart failure (CHF), and stroke were significantly associated with fewer daily steps and minutes of MVPA (P < 0.05).
Conclusions: Bilateral VF loss is associated with less walking and physical activity in American adults. Patients with bilateral VF loss should be encouraged to engage safely in more physical activity.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:2486-2492 (C) 2012 by the American Academy of Ophthalmology.
C1 [van Landingham, Suzanne W.; Willis, Jeffrey R.; Ramulu, Pradeep Y.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
[Vitale, Susan] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Ramulu, PY (reprint author), 600 N Wolfe St,Maumenee B-110, Baltimore, MD 21287 USA.
EM pramulu1@jhmi.edu
FU National Institutes of Health [EY018595]; Research to Prevent Blindness
Robert and Helen Schaub Special Scholar Award; Dennis W. Jahnigen
Memorial Award; Doris Duke Charitable Research Foundation Clinical
Research Fellowship
FX Supported in part by National Institutes of Health Grant EY018595, the
Research to Prevent Blindness Robert and Helen Schaub Special Scholar
Award, the Dennis W. Jahnigen Memorial Award, and the Doris Duke
Charitable Research Foundation Clinical Research Fellowship. The funding
organizations had no role in the design or conduct of this research.
NR 34
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U1 1
U2 8
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 DEC
PY 2012
VL 119
IS 12
BP 2486
EP 2492
DI 10.1016/j.ophtha.2012.06.034
PG 7
WC Ophthalmology
SC Ophthalmology
GA 049AL
UT WOS:000311954300010
PM 22892152
ER
PT J
AU Priya, RR
Chew, EY
Swaroop, A
AF Priya, Rinki Ratna
Chew, Emily Y.
Swaroop, Anand
TI Genetic Studies of Age-related Macular Degeneration Lessons, Challenges,
and Opportunities for Disease Management
SO OPHTHALMOLOGY
LA English
DT Article
ID COMPLEMENT FACTOR-H; MOLECULAR-GENETICS; RISK-FACTORS; ASSOCIATION;
SUSCEPTIBILITY; RANIBIZUMAB; VARIANTS; LOCI; CFH; PATHOGENESIS
AB Background: Age-related macular degeneration (AMD) is a common cause of visual impairment in individuals >55 years of age worldwide. The varying clinical phenotypes of AMD result from contributions of genetic, epigenetic, and nongenetic (environmental) factors. Genetic studies of AMD have come of age as a direct result of tremendous gains from the human genome project, genome-wide association studies, and identification of numerous susceptibility loci. These findings have implicated immune response, high-density lipoprotein cholesterol metabolism, extracellular matrix, and angiogenesis signaling pathways in disease pathophysiology.
Main Outcome Measures: Herein, we address how the wealth of genetic findings in AMD is expected to impact the practice of medicine, providing opportunities for improved risk assessment, molecular diagnosis, preventive, and therapeutic intervention.
Conclusions: We propose that the potential of using genetic variants for monitoring treatment response (pharmacogenetics) may usher in a new era of personalized medicine in the clinical management of AMD.
Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references. Ophthalmology 2012;119:2526-2536 (C) 2012 by the American Academy of Ophthalmology.
C1 [Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, MSC0610,6 Ctr Dr, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
OI Swaroop, Anand/0000-0002-1975-1141
FU National Eye Institute of the National Institutes of Health
FX Supported by the intramural program of the National Eye Institute of the
National Institutes of Health.
NR 52
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U1 1
U2 10
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 DEC
PY 2012
VL 119
IS 12
BP 2526
EP 2536
DI 10.1016/j.ophtha.2012.06.042
PG 11
WC Ophthalmology
SC Ophthalmology
GA 049AL
UT WOS:000311954300016
PM 23009893
ER
PT J
AU Toy, BC
Agron, E
Nigam, D
Chew, EY
Wong, WT
AF Toy, Brian C.
Agron, Elvira
Nigam, Divya
Chew, Emily Y.
Wong, Wai T.
TI Longitudinal Analysis of Retinal Hemangioblastomatosis and Visual
Function in Ocular von Hippel-Lindau Disease
SO OPHTHALMOLOGY
LA English
DT Article
ID TUMOR-SUPPRESSOR PROTEIN; GENOTYPE-PHENOTYPE CORRELATION; ANGIOMATOSIS;
CANCER; MUTATION; FEATURES; GENE
AB Objective: Characterization of the structural and functional progression of ocular von Hippel-Lindau (VHL) disease and analysis of patient factors influencing disease progression.
Design: Retrospective analysis of a case series from a longitudinal, observational study.
Participants: Two hundred forty-nine participants with clinically defined systemic VHL disease and more than 2 years of ophthalmic follow-up.
Methods: Standardized scoring of ocular phenotype and systemic characteristics was performed at each study visit and was analyzed longitudinally to determine progression of ocular VHL disease.
Main Outcome Measures: Measures evaluated include: visual acuity, features of ocular VHL disease (presence, location, number, and extent of retinal capillary hemangioblastomas [RCHs]), germline mutation in the VHL gene, demographics (age, gender, age at onset of ocular disease), and patient characteristics (smoking status, body mass index).
Results: Most participants demonstrated relative anatomic and functional stability in ocular VHL disease status over a mean follow-up of 8.2 +/- 4.0 years. Approximately three quarters (73%) of participants without ocular VHL disease at baseline remained disease free at the end of follow-up. Among eyes with ocular VHL disease at baseline, 88% did not demonstrate RCHs in a new retinal location, 70% remained stable in RCH number, and 79% remained stable in the extent of RCH involvement. Mean visual acuity for all study eyes (n = 498) decreased by 5.1 +/- 0.6 letters across follow-up, with 16.1% of study eyes decreasing by more than 10 letters in visual acuity. Among eyes affected at baseline, greater vision loss was associated with the presence of juxtapapillary RCHs, development of RCH in a new location, and increase in peripheral RCH number and extent. Younger baseline age, younger age at onset of ocular VHL disease, involvement of the fellow eye with ocular VHL disease, and missense or protein-truncating germline mutations were associated significantly with increased anatomic involvement and functional deterioration.
Conclusions: Patients with ocular VHL disease maintain relative anatomic and functional stability, with only a minority demonstrating marked anatomic progression and vision loss. Systemic and ocular risk factors for anatomic progression and vision loss can help practitioners identify patients with a higher risk profile for counseling, closer follow-up, and proactive treatment.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:2622-2630 (C) 2012 by the American Academy of Ophthalmology.
C1 [Wong, Wai T.] NEI, Unit Neuron Glia Interact, NIH, Bethesda, MD 20892 USA.
[Toy, Brian C.; Agron, Elvira; Nigam, Divya; Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Wong, WT (reprint author), NEI, Unit Neuron Glia Interact, NIH, 6 Ctr Dr,Bldg 6,Room 215, Bethesda, MD 20892 USA.
EM wongw@nei.nih.gov
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
FU National Eye Institute; National Institutes of Health, Bethesda,
Maryland; Pfizer, Inc, New York, New York; Pfizer
FX Supported by the National Eye Institute Intramural Research Program. Mr.
Toy was supported by the Clinical Research Training Program, a
public-private partnership supported jointly by the National Institutes
of Health, Bethesda, Maryland, and Pfizer, Inc, New York, New York (via
a grant to the Foundation for NIH from Pfizer). The sponsor or funding
organization had no role in the design or conduct of this research.
NR 28
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U1 0
U2 2
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 DEC
PY 2012
VL 119
IS 12
BP 2622
EP 2630
DI 10.1016/j.ophtha.2012.06.026
PG 9
WC Ophthalmology
SC Ophthalmology
GA 049AL
UT WOS:000311954300028
PM 22906772
ER
PT J
AU Harabin, AL
Kiley, JP
AF Harabin, Andrea L.
Kiley, James P.
TI How the National Heart, Lung, and Blood Institute (NHLBI) Develops
Research Priorities and Supports Critical Care Research
SO PHYSICAL THERAPY
LA English
DT Article
ID RESPIRATORY-DISTRESS-SYNDROME; CONTROLLED-TRIAL; TASK-FORCE; INJURY
AB This report provides a brief overview of some relevant ongoing research on critical care and how research priorities are determined by the National Heart, Lung, and Blood Institute. Long-term and patient-centered outcomes have become more prominent research questions for clinical studies in patients who are critically ill. Rehabilitation research would be appropriate in this context, and funding is most likely received through investigator-initiated R01 applications. National Institutes of Health program staff are available for discussion and advice and encourage contact from extramural investigators.
C1 [Harabin, Andrea L.] NHLBI, NIH, Div Lung Dis, Rockledge Ctr 2, Bethesda, MD 20892 USA.
RP Harabin, AL (reprint author), NHLBI, NIH, Div Lung Dis, Rockledge Ctr 2, 6701 Rockledge Dr,Suite 10042, Bethesda, MD 20892 USA.
EM harabin@nih.gov
NR 14
TC 4
Z9 4
U1 0
U2 6
PU AMER PHYSICAL THERAPY ASSOC
PI ALEXANDRIA
PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA
SN 0031-9023
J9 PHYS THER
JI Phys. Ther.
PD DEC
PY 2012
VL 92
IS 12
BP 1489
EP 1493
DI 10.2522/ptj.20110436
PG 5
WC Orthopedics; Rehabilitation
SC Orthopedics; Rehabilitation
GA 050KJ
UT WOS:000312051900003
PM 22836006
ER
PT J
AU Sosa, JA
Balkissoon, J
Lu, SP
Langecker, P
Elisei, R
Jarzab, B
Bal, CS
Marur, S
Gramza, A
Ondrey, F
AF Sosa, Julie A.
Balkissoon, Jai
Lu, Shiao-ping
Langecker, Peter
Elisei, Rossella
Jarzab, Barbara
Bal, C. S.
Marur, Shanthi
Gramza, Ann
Ondrey, Frank
TI Thyroidectomy followed by fosbretabulin (CA4P) combination regimen
appears to suggest improvement in patient survival in anaplastic thyroid
cancer
SO SURGERY
LA English
DT Article
ID COMBRETASTATIN A-4; PROGNOSTIC-FACTORS; CARCINOMA; CHEMOTHERAPY;
PHOSPHATE; AGENT
AB Background. Anaplastic thyroid cancer (ATC) is an aggressive neoplasm for which a paucity of data exist about the relative role of operative procedures in disease management.
Methods. The FACT trial was a randomized, controlled phase 2/3 trial assessing the safety and efficacy of carboplatin/paclitaxel with CA4P (experimental arm) or without CA4P (control arm) in ATC, 2007-11. Patients were permitted to have had an operation before enrollment, which was stratified on the basis of exposure to operation. A subpopulation of patients who had a cancer-related operation (thyroidectomy) was compared with those who did not, and 1-year and median survival were estimated.
Results. A total of 80 patients were enrolled; 55 % had undergone a cancer-related operation, of whom 70% had near-total/total thyroidectomy. Baseline characteristics for operative and nonoperative patients were not substantially different. Median survival for patients who had cancer-related operation was 8.2 months in the CA 4P arm versus 4.0 months in the control arm, resulting in a hazard ratio of 0.66 (P = .25) and a suggested associated reduction in risk of death of 35%. 1-year survival was 33.3% in the CA4P arm versus 7.7% in the control arm.
Conclusion. In this largest prospective study ever conducted in ATC, thyroidectomy followed by CA4P combination regimen showed a nonsignificant trend toward improvement in patient survival. (Surgery 2012;152:1078-87.)
C1 [Sosa, Julie A.] Yale Univ, Div Endocrine Surg, Dept Surg, Sch Med, New Haven, CT 06520 USA.
[Sosa, Julie A.] Yale Univ, Div Surg Oncol, Dept Surg, Sch Med, New Haven, CT 06520 USA.
[Balkissoon, Jai; Lu, Shiao-ping; Langecker, Peter] Oxigene, San Francisco, CA USA.
[Elisei, Rossella] Univ Pisa, Dept Endocrinol, Pisa, Italy.
[Jarzab, Barbara] MSC Mem Canc Ctr, Dept Nucl Med, Gliwice, Poland.
Inst Oncol, Gliwice, Poland.
[Bal, C. S.] All India Inst Med Sci, Dept Nucl Med, New Delhi, India.
[Marur, Shanthi] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA.
[Gramza, Ann] NCI, Branch Endocrine Oncol, Bethesda, MD 20892 USA.
[Ondrey, Frank] Univ Minnesota, Dept Otolaryngol Head & Neck Surg, Minneapolis, MN USA.
RP Sosa, JA (reprint author), Yale Univ, Div Endocrine Surg, Dept Surg, Sch Med, FMB 130B,330 Cedar St, New Haven, CT 06520 USA.
EM Julie.sosa@yale.edu
FU Oxigene, South San Francisco, CA
FX This study was supported by Oxigene, South San Francisco, CA. Drs
Balkissoon and Langecker are employed by Oxigene, and Shiao-ping Lu is a
consultant for Oxigene.
NR 23
TC 19
Z9 19
U1 1
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD DEC
PY 2012
VL 152
IS 6
BP 1078
EP 1086
DI 10.1016/j.surg.2012.08.036
PG 9
WC Surgery
SC Surgery
GA 052AQ
UT WOS:000312170500034
PM 23158178
ER
PT J
AU Kebebew, E
AF Kebebew, Electron
TI Anaplastic thyroid cancer: Rare, fatal, and neglected
SO SURGERY
LA English
DT Editorial Material
ID VEMURAFENIB; CARCINOMA; SURVIVAL; MELANOMA
C1 NCI, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, Bldg 10CRC,Room 3-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
NR 9
TC 9
Z9 9
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD DEC
PY 2012
VL 152
IS 6
BP 1088
EP 1089
DI 10.1016/j.surg.2012.08.059
PG 2
WC Surgery
SC Surgery
GA 052AQ
UT WOS:000312170500036
PM 23158179
ER
PT J
AU Turcotte, S
Turkbey, B
Barak, S
Libutti, SK
Alexander, HR
Linehan, WM
Hughes, MS
Nilubol, N
Gesuwan, K
Millo, C
Quezado, M
Choyke, PL
Kebebew, E
Phan, GQ
AF Turcotte, Simon
Turkbey, Bans
Barak, Stephanie
Libutti, Steven K.
Alexander, H. Richard
Linehan, W. Marston
Hughes, Marybeth S.
Nilubol, Naris
Gesuwan, Krisana
Millo, Corina
Quezado, Martha
Choyke, Peter L.
Kebebew, Electron
Phan, Giao Q.
TI von Hippel-Lindau disease-associated solid microcystic serous adenomas
masquerading as pancreatic neuroendocrine neoplasms
SO SURGERY
LA English
DT Article
ID TUMORS; CYSTADENOMA; GENETICS; VARIANT
AB Background. Patients with von Hippel-Lindau disease (VHL) commonly develop pancreatic cysts and neuroendocrine neoplasms (PNENs or PNETs). Solid microcystic serous adenoma (SMSA), a rare neoplasm described in VHL patients, can be mistaken for PNEN on imaging.
Methods. Clinical, pathologic, and radiologic data were reviewed on VHL patients who underwent surgery for a preoperative diagnosis of PNEN since 1994 at I institution. Blinded to the pathologic diagnoses, radiologists reassessed available imaging.
Results. For 55 patients, 79 pancreatectomies were performed for presumed PNENs. Ten (18%) patients underwent 12 (15%) resections for neoplasms diagnosed as SMSA on final pathology. The average size of a SMSA leading to operation was 3.6 +/- 0.4 cm. Four out of 11 SMSAs were still mistaken for PNENs when imaging was reassessed. The mean FDG-positron emission tomography (PET) standardized uptake value was greater for 17 PNENs (12.1 +/- 1.2) compared with 6 SMSAs (4.2 +/- 0.5; P =.002). The mean doubling time of SMSAs and PNENs was similar. Seven (15%) patients with pathologically proven PNENs had malignant disease.
Conclusion. SMSAs can mimic PNENs on nonfunctional imaging; FDG-PET may help to differentiate them. A high index of suspicion is needed to minimize operations performed for SMSA and to counsel VHL patients of their risks of undergoing operation for a lesion with no known malignant potential. (Surgery 2012; 152: 1106-17.)
C1 [Turcotte, Simon; Hughes, Marybeth S.; Nilubol, Naris; Gesuwan, Krisana; Kebebew, Electron; Phan, Giao Q.] NCI, Endocrine Oncol Sect, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Turkbey, Bans; Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA.
[Barak, Stephanie; Quezado, Martha] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Libutti, Steven K.] Albert Einstein Coll Med, Dept Surg, Bronx, NY 10467 USA.
[Alexander, H. Richard] Univ Maryland, Sch Med, Div Surg Oncol, Dept Surg, Baltimore, MD 21201 USA.
Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Linehan, W. Marston] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Millo, Corina] NIH, Positron Emiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA.
RP Phan, GQ (reprint author), Bldg 10 CRC,Room 3-5760,10 Ctr Dr, Bethesda, MD 20892 USA.
EM Giao.Phan@nih.gov
FU National Institutes of Health
FX Funded by the National Institutes of Health.
NR 21
TC 8
Z9 10
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD DEC
PY 2012
VL 152
IS 6
BP 1106
EP 1117
DI 10.1016/j.surg.2012.08.010
PG 12
WC Surgery
SC Surgery
GA 052AQ
UT WOS:000312170500041
PM 23107912
ER
PT J
AU Schlick, T
Arora, K
Beard, WA
Wilson, SH
AF Schlick, Tamar
Arora, Karunesh
Beard, William A.
Wilson, Samuel H.
TI Perspective: pre-chemistry conformational changes in DNA polymerase
mechanisms
SO THEORETICAL CHEMISTRY ACCOUNTS
LA English
DT Article
DE Enzyme catalysis; Intrinsic protein dynamics; Pre-chemistry
conformational adjustments; Nucleotidyl transfer; DNA polymerase beta;
Catalytic cycle chemical step
ID INDUCED FIT MECHANISM; BASE EXCISION-REPAIR; ENZYME CATALYSIS;
ACTIVE-SITE; PRIMER/TEMPLATE COMPLEXES; NUCLEOTIDE INCORPORATION;
DYNAMICS SIMULATIONS; ADENYLATE KINASE; GASTRIC-CANCER; G-A
AB In recent papers, there has been a lively exchange concerning theories for enzyme catalysis, especially the role of protein dynamics/pre-chemistry conformational changes in the catalytic cycle of enzymes. Of particular interest is the notion that substrate-induced conformational changes that assemble the polymerase active site prior to chemistry are required for DNA synthesis and impact fidelity (i.e., substrate specificity). High-resolution crystal structures of DNA polymerase beta representing intermediates of substrate complexes prior to the chemical step are available. These structures indicate that conformational adjustments in both the protein and substrates must occur to achieve the requisite geometry of the reactive participants for catalysis. We discuss computational and kinetic methods to examine possible conformational change pathways that lead from the observed crystal structure intermediates to the final structures poised for chemistry. The results, as well as kinetic data from site-directed mutagenesis studies, are consistent with models requiring pre-chemistry conformational adjustments in order to achieve high fidelity DNA synthesis. Thus, substrate-induced conformational changes that assemble the polymerase active site prior to chemistry contribute to DNA synthesis even when they do not represent actual rate-determining steps for chemistry.
C1 [Schlick, Tamar] NYU, Dept Chem, New York, NY 10003 USA.
[Schlick, Tamar] NYU, Courant Inst Math Sci, New York, NY 10012 USA.
[Arora, Karunesh] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA.
[Arora, Karunesh] Univ Michigan, Dept Biophys, Ann Arbor, MI 48109 USA.
[Beard, William A.; Wilson, Samuel H.] Natl Inst Environm Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Schlick, T (reprint author), NYU, Dept Chem, 100 Washington Sq E,Silver Bldg, New York, NY 10003 USA.
EM schlick@nyu.edu
FU Philip Morris USA Inc.; Philip Morris International; NSF [MCB-0316771];
NIH [R01 ES012692]; National Institutes of Health, National Institute of
Environmental Health Sciences; NIH award [1U19CA105010];
[Z01-ES050158]; [Z01-ES050161]
FX Research described in this Article was supported in part by Philip
Morris USA Inc. and Philip Morris International and by NSF award
MCB-0316771, and NIH award R01 ES012692 to T. S., and Research Project
Numbers Z01-ES050158 and Z01-ES050161 to S. H. W. in the Intramural
Research Program of the National Institutes of Health, National
Institute of Environmental Health Sciences and was in association with
NIH award 1U19CA105010.
NR 59
TC 14
Z9 14
U1 0
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1432-881X
J9 THEOR CHEM ACC
JI Theor. Chem. Acc.
PD DEC
PY 2012
VL 131
IS 12
AR 1287
DI 10.1007/s00214-012-1287-7
PG 8
WC Chemistry, Physical
SC Chemistry
GA 050TO
UT WOS:000312077100003
PM 23459563
ER
PT J
AU Metcalf, CJE
Lessler, J
Klepac, P
Morice, A
Grenfell, BT
Bjornstad, ON
AF Metcalf, C. J. E.
Lessler, J.
Klepac, P.
Morice, A.
Grenfell, B. T.
Bjornstad, O. N.
TI Structured models of infectious disease: Inference with discrete data
SO THEORETICAL POPULATION BIOLOGY
LA English
DT Article
DE Congenital rubella syndrome; CRS; Epidemiology; Matrix model; Catalytic
model; Perturbation analysis
ID CONGENITAL-RUBELLA-SYNDROME; MEASLES EPIDEMICS; COSTA-RICA; VACCINATION;
DYNAMICS; TRANSMISSION; SEASONALITY; POPULATIONS; BURDEN; EUROPE
AB The usage of structured population models can make substantial contributions to public health, particularly for infections where clinical outcomes vary over age. There are three theoretical challenges in implementing such analyses: (i) developing an appropriate framework that models both demographic and epidemiological transitions; (ii) parameterizing the framework, where parameters may be based on data ranging from the biological course of infection, basic patterns of human demography, specific characteristics of population growth, and details of vaccination regimes implemented: (iii) evaluating public health strategies in the face of changing human demography. We illustrate the general approach by developing a model of rubella in Costa Rica. The demographic profile of this infection is a crucial aspect of its public health impact, and we use a transient perturbation analysis to explore the impact of changing human demography on immunization strategies implemented. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Metcalf, C. J. E.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
[Lessler, J.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Klepac, P.; Grenfell, B. T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Morice, A.] Minist Hlth, San Jose, Costa Rica.
[Grenfell, B. T.; Bjornstad, O. N.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Bjornstad, O. N.] Penn State Univ, Ctr Infect Dis Dynam, State Coll, PA USA.
RP Metcalf, CJE (reprint author), Univ Oxford, Dept Zool, S Parks Rd, Oxford OX1 3PS, England.
EM charlotte.metcalf@zoo.ox.ac.uk
OI Lessler, Justin/0000-0002-9741-8109
FU Royal Society; Bill and Melinda Gates Foundation; RAPIDD program of the
Science & Technology Directorate of the Department of Homeland Security;
Fogarty International Center National Institute of Health (BTG); NIH
[NIFI/GM R01-GM083983-01]
FX We thank the people of the Costa Rica national network of epidemiology
for all their hard work in conducting surveillance activities and
providing the rubella data used in this study, and the POLYMOD project.
This work was funded by the Royal Society (CJEM), the Bill and Melinda
Gates Foundation (CJEM, BTG, JL, PK), the RAPIDD program of the Science
& Technology Directorate of the Department of Homeland Security, and the
Fogarty International Center National Institute of Health (BTG) and NIH
grant NIFI/GM R01-GM083983-01 (CJEM, BTG).
NR 39
TC 9
Z9 9
U1 4
U2 28
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0040-5809
J9 THEOR POPUL BIOL
JI Theor. Popul. Biol.
PD DEC
PY 2012
VL 82
IS 4
SI SI
BP 275
EP 282
DI 10.1016/j.tpb.2011.12.001
PG 8
WC Ecology; Evolutionary Biology; Genetics & Heredity
SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics &
Heredity
GA 049KH
UT WOS:000311981400005
PM 22178687
ER
PT J
AU Anticevic, A
Cole, MW
Murray, JD
Corlett, PR
Wang, XJ
Krystal, JH
AF Anticevic, Alan
Cole, Michael W.
Murray, John D.
Corlett, Philip R.
Wang, Xiao-Jing
Krystal, John H.
TI The role of default network deactivation in cognition and disease
SO TRENDS IN COGNITIVE SCIENCES
LA English
DT Review
ID INTRINSIC FUNCTIONAL CONNECTIVITY; POSTERIOR CINGULATE CORTEX; DOWN
SUPPRESSION DEFICIT; CONSCIOUS RESTING STATE; SHORT-TERM-MEMORY;
WORKING-MEMORY; MODE NETWORK; PREFRONTAL CORTEX; HUMAN BRAIN; DEPRESSIVE
DISORDER
AB A considerable body of evidence has accumulated over recent years on the functions of the default-mode network (DMN) - a set of brain regions whose activity is high when the mind is not engaged in specific behavioral tasks and low during focused attention on the external environment. In this review, we focus on DMN suppression and its functional role in health and disease, summarizing evidence that spans several disciplines, including cognitive neuroscience, pharmacological neuroimaging, clinical neuroscience, and theoretical neuroscience. Collectively, this research highlights the functional relevance of DMN suppression for goal-directed cognition, possibly by reducing goal-irrelevant functions supported by the DMN (e.g., mind-wandering), and illustrates the functional significance of DMN suppression deficits in severe mental illness.
C1 [Anticevic, Alan; Corlett, Philip R.; Krystal, John H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA.
[Anticevic, Alan; Krystal, John H.] Yale Univ, NIAAA, CTNA, New Haven, CT 06519 USA.
[Anticevic, Alan; Corlett, Philip R.; Krystal, John H.] Yale Univ, Dept Psychiat, Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA.
[Cole, Michael W.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA.
[Murray, John D.; Wang, Xiao-Jing] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
[Murray, John D.; Wang, Xiao-Jing] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA.
[Murray, John D.; Wang, Xiao-Jing] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA.
[Krystal, John H.] Yale New Haven Med Ctr, Dept Psychiat, Psychiat Serv, New Haven, CT 06510 USA.
[Krystal, John H.] VA Connecticut Healthcare Syst, Clin Neurosci Div, Vet Affairs VA Natl Ctr Posttraumat Stress Disord, West Haven, CT 06516 USA.
[Wang, Xiao-Jing] NYU, Ctr Neural Sci, New York, NY 10003 USA.
RP Anticevic, A (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA.
EM alan.anticevic@yale.edu; john.krystal@yale.edu
RI Wang, Xiao-Jing/D-2722-2009; Murray, John/B-2835-2009; Cole,
Michael/G-1056-2010;
OI Murray, John/0000-0003-4115-8181; Cole, Michael/0000-0003-4329-438X;
Corlett, Philip/0000-0002-5368-1992
FU NIH [DP5OD012109-01, MH096801]; NIAAA [2P50AA012870-11]; CTSA from the
National Center for Research Resources (NCRR) [UL1 RR024139]; National
Center for Advancing Translational Science (NCATS), National Institutes
of Health (NIH); NIH roadmap for Medical Research; Pfizer; AstraZeneca
FX J.H.K. has been a paid consultant for AbbVie, Inc. (formerly Abbott
Laboratories), Aisling Capital, LLC, AstraZeneca Pharmaceuticals,
Bristol-Myers Squibb, Eisai, Inc., Eli Lilly and Co., Gilead Sciences,
Inc., Lundbeck Research USA, Medivation, Inc., Otsuka Pharmaceutical
Development & Commercialization, Inc., Roche F. Hoffmann-La Roche Ltd,
Sage Therapeutics, Inc., Shire Pharmaceuticals, Takeda Industries, and
Teva Pharmaceutical Industries, Ltd. J.H.K. serves as a member of the
Scientific Advisory Boards for CHDI Foundation, Inc., Lohocla Research
Corporation, Mnemosyne Pharmaceuticals, Inc., Naurex, Inc., and Pfizer
Pharmaceuticals. J.H.K. is a member of the Board of Directors for the
Coalition for Translational Research in Alcohol and Substance Use
Disorders, is the President Elect of the American College of
Neuropsychopharmacology, and is the Editor of Biological Psychiatry.
J.H.K. is listed as an inventor on the patent: Seibyl JP, Krystal JH,
Charney DS (1995) US Patent 5,447,948. J.H.K. is listed as an inventor
on a patent application by Yale University related to targeting the
glutamatergic system for the treatment of neuropsychiatric disorders
(application no. PCTWO06108055A1). J.H.K. is listed on a pending patent
application related to intranasal administration of ketamine to treat
depression. Dr. Corlett reports no biomedical financial interests or
potential conflicts of interest relevant to this work but, for unrelated
activities, he consults for Pfizer, Johnson and Johnson, is on the
scientific advisory board for Janssen, and has received research support
from Pfizer and AstraZeneca. All other authors report no biomedical
financial interests or potential conflicts of interest.; We thank Megan
Ichinose for assistance with this manuscript and Deanna M. Barch for
insightful discussions and input. We also thank three anonymous
reviewers for helpful comments and constructive criticism on how to
improve the manuscript. Lastly, we thank our funding sources. This work
was supported by the NIH grant DP5OD012109-01 (AA), NIAAA grant
2P50AA012870-11 (JHK, AA), NIH grant MH096801 (MWC), and CTSA Grant
Number UL1 RR024139 from the National Center for Research Resources
(NCRR) and the National Center for Advancing Translational Science
(NCATS), components of the National Institutes of Health (NIH), and NIH
roadmap for Medical Research (PRC).
NR 106
TC 199
Z9 200
U1 11
U2 112
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1364-6613
J9 TRENDS COGN SCI
JI TRENDS COGN. SCI.
PD DEC
PY 2012
VL 16
IS 12
BP 584
EP 592
DI 10.1016/j.tics.2012.10.008
PG 9
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 050LR
UT WOS:000312055300006
PM 23142417
ER
PT J
AU Bhattacharyya, N
Chong, WH
Gafni, RI
Collins, MT
AF Bhattacharyya, Nisan
Chong, William H.
Gafni, Rachel I.
Collins, Michael T.
TI Fibroblast growth factor 23: state of the field and future directions
SO TRENDS IN ENDOCRINOLOGY AND METABOLISM
LA English
DT Review
ID TUMOR-INDUCED OSTEOMALACIA; DOMINANT HYPOPHOSPHATEMIC RICKETS; CHRONIC
KIDNEY-DISEASE; VITAMIN-D METABOLISM; HYPEROSTOSIS-HYPERPHOSPHATEMIA
SYNDROME; AUTOSOMAL RECESSIVE HYPOPHOSPHATEMIA; HOMOZYGOUS MISSENSE
MUTATION; X-LINKED HYPOPHOSPHATEMIA; RENAL PHOSPHATE-TRANSPORT;
MCCUNE-ALBRIGHT-SYNDROME
AB Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates and is regulated by blood levels of phosphate and active vitamin D. Post-translational glycosylation by the enzyme GALNT3 and subsequent processing by furin have been demonstrated to be a regulated process that plays a role in regulating FGF23 levels. In physiologic states, FGF23 signaling is mediated by an FGF receptor and the coreceptor, Klotho. Recent work identifying a role for iron/hypoxia pathways in FGF23 physiology and their implications are discussed. Beyond its importance in primary disorders of mineral metabolism, recent work implicates FGF23 in renal disease-associated morbidity, as well as possible roles in cardiovascular disease and skeletal fragility.
C1 [Bhattacharyya, Nisan; Chong, William H.; Gafni, Rachel I.; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
RP Collins, MT (reprint author), Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
EM mc247k@nih.gov
FU Division of Intramural Research, National Institute of Dental and
Craniofacial Research, National Institutes of Health, Department of
Health and Human Services
FX This research was supported by the Division of Intramural Research,
National Institute of Dental and Craniofacial Research, National
Institutes of Health, Department of Health and Human Services.
NR 99
TC 42
Z9 43
U1 1
U2 43
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1043-2760
J9 TRENDS ENDOCRIN MET
JI Trends Endocrinol. Metab.
PD DEC
PY 2012
VL 23
IS 12
BP 610
EP 618
DI 10.1016/j.tem.2012.07.002
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 050HM
UT WOS:000312043900004
PM 22921867
ER
PT J
AU Croteau, DL
Singh, DK
Ferrarelli, LH
Lu, HM
Bohr, VA
AF Croteau, Deborah L.
Singh, Dharmendra Kumar
Ferrarelli, Leslie Hoh
Lu, Huiming
Bohr, Vilhelm A.
TI RECQL4 in genomic instability and aging
SO TRENDS IN GENETICS
LA English
DT Review
ID ROTHMUND-THOMSON-SYNDROME; SYNDROME GENE-PRODUCT; BASE EXCISION-REPAIR;
DNA-REPLICATION; OXIDATIVE STRESS; CHROMOSOMAL INSTABILITY; SYNDROME
PROTEINS; FAMILY HELICASES; HUMAN-CELLS; MITOCHONDRIA
AB Helicases are ubiquitous proteins that unwind DNA and participate in DNA metabolism including replication, repair, transcription, and chromatin organization. The highly conserved RecQ helicase family proteins are important in these transactions and have been termed the guardians of the genome. Humans have five members of this family: WRN, BLM, RECQL4, RECOL1, and RECQL5. The first three of are associated with premature aging and cancer prone syndromes, but the latter two proteins have not yet been implicated in any human disease. Although WRN and BLM have been fairly well characterized, RECOL4 has only recently been intensively investigated. The sum of this work to date has shown that RECQL4 has helicase activity and localizes to telomeres and mitochondria. In addition, new protein partners are emerging, implicating RECQL4 in novel processes. Here, we describe these recent findings which place RECQL4 at the crossroads of genomic instability and aging processes.
C1 [Croteau, Deborah L.; Singh, Dharmendra Kumar; Ferrarelli, Leslie Hoh; Lu, Huiming; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21040 USA.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21040 USA.
EM vbohr@nih.gov
RI LU, HUIMING/C-1996-2014
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging [AG000726-20]
FX We would like to thank Martin Borch Jensen and Dr Venkateswarlu Popuri
for critically reading the manuscript. We would like to thank Thomas
Wynn for his artwork. This research was supported entirely by the
Intramural Research Program of the National Institutes of Health,
National Institute on Aging, AG000726-20.
NR 63
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U1 0
U2 21
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0168-9525
J9 TRENDS GENET
JI Trends Genet.
PD DEC
PY 2012
VL 28
IS 12
BP 624
EP 631
DI 10.1016/j.tig.2012.08.003
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 050LN
UT WOS:000312054900007
PM 22940096
ER
PT J
AU Guo, LY
Junttila, IS
Paul, WE
AF Guo, Liying
Junttila, Ilkka S.
Paul, William E.
TI Cytokine-induced cytokine production by conventional and innate lymphoid
cells
SO TRENDS IN IMMUNOLOGY
LA English
DT Review
DE cytokine; IL-1; STAT; ILC; T helper cells; innate; effector
ID CD8(+) T-CELLS; NATURAL-KILLER-CELLS; INTERFERON-GAMMA PRODUCTION;
NF-KAPPA-B; INVARIANT NKT CELLS; ROR-GAMMA; IFN-GAMMA; TYPE-2 IMMUNITY;
CUTTING EDGE; IN-VIVO
AB Innate immune and differentiated T cells produce signature cytokines in response to cytokine stimulation. Optimal production requires stimulation by an NF-kappa B inducer, most commonly an interleukin (IL)-1 family member, and a STAT activator. Usually, there is linkage between the IL-1 family member, the activated STAT and the cytokines produced: IFN gamma producers respond to the IL-1 family member, IL-18 and IL-12, a STAT4 activator; IL-13 producers respond to IL-33 (although for ILC2 cells this may be replaced by IL-25) and STAT5 activators; for cells producing IL-17A or IL-22, the combination is IL-1 and a STAT3 inducer. Cytokine-induced cytokine production may have broad significance in orchestrating innate responses to distinct infectious agents and in maintaining inflammatory responses after elimination of the inciting antigen.
C1 [Guo, Liying; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Junttila, Ilkka S.] Univ Tampere, Sch Med, Tampere 33100, Finland.
[Junttila, Ilkka S.] Pirkanmaa Hosp Dist, Fimlab Labs, Tampere, Finland.
RP Guo, LY (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM lguo@niaid.nih.gov; wpaul@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy, and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy, and Infectious Diseases, National Institutes of
Health.
NR 115
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U1 0
U2 20
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4906
J9 TRENDS IMMUNOL
JI Trends Immunol.
PD DEC
PY 2012
VL 33
IS 12
BP 598
EP 606
DI 10.1016/j.it.2012.07.006
PG 9
WC Immunology
SC Immunology
GA 050LV
UT WOS:000312055700003
PM 22959641
ER
PT J
AU Shevach, EM
AF Shevach, Ethan M.
TI Application of IL-2 therapy to target T regulatory cell function
SO TRENDS IN IMMUNOLOGY
LA English
DT Review
DE interleukin-2; regulatory T cells; Foxp3; autoimmunity; graft versus
host disease; immune complexes
ID VERSUS-HOST-DISEASE; IN-VIVO EXPANSION; CUTTING EDGE; INTERLEUKIN-2
THERAPY; SELECTIVE STIMULATION; MULTIPLE-SCLEROSIS; ANTIBODY COMPLEXES;
AUTOIMMUNE-DISEASE; IMMUNE-COMPLEXES; NK CELLS
AB Interleukin-2 (IL-2) was originally discovered as a growth factor for activated T cells in vitro. IL-2 promotes CD8(+) T cell growth and differentiation in vivo, but has little effect on CD4(+) T cell function. Regulatory T cells (Treg cells) express all three chains (CD25, CD122, and CD132) of the IL-2 receptor complex and are dependent on IL-2 for survival and function. Exogenous IL-2 can augment Treg cell numbers in vivo and may have therapeutic value in the treatment of autoimmune and inflammatory diseases. Complexes of IL-2 with different IL-2 antibodies can target delivery to cells expressing all three receptor chains (Treg cells and activated T effector cells) or to cells expressing just CD122 and CD132 (NK cells and memory phenotype CD8(+) T cells).
C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM eshevach@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000959-03]
NR 63
TC 31
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U1 2
U2 29
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4906
J9 TRENDS IMMUNOL
JI Trends Immunol.
PD DEC
PY 2012
VL 33
IS 12
BP 626
EP 632
DI 10.1016/j.it.2012.07.007
PG 7
WC Immunology
SC Immunology
GA 050LV
UT WOS:000312055700006
PM 22951308
ER
PT J
AU Carrasco, M
Eckstein, M
Krauzlis, R
Verghese, P
AF Carrasco, Marisa
Eckstein, Miguel
Krauzlis, Rich
Verghese, Preeti
TI Vision Research special issue on "Visual attention"
SO VISION RESEARCH
LA English
DT Editorial Material
C1 [Carrasco, Marisa] NYU, New York, NY 10003 USA.
[Eckstein, Miguel] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA.
[Krauzlis, Rich] NIH, Bethesda, MD 20892 USA.
[Verghese, Preeti] Smith Kettlewell Eye Inst, San Francisco, CA USA.
RP Carrasco, M (reprint author), NYU, New York, NY 10003 USA.
EM marisa.carrasco@nyu.edu; eckstein@psych.ucsb.edu;
richard.krauzlis@nih.gov; preeti@ski.org
NR 0
TC 2
Z9 2
U1 0
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD DEC 1
PY 2012
VL 74
SI SI
BP 1
EP 1
DI 10.1016/j.visres.2012.11.001
PG 1
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 051IA
UT WOS:000312118600001
PM 23158417
ER
PT J
AU Krauzlis, RJ
Dill, N
Fowler, GA
AF Krauzlis, Richard J.
Dill, Natalie
Fowler, Garth A.
TI Dissociation of pursuit target selection from saccade execution
SO VISION RESEARCH
LA English
DT Article
DE Target selection; Attention; Saccade; Smooth pursuit; Superior
colliculus; Eye movement
ID PRIMATE SUPERIOR COLLICULUS; EYE-MOVEMENTS; SMOOTH-PURSUIT;
NEURONAL-ACTIVITY; VISUAL-ATTENTION; GAP PARADIGM; INACTIVATION;
INITIATION; MONKEY; LATENCY
AB Pursuit and saccades almost always select the same target. Is this the results of a common selection process or does smooth pursuit obligatorily follow the stimulus targeted by saccades? To address this question, we used microstimulation of the primate superior colliculus (SC) to redirect the eyes from a selected pursuit target to a distracter moving in the opposite direction. During each trial, monkeys pursued a horizontally moving array of colored target stimuli. In half of the trials, this target array was accompanied by a distracter array moving horizontally in the opposite direction, offset by the vertical amplitude of the stimulation-evoked saccade. We stimulated the SC during maintained pursuit on half of the trials, and measured pursuit eye velocity during the 50-ms interval immediately following the stimulation-evoked saccade to the distracter array. Saccades evoked by SC stimulation did not alter pursuit target selection. Pursuit velocity on average changed by less than 10% of that expected if the monkey had completely switched targets. Moreover, the same changes in velocity occurred when there was no distracter, indicating that even these small changes in pursuit velocity were a direct effect of the evoked saccade, not partial selection of the distracter. These results show that motor execution of saccades is not sufficient to select a pursuit target, and support the idea that the coordination of pursuit and saccades is accomplished by a shared target selection process. Published by Elsevier Ltd.
C1 [Krauzlis, Richard J.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
[Krauzlis, Richard J.; Dill, Natalie] Salk Inst Biol Studies, Syst Neurobiol Lab, La Jolla, CA 92037 USA.
[Fowler, Garth A.] Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA.
RP Krauzlis, RJ (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM richard.krauzlis@nih.gov
FU NIH [EY12212, RO1 EY-012212]; National Eye Institute Intramural Research
Program at the NIH
FX This work was supported by NIH Grant EY12212 and the National Eye
Institute Intramural Research Program at the NIH. We thank Eileen Boehle
for technical assistance, and Mary Garcia for administrative help. This
research was supported by the National Institutes of Health Grant RO1
EY-012212 and by the National Eye Institute Intramural Research Program
at the NIH.
NR 43
TC 3
Z9 3
U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD DEC 1
PY 2012
VL 74
SI SI
BP 72
EP 79
DI 10.1016/j.visres.2012.09.006
PG 8
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 051IA
UT WOS:000312118600008
PM 23022138
ER
PT J
AU Mascette, AM
Bernard, GR
DiMichele, D
Goldner, JA
Harrington, R
Harris, PA
Leeds, HS
Pearson, TA
Ramsey, B
Wagner, TH
AF Mascette, Alice M.
Bernard, Gordon R.
DiMichele, Donna
Goldner, Jesse A.
Harrington, Robert
Harris, Paul A.
Leeds, Hilary S.
Pearson, Thomas A.
Ramsey, Bonnie
Wagner, Todd H.
TI Are Central Institutional Review Boards the Solution? The National
Heart, Lung, and Blood Institute Working Group's Report on Optimizing
the IRB Process
SO ACADEMIC MEDICINE
LA English
DT Article
ID VARIABILITY; TRIALS
AB The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health convened a working group in June 2011 to examine alternative institutional review board (IRB) models. The working group was held in response to proposed changes in the regulations for government-supported research and the proliferation of multicenter clinical trials where multiple individual reviews may be inefficient. Group members included experts in heart, lung, and blood research, research oversight, bioethics, health economics, regulations, and information technology (IT). The group discussed alternative IRB models, ethical concerns, metrics for evaluating IRBs, IT needs, and economic considerations. Participants noted research gaps in IRB best practices and in metrics. The group arrived at recommendations for process changes, such as defining specific IRB performance requirements in funding announcements, requiring funded researchers to use more efficient alternative IRB models, and developing IT systems to facilitate information sharing and collaboration among IRBs. Despite the success of the National Cancer Institute's central IRB (CIRB), the working group, concerned about the creation costs and unknown cost-efficiency of a new CIRB, and about the risk of shifting the burden of dealing with multiple IRBs from sponsors to research institutions, did not recommend the creation of an NHLBI-funded CIRB.
C1 [Mascette, Alice M.] NHLBI, Off Special Projects, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Harris, Paul A.] Vanderbilt Univ, Med Ctr, Off Res Informat, Nashville, TN USA.
[DiMichele, Donna] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA.
[Goldner, Jesse A.] St Louis Univ, Sch Law, St Louis, MO 63103 USA.
[Goldner, Jesse A.] St Louis Univ, Sch Med, St Louis, MO USA.
[Harrington, Robert] Stanford Univ, Dept Med, Stanford, CA 94305 USA.
[Harrington, Robert] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
[Harrington, Robert] Duke Univ, Sch Med, Div Cardiol, Durham, NC USA.
[Leeds, Hilary S.] NHLBI, Off Sci & Technol, NIH, Bethesda, MD 20892 USA.
[Pearson, Thomas A.] Univ Rochester, Sch Med & Dent, Rochester Clin & Translat Sci Inst, Rochester, NY USA.
[Ramsey, Bonnie] Univ Washington, Sch Med, Cyst Fibrosis Therapeut Dev Network Coordinating, Seattle, WA USA.
[Wagner, Todd H.] VA Palo Alto Hlth Care Syst, Menlo Pk, CA USA.
[Wagner, Todd H.] Stanford Univ, Ctr Hlth Policy, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA.
RP Mascette, AM (reprint author), 6701 Rockledge Dr,MSC 7940,Room 8144, Bethesda, MD 20892 USA.
EM Alice.Mascette@NIH.gov
FU National Heart, Lung, and Blood Institute
FX The meeting and travel support for invited participants were funded by
the National Heart, Lung, and Blood Institute.
NR 25
TC 8
Z9 8
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-2446
J9 ACAD MED
JI Acad. Med.
PD DEC
PY 2012
VL 87
IS 12
BP 1710
EP 1714
DI 10.1097/ACM.0b013e3182720859
PG 5
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 047JR
UT WOS:000311836800021
PM 23095928
ER
PT J
AU Chen, C
Chen, F
Mullan, F
AF Chen, Candice
Chen, Frederick
Mullan, Fitzhugh
TI Teaching Health Centers: A New Paradigm in Graduate Medical Education
SO ACADEMIC MEDICINE
LA English
DT Article
ID PRIMARY-CARE; INTERNAL-MEDICINE; RESIDENCY; PHYSICIANS; WORKFORCE;
OUTCOMES
AB The Patient Protection and Affordable Care Act of 2010 created the Teaching Health Center Graduate Medical Education (THCGME) program to provide graduate medical education (GME) funding directly to community-based health centers that expand or establish new primary care residency programs. The THCGME program was the legislation's only new investment in GME, and it represents a significant departure from the Medicare GME funding system. It provides payments to ambulatory care centers for both direct and indirect GME expenses, and mandates a level of reporting from recipients that is not required for Medicare GME support. This initial look at the 11 inaugural teaching health centers (THCs) shows that they are training primary care residents in relevant delivery models (e. g., interprofessional teams, patient-centered medical homes), developing educational initiatives that address primary care practice in underserved areas, and transforming organizational and funding structures to support community-based training. The THCs plan to evaluate and report resident performance, patient quality of care, and graduate outcomes. The work of the first THCs has implications for primary care training, the GME system, and future policies and legislation aimed at strengthening the health care workforce.
C1 [Chen, Candice] Natl Inst Minor Hlth & Hlth Dispar, NIH, Washington, DC USA.
[Chen, Candice; Mullan, Fitzhugh] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Hlth Policy, Washington, DC USA.
[Chen, Frederick] Univ Washington, Sch Med, Dept Family Med, Seattle, WA 98195 USA.
RP Chen, C (reprint author), 2121 K St NW,Suite 210, Washington, DC 20037 USA.
EM cpchen@gwu.edu
FU Josiah Macy Jr. Foundation; National Institute of Minority Health and
Health Disparities, National Institutes of Health
FX The Josiah Macy Jr. Foundation supported this work through the grant
entitled "Assessing Graduate Medical Education: How Are Teaching
Hospitals and Teaching Health Centers Meeting Society's Needs?" Dr. C.
Chen was supported through a DREAM Award by the National Institute of
Minority Health and Health Disparities, National Institutes of Health.
NR 22
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U1 1
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-2446
J9 ACAD MED
JI Acad. Med.
PD DEC
PY 2012
VL 87
IS 12
BP 1752
EP 1756
DI 10.1097/ACM.0b013e3182720f4d
PG 5
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 047JR
UT WOS:000311836800029
PM 23095929
ER
PT J
AU Driscoll, I
Troncoso, JC
Rudow, G
Sojkova, J
Pletnikova, O
Zhou, Y
Kraut, MA
Ferrucci, L
Mathis, CA
Klunk, WE
O'Brien, RJ
Davatzikos, C
Wong, DF
Resnick, SM
AF Driscoll, Ira
Troncoso, Juan C.
Rudow, Gay
Sojkova, Jitka
Pletnikova, Olga
Zhou, Yun
Kraut, Michael A.
Ferrucci, Luigi
Mathis, Chester A.
Klunk, William E.
O'Brien, Richard J.
Davatzikos, Christos
Wong, Dean F.
Resnick, Susan M.
TI Correspondence between in vivo C-11-PiB-PET amyloid imaging and
postmortem, region-matched assessment of plaques
SO ACTA NEUROPATHOLOGICA
LA English
DT Article
DE Plaques; Tangles; Stereology; PiB; Alzheimer; Neuroimaging
ID PITTSBURGH COMPOUND-B; MILD COGNITIVE IMPAIRMENT;
POSITRON-EMISSION-TOMOGRAPHY; REFERENCE TISSUE MODEL;
ALZHEIMERS-DISEASE; OLDER-ADULTS; LEWY BODIES; SPATIAL CONSTRAINT; PET;
DEMENTIA
AB The definitive Alzheimer's disease (AD) diagnosis requires postmortem confirmation of neuropathological hallmarks-amyloid-beta (A beta) plaques and neurofibrillary tangles (NFTs). The advent of radiotracers for amyloid imaging presents an opportunity to investigate amyloid deposition in vivo. The C-11-Pittsburgh compound-B (PiB)-PET ligand remains the most widely studied to date; however, regional variations in C-11-PiB binding and the extent of agreement with neuropathological assessment have not been thoroughly investigated. Sojkova and colleagues [35] reported variable agreement between CERAD-based neuropathologic diagnosis of AD lesions and mean cortical PiB, suggesting the need for a more direct quantification of regional A beta in relation to in vivo imaging. In the present study, we extend these findings by examining the correspondence among regional C-11-PiB load, region-matched quantitative immunohistological assessments of A beta and NFTs, and brain atrophy (MRI) in six older Baltimore Longitudinal Study of Aging participants who came to autopsy (imaging-autopsy interval range 0.2-2.4 years). The total number of A beta plaques (6E10) and NFTs (PHF1) in paraffin sections from hippocampus, orbito-frontal cortex, anterior and posterior cingulate gyrus, precuneus and cerebellum was quantified using a technique guided by unbiased stereological principles. We report a general agreement between the regional measures of amyloid obtained via stereological assessment and imaging, with significant relationships evident for the anterior (r = 0.83; p = 0.04) and posterior (r = 0.94; p = 0.005) cingulate gyri, and the precuneus (r = 0.94; p = 0.005). No associations were observed between C-11-PiB load and NFT count for any of the regions examined (p > 0.2 in all regions), or between regional A beta or NFT counts and corresponding brain volumes. The strong associations of PiB retention with region-matched, quantitative analyses of A beta in postmortem tissue offer support for the validity of C-11-PiB-PET imaging as a method for evaluation of plaque burden in vivo.
C1 [Driscoll, Ira] Univ Wisconsin, Dept Psychol, Milwaukee, WI 53211 USA.
[Driscoll, Ira; Sojkova, Jitka; Ferrucci, Luigi; Resnick, Susan M.] NIA, Baltimore, MD 21224 USA.
[Troncoso, Juan C.; Rudow, Gay; Pletnikova, Olga] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Sojkova, Jitka; Zhou, Yun; Kraut, Michael A.; Wong, Dean F.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA.
[Mathis, Chester A.] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA.
[Klunk, William E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Klunk, William E.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
[Troncoso, Juan C.; O'Brien, Richard J.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Davatzikos, Christos] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
RP Driscoll, I (reprint author), Univ Wisconsin, Dept Psychol, 224 Garland Hall,2441 Hartford Ave, Milwaukee, WI 53211 USA.
EM driscoli@uwm.edu
OI Klunk, William/0000-0001-5512-0251
FU NIA Intramural Research Program of National Institutes of Health; JHU
ADRC [NIA AG05146]; Alzheimer's Association [IIRG-09-134090]
FX This work was supported in part by the NIA Intramural Research Program
of the National Institutes of Health. Dr. Troncoso was supported by a
grant from the JHU ADRC (NIA AG05146) and the Alzheimer's Association
(IIRG-09-134090). We thank Andrew Crabb, MS, for image data management,
Beth Nardi, MA, for study management, the staff of the PET facility, the
Brain Bank, and the Autopsy Study at The Johns Hopkins University and
the neuroimaging staff of the National Institute on Aging for their
assistance.
NR 41
TC 39
Z9 39
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD DEC
PY 2012
VL 124
IS 6
BP 823
EP 831
DI 10.1007/s00401-012-1025-1
PG 9
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 046FU
UT WOS:000311751700006
PM 22864813
ER
PT J
AU Samelson, EJ
Booth, SL
Fox, CS
Tucker, KL
Wang, TJ
Hoffmann, U
Cupples, LA
O'Donnell, CJ
Kiel, DP
AF Samelson, Elizabeth J.
Booth, Sarah L.
Fox, Caroline S.
Tucker, Katherine L.
Wang, Thomas J.
Hoffmann, Udo
Cupples, L. Adrienne
O'Donnell, Christopher J.
Kiel, Douglas P.
TI Calcium intake is not associated with increased coronary artery
calcification: the Framingham Study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID FOOD FREQUENCY QUESTIONNAIRE; BONE-VASCULAR AXIS; VITAMIN-D;
MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; AORTIC CALCIFICATION;
DIETARY ASSESSMENT; WOMENS HEALTH; HEART-DISEASE; RISK
AB Background: Adequate calcium intake is known to protect the skeleton. However, studies that have reported adverse effects of calcium supplementation on vascular events have raised widespread concern.
Objective: We assessed the association between calcium intake (from diet and supplements) and coronary artery calcification, which is a measure of atherosclerosis that predicts risk of ischemic heart disease independent of other risk factors.
Design: This was an observational, prospective cohort study. Participants included 690 women and 588 men in the Framingham Offspring Study (mean age: 60 y; range: 36-83 y) who attended clinic visits and completed food-frequency questionnaires in 1998 2001 and underwent computed tomography scans 4 y later in 2002 2005.
Results: The mean age-adjusted coronary artery calcification Agatston score decreased with increasing total calcium intake, and the trend was not significant after adjustment for age, BMI, smoking, alcohol consumption, vitamin D supplement use, energy intake, and, for women, menopause status and estrogen use. Mu Invariable-adjusted mean Agatston scores were 2.36, 2.52, 2.16, and 2.39 (P-trend = 0.74) with an increasing quartile of total calcium intake in women and 4.32, 4.39, 4.19, and 4.37 (P-trend = 0.94) in men, respectively. Results were similar for dietary calcium and calcium supplement use.
Conclusions: Our study does not support the hypothesis that high calcium intake increases coronary artery calcification, which is an important measure of atherosclerosis burden. The evidence is not sufficient to modify current recommendations for calcium intake to protect skeletal health with respect to vascular calcification risk. Am Clin Nutr 2012;96:1274-80.
C1 [Samelson, Elizabeth J.; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.
[Samelson, Elizabeth J.; Kiel, Douglas P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Booth, Sarah L.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Fox, Caroline S.; O'Donnell, Christopher J.] Natl Heart Lung & Blood Insts Framingham Heart St, Framingham, MA USA.
[Tucker, Katherine L.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA.
[Wang, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
RP Samelson, EJ (reprint author), Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA.
EM samelson@hsl.harvard.edu
OI Cupples, L. Adrienne/0000-0003-0273-7965; Kiel,
Douglas/0000-0001-8474-0310; Tucker, Katherine/0000-0001-7640-662X
FU National Institute of Arthritis. Musculoskeletal, and Skin Diseases [K01
AR053118, R01 AR/AG41398]; National Heart, Lung, and Blood Institute
(NHLBI) Framingham Heart Study (NIH/NHLBI ) [N01-HC-25195]
FX Supported by National Institute of Arthritis. Musculoskeletal, and Skin
Diseases grants K01 AR053118 and R01 AR/AG41398 and the National Heart,
Lung, and Blood Institute (NHLBI) Framingham Heart Study (NIH/NHLBI
contract N01-HC-25195).
NR 55
TC 36
Z9 37
U1 1
U2 17
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD DEC
PY 2012
VL 96
IS 6
BP 1274
EP 1280
DI 10.3945/ajcn.112.044230
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 043HK
UT WOS:000311533300005
PM 23134889
ER
PT J
AU Kant, AK
Graubard, BI
Mattes, RD
AF Kant, Ashima K.
Graubard, Barry I.
Mattes, Richard D.
TI Association of food form with self-reported 24-h energy intake and meal
patterns in US adults: NHANES 2003-2008
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID SOFT DRINK CONSUMPTION; NUTRITION EXAMINATION SURVEYS; BODY-WEIGHT;
BEVERAGE CONSUMPTION; NATIONAL-HEALTH; DIET QUALITY; MACRONUTRIENT
INTAKE; AMERICAN ADULTS; NUTRIENT INTAKE; PORTION SIZE
AB Background: Laboratory studies suggest that food form (beverages compared with solid foods) evokes behavioral and physiologic responses that modify short-term appetite and food intake. Beverage energy may be less satiating and poorly compensated, which leads to higher energy intake.
Objective: We examined associations between 24-h energy consumed in beverages and a variety of meal and dietary attributes to quantify the contribution of beverage consumption to the energy content of diets in free-living individuals consuming their self-selected diets.
Design: We used dietary recall data for adults (n = 13,704) in NHANES 2003-2008 to examine the multiple covariate-adjusted associations between 24-h energy from beverages and nonbeverages and associations between beverage intake, eating behaviors, and the energy density of beverage and nonbeverage foods.
Results: In the highest tertile of 24-h beverage energy intake, beverages provided >30% of energy. Total 24-h energy and nonbeverage energy consumption and energy density (kcal/g) of both beverage and nonbeverage foods increased with increasing energy from beverages (P < 0.0001). With increasing 24-h beverage energy consumption, the reported frequency of all, snack, and beverage-only ingestive episodes and length of the ingestive period increased, whereas the percentage of energy from main meals decreased (P < 0.0001).
Conclusions: Higher 24-h beverage energy intake was related to higher energy intake from nonbeverage foods, quality of food selections, and distribution of 24-h energy into main meal and snack episodes. Moderation of beverage-only ingestive episodes and curtailing the length of the ingestion period may hold potential to lower uncompensated beverage energy consumption in the US population. Am J Clin Nutr 2012;96:1369-78.
C1 [Kant, Ashima K.] CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA.
[Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, NIH, Bethesda, MD 20892 USA.
[Mattes, Richard D.] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA.
RP Kant, AK (reprint author), CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Remsen Hall,Room 306E, Flushing, NY 11367 USA.
EM ashima.kant@qc.cuny.edu
FU Professional Staff Congress of the City University of New York;
Department of Health and Human Services, National Cancer Institute, NIH
FX Supported in part by a research grant award from the Professional Staff
Congress of the City University of New York (to AKK) and the intramural
research program of the Department of Health and Human Services,
National Cancer Institute, NIH (BIG).
NR 61
TC 14
Z9 15
U1 1
U2 12
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD DEC
PY 2012
VL 96
IS 6
BP 1369
EP 1378
DI 10.3945/ajen.112.044974
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 043HK
UT WOS:000311533300015
PM 23097271
ER
PT J
AU Chambers, DA
AF Chambers, David A.
TI The Interactive Systems Framework for Dissemination and Implementation:
Enhancing the Opportunity for Implementation Science
SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY
LA English
DT Article
DE Dissemination; Implementation; Framework; Model; Research; Translation
ID HEALTH
AB This article reflects on the progress made in the development of the Interactive Systems Framework (ISF) for Dissemination and Implementation in recent years. Considering the ISF in the context of the broader field of dissemination and implementation research, the author offers commentary on the strengths of the framework and opportunities for further expansion and refinement.
C1 NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
RP Chambers, DA (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd,Room 7164, Bethesda, MD 20892 USA.
EM dchamber@mail.nih.gov
NR 7
TC 11
Z9 11
U1 1
U2 16
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0091-0562
J9 AM J COMMUN PSYCHOL
JI Am. J. Community Psychol.
PD DEC
PY 2012
VL 50
IS 3-4
SI SI
BP 282
EP 284
DI 10.1007/s10464-012-9528-4
PG 3
WC Public, Environmental & Occupational Health; Psychology,
Multidisciplinary; Social Work
SC Public, Environmental & Occupational Health; Psychology; Social Work
GA 042TS
UT WOS:000311494500002
PM 22688847
ER
PT J
AU Houston, DK
Tooze, JA
Neiberg, RH
Hausman, DB
Johnson, MA
Cauley, JA
Bauer, DC
Cawthon, PM
Shea, MK
Schwartz, GG
Williamson, JD
Tylavsky, FA
Visser, M
Simonsick, EM
Harris, TB
Kritchevsky, SB
AF Houston, Denise K.
Tooze, Janet A.
Neiberg, Rebecca H.
Hausman, Dorothy B.
Johnson, Mary Ann
Cauley, Jane A.
Bauer, Doug C.
Cawthon, Peggy M.
Shea, M. Kyla
Schwartz, Gary G.
Williamson, Jeff D.
Tylavsky, Frances A.
Visser, Marjolein
Simonsick, Eleanor M.
Harris, Tamara B.
Kritchevsky, Stephen B.
CA Hlth ABC Study
TI 25-Hydroxyvitamin D Status and Change in Physical Performance and
Strength in Older Adults
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE aged; 25-hydroxyvitamin D; muscle strength; physical performance
ID VITAMIN-D DEFICIENCY; LOWER-EXTREMITY FUNCTION; MUSCLE STRENGTH;
CLINICAL-PRACTICE; HEALTH ABC; ASSOCIATION; WOMEN; DISABILITY;
FRACTURES; DECLINE
AB Low 25-hydroxyvitamin D (25(OH)D) concentrations are common among older adults and are associated with poorer physical performance and strength, but results from longitudinal studies have been inconsistent. The 25(OH)D threshold for physical performance and strength was determined, and both cross-sectional and longitudinal associations between 25(OH)D and physical performance and strength were examined, in men and women aged 7180 years from the Health, Aging, and Body Composition Study (n 2,641). Baseline serum 25(OH)D was measured in 19981999, and physical performance and strength were measured at baseline and at 2- and 4-year follow-up. Piecewise regression models were used to determine 25(OH)D thresholds. Linear regression and mixed models were used to examine cross-sectional and longitudinal associations. The 25(OH)D thresholds were 7080 nmol/L for physical performance and 5570 nmol/L for strength. Participants with 25(OH)D 50 nmol/L had poorer physical performance at baseline and at 2- and 4-year follow-up than participants with 25(OH)D epsilon 75 nmol/L (P 0.01). Although physical performance and strength declined over 4 years of follow-up (P 0.0001), in general, the rate of decline was not associated with baseline 25(OH)D. Older adults with low 25(OH)D concentrations had poorer physical performance over 4 years of follow-up, but low 25(OH)D concentrations were not associated with a faster rate of decline in physical performance or strength.
C1 [Houston, Denise K.; Shea, M. Kyla; Williamson, Jeff D.; Kritchevsky, Stephen B.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA.
[Tooze, Janet A.; Neiberg, Rebecca H.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.
[Schwartz, Gary G.] Wake Forest Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA.
[Hausman, Dorothy B.; Johnson, Mary Ann] Univ Georgia, Dept Foods & Nutr, Coll Family & Consumer Sci, Athens, GA 30602 USA.
[Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Bauer, Doug C.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA USA.
[Cawthon, Peggy M.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Tylavsky, Frances A.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Visser, Marjolein] Vrije Univ Amsterdam, Dept Hlth Sci, Amsterdam, Netherlands.
[Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Houston, DK (reprint author), Wake Forest Sch Med, Dept Internal Med, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM dhouston@wakehealth.edu
OI Cauley, Jane A/0000-0003-0752-4408
FU National Institutes of Health, National Institute on Aging (NIA); NIA
[N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01 AG028050, R01
AG029364, K01 AG030506]; National Institute of Nursing Research [R01
NR012459]; Wake Forest University Claude D. Pepper Older Americans
Independence Center [P30 AG021332]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging (NIA);
NIA contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA
grants R01 AG028050, R01 AG029364, and K01 AG030506 (to D. K. H.);
National Institute of Nursing Research grant R01 NR012459; and the Wake
Forest University Claude D. Pepper Older Americans Independence Center
(grant P30 AG021332).
NR 33
TC 30
Z9 31
U1 1
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD DEC 1
PY 2012
VL 176
IS 11
BP 1025
EP 1034
DI 10.1093/aje/kws147
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 048HB
UT WOS:000311900700009
PM 23118104
ER
PT J
AU Lin, SW
Chen, W
Fan, JH
Dawsey, SM
Taylor, PR
Qiao, YL
Abnet, CC
AF Lin, Shih-Wen
Chen, Wen
Fan, Jin-Hu
Dawsey, Sanford M.
Taylor, Philip R.
Qiao, You-Lin
Abnet, Christian C.
TI Prospective Study of Serum 25-Hydroxyvitamin D Concentration and
Mortality in a Chinese Population
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cancer; cardiovascular diseases; China; mortality; vitamin D
ID VITAMIN-D INSUFFICIENCY; GENOME-WIDE ASSOCIATION; GENERAL-POPULATION;
CANCER-MORTALITY; GASTRIC CANCERS; RISK; LINXIAN; ESOPHAGEAL; DISEASE;
HEALTH
AB Prospective epidemiologic data on the association between vitamin D and mortality are limited, particularly in Asian populations. Among subjects in Linxian, China, the authors aimed to test whether baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations in a prospective cohort were associated with all-cause mortality and cause-specific mortality rates over 24 years of follow-up (19862010). Serum 25(OH)D concentrations were measured in 1,101 subjects using an immunoassay. Hazard ratios and 95 confidence intervals were calculated using Cox regression models that were adjusted for age, sex, tobacco smoking, alcohol drinking, and hypertension. The 25th, 50th, and 75th percentile concentrations of 25(OH)D were 19.6, 31.9, and 48.4 nmol/L, respectively. During follow-up, 793 subjects died, including 279 who died of cerebrovascular accident, 217 who died of cancer, and 200 cardiovascular disease deaths. All-cause mortality was not associated with 25(OH)D concentrations using continuous models (for every 15 nmol/L, hazard ratio 1.01, 95 confidence interval: 0.97, 1.05) or quartile models (fourth vs. first quartiles, hazard ratio 1.06, 95 confidence interval: 0.87, 1.30; P for trend 0.731). The authors also found no association with the cause-specific mortality outcomes. Results were similar for men and women. This study showed that prediagnostic serum 25(OH)D concentrations were not associated with all-cause or cause-specific mortality rates in this Chinese population who had low levels of vitamin D.
C1 [Lin, Shih-Wen; Dawsey, Sanford M.; Taylor, Philip R.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Chen, Wen; Fan, Jin-Hu; Qiao, You-Lin] Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China.
RP Lin, SW (reprint author), 6120 Execut Blvd,Suite 320, Bethesda, MD 20892 USA.
EM lins4@mail.nih.gov
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 National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics.
NR 25
TC 14
Z9 14
U1 0
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD DEC 1
PY 2012
VL 176
IS 11
BP 1043
EP 1050
DI 10.1093/aje/kws285
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 048HB
UT WOS:000311900700011
PM 23139250
ER
PT J
AU Lewis, FI
McCormick, BJJ
AF Lewis, Fraser I.
McCormick, Benjamin J. J.
TI Revealing the Complexity of Health Determinants in Resource-poor
Settings
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Bayesian network; diarrhea; epidemiologic determinants; graphical model;
socioeconomic factors
ID BAYESIAN NETWORKS; CONDITIONAL PROBABILITIES; STRUCTURE DISCOVERY;
RISK-FACTORS; 2 CULTURES; EPIDEMIOLOGY; REGRESSION; CHILDREN; MODELS;
DEATH
AB An epidemiologic systems analysis of diarrhea in children in Pakistan is presented. Application of additive Bayesian network modeling to 20052006 data from the Pakistan Social and Living Standards Measurement Survey reveals the complexity of child diarrhea as a disease system. The key distinction between standard analytical approaches, such as multivariable regression, and Bayesian network analyses is that the latter attempt to not only identify statistically associated variables but also, additionally and empirically, separate these into those directly and indirectly dependent upon the outcome variable. Such discrimination is vastly more ambitious but has the potential to reveal far more about key features of complex disease systems. Additive Bayesian network analyses across 41 variables from the Pakistan Social and Living Standards Measurement Survey identified 182 direct dependencies but with only 3 variables: 1) access to a dry pit latrine (protective; odds ratio 0.67); 2) access to an atypical water source (protective; odds ratio 0.49); and 3) no formal garbage collection (unprotective; odds ratio 1.32), supported as directly dependent with the presence of diarrhea. All but 2 of the remaining variables were also, in turn, directly or indirectly dependent upon these 3 key variables. These results are contrasted with the use of a standard approach (multivariable regression).
C1 [Lewis, Fraser I.] Univ Zurich, Vetsuisse Fac, Epidemiol Sect, CH-8057 Zurich, Switzerland.
[McCormick, Benjamin J. J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Lewis, FI (reprint author), Univ Zurich, Vetsuisse Fac, Epidemiol Sect, Winterthurerstr 270, CH-8057 Zurich, Switzerland.
EM fraseriain.lewis@uzh.ch
RI Lewis, Fraser/A-3635-2011
OI Lewis, Fraser/0000-0003-1145-8271
FU Bill and Melinda Gates Foundation; Fogarty International Center of the
National Institutes of Health as part of the MAL-ED project network
FX This research was partly funded (B. J. J. M.) by the Bill and Melinda
Gates Foundation and the Fogarty International Center of the National
Institutes of Health as part of the MAL-ED (pronounced "mal a dee")
project network (i.e., the Interactions of Malnutrition and Enteric
Infections: Consequences for Child Health and Development).
NR 48
TC 15
Z9 15
U1 1
U2 23
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD DEC 1
PY 2012
VL 176
IS 11
BP 1051
EP 1059
DI 10.1093/aje/kws183
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 048HB
UT WOS:000311900700012
PM 23139247
ER
PT J
AU Han, SS
Rosenberg, PS
Garcia-Closas, M
Figueroa, JD
Silverman, D
Chanock, SJ
Rothman, N
Chatterjee, N
AF Han, Summer S.
Rosenberg, Philip S.
Garcia-Closas, Montse
Figueroa, Jonine D.
Silverman, Debra
Chanock, Stephen J.
Rothman, Nathaniel
Chatterjee, Nilanjan
TI Likelihood Ratio Test for Detecting Gene (G)-Environment (E)
Interactions Under an Additive Risk Model Exploiting G-E Independence
for Case-Control Data
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE additive risk model; case-control studies; gene-environment
independence; gene-environment interaction; multiplicative risk model
ID GENOME-WIDE ASSOCIATION; ENVIRONMENT INDEPENDENCE; BLADDER-CANCER;
SUSCEPTIBILITY; EFFICIENCY; INFERENCE
AB There has been a long-standing controversy in epidemiology with regard to an appropriate risk scale for testing interactions between genes (G) and environmental exposure (E). Although interaction tests based on the logistic modelwhich approximates the multiplicative risk for rare diseaseshave been more widely applied because of its convenience in statistical modeling, interactions under additive risk models have been regarded as closer to true biologic interactions and more useful in intervention-related decision-making processes in public health. It has been well known that exploiting a natural assumption of G-E independence for the underlying population can dramatically increase statistical power for detecting multiplicative interactions in case-control studies. However, the implication of the independence assumption for tests for additive interaction has not been previously investigated. In this article, the authors develop a likelihood ratio test for detecting additive interactions for case-control studies that incorporates the G-E independence assumption. Numerical investigation of power suggests that incorporation of the independence assumption can enhance the efficiency of the test for additive interaction by 2- to 2.5-fold. The authors illustrate their method by applying it to data from a bladder cancer study.
C1 [Han, Summer S.; Rosenberg, Philip S.; Figueroa, Jonine D.; Silverman, Debra; Chanock, Stephen J.; Rothman, Nathaniel; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM chattern@mail.nih.gov
RI Garcia-Closas, Montserrat /F-3871-2015
OI Garcia-Closas, Montserrat /0000-0003-1033-2650
FU National Institutes of Health, National Cancer Institute (Division of
Cancer Epidemiology and Genetics)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute (Division of
Cancer Epidemiology and Genetics).
NR 21
TC 15
Z9 15
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD DEC 1
PY 2012
VL 176
IS 11
BP 1060
EP 1067
DI 10.1093/aje/kws166
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 048HB
UT WOS:000311900700013
PM 23118105
ER
PT J
AU Roberson, R
Kuddo, T
Benassou, I
Abebe, D
Spong, CY
AF Roberson, Robin
Kuddo, Thea
Benassou, Ines
Abebe, Daniel
Spong, Catherine Y.
TI Neuroprotective peptides influence cytokine and chemokine alterations in
a model of fetal alcohol syndrome
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE fetal alcohol syndrome; fetal death; growth abnormalities; learning
impairment; NAPVSIPQ; neurodevelopmental abnormalities; SALLRSIPA
ID LEARNING-DEFICITS; PROGENITOR CELLS; MOUSE MODEL; MICE; INTERLEUKIN-15;
MOTONEURONS; PREVENTION; EXPOSURE; RECEPTOR; CSF
AB OBJECTIVE: Fetal alcohol syndrome (FAS) is associated with intellectual disability and neurodevelopmental abnormalities. Neuroprotective peptides NAPVSIPQ (NAP) and SALLRSIPA (SAL) can prevent some of the alcohol-induced teratogenesis including fetal death, growth abnormalities, and learning impairment in part by preventing alcohol-induced alterations in N-methyl-D-aspartate receptor gene expression in a mouse model for FAS. We evaluated a panel of cytokines and chemokines to determine whether NAP plus SAL work through a cytokine/chemokine-mediated pathway in preventing these alterations.
STUDY DESIGN: Using a well-characterized FAS model, timed, pregnant C57BL6/J mice were treated on gestational day (E) 8 with alcohol (0.03 mL/g), placebo, or alcohol plus peptides. Embryos were evaluated at 2 time points: after 6 hours and 10 days later at E18. A panel of cytokines/chemokines was measured using a microsphere-based multiplex immunoassay (Luminex xMAP; Millipore, Billerica, MA). Statistical analysis included Kruskal-Wallis, with P < .05 considered significant.
RESULTS: Six hours after treatment, interleukin (IL)-6 and keratinocyte chemoattractant cytokine (KC) were not detectable in the control embryos. Alcohol treatment resulted in detectable levels and significant increases in IL-6 (median, 15.7; range, 10.1-45.9 pg/mL) and KC (median, 45.9; range, 32.5-99.1 pg/mL). Embryos exposed to alcohol plus NAP plus SAL had undetectable IL-6 and KC (both P < .003), similar to the controls. Alcohol exposure resulted in a significant increase of granulocyte colony-stimulating factor (G-CSF) (P < .003) as compared with controls, and treatment with NAP plus SAL prevented the alcohol-induced increase. IL-13 and IL-1 beta were decreased 6 hours after alcohol exposure, and exposure to alcohol plus NAP plus SAL did not completely ameliorate the decrease. At E18, 10 days after exposure, these alterations were no longer present. Several analytes (regulated upon activation, normal T cell expressed, and secreted, tumor necrosis factor-alpha, interferon-gamma, and IL-4) were not detectable at either time point in any of the groups.
CONCLUSION: Prenatal alcohol exposure acutely results in a significant elevation of IL-6, G-CSF and the KC, which are known to affect N-methyl-D-aspartate receptors. NAP plus SAL treatment prevented alcohol-induced increases. This provides additional insight into the mechanism of alcohol damage in FAS and NAP plus SAL prevention of neurodevelopmental anomalies.
C1 [Roberson, Robin; Kuddo, Thea; Benassou, Ines; Abebe, Daniel; Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Unit Perinatal & Dev Neurobiol, Div Intramural Res, Bethesda, MD 20892 USA.
RP Roberson, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Unit Perinatal & Dev Neurobiol, Div Intramural Res, Bldg 9 1W125 & 1W116, Bethesda, MD 20892 USA.
EM robersor@mail.nih.gov
NR 21
TC 2
Z9 2
U1 0
U2 7
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 DEC
PY 2012
VL 207
IS 6
AR 499.e1
DI 10.1016/j.ajog.2012.10.005
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 042PM
UT WOS:000311483300027
PM 23174390
ER
PT J
AU Moss, LAS
Jensen-Taubman, S
Stetler-Stevenson, WG
AF Moss, Laurie A. Shuman
Jensen-Taubman, Sandra
Stetler-Stevenson, William G.
TI Matrix Metalloproteinases Changing Roles in Tumor Progression and
Metastasis
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Review
ID HUMAN COLON-CANCER; IV COLLAGENASE; CARCINOMA-CELLS; GROWTH-FACTOR;
HEPATOCELLULAR-CARCINOMA; BASEMENT-MEMBRANE; BLOOD-VESSELS;
UP-REGULATION; EXPRESSION; MELANOMA
AB Articles on tumor invasion, metastasis, and angiogenesis in normal and disease states have been well represented among the pages of The American Journal of Pathology. In addition to exciting interest in a variety of disease processes, these studies have been central in defining the emerging field in cancer research known as the tumor microenvironment. Early studies in this field established the importance of the extracellular matrix on tumor cell growth and differentiation. With time, the role of the extracellular matrix and matrix metalloproteinases in the regulation of tumor invasion, metastasis, and angiogenesis was recognized, and AJP has published seminal articles in this field. Moreover, recent studies show evidence for a role of matrix metalloproteinases in the regulation of inflammation within tumor lesions, making the targeting of matrix metalloproteinases in cancer therapy even more complex. This review attempts to summarize the contribution of AJP to some of the key changes that have led to the evolution of this field. (Am J Pathol 2012, 181:1895-1899; http://dx.doi.org/10.1016/j.ajpath.2012.08.044)
C1 [Moss, Laurie A. Shuman; Jensen-Taubman, Sandra; Stetler-Stevenson, William G.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Stetler-Stevenson, WG (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10,Room 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA.
EM sstevenw@mail.nih.gov
RI Stetler-Stevenson, William/H-6956-2012
OI Stetler-Stevenson, William/0000-0002-5500-5808
FU National Cancer Institute Center for Cancer Research as part of the NIH
intramural research program [ZIA SC009179-22]
FX Supported by a grant from the National Cancer Institute Center for
Cancer Research (ZIA SC009179-22), as part of the NIH intramural
research program.
NR 43
TC 62
Z9 64
U1 1
U2 31
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD DEC
PY 2012
VL 181
IS 6
BP 1895
EP 1899
DI 10.1016/j.ajpath.2012.08.044
PG 5
WC Pathology
SC Pathology
GA 048NI
UT WOS:000311918800002
ER
PT J
AU Hanifi, A
Bi, XH
Yang, X
Kavukcuoglu, B
Lin, PC
DiCarlo, E
Spencer, RG
Bostrom, MPG
Pleshko, N
AF Hanifi, Arash
Bi, Xiaohong
Yang, Xu
Kavukcuoglu, Beril
Lin, Ping Chang
DiCarlo, Edward
Spencer, Richard G.
Bostrom, Mathias P. G.
Pleshko, Nancy
TI Infrared Fiber Optic Probe Evaluation of Degenerative Cartilage
Correlates to Histological Grading
SO AMERICAN JOURNAL OF SPORTS MEDICINE
LA English
DT Article
DE cartilage; osteoarthritis; Fourier transform infrared spectroscopy;
histological score; arthroscopy
ID AUTOLOGOUS CHONDROCYTE IMPLANTATION; ARTHRITIC HUMAN HIPS;
ARTICULAR-CARTILAGE; METABOLIC ABNORMALITIES; ARTHROSCOPIC EVALUATION;
STRUCTURAL-CHANGES; SPECTROSCOPY; OSTEOARTHRITIS; KNEE; REPAIR
AB Background: Osteoarthritis (OA), a degenerative cartilage disease, results in alterations of the chemical and structural properties of tissue. Arthroscopic evaluation of full-depth tissue composition is limited and would require tissue harvesting, which is inappropriate in daily routine. Fourier transform infrared (FT-IR) spectroscopy is a modality based on molecular vibrations of matrix components that can be used in conjunction with fiber optics to acquire quantitative compositional data from the cartilage matrix.
Purpose: To develop a model based on infrared spectra of articular cartilage to predict the histological Mankin score as an indicator of tissue quality.
Study Design: Comparative laboratory study.
Methods: Infrared fiber optic probe (IFOP) spectra were collected from nearly normal and more degraded regions of tibial plateau articular cartilage harvested during knee arthroplasty (N = 61). Each region was graded using a modified Mankin score. A multi-variate partial least squares algorithm using second-derivative spectra was developed to predict the histological modified Mankin score.
Results: The partial least squares model derived from IFOP spectra predicted the modified Mankin score with a prediction error of approximately 1.4, which resulted in approximately 72% of the Mankin-scored tissues being predicted correctly and 96% being predicted within 1 grade of their true score.
Conclusion: These data demonstrate that IFOP spectral parameters correlate with histological tissue grade and can be used to provide information on tissue composition.
C1 [Pleshko, Nancy] Temple Univ, Dept Bioengn, Philadelphia, PA 19122 USA.
Hosp Special Surg, New York, NY 10021 USA.
NIA, Baltimore, MD 21224 USA.
RP Pleshko, N (reprint author), Temple Univ, Dept Bioengn, 1947 N 12th St, Philadelphia, PA 19122 USA.
EM npleshko@temple.edu
RI Lin, Ping-Chang/C-9811-2009;
OI Lin, Ping-Chang/0000-0003-0918-4072
FU National Institutes of Health (NIH) [EB000744]; National Institute on
Aging (NIH); NIH [AR46121]
FX One or more of the authors has declared the following potential conflict
of interest or source of funding: This study was supported by National
Institutes of Health (NIH) grant EB000744 (N.P.) and the National
Institute on Aging (NIH) intramural program (R.G.S.) and utilized an
NIH-supported Musculoskeletal Core Facility (AR46121).
NR 60
TC 14
Z9 14
U1 1
U2 17
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0363-5465
J9 AM J SPORT MED
JI Am. J. Sports Med.
PD DEC
PY 2012
VL 40
IS 12
BP 2853
EP 2861
DI 10.1177/0363546512462009
PG 9
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA 045KC
UT WOS:000311693700023
PM 23108637
ER
PT J
AU Hisada, M
Ota, Y
Zhang, X
Cameron, AM
Gao, B
Montgomery, RA
Williams, GM
Sun, Z
AF Hisada, M.
Ota, Y.
Zhang, X.
Cameron, A. M.
Gao, B.
Montgomery, R. A.
Williams, G. M.
Sun, Z.
TI Successful Transplantation of Reduced-Sized Rat Alcoholic Fatty Livers
Made Possible by Mobilization of Host Stem Cells
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Fatty liver; HGF; host stem cells; plerixafor; reduced sized graft;
SDF-1
ID HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW-CELLS; IN-VITRO; CD34(+)
PROGENITORS; PERIPHERAL-BLOOD; DONOR LIVER; REGENERATION; MICE;
PROLIFERATION; INTERLEUKIN-6
AB Livers from Lewis rats fed with 7% alcohol for 5 weeks were used for transplantation. Reduced sized (50%) livers or whole livers were transplanted into normal DA recipients, which, in this strain combination, survive indefinitely when the donor has not been fed alcohol. However, none of the rats survived a whole fatty liver transplant while six of seven recipients of reduced sized alcoholic liver grafts survived long term. SDF-1 and HGF were significantly increased in reduced size liver grafts compared to whole liver grafts. Lineage-negative Thy-1+CXCR4+CD133+ stem cells were significantly increased in the peripheral blood and in allografts after reduced size fatty liver transplantation. In contrast, there were meager increases in cells reactive with anti Thy-1, CXCR4 and CD133 in peripheral blood and allografts in whole alcoholic liver recipients. The provision of plerixafor, a stem cell mobilizer, salvaged 5 of 10 whole fatty liver grafts. Conversely, blocking SDF-1 activity with neutralizing antibodies diminished stem cell recruitment and four of five reduced sized fatty liver recipients died. Thus chemokine insufficiency was associated with transplant failure of whole grafts, which was overcome by the increased regenerative requirements promoted by the small grafts and mediated by SDF-1 resulting in stem cell influx.
C1 [Hisada, M.; Ota, Y.; Zhang, X.; Cameron, A. M.; Montgomery, R. A.; Williams, G. M.; Sun, Z.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
[Gao, B.] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
RP Sun, Z (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
EM zlsun@jhmi.edu
FU US National Institutes of Health [UO1 AA018113]
FX This work was supported by US National Institutes of Health (UO1
AA018113 to Z.S.).
NR 43
TC 3
Z9 3
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD DEC
PY 2012
VL 12
IS 12
BP 3246
EP 3256
DI 10.1111/j.1600-6143.2012.04265.x
PG 11
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 047QE
UT WOS:000311854800010
PM 22994609
ER
PT J
AU Love, RR
Ginsburg, OM
Coleman, CN
AF Love, R. R.
Ginsburg, O. M.
Coleman, C. N.
TI Public health oncology: a framework for progress in low- and
middle-income countries
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE cancer in low-income countries; public health oncology
ID CANCER; CARE
AB Background: The problems of cancer are increasing in low- and middle-income countries (LMCs), which now have significant majorities of the global case and mortality burdens. The professional oncology community is being increasingly called upon to define pragmatic and realistic approaches to these problems.
Patients and methods: Focusing on mortality and case burden outcomes defines public health oncology or population-affecting cancer medicine. We use this focus to consider practical approaches.
Results: The greatest cancer burdens are in Asia. A public health oncology perspective mandates: first, addressing the major and social challenges of cancer medicine for populations: human rights, health systems, corruption, and our limited knowledge base for value-conscious interventions. Second, adoption of evolving concepts and models for sustainable development in LMCs. Third, clear and realistic statements of action and inaction affecting populations, grounded in our best cancer science, and attention to these. Finally, framing the goals and challenges for population-affecting cancer medicine requires a change in paradigm from historical top-down models of technology transfer, to one which is community-grounded and local-evidence based.
Conclusion: Public health oncology perspectives define clear focus for much needed research on country-specific practical approaches to cancer control.
C1 [Love, R. R.] Int Breast Canc Res Fdn, Madison, WI USA.
[Ginsburg, O. M.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada.
[Coleman, C. N.] NCI, Div Canc Treatment & Diag, Radiat Res Program, Bethesda, MD 20892 USA.
RP Love, RR (reprint author), 2708 Columbia Rd, Madison, WI 53705 USA.
EM richardibcrf@gmail.com
FU International Breast Cancer Research Foundation; NIH/NCI [CA097375];
Susan B. Komen Foundation for the Cure; Breast Cancer Research
Foundation; Komen; BCRF
FX International Breast Cancer Research Foundation; NIH/NCI (Grant #
CA097375); Susan B. Komen Foundation for the Cure; Breast Cancer
Research Foundation. These funding sources have played no role in the
contents of this communication. (There are no specific grant numbers for
the Komen or BCRF funding which have been provided over years.)
NR 29
TC 12
Z9 12
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD DEC
PY 2012
VL 23
IS 12
BP 3040
EP 3045
DI 10.1093/annonc/mds473
PG 6
WC Oncology
SC Oncology
GA 044RX
UT WOS:000311642100006
PM 23087162
ER
PT J
AU Morton, LM
Gilbert, ES
Hall, P
Andersson, M
Joensuu, H
Vaalavirta, L
Dores, GM
Stovall, M
Holowaty, EJ
Lynch, CF
Curtis, RE
Smith, SA
Kleinerman, RA
Kaijser, M
Storm, HH
Pukkala, E
Weathers, RE
Linet, MS
Rajaraman, P
Fraumeni, JF
Brown, LM
van Leeuwen, FE
Fossa, SD
Johannesen, TB
Langmark, F
Lamart, S
Travis, LB
Aleman, BMP
AF Morton, L. M.
Gilbert, E. S.
Hall, P.
Andersson, M.
Joensuu, H.
Vaalavirta, L.
Dores, G. M.
Stovall, M.
Holowaty, E. J.
Lynch, C. F.
Curtis, R. E.
Smith, S. A.
Kleinerman, R. A.
Kaijser, M.
Storm, H. H.
Pukkala, E.
Weathers, R. E.
Linet, M. S.
Rajaraman, P.
Fraumeni, J. F., Jr.
Brown, L. M.
van Leeuwen, F. E.
Fossa, S. D.
Johannesen, T. B.
Langmark, F.
Lamart, S.
Travis, L. B.
Aleman, B. M. P.
TI Risk of treatment-related esophageal cancer among breast cancer
survivors
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE breast cancer; esophageal cancer; radiotherapy; second cancer
ID LUNG-CANCER; RANDOMIZED-TRIALS; RADIATION-THERAPY; 15-YEAR SURVIVAL;
HODGKINS-DISEASE; RADIOTHERAPY; MALIGNANCIES; WOMEN; ADENOCARCINOMA;
CHEMOTHERAPY
AB Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use.
Nested case-control study of esophageal cancer among 289 748 >= 5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records.
The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P-trend < 0.001), with doses of >= 35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7-28]. Patients with hormonal therapy < 5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2-0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking).
Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.
C1 [Morton, L. M.; Gilbert, E. S.; Dores, G. M.; Curtis, R. E.; Kleinerman, R. A.; Linet, M. S.; Rajaraman, P.; Fraumeni, J. F., Jr.; Lamart, S.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20892 USA.
[Hall, P.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Andersson, M.] Copenhagen Univ Hosp, Dept Oncol, Copenhagen, Denmark.
[Joensuu, H.; Vaalavirta, L.] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland.
[Dores, G. M.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA.
[Stovall, M.; Smith, S. A.; Weathers, R. E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Holowaty, E. J.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Lynch, C. F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Kaijser, M.] Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
[Storm, H. H.] Danish Canc Soc, Copenhagen, Denmark.
[Pukkala, E.] Finnish Canc Registry, Inst Stat & Epidemiol Canc Res, FIN-00170 Helsinki, Finland.
[Brown, L. M.] RTI Int, Stat & Epidemiol, Rockville, MD USA.
[van Leeuwen, F. E.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands.
[Fossa, S. D.] Oslo Univ Hosp, Dept Oncol, Oslo, Norway.
[Fossa, S. D.] Univ Oslo, Oslo, Norway.
[Johannesen, T. B.; Langmark, F.] Canc Registry Norway, Oslo, Norway.
[Travis, L. B.] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14627 USA.
[Aleman, B. M. P.] Netherlands Canc Inst, Dept Radiotherapy, Amsterdam, Netherlands.
RP Morton, LM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 7040,MSC 7238, Rockville, MD 20892 USA.
EM mortonli@mail.nih.gov
RI Morton, Lindsay/B-5234-2015;
OI Morton, Lindsay/0000-0001-9767-2310; Storm, Hans/0000-0001-7223-8198;
Kleinerman, Ruth/0000-0001-7415-2478; Joensuu,
Heikki/0000-0003-0281-2507
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services; National Cancer Institute [NO1-CP-31157];
Danish Cancer Society, Copenhagen, Denmark [NO1-CP-31019]; Finnish
Cancer Registry, Helsinki, Finland [NO1-CP-31154]; Information
Management Services, Inc., Silver Spring, USA [N01-CP-31003]; Karolinska
Institute, Stockholm, Sweden [NO1-CP-31156]; University of Iowa, Iowa
City, USA [NO1-CP-31155]; University of Texas MD Anderson Cancer Center,
Houston, USA [N02-CP-55503]; Westat, Inc., Rockville, USA [N02-CP-31136]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health, Department of
Health and Human Services, and National Cancer Institute contracts to
Cancer Care Ontario, Toronto, Canada (NO1-CP-31157); Danish Cancer
Society, Copenhagen, Denmark (NO1-CP-31019); Finnish Cancer Registry,
Helsinki, Finland (NO1-CP-31154); Information Management Services, Inc.,
Silver Spring, USA (N01-CP-31003); Karolinska Institute, Stockholm,
Sweden (NO1-CP-31156); University of Iowa, Iowa City, USA
(NO1-CP-31155); The University of Texas MD Anderson Cancer Center,
Houston, USA (N02-CP-55503); and Westat, Inc., Rockville, USA
(N02-CP-31136).
NR 42
TC 21
Z9 21
U1 0
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD DEC
PY 2012
VL 23
IS 12
BP 3081
EP 3091
DI 10.1093/annonc/mds144
PG 11
WC Oncology
SC Oncology
GA 044RX
UT WOS:000311642100013
PM 22745217
ER
PT J
AU Trimble, EL
Ledermann, J
Law, K
Miyata, T
Imamura, CK
Nam, BH
Kim, YH
Bang, YJ
Michaels, M
Ardron, D
Amano, S
Ando, Y
Tominaga, T
Kurokawa, K
Takebe, N
AF Trimble, E. L.
Ledermann, J.
Law, K.
Miyata, T.
Imamura, C. K.
Nam, B. -H.
Kim, Y. H.
Bang, Y. -J.
Michaels, M.
Ardron, D.
Amano, S.
Ando, Y.
Tominaga, T.
Kurokawa, K.
Takebe, N.
TI International models of investigator-initiated trials: implications for
Japan
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE academic; institutional investigator-initiated clinical trials;
anticancer drugs; good clinical practice; health care policy;
international clinical trials; patient advocates
ID CLINICAL-TRIALS; CANCER TRIALS; RECOMMENDATIONS; SCIENCE
AB Academic/institutional investigator-initiated clinical trials benefit individuals and society by supplementing gaps in industry-sponsored clinical trials.
In May 2010, experts from Japan, the Republic of Korea, the UK, and the United States, met at a symposium in Tokyo, Japan, to discuss how policies related to the conduct of clinical trials, which have been shown to be effective, may be applied to other regions of the world.
In order to increase the availability of anticancer drugs world-wide, nations including Japan should examine the benefits of increasing the number of investigator-initiated clinical trials. These trials represent one of the most effective ways to translate basic scientific knowledge into clinical practice. These trials should be conducted under GCP guidelines and include Investigational New Drug application submissions with the ultimate goal of future drug approval.
To maximize the effectiveness of these trials, a policy to educate health care professionals, cancer patients and their families, and the public in general on the benefits of clinical trials should be strengthened. Finally, policies that expedite the clinical development of novel cancer drugs which have already been shown to be effective in other countries are needed in many nations including Japan to accelerate drug approval.
C1 [Takebe, N.] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, DCTD,NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Ledermann, J.] UCL, UCL & UCL Hosp Comprehens Biomed Res Ctr, London, England.
[Law, K.] Canc Res UK, London, England.
[Miyata, T.] Govt Japan, Minist Heath Labour & Welf, Hlth Policy Bur, Div Res & Dev, Tokyo, Japan.
[Imamura, C. K.] Keio Univ, Sch Med, Dept Clin Pharmacokinet & Pharmacodynam, Tokyo, Japan.
[Nam, B. -H.] Natl Canc Ctr, Biometr Res Branch, Clin Res Coordinat Ctr, Geonggi Do, South Korea.
[Kim, Y. H.] Korea Univ, Coll Med, Dept Internal Med, Seoul 136705, South Korea.
[Bang, Y. -J.] Seoul Natl Univ, Coll Med, Seoul, South Korea.
[Michaels, M.] Educ Network Adv Clin Trials ENACCT, Bethesda, MD USA.
[Ardron, D.] Univ Leeds, Inst Consumer Liaison Grp, Leeds, W Yorkshire, England.
[Amano, S.] Grp NEXUS Japan, Tokyo, Japan.
[Ando, Y.; Tominaga, T.] PMDA, Tokyo, Japan.
[Kurokawa, K.] Hlth & Global Policy Inst, Tokyo, Japan.
RP Takebe, N (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, DCTD,NIH,Dept Hlth & Human Serv, 6130 Execut Blvd,EPN 7124, Rockville, MD 20852 USA.
EM takeben@mail.nih.gov
FU UK embassy; US National Cancer Institute; Health and Global Policy
Institute, Japan; United States embassy; ROK embassy
FX Support for this meeting was provided by the UK, United States, ROK
embassies in Tokyo, the US National Cancer Institute, and the Health and
Global Policy Institute, Japan.
NR 10
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD DEC
PY 2012
VL 23
IS 12
BP 3151
EP 3155
DI 10.1093/annonc/mds168
PG 5
WC Oncology
SC Oncology
GA 044RX
UT WOS:000311642100023
PM 22843420
ER
PT J
AU Thomas, LA
Brotman, MA
Muhrer, EJ
Rosen, BH
Bones, BL
Reynolds, RC
Deveney, CM
Pine, DS
Leibenluft, E
AF Thomas, Laura A.
Brotman, Melissa A.
Muhrer, Eli J.
Rosen, Brooke H.
Bones, Brian L.
Reynolds, Richard C.
Deveney, Christen M.
Pine, Daniel S.
Leibenluft, Ellen
TI Parametric Modulation of Neural Activity by Emotion in Youth With
Bipolar Disorder, Youth With Severe Mood Dysregulation, and Healthy
Volunteers
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID FACIAL EXPRESSIONS; FUNCTIONAL CONNECTIVITY; LABELING DEFICITS; SOCIAL
COGNITION; AMYGDALA; CHILDREN; ATTENTION; RECOGNITION; PERCEPTION;
DEPRESSION
AB Context: Youth with bipolar disorder (BD) and those with severe, nonepisodic irritability (severe mood dysregulation [SMD]) exhibit amygdala dysfunction during facial emotion processing. However, studies have not compared such patients with each other and with comparison individuals in neural responsiveness to subtle changes in facial emotion; the ability to process such changes is important for social cognition. To evaluate this, we used a novel, parametrically designed faces paradigm.
Objective: To compare activation in the amygdala and across the brain in BD patients, SMD patients, and healthy volunteers (HVs).
Design: Case-control study.
Setting: Government research institute.
Participants: Fifty-seven youths (19 BD, 15 SMD, and 23 HVs).
Main Outcome Measure: Blood oxygenation level-dependent data. Neutral faces were morphed with angry and happy faces in 25% intervals; static facial stimuli appeared for 3000 milliseconds. Participants performed hostility or nonemotional facial feature (ie, nose width) ratings. The slope of blood oxygenation level-dependent activity was calculated across neutral-to-angry and neutral-to-happy facial stimuli.
Results: In HVs, but not BD or SMD participants, there was a positive association between left amygdala activity and anger on the face. In the neutral-to-happy whole-brain analysis, BD and SMD participants modulated parietal, temporal, and medial-frontal areas differently from each other and from that in HVs; with increasing facial happiness, SMD patients demonstrated increased, and BD patients decreased, activity in the parietal, temporal, and frontal regions.
Conclusions: Youth with BD or SMD differ from HVs in modulation of amygdala activity in response to small changes in facial anger displays. In contrast, individuals with BD or SMD show distinct perturbations in regions mediating attention and face processing in association with changes in the emotional intensity of facial happiness displays. These findings demonstrate similarities and differences in the neural correlates of facial emotion processing in BD and SMD, suggesting that these distinct clinical presentations may reflect differing dysfunctions along a mood disorders spectrum.
C1 [Thomas, Laura A.; Brotman, Melissa A.; Muhrer, Eli J.; Rosen, Brooke H.; Bones, Brian L.; Deveney, Christen M.; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Emot & Dev Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Reynolds, Richard C.] NIMH, Sci & Stat Comp Core, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Thomas, LA (reprint author), NIDA, Off Director, 6001 Execut Blvd,Room 5252,Mailstop 9581, Rockville, MD 20852 USA.
EM tlaura@mail.nih.gov
RI Brotman, Melissa/H-7409-2013;
OI Thomas, Laura/0000-0002-4106-1358
FU National Institute of Mental Health
FX This study was supported by the Intramural Research Program of the
National Institute of Mental Health.
NR 53
TC 22
Z9 22
U1 4
U2 12
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-990X
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD DEC
PY 2012
VL 69
IS 12
BP 1257
EP 1266
DI 10.1001/archgenpsychiatry.2012.913
PG 10
WC Psychiatry
SC Psychiatry
GA 046ZL
UT WOS:000311804500008
PM 23026912
ER
PT J
AU Horowitz, LM
Bridge, JA
Teach, SJ
Ballard, E
Klima, J
Rosenstein, DL
Wharff, EA
Ginnis, K
Cannon, E
Joshi, P
Pao, M
AF Horowitz, Lisa M.
Bridge, Jeffrey A.
Teach, Stephen J.
Ballard, Elizabeth
Klima, Jennifer
Rosenstein, Donald L.
Wharff, Elizabeth A.
Ginnis, Katherine
Cannon, Elizabeth
Joshi, Paramjit
Pao, Maryland
TI Ask Suicide-Screening Questions (ASQ) A Brief Instrument for the
Pediatric Emergency Department
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Article
ID MENTAL-HEALTH; PRIMARY-CARE; RISK; BEHAVIOR; CHILDREN; IMPLEMENTATION;
ADOLESCENTS; MEDICINE
AB Objective: To develop a brief screening instrument to assess the risk for suicide in pediatric emergency department patients.
Design: A prospective, cross-sectional instrument-development study evaluated 17 candidate screening questions assessing suicide risk in young patients. The Suicidal Ideation Questionnaire served as the criterion standard.
Setting: Three urban, pediatric emergency departments associated with tertiary care teaching hospitals.
Participants: A convenience sample of 524 patients aged 10 to 21 years who presented with either medical/surgical or psychiatric chief concerns to the emergency department between September 10, 2008, and January 5, 2011.
Main Exposures: Participants answered 17 candidate questions followed by the Suicidal Ideation Questionnaire.
Main Outcome Measures: Sensitivity, specificity, predictive values, likelihood ratios, and area under the receiver operating characteristic curves of the best-fitting combinations of screening questions for detecting elevated risk for suicide.
Results: A total of 524 patients were screened (344 medical/surgical and 180 psychiatric). Fourteen of the medical/surgical patients (4%) and 84 of the psychiatric patients (47%) were at elevated suicide risk on the Suicidal Ideation Questionnaire. Of the 17 candidate questions, the best-fitting model comprised 4 questions assessing current thoughts of being better off dead, current wish to die, current suicidal ideation, and past suicide attempt. This model had a sensitivity of 96.9% (95% CI, 91.3-99.4), specificity of 87.6% (95% CI, 84.0-90.5), and negative predictive values of 99.7% (95% CI, 98.2-99.9) for medical/surgical patients and 96.9% (95% CI, 89.3-99.6) for psychiatric patients.
Conclusions: A 4-question screening instrument, the Ask Suicide-Screening Questions (ASQ), with high sensitivity and negative predictive value, can identify the risk for suicide in patients presenting to pediatric emergency departments.
C1 [Horowitz, Lisa M.] NIMH, Clin Res Ctr, NIH, Bethesda, MD 20892 USA.
[Bridge, Jeffrey A.] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA.
[Bridge, Jeffrey A.] Ohio State Univ, Columbus Childrens Res Inst, Columbus, OH 43210 USA.
[Klima, Jennifer; Cannon, Elizabeth] Nationwide Childrens Hosp, Ctr Innovat Pediat Practice, Columbus, OH USA.
[Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA.
[Ballard, Elizabeth] Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA.
[Joshi, Paramjit] George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Psychiat & Behav Sci, Washington, DC USA.
[Rosenstein, Donald L.] Univ N Carolina, Comprehens Canc Support Program, Chapel Hill, NC USA.
[Wharff, Elizabeth A.; Ginnis, Katherine] Harvard Univ, Sch Med, Dept Psychiat, Childrens Hosp Boston, Boston, MA 02115 USA.
RP Horowitz, LM (reprint author), NIMH, Clin Res Ctr, NIH, Bldg 10,Room 6-5362, Bethesda, MD 20892 USA.
EM horowitzl@mail.nih.gov
FU AstraZeneca; Dainippon Sumitomo; Eli Lilly; Forest Research Institute;
Janssen, a division of Ortho-McNeil-Janssen Pharmaceuticals Inc; Roche
Pharmaceuticals; Sanofi-Aventis; Schering-Plough; Sepracor; United
BioSource; National Institutes of Health; National Institute of Mental
Health; Research Institute at Nationwide Children's Hospital; National
Institute of Mental Health [K01 MH-69948]; Children's Hospital Boston
FX Dr Bridge has received honoraria from Best Practice Project Management
for participation in a suicidality consensus conference that was
supported by independent education or other unrestricted grant support
from AstraZeneca; Dainippon Sumitomo; Eli Lilly; Forest Research
Institute; Janssen, a division of Ortho-McNeil-Janssen Pharmaceuticals
Inc administered by Ortho-McNeil-Janssen Scientific Affairs LLC; Roche
Pharmaceuticals; Sanofi-Aventis; Schering-Plough; Sepracor; and United
BioSource.; The research in this article was supported by the Intramural
Research Program of the National Institutes of Health and the National
Institute of Mental Health. Dr Bridge's work was supported by
institutional research funds from the Research Institute at Nationwide
Children's Hospital and grant K01 MH-69948 from the National Institute
of Mental Health. Dr Wharff and Ms Ginnis' work was supported by
institutional research funds from the Program for Patient Safety and
Quality at Children's Hospital Boston.
NR 32
TC 40
Z9 40
U1 1
U2 14
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 1072-4710
J9 ARCH PEDIAT ADOL MED
JI Arch. Pediatr. Adolesc. Med.
PD DEC
PY 2012
VL 166
IS 12
BP 1170
EP 1176
DI 10.1001/archpediatrics.2012.1276
PG 7
WC Pediatrics
SC Pediatrics
GA 046ZR
UT WOS:000311805300015
PM 23027429
ER
PT J
AU Wang, QJ
Hanada, K
Robbins, PF
Li, YF
Yang, JC
AF Wang, Qiong J.
Hanada, Ken-ichi
Robbins, Paul F.
Li, Yong F.
Yang, James C.
TI Distinctive Features of the Differentiated Phenotype and Infiltration of
Tumor-Reactive Lymphocytes in Clear Cell Renal Cell Carcinoma
SO CANCER RESEARCH
LA English
DT Article
ID METASTATIC MELANOMA; T-CELLS; CD27-CD70 INTERACTIONS; CANCER REGRESSION;
IMMUNE ESCAPE; CD70; EXPRESSION; CD27; IDENTIFICATION; ACTIVATION
AB Clear cell renal cell carcinoma (RCC) is considered an immunogenic tumor, but it has been difficult to identify tumor-infiltrating lymphocytes (TIL) that show in vitro tumor recognition. We compared the characteristics of fresh RCC TIL to peripheral blood lymphocytes (PBL) or melanoma TIL. Our results showed that RCC TIL contained fewer CD27(+) T cells, and fewer naive and central memory (CM) T cells, but more effector memory (EM) T cells than melanoma TIL or renal PBL. We hypothesized that factors in the RCC microenvironment were skewing TIL phenotype toward EM. One possibility was the expression of CD70 on nearly all human RCCs, but not melanomas. Differentiation of naive T cells to EM cells only occurred from CD70 costimulation in concert with T-cell receptor (TCR) stimulation (signal one), suggesting that EM TIL responding to CD70 would be enriched for T cells reactive with local antigens, including those associated with RCC. Clonotypic analysis of TCRs in fresh RCCs showed that EM T cells were more clonally expanded than CM or naive T cells, and the clonal expansion occurred at the tumor site as oligoclonal TCRs were distinct from PBL TCRs from the same patient. In addition, we found that 2 TCRs from the highly represented EM TIL clones, when reexpressed in fresh PBL, recognized an MHC-class II or MHC-class I-restricted antigens shared by multiple RCC lines. Our results suggest that RCC-reactive TIL do exist in situ, but may be difficult to recover and study because of proliferative exhaustion, driven by tumor-expressed CD70. Cancer Res; 72(23); 6119-29. (C) 2012 AACR.
C1 [Wang, Qiong J.; Hanada, Ken-ichi; Robbins, Paul F.; Li, Yong F.; Yang, James C.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Wang, QJ (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10 CRC,Room 3W-3840, Bethesda, MD 20892 USA.
EM qiongwang@mail.nih.gov; James_Yang@nih.gov
RI Hanada, Ken-ichi/L-2481-2013
OI Hanada, Ken-ichi/0000-0003-2959-1257
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, and Center for Cancer Research.
NR 33
TC 24
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U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD DEC 1
PY 2012
VL 72
IS 23
BP 6119
EP 6129
DI 10.1158/0008-5472.CAN-12-0588
PG 11
WC Oncology
SC Oncology
GA 048EN
UT WOS:000311893100006
PM 23071066
ER
PT J
AU Srivastava, R
Geng, DG
Liu, YJ
Zheng, LQ
Li, ZY
Joseph, MA
McKenna, C
Bansal, N
Ochoa, A
Davila, E
AF Srivastava, Ratika
Geng, Degui
Liu, Yingjia
Zheng, Liqin
Li, Zhaoyang
Joseph, Mary Ann
McKenna, Colleen
Bansal, Navneeta
Ochoa, Augusto
Davila, Eduardo
TI Augmentation of Therapeutic Responses in Melanoma by Inhibition of
IRAK-1,-4
SO CANCER RESEARCH
LA English
DT Article
ID METASTATIC MELANOMA; SIGNALING PATHWAY; IN-VITRO; CELLS; KINASE;
EXPRESSION; ACTIVATION; RECEPTOR; PROGRESSION; APOPTOSIS
AB Toll-like receptors (TLR) are expressed by a variety of cancers, including melanoma, but their functional contributions in cancer cells are uncertain. To approach this question, we evaluated the effects of stimulating or inhibiting the TLR/IL-1 receptor-associated kinases IRAK-1 and IRAK-4 in melanoma cells where their functions are largely unexplored. TLRs and TLR-related proteins were variably expressed in melanoma cell lines, with 42% expressing activated phospho-IRAK-1 constitutively and 85% expressing high levels of phospho-IRAK-4 in the absence of TLR stimulation. Immunohistochemical evaluation of melanoma tumor biopsies (n = 242) revealed two distinct patient populations, one that expressed p-IRAK-4 levels similar to normal skin (55%) and one with significantly higher levels than normal skin (45%). Levels of p-IRAK-4 levels did not correlate with clinical stage, gender, or age, but attenuated IRAK-1,-4 signaling with pharmacologic inhibitors or siRNA-enhanced cell death in vitro in combination with vinblastine. Moreover, in a xenograft mouse model of melanoma, the combined pharmacologic treatment delayed tumor growth and prolonged survival compared with subjects receiving single agent therapy. We propose p-IRAK-4 as a novel inflammation and prosurvival marker in melanoma with the potential to serve as a therapeutic target to enhance chemotherapeutic responses. Cancer Res; 72(23); 6209-16. (C) 2012 AACR.
C1 [Srivastava, Ratika; Geng, Degui; Liu, Yingjia; Li, Zhaoyang; Joseph, Mary Ann; McKenna, Colleen; Bansal, Navneeta; Davila, Eduardo] Univ Maryland, Marlene & Stewart Greenebaum NCI Canc Ctr, Baltimore, MD 21201 USA.
[Davila, Eduardo] Dept Otorhinolaryngol Head & Neck Surg, Baltimore, MD USA.
[Zheng, Liqin; Ochoa, Augusto] Louisiana State Univ, Stanley S Scott Canc Ctr, New Orleans, LA USA.
RP Davila, E (reprint author), Univ Maryland, Greenebaum Canc Ctr, Room 10-041,Bressler Res Bldg,655 W Baltimore St, Baltimore, MD 21201 USA.
EM EDavila@som.umaryland.edu
FU National Cancer Institute [1R01CA140917-01]; NIH Center for Biomedical
Research Center Excellence [1P20 RR021970]; University of Maryland,
Marlene and Stewart Greenebaum Cancer Center
FX National Cancer Institute 1R01CA140917-01, NIH Center for Biomedical
Research Center Excellence grants 1P20 RR021970, and University of
Maryland, Marlene and Stewart Greenebaum Cancer Center.
NR 28
TC 19
Z9 19
U1 1
U2 4
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 DEC 1
PY 2012
VL 72
IS 23
BP 6209
EP 6216
DI 10.1158/0008-5472.CAN-12-0337
PG 8
WC Oncology
SC Oncology
GA 048EN
UT WOS:000311893100015
PM 23041547
ER
PT J
AU Juarez, P
Mohammad, KS
Yin, JJ
Fournier, PGJ
McKenna, RC
Davis, HW
Peng, XH
Niewolna, M
Javelaud, D
Chirgwin, JM
Mauviel, A
Guise, TA
AF Juarez, Patricia
Mohammad, Khalid S.
Yin, Juan Juan
Fournier, Pierrick G. J.
McKenna, Ryan C.
Davis, Holly W.
Peng, Xiang H.
Niewolna, Maria
Javelaud, Delphine
Chirgwin, John M.
Mauviel, Alain
Guise, Theresa A.
TI Halofuginone Inhibits the Establishment and Progression of Melanoma Bone
Metastases
SO CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR-BETA; BREAST-CANCER METASTASIS; TGF-BETA; STABLE
OVEREXPRESSION; MALIGNANT-MELANOMA; I SYNTHESIS; CELLS; EXPRESSION;
FIBROSIS; ANGIOGENESIS
AB TGF-beta derived from bone fuels melanoma bone metastases by inducing tumor secretion of prometastatic factors that act on bone cells to change the skeletal microenvironment. Halofuginone is a plant alkaloid derivative that blocks TGF-beta signaling with antiangiogenic and antiproliferative properties. Here, we show for the first time that halofuginone therapy decreases development and progression of bone metastasis caused by melanoma cells through the inhibition of TGF-beta signaling. Halofuginone treatment of human melanoma cells inhibited cell proliferation, phosphorylation of SMAD proteins in response to TGF-beta, and TGF-beta-induced SMAD-driven transcription. In addition, halofuginone reduced expression of TGF-beta target genes that enhance bone metastases, including PTHrP, CTGF, CXCR4, and IL11. Also, cell apoptosis was increased in response to halofuginone. In nude mice inoculated with 1205Lu melanoma cells, a preventive protocol with halofuginone inhibited bone metastasis. The beneficial effects of halofuginone treatment were comparable with those observed with other anti-TGF-beta strategies, including systemic administration of SD208, a small-molecule inhibitor of TGF-beta receptor I kinase, or forced overexpression of Smad7, a negative regulator of TGF-beta signaling. Furthermore, mice with established bone metastases treated with halofuginone had significantly less osteolysis than mice receiving placebo assessed by radiography. Thus, halofuginone is also effective in reducing the progression of melanoma bone metastases. Moreover, halofuginone treatment reduced melanoma metastasis to the brain, showing the potential of this novel treatment against cancer metastasis. Cancer Res; 72(23); 6247-56. (C) 2012 AACR.
C1 [Juarez, Patricia; Mohammad, Khalid S.; Fournier, Pierrick G. J.; Peng, Xiang H.; Niewolna, Maria; Chirgwin, John M.; Guise, Theresa A.] Indiana Univ Purdue Univ, Dept Med, Div Endocrinol, Indianapolis, IN 46202 USA.
[Yin, Juan Juan] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[McKenna, Ryan C.; Davis, Holly W.] Univ Virginia, Div Endocrinol, Charlottesville, VA USA.
[Javelaud, Delphine; Mauviel, Alain] Inst Curie, F-91405 Orsay, France.
[Javelaud, Delphine; Mauviel, Alain] Univ Paris 11, INSERM, U1021, F-91405 Orsay, France.
[Javelaud, Delphine; Mauviel, Alain] CNRS, UMR3347, F-91405 Orsay, France.
RP Guise, TA (reprint author), Indiana Univ Purdue Univ, Dept Med, Div Endocrinol & Metab, Walther Hall,C132 980 W Walnut St, Indianapolis, IN 46202 USA.
EM tguise@iupui.edu
RI MAUVIEL, Alain/F-6251-2013; Fournier, Pierrick/B-6560-2015
OI Fournier, Pierrick/0000-0001-7633-8129
FU NIH [R01CA69158, R01DK067333, R01DK065837]; Mary Kay Ash Foundation;
V-Foundation; Aurbach Endowment of the University of Virginia; Jerry W.
and Peggy S. Throgmartin Endowment of Indiana University; Indiana
Economic Development Fund; Susan Komen Foundation; Ligue Nationale
Contre le Cancer (Equipe Labellisee LIGUE EL2011-AM); INCa
[PLBIO08-126]; Institut Curie; INSERM; CNRS; Association pour la
Recherche contre le Cancer
FX This work was supported by NIH grants R01CA69158, R01DK067333, and
R01DK065837; the Mary Kay Ash Foundation, the V-Foundation, Aurbach
Endowment of the University of Virginia, Jerry W. and Peggy S.
Throgmartin Endowment of Indiana University, and Indiana Economic
Development Fund (T. A. Guise) as well as a grant from the Susan Komen
Foundation (P. Juarez and T. A. Guise) and by Ligue Nationale Contre le
Cancer (Equipe Labellisee LIGUE EL2011-AM), INCa (PLBIO08-126), a
donation from Emile and Henriette Goutiere, and institutional funding
from Institut Curie, INSERM and CNRS (A. Mauviel), and Association pour
la Recherche contre le Cancer (D. Javelaud).
NR 48
TC 18
Z9 19
U1 1
U2 18
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 DEC 1
PY 2012
VL 72
IS 23
BP 6247
EP 6256
DI 10.1158/0008-5472.CAN-12-1444
PG 10
WC Oncology
SC Oncology
GA 048EN
UT WOS:000311893100019
PM 23002206
ER
PT J
AU Li, X
Li, HT
Li, SQ
Zhu, F
Kim, DJ
Xie, H
Li, Y
Nadas, J
Oi, N
Zykova, TA
Yu, DH
Lee, MH
Kim, MO
Wang, L
Ma, WY
Lubet, RA
Bode, AM
Dong, ZM
Dong, ZG
AF Li, Xiang
Li, Haitao
Li, Shengqing
Zhu, Feng
Kim, Dong Joon
Xie, Hua
Li, Yan
Nadas, Janos
Oi, Naomi
Zykova, Tatyana A.
Yu, Dong Hoon
Lee, Mee-Hyun
Kim, Myoung Ok
Wang, Lei
Ma, Weiya
Lubet, Ronald A.
Bode, Ann M.
Dong, Ziming
Dong, Zigang
TI Ceftriaxone, an FDA-approved cephalosporin antibiotic, suppresses lung
cancer growth by targeting Aurora B
SO CARCINOGENESIS
LA English
DT Article
ID FATTY-ACID SYNTHASE; CELL-GROWTH; HISTONE H3; DRUG-RESISTANCE;
INHIBITOR; KINASE; TRANSFORMATION; EXPRESSION; CARCINOMA;
PHOSPHORYLATION
AB Ceftriaxone, an FDA-approved third-generation cephalosporin antibiotic, has antimicrobial activity against both gram-positive and gram-negative organisms. Generally, ceftriaxone is used for a variety of infections such as community-acquired pneumonia, meningitis and gonorrhea. Its primary molecular targets are the penicillin-binding proteins. However, other activities of ceftriaxone remain unknown. Herein, we report for the first time that ceftriaxone has antitumor activity in vitro and in vivo. Kinase profiling results predicted that Aurora B might be a potential ooff' target of ceftriaxone. Pull-down assay data confirmed that ceftriaxone could bind with Aurora B in vitro and in A549 cells. Furthermore, ceftriaxone (500 M) suppressed anchorage-independent cell growth by targeting Aurora B in A549, H520 and H1650 lung cancer cells. Importantly, in vivo xenograft animal model results showed that ceftriaxone effectively suppressed A549 and H520 lung tumor growth by inhibiting Aurora B. These data suggest the anticancer efficacy of ceftriaxone for the treatment of lung cancers through its inhibition of Aurora B.
C1 [Dong, Zigang] Univ Minnesota, Hormel Inst, Mayo Clin, Austin, MN 55912 USA.
[Li, Xiang; Dong, Ziming] Zhengzhou Univ, Basic Med Coll, Zhengzhou 450001, Henan, Peoples R China.
[Lubet, Ronald A.] NCI, Bethesda, MD 20892 USA.
RP Dong, ZG (reprint author), Univ Minnesota, Hormel Inst, Mayo Clin, 801 16th Ave NE, Austin, MN 55912 USA.
EM Dongzm@zzu.edu.cn; zgdong@hi.umn.edu
RI ZHU, Feng/G-3567-2010; Li, Yan/L-2129-2013
FU Hormel Foundation; National Institutes of Health [R37 CA081064,
CA120388, ES016548, CA0227501]; National Cancer Institute
[HHSN-261200533001C-NO1-CN-53301]
FX The Hormel Foundation and National Institutes of Health (R37 CA081064,
CA120388, ES016548, CA0227501); National Cancer Institute Contract No.
HHSN-261200533001C-NO1-CN-53301.
NR 44
TC 6
Z9 7
U1 2
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD DEC
PY 2012
VL 33
IS 12
BP 2548
EP 2557
DI 10.1093/carcin/bgs283
PG 10
WC Oncology
SC Oncology
GA 048IB
UT WOS:000311903500028
PM 22962305
ER
PT J
AU Senbagavalli, P
Hilda, JN
Ramanathan, VD
Kumaraswami, V
Nutman, TB
Babu, S
AF Senbagavalli, P.
Hilda, J. Nancy
Ramanathan, V. D.
Kumaraswami, V.
Nutman, Thomas B.
Babu, Subash
TI Immune Complexes Isolated from Patients with Pulmonary Tuberculosis
Modulate the Activation and Function of Normal Granulocytes
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID BLOOD MONONUCLEAR-CELLS; FC-GAMMA RECEPTORS; MYCOBACTERIUM-TUBERCULOSIS;
CYTOKINE PRODUCTION; OXIDATIVE BURST; TISSUE-INJURY; NEUTROPHILS;
COMPLEMENT; INFLAMMATION; MACROPHAGES
AB Circulating immune complexes (ICs) are associated with the pathogenesis of several diseases. Very little is known about the effect of ICs on the host immune response in patients with tuberculosis (TB). The effects of ICs isolated from patients with TB in modulating the release of calcium, cytokines, and granular proteins were studied in normal granulocytes, as were their chemotactic, phagocytic, and oxidative burst processes. ICs from TB patients induced decreased production of cytokines and platelet-activating factor (PAF) from normal granulocytes. ICs from TB patients also induced enhanced chemotaxis and phagocytosis but caused diminished oxidative burst. This was accompanied by an increased release in intracellular calcium. On the other hand, ICs from TB patients induced increased release of the granular proteins human neutrophil peptides 1 to 3 (HNP1-3). Thus, ICs from patients with TB exhibit a profound effect on granulocyte function with activation of certain effector mechanisms and dampening of others.
C1 [Senbagavalli, P.; Hilda, J. Nancy; Babu, Subash] Int Ctr Excellence Res, Natl Inst Hlth, Madras, Tamil Nadu, India.
[Senbagavalli, P.; Hilda, J. Nancy; Ramanathan, V. D.; Kumaraswami, V.] Natl Inst Res TB, Madras, Tamil Nadu, India.
[Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Babu, S (reprint author), Int Ctr Excellence Res, Natl Inst Hlth, Madras, Tamil Nadu, India.
EM sbabu@trcchennai.in
FU Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health; Indian Council of Medical Research
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. Financial assistance
provided in the form of a Research Associate fellowship to P. S. by the
Indian Council of Medical Research is gratefully acknowledged.
NR 40
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD DEC
PY 2012
VL 19
IS 12
BP 1965
EP 1971
DI 10.1128/CVI.00437-12
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 047NU
UT WOS:000311848400010
PM 23100480
ER
PT J
AU Suryadevara, M
Tabarani, CM
Bartholoma, N
Rosenberg, HF
Domachowske, JB
AF Suryadevara, Manika
Tabarani, Christy M.
Bartholoma, Nadine
Rosenberg, Helene F.
Domachowske, Joseph B.
TI Nasopharyngeal Detection of Respiratory Viruses in Febrile Neutropenic
Children
SO CLINICAL PEDIATRICS
LA English
DT Article
DE respiratory viruses; fever; neutropenia
ID VIRAL-INFECTIONS; CANCER; CHEMOTHERAPY; LEUKEMIA
AB Background. Although fever is common in neutropenic children, a microbiological etiology is determined in only 15% to 30% of cases. The authors investigated the frequency of respiratory virus detection in the upper airways of febrile neutropenic children with negative bacterial cultures. Methods. This is a 3-year prospective study of children younger than 19 years, hospitalized with febrile neutropenia and negative bacterial cultures. Respiratory samples were obtained for amplification of viral nucleic acids via Luminex xTAG technology. Results. There were 50 febrile neutropenic episodes among 42 patients. Respiratory viruses were detected in 26 (52%) febrile episodes. A single virus was detected in 22 febrile episodes; multiple viruses were detected in the remaining 4. Rhinovirus/Enterovirus was most frequently detected. Conclusion. Respiratory viruses were detected frequently in nasopharyngeal samples from febrile neutropenic patients with negative bacterial cultures, thus providing an impetus to determine the relationship between virus detection, infection, and pathology in this unique patient population.
C1 [Suryadevara, Manika] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA.
[Rosenberg, Helene F.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Suryadevara, M (reprint author), SUNY Upstate Med Univ, Dept Pediat, 750 E Adams St, Syracuse, NY 13210 USA.
EM suryadem@upstate.edu
FU NIAID Division of Intramural Research [AI000943]; Children's Miracle
Network of New York
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: Funding for
this project was provided by NIAID Division of Intramural Research
#AI000943 (to HFR) and the Children's Miracle Network of New York (to
JBD).
NR 15
TC 2
Z9 2
U1 0
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0009-9228
J9 CLIN PEDIATR
JI Clin. Pediatr.
PD DEC
PY 2012
VL 51
IS 12
BP 1164
EP 1167
DI 10.1177/0009922812456736
PG 4
WC Pediatrics
SC Pediatrics
GA 046HZ
UT WOS:000311757400008
PM 22893186
ER
PT J
AU Becker, RE
Greig, NH
AF Becker, Robert E.
Greig, Nigel H.
TI Was Phenserine a Failure or Were Investigators Mislead by Methods?
SO CURRENT ALZHEIMER RESEARCH
LA English
DT Article
DE Neuropsychiatric drug development; placebo group improvement; variance;
validity; phenserine; scientific practices in drug development;
alzheimer's disease; clinical translation
ID PROTEIN MESSENGER-RNA; TASK-FORCE REPORT; ALZHEIMERS-DISEASE;
CLINICAL-TRIALS; 5'-UNTRANSLATED REGION; RESPONSIVE ELEMENT; COGNITIVE
DECLINE; DRUG DEVELOPMENT; RATING-SCALE; DOUBLE-BLIND
AB Over 200 Alzheimer's disease (AD) drug candidates have failed in development, and other neuropsychiatric trials have had their validity compromised. Studies suggest that methodological errors can be a source for these compromises and failures. We gained access to documentation for phenserine, an experimental AD drug that reached phase III clinical trials. The 06 Phase III trial was cited by the developers as grounds for their abandonment of the development. We compared evidence for interventions to control methodological errors and grounds for moving through phases of drug development to 40 other randomly selected AD developments we had studied. We analyzed methods and conditions of the 06 phenserine clinical trial, for biases able to account for its abandonment during development. The phenserine development failed to control error sources able to affect the outcomes. There are statistically significant relationships in the 06 clinical trial between outcomes at research sites and levels of variance, placebo group improvements and other factors. We conclude that phenserine was abandoned, at least in part, due to a clinical trial invalidated by relationships among its methods and outcomes.
C1 [Becker, Robert E.] Aristea Translat Med Corp, Freeport, ME 04078 USA.
[Becker, Robert E.; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Lab Neurosci, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Becker, RE (reprint author), Aristea Translat Med Corp, O4078,POB 442, Freeport, ME 04078 USA.
EM rebecker2008@comcast.net
FU National Institute on Aging, NIH
FX NHG is supported by the Intramural Research Program, National Institute
on Aging, NIH. REB is the founder of Aristea Translational Medicine
Corp., which has ownership of the phenserine documentation, and received
no funding support for this work.
NR 39
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 1567-2050
J9 CURR ALZHEIMER RES
JI Curr. Alzheimer Res.
PD DEC
PY 2012
VL 9
IS 10
BP 1174
EP 1181
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 045XU
UT WOS:000311730900007
PM 23227991
ER
PT J
AU Burstein, M
Georgiades, K
He, JP
Schmitz, A
Feig, E
Khazanov, GK
Merikangas, K
AF Burstein, Marcy
Georgiades, Katholiki
He, Jian-Ping
Schmitz, Anja
Feig, Emily
Khazanov, Gabriela Kattan
Merikangas, Kathleen
TI SPECIFIC PHOBIA AMONG U.S. ADOLESCENTS: PHENOMENOLOGY AND TYPOLOGY
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE epidemiology; child/adolescent; phobia/phobic disorders; anxiety/anxiety
disorders; assessment/diagnosis
ID COMORBIDITY SURVEY REPLICATION; IV-SPECIFIC PHOBIA; MENTAL-HEALTH
SURVEY; SUPPLEMENT NCS-A; ANXIETY DISORDERS; NATIONAL COMORBIDITY;
DSM-IV; SOCIAL PHOBIA; EPIDEMIOLOGY; FEARS
AB Background Investigators have proposed the diagnostic value of a generalized subtype of specific phobia, with classification based upon the number of phobic fears. However, current and future typologies of specific phobia classify the condition by the nature of phobic fears. This study investigated the clinical relevance of these alternative typologies by: (1) presenting the prevalence and correlates of specific phobia separately by the number and nature of phobia types; and (2) examining the clinical and psychiatric correlates of specific phobia according to these alternative typologies. Methods The National Comorbidity Survey Replication-Adolescent Supplement (NCS-A) is a nationally representative face-to-face survey of 10,123 adolescents aged 1318 years in the continental United States. Results Most adolescents with specific phobia met criteria for more than one type of phobia in their lifetime, however rates were fairly similar across DSM-IV/5 subtypes. Sex differences were consistent across DSM-IV/5 subtypes, but varied by the number of phobic types, with a female predominance observed among those with multiple types of phobias. Adolescents with multiple types of phobias exhibited an early age of onset, elevated severity and impairment, and among the highest rates of other psychiatric disorders. However, certain DSM-IV/5 subtypes (i.e. blood-injection-injury and situational) were also uniquely associated with severity and psychiatric comorbidity. Conclusions Results indicate that both quantitative and DSM-IV/5 typologies of specific phobia demonstrate diagnostic value. Moreover, in addition to certain DSM-IV/5 subtypes, a generalized subtype based on the number of phobias may also characterize youth who are at greatest risk for future difficulties. Depression and Anxiety 29: 1072-1082, 2012. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Burstein, Marcy; He, Jian-Ping; Schmitz, Anja; Feig, Emily; Khazanov, Gabriela Kattan; Merikangas, Kathleen] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
[Georgiades, Katholiki] McMaster Univ, Hamilton, ON, Canada.
RP Merikangas, K (reprint author), NIMH, Genet Epidemiol Res Branch, Bldg 35,Room 1A201,35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
EM kathleen.merikangas@nih.gov
FU National Institute of Mental Health [U01-MH60220]; National Institute of
Drug Abuse [R01DA016558]; Intramural Research Program of the National
Institute of Mental Health
FX The National Comorbidity Survey-Adolescent Supplement (NCS-A) is
supported by the National Institute of Mental Health (U01-MH60220) and
the National Institute of Drug Abuse (R01DA016558) with supplemental
support from the Substance Abuse and Mental Health Services
Administration (SAMHSA), the Robert Wood Johnson Foundation (RWJF;
044708), and the John W. Alden Trust. The NCS-A was carried out in
conjunction with the World Health Organization World Mental Health (WMH)
Survey Initiative. This work was supported by the Intramural Research
Program of the National Institute of Mental Health. 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 43
TC 11
Z9 11
U1 3
U2 28
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
EI 1520-6394
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD DEC
PY 2012
VL 29
IS 12
BP 1072
EP 1082
DI 10.1002/da.22008
PG 11
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 048KT
UT WOS:000311911000011
PM 23108894
ER
PT J
AU Mather, KJ
Christophi, CA
Jablonski, KA
Knowler, WC
Goldberg, RB
Kahn, SE
Spector, T
Dastani, Z
Waterworth, D
Richards, JB
Funahashi, T
Pi-Sunyer, FX
Pollin, TI
Florez, JC
Franks, PW
AF Mather, K. J.
Christophi, C. A.
Jablonski, K. A.
Knowler, W. C.
Goldberg, R. B.
Kahn, S. E.
Spector, T.
Dastani, Z.
Waterworth, D.
Richards, J. B.
Funahashi, T.
Pi-Sunyer, F. X.
Pollin, T. I.
Florez, J. C.
Franks, P. W.
CA Diabetes Prevention Program Res
TI Common variants in genes encoding adiponectin (ADIPOQ) and its receptors
(ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the
Diabetes Prevention Program
SO DIABETIC MEDICINE
LA English
DT Article
ID SINGLE-NUCLEOTIDE POLYMORPHISM; INSULIN-RESISTANCE; CAUCASIAN
POPULATION; METABOLIC SYNDROME; FRENCH CAUCASIANS; APM1 GENE; TYPE-2;
ASSOCIATION; PROMOTER; RISK
AB Diabet. Med. 29, 15791588 (2012) Abstract Aims Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population. Methods Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling. Results Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions of rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with similar to 18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations. Conclusions ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations.
C1 [Mather, K. J.] Indiana Univ, Div Endocrinol & Metab, Indianapolis, IN 46204 USA.
[Christophi, C. A.; Jablonski, K. A.] George Washington Univ, Ctr Biostat, Rockville, MD USA.
[Knowler, W. C.] NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA.
[Goldberg, R. B.] Univ Miami, Lipid Disorders Clin, Div Endocrinol Diabet & Metab, Miami, FL USA.
[Goldberg, R. B.] Univ Miami, Diabet Res Inst, Leonard M Miller Sch Med, Miami, FL USA.
[Kahn, S. E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA.
[Kahn, S. E.] Univ Washington, Seattle, WA 98195 USA.
[Spector, T.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Dastani, Z.; Richards, J. B.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Dastani, Z.; Richards, J. B.] McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
[Dastani, Z.; Richards, J. B.] McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada.
[Waterworth, D.] GlaxoSmithKline, Genet, King Of Prussia, PA USA.
[Funahashi, T.] Osaka Univ, Grad Sch Med, Dept Internal Med & Mol Sci, Suita, Osaka, Japan.
[Pi-Sunyer, F. X.] Columbia Univ Coll Phys & Surg, Dept Med, St Lukes Roosevelt Hosp, New York, NY 10032 USA.
[Pollin, T. I.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Pollin, T. I.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, J. C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Florez, J. C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Florez, J. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Franks, P. W.] Lund Univ, Skania Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
[Franks, P. W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
RP Mather, KJ (reprint author), Indiana Univ, Div Endocrinol & Metab, Indianapolis, IN 46204 USA.
EM dppmail@biostat.bsc.gwu.edu
OI Franks, Paul/0000-0002-0520-7604; Kahn, Steven/0000-0001-7307-9002
FU Swedish Research Council; Swedish Heart-Lung Foundation; Pahlssons
Foundation; Swedish Diabetes Association; Novo Nordisk; National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the
National Institutes of Health; NIDDK; Indian Health Service; Office of
Research on Minority Health; National Institute of Child Health and
Human Development; National Institute on Aging; Centers for Disease
Control and Prevention; Office of Research on Women's Health; American
Diabetes Association; Henry M. Jackson Foundation; [DK072041]
FX The Investigators gratefully acknowledge the commitment and dedication
of the participants of the DPP. The design and conduct of the trial was
made possible in large part by the National Institutes of Health, along
with Foundation and Industry partners as listed in the Support section.
The genetic analyses were supported by DK072041 (to JCF). PWF was
supported by grants from the Swedish Research Council, Swedish
Heart-Lung Foundation, Pahlssons Foundation, Swedish Diabetes
Association, and Novo Nordisk. Adiponectin analyses were supported by
the Sandra A. Daugherty foundation (to KJM). The National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) of the National
Institutes of Health provided funding to the clinical centres and the
Coordinating Center for the design and conduct of the study; and
collection, management, analysis and interpretation of the data. The
Southwestern American Indian Centers were supported directly by the
NIDDK and the Indian Health Service. The General Clinical Research
Center Program, National Center for Research Resources supported data
collection at many of the clinical centres. Funding for data collection
and participant support was also provided by the Office of Research on
Minority Health, the National Institute of Child Health and Human
Development, the National Institute on Aging, the Centers for Disease
Control and Prevention, the Office of Research on Women's Health and the
American Diabetes Association. Bristol-Myers Squibb and Parke-Davis
provided medication. This research was also supported, in part, by the
intramural research program of the NIDDK. LifeScan Inc., Health O Meter,
Hoechst Marion Roussel Inc., Merck-Medco Managed Care Inc., Merck and
Co., Nike Sports Marketing, Slim Fast Foods Co. and Quaker Oats Co.
donated materials, equipment or medicines for concomitant conditions.
McKesson BioServices Corp., Matthews Media Group Inc. and the Henry M.
Jackson Foundation provided support services under subcontract with the
Coordinating Center. The opinions expressed are those of the
investigators and do not necessarily reflect the views of the Indian
Health Service or other funding agencies. A complete list of centres,
investigators and staff can be found in the Supporting Information
(Appendix S1).
NR 30
TC 11
Z9 11
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0742-3071
J9 DIABETIC MED
JI Diabetic Med.
PD DEC
PY 2012
VL 29
IS 12
BP 1579
EP 1588
DI 10.1111/j.1464-5491.2012.03662.x
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 036TO
UT WOS:000311054600026
PM 22443353
ER
PT J
AU Anderson, KS
Segars, JH
AF Anderson, Katherine S.
Segars, James H.
TI Predicting fertility with antimullerian hormone: Is a cutoff value
adequate?
SO FERTILITY AND STERILITY
LA English
DT Editorial Material
C1 [Anderson, Katherine S.] William Beaumont Hosp, Dept Obstet & Gynecol, Royal Oak, MI 48072 USA.
[Segars, James H.] NIH, Bethesda, MD 20892 USA.
RP Anderson, KS (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Royal Oak, MI 48072 USA.
FU Intramural NIH HHS [ZIE HD008737-12]
NR 5
TC 1
Z9 1
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD DEC
PY 2012
VL 98
IS 6
BP 1421
EP 1422
DI 10.1016/j.fertnstert.2012.08.054
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 044QM
UT WOS:000311637300016
PM 23036803
ER
PT J
AU Gilden, M
Malik, M
Britten, J
Delgado, T
Levy, G
Catherino, WH
AF Gilden, Melissa
Malik, Minnie
Britten, Joy
Delgado, Tania
Levy, Gary
Catherino, William H.
TI Leiomyoma fibrosis inhibited by liarozole, a retinoic acid metabolic
blocking agent
SO FERTILITY AND STERILITY
LA English
DT Article
DE Extracellular matrix; liarozole; leiomyomas; retinoic acid
ID UTERINE LEIOMYOMAS; ORAL LIAROZOLE; EXTRACELLULAR-MATRIX; MYOMETRIAL
CELLS; DOUBLE-BLIND; EXPRESSION; GENES; PSORIASIS; FIBROIDS; CANCER
AB Objective: To study the influence of liarozole on leiomyoma cell proliferation and extracellular matrix (ECM) gene expression in immortalized leiomyoma cells.
Design: Laboratory study.
Setting: University hospital.
Patient(s): None.
Intervention(s): Tissue culture, real-time reverse transcription-polymerase chain reaction, Western blot.
Main Outcome Measure(s): Proliferation, messenger RNA (mRNA), and ECM protein expression.
Result(s): Proliferation of leiomyoma cells was inhibited by treatment with liarozole at suprapharmacologic concentrations. The mRNA and protein expression of COL1A1, COL4A2, versican, fibromodulin, and fibronectin was increased in untreated leiomyoma cells compared with untreated patient-matched myometrial cells. Extracellular matrix mRNA expression was decreased in a dose-dependent manner in leiomyoma cells treated with pharmacologic concentrations of liarozole. In addition, myometrial cells treated with liarozole demonstrated no statistically significant alteration in ECM regulation.
Conclusion(s): Liarozole inhibited ECM protein production at pharmacologic concentrations in immortalized human leiomyoma cells. Retinoic acid metabolic blocking agents represent a potential therapeutic drug family for human leiomyomas. (Fertil Steril (R) 2012; 98: 1557-62. (C) 2012 by American Society for Reproductive Medicine.)
C1 [Gilden, Melissa; Malik, Minnie; Britten, Joy; Delgado, Tania; Levy, Gary; Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
[Levy, Gary; Catherino, William H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM william.catherino@usuhs.edu
OI Malik, Minnie/0000-0003-1129-6575
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; American Association of Gynecologists and Obstetricians
Foundation
FX Supported by the Eunice Kennedy Shriver National Institute of Child
Health and Human Development and the American Association of
Gynecologists and Obstetricians Foundation.
NR 33
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Z9 8
U1 0
U2 2
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 DEC
PY 2012
VL 98
IS 6
BP 1557
EP 1562
DI 10.1016/j.fertnstert.2012.07.1132
PG 6
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 044QM
UT WOS:000311637300037
PM 22925684
ER
PT J
AU Wolff, EF
Hill, MJ
Simonds, WF
Segars, JH
AF Wolff, Erin F.
Hill, Micah J.
Simonds, William F.
Segars, James H.
TI Aromatase inhibitor treatment of menorrhagia and subsequent pregnancy in
a patient with familial hyperparathyroidism-jaw tumor syndrome
SO FERTILITY AND STERILITY
LA English
DT Article
DE Hyperparathyroidism-jaw tumor syndrome; menorrhagia; adenomyoma;
aromatase inhibitor
ID ENDOMETRIOSIS; PARAFIBROMIN; EXPRESSION
AB Objective: To describe the clinical management of menorrhagia in a woman with hyperparathyroidism-jaw tumor syndrome (HPT-JT).
Design: Case report.
Setting: Large translation research hospital.
Patient(s): A 26-year-old nulligravid woman with familial HPT-JT presented with life-long menorrhagia resistant to progesterone intrauterine device (IUD) therapy and a desire for fertility.
Intervention(s): Aromatase inhibitor therapy.
Main Outcome Measure(s): Clinical response to therapy and pregnancy.
Result(s): Imaging demonstrated an enlarged endometrial lining and thickening of the junctional zone. At operative hysteroscopy, multiple atypical endometrial polyp-like lesions filled the entire uterine cavity and were removed. Histologic evaluation demonstrated the lesions to be adenomyomas with an abundance of aromatase expression. Postoperative treatment included an aromatase inhibitor. The patient's menorrhagia, which had previously been resistant to progesterone IUD therapy, resolved with the aromatase inhibitor. After 10 months of this treatment, the aromatase inhibitor was discontinued and a repeated hysteroscopy revealed a markedly improved uterine cavity. The patient subsequently became pregnant on her first natural cycle and delivered a healthy term infant.
Conclusion(s): Aromatase inhibitors may represent a novel treatment for benign uterine pathology in HPT-JT. (Fertil Steril (R) 2012; 98: 1616-9. (C) 2012 by American Society for Reproductive Medicine.)
C1 [Wolff, Erin F.; Hill, Micah J.; Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Simonds, William F.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA.
RP Wolff, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC Rm 1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wolffe@mail.nih.gov
FU National Institute of Child Health and Human Development [Z01
HD008924-01, Z01 ND008737-12]; National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
FX Supported in part by the Intramural Research Program of the Program in
Reproductive and Adult Endocrinology, National Institute of Child Health
and Human Development (Z01 HD008924-01 and Z01 ND008737-12), and the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.
NR 16
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 DEC
PY 2012
VL 98
IS 6
BP 1616
EP 1619
DI 10.1016/j.fertnstert.2012.08.017
PG 4
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 044QM
UT WOS:000311637300044
PM 22963808
ER
PT J
AU James, SP
AF James, Stephen P.
TI Funding for Research in Digestive Diseases by NIH and NIDDK
SO GASTROENTEROLOGY
LA English
DT Editorial Material
C1 NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA.
RP James, SP (reprint author), NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA.
NR 1
TC 2
Z9 2
U1 0
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 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD DEC
PY 2012
VL 143
IS 6
BP 1407
EP 1409
DI 10.1053/j.gastro.2012.10.012
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 042XJ
UT WOS:000311505100009
PM 23078988
ER
PT J
AU Sherman, ME
Guido, R
Wentzensen, N
Yang, HP
Mai, PL
Greene, MH
AF Sherman, Mark E.
Guido, Richard
Wentzensen, Nicolas
Yang, Hannah P.
Mai, Phuong L.
Greene, Mark H.
TI New views on the pathogenesis of high-grade pelvic serous carcinoma with
suggestions for advancing future research
SO GYNECOLOGIC ONCOLOGY
LA English
DT Editorial Material
ID TUBAL INTRAEPITHELIAL CARCINOMA; OVARIAN SURFACE EPITHELIUM; REDUCING
SALPINGO-OOPHORECTOMIES; FALLOPIAN-TUBE; BRCA MUTATIONS; CANCER; WOMEN;
RISK; FEATURES; TUMORS
C1 [Sherman, Mark E.; Wentzensen, Nicolas; Yang, Hannah P.] NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Rockville, MD 20852 USA.
[Guido, Richard] UPMC, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Mai, Phuong L.; Greene, Mark H.] NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD 20852 USA.
RP Sherman, ME (reprint author), NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM shermanm@mail.nih.gov
FU Intramural NIH HHS [ZIA CP010158-13]
NR 50
TC 4
Z9 5
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD DEC
PY 2012
VL 127
IS 3
BP 645
EP 650
DI 10.1016/j.ygyno.2012.08.023
PG 6
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 043FO
UT WOS:000311528500036
PM 22940485
ER
PT J
AU Liu, JM
Chang, KW
Yao, JH
Summers, RM
AF Liu, Jiamin
Chang, Kevin W.
Yao, Jianhua
Summers, Ronald M.
TI Predicting Polyp Location on Optical Colonoscopy From CT Colonography by
Minimal-Energy Curve Modeling of the Colonoscope Path
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Colonic polyps; CT colonography; minimal-energy curve; optical
colonoscopy
ID COLORECTAL-CANCER; REGISTRATION; SUPINE; PRONE; DISTANCE
AB The ability to accurately locate a polyp found on computed tomographic colonography (CTC) at subsequent optical colonoscopy (OC) is an important task in colorectal cancer screening. We present a method to more accurately match polyp locations at CTC and OC. A colonoscope was modeled as a flexible tube with negligible stretch and minimal strain. The path of the colonoscope was estimated using a minimal-energy curve method. The energy function was defined and optimized by a subdivision scheme. The prediction of polyp locations at OC from CTC was converted to an optimization problem. The prediction performance was evaluated on 134 polyps by comparing the predicted with the true polyp locations at OC. The method can accurately predict polyp locations at OC to within +/-0.5 colonoscope mark (5 cm) for more than 58% of polyps and to within +/-1 colonoscope mark (10 cm) for more than 96% of polyps, significantly improving upon previously published methods. This method can be easily incorporated into routine OC practice and allow the colonoscopist to begin the examination by targeting locations of potential polyps found at CTC.
C1 [Liu, Jiamin; Chang, Kevin W.; Yao, Jianhua; Summers, Ronald M.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
RP Summers, RM (reprint author), NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
EM liujiamin@cc.nih.gov; kevinweskimo@hotmail.com; jyao@cc.nih.gov;
rms@nih.gov
FU Intramural Research Program of the NIH Clinical Center
FX This work was supported by the Intramural Research Program of the NIH
Clinical Center. Asterisk indicates corresponding author.
NR 21
TC 1
Z9 1
U1 0
U2 0
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
EI 1558-2531
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD DEC
PY 2012
VL 59
IS 12
BP 3531
EP 3540
DI 10.1109/TBME.2012.2217960
PG 10
WC Engineering, Biomedical
SC Engineering
GA 047LX
UT WOS:000311843500030
PM 23033425
ER
PT J
AU Matheson, BE
Tanofsky-Kraff, M
Shafer-Berger, S
Sedaka, NM
Mooreville, M
Reina, SA
Vannucci, A
Shomaker, LB
Yanovski, SZ
Yanovski, JA
AF Matheson, Brittany E.
Tanofsky-Kraff, Marian
Shafer-Berger, Sarah
Sedaka, Nicole M.
Mooreville, Mira
Reina, Samantha A.
Vannucci, Anna
Shomaker, Lauren B.
Yanovski, Susan Z.
Yanovski, Jack A.
TI Eating patterns in youth with and without loss of control eating
SO INTERNATIONAL JOURNAL OF EATING DISORDERS
LA English
DT Article
DE loss of control eating; adolescents; meal patterns
ID WEIGHT-GAIN; BODY-WEIGHT; BREAKFAST; CHILDREN; ADOLESCENTS; DISORDER;
CONSUMPTION
AB Objective: To compare the characteristic meal patterns of adolescents with and without loss of control (LOC) eating episodes.
Method: The Eating Disorder Examination was administered to assess self-reported LOC and frequency of meals consumed in an aggregated sample of 574 youths (1217 years; 66.6% female; 51.2% Caucasian; BMI-z: 1.38 +/- 1.11), among whom 227 (39.6%) reported LOC eating.
Results: Compared to those without LOC, youth with LOC were less likely to consume lunch and evening meals (p's < .05), but more likely to consume morning, afternoon, and nocturnal snacks (p's = .05), accounting for age, sex, race, socio-economic status, BMI-z, and treatment-seeking status.
Discussion: Adolescents with reported LOC eating appear to engage in different meal patterns compared to youth without LOC, and adults with binge eating. Further research is needed to determine whether the meal patterns that characterize adolescents with LOC play a role in worsening disordered eating and/or excessive weight gain. Published 2012 Wiley Periodicals, Inc.
C1 [Matheson, Brittany E.; Tanofsky-Kraff, Marian; Shafer-Berger, Sarah; Vannucci, Anna; Shomaker, Lauren B.] USUHS, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Matheson, Brittany E.; Tanofsky-Kraff, Marian; Shafer-Berger, Sarah; Sedaka, Nicole M.; Mooreville, Mira; Reina, Samantha A.; Vannucci, Anna; Shomaker, Lauren B.; Yanovski, Susan Z.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD USA.
[Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, NIH, DHHS, Bethesda, MD USA.
RP Tanofsky-Kraff, M (reprint author), USUHS, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM marian.tanofsky-kraff@usuhs.edu
OI Yanovski, Jack/0000-0001-8542-1637
FU Intramural Research Program, NIH; NICHD [1ZIAHD000641, 1F32HD056762,
1K99HD069516]; NIMHD; OBSSR; NIDDK [1R01DK080906]; USUHS [R0721C]
FX Supported by Intramural Research Program, NIH, by 1ZIAHD000641 from
NICHD, with NIMHD and OBSSR supplemental funding, by 1R01DK080906 from
NIDDK, by R0721C from USUHS, by 1F32HD056762, 1K99HD069516 from NICHD.
NR 20
TC 13
Z9 13
U1 1
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0276-3478
J9 INT J EAT DISORDER
JI Int. J. Eating Disord.
PD DEC
PY 2012
VL 45
IS 8
BP 957
EP 961
DI 10.1002/eat.22063
PG 5
WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology
SC Psychology; Nutrition & Dietetics; Psychiatry
GA 040AB
UT WOS:000311289700007
PM 23015352
ER
PT J
AU Hyodo, F
Davis, RM
Hyodo, E
Matsumoto, S
Krishna, MC
Mitchell, JB
AF Hyodo, Fuminori
Davis, Ryan M.
Hyodo, Emi
Matsumoto, Shingo
Krishna, Murali C.
Mitchell, James B.
TI The relationship between tissue oxygenation and redox status using
magnetic resonance imaging
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE redox status; hypoxia; electron paramagnetic resonance imaging; magnetic
resonance imaging; nitroxide; non-invasive imaging; Tempol
ID SQUAMOUS-CELL CARCINOMA; TUMOR SIZE; OXIDATIVE STRESS;
RADIATION-THERAPY; CONTRAST AGENTS; GLUTATHIONE; REDUCTION; FRACTION;
HYPOXIA; CANCER
AB The recent development of a bi-modality magnetic resonance imaging/electron paramagnetic resonance imaging (MRI/EPRI) platform has enabled longitudinal monitoring of both tumor oxygenation and redox status in murine cancer models. The current study used this imaging platform to test the hypothesis that a more reducing tumor microenvironment accompanies the development of tumor hypoxia. To test this, the redox status of the tumor was measured using Tempo! as a redox-sensitive MRI contrast agent, and tumor hypoxia was measured with wOxo63, which is an oxygen-sensitive EPRI spin probe. Images were acquired every 1-2 days in mice bearing SCCVII tumors. The median PO2 decreased from 14 mmHg at 7 days after tumor implantation to 7 mmHg at 15 days after implantation. Additionally, the hypoxic fraction, defined as the percentage of the tumor that exhibited a pO(2)<10mmHg, increased with tumor size (from 10% at 500 m(3) to 60% at 3,500 mm(3)). The rate of Tempol reduction increased as a function of tumor volume (0.4 min(-1) at 500 mm(3) to 1.7 min(-1) at 3,500 mm(3)), suggesting that the tumor microenvironment became more reduced as the tumor grew. The results show that rapid Tempol reduction correlates with decreased tumor oxygenation, and that the Tempol decay rate constant may be a surrogate marker for tumor hypoxia.
C1 [Hyodo, Fuminori; Davis, Ryan M.; Hyodo, Emi; Matsumoto, Shingo; Krishna, Murali C.; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Room B3-B69,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jbm@helix.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, NIH
FX This study was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, NIH.
NR 36
TC 6
Z9 6
U1 2
U2 15
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 DEC
PY 2012
VL 41
IS 6
BP 2103
EP 2108
DI 10.3892/ijo.2012.1638
PG 6
WC Oncology
SC Oncology
GA 043YZ
UT WOS:000311587900024
PM 23007796
ER
PT J
AU Myers, RA
Himes, BE
Gignoux, CR
Yang, JJ
Gauderman, WJ
Rebordosa, C
Xie, JM
Torgerson, DG
Levin, AM
Baurley, J
Graves, PE
Mathias, RA
Romieu, I
Roth, LA
Conti, D
Avila, L
Eng, C
Vora, H
LeNoir, MA
Soto-Quiros, M
Liu, JH
Celedon, JC
Farber, HJ
Kumar, R
Avila, PC
Meade, K
Serebrisky, D
Thyne, S
Rodriguez-Cintron, W
Rodriguez-Santana, JR
Borrell, LN
Lemanske, RF
Bleecker, ER
Meyers, DA
London, SJ
Barnes, KC
Raby, BA
Martinez, FD
Gilliland, FD
Williams, LK
Burchard, EG
Weiss, ST
Nicolae, DL
Ober, C
AF Myers, Rachel A.
Himes, Blanca E.
Gignoux, Christopher R.
Yang, James J.
Gauderman, W. James
Rebordosa, Cristina
Xie, Jianming
Torgerson, Dara G.
Levin, Albert M.
Baurley, James
Graves, Penelope E.
Mathias, Rasika A.
Romieu, Isabelle
Roth, Lindsey A.
Conti, David
Avila, Lydiana
Eng, Celeste
Vora, Hita
LeNoir, Michael A.
Soto-Quiros, Manuel
Liu, Jinghua
Celedon, Juan C.
Farber, Harold J.
Kumar, Rajesh
Avila, Pedro C.
Meade, Kelley
Serebrisky, Denise
Thyne, Shannon
Rodriguez-Cintron, William
Rodriguez-Santana, Jose R.
Borrell, Luisa N.
Lemanske, Robert F., Jr.
Bleecker, Eugene R.
Meyers, Deborah A.
London, Stephanie J.
Barnes, Kathleen C.
Raby, Benjamin A.
Martinez, Fernando D.
Gilliland, Frank D.
Williams, L. Keoki
Burchard, Esteban G.
Weiss, Scott T.
Nicolae, Dan L.
Ober, Carole
TI Further replication studies of the EVE Consortium meta-analysis
identifies 2 asthma risk loci in European Americans
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma; genetic risk factors; meta-analysis; KLK3
ID GENOME-WIDE ASSOCIATION; PROSTATE-SPECIFIC ANTIGEN; SUSCEPTIBILITY LOCI;
INNATE IMMUNITY; POPULATION; VARIANTS; GENETICS; SCREEN; ANNOTATION;
SEQUENCE
AB Background: Genome-wide association studies of asthma have implicated many genetic risk factors, with well-replicated associations at approximately 10 loci that account for only a small proportion of the genetic risk.
Objectives: We aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis.
Methods: We selected 3186 single nucleotide polymorphisms for replication based on the P values from the EVE Consortium meta-analysis. These single nucleotide polymorphisms were genotyped in ethnically diverse replication samples from 9 different studies, totaling 7202 cases, 6426 controls, and 507 case-parent trios. Association analyses were conducted within each participating study, and the resulting test statistics were combined in a meta-analysis.
Results: Two novel associations were replicated in European Americans: rs1061477 in the KLK3 gene on chromosome 19 (combined odds ratio = 1.18; 95% CI, 1.10-1.25) and rs9570077 (combined odds ratio =1.20; 95% CI, 1.12-1.29) on chromosome 13q21. We could not replicate any additional associations in the African Americans or Latinos.
Conclusions: This extended replication study identified 2 additional asthma risk loci in populations of European descent. The absence of additional loci for African Americans and Latinos highlights the difficulty in replicating associations in admixed populations. (J Allergy Clin Immunol 2012;130:1294-301.)
C1 [Myers, Rachel A.; Xie, Jianming; Nicolae, Dan L.; Ober, Carole] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Himes, Blanca E.; Raby, Benjamin A.; Weiss, Scott T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Div Network Med, Boston, MA 02115 USA.
[Gignoux, Christopher R.; Torgerson, Dara G.; Roth, Lindsey A.; Eng, Celeste; Burchard, Esteban G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Yang, James J.; Levin, Albert M.] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA.
[Gauderman, W. James; Baurley, James; Conti, David; Vora, Hita; Liu, Jinghua; Gilliland, Frank D.] Univ So Calif, Dept Preventat Med, Los Angeles, CA USA.
[Rebordosa, Cristina; Graves, Penelope E.; Martinez, Fernando D.] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA.
[Rebordosa, Cristina; Graves, Penelope E.; Martinez, Fernando D.] Univ Arizona, Inst BIO5, Tucson, AZ USA.
[Xie, Jianming] Southeast Univ, Sch Biol Sci & Med Engn, Nanjing, Jiangsu, Peoples R China.
[Mathias, Rasika A.; Barnes, Kathleen C.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Romieu, Isabelle] Inst Nacl Salud Publ, Mexico City, DF, Mexico.
[Romieu, Isabelle] Int Agcy Res Canc, F-69372 Lyon, France.
[Avila, Lydiana; Soto-Quiros, Manuel] Hosp Nacl Ninos Dr Carlos Saenz Herrera, San Jose, Costa Rica.
[LeNoir, Michael A.] Bay Area Pediat, Oakland, CA USA.
[Celedon, Juan C.] Univ Pittsburgh, Div Pediat Pulmonol, Pittsburgh, PA USA.
[Farber, Harold J.] Baylor Coll Med, Dept Pediat, Sect Pulmonol, Houston, TX 77030 USA.
[Kumar, Rajesh] Ann & Robert H Lurie Childrens Hosp Chicago, Div Allergy & Immunol, Chicago, IL USA.
[Avila, Pedro C.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Meade, Kelley] Childrens Hosp Oakland, Oakland, CA USA.
[Serebrisky, Denise] Albert Einstein Coll Med, Jacobi Med Ctr, Bronx, NY 10467 USA.
[Serebrisky, Denise] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
[Thyne, Shannon] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
[Rodriguez-Cintron, William] Vet Affairs Med Ctr, San Juan, PR USA.
[Rodriguez-Santana, Jose R.] Ctr Neumol Pediat, San Juan, PR USA.
[Borrell, Luisa N.] CUNY Herbert H Lehman Coll, Dept Hlth Sci, New York, NY USA.
[Lemanske, Robert F., Jr.] Univ Wisconsin, Dept Pediat, Madison, WI USA.
[Bleecker, Eugene R.] Wake Forest Sch Med, Ctr Human Genom, Winston Salem, NC USA.
[Meyers, Deborah A.; London, Stephanie J.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Williams, L. Keoki] Henry Ford Hlth Syst, Ctr Hlth Serv Res, Dept Internal Med, Detroit, MI USA.
[Burchard, Esteban G.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Nicolae, Dan L.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Nicolae, Dan L.] Univ Chicago, Dept Stat, Chicago, IL 60637 USA.
RP Ober, C (reprint author), 920 E 58th St,CLSC Room 425, Chicago, IL 60637 USA.
EM ober@genetics.uchicago.edu
RI liu, jinghua/H-4516-2014;
OI London, Stephanie/0000-0003-4911-5290
FU National Heart, Lung, and Blood Institute (NHLBI); National Institutes
of Health (NIH); NIH; UpToDate; EMD China; American Academy of
Pediatrics; University of California; NHLBI; Pharmaxis; Michigan Public
Health Institute; Allegheny General Hospital; West Allegheny Health
Systems, Inc; California Chapter 4; AAP; Colorado Allergy Society;
Pennsylvania Allergy and Asthma Association; Harvard Pilgrim Health;
California Society of Allergy; NYC Allergy Society; World Allergy
Organization; American College of Chest Physicians; American Academy of
Allergy, Asthma, Immunology; Elsevier; Abbott; Merck; National Institute
of Allergy and Infectious Diseases; Office of the Director, National
Institutes of Health (NIH); National Heart, Lung, and Blood Institute
[HL087665, HL070831, HL072414, HL049596, HL064307, HL064313, HL075419,
HL65899, HL083069, HL066289, HL101543, HL101651, HL079055, HL087699,
HL49612, HL075417, HL04266, HL072433, HL061768, HL076647, HL087680,
HL078885, HL088133, HL87665]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK064695]; National Institutes of
Environmental Health Sciences [ES09606, ES018176, ES015903, ES007048,
ES009581, R826708, RD831861, ES011627, ES015794]; Division of Intramural
Research [Z01 ES049019]; National Center for Research Resources
[RR03048, RR00188]; Environmental Protection Agency [83213901,
R-826724]; American Asthma Foundation; Fund for Henry Ford Hospital;
Mary Beryl Patch Turnbull Scholar Program; Flight Attendant Medical
Research Institute (FAMRI); Robert Wood Johnson Foundation (RWJF); Amos
Medical Faculty Development Award; Sandler Foundation
FX C. R. Gignoux has received grants and travel support from the National
Heart, Lung, and Blood Institute (NHLBI) and has stock/ stock options in
23andMe, Inc. A. M. Levin has received grants and travel support from
the National Institutes of Health (NIH) and is employed by Henry Ford
Health System. R. A. Mathias has received grants from the NIH and the
NHLBI and is employed by Johns Hopkins University. W. J. Gauderman, J.
Baurley, L. A. Roth, D. Conti, R. Kumar, P. C. Avila, S. Thyne, J. R.
Rodriguez-Santana, L. N. Borrell, F. D. Gilliland, E. G. Burchard, and
D. L. Nicolae have received grants from the NIH. L. Avila has received
payment for lectures, including service on speakers' bureaus, from Merck
Sharpe Dohme and AstraZeneca. M. A. LeNoir receives payment for
lectures, including service on speakers' bureaus, from Teva and
GlaxoSmithKline. J. C. Celedon has received grants from the NIH, has
consultant arrangements with Genentech, and receives royalties from
UpToDate. H. J. Farber has received grants from the NIH, is employed by
the Texas Children's Health Plan, has received payment for lectures from
EMD China, has received payment for manuscript preparation from Web MD,
has received travel expenses from the American Academy of Pediatrics,
and has received honoraria for service as the Editor of Pediatric
Allergy, Immunology, and Pulmonology from Mary Ann Liebert, Inc. D.
Serebrisky has received grants from the NIH and has received payment for
lectures, including service on speakers' bureaus, from Teva. W.
Rodriguez-Cintron has received grants from the University of California,
San Francisco. R. F. Lemankse, Jr has received travel support and fees
for participation in review activities from the NIH; has consultant
arrangements with Merck, Sepracor, SA Boney and Associates, LTD,
GlaxoSmithKline, American Institute of Research, Genentech, Inc, Double
Helix Development, Inc, and Boerhinger Ingelheim; is employed by the
University of Wisconsin School of Medicine and Public Health; has
received grants from the NHLBI and Pharmaxis; has received payment for
lectures, including service on speakers' bureaus, from the Michigan
Public Health Institute, Allegheny General Hospital, the American
Academy of Pediatrics, West Allegheny Health Systems, Inc, California
Chapter 4, AAP, the Colorado Allergy Society, the Pennsylvania Allergy
and Asthma Association, Harvard Pilgrim Health, the California Society
of Allergy, the NYC Allergy Society, the World Allergy Organization, and
the American College of Chest Physicians; has received payment for
manuscript preparation from the American Academy of Allergy, Asthma,&
Immunology; and has received royalties from Elsevier and UpToDate. D. A.
Meyers has received grants from the NHLBI. K. C. Barnes has received
grants from the NIH and the NHLBI; has board membership with Genentech;
has consultant arrangements with Sanofi-Aventis and Sirius Genomics; is
employed by Johns Hopkins University; and has received payments for
lectures, including service on speakers' bureaus, from the "Evolution
and Diseases of Modern Environments" Symposium, the American Academy of
Allergy, Asthma, & Immunology, the Cincinnati CHMC Allergy Conference,
and the 50th Annual Swineford Allergy Conference. B. A. Raby has
received grants from the NIH and has received royalties from UpToDate,
Inc. F. D. Martinez has consultant arrangements with MedImmune, has
received grants from the NIH, has received payment for lectures,
including service on speakers' bureaus, from Abbott and Merck, and has
received travel expenses from Abbott and Merck.; L. K. Williams has
received grants from the National Institute of Allergy and Infectious
Diseases and the NHLBI. C. Ober has received grants, travel support,
fees for participation in review activities, and payment for lectures,
including service on speakers' bureaus, from the NIH. The rest of the
authors declare that they have no relevant conflicts of interest.;
Supported by grants from the Office of the Director, National Institutes
of Health (NIH) to C.O. and D.L.N.; the National Heart, Lung, and Blood
Institute (HL101651 to C.O. and D.L.N.; HL087665 to D. L. N.; HL070831,
HL072414, and HL049596 to C.O.; HL064307 and HL064313 to F. D. M.;
HL075419, HL65899, HL083069, HL066289, HL087680, HL101543, and HL101651
to S. T. W.; HL079055 to L. K. W.; HL087699, HL49612, HL075417, HL04266,
and HL072433 to K. C. B.; HL061768 and HL076647 to F. D. G.; HL087680 to
W.J.G.; HL078885 and HL088133 to E. G. B.; and HL87665 to D. A. M.); the
National Institutes of Allergy and Infectious Disease (AI070503 to C.O.;
AI079139 and AI061774 to L. K. W.; AI50024, AI44840, and AI41040 to K.
C. B.; and AI077439 to E. G. B.); the National Institute of Diabetes and
Digestive and Kidney Diseases to L. K. W. (DK064695); the National
Institutes of Environmental Health Sciences (ES09606, ES018176, and
ES015903 to K. C. B.; ES007048, ES009581, R826708, RD831861, and
ES011627 to F. D. G.; ES015794 to E. G. B.; and the Division of
Intramural Research, Z01 ES049019 to S.J.L.); the National Center for
Research Resources (RR03048 to K. C. B., RR00188 to H.J.F.); the
Environmental Protection Agency (83213901 and R-826724 to K. C. B.); the
American Asthma Foundation and the Fund for Henry Ford Hospital (to L.
K. W.); Mary Beryl Patch Turnbull Scholar Program (to K. C. B.); and the
Flight Attendant Medical Research Institute (FAMRI), Robert Wood Johnson
Foundation (RWJF) Amos Medical Faculty Development Award, the American
Asthma Foundation, and the Sandler Foundation (to E. G. B.).
NR 36
TC 15
Z9 15
U1 0
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD DEC
PY 2012
VL 130
IS 6
BP 1294
EP 1301
DI 10.1016/j.jaci.2012.07.054
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 044RP
UT WOS:000311641100007
PM 23040885
ER
PT J
AU Cuburu, N
Graham, BS
Buck, CB
Kines, RC
Pang, YYS
Day, PM
Lowy, DR
Schiller, JT
AF Cuburu, Nicolas
Graham, Barney S.
Buck, Christopher B.
Kines, Rhonda C.
Pang, Yuk-Ying S.
Day, Patricia M.
Lowy, Douglas R.
Schiller, John T.
TI Intravaginal immunization with HPV vectors induces tissue-resident
CD8(+) T cell responses
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID CERVICAL INTRAEPITHELIAL NEOPLASIA; HERPES-SIMPLEX-VIRUS;
HUMAN-PAPILLOMAVIRUS; DENDRITIC CELLS; NONLYMPHOID TISSUE;
MEDIATED-IMMUNITY; VIRAL-INFECTION; VACCINIA VIRUS; VAGINAL MUCOSA;
MEMORY CELLS
AB The induction of persistent intraepithelial CD8(+) T cell responses may be key to the development of Vaccines against mucosally transmitted pathogens, particularly for sexually transmitted diseases; Here we investigated CD8(+) T cell responses in the female mouse cervicovaginal mucosa after intravaginal immunization with human papillomavirus vectors (HPV pseudoviruses) that transiently expressed a model antigen, respiratory syncytial virus (RSV) M/M2, in cervicovaginal keratinocytes. An HPV intravaginal prime/boost with different HPV serotypes induced 10 fold more cervicovaginal antigen specific CD8(+) T cells than priming alone Antigen specific T cell numbers decreased only 2-fold after 6 months. Most genital antigen specific CD8(+), T cells were intra- or subepithelial, expressed alpha(E)-integrin CD103, produced IFN-gamma and TNF-alpha, and displayed in vivo cytotoxicity. Using a sphingosine-l-phosphate analog (FTY720), we found that the primed CD8(+) T cells proliferated in the cervicovaginal mucosa upon HPV intravaginal boost Intravaginal HPV prime/boost reduced cervicovaginal viral titers 1,000 fold after intravaginal challenge with vaccinia virus expressing the CD8 epitope M2. In contrast, intramuscular prime/boost with an adenovirus type 5 vector induced a higher level of systemic CD8(+) T cells but failed to induce intraepithelial CD103(+)CD8(+) T cells or protect against recombinant vaccinia vaginal challenge. Thus, HPV vectors are attractive gene-delivery platforms for inducing durable intraepithelial cervicovaginal CD8(+) T cell responses by promoting local proliferation and retention of primed antigen specific CD8(+) T cells.
C1 [Cuburu, Nicolas; Buck, Christopher B.; Kines, Rhonda C.; Pang, Yuk-Ying S.; Day, Patricia M.; Lowy, Douglas R.; Schiller, John T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
[Graham, Barney S.] NIAID, Viral Pathogenesis Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
EM schillej@dc37a.nci.nih.gov
OI Buck, Christopher/0000-0003-3165-8094
FU NIH, National Cancer Institute, CCR
FX We acknowledge Amy Stout and Dale Long for outstanding support at the
NIH Tetramer Core Facility (Emory University, Atlanta, Georgia, USA). We
gratefully acknowledge Brian Murphy (NIAID, Bethesda, Maryland, USA) for
providing the M2 recombinant VV. This work was supported by the
Intramural Research Program of the NIH, National Cancer Institute, CCR.
NR 70
TC 46
Z9 47
U1 0
U2 6
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD DEC
PY 2012
VL 122
IS 12
BP 4606
EP 4620
DI 10.1172/JCI63287
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 048PY
UT WOS:000311926200033
PM 23143305
ER
PT J
AU Siddique, J
Chung, JY
Brown, CH
Miranda, J
AF Siddique, Juned
Chung, Joyce Y.
Brown, C. Hendricks
Miranda, Jeanne
TI Comparative Effectiveness of Medication Versus Cognitive-Behavioral
Therapy in a Randomized Controlled Trial of Low-Income Young Minority
Women With Depression
SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
LA English
DT Article
DE personalized medicine; paroxetine; buproprion; CBT; growth mixture model
ID FOLLOW-UP; TREATING DEPRESSION; RATING-SCALE; PRIMARY-CARE;
PHARMACOTHERAPY; DISORDER; MODERATE; RELAPSE; ANTIDEPRESSANTS;
INTERVENTIONS
AB Objective: To examine whether there are latent trajectory classes in response to treatment and whether they moderate the effects of medication versus psychotherapy. Method: Data come from a 1-year randomized controlled trial of 267 low-income, young (M = 29 years), minority (44% Black, 50% Latina, 6% White) women with current major depression randomized to antidepressants, cognitive-behavioral therapy (CBT), or referral to community mental health services. Growth mixture modeling was used to determine whether there were differential effects of medication versus CBT. Depression was measured via the Hamilton Depression Rating Scale (Hamilton, 1960). Results: We identified 2 latent trajectory classes. The first was characterized by severe depression at baseline. At 6 months, mean depression scores for the medication and CBT groups in this class were 13.9 and 14.9, respectively (difference not significant). At 12 months, mean depression scores were 16.4 and 11.0, respectively (p for difference = .04). The second class was characterized by moderate depression and anxiety at baseline. At 6 months, mean depression scores for the medication and CBT groups were 4.4 and 6.8, respectively (p for difference = .03). At 12 months, the mean depression scores were 7.1 and 7.8, respectively, and the difference was no longer significant. Conclusions: Among depressed women with moderate baseline depression and anxiety, medication was superior to CBT at 6 months, but the difference was not sustained at 1 year. Among women with severe depression, there was no significant treatment group difference at 6 months, but CBT was superior to medication at 1 year.
C1 [Siddique, Juned] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Chung, Joyce Y.] NIMH, Bethesda, MD 20892 USA.
[Brown, C. Hendricks] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Coral Gables, FL 33124 USA.
[Miranda, Jeanne] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
RP Siddique, J (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA.
EM siddique@northwestern.edu
OI Brown, C Hendricks/0000-0002-0294-2419
FU AHRQ HHS [R03 HS018815, R03-HS018815]; NCATS NIH HHS [UL1 TR000150]; NCI
NIH HHS [K07 CA154862, K07-CA154862]; NIMH NIH HHS [R01 MH040859, R01
MH080122, R01-MH040859, R01-MH080122]
NR 60
TC 9
Z9 9
U1 2
U2 46
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-006X
EI 1939-2117
J9 J CONSULT CLIN PSYCH
JI J. Consult. Clin. Psychol.
PD DEC
PY 2012
VL 80
IS 6
BP 995
EP 1006
DI 10.1037/a0030452
PG 12
WC Psychology, Clinical
SC Psychology
GA 047DI
UT WOS:000311817500004
PM 23088620
ER
PT J
AU Nastase, MV
Young, MF
Schaefer, L
AF Nastase, Madalina V.
Young, Marian F.
Schaefer, Liliana
TI Biglycan: A Multivalent Proteoglycan Providing Structure and Signals
SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
LA English
DT Article
DE extracellular matrix; proteoglycan; Toll-like receptor; inflammasome;
TGF beta; inflammation; bone; skeletal muscle; Duchenne's muscular
dystrophy; sepsis; Wnt
ID LEUCINE-RICH PROTEOGLYCANS; TOLL-LIKE RECEPTOR-4;
TEMPOROMANDIBULAR-JOINT OSTEOARTHRITIS; DERMATAN SULFATE PROTEOGLYCANS;
DUCHENNE MUSCULAR-DYSTROPHY; MATRIX COMPONENT BIGLYCAN; HUMAN
ARTICULAR-CARTILAGE; MARROW STROMAL CELLS; GROWTH-FACTOR-BETA; COLLAGEN
TYPE-I
AB Research over the past few years has provided fascinating results indicating that biglycan, besides being a ubiquitous structural component of the extracellular matrix (ECM), may act as a signaling molecule. Proteolytically released from the ECM, biglycan acts as a danger signal signifying tissue stress or injury. As a ligand of innate immunity receptors and activator of the inflammasome, biglycan stimulates multifunctional proinflammatory signaling linking the innate to the adaptive immune response. By clustering several types of receptors on the cell surface and orchestrating their downstream signaling events, biglycan is capable to autonomously trigger sterile inflammation and to potentiate the inflammatory response to microbial invasion. Besides operating in a broad biological context, biglycan also displays tissue-specific affinities to certain receptors and structural components, thereby playing a crucial role in bone formation, muscle integrity, and synapse stability at the neuromuscular junction. This review attempts to provide a concise summary of recent data regarding the involvement of biglycan in the regulation of inflammation and the musculoskeletal system, pointing out both a signaling and a structural role for this proteoglycan. The potential of biglycan as a novel therapeutic target or agent for the treatment of inflammatory diseases and skeletal muscular dystrophies is also addressed. (J Histochem Cytochem 60:963-975, 2012)
C1 [Nastase, Madalina V.; Schaefer, Liliana] Klinikum Goethe Univ Frankfurt Main, Inst Allgemeine Pharmakol & Toxikol, Pharmazentrum Frankfurt ZAFES, Frankfurt, Germany.
[Young, Marian F.] NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Schaefer, L (reprint author), Klinikum JW Goethe Univ Frankfurt Main, Inst Allgemeine Pharmakol & Toxikol, Pharmazentrum Frankfurt, Haus 74,Z3-108A,Theodor Stern Kai 7, D-60590 Frankfurt, Germany.
EM Schaefer@med.uni-frankfurt.de
FU German Research Council [SFB 815]; SCHA [1082/2-1]; Excellence Cluster
ECCPS; Division of Intramural Research, NIDCR of the Intramural Program
NIH, Department of Health and Human Services; [GRK1172]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: Research in
the authors' laboratory regarding the subject area covered by this
review was supported by the German Research Council: SFB 815, project
A5, SCHA 1082/2-1, Excellence Cluster ECCPS to LS and GRK1172 to MVN and
LS and in part by the Division of Intramural Research, NIDCR of the
Intramural Program NIH, Department of Health and Human Services.
NR 125
TC 41
Z9 42
U1 1
U2 28
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0022-1554
J9 J HISTOCHEM CYTOCHEM
JI J. Histochem. Cytochem.
PD DEC
PY 2012
VL 60
IS 12
BP 963
EP 975
DI 10.1369/0022155412456380
PG 13
WC Cell Biology
SC Cell Biology
GA 045GN
UT WOS:000311683500009
PM 22821552
ER
PT J
AU Nwaneshiudu, A
Kuschal, C
Sakamoto, FH
Anderson, RR
Schwarzenberger, K
Young, RC
AF Nwaneshiudu, Adaobi
Kuschal, Christiane
Sakamoto, Fernanda H.
Anderson, R. Rox
Schwarzenberger, Kathryn
Young, Roger C.
TI Introduction to Confocal Microscopy
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Review
C1 [Nwaneshiudu, Adaobi] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA.
[Kuschal, Christiane] NIH, Bethesda, MD 20892 USA.
[Sakamoto, Fernanda H.; Anderson, R. Rox] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Schwarzenberger, Kathryn] Univ Vermont, Coll Med, Dept Med, Div Dermatol, Burlington, VT 05405 USA.
[Young, Roger C.] Univ Vermont, Coll Med, Dept Obstet & Gynecol, Burlington, VT 05405 USA.
RP Nwaneshiudu, A (reprint author), Univ Chicago, Dept Med, Dermatol Sect, 5841 S Maryland Ave,MC 5067, Chicago, IL 60637 USA.
EM adaobi.nwaneshiudu@uchospitals.edu
OI Kuschal, Christiane/0000-0001-6113-3585
NR 6
TC 19
Z9 20
U1 6
U2 57
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD DEC
PY 2012
VL 132
IS 12
BP 1
EP 5
DI 10.1038/jid.2012.429
PG 5
WC Dermatology
SC Dermatology
GA 046PY
UT WOS:000311778100001
PM 23187113
ER
PT J
AU Gomes, R
Oliveira, F
Teixeira, C
Meneses, C
Gilmore, DC
Elnaiem, DE
Kamhawi, S
Valenzuela, JG
AF Gomes, Regis
Oliveira, Fabiano
Teixeira, Clarissa
Meneses, Claudio
Gilmore, Dana C.
Elnaiem, Dia-Eldin
Kamhawi, Shaden
Valenzuela, Jesus G.
TI Immunity to Sand Fly Salivary Protein LJM11 Modulates Host Response to
Vector-Transmitted Leishmania Conferring Ulcer-Free Protection
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID CUTANEOUS LEISHMANIASIS; LUTZOMYIA-LONGIPALPIS; FLIES; IDENTIFICATION;
CHAGASI; BITES; CELLS; MODEL
AB Leishmania vaccines that protect against needle challenge fail against the potency of a Leishmania-infected sand fly transmission. Here, we demonstrate that intradermal immunization of mice with 500 ng of the sand fly salivary recombinant protein LJM11 (rLJM11) from Lutzomyia longipalpis, in the absence of adjuvant, induces long-lasting immunity that results in ulcer-free protection against Leishmania major delivered by vector bites. This protection is antibody independent and abrogated by depletion of CD4(+) T cells. Two weeks after challenge, early induction of IFN-gamma specifically to rLJM11 correlates to diminished parasite replication in protected animals. At this time point, Leishmania-specific induction of IFN-gamma in these mice is low in comparison with its high level in non-protected controls. We hypothesize that early control of parasites in a T-cell helper type 1 environment induced by immunity to LJM11 permits the slow development of Leishmania-specific immunity in the absence of open ulcers. Leishmania-specific immunity observed 5 weeks after infection in rLJM11-immunized mice shows a twofold increase over controls in the percentage of IFN-gamma-producing CD4(+) T cells. We propose LJM11 as an immunomodulator that drives an efficient and controlled protective immune response to a sand fly-transmitted Leishmania somewhat mimicking "leishmanization"-induced protective immunity but without its associated lesions. Journal of Investigative Dermatology (2012) 132, 2735-2743; doi:10.1038/jid.2012.205; published online 28 June 2012
C1 [Gomes, Regis; Oliveira, Fabiano; Teixeira, Clarissa; Meneses, Claudio; Gilmore, Dana C.; Kamhawi, Shaden; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Elnaiem, Dia-Eldin] Univ Maryland Eastern Shore, Dept Zool, Princess Anne, MD USA.
RP Valenzuela, JG (reprint author), NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM skamhawi@niaid.nih.gov; jvalenzuela@niaid.nih.gov
RI Oliveira, Fabiano/B-4251-2009
OI Oliveira, Fabiano/0000-0002-7924-8038
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX We thank Elvin Morales, Anika T. Haque, and Nathan Smith for their help
with sand fly colonization. We thank David Sacks and Nathan Peters and
members of the VMBS for critical comments and revision of the
manuscript; Robert Gwadz and Thomas Wellems for continuous support; and
NIAID intramural editor Brenda Rae Marshall for assistance. The study
was funded by the Intramural Research Program of the Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health. As RG, FO, CM, DCG, SK, and JGV
are government employees and this is a government work, the work is in
the public domain in the United States. Notwithstanding any other
agreements, the NIH reserves the right to provide the work to PubMed
Central for display and use by the public, and PubMed Central may tag or
modify the work consistent with its customary practices. You can
establish rights outside of the United States subject to a government
use license.
NR 20
TC 28
Z9 28
U1 1
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD DEC
PY 2012
VL 132
IS 12
BP 2735
EP 2743
DI 10.1038/jid.2012.205
PG 9
WC Dermatology
SC Dermatology
GA 046PY
UT WOS:000311778100012
PM 22739793
ER
PT J
AU Kawaguchi, M
Valencia, JC
Namiki, T
Suzuki, T
Hearing, VJ
AF Kawaguchi, Masakazu
Valencia, Julio C.
Namiki, Takeshi
Suzuki, Tamio
Hearing, Vincent J.
TI Diacylglycerol Kinase Regulates Tyrosinase Expression and Function in
Human Melanocytes
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID MELANOMA-CELLS; PROTEASOMAL DEGRADATION; TRANSCRIPTION FACTOR; HUMAN
MELANOGENESIS; PHOSPHATIDIC-ACID; DOWN-REGULATION; DELTA;
MICROPHTHALMIA; PIGMENTATION; RETENTION
AB Diacylglycerol (DAG) increases the melanin content of human melanocytes in vitro and increases the pigmentation of guinea pig skin in vivo, but the mechanism(s) underlying those effects remain unknown. In this study, we characterized the role of diacylglycerol kinase (DGK), which phosphorylates DAG to generate phosphatidic acid, in the regulation of pigmentation. Ten isoforms of DGK have been identified, and we show that DGK zeta is the most abundant isoform expressed by human melanocytic cells. Melanin content, tyrosinase activity, and tyrosinase protein levels were significantly reduced by a DGK inhibitor, but tyrosinase and microphthalmia-associated transcription factor messenger RNA (mRNA) levels were not changed by that inhibition, and there were no effects on the expression of other melanogenesis-related proteins. Isoform-specific small interfering RNAs showed that knockdown of DGK zeta decreased melanin content and tyrosinase expression in melanocytic cells. Overexpression of DGK zeta increased tyrosinase protein levels, but did not increase tyrosinase mRNA levels. Glycosidase digestion revealed that inhibition of DGK reduced only the mature form of tyrosinase, and the decrease of tyrosinase resulting from DGK inhibition could be blocked partially by protease inhibitors. These results suggest that DGK regulates melanogenesis via modulation of the posttranslational processing of tyrosinase, which may be related with the protein degradation machinery. Journal of Investigative Dermatology (2012) 132, 2791-2799; doi:10.1038/jid.2012.261; published online 16 August 2012
C1 [Kawaguchi, Masakazu; Valencia, Julio C.; Namiki, Takeshi; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Suzuki, Tamio] Yamagata Univ, Sch Med, Dept Dermatol, Yamagata 99023, Japan.
RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 2132,MSC 4256, Bethesda, MD 20892 USA.
EM hearingv@nih.gov
FU National Cancer Institute at the National Institutes of Health
FX We thank Dr Hideya Ando for helpful discussion of the manuscript. This
research was supported in part by the Intramural Research Program of the
National Cancer Institute at the National Institutes of Health.
NR 41
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Z9 3
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD DEC
PY 2012
VL 132
IS 12
BP 2791
EP 2799
DI 10.1038/jid.2012.261
PG 9
WC Dermatology
SC Dermatology
GA 046PY
UT WOS:000311778100018
PM 22895365
ER
PT J
AU Serra-Pages, M
Olivera, A
Torres, R
Picado, C
de Mora, F
Rivera, J
AF Serra-Pages, Mariona
Olivera, Ana
Torres, Rosa
Picado, Cesar
de Mora, Fernando
Rivera, Juan
TI E-prostanoid 2 receptors dampen mast cell degranulation via
cAMP/PKA-mediated suppression of IgE-dependent signaling
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE Butaprost calcium; Fc epsilon I; Fyn; PGE(2)
ID FC-EPSILON-RI; MITE-SENSITIVE MICE; PROSTAGLANDIN E-2; ALLERGIC
INFLAMMATION; CA2+ INFLUX; ACTIVATION; RESPONSES; KINASE; ASTHMA;
CONTRIBUTES
AB The experimental administration of PGE(2) for the treatment of asthma dampens clinical symptoms, and similar efficacy has been found in dust mite-induced hypersensitivity reactions in animal models. Here, we investigate the mechanism by which PGE(2) mediates suppression of MC degranulation. We find that the effect of PGE(2) on Fc epsilon RI-dependent MC degranulation varies from activating to suppressing, depending on the relative ratio of EP2 to EP3 expression on these cells with suppression evident only in cells having increased EP2 to EP3 expression. Consistent with a role for EP2 in suppressing MC responses in vitro, we found that a selective EP2 agonist, Butaprost, inhibited MC-mediated Fc epsilon RI-induced immediate hypersensitivity in a model of PCA. EP2 engagement on MCs increased cAMP production and inhibited Fc epsilon RI-mediated calcium influx. In addition, it also decreased the extent of Fc epsilon RI-induced Fyn kinase activity, leading to decreased phosphorylation of key signaling molecules such as Gab2 and Akt. Treatment with an antagonist of cAMP or shRNA down-regulation of PKA (the principal intracellular target of cAMP) reversed the EP2-mediated inhibitory effect on MC degranulation and restored calcium influx and phosphorylation of Akt. Collectively, the findings demonstrate that EP2 suppresses the Fyn-mediated signals that are central to Fc epsilon RI-dependent MC degranulation, suggesting that engagement of the EP2 on MCs may be beneficial in dampening allergic responses. J. Leukoc. Biol. 92: 1155-1165; 2012.
C1 [Serra-Pages, Mariona; Olivera, Ana; Rivera, Juan] NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA.
[Serra-Pages, Mariona; Torres, Rosa; de Mora, Fernando] Univ Autonoma Barcelona, Dept Pharmacol Therapeut & Toxicol, E-08193 Barcelona, Spain.
[Torres, Rosa; Picado, Cesar] Hosp Clin Barcelona, Dept Pneumol & Resp Allergy, Barcelona, Spain.
[Torres, Rosa; Picado, Cesar] Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, CIBER Enfermedades Resp CIBERES, Barcelona, Spain.
RP Rivera, J (reprint author), NIAMS, Immunogenet Mol Lab, NIH, Bldg 10,Room 13C103, Bethesda, MD 20892 USA.
EM juan.rivera@nih.gov
RI Torres, Rosa/D-1189-2014; de Mora, Fernando/O-4636-2014
OI Torres, Rosa/0000-0002-9109-4035; de Mora, Fernando/0000-0002-3002-6004
FU Intramural Research Program of NIAMS of the U.S. National Institutes of
Health; Fondo de Investigacion Sanitaria [PS09/00171]; Laboratory Animal
Care and Use Section of the Office of Science and Technology, NIAMS;
Flow Cytometry Section
FX This work was supported by the Intramural Research Program of NIAMS of
the U.S. National Institutes of Health and by a grant from Fondo de
Investigacion Sanitaria (Ref. PS09/00171) managed by the Instituto de
Salud Carlos III of the Spanish Ministry of Health and by CIBERES. We
are grateful for the support of the Flow Cytometry Section and the
Laboratory Animal Care and Use Section of the Office of Science and
Technology, NIAMS.
NR 52
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Z9 19
U1 2
U2 9
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
EI 1938-3673
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD DEC
PY 2012
VL 92
IS 6
BP 1155
EP 1165
DI 10.1189/jlb.0212109
PG 11
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 048FL
UT WOS:000311895600006
PM 22859831
ER
PT J
AU Ma, C
Kapanadze, T
Gamrekelashvili, J
Manns, MP
Korangy, F
Greten, TF
AF Ma, Chi
Kapanadze, Tamar
Gamrekelashvili, Jaba
Manns, Michael P.
Korangy, Firouzeh
Greten, Tim F.
TI Anti-Gr-1 antibody depletion fails to eliminate hepatic myeloid-derived
suppressor cells in tumor-bearing mice
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE MDSC; liver; RB6-8C5; tolerance; inflammatory neutrophils
ID NATURAL-KILLER-CELLS; A-INDUCED HEPATITIS; HEPATOCELLULAR-CARCINOMA;
ANTITUMOR IMMUNITY; CANCER; RECRUITMENT; LIVER; IMMUNOSUPPRESSION;
ACCUMULATION; RECEPTOR
AB Recent studies show that the liver is a preferred organ for the accumulation of MDSC. In this study, we examined the effect of systemic RB6-8C5 treatment on hepatic MDSC in tumor-bearing mice. EL4 tumor-bearing mice were injected i.p. with RB6-8C5, and hepatic, splenic, and blood MDSCs were analyzed by flow cytometry. Unexpectedly, hepatic MDSC remained in the liver, although RB6-8C5 completely eliminated them from the spleen and peripheral blood 24 h after treatment. Secondary antibody staining confirmed the presence of RB6-8C5-bound MDSC in the liver of mice with s.c. tumors. Similar observations were made in two other (colon and melanoma) tumor models. Whereas RB6-8C5 injection induced cell death of hepatic MDSC, as shown by Annexin V/7-AAD staining, these cells were replaced immediately, leading to a constant, increased frequency of hepatic MDSC. Adoptively transferred MDSC migrated preferentially to the liver after RB6-8C5 treatment, suggesting that hepatic MDSCs are reconstituted rapidly after depletion. Finally, hepatic MDSC remained immunosuppressive despite RB6-8C5 injection. Our study demonstrates that RB6-8C5 is not suitable for depletion of hepatic MDSCs and analysis of their function. J. Leukoc. Biol. 92: 1199-1206; 2012.
C1 [Greten, Tim F.] NCI, NIH, CCR, Gastrointestinal Malignancy Sect,Med Oncol Branch, Bethesda, MD 20892 USA.
[Kapanadze, Tamar; Gamrekelashvili, Jaba; Manns, Michael P.] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-3000 Hannover, Germany.
RP Greten, TF (reprint author), NCI, NIH, CCR, Gastrointestinal Malignancy Sect,Med Oncol Branch, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tim.greten@nih.gov
RI Greten, Tim/B-3127-2015
OI Greten, Tim/0000-0002-0806-2535
FU NCI, U.S. National Institutes of Health; Initiative and Networking Fund
of the Helmholtz Association within the Helmholtz Alliance on
Immunotherapy of Cancer
FX This research was supported by the Intramural Research Program of the
NCI, U.S. National Institutes of Health, and by the Initiative and
Networking Fund of the Helmholtz Association within the Helmholtz
Alliance on Immunotherapy of Cancer. We thank Austin Duffy for critical
reading of this manuscript.
NR 37
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Z9 24
U1 0
U2 11
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD DEC
PY 2012
VL 92
IS 6
BP 1199
EP 1206
DI 10.1189/jlb.0212059
PG 8
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 048FL
UT WOS:000311895600010
PM 23077247
ER
PT J
AU Mazilu, D
Li, M
Kocaturk, O
Horvath, KA
AF Mazilu, Dumitru
Li, Ming
Kocaturk, Ozgur
Horvath, Keith A.
TI Self-Expanding Stent and Delivery System for Aortic Valve Replacement
SO JOURNAL OF MEDICAL DEVICES-TRANSACTIONS OF THE ASME
LA English
DT Article
DE minimally invasive aortic valve replacement; self-expanding nitinol
stents; shape memory materials; real-time MRI guidance
ID HIGH-RISK PATIENTS; IMPLANTATION; STENOSIS; PROSTHESIS; FEASIBILITY;
EXPERIENCE; DESIGN
AB Currently, aortic valve replacement procedures require a sternotomy and use of cardiopulmonary bypass (CPB) to arrest the heart and provide a bloodless field in which to operate. A less invasive alternative to open heart surgery is transapical or transcatheter aortic valve replacement (TAVR), already emerging as a feasible treatment for patients with high surgical risk. The bioprosthetic valves are delivered via catheters using transarterial or transapical approaches and are implanted within diseased aortic valves. This paper reports the development of a new self-expanding stent for minimally invasive aortic valve replacement and its delivery device for the transapical approach under real-time magnetic resonance imaging (MRI) guidance. Made of nitinol, the new stent is designed to implant and embed a commercially available bioprosthetic aortic valve in aortic root. An MRI passive marker was affixed onto the stent and an MRI active marker to the delivery device. These capabilities were tested in ex vivo and in vivo experiments. Radial resistive force, chronic outward force, and the integrity of bioprosthesis on stent were measured through custom design dedicated test equipment. In vivo experimental evaluation was done using a porcine large animal model. Both ex vivo and in vivo experiment results indicate that the self-expanding stent provides adequate reinforcement of the bioprosthetic aortic valve and it is easier to implant the valve in the correct position. The orientation and positioning of the implanted valve is more precise and predictable with the help of the passive marker on stent and the active marker on delivery device. The new self-expanding nitinol stent was designed to exert a constant radial force and, therefore, a better fixation of the prosthesis in the aorta, which would result in better preservation of long-term heart function. The passive marker affixed on the stent and active marker embedded in the delivery devices helps to achieve precise orientation and positioning of the stent under MRI guidance. The design allows the stent to be retracted in the delivery device with a snaring catheter if necessary. Histopathology reports reveal that the stent is biocompatible and fully functional. All the stented bioprosthesis appeared to be properly seated in the aortic root. [DOI: 10.1115/1.4007750]
C1 [Mazilu, Dumitru; Li, Ming] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Kocaturk, Ozgur] NHLBI, Cardiovasc Intervent Program, NIH, Bethesda, MD 20892 USA.
[Horvath, Keith A.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
RP Mazilu, D (reprint author), NHLBI, Cardiothorac Surg Res Program, NIH, 10 Ctr Dr,MSC 1550,Bldg 10,Room B1D47, Bethesda, MD 20892 USA.
EM mazilud@nhlbi.nih.gov; lim2@nhlbi.nih.gov; kocaturko@nhlbi.nih.gov;
horvathka@nhlbi.nih.gov
RI Kocaturk, Ozgur/A-1419-2016
FU Intramural Research Program of the National Heart, Lung, and Blood
Institute, National Institutes of Health, United States Department of
Health and Human Services (HHS)
FX The authors are supported through the Intramural Research Program of the
National Heart, Lung, and Blood Institute, National Institutes of
Health, United States Department of Health and Human Services (HHS).
Also, the authors would like to thank Dr. Renu Virmani and Naima
Carter-Monroe from CV Path Institute, Inc. for the pathology analysis.
NR 36
TC 1
Z9 1
U1 0
U2 15
PU ASME-AMER SOC MECHANICAL ENG
PI NEW YORK
PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA
SN 1932-6181
J9 J MED DEVICES
JI J. Med. Devices
PD DEC
PY 2012
VL 6
IS 4
AR 041006
DI 10.1115/1.4007750
PG 9
WC Engineering, Biomedical
SC Engineering
GA 049EI
UT WOS:000311964600006
ER
PT J
AU Talegawkar, SA
Bandinelli, S
Bandeen-Roche, K
Chen, P
Milaneschi, Y
Tanaka, T
Semba, RD
Guralnik, JM
Ferrucci, L
AF Talegawkar, Sameera A.
Bandinelli, Stefania
Bandeen-Roche, Karen
Chen, Ping
Milaneschi, Yuri
Tanaka, Toshiko
Semba, Richard D.
Guralnik, Jack M.
Ferrucci, Luigi
TI A Higher Adherence to a Mediterranean-Style Diet Is Inversely Associated
with the Development of Frailty in Community-Dwelling Elderly Men and
Women
SO JOURNAL OF NUTRITION
LA English
DT Article
ID OLDER PERSONS; OXIDATIVE STRESS; HEALTH; INFLAMMATION; DECLINE; ADULTS;
METAANALYSIS; TRANSITIONS; PHENOTYPE; PATTERNS
AB Adherence to a Mediterranean-style diet is associated with a lower risk for mortality, cognitive decline, and dementia. Whether adherence to a Mediterranean-style diet protects against age-related frailty is unclear. Therefore, our objective was to examine the association between a Mediterranean-style diet with the risk of frailty in community-dwelling older persons. We conducted longitudinal analyses using data from 690 community-living persons (>= 65 y) who were randomly selected from a population registry in Tuscany, Italy. Participants of the Invecchiare in Chianti study of aging completed the baseline examination in 1998-2000 and were re-examined at least once over 6 y. Adherence to a Mediterranean-style diet (scored 0-9, modeled categorically as <= 3, 4-5, and >= 6) was computed from the European Prospective Investigation into Cancer and nutrition FFQ previously validated in this cohort. Frailty was defined as having at least 2 of the following criteria: poor muscle strength, feeling of exhaustion, low walking speed, and low physical activity. After a 6-y follow-up, higher adherence (score to a Mediterranean-style diet was associated with lower odds of developing frailty [OR = 0.30 (95% CI: 0.14, 0.66)] compared with those with lower adherence (score <= 3). A higher adherence to a Mediterranean-style diet at baseline was also associated with a lower risk of low physical activity (OR = 0.62; 95% CI: 0.40, 0.96) and low walking speed [OR = 0.48(95% CI: 0.27, 0.86)] but not with feelings of exhaustion and poor muscle strength. In community-dwelling older adults, higher adherence to a Mediterranean-style diet was inversely associated with the development of frailty. J. Nutr. 142: 2161-2166, 2012.
C1 [Talegawkar, Sameera A.; Chen, Ping] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Human Nutr, Baltimore, MD USA.
[Bandeen-Roche, Karen] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Bandinelli, Stefania] Azienda Sanit Firenze, Florence, Italy.
[Milaneschi, Yuri; Tanaka, Toshiko; Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
[Milaneschi, Yuri] Vrije Univ Amsterdam, Med Ctr GGZ Ingest, Dept Psychiat, Amsterdam, Netherlands.
[Semba, Richard D.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
RP Talegawkar, SA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Human Nutr, Baltimore, MD USA.
EM sameera.talegawkar@alumni.tufts.edu
FU National Institute on Aging (NIA); Johns Hopkins University Claude D.
Pepper Older Americans Independence Center [P30AG021334]; NIA [R01
AG027012, 263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111,
N01-AG-5-0002]; Italian Ministry of Health [ICS110.1/RF97.71]; NIA, NIH,
Baltimore, Maryland
FX Supported by National Institute on Aging (NIA), Johns Hopkins University
Claude D. Pepper Older Americans Independence Center, P30AG021334; NIA
grant R01 AG027012; the Italian Ministry of Health (ICS110.1/RF97.71);
and NIA contracts 263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111,
and N01-AG-5-0002, the Intramural Research Program of the NIA, NIH,
Baltimore, Maryland.
NR 42
TC 43
Z9 43
U1 3
U2 16
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD DEC
PY 2012
VL 142
IS 12
BP 2161
EP 2166
DI 10.3945/jn.112.165498
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 044XK
UT WOS:000311658300013
PM 23096005
ER
PT J
AU Pencharz, PB
Russell, RM
AF Pencharz, Paul B.
Russell, Robert M.
TI Application of Key Events Dose Response Framework to Defining the Upper
Intake Level of Leucine in Young Men
SO JOURNAL OF NUTRITION
LA English
DT Article; Proceedings Paper
CT 8th Workshop on the Assessment of Adequate and Safe Intake of Dietary
Amino Acids
CY NOV 10-11, 2011
CL undefined, WA
AB Leucine is sold in large doses in health food stores and is ingested by weight-training athletes. The safety of ingestion of large doses of leucine is unknown. Before designing chronic high-dose leucine supplementation experiments, we decided to determine the effect of graded doses of leucine in healthy participants. the Key Events Dose Response Framework is an organizational and analytical framework that dissects the various biologic steps (key events) that occur between exposure to a substance and an eventual adverse effect. Each biologic event is looked at for its unique dose-response characteristics. For nutrients, there are a number of biologic homeostatic mechanisms that work to keep circulating/tissue levels in a safe, nontoxic range. If a response mechanism at a particular key event is especially vulnerable and easily overwhelmed, this is known as a determining event, because this event drives the overall slope or shape of the dose-response relationship. In this paper, the Key Events Dose Framework has been applied to the problem of leucine toxicity and leucine's tolerable upper level. After analyzing the experimental data vis a vis key events for leucine leading to toxicity, it became evident that the rate of leucine oxidation was the determining event. A dose-response study has been conducted to graded intakes of leucine in healthy human adult male volunteers. All participants were started at the mean requirement level of leucine [50 mg/(kg . d)] and the highest leucine intake was 1250 mg/(kg . d), which is 25 times the mean requirement. No gut intolerance was seen. Blood glucose fell progressively but remained within normal values without any changes in plasma insulin. Maximal leucine oxidation levels occurred at an intake of 550 mg leucine/(kg . d), after which plasma leucine progressively increased and plasma ammonia also increased in response to leucine intakes >500 mg/(kg . d). Thus, the "key determining event" appears to be when the participants reach their maximal leucine oxidation level, after which the risk of metabolic adverse effects progressively increased. J. Nutr. 142: 2225S-2226S, 2012.
C1 [Pencharz, Paul B.] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada.
[Pencharz, Paul B.] Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada.
[Pencharz, Paul B.] Univ Alberta, Dept Agr Food & Nutr Sci, Edmonton, AB, Canada.
[Russell, Robert M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Russell, Robert M.] Tufts Univ, Boston, MA 02111 USA.
RP Pencharz, PB (reprint author), Hosp Sick Children, Res Inst, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
EM paul.pencharz@sickkids.ca
FU International Council on Amino Acid Science (ICAAS); International Life
Sciences Institute (ILSI) Research Foundation; International Life
Sciences Institute
FX Published in a supplement to The Journal of Nutrition. Presented at the
8th Workshop on the Assessment of Adequate and Safe Intake of Dietary
Amino Acids, held in Washington, DC, November 10-11, 2011. The
conference was sponsored by the International Council on Amino Acid
Science (ICAAS) and the International Life Sciences Institute (ILSI)
Research Foundation. The Organizing Committee for the workshop included
Sidney M. Morris, Jr, Dennis M. Bier, Luc A. Cynober, Motoni Kadowaki,
and Andrew G. Renwick. The views expressed in these papers are not
necessarily those of the Supplement Coordinator or Guest Editors. The
Supplement Coordinator for this supplement was D'Ann Finley, University
California, Davis. Supplement Coordinator disclosures: D'Ann Finley
received travel support and compensation from ICAAS for editorial
services provided for this supplement publication. The supplement is the
responsibility of the Guest Editor to whom the Editor of The Journal of
Nutrition has delegated supervision of both technical conformity to the
published regulations of The Journal of Nutrition and general oversight
of the scientific merit of each article. The Guest Editor for this
supplement was Harry Dawson. Guest Editor disclosure: Harry Dawson had
no conflicts to disclose. Publication costs for this supplement were
defrayed in part by the payment of page charges. This publication must
therefore be hereby marked "advertisement" in accordance with 18 USC
section 1734 solely to indicate this fact. The opinions expressed in
this publication are those of the authors and are not attributable to
the sponsors or the Publisher, Editor, or Editorial Board of The Journal
of Nutrition.; Supported by the International Council on Amino Acid
Sciences (P. B. Pencharz to attend the workshop) and by the
International Life Sciences Institute (R. M. Russell).
NR 4
TC 1
Z9 1
U1 0
U2 3
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD DEC
PY 2012
VL 142
IS 12
BP 2225S
EP 2226S
DI 10.3945/jn.112.159079
PG 2
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 044XK
UT WOS:000311658300023
PM 23077195
ER
PT J
AU Kimura, T
Bier, DM
Taylor, CL
AF Kimura, Takeshi
Bier, Dennis M.
Taylor, Christine L.
TI Summary of Workshop Discussions on Establishing Upper Limits for Amino
Acids with Specific Attention to Available Data for the Essential Amino
Acids Leucine and Tryptophan
SO JOURNAL OF NUTRITION
LA English
DT Article; Proceedings Paper
CT 8th Workshop on the Assessment of Adequate and Safe Intake of Dietary
Amino Acids
CY NOV 10-11, 2011
CL undefined, WA
ID UPPER INTAKE LEVEL; HUMANS; RATS; MEN
AB The morning of the first day of the 8th Amino Acid Assessment Workshop was organized and co-sponsored by the International Council on Amino Acid Science (ICAAS) and the International Life Sciences Institute Research Foundation and was focused on the International Life Sciences Institute Research Foundation's approach to establishing upper limits of nutrients. The remainder of d 1 and all of d 2 were focused on the safety of leucine and tryptophan, with special emphasis on determining the upper level of the safe range of intake. It was recognized that some toxicological frameworks, mainly the key-events dose response framework, might be applicable to amino acids and provide appropriate assistance to regulators in establishing upper limits for amino acids as a group of nutrients used in dietary supplements. ICAAS-funded projects for determining the upper intake limits for the essential amino acid leucine provided the main pool of leucine data discussed at the workshop. The acute clinical study suggests 500 mg/(kg . d) as a possible upper limit for leucine in healthy humans, but the safety margin needed to widen this limit to the general population has not been determined. For tryptophan, the workshop participants found less ground for consensus. Older efficacy studies suggested that tryptophan at 8-15 g/d was well tolerated, but human research was abruptly terminated in the late 1980s and no new data are available. Animal results obtained in pigs and rodents were discussed and 2 possible strategies for applying those outcomes to humans were described. J. Nutr. 142: 2245S-2248S, 2012.
C1 [Kimura, Takeshi] Ajinomoto Co Inc, Chuo Ku, Tokyo, Japan.
[Bier, Dennis M.] ARS, USDA, Childrens Nutr Res Ctr, Baylor Coll Med, Houston, TX USA.
[Taylor, Christine L.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Kimura, T (reprint author), Ajinomoto Co Inc, Chuo Ku, Tokyo, Japan.
EM takeshi_kimura@ajinomoto.com
FU ICAAS secretariat; International Council on Amino Acid Science (ICAAS);
International Life Sciences Institute (ILSI) Research Foundation
FX The authors thank the ICAAS secretariat for their support during and
after the workshop. T.K. wrote the manuscript based on the tapes from
the discussion sections with the assistance of Dr. Miroslav Smriga; and
D.M.B. and C.L.T. critically reviewed the manuscript and contributed to
the final version. All authors read and approved the final manuscript.;
Published in a supplement to The Journal of Nutrition. Presented at the
8th Workshop on the Assessment of Adequate and Safe Intake of Dietary
Amino Acids, held in Washington, DC, November 10-11, 2011. The
conference was sponsored by the International Council on Amino Acid
Science (ICAAS) and the International Life Sciences Institute (ILSI)
Research Foundation. The Organizing Committee for the workshop included
Sidney M. Morris, Jr, Dennis M. Bier, Luc A. Cynober, Motoni Kadowaki,
and Andrew G. Renwick. The views expressed in these papers are not
necessarily those of the Supplement Coordinator or Guest Editors. The
Supplement Coordinator for this supplement was D'Ann Finley, University
California, Davis. Supplement Coordinator disclosures: D'Ann Finley
received travel support and compensation from ICAAS for editorial
services provided for this supplement publication. The supplement is the
responsibility of the Guest Editor to whom the Editor of The Journal of
Nutrition has delegated supervision of both technical conformity to the
published regulations of The Journal of Nutrition and general oversight
of the scientific merit of each article. The Guest Editor for this
supplement was Harry Dawson. Guest Editor disclosure: Harry Dawson had
no conflicts to disclose. Publication costs for this supplement were
defrayed in part by the payment of page charges. This publication must
therefore be hereby marked "advertisement" in accordance with 18 USC
section 1734 solely to indicate this fact. The opinions expressed in
this publication are those of the authors and are not attributable to
the sponsors or the Publisher, Editor, or Editorial Board of The Journal
of Nutrition.
NR 14
TC 2
Z9 2
U1 0
U2 3
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD DEC
PY 2012
VL 142
IS 12
BP 2245S
EP 2248S
DI 10.3945/jn.112.160846
PG 4
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 044XK
UT WOS:000311658300027
PM 23077196
ER
PT J
AU Kluk, MW
Ji, YM
Shin, EH
Amrani, O
Onodera, J
Jackson, WM
Nesti, LJ
AF Kluk, Matthew W.
Ji, Youngmi
Shin, Emily H.
Amrani, Orna
Onodera, Jun
Jackson, Wesley M.
Nesti, Leon J.
TI Fibroregulation of Mesenchymal Progenitor Cells by BMP-4 After Traumatic
Muscle Injury
SO JOURNAL OF ORTHOPAEDIC TRAUMA
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the Orthopaedic-Trauma-Association
CY OCT 12-15, 2011
CL San Antonio, TX
SP Orthopaed Trauma Assoc
DE heterotopic ossification; mesenchymal stem cells; fibrosis; polytrauma
ID FIBRODYSPLASIA-OSSIFICANS-PROGRESSIVA; HETEROTOPIC OSSIFICATION;
SKELETAL-MUSCLE; DIFFERENTIATION; FIBROBLASTS; EXPRESSION; PROTEIN;
TISSUE
AB Objectives: Traumatized muscle is a complex healing environment containing cells with robust reparative and regenerative potential interacting in a cytokine milieu that influences the function and differentiation of these cells, leading to a spectrum of healing responses. In particular, bone morphogenetic protein-4 (BMP-4) is of interest as a potential modulator of healing because its dysregulation has been associated with fibrosis and heterotopic ossification formation. We propose a descriptive study of altered BMP-4 expression in traumatized muscle tissue and to evaluate its role in the fibroregulatory function of resident mesenchymal progenitor cells (MPCs) at the protein-and gene-expression levels.
Methods: Protein-level expression of BMP-4 from cells resident in traumatized muscle specimens was evaluated using ELISA and also using sodium dodecyl sulfate-polyacrylamide gel electrophoresis to compare BMP-4 in homogenized muscle tissue specimens. BMP-4, cartilage oligomeric matrix protein (COMP), and osteocalcin expression localization was analyzed via immunohistochemistry. Reverse transcription-polymerase chain reaction was performed to evaluate fibroregulatory gene expression in MPCs after treatment with BMP-4.
Results: BMP-4 was present in all traumatized muscle tissue specimens. Immunohistochemistry demonstrated that traumatized muscle fibers contained greater number of cells expressing BMP-4 in a more disorganized fashion compared with control samples. Reverse transcription-polymerase chain reaction demonstrated that COMP, growth and differentiation factor-10, and integrin beta-2 were up-regulated, whereas tumor necrosis factor-alpha was significantly down-regulated. COMP expression was colocalized in the traumatized muscle tissue with osteocalcin.
Conclusions: BMP-4 has an effect on MPCs that seems to promote fibrotic tissue formation. These findings suggest that BMP-4, while promoting osteoinduction, may also act on MPCs to promote formation of a fibrotic osteoinductive matrix. Thus, this signaling axis might be a potential target for heterotopic ossification prevention.
C1 [Kluk, Matthew W.; Ji, Youngmi; Shin, Emily H.; Amrani, Orna; Onodera, Jun; Nesti, Leon J.] NIAMSD, Clin & Expt Orthopaed Lab, NIH, Bethesda, MD 20892 USA.
[Kluk, Matthew W.; Shin, Emily H.; Nesti, Leon J.] Walter Reed Natl Mil Med Ctr, Dept Orthopaed & Rehabil, Washington, DC USA.
[Jackson, Wesley M.; Nesti, Leon J.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA.
RP Nesti, LJ (reprint author), NIAMSD, Clin & Expt Orthopaed Lab, NIH, 50 South Dr,Room 1525, Bethesda, MD 20892 USA.
EM nestil@mail.nih.gov
RI Amrani, OFer/K-3813-2015
FU Intramural NIH HHS; NIAMS NIH HHS [Z01AR41131]
NR 16
TC 8
Z9 8
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-5339
J9 J ORTHOP TRAUMA
JI J. Orthop. Trauma
PD DEC
PY 2012
VL 26
IS 12
BP 693
EP 698
DI 10.1097/BOT.0b013e3182712adf
PG 6
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA 045TG
UT WOS:000311719100006
PM 23010644
ER
PT J
AU Chan, W
McCrae, RR
De Fruyt, F
Jussim, L
Lockenhoff, CE
De Bolle, M
Costa, PT
Sutin, AR
Realo, A
Allik, J
Nakazato, K
Shimonaka, Y
Hrebickova, M
Graf, S
Yik, M
Brunner-Sciarra, M
de Figueora, NL
Schmidt, V
Ahn, CK
Ahn, HN
Aguilar-Vafaie, ME
Siuta, J
Szmigielska, B
Cain, TR
Crawford, JT
Mastor, KA
Rolland, JP
Nansubuga, F
Miramontez, DR
Benet-Martinez, V
Rossier, J
Bratko, D
Marusic, I
Halberstadt, J
Yamaguchi, M
Knezevic, G
Martin, TA
Gheorghiu, M
Smith, PB
Barbaranelli, C
Wang, L
Shakespeare-Finch, J
Lima, MP
Klinkosz, W
Sekowski, A
Alcalay, L
Simonetti, F
Avdeyeva, TV
Pramila, VS
Terracciano, A
AF Chan, Wayne
McCrae, Robert R.
De Fruyt, Filip
Jussim, Lee
Loeckenhoff, Corinna E.
De Bolle, Marleen
Costa, Paul T., Jr.
Sutin, Angelina R.
Realo, Anu
Allik, Jueri
Nakazato, Katsuharu
Shimonaka, Yoshiko
Hrebickova, Martina
Graf, Sylvie
Yik, Michelle
Brunner-Sciarra, Marina
de Figueora, Nora Leibovich
Schmidt, Vanina
Ahn, Chang-kyu
Ahn, Hyun-nie
Aguilar-Vafaie, Maria E.
Siuta, Jerzy
Szmigielska, Barbara
Cain, Thomas R.
Crawford, Janet T.
Mastor, Khairul Anwar
Rolland, Jean-Pierre
Nansubuga, Florence
Miramontez, Daniel R.
Benet-Martinez, Veronica
Rossier, Jerome
Bratko, Denis
Marusic, Iris
Halberstadt, Jamin
Yamaguchi, Mami
Knezevic, Goran
Martin, Thomas A.
Gheorghiu, Mirona
Smith, Peter B.
Barbaranelli, Claudio
Wang, Lei
Shakespeare-Finch, Jane
Lima, Margarida P.
Klinkosz, Waldemar
Sekowski, Andrzej
Alcalay, Lidia
Simonetti, Franco
Avdeyeva, Tatyana V.
Pramila, V. S.
Terracciano, Antonio
TI Stereotypes of Age Differences in Personality Traits: Universal and
Accurate?
SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY
LA English
DT Article
DE aging; stereotypes; cross-cultural; five factor model; personality
perception
ID 5 FACTOR MODEL; NATIONAL CHARACTER; LIFE-SPAN; 5-FACTOR MODEL;
MEAN-LEVEL; CULTURES; BELIEFS; PERSPECTIVE; ADULTS; PERCEPTIONS
AB Age trajectories for personality traits are known to be similar across cultures. To address whether stereotypes of age groups reflect these age-related changes in personality, we asked participants in 26 countries (N = 3,323) to rate typical adolescents, adults, and old persons in their own country. Raters across nations tended to share similar beliefs about different age groups; adolescents were seen as impulsive, rebellious, undisciplined, preferring excitement and novelty, whereas old people were consistently considered lower on impulsivity, activity, antagonism, and Openness. These consensual age group stereotypes correlated strongly with published age differences on the five major dimensions of personality and most of 30 specific traits, using as criteria of accuracy both self-reports and observer ratings, different survey methodologies, and data from up to 50 nations. However, personal stereotypes were considerably less accurate, and consensual stereotypes tended to exaggerate differences across age groups.
C1 [Chan, Wayne; Costa, Paul T., Jr.; Sutin, Angelina R.; Terracciano, Antonio] NIA, Baltimore, MD 21224 USA.
[De Fruyt, Filip; De Bolle, Marleen] Univ Ghent, Dept Dev Personal & Social Psychol, B-9000 Ghent, Belgium.
[Jussim, Lee] Rutgers State Univ, Dept Psychol, Piscataway, NJ 08855 USA.
[Loeckenhoff, Corinna E.] Cornell Univ, Dept Human Dev, Ithaca, NY 14853 USA.
[Realo, Anu; Allik, Jueri] Univ Tartu, Dept Psychol, EE-50090 Tartu, Estonia.
[Allik, Jueri] Estonian Acad Sci, EE-200103 Tallinn, Estonia.
[Nakazato, Katsuharu] Iwate Prefectural Univ, Fac Social Welfare, Takizawa, Iwate, Japan.
[Shimonaka, Yoshiko] Bunkyo Gakuin Univ, Dept Human Studies, Bunkyo Ku, Bunkyo, Japan.
[Hrebickova, Martina; Graf, Sylvie] Acad Sci Czech Republic, Inst Psychol, Prague, Czech Republic.
[Yik, Michelle] Hong Kong Univ Sci & Technol, Div Social Sci, Kowloon, Hong Kong, Peoples R China.
[Brunner-Sciarra, Marina] Univ Peruana Cayetano Heredia, Fac Psychol, Lima, Peru.
[de Figueora, Nora Leibovich; Schmidt, Vanina] Univ Buenos Aires, Dept Psychol, Buenos Aires, DF, Argentina.
[Ahn, Chang-kyu] Pusan Natl Univ, Dept Educ, Pusan, South Korea.
[Ahn, Hyun-nie] Ewha Womans Univ, Dept Psychol, Seoul, South Korea.
[Aguilar-Vafaie, Maria E.] Tarbiat Modares Univ, Dept Psychol, Tehran, Iran.
[Siuta, Jerzy; Szmigielska, Barbara] Jagiellonian Univ, Inst Psychol, Krakow, Poland.
[Cain, Thomas R.] Hampshire Coll, Sch Cognit Sci, Amherst, MA 01002 USA.
[Mastor, Khairul Anwar] Univ Kebangsaan Malaysia, Sch Gen Studies, Bangi 43600, Malaysia.
[Rolland, Jean-Pierre] Univ Paris Ouest Nanterre Def, UFR STAPS, Nanterre, France.
[Nansubuga, Florence] Makerere Univ, Inst Psychol, Kampala, Uganda.
[Miramontez, Daniel R.] San Diego Community Coll Dist, Off Inst Res & Planning, San Diego, CA USA.
[Benet-Martinez, Veronica] Pompeu Fabra Univ, Dept Polit & Social Sci, Barcelona, Spain.
[Rossier, Jerome] Univ Lausanne, Inst Psychol, Lausanne, Switzerland.
[Bratko, Denis] Univ Zagreb, Dept Psychol, Zagreb 41000, Croatia.
[Marusic, Iris] Inst Social Res Zagreb, Zagreb, Croatia.
[Halberstadt, Jamin; Yamaguchi, Mami] Univ Otago, Dept Psychol, Dunedin, New Zealand.
[Knezevic, Goran] Univ Belgrade, Dept Psychol, Belgrade, Serbia.
[Martin, Thomas A.] Susquehanna Univ, Dept Psychol, Selinsgrove, PA 17870 USA.
[Gheorghiu, Mirona] Queens Univ Belfast, Sch Psychol, Belfast BT7 1NN, Antrim, North Ireland.
[Barbaranelli, Claudio] Univ Roma La Sapienza, Dept Psychol, Rome, Italy.
[Wang, Lei] Peking Univ, Dept Psychol, Beijing 100871, Peoples R China.
[Shakespeare-Finch, Jane] Queensland Univ Technol, Sch Psychol & Counseling, Brisbane, Qld 4001, Australia.
[Lima, Margarida P.] Univ Coimbra, Fac Psychol & Educ Sci, Coimbra, Portugal.
[Klinkosz, Waldemar; Sekowski, Andrzej] John Paul II Catholic Univ Lublin, Dept Psychol, Lublin, Poland.
[Alcalay, Lidia; Simonetti, Franco] Pontificia Univ Catolica Chile, Escuela Psicol, Santiago, Chile.
[Avdeyeva, Tatyana V.] Univ St Thomas, Grad Sch Profess Psychol, St Paul, MN 55105 USA.
[Pramila, V. S.] Andhra Univ, Dept Psychol, Visakhapatnam, Andhra Pradesh, India.
RP Chan, W (reprint author), NIA, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM wayne.chan@nih.gov; Terraccianoa@mail.nih.gov
RI terracciano, antonio/B-1884-2008; Benet-Martinez, Veronica/B-5398-2011;
Graf, Sylvie/D-9732-2014; Hrebickova, Martina/H-4410-2014; Rossier,
Jerome/A-3494-2009; Allik, Juri/D-5609-2009; Wang, Lei/D-2501-2016;
Realo, Anu/M-9524-2016; Sekowski, Andrzej/O-7807-2016;
OI Shakespeare-Finch, Jane/0000-0003-4237-1320; Benet-Martinez,
Veronica/0000-0002-3352-9731; Graf, Sylvie/0000-0002-7810-5457;
Hrebickova, Martina/0000-0003-4356-567X; Rossier,
Jerome/0000-0002-9924-3672; Allik, Juri/0000-0002-8358-4747; Wang,
Lei/0000-0002-6156-9028; Chan, Wayne/0000-0001-5061-1713; Costa,
Paul/0000-0003-4375-1712; Nansubuga, Florence/0000-0001-6569-8700;
Loeckenhoff, Corinna/0000-0003-1605-1323
FU Intramural NIH HHS [ZIA AG000180-25, Z99 AG999999, ZIA AG000180-26]
NR 61
TC 22
Z9 22
U1 4
U2 95
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-3514
J9 J PERS SOC PSYCHOL
JI J. Pers. Soc. Psychol.
PD DEC
PY 2012
VL 103
IS 6
BP 1050
EP 1066
DI 10.1037/a0029712
PG 17
WC Psychology, Social
SC Psychology
GA 046MT
UT WOS:000311769800010
PM 23088227
ER
PT J
AU Hoerger, TJ
Wittenborn, JS
Zhuo, XH
Pavkov, ME
Burrows, NR
Eggers, P
Jordan, R
Saydah, S
Williams, DE
AF Hoerger, Thomas J.
Wittenborn, John S.
Zhuo, Xiaohui
Pavkov, Meda E.
Burrows, Nilka R.
Eggers, Paul
Jordan, Regina
Saydah, Sharon
Williams, Desmond E.
TI Cost-Effectiveness of Screening for Microalbuminuria among African
Americans
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; CONTROLLED TRIAL;
RENAL OUTCOMES; UNITED-STATES; NEPHROPATHY; HEALTH; PROTEINURIA;
PROGRESSION; PREVALENCE
AB Compared with other racial groups, African Americans have a similar prevalence of CKD but are much more likely to progress to ESRD, suggesting that the cost-effectiveness of screening strategies requires dedicated study in this population. Here, we calibrated the CKD Health Policy Model so that it accurately forecasts the higher rates for ESRD observed for African Americans. We then used the calibrated model to estimate the cost-effectiveness of screening for microalbuminuria followed by treatment with angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers. Incorporating racial differences in risk factors did not fully explain the much higher lifetime incidence of ESRD among African Americans. Thus, to calibrate the model, we applied a 20% increase in the rate of GFR decline at stage 3 and a 60% increase in the rate of GFR decline at stage 4, which resulted in a model that closely reflects lifetime ESRD incidence among African Americans. Compared with usual care, screening African Americans for microalbuminuria at 10-, 5-, 2-, and 1-year intervals had incremental cost-effectiveness ratios of $9000, $11,000, $19,000, and $35,000 per quality-adjusted life year, respectively. Incremental cost-effectiveness ratios for the same screening intervals were higher for non-African Americans: $17,000, $23,000, $44,000, and $81,000 per quality-adjusted life year, respectively. In summary, these models suggest that screening African Americans for microalbuminuria at either 5- or 10-year intervals is highly cost-effective.
C1 [Hoerger, Thomas J.] RTI Int, Res Triangle Pk, NC 27709 USA.
[Wittenborn, John S.] Univ Chicago, NORC, Chicago, IL 60637 USA.
[Zhuo, Xiaohui; Pavkov, Meda E.; Burrows, Nilka R.; Jordan, Regina; Saydah, Sharon; Williams, Desmond E.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Eggers, Paul] NIDDKD, Bethesda, MD 20892 USA.
RP Hoerger, TJ (reprint author), RTI Int, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA.
EM tjh@rti.org
FU Centers for Disease Control and Prevention (CDC) [200-2002-00776,
200-2008-F-27527]
FX This research was supported by funding from the Centers for Disease
Control and Prevention (CDC) (Contracts 200-2002-00776 and
200-2008-F-27527). The findings and conclusions in this report are those
of the authors and do not necessarily represent the official position of
the CDC.
NR 20
TC 15
Z9 15
U1 0
U2 0
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD DEC
PY 2012
VL 23
IS 12
BP 2035
EP 2041
DI 10.1681/ASN.2012040347
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 047DX
UT WOS:000311819000016
PM 23204444
ER
PT J
AU Maiga, H
Dabire, RK
Lehmann, T
Tripet, F
Diabate, A
AF Maiga, Hamidou
Dabire, Roch K.
Lehmann, Tovi
Tripet, Frederic
Diabate, Abdoulaye
TI Variation in energy reserves and role of body size in the mating system
of Anopheles gambiae
SO JOURNAL OF VECTOR ECOLOGY
LA English
DT Article
DE Anopheles gambiae; males; sugar-feeding; mating success; energy
ID MOLECULAR M-FORM; DIPTERA-CULICIDAE; RAPID-DETERMINATION; SWARMING
BEHAVIOR; MALE MOSQUITOS; AEDES-AEGYPTI; FAT-BODY; SUCCESS; SUGAR;
GLYCOGEN
AB Anopheles gambiae mates in flight. Males gather at stationary places at sunset and compete for incoming females. Factors that account for male mating success are not known but are critical for the future of any genetic control strategy. The current study explored variations in nutritional reserves (sugars, glycogen, lipids, and proteins) in wild-caught swarming and resting males and evaluated the effect of body size and wing symmetry on male mating success. Our results showed that glycogen and sugar reserves are mobilized for flight. Males consume proportionally 5.9-fold as much energy derived from sugars in swarming activities than when they are at rest. Mated males were on average bigger than unmated ones (P<0.0001). A strong correlation between the left and right wings in both mated and unmated males was found and additional analysis on fluctuating asymmetry did not show any indication of mated males being more symmetrical than unmated ones. The distribution of wing size of mated males was focused around a central value, suggesting that intermediate size of males is advantageous in the An. gambiae mating system. The results are discussed in the context of sexual selection.
C1 [Maiga, Hamidou; Dabire, Roch K.; Diabate, Abdoulaye] Inst Natl Rech Sci Sante, Ctr Muraz, Bobo Dioulasso, Burkina Faso.
[Lehmann, Tovi] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Tripet, Frederic] Keele Univ, Keele ST5 5BG, Staffs, England.
RP Diabate, A (reprint author), Inst Natl Rech Sci Sante, Ctr Muraz, Bobo Dioulasso, Burkina Faso.
EM maigahamid@yahoo.fr
RI Tripet, Frederic/M-6693-2015
OI Tripet, Frederic/0000-0002-7939-0712
FU Multilateral Initiative on Malaria [TDR-MIM A80690]; MRC/DfID African
Research Leadership Award [97014]
FX We are grateful to Seni Ilboudo and Hyacinthe Guel for technical
assistance and Dr. Frederic Simard, Dr. Karine Mouline, Dr. Louis
Clement Gouagna, and Cecile Brengues for guidance on energy reserve
analysis. Many thanks to the mosquito collectors and the villagers who
allowed us to collect mosquitoes in their houses. This investigation was
funded by the Multilateral Initiative on Malaria (Grant ID: TDR-MIM
A80690) and the MRC/DfID African Research Leadership Award (Grant ID
97014).
NR 45
TC 8
Z9 9
U1 2
U2 22
PU SOC VECTOR ECOLOGY
PI CORONA
PA 1966 COMPTON AVE, CORONA, CA 92881 USA
SN 1081-1710
J9 J VECTOR ECOL
JI J. Vector Ecol.
PD DEC
PY 2012
VL 37
IS 2
BP 289
EP 297
DI 10.1111/j.1948-7134.2012.00230.x
PG 9
WC Entomology
SC Entomology
GA 044FK
UT WOS:000311604600006
PM 23181851
ER
PT J
AU Mott, BT
Cheng, KCC
Guha, R
Kommer, VP
Williams, DL
Vermeire, JJ
Cappello, M
Maloney, DJ
Rai, G
Jadhav, A
Simeonov, A
Inglese, J
Posner, GH
Thomas, CJ
AF Mott, Bryan T.
Cheng, Ken Chih-Chien
Guha, Rajarshi
Kommer, Valerie P.
Williams, David L.
Vermeire, Jon J.
Cappello, Michael
Maloney, David J.
Rai, Ganesha
Jadhav, Ajit
Simeonov, Anton
Inglese, James
Posner, Gary H.
Thomas, Craig J.
TI A furoxan-amodiaquine hybrid as a potential therapeutic for three
parasitic diseases
SO MEDCHEMCOMM
LA English
DT Article
ID INFECTED MICE; NITRIC-OXIDE; MALARIA; IDENTIFICATION; MEFLOQUINE;
DISCOVERY; HOOKWORM
AB Parasitic diseases continue to have a devastating impact on human populations worldwide. Lack of effective treatments, the high cost of existing ones, and frequent emergence of resistance to these agents provide a strong argument for the development of novel therapies. Here we report the results of a hybrid approach designed to obtain a dual acting molecule that would demonstrate activity against a variety of parasitic targets. The antimalarial drug amodiaquine has been covalently joined with a nitric oxide-releasing furoxan to achieve multiple mechanisms of action. Using in vitro and ex vivo assays, the hybrid molecule shows activity against three parasites - Plasmodium falciparum, Schistosoma mansoni, and Ancylostoma ceylanicum.
C1 [Mott, Bryan T.; Cheng, Ken Chih-Chien; Guha, Rajarshi; Maloney, David J.; Rai, Ganesha; Jadhav, Ajit; Simeonov, Anton; Inglese, James; Thomas, Craig J.] NIH, Div Preclin Innovat, Natl Ctr Advancing Translat Sci, Bethesda, MD 20892 USA.
[Mott, Bryan T.; Posner, Gary H.] Johns Hopkins Univ, Dept Chem, Zanvyl Krieger Sch Arts & Sci, Baltimore, MD 21218 USA.
[Kommer, Valerie P.; Williams, David L.] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA.
[Vermeire, Jon J.; Cappello, Michael] Yale Univ, Sch Med, Dept Pediat, Yale Child Hlth Res Ctr, New Haven, CT 06520 USA.
[Inglese, James] NHGRI, NIH, Bethesda, MD 20892 USA.
[Posner, Gary H.] Bloomberg Sch Publ Hlth, Johns Hopkins Malaria Res Inst, Baltimore, MD 21205 USA.
RP Thomas, CJ (reprint author), NIH, Div Preclin Innovat, Natl Ctr Advancing Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
EM craigt@mail.nih.gov
FU National Institute of Allergy and Infectious Diseases [AI065622]; NIH
Roadmap for Medical Research; Career Development Award [K22 A08476];
NIH/NIAID [HHSN272201000005I]; NIH [R37-AI-34885]
FX BTM would like to thank the NIH Graduate Partnership Program for
providing the opportunity to perform research across institutions. This
work was funded by National Institute of Allergy and Infectious Diseases
Grant AI065622 (DLW), the NIH Roadmap for Medical Research (CJT and JI),
and a Career Development Award to JJV (K22 A08476). Schistosome
materials for this work were supplied in part through NIH/NIAID contract
HHSN272201000005I to Dr Fred Lewis at the Biomedical Research Institute,
Rockville, MD. GHP acknowledges financial support from the NIH in the
form of grant R37-AI-34885.
NR 34
TC 8
Z9 8
U1 1
U2 16
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2040-2503
J9 MEDCHEMCOMM
JI MedChemComm
PD DEC
PY 2012
VL 3
IS 12
BP 1505
EP 1511
DI 10.1039/c2md20238g
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 043CM
UT WOS:000311520500004
PM 23205265
ER
PT J
AU Eccleston, JL
Koh, C
Markello, TC
Gahl, WA
Heller, T
AF Eccleston, Jason L.
Koh, Christopher
Markello, Thomas C.
Gahl, William A.
Heller, Theo
TI An apparent homozygous deletion in maltase-glucoamylase, a lesson in the
evolution of SNP arrays
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Single nucleotide polymorphism; Maltase-glucoamylase; Gene array
analysis; Genetic polymorphism; Genome-wide association study
ID GENOME-WIDE ASSOCIATION; DATABASE; DIGESTION; GLUCOSE
AB Single nucleotide polymorphism (SNP) arrays possess clinical potential due to their high throughput capacity, sensitivity and versatility. We used such an array to perform a genome-wide SNP analysis of a patient with a multi-system undiagnosed disease involving peripheral neuropathies and food intolerances. The patient had a homozygous deletion within the gene encoding maltase-glucoamylase (MGAM), an intestinal starch digestion enzyme, predicting absence of enzyme activity and potential starch indigestion. We then performed validation testing using a functional MGAM analysis that involved starch ingestion followed by measuring blood glucose and insulin levels as well as hydrogen breath levels. Gastrointestinal tissue was also obtained via endoscopy and immunohistochemical staining for intestinal MGAM was performed. Our results strongly suggest the presence and functioning of MGAM which disproved deficiency predictions based on SNP array analysis findings, classifying the deletion as a functional polymorphism. This study highlights a current clinical limitation of SNP arrays, i.e., distinguishing deleterious genomic alterations from misleading functional polymorphisms. We conclude that novel findings from SNP arrays should be clinically validated and published. Published by Elsevier Inc.
C1 [Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Eccleston, Jason L.; Koh, Christopher; Heller, Theo] NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Markello, Thomas C.; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Markello, Thomas C.; Gahl, William A.] NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA.
RP Gahl, WA (reprint author), NHGRI, Off Clin Director, NIH, Bldg 10,Room 10C103,10 Ctr Dr,MSC 1851, Bethesda, MD 20892 USA.
EM Bgahl@helix.nih.gov; TheoH@intra.niddk.nih.gov
FU NHGRI; NIDDK, NIH
FX This document was supported by the Intramural Research Programs of the
NHGRI and NIDDK, NIH. None of the authors has any conflict of interest
related to this research.
NR 23
TC 2
Z9 2
U1 1
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD DEC
PY 2012
VL 107
IS 4
BP 674
EP 678
DI 10.1016/j.ymgme.2012.10.013
PG 5
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 047CV
UT WOS:000311816200007
PM 23137569
ER
PT J
AU Niethamer, TK
Yardeni, T
Leoyklang, P
Ciccone, C
Astiz-Martinez, A
Jacobs, K
Dorward, HM
Zerfas, PM
Gahl, WA
Huizing, M
AF Niethamer, Terren K.
Yardeni, Tal
Leoyklang, Petcharat
Ciccone, Carla
Astiz-Martinez, Adrian
Jacobs, Katherine
Dorward, Heidi M.
Zerfas, Patricia M.
Gahl, William A.
Huizing, Marjan
TI Oral monosaccharide therapies to reverse renal and muscle
hyposialylation in a mouse model of GNE myopathy
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Glomerulopathy; Hyposialylation; Mannosamine; Myopathy; Sialic acid;
UDP-GlcNAc-2-epimerase/ManNAc kinase
ID INCLUSION-BODY MYOPATHY; ACETYLGLUCOSAMINE
2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; PHOSPHOMANNOSE ISOMERASE
DEFICIENCY; SINGLE PATIENT RESPONSE; N-ACETYLNEURAMINIC ACID; RIMMED
VACUOLES; SIALIC-ACID; DISTAL MYOPATHY; MANNOSE THERAPY; GENE LIPOPLEX
AB GNE myopathy, previously termed hereditary inclusion body myopathy (HIBM), is an adult-onset neuromuscular disorder characterized by progressive muscle weakness. The disorder results from biallelic mutations in GNE, encoding UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, the key enzyme of sialic acid synthesis. GNE myopathy, associated with impaired glycan sialylation, has no approved therapy. Here we test potential sialylation-increasing monosaccharides for their effectiveness in prophylaxis (at the embryonic and neonatal stages) and therapy (after the onset of symptoms) by evaluating renal and muscle hyposialylation in a knock-in mouse model (Gne p.M712T) of GNE myopathy. We demonstrate that oral mannosamine (ManN), but not sialic acid (Neu5Ac), mannose (Man), galactose (Gal), or glucosamine (GlcN), administered to pregnant female mice has a similar prophylactic effect on renal hyposialylation, pathology and neonatal survival of mutant offspring, as previously shown for N-acetylmannosamine (ManNAc) therapy. ManN may be converted to ManNAc by a direct, yet unknown, pathway, or may act through another mode of action. The other sugars (Man, Gal, GlcN) may either not cross the placental barrier (Neu5Ac) and/or may not be able to directly increase sialylation. Because GNE myopathy patients will likely require treatment in adulthood after onset of symptoms, we also administered ManNAc (1 or 2 g/kg/day for 12 weeks), Neu5Ac (2 g/kg/day for 12 weeks), or ManN (2 g/kg/day for 6 weeks) in drinking water to 6 month old mutant Gne p.M712T mice. All three therapies markedly improved the muscle and renal hyposialylation, as evidenced by lectin histochemistry for overall sialylation status and immunoblotting of specific sialoproteins. These preclinical data strongly support further evaluation of oral ManNAc, Neu5Ac and ManN as therapy for GNE myopathy and conceivably for certain glomerular diseases with hyposialylation. Published by Elsevier Inc.
C1 [Niethamer, Terren K.; Yardeni, Tal; Leoyklang, Petcharat; Ciccone, Carla; Astiz-Martinez, Adrian; Jacobs, Katherine; Dorward, Heidi M.; Gahl, William A.; 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.
[Zerfas, Patricia M.] NIH, Off Res Serv, Off Director, Bethesda, MD 20892 USA.
[Gahl, William A.] NIH, Off Rare Dis Res, Off Director, Bethesda, MD 20892 USA.
RP Huizing, M (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851,Bld 10,Rm 10C103, Bethesda, MD 20892 USA.
EM mhuizing@mail.nih.gov
FU National Human Genome Research Institute, National Institutes of Health,
Bethesda, Maryland, USA
FX This work was performed in partial fulfillment of the requirements for a
Ph.D. degree of T.Y. in the Sackler Faculty of Medicine of Tel Aviv
University. This study was supported by the Intramural Research Program
of the National Human Genome Research Institute, National Institutes of
Health, Bethesda, Maryland, USA.
NR 48
TC 16
Z9 17
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD DEC
PY 2012
VL 107
IS 4
BP 748
EP 755
DI 10.1016/j.ymgme.2012.10.011
PG 8
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 047CV
UT WOS:000311816200018
PM 23122659
ER
PT J
AU Sheehy, SH
Duncan, CJA
Elias, SC
Choudhary, P
Biswas, S
Halstead, FD
Collins, KA
Edwards, NJ
Douglas, AD
Anagnostou, NA
Ewer, KJ
Havelock, T
Mahungu, T
Bliss, CM
Miura, K
Poulton, ID
Lillie, PJ
Antrobus, RD
Berrie, E
Moyle, S
Gantlett, K
Colloca, S
Cortese, R
Long, CA
Sinden, RE
Gilbert, SC
Lawrie, AM
Doherty, T
Faust, SN
Nicosia, A
Hill, AVS
Draper, SJ
AF Sheehy, Susanne H.
Duncan, Christopher J. A.
Elias, Sean C.
Choudhary, Prateek
Biswas, Sumi
Halstead, Fenella D.
Collins, Katharine A.
Edwards, Nick J.
Douglas, Alexander D.
Anagnostou, Nicholas A.
Ewer, Katie J.
Havelock, Tom
Mahungu, Tabitha
Bliss, Carly M.
Miura, Kazutoyo
Poulton, Ian D.
Lillie, Patrick J.
Antrobus, Richard D.
Berrie, Eleanor
Moyle, Sarah
Gantlett, Katherine
Colloca, Stefano
Cortese, Riccardo
Long, Carole A.
Sinden, Robert E.
Gilbert, Sarah C.
Lawrie, Alison M.
Doherty, Tom
Faust, Saul N.
Nicosia, Alfredo
Hill, Adrian V. S.
Draper, Simon J.
TI ChAd63-MVA-vectored Blood-stage Malaria Vaccines Targeting MSP1 and
AMA1: Assessment of Efficacy Against Mosquito Bite Challenge in Humans
SO MOLECULAR THERAPY
LA English
DT Article
ID APICAL MEMBRANE ANTIGEN-1; MEROZOITE SURFACE PROTEIN-1;
POLYMERASE-CHAIN-REACTION; PLASMODIUM-FALCIPARUM; IMMUNE-RESPONSES;
PARASITE GROWTH; IN-VITRO; T-CELLS; ANTIBODY; PROTECTION
AB The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63 (ChAd63) followed by the attenuated orthopoxvirus MVA is safe and immunogenic in healthy adults. Here, we report on vaccine efficacy against controlled human malaria infection delivered by mosquito bites. The blood-stage malaria vaccines were administered alone, or together (MSP1+AMA1), or with a pre-erythrocytic malaria vaccine candidate (MSP1+ME-TRAP). In this first human use of coadministered ChAd63-MVA regimes, we demonstrate immune interference whereby responses against merozoite surface protein 1 (MSP1) are dominant over apical membrane antigen 1 (AMA1) and ME-TRAP. We also show that induction of strong cellular immunity against MSP1 and AMA1 is safe, but does not impact on parasite growth rates in the blood. In a subset of vaccinated volunteers, a delay in time to diagnosis was observed and sterilizing protection was observed in one volunteer coimmunized with MSP1+AMA1-results consistent with vaccine-induced pre-erythrocytic, rather than blood-stage, immunity. These data call into question the utility of T cell-inducing blood-stage malaria vaccines and suggest that the focus should remain on high-titer antibody induction against susceptible antigen targets.
C1 [Sheehy, Susanne H.; Duncan, Christopher J. A.; Anagnostou, Nicholas A.; Poulton, Ian D.; Lillie, Patrick J.; Antrobus, Richard D.; Gantlett, Katherine; Lawrie, Alison M.] Univ Oxford, Churchill Hosp, Ctr Clin Vaccinol & Trop Med, Jenner Inst, Oxford OX3 7LE, England.
[Elias, Sean C.; Choudhary, Prateek; Biswas, Sumi; Halstead, Fenella D.; Collins, Katharine A.; Edwards, Nick J.; Douglas, Alexander D.; Ewer, Katie J.; Bliss, Carly M.; Sinden, Robert E.; Gilbert, Sarah C.; Hill, Adrian V. S.; Draper, Simon J.] Univ Oxford, Jenner Inst Labs, Oxford OX3 7LE, England.
[Havelock, Tom; Faust, Saul N.] Univ Southampton, NIHR Wellcome Trust Clin Res Facil, Southampton, Hants, England.
[Havelock, Tom; Faust, Saul N.] Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England.
[Havelock, Tom; Faust, Saul N.] Univ Southampton, Fac Med, Acad Unit Clin & Expt Sci, Southampton SO9 5NH, Hants, England.
[Mahungu, Tabitha; Doherty, Tom] UCL, Clin Res Facil, Univ Coll Hosp, London, England.
[Miura, Kazutoyo; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Berrie, Eleanor; Moyle, Sarah] Univ Oxford, Churchill Hosp, Clin Biomfg Facil, Oxford OX3 7LE, England.
[Colloca, Stefano; Cortese, Riccardo; Nicosia, Alfredo] Okairos AG, Rome, Italy.
[Colloca, Stefano; Cortese, Riccardo; Nicosia, Alfredo] CEINGE, Naples, Italy.
[Sinden, Robert E.] Univ London Imperial Coll Sci Technol & Med, Div Cell & Mol Biol, London, England.
[Nicosia, Alfredo] Univ Naples Federico II, Dept Biochem & Med Biotechnol, Naples, Italy.
RP Sheehy, SH (reprint author), Univ Oxford, Churchill Hosp, Ctr Clin Vaccinol & Trop Med, Jenner Inst, Old Rd, Oxford OX3 7LE, England.
EM susanne.sheehy@ndm.ox.ac.uk
RI Draper, Simon/F-1758-2011; Faust, Saul/J-9779-2014; Douglas,
Alexander/E-7040-2012; Ewer, Katie/B-4328-2011;
OI Draper, Simon/0000-0002-9415-1357; Faust, Saul/0000-0003-3410-7642;
Douglas, Alexander/0000-0002-5410-7562; Ewer, Katie/0000-0001-9827-9836;
Edwards, Nick/0000-0002-7030-7839; Gilbert, Sarah/0000-0002-6823-9750;
Lillie, Patrick/0000-0002-4811-4774; Collins,
Katharine/0000-0002-7080-2215
FU European Malaria Vaccine Development Association; European Commission
[LSHP-CT-2007-037506, 242095]; UK Medical Research Council [G0700735,
G1000527]; UK National Institute of Health Research through the Oxford
Biomedical Research Centre [A91301]; Southampton NIHR Wellcome Trust
Clinical Research Facility; Wellcome Trust [084113/Z/07/Z, 45488/Z/05,
094449/Z/10/Z]; EVIMalaR; PATH Malaria Vaccine Initiative; Intramural
Program of the National Institutes of Health, National Institute of
Allergy and Infectious Diseases
FX We thank Cynthia Bateman, Mary Smith, Joel Meyer, Raquel Lopez-Ramon,
Roldan Singzon, Jung Ryu, Clare Grocott, and Filipa Martins for clinical
assistance; Laura Dinsmore for logistical support; Simon Correa, Kebba
Konteh, Peter Kalume, and Wycliffe Asava for microscopy expertise;
Jittawadee Murphy, Ken Baker, Andrew Blagborough, Mark Tunnicliff,
Brooke Bozick, Melissa Kapulu, and Arturo Reyes-Sandoval for assistance
with the controlled human malaria infection studies; Julie Furze,
Alexandra Spencer, Andrew Williams, Simon de Cassan, Emily Forbes, and
Drew Worth for laboratory assistance; Philip Bejon and Fiona Thompson
for advice on modeling parasite growth rates; and Laura Andrews, Chris
Schultz, Jake Matthews, Aisling Vaughan, Matthew Dicks, and Fionnadh
Carroll for assistance in quantitative PCR; the Jenner Institute Flow
Cytometry Core Facility for technical assistance; Sam Moretz, Ababacar
Diouf, and Gregory Tullo for technical support performing the growth
inhibitory activity assays; and all the study volunteers. This work was
supported by the European Malaria Vaccine Development Association, a
European Commission FP6-funded consortium (LSHP-CT-2007-037506); the UK
Medical Research Council (grant no. G0700735); the UK National Institute
of Health Research through the Oxford Biomedical Research Centre (A91301
Adult Vaccine), and the Southampton NIHR Wellcome Trust Clinical
Research Facility; the Wellcome Trust (084113/Z/07/Z); and EVIMalaR, an
European Commission FP7-funded programme (grant agreement no. 242095).
The growth inhibitory activity work was supported by the PATH Malaria
Vaccine Initiative and the Intramural Program of the National Institutes
of Health, National Institute of Allergy and Infectious Diseases.
S.C.G., A.V.S.H., and S.J.D. are Jenner Investigators; A.V.S.H. was
supported by a Wellcome Trust Principal Research Fellowship
(45488/Z/05); C.J.A.D. holds a Wellcome Trust Research Training
Fellowship (094449/Z/10/Z); and S.J.D. is a UK Medical Research Council
Career Development Fellow (G1000527). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript. A.D.D., S.C.G., A.V.S.H., and S.J.D. are
named inventors on patent applications covering malaria-vectored
vaccines and immunization regimens. Authors from Okairos are employees
of and/or shareholders in Okairos which is developing vectored vaccines
for malaria and other diseases. The others authors declared no conflict
of interest.
NR 50
TC 86
Z9 87
U1 0
U2 21
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD DEC
PY 2012
VL 20
IS 12
BP 2355
EP 2368
DI 10.1038/mt.2012.223
PG 14
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 048XO
UT WOS:000311946700018
PM 23089736
ER
PT J
AU Le Gallo, M
O'Hara, AJ
Rudd, ML
Urick, ME
Hansen, NF
O'Neil, NJ
Price, JC
Zhang, S
England, BM
Godwin, AK
Sgroi, DC
Hieter, P
Mullikin, JC
Merino, MJ
Bell, DW
AF Le Gallo, Matthieu
O'Hara, Andrea J.
Rudd, Meghan L.
Urick, Mary Ellen
Hansen, Nancy F.
O'Neil, Nigel J.
Price, Jessica C.
Zhang, Suiyuan
England, Bryant M.
Godwin, Andrew K.
Sgroi, Dennis C.
Hieter, Philip
Mullikin, James C.
Merino, Maria J.
Bell, Daphne W.
CA NIH Intramural Sequencing Ctr NISC
TI Exome sequencing of serous endometrial tumors identifies recurrent
somatic mutations in chromatin-remodeling and ubiquitin ligase complex
genes
SO NATURE GENETICS
LA English
DT Article
ID DNA-DAMAGE; HISTONE DEACETYLASE; FREQUENT MUTATIONS; RENAL-CARCINOMA;
PROSTATE-CANCER; CELL CARCINOMA; FACTOR CHD4; ARID1A; NURD; SUPPRESSOR
AB Endometrial cancer is the sixth most commonly diagnosed cancer in women worldwide, causing similar to 74,000 deaths annually(1). Serous endometrial cancers are a clinically aggressive subtype with a poorly defined genetic etiology(2-4). We used whole-exome sequencing to comprehensively search for somatic mutations within similar to 22,000 protein-encoding genes in 13 primary serous endometrial tumors. We subsequently resequenced 18 genes, which were mutated in more than 1 tumor and/or were components of an enriched functional grouping, from 40 additional serous tumors. We identified high frequencies of somatic mutations in CHD4 (17%), EP300 (8%), ARID1A (6%), TSPYL2 (6%), FBXW7 (29%), SPOP (8%), MAP3K4 (6%) and ABCC9 (6%). Overall, 36.5% of serous tumors had a mutated chromatin-remodeling gene, and 35% had a mutated ubiquitin ligase complex gene, implicating frequent mutational disruption of these processes in the molecular pathogenesis of one of the deadliest forms of endometrial cancer.
C1 [Le Gallo, Matthieu; O'Hara, Andrea J.; Rudd, Meghan L.; Urick, Mary Ellen; Price, Jessica C.; England, Bryant M.; Bell, Daphne W.] NHGRI, Canc Genet Branch, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA.
[Hansen, Nancy F.; Zhang, Suiyuan; Mullikin, James C.] NHGRI, Genome Technol Branch, US NIH, Bethesda, MD 20892 USA.
[O'Neil, Nigel J.; Hieter, Philip] Univ British Columbia, Michael Smith Labs, Vancouver, BC, Canada.
[Sgroi, Dennis C.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA.
[Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA.
[Mullikin, James C.; NIH Intramural Sequencing Ctr NISC] NISC, US NIH, Bethesda, MD USA.
[Merino, Maria J.] NCI, US NIH, Bethesda, MD 20892 USA.
RP Bell, DW (reprint author), NHGRI, Canc Genet Branch, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA.
EM belldaph@mail.nih.gov
RI O'Neil, Nigel/J-4012-2014;
OI O'Neil, Nigel/0000-0002-1992-6976; Le Gallo,
Matthieu/0000-0001-9085-8155
FU National Human Genome Research Institute, US NIH; NIH [R01CA112021,
R01CA140323, CA016519]; Avon Foundation; Ovarian Cancer Fund; Canadian
Institutes for Health Research [MOP-38096]
FX The study was funded in part by the Intramural Program of the National
Human Genome Research Institute, US NIH (D.W.B., J.C.M. and M.J.M.); NIH
grant R01CA112021 (D.C.S.); the Avon Foundation (D.C.S.); NIH grant
R01CA140323 (A.K.G.); and the Ovarian Cancer Fund (A.K.G.). P.H. is
supported by grants from the NIH (CA016519) and by the Canadian
Institutes for Health Research (MOP-38096).
NR 59
TC 140
Z9 143
U1 4
U2 37
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 DEC
PY 2012
VL 44
IS 12
BP 1310
EP 1315
DI 10.1038/ng.2455
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 045QZ
UT WOS:000311713200007
PM 23104009
ER
PT J
AU Lan, Q
Hsiung, CA
Matsuo, K
Hong, YC
Seow, A
Wang, ZM
Hosgood, HD
Chen, KX
Wang, JC
Chatterjee, N
Hu, W
Wong, MP
Zheng, W
Caporaso, N
Park, JY
Chen, CJ
Kim, YH
Kim, YT
Landi, MT
Shen, HB
Lawrence, C
Burdett, L
Yeager, M
Yuenger, J
Jacobs, KB
Chang, IS
Mitsudomi, T
Kim, HN
Chang, GC
Bassig, BA
Tucker, M
Wei, FS
Yin, ZH
Wu, C
An, SJ
Qian, BY
Lee, VHF
Lu, DR
Liu, JJ
Jeon, HS
Hsiao, CF
Sung, JS
Kim, JH
Gao, YT
Tsai, YH
Jung, YJ
Guo, H
Hu, ZB
Hutchinson, A
Wang, WC
Klein, R
Chung, CC
Oh, IJ
Chen, KY
Berndt, SI
He, XZ
Wu, W
Chang, J
Zhang, XC
Huang, MS
Zheng, H
Wang, JW
Zhao, XY
Li, YQ
Choi, JE
Su, WC
Park, KH
Sung, SW
Shu, XO
Chen, YM
Liu, L
Kang, CH
Hu, LM
Chen, CH
Pao, W
Kim, YC
Yang, TY
Xu, J
Guan, P
Tan, W
Su, J
Wang, CL
Li, HX
Sihoe, ADL
Zhao, ZH
Chen, Y
Choi, YY
Hung, JY
Kim, JS
Yoon, HI
Cai, QY
Lin, CC
Park, IK
Xu, P
Dong, J
Kim, C
He, QC
Perng, RP
Kohno, T
Kweon, SS
Chen, CY
Vermeulen, R
Wu, JJ
Lim, WY
Chen, KC
Chow, WH
Ji, BT
Chan, JKC
Chu, MJ
Li, YJ
Yokota, J
Li, JH
Chen, HY
Xiang, YB
Yu, CJ
Kunitoh, H
Wu, GP
Jin, L
Lo, YL
Shiraishi, K
Chen, YH
Lin, HC
Wu, TC
Wu, YL
Yang, PC
Zhou, BS
Shin, MH
Fraumeni, JF
Lin, DX
Chanock, SJ
Rothman, N
AF Lan, Qing
Hsiung, Chao A.
Matsuo, Keitaro
Hong, Yun-Chul
Seow, Adeline
Wang, Zhaoming
Hosgood, H. Dean, III
Chen, Kexin
Wang, Jiu-Cun
Chatterjee, Nilanjan
Hu, Wei
Wong, Maria Pik
Zheng, Wei
Caporaso, Neil
Park, Jae Yong
Chen, Chien-Jen
Kim, Yeul Hong
Kim, Young Tae
Landi, Maria Teresa
Shen, Hongbing
Lawrence, Charles
Burdett, Laurie
Yeager, Meredith
Yuenger, Jeffrey
Jacobs, Kevin B.
Chang, I-Shou
Mitsudomi, Tetsuya
Kim, Hee Nam
Chang, Gee-Chen
Bassig, Bryan A.
Tucker, Margaret
Wei, Fusheng
Yin, Zhihua
Wu, Chen
An, She-Juan
Qian, Biyun
Lee, Victor Ho Fun
Lu, Daru
Liu, Jianjun
Jeon, Hyo-Sung
Hsiao, Chin-Fu
Sung, Jae Sook
Kim, Jin Hee
Gao, Yu-Tang
Tsai, Ying-Huang
Jung, Yoo Jin
Guo, Huan
Hu, Zhibin
Hutchinson, Amy
Wang, Wen-Chang
Klein, Robert
Chung, Charles C.
Oh, In-Jae
Chen, Kuan-Yu
Berndt, Sonja I.
He, Xingzhou
Wu, Wei
Chang, Jiang
Zhang, Xu-Chao
Huang, Ming-Shyan
Zheng, Hong
Wang, Junwen
Zhao, Xueying
Li, Yuqing
Choi, Jin Eun
Su, Wu-Chou
Park, Kyong Hwa
Sung, Sook Whan
Shu, Xiao-Ou
Chen, Yuh-Min
Liu, Li
Kang, Chang Hyun
Hu, Lingmin
Chen, Chung-Hsing
Pao, William
Kim, Young-Chul
Yang, Tsung-Ying
Xu, Jun
Guan, Peng
Tan, Wen
Su, Jian
Wang, Chih-Liang
Li, Haixin
Sihoe, Alan Dart Loon
Zhao, Zhenhong
Chen, Ying
Choi, Yi Young
Hung, Jen-Yu
Kim, Jun Suk
Yoon, Ho-Il
Cai, Qiuyin
Lin, Chien-Chung
Park, In Kyu
Xu, Ping
Dong, Jing
Kim, Christopher
He, Qincheng
Perng, Reury-Perng
Kohno, Takashi
Kweon, Sun-Seog
Chen, Chih-Yi
Vermeulen, Roel
Wu, Junjie
Lim, Wei-Yen
Chen, Kun-Chieh
Chow, Wong-Ho
Ji, Bu-Tian
Chan, John K. C.
Chu, Minjie
Li, Yao-Jen
Yokota, Jun
Li, Jihua
Chen, Hongyan
Xiang, Yong-Bing
Yu, Chong-Jen
Kunitoh, Hideo
Wu, Guoping
Jin, Li
Lo, Yen-Li
Shiraishi, Kouya
Chen, Ying-Hsiang
Lin, Hsien-Chih
Wu, Tangchun
Wu, Yi-Long
Yang, Pan-Chyr
Zhou, Baosen
Shin, Min-Ho
Fraumeni, Joseph F., Jr.
Lin, Dongxin
Chanock, Stephen J.
Rothman, Nathaniel
TI Genome-wide association analysis identifies new lung cancer
susceptibility loci in never-smoking women in Asia
SO NATURE GENETICS
LA English
DT Article
ID RISK; SMOKERS; ADENOCARCINOMA; CHINESE; VARIANTS; KINASES; DISEASE;
VTI1A; 15Q25; POPULATIONS
AB To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer' cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 x 10(-6)) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 x 10(-18)), 6q22.2 (rs9387478, P = 4.14 x 10(-10)) and 6p21.32 (rs2395185, P = 9.51 x 10(-9)). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.
C1 [Lan, Qing; Wang, Zhaoming; Burdett, Laurie; Yeager, Meredith; Yuenger, Jeffrey; Jacobs, Kevin B.; Hutchinson, Amy] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Hsiung, Chao A.; Hsiao, Chin-Fu; Wang, Wen-Chang; Lo, Yen-Li; Chen, Ying-Hsiang; Lin, Hsien-Chih] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan, Taiwan.
[Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan.
[Hong, Yun-Chul] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Seow, Adeline; Chen, Ying; Lim, Wei-Yen] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Hosgood, H. Dean, III] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Chen, Kexin; Qian, Biyun; Zheng, Hong; Li, Haixin] Tianjin Med Univ, Canc Inst & Hosp, Dept Epidemiol & Biostat, Tianjin, Peoples R China.
[Wang, Jiu-Cun; Lu, Daru; Zhao, Xueying; Zhao, Zhenhong; Wu, Junjie; Chen, Hongyan; Jin, Li] Fudan Univ, Sch Life Sci, Key Lab Contemporary Anthropol, Minist Educ, Shanghai 200433, Peoples R China.
[Wang, Jiu-Cun; Lu, Daru; Zhao, Xueying; Zhao, Zhenhong; Wu, Junjie; Chen, Hongyan; Jin, Li] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
[Wong, Maria Pik] Univ Hong Kong, Li Ka Shing LKS Fac Med, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Zheng, Wei; Shu, Xiao-Ou; Cai, Qiuyin] Vanderbilt Univ, Dept Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Inst Med & Publ Hlth, Nashville, TN USA.
[Park, Jae Yong] Kyungpook Natl Univ, Med Ctr, Lung Canc Ctr, Taegu, South Korea.
[Chen, Chien-Jen; Li, Yao-Jen] Genom Res Ctr, Taipei, Taiwan.
[Kim, Yeul Hong; Sung, Jae Sook; Park, Kyong Hwa] Korea Univ, Coll Med, Anam Hosp, Dept Internal Med,Div Oncol Hematol, Seoul 136705, South Korea.
[Kim, Young Tae; Jung, Yoo Jin; Kang, Chang Hyun; Park, In Kyu] Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Thorac & Cardiovasc Surg, Seoul, South Korea.
[Shen, Hongbing; Hu, Zhibin; Hu, Lingmin; Dong, Jing; Chu, Minjie] Nanjing Med Univ, Key Lab Modern Toxicol, Minist Educ, Nanjing, Jiangsu, Peoples R China.
[Shen, Hongbing; Hu, Zhibin; Hu, Lingmin; Dong, Jing; Chu, Minjie] Nanjing Med Univ, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Jiangsu, Peoples R China.
[Lawrence, Charles] Westat Corp, Rockville, MD USA.
[Chang, I-Shou; Chen, Chung-Hsing] Natl Hlth Res Inst, Natl Inst Canc Res, Zhunan, Taiwan.
[Mitsudomi, Tetsuya] Kinki Univ, Sch Med, Div Thorac Surg, Sayama, Osaka 589, Japan.
[Kim, Hee Nam] Chonnam Natl Univ, Hwasun Hosp, Genome Res Ctr Hematopoiet Dis, Hwasun Eup, South Korea.
[Chang, Gee-Chen; Chen, Yuh-Min] Natl Yang Ming Univ, Sch Med, Dept Med, Taipei, Taiwan.
[Chang, Gee-Chen; Yang, Tsung-Ying; Chen, Kun-Chieh] Taichung Vet Gen Hosp, Dept Internal Med, Div Chest Med, Taichung, Taiwan.
[Bassig, Bryan A.] Yale Univ, Sch Publ Hlth, Div Environm Hlth Sci, New Haven, CT USA.
[Wei, Fusheng; Wu, Guoping] China Natl Environm Monitoring Ctr, Beijing, Peoples R China.
[Yin, Zhihua; Wu, Wei; Guan, Peng; He, Qincheng; Zhou, Baosen] China Med Univ, Sch Publ Hlth, Dept Epidemiol, Shenyang, Peoples R China.
[Wu, Chen; Chang, Jiang; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Etiol & Carcinogenesis, Beijing 100730, Peoples R China.
[Wu, Chen; Chang, Jiang; Tan, Wen; Lin, Dongxin] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Wu, Chen; Chang, Jiang; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100021, Peoples R China.
[An, She-Juan; Zhang, Xu-Chao; Su, Jian; Wu, Yi-Long] Guangdong Acad Med Sci, Guangdong Gen Hosp, Med Res Ctr, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China.
[An, She-Juan; Zhang, Xu-Chao; Su, Jian; Wu, Yi-Long] Guangdong Acad Med Sci, Guangdong Gen Hosp, Ctr Canc, Guangzhou, Guangdong, Peoples R China.
[Lee, Victor Ho Fun] Univ Hong Kong, LKS Fac Med, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China.
[Liu, Jianjun; Li, Yuqing] Genome Inst Singapore, Dept Human Genet, Singapore, Singapore.
[Liu, Jianjun] Anhui Med Univ, Sch Life Sci, Hefei, Peoples R China.
[Jeon, Hyo-Sung; Choi, Jin Eun; Choi, Yi Young] Kyungpook Natl Univ, Med Ctr, Canc Res Ctr, Taegu, South Korea.
[Kim, Jin Hee] Seoul Natl Univ, Med Res Ctr, Inst Environm Med, Seoul, South Korea.
[Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Tsai, Ying-Huang] Chang Gung Mem Hosp, Dept Resp Therapy, Chiayi, Taiwan.
[Guo, Huan; Wu, Tangchun] Huazhong Univ Sci & Technol, Sch Publ Hlth, Inst Occupat Med, Wuhan 430074, Peoples R China.
[Guo, Huan; Wu, Tangchun] Huazhong Univ Sci & Technol, Sch Publ Hlth, Minist Educ, Key Lab Environm & Hlth, Wuhan 430074, Peoples R China.
[Klein, Robert; Wu, Tangchun] Mem Sloan Kettering Canc Ctr, Program Canc Biol & Genet, New York, NY 10021 USA.
[Oh, In-Jae; Kim, Young-Chul] Chonnam Natl Univ, Hwasun Hosp, Lung & Esophageal Canc Clin, Hwasun Eup, South Korea.
[Oh, In-Jae; Kim, Young-Chul] Chonnam Natl Univ, Sch Med, Dept Internal Med, Kwangju, South Korea.
[Chen, Kuan-Yu; Yu, Chong-Jen] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan.
[He, Xingzhou] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China.
[Huang, Ming-Shyan; Hung, Jen-Yu] Kaohsiung Med Univ, Sch Med, Kaohsiung Med Univ Hosp, Dept Internal Med, Kaohsiung, Taiwan.
[Wang, Junwen] Univ Hong Kong, LKS Fac Med, Dept Biochem, Hong Kong, Hong Kong, Peoples R China.
[Wang, Junwen] Univ Hong Kong, LKS Fac Med, Ctr Genom Sci, Hong Kong, Hong Kong, Peoples R China.
[Su, Wu-Chou; Lin, Chien-Chung] Natl Cheng Kung Univ, Coll Med, Natl Cheng Kung Univ Hosp, Dept Internal Med, Tainan 70101, Taiwan.
[Sung, Sook Whan] Seoul Natl Univ, Bundang Hosp, Dept Thorac & Cardiovasc Surg, Songnam, South Korea.
[Chen, Yuh-Min; Perng, Reury-Perng] Taipei Vet Gen Hosp, Chest Dept, Taipei, Taiwan.
[Liu, Li] Huazhong Univ Sci & Technol, Union Hosp, Ctr Canc, Wuhan 430074, Peoples R China.
[Pao, William] Vanderbilt Univ, Med Ctr, Div Hematol & Oncol, Nashville, TN USA.
[Xu, Jun] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
[Wang, Chih-Liang] Chang Gung Mem Hosp, Dept Pulm & Crit Care, Tao Yuan, Taiwan.
[Sihoe, Alan Dart Loon] Queen Mary Hosp, Div Cardiothorac Surg, Dept Surg, Hong Kong, Hong Kong, Peoples R China.
[Kim, Jun Suk] Korea Univ, Coll Med, Guro Hosp, Dept Internal Med,Div Med Oncol, Seoul 136705, South Korea.
[Yoon, Ho-Il] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, South Korea.
[Xu, Ping] Wuhan Iron & Steel Corp Staff Worker Hosp, Dept Oncol, Wuhan, Peoples R China.
[Kohno, Takashi; Shiraishi, Kouya] Natl Canc Ctr, Res Inst, Div Genome Biol, Tokyo 104, Japan.
[Kweon, Sun-Seog] Chonnam Natl Univ, Hwasun Hosp, Jeonnam Reg Canc Ctr, Hwasun Eup, South Korea.
[Kweon, Sun-Seog; Shin, Min-Ho] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Kwangju, South Korea.
[Chen, Chih-Yi] China Med Univ & Hosp, Ctr Canc, Taichung, Taiwan.
[Vermeulen, Roel] Univ Utrecht, IRAS, Div Environm Epidemiol, Utrecht, Netherlands.
[Chan, John K. C.] Queen Elizabeth Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Yokota, Jun] Natl Canc Ctr, Res Inst, Div Multistep Carcinogenesis, Tokyo 104, Japan.
[Li, Jihua] Qujing Ctr Dis Control & Prevent, Sanjiangdadao, Qujing, Peoples R China.
[Kunitoh, Hideo] Mitsui Mem Hosp, Dept Resp Med, Tokyo 101, Japan.
[Yang, Pan-Chyr] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei, Taiwan.
RP Lan, Q (reprint author), NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM qingl@mail.nih.gov
RI Wang, Jiucun/J-8744-2012; Kang, Chang-Hyun/J-5364-2012; Yoon, Ho
Il/J-5567-2012; Chen, Chien-Jen/C-6976-2008; Chang, I-Shou/D-2084-2010;
Klein, Robert/K-1888-2013; Hsiung, Chao Agnes/E-3994-2010; Hu,
Wei/M-3524-2013; Hsiao, Chin-Fu/E-3993-2010; Wang, Junwen/C-4432-2009;
Jin, Li/C-1468-2009; Tucker, Margaret/B-4297-2015; Vermeulen,
Roel/F-8037-2011; Wang, Junwen/D-3700-2011;
OI Wang, Jiucun/0000-0003-2765-0620; Klein, Robert/0000-0003-3539-5391;
Jin, Li/0000-0002-4546-2415; Vermeulen, Roel/0000-0003-4082-8163; Wang,
Junwen/0000-0002-4432-4707; Kim, Hee Nam/0000-0002-6153-2612; Wu,
Yi-Long/0000-0002-3611-0258; Mitsudomi, Tetsuya/0000-0001-9860-8505; Yu,
Chong-Jen/0000-0001-5664-9392; YANG, PAN-CHYR/0000-0001-6330-6048; Shin,
Min-Ho/0000-0002-2217-5624; KWEON, SUNSEOG/0000-0003-2378-8550; Matsuo,
Keitaro/0000-0003-1761-6314
FU US National Institutes of Health/National Cancer Institute
FX We thank J.-J. Yang, X.-N. Yang, Q. Zhou, W.-B. Guo, S.-L. Chen, Y.
Huang, Z. Xie, J.-G. Chen, H.-H. Yan, K. Tajima, Y. Yatabe, T. Hida,
K.-L. Chuah, A. Ng, P. Cog, S.-S. Leong, M.-K. Ang, E. Lim, T.-K. Lim,
M.Teh, W-T. Poh and A. Tee. The overall GWAS project was supported by
the intramural program of the US National Institutes of Health/National
Cancer Institute. A list of support provided to individual studies is
provided in the Supplementary Note.
NR 48
TC 105
Z9 109
U1 9
U2 67
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 DEC
PY 2012
VL 44
IS 12
BP 1330
EP 1335
DI 10.1038/ng.2456
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 045QZ
UT WOS:000311713200011
PM 23143601
ER
PT J
AU Tsoi, LC
Spain, SL
Knight, J
Ellinghaus, E
Stuart, PE
Capon, F
Ding, J
Li, YM
Tejasvi, T
Gudjonsson, JE
Kang, HM
Allen, MH
McManus, R
Novelli, G
Samuelsson, L
Schalkwijk, J
Stahle, M
Burden, AD
Smith, CH
Cork, MJ
Estivill, X
Bowcock, AM
Krueger, GG
Weger, W
Worthington, J
Tazi-Ahnini, R
Nestle, FO
Hayday, A
Hoffmann, P
Winkelmann, J
Wijmenga, C
Langford, C
Edkins, S
Andrews, R
Blackburn, H
Strange, A
Band, G
Pearson, RD
Vukcevic, D
Spencer, CCA
Deloukas, P
Mrowietz, U
Schreiber, S
Weidinger, S
Koks, S
Kingo, K
Esko, T
Metspalu, A
Lim, HW
Voorhees, JJ
Weichenthal, M
Wichmann, HE
Chandran, V
Rosen, CF
Rahman, P
Gladman, DD
Griffiths, CEM
Reis, A
Kere, J
Nair, RP
Franke, A
Barker, JNWN
Abecasis, GR
Elder, JT
Trembath, RC
Duffin, KC
Helms, C
Goldgar, D
Li, Y
Paschall, J
Malloy, MJ
Pullinger, CR
Kane, JP
Gardner, J
Perlmutter, A
Miner, A
Feng, BJ
Hiremagalore, R
Ike, RW
Christophers, E
Henseler, T
Ruether, A
Schrodi, SJ
Prahalad, S
Guthery, SL
Fischer, J
Liao, W
Kwok, P
Menter, A
Lathrop, GM
Wise, C
Begovich, AB
Onoufriadis, A
Weale, ME
Hofer, A
Salmhofer, W
Wolf, P
Kainu, K
Saarialho-Kere, U
Suomela, S
Badorf, P
Huffmeier, U
Kurrat, W
Kuster, W
Lascorz, J
Mossner, R
Schurmeier-Horst, F
Stander, M
Traupe, H
Bergboer, JGM
den Heijer, M
van de Kerkhof, PCV
Zeeuwen, PLJM
Barnes, L
Campbell, LE
Cusack, C
Coleman, C
Conroy, J
Ennis, S
Fitzgerald, O
Gallagher, P
Irvine, AD
Kirby, B
Markham, T
McLean, WHI
McPartlin, J
Rogers, SF
Ryan, AW
Zawirska, A
Giardina, E
Lepre, T
Perricone, C
Martin-Ezquerra, G
Pujol, RM
Riveira-Munoz, E
Inerot, A
Naluai, AT
Mallbris, L
Wolk, K
Leman, J
Barton, A
Warren, RB
Young, HS
Ricano-Ponce, I
Trynka, G
Pellett, FJ
Henschel, A
Aurand, M
Bebo, B
Gieger, C
Illig, T
Moebus, S
Jockel, KH
Erbe, R
Donnelly, P
Peltonen, L
Blackwell, JM
Bramon, E
Brown, MA
Casas, JP
Corvin, A
Craddock, N
Duncanson, A
Jankowski, J
Markus, HS
Mathew, CG
McCarthy, MI
Palmer, CNA
Plomin, R
Rautanen, A
Sawcer, SJ
Samani, N
Viswanathan, AC
Wood, NW
Bellenguez, C
Freeman, C
Hellenthal, G
Giannoulatou, E
Pirinen, M
Su, Z
Hunt, SE
Gwilliam, R
Bumpstead, SJ
Dronov, S
Gillman, M
Gray, E
Hammond, N
Jayakumar, A
McCann, OT
Liddle, J
Perez, ML
Potter, SC
Ravindrarajah, R
Ricketts, M
Waller, M
Weston, P
Widaa, S
Whittaker, P
AF Tsoi, Lam C.
Spain, Sarah L.
Knight, Jo
Ellinghaus, Eva
Stuart, Philip E.
Capon, Francesca
Ding, Jun
Li, Yanming
Tejasvi, Trilokraj
Gudjonsson, Johann E.
Kang, Hyun M.
Allen, Michael H.
McManus, Ross
Novelli, Giuseppe
Samuelsson, Lena
Schalkwijk, Joost
Stahle, Mona
Burden, A. David
Smith, Catherine H.
Cork, Michael J.
Estivill, Xavier
Bowcock, Anne M.
Krueger, Gerald G.
Weger, Wolfgang
Worthington, Jane
Tazi-Ahnini, Rachid
Nestle, Frank O.
Hayday, Adrian
Hoffmann, Per
Winkelmann, Juliane
Wijmenga, Cisca
Langford, Cordelia
Edkins, Sarah
Andrews, Robert
Blackburn, Hannah
Strange, Amy
Band, Gavin
Pearson, Richard D.
Vukcevic, Damjan
Spencer, Chris C. A.
Deloukas, Panos
Mrowietz, Ulrich
Schreiber, Stefan
Weidinger, Stephan
Koks, Sulev
Kingo, Kuelli
Esko, Tonu
Metspalu, Andres
Lim, Henry W.
Voorhees, John J.
Weichenthal, Michael
Wichmann, H. Erich
Chandran, Vinod
Rosen, Cheryl F.
Rahman, Proton
Gladman, Dafna D.
Griffiths, Christopher E. M.
Reis, Andre
Kere, Juha
Nair, Rajan P.
Franke, Andre
Barker, Jonathan N. W. N.
Abecasis, Goncalo R.
Elder, James T.
Trembath, Richard C.
Duffin, Kristina Callis
Helms, Cindy
Goldgar, David
Li, Yun
Paschall, Justin
Malloy, Mary J.
Pullinger, Clive R.
Kane, John P.
Gardner, Jennifer
Perlmutter, Amy
Miner, Andrew
Feng, Bing Jian
Hiremagalore, Ravi
Ike, Robert W.
Christophers, Enno
Henseler, Tilo
Ruether, Andreas
Schrodi, Steven J.
Prahalad, Sampath
Guthery, Stephen L.
Fischer, Judith
Liao, Wilson
Kwok, Pui
Menter, Alan
Lathrop, G. Mark
Wise, C.
Begovich, Ann B.
Onoufriadis, Alexandros
Weale, Michael E.
Hofer, Angelika
Salmhofer, Wolfgang
Wolf, Peter
Kainu, Kati
Saarialho-Kere, Ulpu
Suomela, Sari
Badorf, Petra
Hueffmeier, Ulrike
Kurrat, Werner
Kuester, Wolfgang
Lascorz, Jesus
Moessner, Rotraut
Schuermeier-Horst, Funda
Staender, Markward
Traupe, Heiko
Bergboer, Judith G. M.
den Heijer, Martin
van de Kerkhof, Peter C.
Zeeuwen, Patrick L. J. M.
Barnes, Louise
Campbell, Linda E.
Cusack, Caitriona
Coleman, Ciara
Conroy, Judith
Ennis, Sean
Fitzgerald, Oliver
Gallagher, Phil
Irvine, Alan D.
Kirby, Brian
Markham, Trevor
McLean, W. H. Irwin
McPartlin, Joe
Rogers, Sarah F.
Ryan, Anthony W.
Zawirska, Agnieszka
Giardina, Emiliano
Lepre, Tiziana
Perricone, Carlo
Martin-Ezquerra, Gemma
Pujol, Ramon M.
Riveira-Munoz, Eva
Inerot, Annica
Naluai, Asa T.
Mallbris, Lotus
Wolk, Katarina
Leman, Joyce
Barton, Anne
Warren, Richard B.
Young, Helen S.
Ricano-Ponce, Isis
Trynka, Gosia
Pellett, Fawnda J.
Henschel, Andrew
Aurand, Marin
Bebo, Bruce
Gieger, Christian
Illig, Thomas
Moebus, Susanne
Joeckel, Karl-Heinz
Erbe, Raimund
Donnelly, Peter
Peltonen, Leena
Blackwell, Jenefer M.
Bramon, Elvira
Brown, Matthew A.
Casas, Juan P.
Corvin, Aiden
Craddock, Nicholas
Duncanson, Audrey
Jankowski, Janusz
Markus, Hugh S.
Mathew, Christopher G.
McCarthy, Mark I.
Palmer, Colin N. A.
Plomin, Robert
Rautanen, Anna
Sawcer, Stephen J.
Samani, Nilesh
Viswanathan, Ananth C.
Wood, Nicholas W.
Bellenguez, Celine
Freeman, Colin
Hellenthal, Garrett
Giannoulatou, Eleni
Pirinen, Matti
Su, Zhan
Hunt, Sarah E.
Gwilliam, Rhian
Bumpstead, Suzannah J.
Dronov, Serge
Gillman, Matthew
Gray, Emma
Hammond, Naomi
Jayakumar, Alagurevathi
McCann, Owen T.
Liddle, Jennifer
Perez, Marc L.
Potter, Simon C.
Ravindrarajah, Radhi
Ricketts, Michelle
Waller, Matthew
Weston, Paul
Widaa, Sara
Whittaker, Pamela
CA Collaborative Assoc Study Psoriasi
Genetic Anal Psoriasis Consortium
Psoriasis Assoc Genetics Extension
Wellcome Trust Case Control Consor
TI Identification of 15 new psoriasis susceptibility loci highlights the
role of innate immunity
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; T-CELL DEVELOPMENT; GENE-EXPRESSION;
CELIAC-DISEASE; TH17 DIFFERENTIATION; SIGNALING PATHWAYS; NEGATIVE
REGULATOR; INTERFERON-GAMMA; COMMON VARIANTS; MULTIPLE COMMON
AB To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TA GAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-kappa B signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.
C1 [Spain, Sarah L.; Capon, Francesca; Allen, Michael H.; Nestle, Frank O.; Barker, Jonathan N. W. N.; Trembath, Richard C.; Onoufriadis, Alexandros; Weale, Michael E.; Mathew, Christopher G.; Viswanathan, Ananth C.] Kings Coll London, Div Genet & Mol Med, London WC2R 2LS, England.
[Tsoi, Lam C.; Ding, Jun; Li, Yanming; Kang, Hyun M.; Abecasis, Goncalo R.; Li, Yun] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Knight, Jo] Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Knight, Jo] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Biomed Res Ctr, NIHR, London, England.
[Ellinghaus, Eva; Schreiber, Stefan; Franke, Andre; Ruether, Andreas] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
[Stuart, Philip E.; Tejasvi, Trilokraj; Gudjonsson, Johann E.; Voorhees, John J.; Nair, Rajan P.; Elder, James T.; Hiremagalore, Ravi] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA.
[McManus, Ross; Barnes, Louise; Coleman, Ciara; Conroy, Judith; Ennis, Sean; McPartlin, Joe; Ryan, Anthony W.] St James Hosp, Trinity Coll Dublin, Dept Clin Med, Dublin, Ireland.
[McManus, Ross; Barnes, Louise; Coleman, Ciara; Conroy, Judith; Ennis, Sean; McPartlin, Joe; Ryan, Anthony W.] Trinity Coll Dublin, Inst Mol Med, Dublin, Ireland.
[Novelli, Giuseppe; Giardina, Emiliano; Lepre, Tiziana; Perricone, Carlo] Natl Agcy Evaluat Univ & Res Inst ANVUR, Rome, Italy.
[Novelli, Giuseppe] San Pietro Hosp, Res Ctr, Rome, Italy.
[Samuelsson, Lena; Naluai, Asa T.] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med & Clin Genet, Gothenburg, Sweden.
[Schalkwijk, Joost; Bergboer, Judith G. M.; van de Kerkhof, Peter C.; Zeeuwen, Patrick L. J. M.] Radboud Univ Nijmegen, Med Ctr, Dept Dermatol, NL-6525 ED Nijmegen, Netherlands.
[Stahle, Mona; Mallbris, Lotus; Wolk, Katarina] Karolinska Inst, Dept Med, Dermatol Unit, Stockholm, Sweden.
[Burden, A. David; Leman, Joyce] Univ Glasgow, Western Infirm, Dept Dermatol, Glasgow G11 6NT, Lanark, Scotland.
[Smith, Catherine H.; Barker, Jonathan N. W. N.] Kings Coll London, St Johns Inst Dermatol, London WC2R 2LS, England.
[Cork, Michael J.; Tazi-Ahnini, Rachid] Univ Sheffield, Dept Infect & Immun, Acad Unit Dermatol Res, Sheffield, S Yorkshire, England.
[Estivill, Xavier; Riveira-Munoz, Eva] CRG, Genes & Dis Programme, Barcelona, Spain.
[Estivill, Xavier; Riveira-Munoz, Eva] Pompeu Fabra Univ, Hosp Mar, Res Inst, Barcelona, Spain.
[Estivill, Xavier; Riveira-Munoz, Eva] Publ Hlth & Epidemiol Network Biomed Res Ctr CIBE, Barcelona, Spain.
[Bowcock, Anne M.; Helms, Cindy; Gardner, Jennifer] Washington Univ, Sch Med, Dept Genet, Div Human Genet, St Louis, MO 63110 USA.
[Krueger, Gerald G.; Duffin, Kristina Callis; Goldgar, David; Feng, Bing Jian] Univ Utah, Dept Dermatol, Salt Lake City, UT USA.
[Weger, Wolfgang; Hofer, Angelika; Salmhofer, Wolfgang; Wolf, Peter] Med Univ Graz, Dept Dermatol, Graz, Austria.
[Worthington, Jane; Barton, Anne] Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Epidemiol Unit, Manchester, Lancs, England.
[Hayday, Adrian] Kings Coll London, Div Immunol Infect & Inflammatory Dis, London WC2R 2LS, England.
[Hoffmann, Per] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Hoffmann, Per] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany.
[Winkelmann, Juliane] Tech Univ Munich, Dept Neurol, Munich, Germany.
[Winkelmann, Juliane; Duncanson, Audrey] Tech Univ Munich, Inst Human Genet, Munich, Germany.
[Winkelmann, Juliane] German Res Ctr Environm Hlth, Helmholtz Zentrum Munich, Inst Human Genet, Munich, Germany.
[Wijmenga, Cisca; Ricano-Ponce, Isis; Trynka, Gosia] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands.
[Wijmenga, Cisca; Ricano-Ponce, Isis; Trynka, Gosia] Univ Groningen, Groningen, Netherlands.
[Langford, Cordelia; Edkins, Sarah; Andrews, Robert; Blackburn, Hannah; Deloukas, Panos; Peltonen, Leena; Hunt, Sarah E.; Gwilliam, Rhian; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Perez, Marc L.; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela] Wellcome Trust Sanger Inst, Cambridge, England.
[Strange, Amy; Band, Gavin; Pearson, Richard D.; Vukcevic, Damjan; Spencer, Chris C. A.; Donnelly, Peter; Rautanen, Anna; Bellenguez, Celine; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Su, Zhan] Wellcome Trust Ctr Human Genet, Oxford, England.
[Mrowietz, Ulrich; Weidinger, Stephan; Weichenthal, Michael; Christophers, Enno; Henseler, Tilo] Univ Kiel, Dept Dermatol, Univ Hosp, D-2300 Kiel, Germany.
[Schreiber, Stefan] Univ Hosp Schleswig Holstein, PopGen Biobank, Kiel, Germany.
[Koks, Sulev] Univ Tartu, Ctr Translat Med, Dept Physiol, EE-50090 Tartu, Estonia.
[Koks, Sulev] Univ Tartu, Ctr Translat Genom, EE-50090 Tartu, Estonia.
[Kingo, Kuelli] Univ Tartu, Dept Dermatol & Venerol, EE-50090 Tartu, Estonia.
[Esko, Tonu; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Lim, Henry W.] Henry Ford Hosp, Dept Dermatol, Detroit, MI 48202 USA.
[Wichmann, H. Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munich, Inst Epidemiol 1, Neuherberg, Germany.
[Wichmann, H. Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H. Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Chandran, Vinod; Gladman, Dafna D.; Pellett, Fawnda J.] Univ Toronto, Toronto Western Hosp, Div Rheumatol, Dept Med, Toronto, ON M5T 2S8, Canada.
[Rosen, Cheryl F.] Univ Toronto, Toronto Western Hosp, Div Dermatol, Dept Med, Toronto, ON M5T 2S8, Canada.
[Rahman, Proton] Mem Univ Newfoundland, Dept Med, St John, NF, Canada.
[Griffiths, Christopher E. M.; Warren, Richard B.; Young, Helen S.] Univ Manchester, Salford Royal NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Reis, Andre; Badorf, Petra; Hueffmeier, Ulrike] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany.
[Kere, Juha] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
[Kere, Juha] Folkhalsan Inst Genet, Helsinki, Finland.
[Kere, Juha] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
[Elder, James T.] Ann Arbor Vet Affairs Hosp, Ann Arbor, MI USA.
[Trembath, Richard C.] Queen Mary Univ London, Barts & London Sch Med & Dent, London, England.
[Paschall, Justin] US Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD USA.
[Malloy, Mary J.; Pullinger, Clive R.; Kane, John P.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
[Malloy, Mary J.; Pullinger, Clive R.; Kane, John P.] Univ Calif San Francisco, Ctr Human Genet, San Francisco, CA 94143 USA.
[Perlmutter, Amy; Miner, Andrew] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Ike, Robert W.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Schrodi, Steven J.; Begovich, Ann B.] Celera, Alameda, CA USA.
[Prahalad, Sampath; Guthery, Stephen L.] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[Prahalad, Sampath; Guthery, Stephen L.] Univ Utah, Dept Rheumatol, Salt Lake City, UT USA.
[Prahalad, Sampath; Guthery, Stephen L.] Univ Utah, Dept Gastroenterol, Salt Lake City, UT USA.
[Fischer, Judith; Lathrop, G. Mark] Inst Genom Commissariat Energie Atom, Ctr Natl Genotypage, Evry, France.
[Liao, Wilson; Kwok, Pui] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Menter, Alan] Baylor Univ, Med Ctr, Dept Dermatol, Dallas, TX USA.
[Wise, C.] Texas Scottish Rite Hosp Children, Seay Ctr Musculoskeletal Res, Dallas, TX 75219 USA.
[Kainu, Kati; Saarialho-Kere, Ulpu; Suomela, Sari] Univ Helsinki, Dept Dermatol & Venerol, Helsinki, Finland.
[Kurrat, Werner] Asklepios Nordseeklin, Westerland Sylt, Germany.
[Kuester, Wolfgang] TOMESA Clin, Bad Salzschlirf, Germany.
[Lascorz, Jesus] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany.
[Moessner, Rotraut] Univ Gottingen, Dept Dermatol, Gottingen, Germany.
[Schuermeier-Horst, Funda; Traupe, Heiko] Univ Munster, Dept Dermatol, D-4400 Munster, Germany.
[Staender, Markward] Psoriasis Rehabil Hosp, Bad Bentheim, Germany.
[den Heijer, Martin] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands.
[den Heijer, Martin] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol & Biostat, NL-6525 ED Nijmegen, Netherlands.
[Campbell, Linda E.; McLean, W. H. Irwin] Univ Dundee, Dundee, Scotland.
[Cusack, Caitriona; Markham, Trevor] Univ Coll Hosp Galway, Dept Dermatol, Galway, Ireland.
[Fitzgerald, Oliver; Gallagher, Phil; Kirby, Brian; Rogers, Sarah F.; Zawirska, Agnieszka] St Vincents Univ Hosp, Dept Dermatol, Dublin 4, Ireland.
[Irvine, Alan D.] Our Ladys Childrens Hosp Crumlin, Trinity Coll Dublin, Dept Clin Med, Dublin, Ireland.
[Martin-Ezquerra, Gemma; Pujol, Ramon M.] Hosp Mar, IMAS, Dermatol Serv, Barcelona, Spain.
[Inerot, Annica] Sahlgrens Univ Hosp, Dept Dermatol & Venerol, Gothenburg, Sweden.
[Henschel, Andrew; Aurand, Marin; Bebo, Bruce] Natl Psoriasis Fdn, Portland, OR USA.
[Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munich, Inst Genet Epidemiol, Neuherberg, Germany.
[Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munich, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Moebus, Susanne; Joeckel, Karl-Heinz] Univ Duisburg Essen, IMIBE, Essen, Germany.
[Erbe, Raimund] Univ Duisburg Essen, Univ Hosp Essen, W German Heart Ctr, Clin Cardiol, Essen, Germany.
[Donnelly, Peter] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
[Blackwell, Jenefer M.] Univ Western Australia, Ctr Child Hlth Res, Telethon Inst Child Hlth Res, Suciaco, WA, Australia.
[Blackwell, Jenefer M.] Addenbrookes Hosp, Cambridge Inst Med Res, Genet & Infect Lab, Cambridge, England.
[Bramon, Elvira] Kings Coll London, Inst Psychiat, Biomed Res Ctr Mental Hlth, Div Psychol Med & Psychiat, London WC2R 2LS, England.
[Bramon, Elvira] S London & Maudsley NHS Fdn Trust, London, England.
[Brown, Matthew A.] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst Canc Immunol & Metab Med, Brisbane, Qld, Australia.
[Casas, Juan P.] Univ London London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1E 7HT, England.
[Corvin, Aiden] Trinity Coll Dublin, Inst Mol Med, Neuropsychiat Genet Res Grp, Dublin, Ireland.
[Craddock, Nicholas] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales.
[Duncanson, Audrey] Wellcome Trust Res Labs, London, England.
[Jankowski, Janusz] Barts & London Queen Marys Sch Med & Dent, Ctr Gastroenterol, London, England.
[Markus, Hugh S.] St Georges Univ London, London, England.
[McCarthy, Mark I.] Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab ICDEM, Oxford OX3 7LJ, England.
[Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Dundee DD1 9SY, Scotland.
[Plomin, Robert] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England.
[Sawcer, Stephen J.] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England.
[Sawcer, Stephen J.; Samani, Nilesh] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.
[Viswanathan, Ananth C.] Moorfields Eye Hosp NHS Fdn Trust, Glaucoma Res Unit, London, England.
[Viswanathan, Ananth C.] UCL, Inst Ophthalmol, Dept Genet, London, England.
[Wood, Nicholas W.] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
RP Trembath, RC (reprint author), Kings Coll London, Div Genet & Mol Med, London WC2R 2LS, England.
EM goncalo@umich.edu; jelder@umich.edu; vp-health@qmul.ac.uk
RI Spain, Sarah/G-1968-2010; Smith, Catherine/G-5268-2012; Fischer,
Judith/E-6327-2016; Koks, Sulev/H-3655-2015; Wood, Nicholas/C-2505-2009;
Franke, Andre/B-2151-2010; Reis, Andre/D-2309-2009; Worthington,
Jane/M-9770-2014; Barton, Anne/N-2053-2014; Schalkwijk,
Joost/N-1774-2013; Griffiths, Christopher/P-5448-2014; Giardina,
Emiliano/J-1965-2012; Warren, Richard/G-4929-2015; Jankowski,
Janusz/H-2706-2012; Blackwell, Jenefer/H-3015-2015; Young,
Helen/H-5247-2015; Zeeuwen, Patrick/N-1779-2013; Torinsson Naluai,
Asa/P-3269-2015; Mathew, Christopher/G-3434-2015; Ellinghaus,
Eva/E-6490-2012; Palmer, Colin/C-7053-2008; Huffmeier,
Ulrike/D-2806-2013; Ding, Jun/G-3918-2011; Abecasis,
Goncalo/B-7840-2010; Weidinger, Stephan/C-8461-2011; Kere,
Juha/A-9179-2008; Schreiber, Stefan/B-6748-2008; Wijmenga,
Cisca/D-2173-2009; Weale, Michael/F-2587-2010; Estivill,
Xavier/A-3125-2013; Capon, Francesca/F-4763-2011; Ryan,
Anthony/A-1336-2010; Deloukas, Panos/B-2922-2013
OI McManus, Ross/0000-0002-0529-9617; Trembath,
Richard/0000-0003-0550-3400; Cork, Michael/0000-0003-4428-2428; Schrodi,
Steven/0000-0003-2304-8528; Hoffmann, Per/0000-0002-6573-983X; Knight,
Joanne/0000-0002-7148-1660; Pirinen, Matti/0000-0002-1664-1350; Irvine,
Alan/0000-0002-9048-2044; Winkelmann, Juliane/0000-0003-2667-9691;
Gillman, Matthew/0000-0002-2340-6930; Plomin,
Robert/0000-0002-0756-3629; Gieger, Christian/0000-0001-6986-9554;
Wijmenga, Cisca/0000-0002-5635-1614; Tsoi, Lam
Cheung/0000-0003-1627-5722; Spain, Sarah/0000-0002-7591-8364; Novelli,
Giuseppe/0000-0002-7781-602X; Brown, Matthew A/0000-0003-0538-8211;
Abecasis, Goncalo/0000-0003-1509-1825; Esko, Tonu/0000-0003-1982-6569;
Perricone, Carlo/0000-0003-4771-6981; Smith,
Catherine/0000-0001-9918-1144; Koks, Sulev/0000-0001-6087-6643; Wood,
Nicholas/0000-0002-9500-3348; Franke, Andre/0000-0003-1530-5811; Reis,
Andre/0000-0002-6301-6363; McLean, William Henry
Irwin/0000-0001-5539-5757; Ryan, Anthony/0000-0001-5005-3344; Corvin,
Aiden/0000-0001-6717-4089; giardina, emiliano/0000-0002-2741-5009; Wise,
Carol/0000-0002-6790-2194; Trynka, Gosia/0000-0002-6955-9529;
Worthington, Jane/0000-0003-0544-042X; Barton, Anne/0000-0003-3316-2527;
Griffiths, Christopher/0000-0001-5371-4427; Warren,
Richard/0000-0002-2918-6481; Jankowski, Janusz/0000-0003-2130-9181;
Young, Helen/0000-0003-1538-445X; Torinsson Naluai,
Asa/0000-0002-0504-6492; Mathew, Christopher/0000-0003-4178-1838;
Ellinghaus, Eva/0000-0003-2914-3382; Palmer, Colin/0000-0002-6415-6560;
Huffmeier, Ulrike/0000-0001-6448-4671; Kere, Juha/0000-0003-1974-0271;
Schreiber, Stefan/0000-0003-2254-7771; Weale,
Michael/0000-0003-4593-1186; Estivill, Xavier/0000-0002-0723-2256;
Capon, Francesca/0000-0003-2432-5793; Deloukas,
Panos/0000-0001-9251-070X
FU UK Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02]; UK
National Blood Service controls; Welcome Trust; Barbara and Neal
Henschel Charitable Foundation; Health Research Board
FX Major support for this study was provided by the US National Institutes
of Health, the Wellcome Trust and the German Research Foundation. We
thank J.C. Barrett for contribution to the design of the Immunochip and
helpful analytical discussion, as well as E. Gray, S. Bumpstead, D.
Simpkin and the staff of the Wellcome Trust Sanger Institute Sample
Management and Genotyping teams for their genotyping and analytical
contributions. We acknowledge use of the British 1958 Birth Cohort DNA
collection, funded by the UK Medical Research Council (G0000934) and the
Wellcome Trust (068545/Z/02), and the UK National Blood Service
controls, funded by the Welcome Trust. We acknowledge CASP for the
contribution of GWAS data, as well as the provision of control DNA
samples by the Cooperative Research in the Region of Augsburg (KORA) and
Heinz-Nixdorf Recall (Risk Factors, Evaluation of Coronary Calcification
and Lifestyle) study (HNR) and genotyping data generated by the Dietary,
Lifestyle and Genetic determinants of Obesity and Metabolic syndrome
(DILGOM) Consortium. We thank the Barbara and Neal Henschel Charitable
Foundation for their support of the National Psoriasis Victor Henschel
BioBank. We acknowledge the Genetic repository in Ireland for Psoriasis
and Psoriatic Arthritis (GRIPPsA), the Irish blood transfusion
service/Trinity College Dublin Biobank and the Dublin Centre for
Clinical Research (funded by the Health Research Board and the Wellcome
Trust). A detailed list of contributing consortia and relevant funding
support is provided in the Supplementary Note.
NR 70
TC 303
Z9 311
U1 4
U2 78
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 DEC
PY 2012
VL 44
IS 12
BP 1341
EP 1348
DI 10.1038/ng.2467
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 045QZ
UT WOS:000311713200013
PM 23143594
ER
PT J
AU Justice, CM
Yagnik, G
Kim, Y
Peter, I
Jabs, EW
Erazo, M
Ye, XQ
Ainehsazan, E
Shi, LS
Cunningham, ML
Kimonis, V
Roscioli, T
Wall, SA
Wilkie, AOM
Stoler, J
Richtsmeier, JT
Heuze, Y
Sanchez-Lara, PA
Buckley, MF
Druschel, CM
Mills, JL
Caggana, M
Romitti, PA
Kay, DM
Senders, C
Taub, PJ
Klein, OD
Boggan, J
Zwienenberg-Lee, M
Naydenov, C
Kim, J
Wilson, AF
Boyadjiev, SA
AF Justice, Cristina M.
Yagnik, Garima
Kim, Yoonhee
Peter, Inga
Jabs, Ethylin Wang
Erazo, Monica
Ye, Xiaoqian
Ainehsazan, Edmond
Shi, Lisong
Cunningham, Michael L.
Kimonis, Virginia
Roscioli, Tony
Wall, Steven A.
Wilkie, Andrew O. M.
Stoler, Joan
Richtsmeier, Joan T.
Heuze, Yann
Sanchez-Lara, Pedro A.
Buckley, Michael F.
Druschel, Charlotte M.
Mills, James L.
Caggana, Michele
Romitti, Paul A.
Kay, Denise M.
Senders, Craig
Taub, Peter J.
Klein, Ophir D.
Boggan, James
Zwienenberg-Lee, Marike
Naydenov, Cyrill
Kim, Jinoh
Wilson, Alexander F.
Boyadjiev, Simeon A.
TI A genome-wide association study identifies susceptibility loci for
nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9
SO NATURE GENETICS
LA English
DT Article
ID TRANSCRIPTION FACTOR; PLASMA-MEMBRANE; GENETIC-BASIS; NEURAL CREST; MSX2
GENE; MUTATIONS; TWIST; CILIA; RISK; DEFECTS
AB Sagittal craniosynostosis is the most common form of craniosynostosis, affecting approximately one in 5,000 newborns. We conducted, to our knowledge, the first genome-wide association study for nonsyndromic sagittal craniosynostosis (sNSC) using 130 non-Hispanic case-parent trios of European ancestry (NHW). We found robust associations in a 120-kb region downstream of BMP2 flanked by rs1884302 (P = 1.13 x 10(-14), odds ratio (OR) = 4.58) and rs6140226 (P = 3.40 x 10(-11), OR = 0.24) and within a 167-kb region of BBS9 between rs10262453 (P = 1.61 x 10(-10), OR = 0.19) and rs17724206 (P = 1.50 x 10(-8), OR = 0.22). We replicated the associations to both loci (rs1884302, P = 4.39 x 10(-31) and rs10262453, P= 3.50 x 10(-14)) in an independent NHW population of 172 unrelated probands with sNSC and 548 controls. Both BMP2 and BBS9 are genes with roles in skeletal development that warrant functional studies to further understand the etiology of sNSC.
C1 [Yagnik, Garima; Kim, Jinoh; Boyadjiev, Simeon A.] Univ Calif Davis, Dept Pediat, Genet Sect, Sacramento, CA 95817 USA.
[Justice, Cristina M.; Kim, Yoonhee; Wilson, Alexander F.] NHGRI, Genometr Sect, Inherited Dis Res Branch, Div Intramural Res,US Natl Inst Hlth NIH, Baltimore, MD USA.
[Peter, Inga; Jabs, Ethylin Wang; Erazo, Monica; Ye, Xiaoqian; Ainehsazan, Edmond; Shi, Lisong] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.
[Cunningham, Michael L.] Univ Washington, Dept Pediat, Div Craniofacial Med, Seattle, WA 98195 USA.
[Cunningham, Michael L.] Seattle Childrens Res Inst, Seattle, WA USA.
[Kimonis, Virginia] Univ Calif Irvine, Dept Pediat, Div Genet, Irvine, CA 92717 USA.
[Roscioli, Tony] Univ New S Wales, Sydney Childrens Hosp, Sch Womens & Childrens Hlth, Sydney, NSW, Australia.
[Wall, Steven A.; Wilkie, Andrew O. M.] John Radcliffe Hosp, Craniofacial Unit, Oxford Univ Hosp Natl Hlth Serv Trust, Oxford OX3 9DU, England.
[Wilkie, Andrew O. M.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England.
[Stoler, Joan] Harvard Univ, Div Genet, Childrens Hosp Boston, Boston, MA 02115 USA.
[Richtsmeier, Joan T.; Heuze, Yann] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA.
[Sanchez-Lara, Pedro A.] Univ So Calif, Childrens Hosp Los Angeles, Dept Pathol & Pediat, Los Angeles, CA USA.
[Buckley, Michael F.] SE Area Lab Serv, Dept Haematol & Genet, Sydney, NSW, Australia.
[Druschel, Charlotte M.] New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA.
[Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Caggana, Michele; Kay, Denise M.] New York State Dept Hlth, Div Genet, Wadsworth Ctr, Albany, NY USA.
[Romitti, Paul A.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA.
[Senders, Craig] Univ Calif Davis, Dept Otolaryngol, Sacramento, CA 95817 USA.
[Taub, Peter J.] Mt Sinai Med Ctr, Kravis Childrens Hosp, Div Plast & Reconstruct Surg, New York, NY 10029 USA.
[Klein, Ophir D.] Univ Calif San Francisco, Dept Orofacial Sci, San Francisco, CA 94143 USA.
[Klein, Ophir D.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
[Klein, Ophir D.] Univ Calif San Francisco, Program Craniofacial & Mesenchymal Biol, San Francisco, CA 94143 USA.
[Boggan, James; Zwienenberg-Lee, Marike] Univ Calif Davis, Dept Neurol Surg, Sacramento, CA 95817 USA.
[Naydenov, Cyrill] Med Univ Sofia, Dept Chem & Biochem, Sofia, Bulgaria.
RP Boyadjiev, SA (reprint author), Univ Calif Davis, Dept Pediat, Genet Sect, Sacramento, CA 95817 USA.
EM simeon.boyd@ucdmc.ucdavis.edu
OI Klein, Ophir/0000-0002-6254-7082; Kay, Denise/0000-0002-9928-2698; Kim,
Jinoh/0000-0003-2841-147X; Wilkie, Andrew/0000-0002-2972-5481; Jabs,
Ethylin/0000-0001-8983-5466
FU Children's Miracle Network Endowed Chair; National Institute of Dental
and Craniofacial Research (NIDCR)/NIH [K23 DE00462, R03 DE016342, R01
DE016886]; National Center for Research Resources/NIH [M01-RR00052];
Zlatka; Anton; Alec Boyadjiev; US Centers for Disease Control and
Prevention (CDC) [5 R01 DD000350]; Wellcome Trust [093329]; CDC
[5U01DD000492]; NIDCR/NIH [R21DE022419]; Intramural Research Program
(IRP) of the NIH, Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD); Robert Wood Johnson Foundation
[3R37DE012711-13S1]; Children's Hospital Los Angeles-University of
Southern California Child Health Research Career Development Program
[NIH K12-HD05954]; NIDCR/NIH; American Recovery and Reinvestment Act
[R01 DE018500, 3R01 DE018500-02S1]; National Center for Advancing
Translational Sciences [NIH UL1TR000067]; Division of Intramural
Research Program of the National Human Genome Research Institute, NIH;
NIH [HHSN268200782096C]; [R01 DE018227]; [HHSN267200703431C]; [NICHD
N01-DK-7-3431]
FX The authors thank all families who contributed to this study. S.A.B. is
partially funded through a Children's Miracle Network Endowed Chair and
through grants K23 DE00462, R03 DE016342 and R01 DE016886 from the
National Institute of Dental and Craniofacial Research (NIDCR)/NIH and
M01-RR00052 from the National Center for Research Resources/NIH and was
fully supported by Zlatka, Anton and Alec Boyadjiev. Partial funding was
also obtained from grants to E.W.J. (US Centers for Disease Control and
Prevention (CDC) 5 R01 DD000350), M.L.C. (R01 DE018227), A.O.M.W.
(Wellcome Trust 093329), P.A.R. (CDC 5U01DD000492), J.K. (NIDCR/NIH
R21DE022419), J.L.M. (Intramural Research Program (IRP) of the NIH,
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD); IRP HHSN267200703431C; NICHD N01-DK-7-3431),
P.A.S.-L. (Robert Wood Johnson Foundation 3R37DE012711-13S1 and
Children's Hospital Los Angeles-University of Southern California Child
Health Research Career Development Program; NIH K12-HD05954), J.T.R.
(NIDCR/NIH and the American Recovery and Reinvestment Act R01 DE018500
and 3R01 DE018500-02S1) and I.P. (National Center for Advancing
Translational Sciences, NIH UL1TR000067). This project was also
supported in part by the Division of Intramural Research Program of the
National Human Genome Research Institute, NIH (C.M.J., Y.K. and A.F.W).
Genotyping services were provided by the Center for Inherited Disease
Research (CIDR). CIDR is fully funded through a federal contract from
the NIH to Johns Hopkins University, contract number HHSN268200782096C.
We thank B. Wilson, N. Issac, C. Nauta, E. Goude, E. Cherkez, L. Peters
and J. Harrison for patient recruitment, C. Boehm and A. Scott for
coordination of discovery-phase genotyping, C. Stevens, A. Stoner, J.L.
Liu, A. Gearhart, A. Atkins and E. McGrath for bench work, D. Mortlock
for bioinformatic analysis and informative discussion and J. Graham
(Cedars-Sinai Hospital, Los Angeles, California, USA), J. Bernstein
(Stanford University, Palo Alto, California, USA), J. Marsh (Washington
University, St. Louis, Missouri, USA), J. Panchal (University of
Oklahoma Health Science Center, Oklahoma, USA), T. Tollefson (University
of California Davis, Sacramento, California, USA) and M. Passos-Bueno
(University of Sao Paolo, Brazil) for contributing clinical information
and biospecimens for this project.
NR 52
TC 30
Z9 30
U1 0
U2 7
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 DEC
PY 2012
VL 44
IS 12
BP 1360
EP 1364
DI 10.1038/ng.2463
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 045QZ
UT WOS:000311713200016
PM 23160099
ER
PT J
AU Perfetto, SP
Ambrozak, D
Nguyen, R
Chattopadhyay, PK
Roederer, M
AF Perfetto, Stephen P.
Ambrozak, David
Nguyen, Richard
Chattopadhyay, Pratip K.
Roederer, Mario
TI Quality assurance for polychromatic flow cytometry using a suite of
calibration beads
SO NATURE PROTOCOLS
LA English
DT Article
AB The quality assurance program presented here provides a means to maximize and maintain the performance of individual flow cytometers in a facility. To optimize performance, we recommend performing all three steps (optimization, calibration and standardization) in this program when a new flow cytometer is installed or whenever the flow cytometer's optical path is altered (e. g., lasers, filters or detectors are replaced). The complete process requires 3-4 h. On a more frequent basis, only a subset of these procedures need to be performed as a part of daily maintenance routines. The data generated can be tracked to monitor the instrument and determine whether service is needed. In addition, the data can provide a metric for whether repairs and upgrades have improved or harmed performance, and for future instrument-to-instrument comparisons. In sum, the procedures presented here represent an updated framework for optimizing, calibrating and standardizing a flow cytometer for daily use.
C1 [Perfetto, Stephen P.; Ambrozak, David; Nguyen, Richard; Chattopadhyay, Pratip K.; Roederer, Mario] NIAID, Flow Cytometry Core Facil, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Perfetto, SP (reprint author), NIAID, Flow Cytometry Core Facil, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sperfetto@mail.nih.gov
OI Chattopadhyay, Pratip/0000-0002-5457-9666
FU Intramural NIH HHS [Z99 AI999999]
NR 13
TC 23
Z9 23
U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
J9 NAT PROTOC
JI Nat. Protoc.
PD DEC
PY 2012
VL 7
IS 12
BP 2067
EP 2079
DI 10.1038/nprot.2012.126
PG 13
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 048EW
UT WOS:000311894100001
PM 23138348
ER
PT J
AU Umar, A
Dunn, BK
Greenwald, P
AF Umar, Asad
Dunn, Barbara K.
Greenwald, Peter
TI Future directions in cancer prevention
SO NATURE REVIEWS CANCER
LA English
DT Review
ID FORCE RECOMMENDATION STATEMENT; RANDOMIZED CONTROLLED-TRIAL; SURGICAL
ADJUVANT BREAST; CYTOLYTIC T-LYMPHOCYTES; CHEMOPREVENTION DRUG
DEVELOPMENT; SPORADIC COLORECTAL ADENOMAS; BOWEL PROJECT P-1;
PROSTATE-CANCER; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY
AB Prevention of cancer remains the most promising strategy for reducing both its incidence and the mortality due to this disease. For more than four decades, findings from epidemiology, basic research and clinical trials have informed the development of lifestyle and medical approaches to cancer prevention. These include selective oestrogen receptor modulators and aromatase inhibitors for breast cancer, the 5-alpha-reductase inhibitors finasteride and dutasteride for prostate cancer, and the development of vaccines for viruses that are associated with specific cancers. Future directions include genetic, proteomic and other molecular approaches for identifying pathways that are associated with cancer initiation and development, as well as refining the search for immunologically modifiable causes of cancer.
C1 [Umar, Asad] NCI, Canc Prevent Div, Gastrointestinal & Other Canc Res Grp, Rockville, MD 20852 USA.
[Dunn, Barbara K.] NCI, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Rockville, MD 20852 USA.
[Greenwald, Peter] NCI, Off Director, Bethesda, MD 20892 USA.
RP Umar, A (reprint author), NCI, Canc Prevent Div, Gastrointestinal & Other Canc Res Grp, Execut Plaza N 2142,6130 Execut Blvd,MSC 7317, Rockville, MD 20852 USA.
EM Asad.Umar@nih.gov
NR 166
TC 71
Z9 74
U1 4
U2 82
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 DEC
PY 2012
VL 12
IS 12
BP 835
EP 848
DI 10.1038/nrc3397
PG 14
WC Oncology
SC Oncology
GA 045RJ
UT WOS:000311714200013
PM 23151603
ER
PT J
AU Shankar, LK
AF Shankar, Lalitha K.
TI The clinical evaluation of novel imaging methods for cancer management
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Article
ID TREATMENT TRIALS; IMMUNOHISTOCHEMISTRY; RECOMMENDATIONS; PROLIFERATION;
ONCOLOGY; TUMORS; PET
AB The National Cancer Institute (NCI) has a long-standing interest in evaluating and using the known advantages of molecular and functional imaging, as well as assessing the potential of novel imaging agents and modalities, to improve clinical cancer research and cancer care. In this Perspectives article, I discuss the strategies and resources being used by the NCI to foster and enhance these evaluations. Although resource and logistical challenges abound in successfully mounting these trials, many examples exist of real and potential solutions to improve the clinical evaluation process for imaging agents and modalities in the USA and in international collaborations.
C1 NCI, Canc Imaging Program, Chief Diagnost Imaging Branch, Bethesda, MD 20892 USA.
RP Shankar, LK (reprint author), NCI, Canc Imaging Program, Chief Diagnost Imaging Branch, 6130 Execut Blvd,MSC 7412, Bethesda, MD 20892 USA.
EM shankarl@mail.nih.gov
NR 39
TC 7
Z9 8
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD DEC
PY 2012
VL 9
IS 12
BP 738
EP 744
DI 10.1038/nrclinonc.2012.186
PG 7
WC Oncology
SC Oncology
GA 047GW
UT WOS:000311828200009
PM 23149888
ER
PT J
AU de Jonge, L
Bray, GA
Smith, SR
Ryan, DH
de Souza, RJ
Loria, CM
Champagne, CM
Williamson, DA
Sacks, FM
AF de Jonge, Lilian
Bray, George A.
Smith, Steven R.
Ryan, Donna H.
de Souza, Russell J.
Loria, Catherine M.
Champagne, Catherine M.
Williamson, Donald A.
Sacks, Frank M.
TI Effect of Diet Composition and Weight Loss on Resting Energy Expenditure
in the POUNDS LOST Study
SO OBESITY
LA English
DT Article
ID METABOLIC-RATE; BODY-WEIGHT; OBESE WOMEN; PHYSICAL-ACTIVITY;
PROTEIN-INTAKE; RISK-FACTORS; WHITE WOMEN; CARBOHYDRATE; FAT;
RESTRICTION
AB Weight loss reduces energy expenditure, but it is unclear whether dietary macronutrient composition affects this reduction. We hypothesized that energy expenditure might be modulated by macronutrient composition of the diet. The Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST study, a prospective, randomized controlled trial in 811 overweight/obese people who were randomized in a 2 x 2 design to diets containing 20en% or 40en% fat and 15en% or 25en% protein (diets with 65%, 55%, 45%, and 35% carbohydrate) provided the data to test this hypothesis. Resting energy expenditure (REE) was measured at baseline, 6, and 24 months using a ventilated hood. REE declined at 6 months by 99.5 +/- 8.0 kcal/day in men and 55.2 +/- 10.6 kcal/day in women during the first 6 months. This decline was related to the weight loss, and there was no difference between the diets. REE had returned to baseline by 24 months, but body weight was still 60% below baseline. Measured REE at 6 months was significantly lower than the predicted (-18.2 +/- 6.7 kcal/day) and was the result of significant reductions from baseline in the low-fat diets (65% or 55% carbohydrate), but not in the high fat diet groups. By 24 months the difference had reversed with measured REE being slightly but significantly higher than predicted (21.8 +/- 10.1 kcal/day). In conclusion, we found that REE fell significantly after weight loss but was not related to diet composition. Adaptive thernnogenesis was evident at 6 months, but not at 24 months.
C1 [de Jonge, Lilian; Bray, George A.; Smith, Steven R.; Ryan, Donna H.; Champagne, Catherine M.; Williamson, Donald A.] Pennington Biomed Res Ctr Baton Rouge, Baton Rouge, LA 70808 USA.
[de Jonge, Lilian; Smith, Steven R.; Loria, Catherine M.] Natl Heart Lung & Blood Inst, Bethesda, MD USA.
[Smith, Steven R.] Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
RP Bray, GA (reprint author), Pennington Biomed Res Ctr Baton Rouge, Baton Rouge, LA 70808 USA.
EM george.bray@pbrc.edu
RI Biguzzi, Felipe/E-4724-2015;
OI de Jonge, Lilian/0000-0001-5900-0695; de Souza,
Russell/0000-0001-8945-513X
FU National Heart, Lung and Blood Institute, NIH [HL 073286]; GCRC [RR
02635]
FX This study was supported by grant: HL 073286 from the National Heart,
Lung and Blood Institute, NIH and GCRC grant RR 02635.
NR 40
TC 12
Z9 12
U1 2
U2 24
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 DEC
PY 2012
VL 20
IS 12
BP 2384
EP 2389
DI 10.1038/oby.2012.127
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 045QX
UT WOS:000311713000009
PM 22627912
ER
PT J
AU Traurig, MT
Perez, JM
Ma, LJ
Bian, L
Kobes, S
Hanson, RL
Knowler, WC
Krakoff, JA
Bogardus, C
Baier, LJ
AF Traurig, Michael T.
Perez, Jessica M.
Ma, Lijun
Bian, Li
Kobes, Sayuko
Hanson, Robert L.
Knowler, William C.
Krakoff, Jonathan A.
Bogardus, Clifton
Baier, Leslie J.
TI Variants in the LEPR Gene Are Nominally Associated With Higher BMI and
Lower 24-h Energy Expenditure in Pima Indians
SO OBESITY
LA English
DT Article
ID LEPTIN RECEPTOR GENE; GENOME-WIDE ASSOCIATION; AMERICAN-INDIANS;
OBESITY; FAT; POLYMORPHISMS; CHAMBER; SEARCH; FOOD
AB Genome-wide association studies (GWASs) have been used to search for susceptibility genes for type 2 diabetes and obesity in the Pima Indians, a population with a high prevalence of both diseases. In these studies, a variant (rs2025804) in the LEPR gene was nominally associated with BMI in 1,082 subjects (P = 0.03 adjusted for age, sex, birth year, and family membership). Therefore the LEPR and leptin overlapping transcript (LEPROT) genes were selected for further sequencing and genotyping in larger population-based samples for association analyses with obesity-related phenotypes. Selected variants (n = 80) spanning these genes were genotyped in a sample of full-heritage Pima Indians (n = 2,842) and several common variants including rs2025804 were nominally associated with BMI (P = 0.05-0.003 adjusted for age, sex, birth year, and family membership). Four common tag variants associated with BMI in the full-heritage Pima Indian sample were genotyped in a second sample of mixed-heritage Native Americans (n = 2,969) and three of the variants showed nominal replication (P = 0.03-0.006 adjusted as above and additionally for Indian heritage). Combining both samples provided the strongest evidence for association (adjusted P = 0.0003-0.0001). A subset of these individuals (n = 403) had been metabolically characterized for predictors of obesity and the BMI risk alleles for the variants tagged by rs2025804 were also associated with lower 24-h energy expenditure (24hEE) as assessed in a human respiratory chamber (P = 0.0007 adjusted for age, sex, fat mass, fat-free mass, activity, and family membership). We conclude that common noncoding variation in the LEPR gene is associated with higher BMI and lower energy expenditure in Native Americans.
C1 [Traurig, Michael T.; Perez, Jessica M.; Bian, Li; Kobes, Sayuko; Hanson, Robert L.; Knowler, William C.; Krakoff, Jonathan A.; Bogardus, Clifton; Baier, Leslie J.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85004 USA.
[Ma, Lijun] Wake Forest Univ, Sch Med, Dept Internal Med Endocrinol, Winston Salem, NC 27109 USA.
RP Baier, LJ (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85004 USA.
EM lbaier@phx.niddk.nih.gov
RI Hanson, Robert/O-3238-2015
OI Hanson, Robert/0000-0002-4252-7068
FU Intramural Research Program of National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
FX We thank the many persons who volunteered for these studies. This work
was funded by the Intramural Research Program of National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health.
NR 25
TC 7
Z9 7
U1 0
U2 5
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 DEC
PY 2012
VL 20
IS 12
BP 2426
EP 2430
DI 10.1038/oby.2012.159
PG 5
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 045QX
UT WOS:000311713000015
PM 22810975
ER
PT J
AU Gyamfi-Bannerman, C
Gilbert, S
Landon, MB
Spong, CY
Rouse, DJ
Varner, MW
Caritis, SN
Meis, PJ
Wapner, RJ
Sorokin, Y
Carpenter, M
Peaceman, AM
O'Sullivan, MJ
Sibai, BM
Thorp, JM
Ramin, SM
Mercer, BM
AF Gyamfi-Bannerman, Cynthia
Gilbert, Sharon
Landon, Mark B.
Spong, Catherine Y.
Rouse, Dwight J.
Varner, Michael W.
Caritis, Steve N.
Meis, Paul J.
Wapner, Ronald J.
Sorokin, Yoram
Carpenter, Marshall
Peaceman, Alan M.
O'Sullivan, Mary J.
Sibai, Baha M.
Thorp, John M.
Ramin, Susan M.
Mercer, Brian M.
CA Eunice Kennedy Shriver Natl Inst C
TI Risk of Uterine Rupture and Placenta Accreta With Prior Uterine Surgery
Outside of the Lower Segment
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT 57th Annual Meeting of the Society-for-Gynecologic-Investigation
CY MAR 24-27, 2010
CL Orlando, FL
SP Soc Gynecol Invest
ID CESAREAN DELIVERIES; MYOMECTOMY; OUTCOMES
AB OBJECTIVE: Women with a prior myomectomy or prior classical cesarean delivery often have early delivery by cesarean because of concern for uterine rupture. Although theoretically at increased risk for placenta accreta, this risk has not been well-quantified. Our objective was to estimate and compare the risks of uterine rupture and placenta accreta in women with prior uterine surgery.
METHODS: Women with prior myomectomy or prior classical cesarean delivery were compared with women with a prior low-segment transverse cesarean delivery to estimate rates of both uterine rupture and placenta accreta.
RESULTS: One hundred seventy-six women with a prior myomectomy, 455 with a prior classical cesarean delivery, and 13,273 women with a prior low-segment transverse cesarean delivery were evaluated. Mean gestational age at delivery differed by group (P<.001), prior myomectomy (37.3 weeks), prior classical cesarean delivery (35.8 weeks), and low-segment transverse cesarean delivery (38.6 weeks). The frequency of uterine rupture in the prior myomectomy group (P-MMX group) was 0% (95% confidence interval [CI] 0-1.98%). The frequency of uterine rupture in the low-segment transverse cesarean delivery group (LTC group) (0.41%) was not statistically different from the risk in the P-MMX group (P>.99) or in the prior classical cesarean delivery group (PC group) (0.88%; P=.13). Placenta accreta occurred in 0% (95% CI 0-1.98%) of the P-MMX group compared with 0.19% in the LTC group (P>.99) and 0.88% in the PC group (P=.01 relative to the LTC group). The adjusted odds ratio for the PC group (relative to LTC group) was 3.23 (95% CI 1.11-9.39) for uterine rupture and 2.09 (95% CI 0.69-6.33) for accreta. The frequency of accreta for those with previa was 11.1% for the PC group and 13.6% for the LTC group (P>.99).
CONCLUSION: A prior myomectomy is not associated with higher risks of either uterine rupture or placenta accreta. The absolute risks of uterine rupture and accreta after prior myomectomy are low. (Obstet Gynecol 2012;120:1332-37) DOI: http://10.1097/AOG.0b013e318273695b
C1 Columbia Univ, Dept Obstet, New York, NY 10032 USA.
Columbia Univ, Dept Gynecol, New York, NY 10032 USA.
Ohio State Univ, Columbus, OH 43210 USA.
Univ Alabama Birmingham, Birmingham, AL USA.
Univ Utah, Salt Lake City, UT USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
Wayne State Univ, Detroit, MI USA.
Brown Univ, Providence, RI 02912 USA.
Northwestern Univ, Chicago, IL 60611 USA.
Univ Miami, Miami, FL USA.
Univ Tennessee, Memphis, TN USA.
Univ N Carolina, Chapel Hill, NC USA.
Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA.
George Washington Univ, Ctr Biostat, Washington, DC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Gyamfi-Bannerman, C (reprint author), Columbia Univ, Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, 622 W 168th St,PH 16, New York, NY 10032 USA.
EM cg2231@columbia.edu
RI Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850;
Varner, Michael/0000-0001-9455-3973
FU NICHD NIH HHS [HD27860, HD21410, HD21414, HD27861, HD27869, HD27915,
HD27917, HD34116, HD34136, HD34208, HD34210, HD36801, HD40485, HD40500,
HD40512, HD40544, HD40545, HD40560, R24 HD050924, U01 HD036801, U10
HD021410, U10 HD027860, U10 HD027869, U10 HD027905, U10 HD027915, U10
HD027917, U10 HD034116, U10 HD034122, U10 HD034136, U10 HD034208, U10
HD036801, U10 HD040485, U10 HD040500, U10 HD040512, U10 HD040544, U10
HD040545, U10 HD040560, UG1 HD027869, UG1 HD027915, UG1 HD034116, UG1
HD034208, UG1 HD040485, UG1 HD040500, UG1 HD040512, UG1 HD040544, UG1
HD040545, UG1 HD040560]
NR 12
TC 17
Z9 20
U1 0
U2 7
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 DEC
PY 2012
VL 120
IS 6
BP 1332
EP 1337
DI 10.1097/AOG.0b013e318273695b
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 041RB
UT WOS:000311417800012
PM 23168757
ER
PT J
AU Pappas, A
Shankaran, S
Hansen, NI
Bell, EF
Stoll, BJ
Laptook, AR
Walsh, MC
Das, A
Bara, R
Hale, EC
Newman, NS
Boghossian, NS
Murray, JC
Cotten, CM
Adams-Chapman, I
Hamrick, S
Higgins, RD
AF Pappas, Athina
Shankaran, Seetha
Hansen, Nellie I.
Bell, Edward F.
Stoll, Barbara J.
Laptook, Abbot R.
Walsh, Michele C.
Das, Abhik
Bara, Rebecca
Hale, Ellen C.
Newman, Nancy S.
Boghossian, Nansi S.
Murray, Jeffrey C.
Cotten, C. Michael
Adams-Chapman, Ira
Hamrick, Shannon
Higgins, Rosemary D.
TI Outcome of Extremely Preterm Infants (< 1,000 g) With Congenital Heart
Defects From the National Institute of Child Health and Human
Development Neonatal Research Network
SO PEDIATRIC CARDIOLOGY
LA English
DT Article
DE Congenital heart defects; Extremely low birth weight; Neurodevelopmental
follow-up
ID LOW-BIRTH-WEIGHT; DISEASE; SURGERY; MORTALITY; VALVULOPLASTY;
EXPERIENCE; FETUSES
AB Little is known about the outcomes of extremely low birth weight (ELBW) preterm infants with congenital heart defects (CHDs). The aim of this study was to assess the mortality, morbidity, and early childhood outcomes of ELBW infants with isolated CHD compared with infants with no congenital defects. Participants were 401-1,000 g infants cared for at National Institute of Child Health and Human Development Neonatal Research Network centers between January 1, 1998, and December 31, 2005. Neonatal morbidities and 18-22 months' corrected age outcomes were assessed. Neurodevelopmental impairment (NDI) was defined as moderate to severe cerebral palsy, Bayley II mental or psychomotor developmental index < 70, bilateral blindness, or hearing impairment requiring aids. Poisson regression models were used to estimate relative risks for outcomes while adjusting for gestational age, small-for-gestational-age status, and other variables. Of 14,457 ELBW infants, 110 (0.8 %) had isolated CHD, and 13,887 (96 %) had no major birth defect. The most common CHD were septal defects, tetralogy of Fallot, pulmonary valve stenosis, and coarctation of the aorta. Infants with CHD experienced increased mortality (48 % compared with 35 % for infants with no birth defect) and poorer growth. Surprisingly, the adjusted risks of other short-term neonatal morbidities associated with prematurity were not significantly different. Fifty-seven (52 %) infants with CHD survived to 18-22 months' corrected age, and 49 (86 %) infants completed follow-up. A higher proportion of surviving infants with CHD were impaired compared with those without birth defects (57 vs. 38 %, p = 0.004). Risk of death or NDI was greater for ELBW infants with CHD, although 20 % of infants survived without NDI.
C1 [Pappas, Athina; Shankaran, Seetha; Bara, Rebecca] Wayne State Univ, Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA.
[Pappas, Athina; Shankaran, Seetha; Bara, Rebecca] Wayne State Univ, Hutzel Womens Hosp, Detroit, MI 48201 USA.
[Hansen, Nellie I.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC 27709 USA.
[Bell, Edward F.; Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Stoll, Barbara J.; Hale, Ellen C.; Adams-Chapman, Ira; Hamrick, Shannon] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30303 USA.
[Stoll, Barbara J.; Hale, Ellen C.; Adams-Chapman, Ira; Hamrick, Shannon] Childrens Healthcare Atlanta, Atlanta, GA 30303 USA.
[Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02905 USA.
[Walsh, Michele C.; Newman, Nancy S.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD 20852 USA.
[Boghossian, Nansi S.; Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20852 USA.
[Cotten, C. Michael] Duke Univ, Dept Pediat, Durham, NC 27710 USA.
RP Pappas, A (reprint author), Wayne State Univ, Childrens Hosp Michigan, Dept Pediat, 3901 Beaubien, 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 The National Institutes of Health and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD)
provided grant support for the Neonatal Research Network's Generic
Database Study and Follow-Up Study. Data collected at participating
sites of the NICHD NRN were transmitted to RTI International, the data
coordinating center (DCC) for the network, which stored, managed, and
analyzed the data for this study. On behalf of the NRN, Dr. Abhik Das
(DCC principal investigator) and Ms. Nellie I. Hansen (DCC statistician)
had full access to all of the data in the study, and with the NRN Center
Principal Investigators, take responsibility for the integrity of the
data and accuracy of the data analysis. We are indebted to our medical
and nursing colleagues as well as the infants and their parents who
agreed to take part in this study. The following investigators, in
addition to those listed as authors, participated in this study:
NR 30
TC 10
Z9 11
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0172-0643
J9 PEDIATR CARDIOL
JI Pediatr. Cardiol.
PD DEC
PY 2012
VL 33
IS 8
BP 1415
EP 1426
DI 10.1007/s00246-012-0375-8
PG 12
WC Cardiac & Cardiovascular Systems; Pediatrics
SC Cardiovascular System & Cardiology; Pediatrics
GA 046VH
UT WOS:000311792000026
PM 22644414
ER
PT J
AU Wong, FL
Hsu, AJ
Pham, PA
Siberry, GK
Hutton, N
Agwu, AL
AF Wong, Frances L.
Hsu, Alice J.
Pham, Paul A.
Siberry, George K.
Hutton, Nancy
Agwu, Allison L.
TI Antiretroviral Treatment Strategies in Highly Treatment Experienced
Perinatally HIV-infected Youth
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article; Proceedings Paper
CT 30th Eastern States Conference
CY MAY, 2011
CL Hershey, PA
DE HIV; antiretroviral; perinatally HIV-infected youth
ID HUMAN-IMMUNODEFICIENCY-VIRUS; DRUG-RESISTANCE; THERAPY; CHILDREN;
ADOLESCENTS; ADHERENCE
AB Background: There is limited information on antiretroviral (ARV) regimens and outcomes in perinatally HIV (PHIV)-infected youth. Substantial drug resistance after long-term ARV use and nonadherence hinder efforts to design suppressive regimens for PHIV-infected youth. This study compares clinical outcomes by expected activity of the prescribed ARV regimens.
Methods: A retrospective cohort study of 13- to 24-year-old PHIV-infected youth on stable ARV regimens for >= 6 months was conducted at a pediatric HIV clinic. ARV regimens were retrospectively categorized as optimal or suboptimal based on accumulated genotypic resistance before study regimen initiation.
Results: Fifty-two patients with similar baseline characteristics met inclusion criteria (21 optimal and 31 suboptimal regimens). Patients receiving optimal regimens had significantly higher increases in CD4 than those given suboptimal regimens by week 48 of treatment (+62 versus +8 cells/mm(3), respectively; P = 0.04) and by the end of study period (+93 versus -1 cells/mm3, respectively; P = 0.03). There were no significant differences between the groups in decline of viral load, frequency of opportunistic infections or hospitalizations or accumulation of resistance mutations. Overall, 60% of the optimal and 45% of the suboptimal groups had nonadherence during the study regimen (P = 0.3).
Conclusions: PHIV-infected youth receiving optimal regimens had greater CD4 improvements but no difference in virologic outcomes compared with those receiving suboptimal regimens. In a patient population with significant nonadherence, providers must weigh the immunologic benefits of initiating an optimal regimen versus the potential risks of further resistance accumulation limiting future treatment options.
C1 [Agwu, Allison L.] Johns Hopkins Univ, Div Pediat Infect Dis, Baltimore, MD 21287 USA.
[Wong, Frances L.] Kaiser Permanente, Fontana Med Ctr, Fontana, CA USA.
[Hsu, Alice J.; Pham, Paul A.] Johns Hopkins Univ Hosp, Dept Pharm, Baltimore, MD 21287 USA.
[Pham, Paul A.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21287 USA.
[Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent Maternal AIDS Branch, NIH, Bethesda, MD USA.
[Hutton, Nancy] Johns Hopkins Univ, Dept Pediat, Div Gen Pediat, Baltimore, MD 21287 USA.
RP Agwu, AL (reprint author), Johns Hopkins Univ, Div Pediat Infect Dis, 200 N Wolfe St,Room 3145, Baltimore, MD 21287 USA.
EM ageorg10@jhmi.edu
FU NIAID NIH HHS [1K23 AI084549, K23 AI084549]
NR 12
TC 9
Z9 9
U1 3
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD DEC
PY 2012
VL 31
IS 12
BP 1279
EP 1283
DI 10.1097/INF.0b013e31826fd3e7
PG 5
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 046WC
UT WOS:000311794100018
PM 22926213
ER
PT J
AU Dong, RH
Fang, ZZ
Zhu, LL
Ge, GB
Cao, YF
Li, XB
Hu, CM
Yang, L
Liu, ZY
AF Dong, Rui-Hua
Fang, Zhong-Ze
Zhu, Liang-Liang
Ge, Guang-Bo
Cao, Yun-Feng
Li, Xiao-Bao
Hu, Cui-Min
Yang, Ling
Liu, Ze-Yuan
TI Identification of CYP isoforms involved in the metabolism of thymol and
carvacrol in human liver microsomes (HLMs)
SO PHARMAZIE
LA English
DT Article
ID CYTOCHROME-P450 ENZYMES; DRUG INTERACTIONS; INHIBITION; EXPRESSION;
POPULATION; MODEL
AB Carvacrol and thymol are phenolic compounds with similar structures isolated from many aromatic plants, and have been demonstrated to exert multiple pharmacological effects. The metabolic and pharmacokinetic behaviour of thymol and carvacrol has received much attention. Carvacrol and thymol have been demonstrated to undergo phase I metabolism such as hydroxylation reaction. However, drug-metabolizing enzymes involved in this process remain unclear. Given that cytochrome P450 s (CYPs) are involved in most phase I metabolism, the aim of the present study was to investigate the role of CYPs in the metabolism of thymol and carvacrol. After incubation with human liver microsomes (HLMs) in the presence of NADPH, a new metabolite and two metabolites were detected for thymol and carvacrol, respectively. A combination of chemical inhibition studies and assays with recombinant CYP isoforms demonstrated that CYP2A6 was the predominant drug-metabolizing enzyme involved in the metabolism of thymol and carvacrol. All these results remind the researchers that special attention should be paid on pharmacokinetic and clinical outcomes when thymol or carvacrol was co-administrated with other compounds mainly undergoing CYP2A6-mediated metabolism.
C1 [Dong, Rui-Hua; Liu, Ze-Yuan] Acad Mil Med Sci, Affiliated Hosp, Dept Clin Pharmacol, Beijing 100071, Peoples R China.
[Fang, Zhong-Ze; Zhu, Liang-Liang; Ge, Guang-Bo; Cao, Yun-Feng; Yang, Ling] Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China.
[Fang, Zhong-Ze] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Li, Xiao-Bao] Acad Mil Med Sci, Affiliated Hosp, Dept Breathing Gastroenterol, Beijing 100071, Peoples R China.
RP Liu, ZY (reprint author), Acad Mil Med Sci, Affiliated Hosp, Dept Clin Pharmacol, Beijing 100071, Peoples R China.
EM yling@dicp.ac.cn; liuzeyuan307@gmail.com
FU National Key Technology RD Program [2009BADB9B02]; National Novel Drug
Innovation Program of China [2012ZX09501001-002, 2012ZX09506001-006];
National Natural Science Foundation of China [81001473, 81102507,
81173124]
FX This work was supported by the the National Key Technology R&D Program
(2009BADB9B02), National Novel Drug Innovation Program of China
(2012ZX09501001-002 & 2012ZX09506001-006), and the National Natural
Science Foundation of China (No. 81001473, 81102507, 81173124).
NR 25
TC 6
Z9 6
U1 1
U2 38
PU GOVI-VERLAG PHARMAZEUTISCHER VERLAG GMBH
PI ESCHBORN
PA PHARMAZEUTISCCARL MANNICH STR 26, D-65760 ESCHBORN, GERMANY
SN 0031-7144
J9 PHARMAZIE
JI Pharmazie
PD DEC
PY 2012
VL 67
IS 12
BP 1002
EP 1006
DI 10.1691/ph.2012.2534
PG 5
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA 048AY
UT WOS:000311883800008
PM 23346763
ER
PT J
AU Orlando, PA
Gatenby, RA
Brown, JS
AF Orlando, Paul A.
Gatenby, Robert A.
Brown, Joel S.
TI Cancer treatment as a game: integrating evolutionary game theory into
the optimal control of chemotherapy
SO PHYSICAL BIOLOGY
LA English
DT Article
ID DRUG-INTERACTIONS; CARCINOGENESIS; RESISTANCE; PREDATION; ONCOLOGY;
MODEL
AB Chemotherapy for metastatic cancer commonly fails due to evolution of drug resistance in tumor cells. Here, we view cancer treatment as a game in which the oncologists choose a therapy and tumors 'choose' an adaptive strategy. We propose the oncologist can gain an upper hand in the game by choosing treatment strategies that anticipate the adaptations of the tumor. In particular, we examine the potential benefit of exploiting evolutionary tradeoffs in tumor adaptations to therapy. We analyze a math model where cancer cells face tradeoffs in allocation of resistance to two drugs. The tumor 'chooses' its strategy by natural selection and the oncologist chooses her strategy by solving a control problem. We find that when tumor cells perform best by investing resources to maximize response to one drug the optimal therapy is a time-invariant delivery of both drugs simultaneously. However, if cancer cells perform better using a generalist strategy allowing resistance to both drugs simultaneously, then the optimal protocol is a time varying solution in which the two drug concentrations negatively covary. However, drug interactions can significantly alter these results. We conclude that knowledge of both evolutionary tradeoffs and drug interactions is crucial in planning optimal chemotherapy schedules for individual patients.
C1 [Orlando, Paul A.] NCI, Biometry Res Grp, Canc Prevent Div, Rockville, MD 20852 USA.
[Gatenby, Robert A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Radiol, Tampa, FL 33612 USA.
[Brown, Joel S.] Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA.
RP Orlando, PA (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Rockville, MD 20852 USA.
EM paul.orlando@nih.gov
FU NIH [U54CA143970-01]
FX We thank two anonymous reviewers whose comments improved the quality of
this paper. This work was supported by grant NIH U54CA143970-01.
NR 16
TC 12
Z9 12
U1 4
U2 37
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1478-3967
J9 PHYS BIOL
JI Phys. Biol.
PD DEC
PY 2012
VL 9
IS 6
AR 065007
DI 10.1088/1478-3975/9/6/065007
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 047KN
UT WOS:000311839500008
PM 23197192
ER
PT J
AU Tanner, K
AF Tanner, Kandice
TI Regulation of the basement membrane by epithelia generated forces
SO PHYSICAL BIOLOGY
LA English
DT Article
ID IMAGE CORRELATION SPECTROSCOPY; FLUORESCENCE CORRELATION SPECTROSCOPY;
EXTRACELLULAR-MATRIX SCAFFOLD; MALIGNANT MAMMARY EPITHELIUM; SOURCE
ANIMAL AGE; COLLAGEN TYPE-IV; BREAST-CANCER; IN-VIVO; INVIVO
BIOSYNTHESIS; CELL-PROLIFERATION
AB Tumor metastasis involves a progressive loss of tissue architecture and dissolution of structural boundaries between the epithelium and connective tissue. The basement membrane ( BM), a specialized network of extracellular matrix proteins forms a barrier that physically restricts pre-invasive lesions such that they remain as local insults. The BM is not a static structure, but one that is constantly regenerated and remodeled in the adult organism. Matrix organization also regulates cell function. Thus alterations in the balance of synthesis, remodeling and proteolytic degradation of the extracellular matrix proteins may contribute to a loss of structural integrity. However, the de novo assembly and maintenance of the complex structural properties of in vivo basement membranes remain elusive. Here, this paper highlights the current understanding on the structural properties and the establishment of the BM, and discusses the potential role of self-generated forces in adult tissue remodeling and the maintenance of the BM as a malignancy suppressor.
C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Tanner, K (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
EM Tannerkd@mail.nih.gov
FU NIH, National Cancer Institute
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute. I would like to thank Walter Orellana
for assistance in figure preparation and Shelly Covington, Judith David
and Gautham Venugopalan for critical reading of the manuscript.
NR 120
TC 10
Z9 10
U1 1
U2 9
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1478-3967
J9 PHYS BIOL
JI Phys. Biol.
PD DEC
PY 2012
VL 9
IS 6
AR 065003
DI 10.1088/1478-3975/9/6/065003
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 047KN
UT WOS:000311839500004
PM 23196920
ER
PT J
AU Bermejo, GA
Clore, GM
Schwieters, CD
AF Bermejo, Guillermo A.
Clore, G. Marius
Schwieters, Charles D.
TI Smooth statistical torsion angle potential derived from a large
conformational database via adaptive kernel density estimation improves
the quality of NMR protein structures
SO PROTEIN SCIENCE
LA English
DT Article
DE knowledge-based torsion angle potential; adaptive kernel density
estimation; NMR protein structure calculation; protein structure
validation
ID SOLID-STATE NMR; MOLECULAR-STRUCTURE DETERMINATION; RESIDUAL DIPOLAR
COUPLINGS; N-TERMINAL DOMAIN; STRUCTURE VALIDATION; ESCHERICHIA-COLI;
HYBRID SOLUTION; MEAN-FORCE; ENZYME I; PHOSPHOTRANSFERASE SYSTEM
AB Statistical potentials that embody torsion angle probability densities in databases of high-quality X-ray protein structures supplement the incomplete structural information of experimental nuclear magnetic resonance (NMR) datasets. By biasing the conformational search during the course of structure calculation toward highly populated regions in the database, the resulting protein structures display better validation criteria and accuracy. Here, a new statistical torsion angle potential is developed using adaptive kernel density estimation to extract probability densities from a large database of more than 106 quality-filtered amino acid residues. Incorporated into the Xplor-NIH software package, the new implementation clearly outperforms an older potential, widely used in NMR structure elucidation, in that it exhibits simultaneously smoother and sharper energy surfaces, and results in protein structures with improved conformation, nonbonded atomic interactions, and accuracy.
C1 [Bermejo, Guillermo A.; 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, 12 South Dr,Bldg 12A,Room 2041, Bethesda, MD 20892 USA.
EM charles.schwieters@nih.gov
RI Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
FU NIH Intramural Research Program of CIT; NIH Intramural Research Program
of NIDDK; AIDS Targeted Antiviral Program of the Office of the Director
of the NIH
FX Grant sponsor: NIH Intramural Research Programs of CIT and NIDDK, and by
the AIDS Targeted Antiviral Program of the Office of the Director of the
NIH.
NR 58
TC 18
Z9 18
U1 0
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD DEC
PY 2012
VL 21
IS 12
BP 1824
EP 1836
DI 10.1002/pro.2163
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 044JT
UT WOS:000311616200004
PM 23011872
ER
PT J
AU Yin, ZQ
Lapkouski, M
Yang, W
Craigie, R
AF Yin, Zhiqi
Lapkouski, Mikalai
Yang, Wei
Craigie, Robert
TI Assembly of prototype foamy virus strand transfer complexes on product
DNA bypassing catalysis of integration
SO PROTEIN SCIENCE
LA English
DT Article
DE integrase; prototype foamy virus; human immunodeficiency virus type 1
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRAL DNA; DISINTEGRATION;
INHIBITION; INTASOME
AB Integrase is the key enzyme that mediates integration of retroviral DNA into cellular DNA which is essential for viral replication. Inhibitors of HIV-1 that target integrase recognize the nucleoprotein complexes formed by integrase and viral DNA substrate (intasomes) rather than the free enzyme. Atomic resolution structures of HIV-1 intasomes are therefore required to understand the mechanisms of inhibition and drug resistance. To date, prototype foamy virus (PFV) is the only retrovirus for which such structures have been determined. We show that PFV strand transfer complexes (STC) can be assembled on product DNA without going through the normal forward reaction pathway. The finding that a retroviral STC can be assembled in this way may provide a powerful tool to alleviate the obstacles that impede structural studies of nucleoprotein intermediates in HIV-1 DNA integration.
C1 [Yin, Zhiqi; Lapkouski, Mikalai; Yang, Wei; Craigie, Robert] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Craigie, R (reprint author), Bldg 5,Room 301,5 Mem Dr, Bethesda, MD 20892 USA.
EM bobc@helix.nih.gov
RI Yang, Wei/D-4926-2011
OI Yang, Wei/0000-0002-3591-2195
FU Intramural Program of NIDDK; NIH; AIDS Targeted Antiviral Program of the
Office of the Director of the NIH
FX Grant sponsors: Intramural Program of NIDDK, NIH, AIDS Targeted
Antiviral Program of the Office of the Director of the NIH.
NR 19
TC 8
Z9 8
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD DEC
PY 2012
VL 21
IS 12
BP 1849
EP 1857
DI 10.1002/pro.2166
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 044JT
UT WOS:000311616200006
PM 23011895
ER
PT J
AU Sousa, AA
Leapman, RD
AF Sousa, Alioscka A.
Leapman, Richard D.
TI Development and application of STEM for the biological sciences
SO ULTRAMICROSCOPY
LA English
DT Article
DE Scanning transmission electron microscopy (STEM); Mass mapping;
Macromolecular assemblies; Graphene; Gold nanoparticles; Electron energy
loss spectroscopy (EELS); Electron tomography; Cellular structure
ID TRANSMISSION ELECTRON-MICROSCOPY; ENERGY-LOSS SPECTROSCOPY; THICK
AMORPHOUS SPECIMENS; BETA-AMYLOID FIBRILS; HET-S PRION; SINGLE ATOMS;
CRYOSECTIONED CELLS; MASS DETERMINATION; GOLD CLUSTERS; TOMOGRAPHY
AB The design of the scanning transmission electron microscope (STEM), as conceived originally by Crewe and coworkers, enables the highly efficient and flexible collection of different elastic and inelastic signals resulting from the interaction of a focused probe of incident electrons with a specimen. In the present paper we provide a brief review for how the STEM today can be applied towards a range of different problems in the biological sciences, emphasizing four main areas of application. (1) For three decades, the most widely used STEM technique has been the mass determination of proteins and other macromolecular assemblies. Such measurements can be performed at low electron dose by collecting the high-angle dark-field signal using an annular detector. STEM mass mapping has proven valuable for characterizing large protein assemblies such as filamentous proteins with a well-defined mass per length.(2) The annular dark-field signal can also be used to image ultra small, functionalized nanoparticles of heavy atoms for labeling specific amino-acid sequences in protein assemblies. (3) By acquiring electron energy loss spectra (EELS) at each pixel in a hyperspectral image, it is possible to map the distributions of specific bound elements like phosphorus, calcium and iron in isolated macromolecular assemblies or in compartments within sectioned cells. Near single atom sensitivity is feasible provided that the specimen can tolerate a very high incident electron dose.( 4) Electron tomography is a new application of STEM that enables three-dimensional reconstruction of micrometer-thick sections of cells. In this technique a probe of small convergence angle gives a large depth of field through out the thickness of the specimen while maintaining a probe diameter of <2 nm; and the use of an on-axis bright-field detect or reduces the effects of beam broadening and thus improves the spatial resolution compared to that attainable by STEM dark-field tomography. Published by Elsevier B.V.
C1 [Sousa, Alioscka A.; Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
RP Leapman, RD (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
EM leapmanr@mail.nih.gov
FU National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health
FX We would like to acknowledge Dr. Guofeng Zhang and Dr. Martin
Hohmann-Marriott for providing the specimens of C. reinhardtii and
pancreatic beta cells; Mr. Daniel Cox for assistance in tomographic
reconstruction and 3D modeling; Dr. Christopher Ackerson for valuable
discussions on the synthesis of the Au144 clusters; and Ms.
April Adams for help in synthesizing the Au144 clusters. This
work was supported by the Intramural Research Programs of the National
Institute of Biomedical Imaging and Bioengineering, National Institutes
of Health.
NR 98
TC 22
Z9 22
U1 8
U2 83
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3991
J9 ULTRAMICROSCOPY
JI Ultramicroscopy
PD DEC
PY 2012
VL 123
BP 38
EP 49
DI 10.1016/j.ultramic.2012.04.005
PG 12
WC Microscopy
SC Microscopy
GA 047FF
UT WOS:000311822600006
PM 22749213
ER
PT J
AU Le Floc'h, S
Cloutier, G
Saijo, Y
Finet, G
Yazdani, SK
Deleaval, F
Rioufol, G
Pettigrew, RI
Ohayon, J
AF Le Floc'h, Simon
Cloutier, Guy
Saijo, Yoshifumi
Finet, Gerard
Yazdani, Saami K.
Deleaval, Flavien
Rioufol, Gilles
Pettigrew, Roderic I.
Ohayon, Jacques
TI A FOUR-CRITERION SELECTION PROCEDURE FOR ATHEROSCLEROTIC PLAQUE
ELASTICITY RECONSTRUCTION BASED ON IN VIVO CORONARY INTRAVASCULAR
ULTRASOUND RADIAL STRAIN SEQUENCES
SO ULTRASOUND IN MEDICINE AND BIOLOGY
LA English
DT Article
DE Atherosclerosis; Vulnerable plaques; Coronary arteries; Radial strain
elastography; Linear elasticity; Inverse problem
ID CIRCUMFERENTIAL STRESS; RADIOFREQUENCY DATA; VULNERABLE PLAQUE; CAP
THICKNESS; ELASTOGRAPHY; RUPTURE; MODEL; RISK; PRESSURE; ARTERIES
AB Plaque elasticity (i.e., modulogram) and morphology are good predictors of plaque vulnerability. Recently, our group developed an intravascular ultrasound (IVUS) elasticity reconstruction method which was successfully implemented in vitro using vessel phantoms. In vivo IVUS modulography, however, remains a major challenge as the motion of the heart prevents accurate strain field estimation. We therefore designed a technique to extract accurate strain fields and modulograms from recorded IVUS sequences. We identified a set of four criteria based on tissue overlapping, RF-correlation coefficient between two successive frames, performance of the elasticity reconstruction method to recover the measured radial strain, and reproducibility of the computed modulograms over the cardiac cycle. This four-criterion selection procedure (4-CSP) was successfully tested on IVUS sequences obtained in twelve patients referred for a directional coronary atherectomy intervention. This study demonstrates the potential of the IVUS modulography technique based on the proposed 4-CSP to detect vulnerable plaques in vivo. (E-mail: Jacques.Ohayon@imag.fr) (c) 2012 World Federation for Ultrasound in Medicine & Biology.
C1 [Le Floc'h, Simon; Deleaval, Flavien; Ohayon, Jacques] CNRS UMR 5525, UJF, Lab TIMC IMAG DyCTiM, Grenoble, France.
[Cloutier, Guy] Univ Montreal Hosp Res Ctr CRCHUM, Lab Biorheol & Med Ultrason, Montreal, PQ, Canada.
[Cloutier, Guy] Univ Montreal, Dept Radiol Radiooncol & Nucl Med, Montreal, PQ, Canada.
[Cloutier, Guy] Univ Montreal, Inst Biomed Engn, Montreal, PQ, Canada.
[Saijo, Yoshifumi] Tohoku Univ, Dept Biomed Engn, Sendai, Miyagi 980, Japan.
[Finet, Gerard; Rioufol, Gilles] Hosp Civiles Lyon, Dept Hemodynam & Intervent Cardiol, Lyon, France.
[Finet, Gerard; Rioufol, Gilles] Univ Lyon 1, INSERM Unit 886, F-69365 Lyon, France.
[Yazdani, Saami K.] CVPath Inst, Gaithersburg, MD USA.
[Pettigrew, Roderic I.] NIDDK, Lab Integrat Cardiovasc Imaging Sci, NIH, Bethesda, MD USA.
[Ohayon, Jacques] Univ Savoie, Le Bourget Du Lac, France.
RP Ohayon, J (reprint author), In3S, CNRS UMR 5525, UJF, Lab TIMC DyCTiM, Grenoble, France.
EM Jacques.Ohayon@imag.fr
RI Ohayon, Jacques/M-6576-2014
FU Agence Nationale de la Recherche (ANR), France (ATHEBIOMECH project);
Natural Sciences and Engineering Research Council of Canada (NSERC)
[323405-06]; Canadian Institutes of Health Research (CIHR) [CPG-80085];
ANR (MELANII) [09-BLANC-0423]; NSERC strategic grant [STPGP-381136-09];
valorization research program of the University Joseph Fourier (UJF),
France in partnership with Floralis-France
FX The authors thank Arnold Fertin, PhD. (TIMC Laboratory, Grenoble,
France) for his help on image analysis processing. Acknowledgements are
also addressed to Dr Younes Majdouline and Dr Marie-Helene Roy Cardinal
of the Laboratory of Biorheology and Medical Ultrasonics, University of
Montreal Hospital Research Center, for their computational supports
regarding segmentation and radial strain elastograms.-Grant supports
were provided by the Agence Nationale de la Recherche (ANR), France
(ATHEBIOMECH project) and by the collaborative health research joint
program of the Natural Sciences and Engineering Research Council of
Canada (NSERC # 323405-06) and Canadian Institutes of Health Research
(CIHR #CPG-80085). This research is now supported by a joint
international program of the ANR (MELANII project # 09-BLANC-0423) and
NSERC strategic grant #STPGP-381136-09. Financial support was also
provided by a post-doctoral appointment (S. Le Floc'h) from a
valorization research program of the University Joseph Fourier (UJF),
France in partnership with Floralis-France.
NR 54
TC 8
Z9 8
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-5629
J9 ULTRASOUND MED BIOL
JI Ultrasound Med. Biol.
PD DEC
PY 2012
VL 38
IS 12
BP 2084
EP 2097
DI 10.1016/j.ultrasmedbio.2012.07.021
PG 14
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 045HB
UT WOS:000311684900006
PM 23196202
ER
PT J
AU Jukic, AM
Wilcox, AJ
AF Jukic, A. M.
Wilcox, A. J.
TI The events of early pregnancy: prying open the black box
SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY
LA English
DT Editorial Material
ID IMPLANTATION
C1 [Jukic, A. M.; Wilcox, A. J.] NIEHS, Epidemiol Branch, Durham, NC 27709 USA.
RP Jukic, AM (reprint author), NIEHS, Epidemiol Branch, POB 12233, Durham, NC 27709 USA.
EM jukica@niehs.nih.gov
OI Wilcox, Allen/0000-0002-3376-1311
FU Intramural NIH HHS
NR 7
TC 1
Z9 1
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0960-7692
J9 ULTRASOUND OBST GYN
JI Ultrasound Obstet. Gynecol.
PD DEC
PY 2012
VL 40
IS 6
BP 617
EP 618
DI 10.1002/uog.12329
PG 2
WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
Medical Imaging
SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
Medical Imaging
GA 047RH
UT WOS:000311857700001
PM 23192991
ER
PT J
AU Canto, JG
Goldberg, RJ
Sopko, G
AF Canto, John G.
Goldberg, Robert J.
Sopko, George
TI A call to standardize symptom presentation in acute coronary syndromes
SO AMERICAN HEART JOURNAL
LA English
DT Editorial Material
ID ACUTE MYOCARDIAL-INFARCTION; CHEST-PAIN; HOSPITAL MORTALITY; PATIENT
DELAY; HEART-DISEASE; REACT TRIAL; INTERVENTION; PREVALENCE; WOMEN; SEX
C1 [Canto, John G.] Watson Clin, Lakeland, FL 33805 USA.
[Canto, John G.] Lakeland Reg Med Ctr, Chest Pain Ctr, Lakeland, FL USA.
[Goldberg, Robert J.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA.
[Sopko, George] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Canto, JG (reprint author), Watson Clin, Lakeland, FL 33805 USA.
EM jcanto@watsonclinic.com
NR 17
TC 7
Z9 7
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD DEC
PY 2012
VL 164
IS 6
BP 801
EP 806
DI 10.1016/j.ahj.2012.08.012
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 044PU
UT WOS:000311634500005
PM 23194478
ER
PT J
AU Simone, CB
Hampshire, MK
Vachani, C
Metz, JM
AF Simone, Charles B., II
Hampshire, Margaret K.
Vachani, Carolyn
Metz, James M.
TI The Utilization of Oncology Web-based Resources in Spanish-speaking
Internet Users
SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS
LA English
DT Article
DE disparities; oncology; Spanish; Internet; cancer resources
ID CANCER SCREENING DISPARITIES; NON-HISPANIC WOMEN; UNITED-STATES;
BREAST-CANCER; SOCIOECONOMIC-STATUS; CERVICAL-CANCER; US WOMEN; HEALTH
INFORMATION; ETHNIC-DIFFERENCES; PROSTATE-CANCER
AB Objectives: There currently are few web-based resources written in Spanish providing oncology-specific information. This study examines utilization of Spanish-language oncology web-based resources and evaluates oncology-related Internet browsing practices of Spanish-speaking patients.
Methods: OncoLink (http://www.oncolink.org) is the oldest and among the largest Internet-based cancer information resources. In September 2005, OncoLink pioneered OncoLink en espanol (OEE) (http://es.oncolink.org), a Spanish translation of OncoLink. Internet utilization data on these sites for 2006 to 2007 were compared.
Results: Visits to OncoLink rose from 4,440,843 in 2006 to 5,125,952 in 2007. OEE had 204,578 unique visitors and 240,442 visits in 2006, and 351,228 visitors and 412,153 visits in 2007. Although there was no time predilection for viewing OncoLink, less relative browsing on OEE was conducted during weekends and early morning hours. Although OncoLink readers searched for information on the most common cancers in the United States, OEE readers most often search for gastric, vaginal, osteosarcoma, leukemia, penile, cervical, and testicular malignancies. Average visit duration on OEE was shorter, and fewer readers surveyed OEE more than 15 minutes (4.5% vs. 14.9%, P < 0.001).
Conclusions: Spanish-speaking users of web-based oncology resources are increasingly using the Internet to supplement their cancer knowledge. Limited available resources written in Spanish contribute to disparities in information access and disease outcomes. Spanish-speaking oncology readers differ from English-speaking readers in day and time of Internet browsing, visit duration, Internet search patterns, and types of cancers searched. By acknowledging these differences, content of web-based oncology resources can be developed to best target the needs of Spanish-speaking viewers.
C1 [Simone, Charles B., II; Hampshire, Margaret K.; Vachani, Carolyn; Metz, James M.] Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
[Simone, Charles B., II] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Simone, CB (reprint author), Hosp Univ Penn, Dept Radiat Oncol, 2 Donner Bldg,3400 Spruce St, Philadelphia, PA 19104 USA.
EM csimone@alumni.upenn.edu
FU Intramural NIH HHS [Z99 CA999999]
NR 79
TC 3
Z9 3
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-3732
J9 AM J CLIN ONCOL-CANC
JI Am. J. Clin. Oncol.-Cancer Clin. Trials
PD DEC
PY 2012
VL 35
IS 6
BP 520
EP 526
DI 10.1097/COC.0b013e31821d4906
PG 7
WC Oncology
SC Oncology
GA 041FO
UT WOS:000311384000003
PM 21654312
ER
PT J
AU Meyers, CM
Briggs, JP
AF Meyers, Catherine M.
Briggs, Josephine P.
TI Silymarin for Diabetic Nephropathy: The Challenges of Botanical Product
Research
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Editorial Material
ID CHRONIC HEPATITIS-C; LIVER-DISEASE; MILK THISTLE; THERAPY; TRIAL
C1 [Meyers, Catherine M.; Briggs, Josephine P.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
RP Briggs, JP (reprint author), 31 Ctr Dr,Room 2B11, Bethesda, MD 20892 USA.
EM briggsj@mail.nih.gov
RI Briggs, Josephine/B-9394-2009
OI Briggs, Josephine/0000-0003-0798-1190
NR 15
TC 2
Z9 2
U1 0
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 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD DEC
PY 2012
VL 60
IS 6
BP 887
EP 889
DI 10.1053/j.ajkd.2012.09.002
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 034BM
UT WOS:000310845100002
PM 23141996
ER
PT J
AU Roshanravan, B
Khatri, M
Robinson-Cohen, C
Levin, G
Patel, KV
de Boer, IH
Seliger, S
Ruzinski, J
Himmelfarb, J
Kestenbaum, B
AF Roshanravan, Baback
Khatri, Minesh
Robinson-Cohen, Cassianne
Levin, Greg
Patel, Kushang V.
de Boer, Ian H.
Seliger, Stephen
Ruzinski, John
Himmelfarb, Jonathan
Kestenbaum, Bryan
TI A Prospective Study of Frailty in Nephrology-Referred Patients With CKD
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Frailty; chronic kidney disease; mortality; functional limitation
ID CHRONIC KIDNEY-DISEASE; SERUM CYSTATIN-C; CHRONIC RENAL-INSUFFICIENCY;
GLOMERULAR-FILTRATION-RATE; BODY-MASS INDEX; QUALITY-OF-LIFE; OLDER
WOMEN; INSULIN-RESISTANCE; PHYSICAL FRAILTY; INFLAMMATION
AB Background: Frailty is a construct developed to characterize a state of reduced functional capacity in older adults. However, there are limited data describing the prevalence or consequences of frailty in middle-aged patients with chronic kidney disease (CKD).
Study Design: Observational study.
Setting & Participants: 336 non-dialysis-dependent patients with stages 1-4 CKD with estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m(2) (by the CKD-EPI [CKD Epidemiology Collaboration] serum creatinine-based equation) or evidence of microalbuminuria enrolled in the Seattle Kidney Study, a clinic-based cohort study. Findings were compared with community-dwelling older adults in the Cardiovascular Health Study.
Outcome: Prevalence and determinants of frailty in addition to its association with the combined outcome of all-cause mortality or renal replacement therapy.
Measurements: We defined frailty according to established criteria as 3 or more of the following characteristics: slow gait, weakness, unintentional weight loss, exhaustion, and low physical activity. We estimated kidney function using serum cystatin C concentrations (eGFR(cys)) to minimize confounding due to relationships of serum creatinine levels with muscle mass and frailty.
Results: The mean age of the study population was 59 years and mean eGFR(cys) was 51 mL/min/1.73 m(2). The prevalence of frailty (14.0%) was twice that of the much older non-CKD reference population (P < 0.01). The most common frailty components were physical inactivity and exhaustion. After adjustment including diabetes, eGFR(cys) categories of < 30 and 30-44 mL/min/1.73 m(2) were associated with a 2.8-(95% CI, 1.3-6.3) and 2.1 (95% CI, 1.0-4.7)-fold greater prevalence of frailty compared with GFR(cys) >= 60 mL/min/1.73 m(2). There were 63 events during a median 987 days of follow-up. After adjustment, the frailty phenotype was associated with an estimated 2.5 (95% CI, 1.4-4.4)-fold greater risk of death or dialysis therapy.
Limitations: Cross-sectional study design obscures inference regarding temporal relationships between CKD and frailty.
Conclusions: Frailty is relatively common in middle-aged patients with CKD and is associated with lower eGFRcys and increased risk of death or dialysis therapy. Am J Kidney Dis. 60(6): 912-921. (C) 2012 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Roshanravan, Baback; de Boer, Ian H.; Ruzinski, John; Himmelfarb, Jonathan; Kestenbaum, Bryan] Univ Washington, Kidney Res Inst, Div Nephrol, Dept Med, Seattle, WA 98104 USA.
[Khatri, Minesh] Columbia Univ, Dept Med, Div Nephrol, New York, NY USA.
[Robinson-Cohen, Cassianne] Univ Washington, Kidney Res Inst, Dept Epidemiol, Seattle, WA 98104 USA.
[Levin, Greg] Univ Washington, Kidney Res Inst, Dept Biostat, Seattle, WA 98104 USA.
[Patel, Kushang V.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Seliger, Stephen] Univ Maryland, Div Nephrol, Baltimore, MD 21201 USA.
RP Roshanravan, B (reprint author), Univ Washington, Kidney Res Inst, Div Nephrol, Dept Med, Box 359606,325 9th Ave, Seattle, WA 98104 USA.
EM broshanr@u.washington.edu
OI Robinson-Cohen, Cassianne/0000-0003-4783-7046
FU National Institutes of Health (NIH) [RO1 HL070938]; NIH [RO1 DK087726];
Kidney Research Institute, NIH [T32]; Northwest Kidney Center
Foundation; National Institute on Aging, NIH; Veterans Affairs Puget
Sound Health Care System, Seattle, WA
FX Support: This work was supported by National Institutes of Health (NIH)
RO1 HL070938 (Drs Himmelfarb and Kestenbaum) and NIH RO1 DK087726 (Dr de
Boer); support from the Kidney Research Institute, NIH T32 (Dr
Roshanravan); and an unrestricted grant from the Northwest Kidney Center
Foundation. This research was supported in part by the Intramural
Research Program of the National Institute on Aging, NIH (Dr Patel).
This study is the result of work supported by resources from the
Veterans Affairs Puget Sound Health Care System, Seattle, WA.
NR 48
TC 72
Z9 72
U1 1
U2 9
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD DEC
PY 2012
VL 60
IS 6
BP 912
EP 921
DI 10.1053/j.ajkd.2012.05.017
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 034BM
UT WOS:000310845100007
PM 22770927
ER
PT J
AU Wong, CJ
Moxey-Mims, M
Jerry-Fluker, J
Warady, BA
Furth, SL
AF Wong, Cynthia J.
Moxey-Mims, Marva
Jerry-Fluker, Judith
Warady, Bradley A.
Furth, Susan L.
TI CKiD (CKD in Children) Prospective Cohort Study: A Review of Current
Findings
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Review
DE Chronic kidney disease; children; CKD progression; neurodevelopment;
cardiovascular disease; growth
ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE;
EVALUATION-PROGRAM KEEP; PLASMA IOHEXOL DISAPPEARANCE; LEFT-VENTRICULAR
HYPERTROPHY; BLOOD-PRESSURE; RACIAL DISPARITIES; RISK-FACTORS; FAILURE
AB Chronic kidney disease (CKD) is a life-long condition associated with substantial morbidity and premature death due to complications from a progressive decrease in kidney function. The incidence and prevalence of all stages of CKD in children continues to increase worldwide. Between 2000 and 2008, the kidney replacement therapy incidence rate in those aged 0-19 years increased 5.9% to 15 per million population, highlighting the importance of CKD research in children. Many comorbid conditions seen in adults with CKD, including cardiovascular disease and cognitive impairment, also are highly prevalent in children, implicitly demonstrating the crucial need for initiating therapy early to improve health outcomes in children with CKD. The CKiD (Chronic Kidney Disease in Children) Study is a prospective cohort study of 586 children aged 1-16 years with an estimated glomerular filtration rate of 30-90 mL/min/1.73 m(2). Since its inception, CKiD has identified risk factors for CKD progression and cardiovascular disease in children with CKD and highlighted the effects of CKD on outcomes unique to children, including neurocognitive development and growth. This review summarizes the findings to date, illustrating the spectrum of CKD-associated complications in children and emphasizing areas requiring further investigation. Taken in sum, these elements stress that initiating treatment at an early age is essential for reducing long-term morbidity and mortality in children with CKD. Am J Kidney Dis. 60(6): 1002-1011. (C) 2012 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Wong, Cynthia J.] Lucile Packard Childrens Hosp, Dept Pediat, Div Nephrol, Palo Alto, CA USA.
[Moxey-Mims, Marva] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Jerry-Fluker, Judith] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Warady, Bradley A.] Univ Missouri Kansas City Sch Med, Dept Pediat, Div Nephrol, Childrens Mercy Hosp, Kansas City, MO USA.
[Furth, Susan L.] Childrens Hosp Philadelphia, Dept Pediat, Div Nephrol, Philadelphia, PA 19104 USA.
RP Wong, CJ (reprint author), 300 Pasteur Dr,Rm G306, Stanford, CA 94305 USA.
EM wongcy8@stanford.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK); National Institute of Neurological Disorders and Stroke;
National Institute of Child Health and Human Development; National
Heart, Lung and Blood Institute
FX The CKiD Study is supported by grants from the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute
of Neurological Disorders and Stroke, National Institute of Child Health
and Human Development, and National Heart, Lung and Blood Institute.
Study sponsors had a role in the study design; collection, analysis, and
interpretation of data; writing this review; and the decision to submit
the review for publication.
NR 62
TC 58
Z9 71
U1 0
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD DEC
PY 2012
VL 60
IS 6
BP 1002
EP 1011
DI 10.1053/j.ajkd.2012.07.018
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 034BM
UT WOS:000310845100018
PM 23022429
ER
PT J
AU Solomon, BD
Bear, KA
Kimonis, V
de Klein, A
Scott, DA
Shaw-Smith, C
Tibboel, D
Reutter, H
Giampietro, PF
AF Solomon, Benjamin D.
Bear, Kelly A.
Kimonis, Virginia
de Klein, Annelies
Scott, Daryl A.
Shaw-Smith, Charles
Tibboel, Dick
Reutter, Heiko
Giampietro, Philip F.
TI Clinical geneticists' views of VACTERL/VATER association
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE VACTERL association; VATER association
ID DE-LANGE-SYNDROME; ULNAR-MAMMARY SYNDROME; HOLT-ORAM-SYNDROME;
ROTHSCHILD/SCHINZEL-PHOCOMELIA-SYNDROME; PALLISTER-HALL-SYNDROME;
TOWNES-BROCKS-SYNDROME; ABSENT RADIUS SYNDROME; FOOT-GENITAL SYNDROME;
FANCONI-ANEMIA; VATER-ASSOCIATION
AB VACTERL association (sometimes termed VATER association depending on which component features are included) is typically defined by the presence of at least three of the following congenital malformations, which tend to statistically co-occur in affected individuals: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities. Although the clinical criteria for VACTERL association may appear to be straightforward, there is wide variability in the way clinical geneticists define the disorder and the genetic testing strategy they use when confronted with an affected patient. In order to describe this variability and determine the most commonly used definitions and testing modalities, we present the results of survey responses by 121 clinical geneticists. We discuss the results of the survey responses, provide a literature review and commentary from a group of physicians who are currently involved in clinical and laboratory-based research on VACTERL association, and offer an algorithm for genetic testing in patients with this association. (C) 2012 Wiley Periodicals, Inc.
C1 [Solomon, Benjamin D.; Bear, Kelly A.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Bear, Kelly A.] Walter Reed Mil Med Ctr, Dept Neonatol, Bethesda, MD USA.
[Kimonis, Virginia] Univ Calif Irvine, Dept Pediat, Div Genet & Metab, Med Ctr, Orange, CA 92668 USA.
[de Klein, Annelies] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Scott, Daryl A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Shaw-Smith, Charles] Royal Devon & Exeter Fdn Trust, Exeter, Devon, England.
[Tibboel, Dick] Erasmus MC, Dept Pediat Surg, Rotterdam, Netherlands.
[Reutter, Heiko] Univ Bonn, Dept Neonatol, Childrens Hosp, Bonn, Germany.
[Reutter, Heiko] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Giampietro, Philip F.] Univ Wisconsin, Dept Pediat, Madison, WI USA.
RP Solomon, BD (reprint author), NIH, MSC 3717,Bldg 35,Room 1B-207, Bethesda, MD 20892 USA.
EM solomonb@mail.nih.gov
FU National Human Genome Research Institute, National Institutes of Health,
Department of Health and Human Services, United States of America; Doris
Duke Charitable Foundation [2007053]
FX Grant sponsor: National Human Genome Research Institute, National
Institutes of Health, Department of Health and Human Services, United
States of America; Grant sponsor: Doris Duke Charitable Foundation;
Grant number: 2007053.
NR 118
TC 23
Z9 23
U1 2
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD DEC
PY 2012
VL 158A
IS 12
BP 3087
EP 3100
DI 10.1002/ajmg.a.35638
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 041KX
UT WOS:000311401800016
PM 23165726
ER
PT J
AU Hall, KL
Stipelman, BA
Eddens, KS
Kreuter, MW
Bame, SI
Meissner, HI
Yabroff, KR
Purnell, JQ
Ferrer, R
Ribisl, KM
Glasgow, R
Linnan, LA
Taplin, S
Fernandez, ME
AF Hall, Kara L.
Stipelman, Brooke A.
Eddens, Katherine S.
Kreuter, Matthew W.
Bame, Sherry I.
Meissner, Helen I.
Yabroff, K. Robin
Purnell, Jason Q.
Ferrer, Rebecca
Ribisl, Kurt M.
Glasgow, Russell
Linnan, Laura A.
Taplin, Stephen
Fernandez, Maria E.
TI Advancing Collaborative Research with 2-1-1 to Reduce Health Disparities
Challenges, Opportunities, and Recommendations
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
C1 [Hall, Kara L.; Stipelman, Brooke A.] NCI, Sci Res & Technol Branch, Rockville, MD USA.
[Ferrer, Rebecca] NCI, Basic Biobehav & Psychol Sci Branch, Rockville, MD USA.
[Taplin, Stephen] NCI, Proc Care Res Branch, Rockville, MD USA.
[Yabroff, K. Robin] NCI, Hlth Serv & Econ Branch, Rockville, MD USA.
[Glasgow, Russell] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Meissner, Helen I.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Eddens, Katherine S.] Univ Kentucky, Coll Publ Hlth, Dept Hlth Behav, Lexington, KY USA.
[Kreuter, Matthew W.] Washington Univ, Hlth Commun Res Lab, St Louis, MO USA.
[Kreuter, Matthew W.; Purnell, Jason Q.] Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63130 USA.
[Bame, Sherry I.] Texas A&M Univ, Urban Planning Program, College Stn, TX USA.
[Fernandez, Maria E.] Univ Texas Houston, Sch Publ Hlth, Ctr Hlth Promot & Prevent Res, Houston, TX USA.
[Ribisl, Kurt M.; Linnan, Laura A.] Univ N Carolina, Dept Hlth Behav, UNC Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
RP Hall, KL (reprint author), 6130 Execut Blvd,Room 4078, Rockville, MD 20850 USA.
EM hallka@mail.nih.gov
RI Ribisl, Kurt/C-4867-2015;
OI Ribisl, Kurt/0000-0003-3318-8524; Yabroff, K. Robin/0000-0003-0644-5572
FU CDC [IU48DP001903]; National Cancer Institute [P50-CA095815]; National
Cancer Institute, NIH; Office of Behavioral and Social Sciences, NIH
[HHSN261201100469P]; National Cancer Institute (NCI); Office of
Behavioral and Social Science Research (OBSSR) of the NIH
[HHSN261201100469P]
FX The authors thank Dhavan Shah (University of Wisconsin-Madison) for his
helpful comments in the preparation of this paper. This work was
supported by grants from the CDC (IU48DP001903) and the National Cancer
Institute (P50-CA095815). This project also was funded, in part, with
federal funds from the National Cancer Institute, NIH, and the Office of
Behavioral and Social Sciences, NIH (contract no. HHSN261201100469P).
The content of this publication does not necessarily reflect the views
or policies of the DHHS, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.;
Publication of this article was supported by funding from the National
Cancer Institute (NCI) and the Office of Behavioral and Social Science
Research (OBSSR) of the NIH (HHSN261201100469P).
NR 26
TC 9
Z9 9
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 DEC
PY 2012
VL 43
IS 6
SU 5
BP S518
EP S528
DI 10.1016/j.amepre.2012.09.026
PG 11
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 037YK
UT WOS:000311142200018
PM 23157775
ER
PT J
AU Kato, GJ
AF Kato, Gregory J.
TI Understanding the Erythrocyte Storage Lesion
SO ANESTHESIOLOGY
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; RED-CELL STORAGE; STORED-BLOOD;
GUINEA-PIGS; HEMOGLOBIN; TRANSFUSION; DESIGN; AGE
C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Kato, GJ (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
EM gkato@mail.nih.gov
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU Intramural NIH HHS [ZIA HL006014-02]; NHLBI NIH HHS [1 ZIA HL006014-03,
ZIA HL006014]
NR 17
TC 2
Z9 2
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD DEC
PY 2012
VL 117
IS 6
BP 1159
EP 1161
DI 10.1097/ALN.0b013e318272d8ac
PG 3
WC Anesthesiology
SC Anesthesiology
GA 041PY
UT WOS:000311414900005
PM 23168421
ER
PT J
AU Acker, MA
Pagani, FD
Stough, WG
Mann, DL
Jessup, M
Kormos, R
Slaughter, MS
Baldwin, T
Stevenson, L
Aaronson, KD
Miller, L
Naftel, D
Yancy, C
Rogers, J
Teuteberg, J
Starling, RC
Griffith, B
Boyce, S
Westaby, S
Blume, E
Wearden, P
Higgins, R
Mack, M
AF Acker, Michael A.
Pagani, Francis D.
Stough, Wendy Gattis
Mann, Douglas L.
Jessup, Mariell
Kormos, Robert
Slaughter, Mark S.
Baldwin, Timothy
Stevenson, Lynne
Aaronson, Keith D.
Miller, Leslie
Naftel, David
Yancy, Clyde
Rogers, Joseph
Teuteberg, Jeffrey
Starling, Randall C.
Griffith, Bartley
Boyce, Steven
Westaby, Stephen
Blume, Elizabeth
Wearden, Peter
Higgins, Robert
Mack, Michael
TI Statement Regarding the Pre and Post Market Assessment of Durable,
Implantable Ventricular Assist Devices in the United States
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID ADVANCED HEART-FAILURE; INTERMACS ANNUAL-REPORT; CLINICAL-TRIAL DESIGN;
CONTINUOUS-FLOW; CARDIOVASCULAR DEVICES; MEDICAL DEVICES;
CARDIAC-RESYNCHRONIZATION; DESTINATION THERAPY; SUPPORT; OUTCOMES
AB The incorporation of complex medical device technologies into clinical practice is governed by critical oversight of the US Food and Drug Administration. This regulatory process requires a judicious balance between assuring safety and efficacy, while providing efficient review to facilitate access to innovative therapies. Recent contrasting views of the regulatory process have emphasized the difficulties in obtaining an optimal balance. Mechanical circulatory support has evolved to become an important therapy for patients who have advanced heart failure with the advent of more durable, implantable ventricular assist devices. The regulatory oversight of these new technologies has been difficult owing to the complexities of these devices, associated adverse event profile, and severity of illness of the intended patient population. Maintaining a regulatory environment to foster efficient introduction of safe and effective technologies is critical to the success of ventricular assist device therapy and the health of patients with advanced heart failure. Physicians representing key surgical and cardiology societies, and representatives from the Food and Drug Administration, National Heart Lung, and Blood Institute, Centers for Medicare and Medicaid Services, Interagency Registry of Mechanically Assisted Circulatory Support, and industry partners gathered to discuss relevant issues regarding the current regulatory environment assessing ventricular assist devices. The goal of the meeting was to explore innovative ways to foster the introduction of technologically advanced, safe, and effective ventricular assist devices. The following summary reflects opinions and conclusions endorsed by The Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, Heart Failure Society of America, International Society for Heart and Lung Transplantation, and Interagency Registry of Mechanically Assisted Circulatory Support.
C1 [Acker, Michael A.] Univ Penn, Div Cardiothorac Surg, Philadelphia, PA 19104 USA.
[Pagani, Francis D.] Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA.
[Stough, Wendy Gattis] Campbell Univ, Coll Pharm & Hlth Sci, Buies Creek, NC 27506 USA.
[Mann, Douglas L.] Washington Univ, Div Cardiovasc, St Louis, MO USA.
[Jessup, Mariell] Univ Penn, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
[Kormos, Robert] Univ Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA USA.
[Slaughter, Mark S.] Univ Louisville, Div Cardiothorac Surg, Louisville, KY 40292 USA.
[Baldwin, Timothy] NHLBI, Bethesda, MD 20892 USA.
[Stevenson, Lynne] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Aaronson, Keith D.] Univ Michigan, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Miller, Leslie] Univ S Florida, Dept Cardiovasc Sci, Tampa, FL USA.
[Naftel, David] Univ Alabama Birmingham, Dept Cardiothorac Surg, Birmingham, AL USA.
[Yancy, Clyde] Northwestern Univ, Div Cardiol, Chicago, IL 60611 USA.
[Rogers, Joseph] Duke Univ, Div Cardiol, Durham, NC USA.
[Teuteberg, Jeffrey] Univ Pittsburgh, Med Ctr, Inst Heart & Vasc, Pittsburgh, PA USA.
[Starling, Randall C.] Cleveland Clin, Cleveland, OH 44106 USA.
[Griffith, Bartley] Univ Maryland, Div Cardiac Surg, Baltimore, MD 21201 USA.
[Boyce, Steven] Washington Hosp Ctr, Dept Cardiac Surg, MedStar Heart Inst, Washington, DC 20010 USA.
[Westaby, Stephen] John Radcliffe Hosp, Oxford Heart Ctr, Oxford OX3 9DU, England.
[Blume, Elizabeth] Bostons Childrens Hosp, Dept Cardiol, Boston, MA USA.
[Wearden, Peter] Childrens Hosp Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA 15213 USA.
[Higgins, Robert] Ohio State Univ, Div Cardiac Surg, Columbus, OH 43210 USA.
[Mack, Michael] Med City Dallas Hosp, Dallas, TX USA.
RP Acker, MA (reprint author), Hosp Univ Penn, 3400 Spruce St,6 Silverstein Pavil, Philadelphia, PA 19104 USA.
EM michael.acker@uphs.upenn.edu
OI Mann, Douglas /0000-0002-2516-0145
NR 35
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 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD DEC
PY 2012
VL 94
IS 6
BP 2147
EP 2158
DI 10.1016/j.athoracsur.2012.09.040
PG 12
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 041XW
UT WOS:000311436300077
PM 23153481
ER
PT J
AU Acker, MA
Pagani, FD
Stough, WG
Mann, DL
Jessup, M
Kormos, R
Slaughter, MS
Baldwin, T
Stevenson, L
Aaronson, KD
Miller, L
Naftel, D
Yancy, C
Rogers, J
Teuteberg, J
Starling, RC
Griffith, B
Boyce, S
Westaby, S
Blume, E
Wearden, P
Higgins, R
Mack, M
AF Acker, Michael A.
Pagani, Francis D.
Stough, Wendy Gattis
Mann, Douglas L.
Jessup, Mariell
Kormos, Robert
Slaughter, Mark S.
Baldwin, Timothy
Stevenson, Lynne
Aaronson, Keith D.
Miller, Leslie
Naftel, David
Yancy, Clyde
Rogers, Joseph
Teuteberg, Jeffrey
Starling, Randall C.
Griffith, Bartley
Boyce, Steven
Westaby, Stephen
Blume, Elizabeth
Wearden, Peter
Higgins, Robert
Mack, Michael
TI Statement Regarding the Pre and Post Market Assessment of Durable,
Implantable Ventricular Assist Devices in the United States: Executive
Summary
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID CLINICAL-TRIAL DESIGN; CARDIOVASCULAR DEVICES; MEDICAL DEVICES;
HEART-FAILURE; SURVEILLANCE; SUPPORT; FDA
AB The incorporation of complex medical device technologies into clinical practice is governed by critical oversight of the US Food and Drug Administration. This regulatory process requires a judicious balance between assuring safety and efficacy, while providing efficient review to facilitate access to innovative therapies. Recent contrasting views of the regulatory process have emphasized the difficulties in obtaining an optimal balance. Mechanical circulatory support has evolved to become an important therapy for patients with advanced heart failure with the advent of more durable, implantable ventricular assist devices. The regulatory oversight of these new technologies has been difficult owing to the complexities of these devices, associated adverse event profile, and severity of illness of the intended patient population. Maintaining a regulatory environment to foster efficient introduction of safe and effective technologies is critical to the success of ventricular assist device therapy and the health of patients with advanced heart failure. Physicians representing key surgical and cardiology societies, and representatives from the Food and Drug Administration, National Heart Lung, and Blood Institute, Centers for Medicare and Medicaid Services, Interagency Registry of Mechanically Assisted Circulatory Support, and industry partners gathered to discuss relevant issues regarding the current regulatory environment assessing ventricular assist devices. The goal of the meeting was to explore innovative ways to foster the introduction of technologically advanced, safe, and effective ventricular assist devices. The following summary reflects opinions and conclusions endorsed by The Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, Heart Failure Society of America, International Society for Heart and Lung Transplantation, and the Interagency Registry of Mechanically Assisted Circulatory Support. (Ann Thorac Surg 2012;94:e163-8) (c) 2012 by The Society of Thoracic Surgeons, American Heart Association, Inc, and International Society for Heart and Lung Transplantation
C1 [Acker, Michael A.] Univ Penn, Div Cardiothorac Surg, Philadelphia, PA 19104 USA.
[Pagani, Francis D.] Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA.
[Stough, Wendy Gattis] Campbell Univ, Coll Pharm & Hlth Sci, Buies Creek, NC 27506 USA.
[Mann, Douglas L.] Washington Univ, Div Cardiovasc, St Louis, MO USA.
[Jessup, Mariell] Univ Penn, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
[Kormos, Robert] Univ Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA USA.
[Slaughter, Mark S.] Univ Louisville, Div Cardiothorac Surg, Louisville, KY 40292 USA.
[Baldwin, Timothy] NHLBI, Bethesda, MD 20892 USA.
[Stevenson, Lynne] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Aaronson, Keith D.] Univ Michigan, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Miller, Leslie] Univ S Florida, Div Cardiovasc Med, Tampa, FL USA.
[Naftel, David] Univ Alabama Birmingham, Dept Cardiothorac Surg, Birmingham, AL USA.
[Yancy, Clyde] Northwestern Univ, Div Cardiol, Chicago, IL 60611 USA.
[Rogers, Joseph] Duke Univ, Div Cardiol, Durham, NC USA.
[Teuteberg, Jeffrey] Univ Pittsburgh, Med Ctr, Inst Heart & Vasc, Pittsburgh, PA USA.
[Starling, Randall C.] Cleveland Clin, Cleveland, OH 44106 USA.
[Griffith, Bartley] Univ Maryland, Div Cardiac Surg, Baltimore, MD 21201 USA.
[Boyce, Steven] Washington Hosp Ctr, MedStar Heart Inst, Dept Cardiac Surg, Washington, DC 20010 USA.
[Westaby, Stephen] John Radcliffe Hosp, Oxford Heart Ctr, Oxford OX3 9DU, England.
[Blume, Elizabeth] Bostons Childrens Hosp, Dept Cardiol, Boston, MA USA.
[Wearden, Peter] Childrens Hosp Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA 15213 USA.
[Higgins, Robert] Ohio State Univ, Div Cardiac Surg, Columbus, OH 43210 USA.
[Mack, Michael] Med City Dallas Hosp, Dallas, TX USA.
RP Acker, MA (reprint author), Hosp Univ Penn, 3400 Spruce St,6 Silverstein Pavil, Philadelphia, PA 19104 USA.
EM michael.acker@uphs.upenn.edu
RI Stough, Wendy/R-4287-2016;
OI Stough, Wendy/0000-0001-8290-1205; Mann, Douglas /0000-0002-2516-0145
NR 14
TC 1
Z9 1
U1 0
U2 2
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 DEC
PY 2012
VL 94
IS 6
BP E163
EP E168
DI 10.1016/j.athoracsur.2012.09.041
PG 6
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 041XW
UT WOS:000311436300011
PM 23153480
ER
PT J
AU Geliebter, A
Gibson, CD
Hernandez, DB
Atalayer, D
Kwon, A
Lee, MI
Mehta, N
Phair, D
Gluck, ME
AF Geliebter, Allan
Gibson, Charlisa D.
Hernandez, Dominica B.
Atalayer, Deniz
Kwon, Anne
Lee, Michelle I.
Mehta, Nandini
Phair, Donna
Gluck, Marci E.
TI Plasma cortisol levels in response to a cold pressor test did not
predict appetite or ad libitum test meal intake in obese women
SO APPETITE
LA English
DT Article
DE Stress; Obesity; Cortisol; Food intake
ID BINGE-EATING DISORDER; X-RAY ABSORPTIOMETRY; BIOELECTRICAL-IMPEDANCE;
BODY-COMPOSITION; STRESS-RESPONSE; UNITED-STATES; BEHAVIOR; OVERWEIGHT
AB Heightened cortisol response to stress due to hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis may stimulate appetite and food intake. In this study, we assessed cortisol responsivity to a cold pressor test (CPT) as well as appetite ratings and subsequent test meal intake (TMI) in obese women. Following an overnight fast on two counterbalanced days, 20 obese women immersed their non-dominant hand for 2 min in ice water (CPT) or warm water (WW) as a control. Plasma cortisol (ng/ml), heart rate, and blood pressure, as well as ratings of stress, pain, and appetite, were serially acquired. An ad libitum liquid meal was offered at 45 min and intake measured covertly. Fasting cortisol was higher at 15 min (mean peak cortisol) following the CPT compared to WW. Higher stress was reported at 2 and 15 min for the CPT compared to WW. Pain, an indirect marker of the acute stress, systolic and diastolic blood pressure increased following the CPT at 2 min compared to WW. Hunger decreased after the CPT at 2 and 15 min, and desire to eat ratings were lower following CPT compared to WW. Subjects did not have greater test meal intake (TMI) following CPT compared to WW. There was also no significant relationship between cortisol levels following stress and TMI, indicating that cortisol did not predict subsequent intake in obese women. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Geliebter, Allan; Gibson, Charlisa D.; Hernandez, Dominica B.; Atalayer, Deniz; Kwon, Anne; Lee, Michelle I.; Mehta, Nandini; Phair, Donna] St Lukes Roosevelt Hosp, NY Obes Nutr Res Ctr, New York, NY 10025 USA.
[Geliebter, Allan] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Geliebter, Allan; Gibson, Charlisa D.; Atalayer, Deniz] Columbia Univ, Inst Human Nutr, New York, NY 10032 USA.
[Geliebter, Allan] Touro Coll, New York, NY 10010 USA.
[Kwon, Anne] Dartmouth Hitchcock Med Ctr, Dept Psychiat, Hanover, NH USA.
[Gluck, Marci E.] NIDDKD, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ 85016 USA.
RP Gibson, CD (reprint author), St Lukes Roosevelt Hosp, NY Obes Nutr Res Ctr, New York, NY 10025 USA.
EM cg2571@columbia.edu
FU NIDDK [RO3 DK068392]; NIH [RO1 DK074046]; NY Obesity Nutrition Research
Center [P30DK026687]; Clinical Research Resource (CRR) at Columbia
University [UL1 RR024156]
FX Supported in part by the Intramural Research Program of the NIDDK - RO3
DK068392 (PI-M.E.G/A.G) and NIH - RO1 DK074046 (PI-A.G.). Assays were
performed by the Hormone-Meatbolite core of the NY Obesity Nutrition
Research Center (#P30DK026687). Clinical services provided by the
Clinical Research Resource (CRR) at Columbia University (#UL1 RR024156).
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the NIH. CTSA. Disclosure
information: All authors have nothing to disclose.
NR 30
TC 3
Z9 3
U1 1
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0195-6663
J9 APPETITE
JI Appetite
PD DEC
PY 2012
VL 59
IS 3
BP 956
EP 959
DI 10.1016/j.appet.2012.08.025
PG 4
WC Behavioral Sciences; Nutrition & Dietetics
SC Behavioral Sciences; Nutrition & Dietetics
GA 037VP
UT WOS:000311134900044
PM 22983369
ER
PT J
AU Avery, CL
Kucharska-Newton, A
Monda, KL
Sharrett, AR
Mosley, TH
Klein, BE
Cotch, MF
Wong, TY
Klein, R
AF Avery, Christy L.
Kucharska-Newton, Anna
Monda, Keri L.
Sharrett, A. Richey
Mosley, Thomas H.
Klein, Barbara E.
Cotch, Mary Frances
Wong, Tien Y.
Klein, Ronald
TI Impact of long-term measures of glucose and blood pressure on the
retinal microvasculature
SO ATHEROSCLEROSIS
LA English
DT Article
DE Epidemiology; Microvascular disease; Retinopathy; Glucose; Blood
pressure
ID ATHEROSCLEROSIS RISK; DIABETES-MELLITUS; RETINOPATHY; COMMUNITIES;
ABNORMALITIES; HYPERTENSION; DISEASE; POPULATION; DIAGNOSIS; TYPE-2
AB Objective: Retinopathy and retinal microvascular abnormalities are common in adult populations, yet few long-term predictors have been identified. We therefore examined the association between systolic blood pressure (SBP) and fasting plasma glucose, assessed over 18 years, with retinopathy and retinal vascular caliber in 2066 Carotid MRI participants, an Atherosclerosis Risk in Communities ancillary study.
Methods: Retinopathy and retinal vascular caliber were assessed by retinal photography. Confounder-adjusted weighted regression models were used to examine exposures defined as cumulative, long-term prospective, concurrent, and 18-year change.
Results: Long-term prospective (prevalence odds ratio (POR) per 10 mm Hg: 1.14 (95% CI: 1.01, 1.30)) and cumulative (POR per 10 mm Hg: 1.30 (95% CI: 1.09, 1.56) effects spanning approximately 18 years were found for SBP and retinopathy. The strongest long-term prospective association for plasma glucose and retinopathy was identified at the baseline visit (POR per 10 mg/dl: 1.26 (95% CI: 1.16, 1.38)); sustained glucose elevations over 18 years were also associated with prevalent retinopathy (POR per 10 mg/dl: 1.33 (95% CI: 1.24, 1.43)). Results were robust to the exclusion of participants with diabetes.
Conclusions: Modest and sustained long-term elevations in glucose and blood pressure are associated with retinopathy and retinal vascular caliber. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Avery, Christy L.; Kucharska-Newton, Anna; Monda, Keri L.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.
[Sharrett, A. Richey] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Klein, Barbara E.; Klein, Ronald] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
[Wong, Tien Y.] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore.
RP Avery, CL (reprint author), Univ N Carolina, Dept Epidemiol, 137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA.
EM christy_avery@unc.edu
OI Cotch, Mary Frances/0000-0002-2046-4350; Klein,
Ronald/0000-0002-4428-6237
FU National Heart, Lung, and Blood Institute [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C]; ARIC Carotid MRI examination; National Institutes of
Health from the National Eye Institute [ZIAEY000426]; [U01HL075572];
[R00HL098458]
FX The Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by National Heart, Lung, and Blood
Institute contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C) with the
ARIC Carotid MRI examination funded by U01HL075572 and National
Institutes of Health Intramural Award ZIAEY000426 from the National Eye
Institute. The authors thank the staff and participants of the ARIC
study for their important contributions.; CLA was partially supported by
grant R00HL098458.
NR 34
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Z9 6
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD DEC
PY 2012
VL 225
IS 2
BP 412
EP 417
DI 10.1016/j.atherosclerosis.2012.10.034
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 040SV
UT WOS:000311344700047
PM 23102597
ER
PT J
AU Maggio, M
Cattabiani, C
Lauretani, F
Artoni, A
Bandinelli, S
Schiavi, G
Vignali, A
Volpi, R
Ceresini, G
Lippi, G
Aloe, R
De Vita, F
Giallauria, F
McDermott, MM
Ferrucci, L
Ceda, GP
AF Maggio, M.
Cattabiani, C.
Lauretani, F.
Artoni, A.
Bandinelli, S.
Schiavi, G.
Vignali, A.
Volpi, R.
Ceresini, G.
Lippi, G.
Aloe, R.
De Vita, F.
Giallauria, F.
McDermott, M. M.
Ferrucci, L.
Ceda, G. P.
TI The relationship between sex hormones, sex hormone binding globulin and
peripheral artery disease in older persons
SO ATHEROSCLEROSIS
LA English
DT Article
DE SHBG; Sex hormones; PAD; Older persons
ID ANKLE-BRACHIAL INDEX; METABOLIC SYNDROME; CARDIOVASCULAR RISK;
FUNCTIONAL PERFORMANCE; EDINBURGH ARTERY; HEART-DISEASE; ELDERLY-MEN;
TESTOSTERONE; ASSOCIATION; WOMEN
AB Objective: The prevalence of peripheral artery disease (PAD) increases with aging and is higher in persons with metabolic syndrome and diabetes. PAD is associated with adverse outcomes, including frailty and disability. The protective effect of testosterone and sex hormone binding globulin (SHBG) for diabetes in men suggests that the biological activity of sex hormones may affect PAD, especially in older populations.
Methods: Nine hundred and twenty-one elderly subjects with data on SHBG, testosterone (T), estradiol (E2) were selected from InCHIANTI study. PAD was defined as an Ankle-Brachial Index (ABI) < 0.90. Logistic regression models adjusted for age (Model 1), age, BMI, insulin, interleukin-6, physical activity, smoking, chronic diseases including metabolic syndrome (Model 2), and a final model including also sex hormones (Model 3) were performed to test the relationship between SHBG, sex hormones and PAD.
Results: The mean age (+/- SD) of the 419 men and 502 women was 75.0 +/- 6.8 years. Sixty two participants (41 men, 21 women) had ABI < 0.90. Men with PAD had SHBG levels lower than men without PAD (p = 0.03). SHBG was negatively and independently associated with PAD in men (p = 0.028) but not in women. The relationship was however attenuated after adjusting for sex hormones (p = 0.07). The E2 was not significantly associated with PAD in both men and women. In women, but not in men, T was positively associated with PAD, even after adjusting for multiple confounders, including E2 (p = 0.01).
Conclusions: Low SHBG and high T levels are significantly and independently associated with the presence of PAD in older men and women, respectively. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Maggio, M.; Cattabiani, C.; Schiavi, G.; Vignali, A.; Volpi, R.; Ceresini, G.; De Vita, F.; Ceda, G. P.] Univ Parma, Sect Geriatr, Dept Clin & Expt Med, I-43100 Parma, Italy.
[Maggio, M.; Lauretani, F.; Artoni, A.; Ceresini, G.; Ceda, G. P.] Univ Hosp Parma, Geriatr Rehabil Dept, Parma, Italy.
[Bandinelli, S.] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
[Giallauria, F.] Univ Naples Federico II, Dept Clin Med Cardiovasc & Immunol Sci, Naples, Italy.
[McDermott, M. M.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Ferrucci, L.] NIA, NIH, Baltimore, MD 21224 USA.
RP Maggio, M (reprint author), Univ Parma, Sect Geriatr, Dept Clin & Expt Med, Via Gramsci 14, I-43100 Parma, Italy.
EM marcellomaggio2001@yahoo.it
RI Giallauria, Francesco/B-5681-2013; Lauretani, Fulvio/K-5115-2016;
OI Giallauria, Francesco/0000-0003-4119-9397; Lauretani,
Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295
FU Italian Ministry of Health [ICS 110.1/RS97.71]; US National Institute on
Aging [N01-AG-916413, N01-AG-821336]; Intramural Research Program of the
US National Institute on Aging [263 MD 9164 13, 263 MD 821336]
FX The InCHIANTI study was supported as a "targeted project" (ICS
110.1/RS97.71) by the Italian Ministry of Health and in part by the US
National Institute on Aging. (Contracts N01-AG-916413 and
N01-AG-821336), and by the Intramural Research Program of the US
National Institute on Aging (Contracts 263 MD 9164 13 and 263 MD
821336). None of the sponsoring institutions interfered with the
collection, analysis, presentation, or interpretation of the data
reported here.
NR 54
TC 10
Z9 10
U1 1
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
EI 1879-1484
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD DEC
PY 2012
VL 225
IS 2
BP 469
EP 474
DI 10.1016/j.atherosclerosis.2012.09.014
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 040SV
UT WOS:000311344700056
PM 23102785
ER
PT J
AU Sotomayor-Zarate, R
Quirozi, G
Araya, KA
Abarea, J
Ibanez, MR
Montecinos, A
Guajardo, C
Nunez, G
Fierro, A
Moya, PR
Iturriaga-Vasquez, P
Gomez-Molina, C
Gysling, K
Reyes-Parada, M
AF Sotomayor-Zarate, Ramon
Quirozi, Gabriel
Araya, Katherine A.
Abarea, Jorge
Ibanez, Maria R.
Montecinos, Alejandro
Guajardo, Carlos
Nunez, Gabriel
Fierro, Angelica
Moya, Pablo R.
Iturriaga-Vasquez, Patricio
Gomez-Molina, Cristobal
Gysling, Katia
Reyes-Parada, Miguel
TI 4-Methylthioamphetamine Increases Dopamine in the Rat Striatum and has
Rewarding Effects In Vivo
SO BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
LA English
DT Article
ID OXIDASE INHIBITORY PROPERTIES; BINDING-SITE; NEUROTRANSMITTER
TRANSPORTERS; AMPHETAMINE DERIVATIVES; P-METHYLTHIOAMPHETAMINE;
MOLECULAR-DYNAMICS; 4-MTA INTOXICATION; BACTERIAL HOMOLOG; LATERAL
SEPTUM; RELEASE
AB 4-Methylthioamphetamine (MTA) is a phenylisopropylamine derivative whose use has been associated with severe intoxications. MTA is usually regarded as a selective serotonin-releasing agent. Nevertheless, previous data have suggested that its mechanism of action probably involves a catecholaminergic component. As little is known about dopaminergic effects of this drug, in this work the actions of MTA upon the dopamine (DA) transporter (DAT) were studied in vitro, in vivo and in silico. Also, the possible abuse liability of MTA was behaviourally assessed. MTA exhibited an in vitro affinity for the rat DAT in the low micromolar range (6.01 mu M) and induced a significant, dose-dependent increase in striatal DA. MTA significantly increased c-Fos-positive cells in striatum and nucleus accumbens, induced conditioned place preference and increased locomotor activity. Docking experiments were performed in a homology model of the DAT. In conclusion, our results show that MTA is able to increase extracellular striatal DA levels and that its administration has rewarding properties. These effects were observed at concentrations or doses that can be relevant to its use in human beings.
C1 [Reyes-Parada, Miguel] Univ Santiago Chile, Fac Med Sci, Sch Med, Santiago, Chile.
[Sotomayor-Zarate, Ramon; Quirozi, Gabriel; Araya, Katherine A.; Abarea, Jorge; Ibanez, Maria R.; Gysling, Katia] Pontificia Univ Catolica Chile, Fac Biol Sci, Dept Cell & Mol Biol, Santiago, Chile.
[Sotomayor-Zarate, Ramon; Quirozi, Gabriel; Araya, Katherine A.; Abarea, Jorge; Ibanez, Maria R.; Gysling, Katia] Pontificia Univ Catolica Chile, Fac Biol Sci, Millennium Sci Nucleus Stress & Addict, Santiago, Chile.
[Sotomayor-Zarate, Ramon] Univ Valparaiso, Fac Ciencias, Dept Fisiol, Valparaiso, Chile.
[Montecinos, Alejandro; Guajardo, Carlos; Nunez, Gabriel; Fierro, Angelica] Univ Santiago Chile, Fac Chem & Biol, PhD Program Biotechnol, Santiago, Chile.
[Fierro, Angelica; Iturriaga-Vasquez, Patricio; Reyes-Parada, Miguel] Millennium Inst Cell Dynam & Biotechnol, Santiago, Chile.
[Moya, Pablo R.] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA.
[Iturriaga-Vasquez, Patricio; Gomez-Molina, Cristobal] Univ Chile, Fac Sci, Dept Chem, Santiago, Chile.
[Reyes-Parada, Miguel] Univ Autonoma Chile, Fac Ciencias Salud, Santiago, Chile.
RP Reyes-Parada, M (reprint author), Univ Santiago Chile, Fac Med Sci, Sch Med, Av Alameda 3363,Estan Cent, Santiago, Chile.
EM miguel.reyes@usach.cl
FU MSI [P10/063-F, P05/001-F]; PBCT [PDA-23]; FONDECYT [111-0392,
110-85002, 109-0037]; NIDA
FX We thank Dr. G. Zapata-Torres for his assistance with the ICM programme
and Dr. B.K. Cassels for critical reading of the manuscript. This work
was funded by MSI Grants P10/063-F and P05/001-F, PBCT grant PDA-23 to
AF and FONDECYT Grants 111-0392 to KG. 110-85002 to AF and 109-0037 to
MR-P. We also thank the support of NIDA for donating the cocaine-HCl
used in this work.
NR 52
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U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-7835
J9 BASIC CLIN PHARMACOL
JI Basic Clin. Pharmacol. Toxicol.
PD DEC
PY 2012
VL 111
IS 6
BP 371
EP 379
DI 10.1111/j.1742-7843.2012.00926.x
PG 9
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 036TX
UT WOS:000311055700004
PM 22788961
ER
PT J
AU Mohamedali, KA
Niu, G
Luster, TA
Thorpe, PE
Gao, HK
Chen, XY
Rosenblum, MG
AF Mohamedali, Khalid A.
Niu, Gang
Luster, Troy A.
Thorpe, Philip E.
Gao, Haokao
Chen, Xiaoyuan
Rosenblum, Michael G.
TI Pharmacodynamics, tissue distribution, toxicity studies and antitumor
efficacy of the vascular targeting fusion toxin VEGF(121)/rGel
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Angiogenesis; Necrosis; Pharmacokinetics; Toxicology; VEGF; Vascular
permeability
ID ENDOTHELIAL GROWTH-FACTOR; AGENT VEGF(121)/RGEL; INHIBITION; CANCER;
TUMORS; THERAPY; PET
AB As a part of an ongoing assessment of its mechanism of action, we evaluated the in vivo pharmacokinetics, tissue distribution, toxicity and antitumor efficacy of VEGF(121)/rGel, a novel fusion protein. Pharmacokinetic studies showed that VEGF(121)/rGel cleared from the circulation in a biphasic manner with calculated half-lives of 0.3 and 6 h for the alpha and beta phases, respectively. Pharmacokinetic evaluation of Cu-64-DOTA-VEGF(121)/rGel showed relatively high blood retention 30 min after injection (26.6 +/- 1.73% ID/g), dropping to 11.8 +/- 2.83% and 0.82 +/- 0.11% ID/g at 60 and 240 min post injection, respectively. Tissue uptake studies showed that kidneys, liver and tumor had the highest drug concentrations 48 h after administration. The maximum tolerated dose (MTD), based on a QOD x 5 i.v. administration schedule, was found to be 18 mg/kg with an LD50 of 25 mg/kg. Treatment of BALB/c mice with VEGF(121)/rGel at doses up to the MID caused no alterations in hematologic parameters. However, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) parameters increased in a dose-related manner. The no-observable-adverse-effect-level (NOAEL) was determined to be 20% of the MTD (3.6 mg/kg). VEGF(121)/rGel treatment of mice bearing orthotopically-placed MDA-MB-231 breast tumors caused increased vascular permeability of tumor tissue by 53% compared to saline-treated controls. Immunohistochemical analysis showed significant tumor hypoxia and necrosis as a consequence of vascular damage. In summary, VEGF(121)/rGel appears to be an effective therapeutic agent causing focused damage to tumor vasculature with minimal toxic effects to normal organs. This agent appears to be an excellent candidate for further clinical development. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Mohamedali, Khalid A.; Rosenblum, Michael G.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Unit 1950, Houston, TX 77030 USA.
[Niu, Gang; Gao, Haokao; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Luster, Troy A.; Thorpe, Philip E.] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA.
RP Mohamedali, KA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Unit 1950, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM kmohamed@mdanderson.org; Gang.Niu@NIH.gov; Troy_Luster@HGSI.com;
Philip.Thorpe@UTSouthwestern.edu; Haokao.Gao@NIH.gov;
ChenX5@mail.NIH.gov; mrosenbl@mdanderson.org
FU National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health; National Institutes of Health through MD
Anderson's Cancer Center [CA016672]
FX Research conducted, in part, by the Clayton Foundation for Research.
This work was supported by the Intramural Research Program, National
Institute of Biomedical Imaging and Bioengineering, National Institutes
of Health and in part by the National Institutes of Health through MD
Anderson's Cancer Center Support Grant CA016672.
NR 25
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Z9 3
U1 0
U2 8
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 DEC 1
PY 2012
VL 84
IS 11
BP 1534
EP 1540
DI 10.1016/j.bcp.2012.09.017
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 042IW
UT WOS:000311465900016
PM 23022224
ER
PT J
AU Luckenbaugh, DA
Ibrahim, L
Brutsche, N
Franco-Chaves, J
Mathews, D
Marquardt, CA
Cassarly, C
Zarate, CA
AF Luckenbaugh, David A.
Ibrahim, Lobna
Brutsche, Nancy
Franco-Chaves, Jose
Mathews, Daniel
Marquardt, Craig A.
Cassarly, Christy
Zarate, Carlos A., Jr.
TI Family history of alcohol dependence and antidepressant response to an
N-methyl-D-aspartate antagonist in bipolar depression
SO BIPOLAR DISORDERS
LA English
DT Article
DE alcohol; bipolar disorder; depression; family history; ketamine;
N-methyl-d-aspartate; predictors of response
ID ADD-ON TRIAL; AFFECTIVE-DISORDER; SUBSTANCE-ABUSE; RATING-SCALE;
REPLICATION; KETAMINE; IMPACT; FUTURE
AB Luckenbaugh DA, Ibrahim L, Brutsche N, Franco-Chaves J, Mathews D, Marquardt CA, Cassarly C, Zarate CA Jr. Family history of alcohol dependence and antidepressant response to an N-methyl-d-aspartate antagonist in bipolar depression. Bipolar Disord 2012: 14: 880887. Published 2012. This article is a U.S. Government work and is in the public domain in the USA. Objectives: Both ketamine and ethanol are N-methyl-d-aspartate (NMDA) receptor antagonists. Ketamine has rapid antidepressant properties in major depressive disorder (MDD) as well as bipolar depression. In individuals with MDD, a positive family history of alcohol dependence (FHP) was associated with greater improvement in depressive symptoms after ketamine administration compared to individuals whose family history of alcohol dependence was negative (FHN). This study investigated whether FHP influences ketamines antidepressant and perceptual effects in individuals with bipolar depression. Methods: A post hoc analysis was conducted on 33 subjects with DSMIV bipolar disorder (BD) type I or II depression pooled from two previously published studies. All subjects had undergone a double-blind, randomized, crossover trial of a single intravenous infusion of ketamine (0.5 mg/kg) combined with lithium or valproate therapy. Subjects were rated at baseline; at 40, 80, 120, and 230 min; and at days 1, 2, 3, 7, 10, and 14 post-infusion. The primary outcome measure was Montgomery-angstrom sberg Depression Rating Scale (MADRS) scores. Patients were categorized as FHP when they reported at least one first-degree relative with alcohol dependence. Measures of psychosis, dissociation, and dysphoria were also collected. Results: After ketamine infusion, subjects with FHP showed significantly greater improvement on MADRS scores than FHN subjects. In addition, patients with FHP had attenuated psychotomimetic and dissociative scores compared to FHN patients. Conclusions: FHP appears to predict a more sustained antidepressant response to ketamine in individuals with BD. Family history of alcoholism may be an important consideration in the development of glutamatergic-based therapies for depression.
C1 [Luckenbaugh, David A.; Ibrahim, Lobna; Brutsche, Nancy; Franco-Chaves, Jose; Mathews, Daniel; Marquardt, Craig A.; Cassarly, Christy; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Program, US Dept HHS,NIH, Bethesda, MD 20892 USA.
RP Zarate, CA (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Program, US Dept HHS,NIH, 10 Ctr Dr,CRC Unit 7 SE,Room 7-3445, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
FU Brain and Behavior Research Foundation; Intramural Research Program of
the National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH)
FX Funding for this work was supported by the Intramural Research Program
of the National Institute of Mental Health, National Institutes of
Health (IRP-NIMH-NIH) and by the Brain and Behavior Research Foundation.
CAZ 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. Ioline Henter provided outstanding editorial assistance.
NR 28
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U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD DEC
PY 2012
VL 14
IS 8
BP 880
EP 887
DI 10.1111/bdi.12003
PG 8
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 041LP
UT WOS:000311403600010
PM 22978511
ER
PT J
AU Thorp, JM
Camargo, CA
McGee, PL
Harper, M
Klebanoff, MA
Sorokin, Y
Varner, MW
Wapner, RJ
Caritis, SN
Iams, JD
Carpenter, MW
Peaceman, AM
Mercer, BM
Sciscione, A
Rouse, DJ
Ramin, SM
Anderson, GB
AF Thorp, J. M.
Camargo, C. A.
McGee, P. L.
Harper, M.
Klebanoff, M. A.
Sorokin, Y.
Varner, M. W.
Wapner, R. J.
Caritis, S. N.
Iams, J. D.
Carpenter, M. W.
Peaceman, A. M.
Mercer, B. M.
Sciscione, A.
Rouse, D. J.
Ramin, S. M.
Anderson, G. B.
CA Eunice Kennedy Shriver Natl Inst C
TI Vitamin D status and recurrent preterm birth: a nested case-control
study in high-risk women
SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
LA English
DT Article
DE Perinatal nutrition; preterm birth; vitamin D
ID D SUPPLEMENTATION; DOUBLE-BLIND; PREGNANCY; OUTCOMES; TRIAL;
PREECLAMPSIA; CALCIUM
AB Please cite this paper as: Thorp J, Camargo C, McGee P, Harper M, Klebanoff M, Sorokin Y, Varner M, Wapner R, Caritis S, Iams J, Carpenter M, Peaceman A, Mercer B, Sciscione A, Rouse D, Ramin S, Anderson G. Vitamin D status and recurrent preterm birth: a nested casecontrol study in high-risk women. BJOG 2012;119:16171623. Objective To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption. Design A nested casecontrol study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. Setting Fourteen academic health centres in the USA. Population Women with prior spontaneous preterm birth. Methods In 131 cases (preterm delivery at <35 weeks of gestation) and 134 term controls, we measured serum 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) from samples collected at baseline (1622 weeks of gestation). Logistic regression models controlled for study centre, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment. Main outcome measures Recurrent preterm birth at <37 and <32 weeks of gestation. Results The median mid-gestation serum 25(OH)D concentration was 67 nmol/l, and 27% had concentrations of <50 nmol/l. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR 1.33; 95% CI 0.483.70 for lowest versus highest quartiles). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/l, or higher, with those with <50 nmol/l generated an odds ratio of 0.80 (95% CI 0.381.69). Contrary to our expectation, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (-0.18, P < 0.01). Conclusions In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth.
C1 [Thorp, J. M.] Univ N Carolina, Dept Obstet & Gynecol, Sch Med, Chapel Hill, NC 27599 USA.
[Camargo, C. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
[McGee, P. L.] George Washington Univ, Biostat Ctr, Washington, DC USA.
[Harper, M.] Wake Forest Univ Hlth Sci, Dept Obstet, Winston Salem, NC USA.
[Harper, M.] Wake Forest Univ Hlth Sci, Dept Gynecol, Winston Salem, NC USA.
[Klebanoff, M. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Sorokin, Y.] Wayne State Univ, Detroit, MI USA.
[Varner, M. W.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
[Wapner, R. J.] Columbia Univ, Columbia, NY USA.
[Caritis, S. N.] Univ Pittsburgh, Pittsburgh, PA USA.
[Iams, J. D.] Ohio State Univ, Columbus, OH 43210 USA.
[Carpenter, M. W.] Brown Univ, Women & Infants Hosp, Providence, RI USA.
[Peaceman, A. M.] Northwestern Univ, Chicago, IL 60611 USA.
[Mercer, B. M.] Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA.
[Sciscione, A.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
[Rouse, D. J.] Univ Alabama Birmingham, Birmingham, AL USA.
[Ramin, S. M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Anderson, G. B.] Univ Texas Med Ctr, Galveston, TX USA.
RP Thorp, JM (reprint author), Univ N Carolina, Dept Obstet & Gynecol, Sch Med, 3027 Old Clin Bldg, Chapel Hill, NC 27599 USA.
EM thorp@med.unc.edu
RI Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850;
Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD27860, HD27917, HD40560, HD34208, HD40485,
HD21410, HD27915, HD 40500, HD40512, HD40544, MO1-RR-000080, HD34136,
HD27869, HD40545, HD36801, HD19897]; Massachusetts General Hospital
Center for D-receptor Activation Research (Boston, MA, USA)
FX The project described was supported by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
(HD27860, HD27917, HD40560, HD34208, HD40485, HD21410, HD27915, HD
40500, HD40512, HD40544, MO1-RR-000080, HD34136, HD27869, HD40545,
HD36801, and HD19897), and does not necessarily represent the official
views of the NICHD or National Institutes of Health (NIH). CAC was
supported, in part, by the Massachusetts General Hospital Center for
D-receptor Activation Research (Boston, MA, USA).
NR 19
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U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1470-0328
J9 BJOG-INT J OBSTET GY
JI BJOG
PD DEC
PY 2012
VL 119
IS 13
BP 1617
EP 1623
DI 10.1111/j.1471-0528.2012.03495.x
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 040AW
UT WOS:000311292300011
PM 23078336
ER
PT J
AU Curiel-Lewandrowski, C
Swetter, SM
Einspahr, JG
Hsu, CH
Nagle, R
Sagerman, P
Tangrea, J
Parnes, H
Alberts, DS
Chow, HH
AF Curiel-Lewandrowski, Clara
Swetter, Susan M.
Einspahr, Janine G.
Hsu, Chiu-Hsieh
Nagle, Ray
Sagerman, Paul
Tangrea, Joseph
Parnes, Howard
Alberts, David S.
Chow, Hsiao-Hui
TI Randomized, double-blind, placebo-controlled trial of sulindac in
individuals at risk for melanoma
SO CANCER
LA English
DT Article
DE melanoma; prevention and control; chemoprevention; nevus;
anti-inflammatory agents; nonsteroidal; atypical nevi
ID ENDOTHELIAL GROWTH-FACTOR; NONSTEROIDAL ANTIINFLAMMATORY DRUGS;
CUTANEOUS MELANOCYTIC LESIONS; DYSPLASTIC NEVI; MALIGNANT-MELANOMA;
TOPICAL TRETINOIN; IMMUNOHISTOCHEMICAL EXPRESSION; CYCLOOXYGENASE
INHIBITORS; ATYPICAL NEVI; SKIN
AB BACKGROUND: Reduced melanoma risk has been reported with regular use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the ability of NSAIDs to reach melanocytes in vivo and modulate key biomarkers in preneoplastic lesions such as atypical nevi has not been evaluated. METHODS: This randomized, double-blind, placebo-controlled trial of sulindac was conducted in individuals with atypical nevi (AN) to determine bioavailability of sulindac and metabolites in nevi and effect on apoptosis and vascular endothelial growth factor A (VEGFA) expression in AN. Fifty subjects with AN =4 mm in size and 1 benign nevus (BN) were randomized to sulindac (150 mg twice a day) or placebo for 8 weeks. Two AN were randomized for baseline excision, and 2 AN and BN were excised after intervention. RESULTS: Postintervention sulindac, sulindac sulfone, and sulindac sulfide concentrations were 0.31 +/- 0.36, 1.56 +/- 1.35, and 2.25 +/- 2.24 mu g/mL in plasma, and 0.51 +/- 1.05, 1.38 +/- 2.86, and 0.12 +/- 0.12 mu g/g in BN, respectively. Sulindac intervention did not significantly change VEGFA expression but did increase expression of the apoptotic marker cleaved caspase-3 in AN (increase of 3 +/- 33 in sulindac vs decrease of 25 +/- 45 in the placebo arm, P = .0056), although significance was attenuated (P = .1103) after adjusting for baseline expression. CONCLUSIONS: Eight weeks of sulindac intervention resulted in high concentrations of sulindac sulfone, a proapoptotic metabolite, in BN but did not effectively modulate VEGFA and cleaved caspase-3 expression. Study limitations included limited exposure time to sulindac and the need to optimize a panel of biomarkers for NSAID intervention studies. Cancer 2012. (c) 2012 American Cancer Society.
C1 [Curiel-Lewandrowski, Clara; Einspahr, Janine G.; Nagle, Ray; Sagerman, Paul; Alberts, David S.; Chow, Hsiao-Hui] Univ Arizona, Arizona Canc Ctr, Coll Med, Tucson, AZ 85724 USA.
[Swetter, Susan M.] Stanford Univ, Med Ctr, Dept Dermatol, Palo Alto, CA 94304 USA.
[Swetter, Susan M.] Inst Canc Res, Palo Alto, CA USA.
[Swetter, Susan M.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Hsu, Chiu-Hsieh] Univ Arizona, Div Epidemiol & Biostat, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85724 USA.
[Tangrea, Joseph; Parnes, Howard] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Curiel-Lewandrowski, C (reprint author), Univ Arizona, Arizona Canc Ctr, Coll Med, 1515 N Campbell Ave,POB 245024, Tucson, AZ 85724 USA.
EM ccuriel@azcc.arizona.edu
FU National Cancer Institute, Division of Cancer Prevention [N01CN35158];
Arizona Cancer Center [CA023074]; Janice and Alan Levine Endowed Chair
in Cancer Research, Arizona Cancer Center, University of Arizona;
National Center for Research Resources, National Institutes of Health
[1UL1 RR025744]
FX Supported by a contract (N01CN35158) from the National Cancer Institute,
Division of Cancer Prevention; the Arizona Cancer Center Support Grant
(CA023074); and Janice and Alan Levine Endowed Chair in Cancer Research,
Arizona Cancer Center, University of Arizona; and in part by the
Clinical and Translational Science Award 1UL1 RR025744 for the Stanford
Center for Clinical and Translational Education and Research (Spectrum)
from the National Center for Research Resources, National Institutes of
Health.
NR 43
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Z9 6
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD DEC 1
PY 2012
VL 118
IS 23
BP 5848
EP 5856
DI 10.1002/cncr.27540
PG 9
WC Oncology
SC Oncology
GA 040EZ
UT WOS:000311306000017
PM 22605570
ER
PT J
AU Chang, CM
Warren, JL
Engels, EA
AF Chang, Cindy M.
Warren, Joan L.
Engels, Eric A.
TI Chronic fatigue syndrome and subsequent risk of cancer among elderly US
adults
SO CANCER
LA English
DT Article
DE lymphoma; chronic fatigue; cancer; etiology
ID LYMPHOMA EPIDEMIOLOGY CONSORTIUM; NON-HODGKINS-LYMPHOMA; RETROVIRUS
XMRV; IMMUNE ACTIVATION; PROSTATE-CANCER; MEDICARE DATA; BLOOD;
MALIGNANCIES; POPULATION; AUTOIMMUNE
AB BACKGROUND: The cause of chronic fatigue syndrome (CFS) is unknown but is thought to be associated with immune abnormalities or infection. Because cancer can arise from similar conditions, associations between CFS and cancer were examined in a population-based case-control study among the US elderly. METHODS: Using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare registry data, approximately 1.2 million cancer cases and 100,000 controls (age range, 66-99 years; 1992-2005) were evaluated. CFS was identified in the period more than 1 year prior to selection, using linked Medicare claims. Unconditional logistic regression was used to estimate the odds ratios (ORs) comparing the CFS prevalence in cases and controls, adjusting for age, sex, and selection year. All statistical tests were 2-sided. RESULTS: CFS was present in 0.5% of cancer cases overall and 0.5% of controls. CFS was associated with an increased risk of non-Hodgkin lymphoma (NHL) (OR = 1.29, 95% confidence interval [CI] = 1.16-1.43, P = 1.7 x 10-6). Among NHL subtypes, CFS was associated with diffuse large B cell lymphoma (OR = 1.34, 95% CI = 1.12-1.61), marginal zone lymphoma (OR = 1.88, 95% CI = 1.38-2.57), and B cell NHL not otherwise specified (OR = 1.51, 95% CI = 1.03-2.23). CFS associations with NHL overall and NHL subtypes remained elevated after excluding patients with medical conditions related to CFS or NHL, such as autoimmune conditions. CFS was also associated, although not after multiple comparison adjustment, with cancers of the pancreas (OR = 1.25, 95% CI = 1.07-1.47), kidney (OR = 1.27, 95% CI = 1.07-1.49), breast (OR = 0.85, 95% CI = 0.74-0.98), and oral cavity and pharynx (OR = 0.70, 95% CI = 0.49-1.00). CONCLUSIONS: Chronic immune activation or an infection associated with CFS may play a role in explaining the increased risk of NHL. Cancer 2012.(c) 2012 American Cancer Society.
C1 [Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
[Warren, Joan L.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20892 USA.
RP Engels, EA (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7076, Rockville, MD 20892 USA.
EM engelse@exchange.nih.gov
FU Intramural Research Program of the National Cancer Institute at the US
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Cancer Institute at the US National Institutes of Health.
NR 45
TC 16
Z9 16
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD DEC 1
PY 2012
VL 118
IS 23
BP 5929
EP 5936
DI 10.1002/cncr.27612
PG 8
WC Oncology
SC Oncology
GA 040EZ
UT WOS:000311306000026
PM 22648858
ER
PT J
AU Etzioni, R
Gulati, R
Tsodikov, A
Wever, EM
Penson, DF
Heijnsdijk, EAM
Katcher, J
Draisma, G
Feuer, EJ
de Koning, HJ
Mariotto, AB
AF Etzioni, Ruth
Gulati, Roman
Tsodikov, Alex
Wever, Elisabeth M.
Penson, David F.
Heijnsdijk, Eveline A. M.
Katcher, Jeffrey
Draisma, Gerrit
Feuer, Eric J.
de Koning, Harry J.
Mariotto, Angela B.
TI The prostate cancer conundrum revisited
SO CANCER
LA English
DT Article
DE computer simulation; mortality; prostatectomy; prostatic neoplasms;
radiotherapy; surveillance
ID RADICAL PROSTATECTOMY; SCREENING TRIAL; ANDROGEN-DEPRIVATION;
UNITED-STATES; TIME TRENDS; MORTALITY; RADIOTHERAPY; SURVEILLANCE; RISK;
LUNG
AB BACKGROUND: Prostate cancer mortality rates in the United States declined by >40% between 1991 and 2005. The impact of changes in primary treatment and adjuvant and neoadjuvant hormone therapy on this decline is unknown. METHODS: The authors applied 3 independently developed models of prostate cancer natural history and disease detection under common assumptions about treatment patterns, treatment efficacy, and survival in the population. Primary treatment patterns were derived from the Surveillance, Epidemiology, and End Results registry; data on the frequency of hormone therapy were obtained from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) database; and treatment efficacy was based on estimates from randomized trials and comparative effectiveness studies of treatment alternatives. The models projected prostate cancer mortality without prostate-specific antigen screening and in the presence and absence of treatment benefit. The impact of primary treatment was expressed as a fraction of the difference between observed mortality and projected mortality in the absence of treatment benefit. RESULTS: The 3 models projected that changes in treatment explained 22% to 33% of the mortality decline by 2005. These contributions were accounted for mostly by surgery and radiation therapy, which increased in frequency until the 1990s, whereas hormone therapies contributed little to the mortality decline by 2005. Assuming that treatment benefit was less for older men, changes in treatment explained only 16% to 23% of the mortality decline by 2005. CONCLUSIONS: Changes in primary treatment explained a minority of the observed decline in prostate cancer mortality. The remainder of the decline probably was because of other interventions, such as prostate-specific antigen screening and advances in the treatment of recurrent and progressive disease. Cancer 2012.(c) 2012 American Cancer Society.
C1 [Etzioni, Ruth; Gulati, Roman; Katcher, Jeffrey] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Tsodikov, Alex] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Wever, Elisabeth M.; Heijnsdijk, Eveline A. M.; Draisma, Gerrit; de Koning, Harry J.] Erasmus Univ, Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands.
[Penson, David F.] Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN USA.
[Feuer, Eric J.; Mariotto, Angela B.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Etzioni, R (reprint author), 1100 Fairview Ave N,M2-B230,POB 19024, Seattle, WA 98109 USA.
EM retzioni@fhcrc.org
FU National Cancer Institute [U01CA88160, U01CA157224]; Centers for Disease
Control and Prevention
FX This research was supported by Award U01CA88160 from the National Cancer
Institute and Award U01CA157224 from the National Cancer Institute and
the Centers for Disease Control and Prevention.
NR 32
TC 50
Z9 51
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD DEC 1
PY 2012
VL 118
IS 23
BP 5955
EP 5963
DI 10.1002/cncr.27594
PG 9
WC Oncology
SC Oncology
GA 040EZ
UT WOS:000311306000029
PM 22605665
ER
PT J
AU Bround, MJ
Asghari, P
Wambolt, RB
Bohunek, L
Smits, C
Philit, M
Kieffer, TJ
Lakatta, EG
Boheler, KR
Moore, EDW
Allard, MF
Johnson, JD
AF Bround, Michael J.
Asghari, Parisa
Wambolt, Rich B.
Bohunek, Lubos
Smits, Claire
Philit, Marjolaine
Kieffer, Timothy J.
Lakatta, Edward G.
Boheler, Kenneth R.
Moore, Edwin D. W.
Allard, Michael F.
Johnson, James D.
TI Cardiac ryanodine receptors control heart rate and rhythmicity in adult
mice
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Heart rate (variability); Bradycardia; Ca2+ channel; Arrhythmia
(mechanisms); Excitationcontraction coupling
ID POLYMORPHIC VENTRICULAR-TACHYCARDIA; LUMINAL CA2+ ACTIVATION;
SUDDEN-DEATH; CALCIUM-RELEASE; MOUSE MODEL; HYPERTROPHY; FAILURE;
MUTATIONS; ALTERNANS; CHANNEL
AB The molecular mechanisms controlling heart function and rhythmicity are incompletely understood. While it is widely accepted that the type 2 ryanodine receptor (Ryr2) is the major Ca-2 release channel in excitationcontraction coupling, the role of these channels in setting a consistent beating rate remains controversial. Gain-of-function RYR2 mutations in humans and genetically engineered mouse models are known to cause Ca-2 leak, arrhythmias, and sudden cardiac death. Embryonic stem-cell derived cardiomyocytes lacking Ryr2 display slower beating rates, but no supporting in vivo evidence has been presented. The aim of the present study was to test the hypothesis that RYR2 loss-of-function would reduce heart rate and rhythmicity in vivo.
We generated inducible, tissue-specific Ryr2 knockout mice with acute approximate to 50 loss of RYR2 protein in the heart but not in other tissues. Echocardiography, working heart perfusion, and in vivo ECG telemetry demonstrated that deletion of Ryr2 was sufficient to cause bradycardia and arrhythmia. Our results also show that cardiac Ryr2 knockout mice exhibit functional and structural hallmarks of heart failure, including sudden cardiac death.
These results illustrate that the RYR2 channel plays an essential role in pacing heart rate. Moreover, we find that RYR2 loss-of-function can lead to fatal arrhythmias typically associated with gain-of-function mutations. Given that RYR2 levels can be reduced in pathological conditions, including heart failure and diabetic cardiomyopathy, we predict that RYR2 loss contributes to disease-associated bradycardia, arrhythmia, and sudden death.
C1 [Bround, Michael J.; Asghari, Parisa; Moore, Edwin D. W.; Johnson, James D.] Univ British Columbia, Inst Life Sci, Cardiovasc Res Grp, Vancouver, BC V6T 1Z3, Canada.
[Bround, Michael J.; Asghari, Parisa; Philit, Marjolaine; Kieffer, Timothy J.; Moore, Edwin D. W.; Johnson, James D.] Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC V6T 1Z3, Canada.
[Bround, Michael J.; Philit, Marjolaine; Kieffer, Timothy J.; Johnson, James D.] Univ British Columbia, Dept Surg, Vancouver, BC V6T 1Z3, Canada.
[Bround, Michael J.; Philit, Marjolaine; Kieffer, Timothy J.; Johnson, James D.] Univ British Columbia, Inst Life Sci, Diabet Res Grp, Vancouver, BC V6T 1Z3, Canada.
[Wambolt, Rich B.; Bohunek, Lubos; Smits, Claire; Allard, Michael F.] St Pauls Hosp, James Hogg Res Ctr, Vancouver, BC, Canada.
[Lakatta, Edward G.; Boheler, Kenneth R.] NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
[Boheler, Kenneth R.] Univ Hong Kong, LKS Fac Med, Stem Cell & Regenerat Med Consortium, Hong Kong, Hong Kong, Peoples R China.
RP Johnson, JD (reprint author), Univ British Columbia, Inst Life Sci, Cardiovasc Res Grp, 5358 Life Sci Bldg,2350 Hlth Sci Mall, Vancouver, BC V6T 1Z3, Canada.
EM james.d.johnson@ubc.ca
FU Canadian Institutes for Health Research (CIHR); Intramural Research
Program of the NIH, National Institute on Aging; Canadian Diabetes
Association (CDA); Michael Smith Foundation for Health Research (MSFHR)
FX This work was supported by individual Canadian Institutes for Health
Research (CIHR) operating grants to J.D.J. and E. M. The generation of
the floxed Ryr2 alleles (K. R. B.) was supported by the Intramural
Research Program of the NIH, National Institute on Aging. J.D.J. was a
CIHR New Investigator and also received salary support from the Canadian
Diabetes Association (CDA) and the Michael Smith Foundation for Health
Research (MSFHR).
NR 44
TC 19
Z9 19
U1 0
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD DEC 1
PY 2012
VL 96
IS 3
BP 372
EP 380
DI 10.1093/cvr/cvs260
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 040FG
UT WOS:000311306800008
PM 22869620
ER
PT J
AU Uwah, AN
Ackler, J
Leighton, JC
Pomerantz, S
Tester, W
AF Uwah, Augusta N.
Ackler, Joan
Leighton, John C., Jr.
Pomerantz, Sherry
Tester, William
TI The Effect of Diabetes on Oxaliplatin-Induced Peripheral Neuropathy
SO CLINICAL COLORECTAL CANCER
LA English
DT Article
DE Chemotherapy; Diabetes; Hypertension; Neuropathy
ID ADVANCED COLORECTAL-CANCER; 1ST-LINE TREATMENT; COLON-CANCER;
CHEMOTHERAPY; LEUCOVORIN; CALCIUM; 5-FLUOROURACIL; NEUROTOXICITY;
IRINOTECAN; THERAPY
AB Chemotherapy-induced neurotoxicity is a significant source of morbidity for cancer patients. This retrospective study assessed for a relationship between preexisting diabetes and oxaliplatin-induced peripheral neuropathy (OXIPN) in patients being treated for colon cancer. Results showed diabetic patients developed OXIPN at a lower cumulative dose of oxaliplatin. The results may have implications for the personalization of chemotherapy for diabetics.
Introduction: Chemotherapy-induced neurotoxicity is a significant source of morbidity for cancer patients. This study aimed to assess the :relationship between preexisting diabetes and clinically significant (National Cancer Institute Common Toxicity Criteria grades 2 and 3) OXIPN; between diabetes, and the cumulative dose at onset of OXIPN; and between other preexisting medical conditions and the development of OXIPN. Materials and Methods: We reviewed medical records of all patients with stage II-IV colon cancer treated in the Albert Einstein Cancer Center, Philadelphia, with oxaliplatin from 2005 to 2009. Exclusion criteria included preexisting neuropathy, previous neurotoxic chemotherapy exposure, and incomplete medical records. The NCI Common Toxicity Criteria was used to grade sensory neuropathy. Univariate analysis was used to estimate odds ratios and confidence limits for prevalence of OXIPN in patients with and without diabetes. The mean level and cumulative doses were compared using the t test. Results: Sixty-two patients met the study criteria; 23 oxaliplatin-treated patients were excluded. The crude incidence of any OXIPN was 65%. There was no relationship found between development of OXIPN and the presence of diabetes, smoking, hypertension, or statin use. However, the mean cumulative dose of oxaliplatin was significantly lower for patients with diabetes who developed neuropathy, compared with those without diabetes (388 vs. 610 mg/m(2); P = .021). Conclusion: Although the presence of diabetes did not appear to affect the severity of OXIPN, patients with diabetes developed OXIPN at a lower cumulative dose of oxaliplatin (P < .05). The results may have implications for treatment of patients with diabetes and colon cancer.
C1 [Uwah, Augusta N.] Howard Univ, Dept Internal Med, Washington, DC 20060 USA.
[Ackler, Joan; Leighton, John C., Jr.; Pomerantz, Sherry; Tester, William] Albert Einstein Canc Ctr, Natl Canc Inst Community Canc Ctr Program, Philadelphia, PA USA.
RP Uwah, AN (reprint author), Howard Univ, Dept Internal Med, Hosp Suite 5C,2041 Georgia Ave NW, Washington, DC 20060 USA.
EM ngozi411@yahoo.com
NR 21
TC 13
Z9 13
U1 0
U2 4
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1533-0028
J9 CLIN COLORECTAL CANC
JI Clin. Colorectal Canc.
PD DEC
PY 2012
VL 11
IS 4
BP 275
EP 279
DI 10.1016/j.clcc.2012.05.002
PG 5
WC Oncology
SC Oncology
GA 043EE
UT WOS:000311524900007
PM 22682776
ER
PT J
AU Lagier, JC
Armougom, F
Million, M
Hugon, P
Pagnier, I
Robert, C
Bittar, F
Fournous, G
Gimenez, G
Maraninchi, M
Trape, JF
Koonin, EV
La Scola, B
Raoult, D
AF Lagier, J. -C.
Armougom, F.
Million, M.
Hugon, P.
Pagnier, I.
Robert, C.
Bittar, F.
Fournous, G.
Gimenez, G.
Maraninchi, M.
Trape, J. -F.
Koonin, E. V.
La Scola, B.
Raoult, D.
TI Microbial culturomics: paradigm shift in the human gut microbiome study
SO CLINICAL MICROBIOLOGY AND INFECTION
LA English
DT Article
DE Culturomics; gut microbiota; MALDI-TOF MS; metagenomic analysis;
uncultured bacteria
ID BACTERIA; TWINS; IDENTIFICATION; COMMUNITIES; ENVIRONMENT; SEQUENCE;
DIET
AB Comprehensive determination of the microbial composition of the gut microbiota and the relationships with health and disease are major challenges in the 21st century. Metagenomic analysis of the human gut microbiota detects mostly uncultured bacteria. We studied stools from two lean Africans and one obese European, using 212 different culture conditions (microbial culturomics), and tested the colonies by using mass spectrometry and 16S rRNA amplification and sequencing. In parallel, we analysed the same three samples by pyrosequencing 16S rRNA amplicons targeting the V6 region. The 32 500 colonies obtained by culturomics have yielded 340 species of bacteria from seven phyla and 117 genera, including two species from rare phyla (Deinococcus-Thermus and Synergistetes, five fungi, and a giant virus (Senegalvirus). The microbiome identified by culturomics included 174 species never described previously in the human gut, including 31 new species and genera for which the genomes were sequenced, generating c. 10 000 new unknown genes (ORFans), which will help in future molecular studies. Among these, the new species Microvirga massiliensis has the largest bacterial genome so far obtained from a human, and Senegalvirus is the largest virus reported in the human gut. Concurrent metagenomic analysis of the same samples produced 698 phylotypes, including 282 known species, 51 of which overlapped with the microbiome identified by culturomics. Thus, culturomics complements metagenomics by overcoming the depth bias inherent in metagenomic approaches.
C1 [Lagier, J. -C.; Armougom, F.; Million, M.; Hugon, P.; Pagnier, I.; Robert, C.; Bittar, F.; Fournous, G.; Gimenez, G.; La Scola, B.; Raoult, D.] Aix Marseille Univ, URMITE, UM63, CNRS 7278,IRD 198,INSERM 1095, F-13385 Marseille 5, France.
[Maraninchi, M.] CHU Timone, Serv Nutr Malad Metab & Endocrinol, UMR INRA U1260, Marseille, France.
[Trape, J. -F.] IRD, UMR CNRS IRD 198 7278, Dakar, Senegal.
[Koonin, E. V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Raoult, D (reprint author), Aix Marseille Univ, Fac Med, UMR CNRS 7278, URMITE,INSERM U1095,IRD 198, 27 Bd Jean Moulin, F-13385 Marseille 5, France.
EM didier.raoult@gmail.com
RI Maraninchi, Marie/M-5813-2016; LA SCOLA, Bernard/P-6477-2016;
OI Maraninchi, Marie/0000-0002-6645-1811; LA SCOLA,
Bernard/0000-0001-8006-7704; Pagnier, Isabelle/0000-0002-1724-3450;
Bittar, Fadi/0000-0003-4052-344X
FU CNRS, Centre National de la Recherche Scientifique; IRD (Institut de
Recherche et Developpement); Aix-Marseille Universite
FX This work was funded by the CNRS, Centre National de la Recherche
Scientifique, the IRD (Institut de Recherche et Developpement), and
Aix-Marseille Universite (credits recurrents). The authors have declared
that no competing interests exist.
NR 29
TC 224
Z9 228
U1 14
U2 153
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1198-743X
J9 CLIN MICROBIOL INFEC
JI Clin. Microbiol. Infect.
PD DEC
PY 2012
VL 18
IS 12
BP 1185
EP 1193
DI 10.1111/1469-0691.12023
PG 9
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 037MJ
UT WOS:000311109100017
PM 23033984
ER
PT J
AU Fernandez, MDB
Torres, C
Riviello-Lopez, G
Poma, HR
Rajal, VB
Nates, S
Cisterna, DM
Campos, RH
Mbayed, VA
AF Blanco Fernandez, M. D.
Torres, C.
Riviello-Lopez, G.
Poma, H. R.
Rajal, V. B.
Nates, S.
Cisterna, D. M.
Campos, R. H.
Mbayed, V. A.
TI Analysis of the circulation of hepatitis A virus in Argentina since
vaccine introduction
SO CLINICAL MICROBIOLOGY AND INFECTION
LA English
DT Article
DE Argentina; environmental surveillance; genotypes; hepatitis A virus;
immunization
ID BAYESIAN COALESCENT INFERENCE; MOLECULAR CHARACTERIZATION; POPULATIONS;
PATTERNS; CHILDREN
AB Hepatitis A virus (HAV) has shown intermediate endemicity in Argentina, but its incidence has decreased since vaccine introduction in 2005. Environmental surveillance was conducted in five rivers from Argentina from 2005 to 2012, complementing clinical information. HAV detection decreased since 2005, although its circulation continues, maintaining viral diversity but not undergoing antigenic drift. Most sequences belonged to subgenotype IA, closely related to Argentinean clinical sequences, but one belonged to proposed subgenotype IC, previously undetected in the country. Environmental surveillance might contribute to monitoring the single-dose vaccination schedule, representing not only strains causing disease but also the circulating population and the viral introductions.
C1 [Blanco Fernandez, M. D.; Torres, C.; Campos, R. H.; Mbayed, V. A.] Univ Buenos Aires, Catedra Virol, Fac Farm & Bioquim, CONICET, RA-1113 Buenos Aires, DF, Argentina.
[Riviello-Lopez, G.] Lab Quim Prefectura Naval Argentina, Buenos Aires, DF, Argentina.
[Poma, H. R.; Rajal, V. B.] Univ Nacl Salta, CONICET, Fac Ingn, INIQUI, Salta, Argentina.
[Rajal, V. B.] Univ Calif Davis, Fogarty Int Ctr, Davis, CA 95616 USA.
[Nates, S.] Univ Nacl Cordoba, Fac Ciencias Med, Inst Virol Dr JM Vanella, RA-5000 Cordoba, Argentina.
[Cisterna, D. M.] INEI ANLIS Dr Carlos G Malbran, Serv Neurovirosis, Buenos Aires, DF, Argentina.
RP Mbayed, VA (reprint author), Univ Buenos Aires, Catedra Virol, Fac Farm & Bioquim, CONICET, Junin 956,4To Piso, RA-1113 Buenos Aires, DF, Argentina.
EM vmbayed@ffyb.uba.ar
OI Torres, Carolina/0000-0001-6786-8769
NR 21
TC 5
Z9 5
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1198-743X
J9 CLIN MICROBIOL INFEC
JI Clin. Microbiol. Infect.
PD DEC
PY 2012
VL 18
IS 12
BP E548
EP E551
DI 10.1111/1469-0691.12034
PG 4
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 037MJ
UT WOS:000311109100011
ER
PT J
AU Polis, CB
Nakigozi, G
Ssempijja, V
Makumbi, FE
Boaz, I
Reynolds, SJ
Ndyanabo, A
Lutalo, T
Wawer, MJ
Gray, RH
AF Polis, Chelsea B.
Nakigozi, Gertrude
Ssempijja, Victor
Makumbi, Fredrick E.
Boaz, Iga
Reynolds, Steven J.
Ndyanabo, Anthony
Lutalo, Tom
Wawer, Maria J.
Gray, Ronald H.
TI Effect of injectable contraceptive use on response to antiretroviral
therapy among women in Rakai, Uganda
SO CONTRACEPTION
LA English
DT Article
DE Family planning; Hormonal contraception; Injectable contraception; HIV;
Antiretroviral therapy; Uganda
ID DEPOT MEDROXYPROGESTERONE ACETATE; RESOURCE-POOR SETTINGS; MEASURING
ADHERENCE; KEY INDICATORS; HIV; PHARMACOKINETICS; PLASMA; IMPACT
AB Background: There is limited evidence on the effect of injectable contraception on response to antiretroviral therapy (ART).
Design: Using modified Poisson regression, we assessed data from 418 female Ugandan ART initiators to examine the effect of injectable contraceptive use on a composite virologic failure outcome (defined as failure to achieve virologic suppression, switch to second line therapy, or death within 12 months of ART initiation) and also assessed ART adherence.
Results: About 12% of women reported using injectable contraceptives at ART initiation, and their composite virologic failure rates 12 months later were similar to women not using injectable contraceptives at ART initiation (11% vs. 12%, p=0.99). Multivariable Poisson regression suggested no significant differences in virologic failure by injectable contraceptive use at baseline (prevalence risk ratio: 0.85, p=0.71), but power was limited. Adherence to ART increased with time since ART initiation, and did not appear to differ between injectable contraceptive users and non-users.
Conclusions: Consistent with current World Health Organization guidelines, our results suggest no deleterious effect of injectable contraceptive use on response to ART, but power was limited, injectable contraceptive use patterns over time were inconsistent and additional evidence is needed. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Polis, Chelsea B.; Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Nakigozi, Gertrude; Ssempijja, Victor; Boaz, Iga; Ndyanabo, Anthony; Lutalo, Tom] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Makumbi, Fredrick E.] Makerere Univ, Coll Hlth Sci, Sch Publ Hlth, Kampala, Uganda.
[Reynolds, Steven J.] NIAID, NIH, Bethesda, MD 20892 USA.
[Reynolds, Steven J.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
RP Polis, CB (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
EM cpolis@jhsph.edu
OI Polis, Chelsea/0000-0002-1031-7074
FU University of North Carolina at Chapel Hill, Carolina Population Center,
through the USAID; Bill and Melinda Gates Foundation [22006.03];
National Institutes of Health, Division of Allergy and Infectious
Diseases [1UO1AI075115-O1A1]
FX The authors are grateful to the University of North Carolina at Chapel
Hill, Carolina Population Center, through the USAID-funded MEASURE
Evaluation Population and Reproductive Health (PRH) project for funding
this analysis. Data collection was supported by grants 22006.03 from the
Bill and Melinda Gates Foundation and 1UO1AI075115-O1A1 from the
National Institutes of Health, Division of Allergy and Infectious
Diseases. Laboratory support was provided in part by the Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health.
NR 27
TC 3
Z9 3
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0010-7824
J9 CONTRACEPTION
JI Contraception
PD DEC
PY 2012
VL 86
IS 6
BP 725
EP 730
DI 10.1016/j.contraception.2012.05.001
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 038SZ
UT WOS:000311195700019
PM 22717186
ER
PT J
AU Murray, PR
Masur, H
AF Murray, Patrick R.
Masur, Henry
TI Current approaches to the diagnosis of bacterial and fungal bloodstream
infections in the intensive care unit
SO CRITICAL CARE MEDICINE
LA English
DT Review
DE bacteremia; blood culture; fungemia; matrix-assisted laser
desorption/ionization; molecular; sepsis
ID FLIGHT MASS-SPECTROMETRY; DESORPTION IONIZATION-TIME; IN-SITU
HYBRIDIZATION; DIRECT IDENTIFICATION; CULTURE BOTTLES; MULTICENTER
EVALUATION; ANAEROBIC BACTEREMIA; PATHOGEN DETECTION; CLINICAL UTILITY;
POVIDONE-IODINE
AB Healthcare systems spend considerable resources collecting and processing blood cultures for the detection of blood stream pathogens. The process is initiated with the collection of blood cultures that depend upon proper skin disinfection, collection of an adequate number of specimens and volume of blood, and prompt processing in a sensitive culture system. Complementing blood cultures and gaining in use are techniques such as nucleic acid amplification tests and mass spectroscopy that allow clinical laboratories to detect and identify organisms from blood cultures substantially faster than conventional systems. Furthermore, certain resistance mutations can be detected within hours of organism detection, thus providing valuable guidance to clinicians who strive to initiate the appropriate antimicrobial therapy as rapidly as possible, and who wish to discontinue unnecessary drugs expeditiously. Molecular and mass spectroscopy techniques are changing sepsis diagnosis rapidly and will provide far more specific information far more quickly, but the performance characteristics of these systems must be understood by intensivists who use such information to guide their patient management. (Crit Care Med 2012; 40:3277-3282)
C1 [Masur, Henry] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Murray, Patrick R.] Becton Dickinson Diagnost Syst, Sparks, MD USA.
RP Masur, H (reprint author), NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
EM hma-sur@nih.gov
FU CLC NIH HHS [NIH0010192010]
NR 56
TC 23
Z9 24
U1 0
U2 21
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 DEC
PY 2012
VL 40
IS 12
BP 3277
EP 3282
DI 10.1097/CCM.0b013e318270e771
PG 6
WC Critical Care Medicine
SC General & Internal Medicine
GA 041UQ
UT WOS:000311427100020
PM 23034460
ER
PT J
AU Carlson, DE
AF Carlson, Drew E.
TI Managing stress in critical illness: A question of balance
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE critical illness; endocrine; resuscitation; stress; trauma
ID ACTH; RELEASE
C1 NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Carlson, DE (reprint author), NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 HL999999]
NR 11
TC 0
Z9 0
U1 0
U2 1
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 DEC
PY 2012
VL 40
IS 12
BP 3327
EP 3328
DI 10.1097/CCM.0b013e318270e38d
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA 041UQ
UT WOS:000311427100038
PM 23164783
ER
PT J
AU Guo, J
Xu, XH
Yuan, W
Jin, T
Wu, YT
AF Guo, Jia
Xu, Xuehua
Yuan, Wen
Jin, Tian
Wu, Yuntao
TI HIV gp120 is an Aberrant Chemoattractant for Blood Resting CD4 T Cells
SO CURRENT HIV RESEARCH
LA English
DT Article
DE HIV-1; CD4; gp120; CXCR4; SDF-1; chemotaxis; actin; signal transduction
ID MACROPHAGE-TROPIC HIV; VIRUS TYPE-1 GP120; CHEMOKINE RECEPTOR; ENVELOPE
GLYCOPROTEIN; ACTIVE MOVEMENT; CHEMOTAXIS; RETROVIRUS; CXCR4; CCR5;
IDENTIFICATION
AB Binding of HIV gp120 to the chemokine coreceptor CXCR4 mediates signal transduction that promotes actin dynamics critical for the establishment of viral latency in resting CD4 T cells. To some extent, this gp120-mediated signal transduction resembles the chemotactic response mediated by chemokines such as the stromal cell-derived factor-1 alpha (SDF-1). It has been suggested that gp120 functions as a bona fide chemokine to attract or repel blood CD4 T cells. To determine whether gp120 is a viral chemoattractant, we compared the chemotactic properties of gp120 with those of SDF-1, and confirmed previous observations that gp120 possesses some chemotactic ability at certain dosages. However, when we examined gp120 in a range of dosages, we found that in general, gp120 only attracts or repels blood resting CD4 T cells at a low level, and there is no clear pattern of dosage-dependency as normally seen in a typical chemokine. These irregularities of gp120 were observed in multiple donors. Nevertheless, gp120 aberrantly interferes with SDF-1-mediated T cell chemotaxis and cell migration. These results suggest that gp120 does not act like a typical chemoattractant, although it triggers actin dynamics to facilitate HIV infection.
C1 [Guo, Jia; Wu, Yuntao] George Mason Univ, Dept Mol & Microbiol, Natl Ctr Biodef & Infect Dis, Manassas, VA 20110 USA.
[Xu, Xuehua; Jin, Tian] NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH,Twinbrook Facil, Rockville, MD 20852 USA.
[Yuan, Wen] Univ Virginia, Div Infect Dis & Int Hlth, Dept Med, Myles H Thaler Ctr AIDS & Human Retrovirus Res, Charlottesville, VA 22908 USA.
RP Wu, YT (reprint author), George Mason Univ, Dept Mol & Microbiol, Natl Ctr Biodef & Infect Dis, 10900 Univ Blvd, Manassas, VA 20110 USA.
EM ywu8@gmu.edu
RI Guo, Jia/L-2102-2013; Guo, Jia/C-8678-2014;
OI xu, xuehua/0000-0002-3863-9593
FU NIH Public Health Service Grant NIAID [1R01AI081568, 1R03AI093157]
FX We thank the George Mason University (GMU) Student Health Center for
blood donations; the NIH AIDS Research and Reference Reagent Program,
NIAID, NIH for reagents; M. Rosen and the donors and riders from the
2010 NYCDC AIDS Ride. This work was supported by NIH Public Health
Service Grant grants 1R01AI081568 and 1R03AI093157 from NIAID to Y. W.
NR 38
TC 2
Z9 2
U1 0
U2 5
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-162X
J9 CURR HIV RES
JI Curr. HIV Res.
PD DEC
PY 2012
VL 10
IS 8
BP 636
EP 642
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 037LL
UT WOS:000311106100002
PM 22954308
ER
PT J
AU Ambudkar, IS
AF Ambudkar, I. S.
TI Polarization of Calcium Signaling and Fluid Secretion in Salivary Gland
Cells
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE Calcium homeostasis; calcium influx; ion channels; fluid secretion;
salivary gland cells; physiology; knockout mouse models
ID STORE-OPERATED CHANNELS; PAROTID ACINAR-CELLS; TRPC CHANNELS; EXOCRINE
SECRETION; MOLECULAR-BASIS; CRAC CHANNEL; CA2+ INFLUX; ORAI1; STIM1;
MICRODOMAINS
AB The secretion of fluid, electrolytes, and protein by exocrine gland acinar cells is a vectorial process that requires the coordinated regulation of multiple channel and transporter proteins, signaling components, as well as mechanisms involved in vesicular fusion and water transport. Most critical in this is the regulation of cytosolic free [Ca2+] ([Ca2+](i)) in response to neurotransmitter stimulation. Control of [Ca2+](i) increase in specific regions of the cell is the main determinant of fluid and electrolyte secretion in salivary gland acinar cells as it regulates several major ion flux mechanisms as well as the water channel that are required for this process. Polarized [Ca2+](i) signals are also essential for protein secretion in pancreatic acinar cells. Thus, the mechanisms that generate and modulate these compartmentalized [Ca2+](i) signals are central to the regulation of exocrine secretion. These mechanisms include membrane receptors for neurotransmitters, intracellular Ca2+ release channels, Ca2+ entry channels, as well Ca2+ as pumps and mitochondria. The spatial arrangement of proteins involved in Ca2+ signaling is of primary significance in the generation of specific compartmentalized [Ca2+](i) signals. Within these domains, both local and global [Ca2+](i) changes are tightly controlled. Control of secretion is also dependent on the targeting of ion channels and transporters to specific domains in the cell where their regulation by [Ca2+](i) signals is facilitated. Together, the polarized localization of Ca2+ signaling and secretory components drive vectorial secretion of fluid, electrolytes, and proteins in the exocrine salivary glands and pancreas. This review will discuss recent findings which have led to resolution of the molecular components underlying the spatio-temporal control of [Ca2+](i) signals in exocrine gland cells and their role in secretion.
C1 NIDCR, MPTB, NIH, Secretory Physiol Sect, Bethesda, MD 20892 USA.
RP Ambudkar, IS (reprint author), NIDCR, MPTB, NIH, Secretory Physiol Sect, Bldg 10,Room 1N-113, Bethesda, MD 20892 USA.
EM indu.ambudkar@nih.gov
FU Intramural NIH HHS [ZIA DE000438-26]
NR 47
TC 16
Z9 16
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 0929-8673
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD DEC
PY 2012
VL 19
IS 34
BP 5774
EP 5781
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 047AE
UT WOS:000311807100003
PM 23061636
ER
PT J
AU Cohen, SD
Kimmel, PL
AF Cohen, Scott D.
Kimmel, Paul L.
TI Long-term sequelae of acute kidney injury in the ICU
SO CURRENT OPINION IN CRITICAL CARE
LA English
DT Review
DE acute kidney injury; chronic kidney disease; survival
ID ACUTE-RENAL-FAILURE; PROGNOSTIC-FACTORS; CELL-CYCLE; DISEASE; SEPSIS;
PROGRESSION; OUTCOMES; RISK; DIALYSIS; AKI
AB Purpose of review
Acute kidney injury (AKI) in the ICU is associated with adverse outcomes. We review the long-term consequences of AKI in ICU patients.
Recent findings
Observational studies show associations between AKI and mortality, prolonged length of ICU stay, dependence on mechanical ventilation, the development and progression of chronic kidney disease (CKD), and need for permanent renal replacement therapy. Few studies evaluate ICU AKI outcomes specifically, and data on long-term outcomes of survivors from this population are sparse. Little information exists comparing AKI in ICU and non-ICU settings, and prospective study designs to address such questions are problematic. AKI in the ICU should be distinguished from AKI in other clinical settings, as the underlying pathophysiology, severity of illness, and risk for permanent sequelae may be different. AKI and CKD are not mutually exclusive, but are part of a clinical spectrum in which AKI can potentiate the risk for CKD and pre-existing CKD increases risks of AKI.
Summary
Further research is necessary to delineate the mechanisms by which AKI may lead to CKD, and to understand how CKD enhances the risk for developing AKI. Whereas restrospective observational studies of this population exist, prospective clinical studies and trials evaluating the long-term clinical outcomes of AKI specifically in ICU patients are needed.
C1 [Kimmel, Paul L.] NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA.
[Cohen, Scott D.; Kimmel, Paul L.] George Washington Univ, Sch Med, Dept Med, Washington, DC USA.
RP Kimmel, PL (reprint author), NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA.
EM kimmelp@extra.niddk.nih.gov
NR 52
TC 11
Z9 11
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1070-5295
EI 1531-7072
J9 CURR OPIN CRIT CARE
JI Curr. Opin. Crit. Care
PD DEC
PY 2012
VL 18
IS 6
BP 623
EP 628
DI 10.1097/MCC.0b013e328358d3f5
PG 6
WC Critical Care Medicine
SC General & Internal Medicine
GA 039IA
UT WOS:000311237000007
PM 22941209
ER
PT J
AU Aghaeepour, N
Jalali, A
O'Neill, K
Chattopadhyay, PK
Roederer, M
Hoos, HH
Brinkman, RR
AF Aghaeepour, Nima
Jalali, Adrin
O'Neill, Kieran
Chattopadhyay, Pratip K.
Roederer, Mario
Hoos, Holger H.
Brinkman, Ryan R.
TI RchyOptimyx: Cellular hierarchy optimization for flow cytometry
SO CYTOMETRY PART A
LA English
DT Article
DE polychromatic flow cytometry; mass cytometry; exploratory data analysis;
cellular hierarchy; graph theory; gating; marker panel; bioinformatics;
statistics
ID PLASMACYTOID DENDRITIC CELLS; HUMAN T-CELLS; PHENOTYPIC ANALYSIS; MASS
CYTOMETRY; B-CELLS; IMMUNE; IDENTIFICATION; ACTIVATION; RESPONSES;
LYMPHOMA
AB Analysis of high-dimensional flow cytometry datasets can reveal novel cell populations with poorly understood biology. Following discovery, characterization of these populations in terms of the critical markers involved is an important step, as this can help to both better understand the biology of these populations and aid in designing simpler marker panels to identify them on simpler instruments and with fewer reagents (i.e., in resource poor or highly regulated clinical settings). However, current tools to design panels based on the biological characteristics of the target cell populations work exclusively based on technical parameters (e.g., instrument configurations, spectral overlap, and reagent availability). To address this shortcoming, we developed RchyOptimyx (cellular hieraRCHY OPTIMization), a computational tool that constructs cellular hierarchies by combining automated gating with dynamic programming and graph theory to provide the best gating strategies to identify a target population to a desired level of purity or correlation with a clinical outcome, using the simplest possible marker panels. RchyOptimyx can assess and graphically present the trade-offs between marker choice and population specificity in high-dimensional flow or mass cytometry datasets. We present three proof-of-concept use cases for RchyOptimyx that involve 1) designing a panel of surface markers for identification of rare populations that are primarily characterized using their intracellular signature; 2) simplifying the gating strategy for identification of a target cell population; 3) identification of a non-redundant marker set to identify a target cell population. (C) 2012 International Society for Advancement of Cytometry
C1 [Brinkman, Ryan R.] British Columbia Canc Agcy, Terry Fox Lab, BC Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada.
[Chattopadhyay, Pratip K.; Roederer, Mario] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Hoos, Holger H.] Univ British Columbia, Dept Comp Sci, Vancouver, BC V5Z 1M9, Canada.
[Brinkman, Ryan R.] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada.
RP Brinkman, RR (reprint author), British Columbia Canc Agcy, Terry Fox Lab, BC Canc Res Ctr, 675 W 10th Ave, Vancouver, BC V5Z 1L3, Canada.
EM rbrinkman@bccrc.ca
RI Brinkman, Ryan/B-1108-2008;
OI Brinkman, Ryan/0000-0002-9765-2990; O'Neill, Kieran/0000-0001-7609-5905;
Chattopadhyay, Pratip/0000-0002-5457-9666
FU ISAC; MSFHR/CIHR scholarship; University of British Columbia's 4YF
scholarship; Michael Smith Foundation for Health Research Scholar Award;
NIH/NIBIB [R01 EB008400]; NSERC; Canadian Cancer Society [700374]; Terry
Fox Foundation; Terry Fox Research Institute; NIAID Intramural Research
Program
FX Grant sponsor: ISAC Scholar Awards (NA and PKC); Grant sponsor:
MSFHR/CIHR scholarship to NA; Grant sponsor: University of British
Columbia's 4YF scholarship to NA; Grant sponsor: Michael Smith
Foundation for Health Research Scholar Award to RRB; Grant sponsor:
NIH/NIBIB; Grant number: R01 EB008400; Grant sponsor: NSERC Discovery
Grant held by HH; Grant sponsor: Canadian Cancer Society; Grant number:
700374; Grant sponsor: The Terry Fox Foundation; Grant sponsor: The
Terry Fox Research Institute; Grant sponsor: NIAID Intramural Research
Program;
NR 46
TC 26
Z9 26
U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD DEC
PY 2012
VL 81A
IS 12
BP 1022
EP 1030
DI 10.1002/cyto.a.22209
PG 9
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 041EU
UT WOS:000311380700004
PM 23044634
ER
PT J
AU Dabelea, D
Mayer-Davis, EJ
Andrews, JS
Dolan, LM
Pihoker, C
Hamman, RF
Greenbaum, C
Marcovina, S
Fujimoto, W
Linder, B
Imperatore, G
D'Agostino, R
AF Dabelea, D.
Mayer-Davis, E. J.
Andrews, J. S.
Dolan, L. M.
Pihoker, C.
Hamman, R. F.
Greenbaum, C.
Marcovina, S.
Fujimoto, W.
Linder, B.
Imperatore, G.
D'Agostino, R., Jr.
TI Clinical evolution of beta cell function in youth with diabetes: the
SEARCH for Diabetes in Youth study
SO DIABETOLOGIA
LA English
DT Article
DE Beta cell function; Decline; Determinants; Epidemiology; Type 1
diabetes; Type 2 diabetes; Youth
ID ANTI-CD3 MONOCLONAL-ANTIBODY; INSULIN-SECRETION; GLUCOSE-TOLERANCE;
CONTROLLED-TRIAL; ORAL INSULIN; DOUBLE-BLIND; 1ST YEAR; ONSET; MELLITUS;
CHILDREN
AB Few studies have explored the epidemiology of beta cell loss in youth with diabetes. This report describes the evolution and major determinants of beta cell function, assessed by fasting C-peptide (FCP), in the SEARCH for Diabetes in Youth study.
Participants were 1,277 youth with diabetes (948 positive for diabetes autoantibodies [DAs] and 329 negative for DAs), diagnosed when aged < 20 years, who were followed from a median of 8 months post diagnosis, for approximately 30 months. We modelled the relationship between rate of change in log FCP and determinants of interest using repeated measures general linear models.
Among DA-positive youth, there was a progressive decline in beta cell function of 4% per month, independent of demographics (age, sex, race/ethnicity), genetic susceptibility to autoimmunity (HLA risk), HbA(1c) and BMI z score, or presence of insulin resistance. Among DA-negative youth, there was marked heterogeneity in beta cell loss, reflecting an aetiologically mixed group. This group likely includes youths with undetected autoimmunity (whose decline is similar to that of DA-positive youth) and youth with non-autoimmune, insulin-resistant diabetes, with limited decline ( 0.7% per month).
SEARCH provides unique estimates of beta cell function decline in a large sample of youth with diabetes, indicating that autoimmunity is the major contributor. These data contribute to a better understanding of clinical evolution of beta cell function in youth with diabetes, provide strong support for the aetiological classification of diabetes type and may inform tertiary prevention efforts targeted at high-risk groups.
C1 [Dabelea, D.; Hamman, R. F.] Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO 80045 USA.
[Mayer-Davis, E. J.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[Andrews, J. S.; D'Agostino, R., Jr.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Dolan, L. M.] Univ Cincinnati Coll Med, Cincinnati Childrens Hosp, Dept Pediat, Cincinnati, OH USA.
[Pihoker, C.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Greenbaum, C.] Benaroya Res Inst, Diabet Res Program, Seattle, WA USA.
[Marcovina, S.] Univ Washington, Dept Med, Seattle, WA USA.
[Fujimoto, W.] Kuakini Med Ctr, Honolulu, HI USA.
[Linder, B.] NIDDK, NIH, Bethesda, MD USA.
[Imperatore, G.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA.
[Mayer-Davis, E. J.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
RP Dabelea, D (reprint author), Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Epidemiol, 13001 E 17th Ave,Box B119, Aurora, CO 80045 USA.
EM Dana.Dabelea@ucdenver.edu
RI Dagostino Jr, Ralph/C-4060-2017
OI Dagostino Jr, Ralph/0000-0002-3550-8395
FU Centers for Disease Control and Prevention [00097, DP-05-069,
DP-10-001]; National Institute of Diabetes and Digestive and Kidney
Diseases; Kaiser Permanente Southern California [U48/CCU919219, U01
DP000246, U18DP002714]; University of Colorado Denver [U48/CCU819241-3,
U01 DP000247, U18DP000247-06A1]; Kuakini Medical Center [U58CCU919256,
U01 DP000245]; Children's Hospital Medical Center (Cincinnati)
[U48/CCU519239, U01 DP000248, 1U18DP002709]; University of North
Carolina at Chapel Hill [U48/CCU419249, U01 DP000254, U18DP002708-01];
University of Washington School of Medicine [U58/CCU019235-4, U01
DP000244, U18DP002710-01]; Wake Forest University School of Medicine
[U48/CCU919219, U01 DP000250, 200-2010-35171]; Medical University of
South Carolina (NIH/NCRR) [UL1RR029882]; Children's Hospital and
Regional Medical Center [M01RR00037]; Colorado Pediatric General
Clinical Research Center [M01 RR00069]; Barbara Davis Center at the
University of Colorado at Denver (DERC NIH) [P30 DK57516]; Institutional
Clinical and Translational Science Award (CTSA); NIH/NCRR at the
University of Cincinnati [1UL1RR026314-01]
FX SEARCH for Diabetes in Youth is funded by the Centers for Disease
Control and Prevention (PA Nos 00097, DP-05-069 and DP-10-001) and
supported by the National Institute of Diabetes and Digestive and Kidney
Diseases.; Site contract Nos: Kaiser Permanente Southern California
(U48/CCU919219, U01 DP000246 and U18DP002714), University of Colorado
Denver (U48/CCU819241-3, U01 DP000247 and U18DP000247-06A1), Kuakini
Medical Center (U58CCU919256 and U01 DP000245), Children's Hospital
Medical Center (Cincinnati) (U48/CCU519239, U01 DP000248 and
1U18DP002709), University of North Carolina at Chapel Hill
(U48/CCU419249, U01 DP000254 and U18DP002708-01), University of
Washington School of Medicine (U58/CCU019235-4, U01 DP000244 and
U18DP002710-01), Wake Forest University School of Medicine
(U48/CCU919219, U01 DP000250 and 200-2010-35171).; The authors wish to
acknowledge the involvement of General Clinical Research Centers (GCRC)
at the South Carolina Clinical & Translational Research (SCTR)
Institute, at the Medical University of South Carolina (NIH/NCRR Grant
No. UL1RR029882); Children's Hospital and Regional Medical Center (Grant
No. M01RR00037); Colorado Pediatric General Clinical Research Center
(Grant No. M01 RR00069) and the Barbara Davis Center at the University
of Colorado at Denver (DERC NIH P30 DK57516); and the Institutional
Clinical and Translational Science Award (CTSA), NIH/NCRR at the
University of Cincinnati (Grant No. 1UL1RR026314-01).
NR 48
TC 23
Z9 25
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD DEC
PY 2012
VL 55
IS 12
BP 3359
EP 3368
DI 10.1007/s00125-012-2719-6
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 027VJ
UT WOS:000310381800024
PM 22990715
ER
PT J
AU Simeon, FG
Liow, JS
Zhang, Y
Hong, JS
Gladding, RL
Zoghbi, SS
Innis, RB
Pike, VW
AF Simeon, Fabrice G.
Liow, Jeih-San
Zhang, Yi
Hong, Jinsoo
Gladding, Robert L.
Zoghbi, Sami S.
Innis, Robert B.
Pike, Victor W.
TI Synthesis and characterization in monkey of [C-11]SP203 as a radioligand
for imaging brain metabotropic glutamate 5 receptors
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE Radioligand; PET; mGluR5; Carbon-11; SP203
ID POSITRON-EMISSION-TOMOGRAPHY; SUBTYPE-5 RECEPTORS; ANXIOLYTIC ACTIVITY;
PET RADIOLIGAND; C-11-ABP688; ANTAGONIST; F-18-SP203; COCAINE; POTENT;
MICE
AB [F-18]SP203 (3-fluoro-5-(2-(2-([F-18]fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile) is an effective high-affinity and selective radioligand for imaging metabotropic 5 receptors (mGluR5) in human brain with PET. To provide a radioligand that may be used for more than one scanning session in the same subject in a single day, we set out to label SP203 with shorter-lived C-11 (t (1/2) = 20.4 min) and to characterize its behavior as a radioligand with PET in the monkey.
Iodo and bromo precursors were obtained by cross-coupling 2-fluoromethyl-4-((trimethylsilyl)ethynyl)-1,3-thiazole with 3,5-diiodofluorobenzene and 3,5-dibromofluorobenzene, respectively. Treatment of either precursor with [C-11]cyanide ion rapidly gave [C-11]SP203, which was purified with high-performance liquid chromatography. PET was used to measure the uptake of radioactivity in brain regions after injecting [C-11]SP203 intravenously into rhesus monkeys at baseline and under conditions in which mGluR5 were blocked with 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP). The emergence of radiometabolites in monkey blood in vitro and in vivo was assessed with radio-HPLC. The stability of [C-11]SP203 in human blood in vitro was also measured.
The iodo precursor gave [C-11]SP203 in higher radiochemical yield (> 98 %) than the bromo precursor (20-52 %). After intravenous administration of [C-11]SP203 into three rhesus monkeys, radioactivity peaked early in brain (average 12.5 min) with a regional distribution in rank order of expected mGluR5 density. Peak uptake was followed by a steady decline. No radioactivity accumulated in the skull. In monkeys pretreated with MTEP before [C-11]SP203 administration, radioactivity uptake in brain was again high but then declined more rapidly than in the baseline scan to a common low level. [C-11]SP203 was unstable in monkey blood in vitro and in vivo, and gave predominantly less lipophilic radiometabolites. By contrast, [C-11]SP203 was stable in human blood in vitro.
[C-11]SP203 emulates [F-18]SP203 with regard to providing a sizeable mGluR5-specific signal in monkey brain, and advantageously avoids troublesome accumulation of radioactivity in bone. Although [C-11]SP203 is unsuitable for mGluR5 quantification in monkey brain, its evaluation as a PET radioligand for studying human brain mGluR5 is nevertheless warranted.
C1 [Simeon, Fabrice G.; Liow, Jeih-San; Zhang, Yi; Hong, Jinsoo; Gladding, Robert L.; Zoghbi, Sami S.; Innis, Robert B.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Rm B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health
(National Institute of Mental Health)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (National Institute of Mental Health). We
thank the National Institutes of Health Clinical PET Center (Chief: Dr.
Peter Herscovitch) for the production of hydrogen [11C]
cyanide and Dr. H. Umesha Shetty for mass spectrometry.
NR 31
TC 6
Z9 6
U1 0
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD DEC
PY 2012
VL 39
IS 12
BP 1949
EP 1958
DI 10.1007/s00259-012-2205-x
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 035MI
UT WOS:000310950900016
PM 22885775
ER
PT J
AU Taieb, D
Timmers, HJ
Hindie, E
Guillet, BA
Neumann, HP
Walz, MK
Opocher, G
de Herder, WW
Boedeker, CC
de Krijger, RR
Chiti, A
Al-Nahhas, A
Pacak, K
Rubello, D
AF Taieb, David
Timmers, Henri J.
Hindie, Elif
Guillet, Benjamin A.
Neumann, Hartmut P.
Walz, Martin K.
Opocher, Giuseppe
de Herder, Wouter W.
Boedeker, Carsten C.
de Krijger, Ronald R.
Chiti, Arturo
Al-Nahhas, Adil
Pacak, Karel
Rubello, Domenico
TI EANM 2012 guidelines for radionuclide imaging of phaeochromocytoma and
paraganglioma
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE Guidelines; Review literature; Radionuclide imaging; Paraganglioma;
Phaeochromocytoma
ID POSITRON-EMISSION-TOMOGRAPHY; SOMATOSTATIN RECEPTOR SCINTIGRAPHY;
I-131/I-123-METAIODOBENZYLGUANIDINE MIBG SCINTIGRAPHY; F-18-DOPA PET-CT;
NECK PARAGANGLIOMAS; IN-111-PENTETREOTIDE SCINTIGRAPHY; METASTATIC
PHEOCHROMOCYTOMA; I-123 METAIODOBENZYLGUANIDINE; MALIGNANT
PHEOCHROMOCYTOMA; OCTREOTIDE SCINTIGRAPHY
AB Radionuclide imaging of phaeochromocytomas (PCCs) and paragangliomas (PGLs) involves various functional imaging techniques and approaches for accurate diagnosis, staging and tumour characterization. The purpose of the present guidelines is to assist nuclear medicine practitioners in performing, interpreting and reporting the results of the currently available SPECT and PET imaging approaches. These guidelines are intended to present information specifically adapted to European practice.
Guidelines from related fields, issued by the European Association of Nuclear Medicine and the Society of Nuclear Medicine, were taken into consideration and are partially integrated within this text. The same was applied to the relevant literature, and the final result was discussed with leading experts involved in the management of patients with PCC/PGL. The information provided should be viewed in the context of local conditions, laws and regulations.
Although several radionuclide imaging modalities are considered herein, considerable focus is given to PET imaging which offers high sensitivity targeted molecular imaging approaches.
C1 [Taieb, David] Aix Marseille Univ, La Timone Univ Hosp, Dept Nucl Med, CERIMED, Marseille, France.
[Timmers, Henri J.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands.
[Hindie, Elif] Univ Bordeaux 2, Haut Leveque Hosp, Dept Nucl Med, F-33076 Bordeaux, France.
[Guillet, Benjamin A.] Aix Marseille Univ, La Timone Univ Hosp, Dept Radiopharm, CERIMED, Marseille, France.
[Neumann, Hartmut P.] Univ Freiburg, Dept Med, Prevent Med Unit, Univ Med Ctr, Freiburg, Germany.
[Walz, Martin K.] Kliniken Essen Mitte, Dept Surg, Essen, Germany.
[Walz, Martin K.] Kliniken Essen Mitte, Ctr Minimally Invas Surg, Essen, Germany.
[Opocher, Giuseppe] Univ Hosp Padova, Dept Med & Surg Sci, Endocrinol Unit, Padua, Italy.
[de Herder, Wouter W.] Erasmus MC, Endocrinol Sect, Dept Internal Med, Rotterdam, Netherlands.
[Boedeker, Carsten C.] Univ Freiburg, Dept Otorhinolaryngol Head & Neck Surg, D-79106 Freiburg, Germany.
[de Krijger, Ronald R.] Univ Med Ctr Rotterdam, Josephine Nefkens Inst, Dept Pathol, Erasmus MC, Rotterdamn, Netherlands.
[Chiti, Arturo] Ist Clin Humanitas, Dept Nucl Med, Rozzano, MI, Italy.
[Al-Nahhas, Adil] Hammersmith Hosp, Dept Nucl Med, London, England.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Rubello, Domenico] Santa Maria della Misericordia Hosp, Dept Nucl Med, PET CT Ctr, Rovigo, Italy.
RP Taieb, D (reprint author), Aix Marseille Univ, La Timone Univ Hosp, Dept Nucl Med, CERIMED, Marseille, France.
EM david.taieb@ap-hm.fr; domenico.rubello@libero.it
RI guillet, benjamin/G-2848-2013; Opocher, Giuseppe/F-3950-2014; Chiti,
Arturo/K-6524-2016
OI Opocher, Giuseppe/0000-0002-9845-9623; Chiti, Arturo/0000-0002-5806-1856
FU Intramural NIH HHS [Z01 HD008735-08]
NR 104
TC 82
Z9 84
U1 1
U2 20
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD DEC
PY 2012
VL 39
IS 12
BP 1977
EP 1995
DI 10.1007/s00259-012-2215-8
PG 19
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 035MI
UT WOS:000310950900020
PM 22926712
ER
PT J
AU Adelstein, DJ
Ridge, JA
Brizel, DM
Holsinger, FC
Haughey, BH
O'Sullivan, B
Genden, EM
Beitler, JJ
Weinstein, GS
Quon, H
Chepeha, DB
Ferris, RL
Weber, RS
Movsas, B
Waldron, J
Lowe, V
Ramsey, S
Manola, J
Yueh, B
Carey, TE
Bekelman, JE
Konski, AA
Moore, E
Forastiere, A
Schuller, DE
Lynn, J
Ullmann, CD
AF Adelstein, David J.
Ridge, John A.
Brizel, David M.
Holsinger, F. Christopher
Haughey, Bruce H.
O'Sullivan, Brian
Genden, Eric M.
Beitler, Jonathan J.
Weinstein, Gregory S.
Quon, Harry
Chepeha, Douglas B.
Ferris, Robert L.
Weber, Randal S.
Movsas, Benjamin
Waldron, John
Lowe, Val
Ramsey, Scott
Manola, Judith
Yueh, Bevan
Carey, Thomas E.
Bekelman, Justin E.
Konski, Andre A.
Moore, Eric
Forastiere, Arlene
Schuller, David E.
Lynn, Jean
Ullmann, Claudio Dansky
TI Transoral resection of pharyngeal cancer: Summary of a National Cancer
Institute Head and Neck Cancer Steering Committee Clinical Trials
Planning Meeting, November 6-7, 2011, Arlington, Virginia
SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND
NECK
LA English
DT Review
ID SQUAMOUS-CELL-CARCINOMA; QUALITY-OF-LIFE; LOCALLY ADVANCED HEAD;
LYMPH-NODE METASTASES; STAGE OROPHARYNGEAL CANCER; UPPER AERODIGESTIVE
TRACT; ADVANCED LARYNGEAL-CANCER; LASER MICROSURGERY TLM; LONG-TERM
DYSPHAGIA; ROBOTIC SURGERY
AB Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 67, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)initiated oropharyngeal cancers, and in those with HPV-unrelated disease. The proceedings of this meeting are summarized. (c) 2012 Wiley Periodicals, Inc. Head Neck, 2012
C1 [Adelstein, David J.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
[Ridge, John A.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Brizel, David M.] Duke Canc Inst, Durham, NC USA.
[Holsinger, F. Christopher; Weber, Randal S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Haughey, Bruce H.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA.
[O'Sullivan, Brian; Waldron, John] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada.
[Genden, Eric M.] Mt Sinai Sch Med, New York, NY USA.
[Beitler, Jonathan J.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
[Weinstein, Gregory S.; Bekelman, Justin E.] Univ Penn, Philadelphia, PA 19104 USA.
[Quon, Harry; Forastiere, Arlene] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Chepeha, Douglas B.; Carey, Thomas E.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Ferris, Robert L.] Univ Pittsburgh, Pittsburgh, PA USA.
[Movsas, Benjamin] Henry Ford Hosp, Detroit, MI 48202 USA.
[Lowe, Val; Moore, Eric] Mayo Clin, Rochester, MN USA.
[Ramsey, Scott] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Manola, Judith] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Yueh, Bevan] Univ Minnesota, Minneapolis, MN USA.
[Konski, Andre A.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Schuller, David E.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Lynn, Jean; Ullmann, Claudio Dansky] NCI, Bethesda, MD 20892 USA.
RP Adelstein, DJ (reprint author), Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
EM adelstd@ccf.org
OI Yueh, Bevan/0000-0003-1380-1053; Ferris, Robert/0000-0001-6605-2071;
Carey, Thomas/0000-0002-5202-7518
FU NCI NIH HHS [P30 CA016672]
NR 119
TC 42
Z9 42
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1043-3074
J9 HEAD NECK-J SCI SPEC
JI Head Neck-J. Sci. Spec. Head Neck
PD DEC
PY 2012
VL 34
IS 12
BP 1681
EP 1703
DI 10.1002/hed.23136
PG 23
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 040AT
UT WOS:000311291900001
PM 23015475
ER
PT J
AU Lui, JLC
Nilsson, O
Chan, YL
Palmer, CD
Andrade, AC
Hirschhorn, JN
Baron, J
AF Lui, Julian C.
Nilsson, Ola
Chan, Yingleong
Palmer, Cameron D.
Andrade, Anenisia C.
Hirschhorn, Joel N.
Baron, Jeffrey
TI Synthesizing genome-wide association studies and expression microarray
reveals novel genes that act in the human growth plate to modulate
height
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID MESSENGER-RNA; BONE-GROWTH; CHONDROCYTE; SENESCENCE; COMPLEX; CANCER;
MICE
AB Previous meta-analysis of genome-wide association (GWA) studies has identified 180 loci that influence adult height. However, each GWA locus typically comprises a set of contiguous genes, only one of which presumably modulates height. We reasoned that many of the causative genes within these loci influence height because they are expressed in and function in the growth plate, a cartilaginous structure that causes bone elongation and thus determines stature. Therefore, we used expression microarray studies of mouse and rat growth plate, human disease databases and a mouse knockout phenotype database to identify genes within the GWAS loci that are likely required for normal growth plate function. Each of these approaches identified significantly more genes within the GWA height loci than at random genomic locations (P 0.0001 each), supporting the validity of the approach. The combined analysis strongly implicates 78 genes in growth plate function, including multiple genes that participate in PTHrP-IHH, BMP and CNP signaling, and many genes that have not previously been implicated in the growth plate. Thus, this analysis reveals a large number of novel genes that regulate human growth plate chondrogenesis and thereby contribute to the normal variations in human adult height. The analytic approach developed for this study may be applied to GWA studies for other common polygenic traits and diseases, thus providing a new general strategy to identify causative genes within GWA loci and to translate genetic associations into mechanistic biological insights.
C1 [Lui, Julian C.; Baron, Jeffrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Nilsson, Ola; Andrade, Anenisia C.] Karolinska Inst, Dept Womens & Childrens Hlth, Ctr Mol Med, SE-17176 Stockholm, Sweden.
[Nilsson, Ola; Andrade, Anenisia C.] Karolinska Inst, Dept Womens & Childrens Hlth, Pediat Endocrinol Unit, SE-17176 Stockholm, Sweden.
[Nilsson, Ola; Andrade, Anenisia C.] Karolinska Univ Hosp, SE-17176 Stockholm, Sweden.
[Chan, Yingleong; Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Chan, Yingleong; Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Chan, Yingleong; Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Chan, Yingleong; Palmer, Cameron D.; Hirschhorn, Joel N.] Broad Inst, Metab Initiat, Cambridge, MA 02142 USA.
[Chan, Yingleong; Palmer, Cameron D.; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Chan, Yingleong; Palmer, Cameron D.; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Lui, JLC (reprint author), CRC, Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA.
EM luichunk@mail.nih.gov
RI Lui, Chun Kin Julian/E-2253-2012;
OI Nilsson, Ola/0000-0002-9986-8138
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), US National Institutes of Health (NIH); National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH
[1R01DK075787]; March of Dimes Foundation [6-FY09-507]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), US National Institutes of Health (NIH); grant 1R01DK075787 from
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), NIH; and grant 6-FY09-507 from March of Dimes Foundation.
NR 31
TC 30
Z9 30
U1 1
U2 18
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 DEC 1
PY 2012
VL 21
IS 23
BP 5193
EP 5201
DI 10.1093/hmg/dds347
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 035SE
UT WOS:000310967900014
PM 22914739
ER
PT J
AU Weickert, CS
Miranda-Angulo, AL
Wong, J
Perlman, WR
Ward, SE
Radhakrishna, V
Straub, RE
Weinberger, DR
Kleinman, JE
AF Weickert, Cynthia Shannon
Miranda-Angulo, Ana L.
Wong, Jenny
Perlman, William R.
Ward, Sarah E.
Radhakrishna, Vakkalanka
Straub, Richard E.
Weinberger, Daniel R.
Kleinman, Joel E.
TI Variants in the estrogen receptor alpha gene and its mRNA contribute to
risk for schizophrenia (vol 17, pg 2293, 2008)
SO HUMAN MOLECULAR GENETICS
LA English
DT Correction
C1 [Weickert, Cynthia Shannon; Miranda-Angulo, Ana L.; Perlman, William R.; Ward, Sarah E.] NIMH, MiNDS Unit, Sect Neuropathol, NIH, Bethesda, MD 20892 USA.
[Kleinman, Joel E.] NIMH, Sect Neuropathol, CBDB, NIH, Bethesda, MD 20892 USA.
[Radhakrishna, Vakkalanka; Straub, Richard E.; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, GCAP, NIH, Bethesda, MD 20892 USA.
[Weickert, Cynthia Shannon; Wong, Jenny] UNSW, POWMRI, Schizophrenia Res Inst, Schizophrenia Res Lab, Sydney, NSW 2031, Australia.
[Miranda-Angulo, Ana L.] Univ Antioquia, Medellin, Colombia.
RP Weickert, CS (reprint author), NIMH, MiNDS Unit, Sect Neuropathol, NIH, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 3
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 DEC 1
PY 2012
VL 21
IS 23
BP 5238
EP 5238
DI 10.1093/hmg/dds366
PG 1
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 035SE
UT WOS:000310967900020
ER
PT J
AU Smith, H
Galmes, R
Gogolina, E
Straatman-Iwanowska, A
Reay, K
Banushi, B
Bruce, CK
Cullinane, AR
Romero, R
Chang, R
Ackermann, O
Baumann, C
Cangul, H
Celik, FC
Aygun, C
Coward, R
Dionisi-Vici, C
Sibbles, B
Inward, C
Kim, CA
Klumperman, J
Knisely, AS
Watson, SP
Gissen, P
AF Smith, Holly
Galmes, Romain
Gogolina, Ekaterina
Straatman-Iwanowska, Anna
Reay, Kim
Banushi, Blerida
Bruce, Christopher K.
Cullinane, Andrew R.
Romero, Rene
Chang, Richard
Ackermann, Oanez
Baumann, Clarisse
Cangul, Hakan
Celik, Fatma Cakmak
Aygun, Canan
Coward, Richard
Dionisi-Vici, Carlo
Sibbles, Barbara
Inward, Carol
Kim, Chong Ae
Klumperman, Judith
Knisely, A. S.
Watson, Steven P.
Gissen, Paul
TI Associations among genotype, clinical phenotype, and intracellular
localization of trafficking proteins in ARC syndrome
SO HUMAN MUTATION
LA English
DT Article
DE ostopenia; cholestasis; HOPS complex; recycling endosomes; VPS33B; VIPAR
ID DEEP-ORANGE; TETHERING COMPLEX; RENAL DYSFUNCTION; BIOGENESIS;
DROSOPHILA; ARTHROGRYPOSIS; MELANOGASTER; MUTATIONS; HOMOLOGS; FUSION
AB Arthrogryposisrenal dysfunctioncholestasis (ARC) syndrome is a rare autosomal recessive multisystem disorder caused by mutations in vacuolar protein sorting 33 homologue B (VPS33B) and VPS33B interacting protein, apicalbasolateral polarity regulator (VIPAR). Cardinal features of ARC include congenital joint contractures, renal tubular dysfunction, cholestasis, severe failure to thrive, ichthyosis, and a defect in platelet alpha-granule biogenesis. Most patients with ARC do not survive past the first year of life. We report two patients presenting with a mild ARC phenotype, now 5.5 and 3.5 years old. Both patients were compound heterozygotes with the novel VPS33B donor splice-site mutation c.1225+5G>C in common. Immunoblotting and complementary DNA analysis suggest expression of a shorter VPS33B transcript, and cell-based assays show that c.1225+5G>C VPS33B mutant retains some ability to interact with VIPAR (and thus partial wild-type function). This study provides the first evidence of genotypephenotype correlation in ARC and suggests that VPS33B c.1225+5G>C mutation predicts a mild ARC phenotype. We have established an interactive online database for ARC (https://grenada.lumc.nl/LOVD2/ARC) comprising all known variants in VPS33B and VIPAR. Also included in the database are 15 novel pathogenic variants in VPS33B and five in VIPAR. Hum Mutat 33:16561664, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Smith, Holly; Gogolina, Ekaterina; Straatman-Iwanowska, Anna; Banushi, Blerida; Gissen, Paul] UCL, MRC, Mol Cell Biol Lab, London WC1E 6BT, England.
[Watson, Steven P.] Univ Birmingham, Coll Med & Dent Sci, Sch Clin & Expt Med, Platelet Grp, Birmingham, W Midlands, England.
[Smith, Holly; Gogolina, Ekaterina; Straatman-Iwanowska, Anna; Banushi, Blerida; Gissen, Paul] UCL, Inst Child Hlth, London WC1E 6BT, England.
[Galmes, Romain; Klumperman, Judith] Univ Med Ctr, Dept Cell Biol, Utrecht, Netherlands.
[Gogolina, Ekaterina] Univ Edinburgh, Sch Med, Edinburgh, Midlothian, Scotland.
[Reay, Kim] Birmingham Womens Hosp, W Midlands Reg Genet Lab, Birmingham, W Midlands, England.
[Cullinane, Andrew R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Romero, Rene] Emory Childrens Ctr, Div Gastroenterol Hepatol & Nutr, Atlanta, GA USA.
[Chang, Richard] Childrens Hosp Orange Cty, Div Metab Disorders, Orange, CA 92668 USA.
[Ackermann, Oanez] CHU Bicetre, Serv Hepatol Pediat, Paris, France.
[Baumann, Clarisse] Hop Robert Debre, Clin Genet Unit, F-75019 Paris, France.
[Celik, Fatma Cakmak; Aygun, Canan] Mayis Univ, Neonatol Unit, Samsun, Turkey.
[Coward, Richard; Inward, Carol] Bristol Royal Hosp Sick Children, Bristol, Avon, England.
[Dionisi-Vici, Carlo] Bambino Gesu Childrens Hosp IRCCS, Div Metab, Rome, Italy.
[Sibbles, Barbara] Erasmus Univ, Sophia Childrens Hosp, Med Ctr, Rotterdam, Netherlands.
[Kim, Chong Ae] Univ Sao Paulo, Dept Pediat, Inst Crianca, Sao Paulo, Brazil.
[Knisely, A. S.] Kings Coll Hosp, Inst Liver Studies Histopathol, London, England.
[Gissen, Paul] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
RP Gissen, P (reprint author), UCL, MRC, Mol Cell Biol Lab, Gower St, London WC1E 6BT, England.
EM p.gissen@ucl.ac.uk
OI Galmes, Romain/0000-0001-5616-5937
FU Wellcome Trust [WT095662MA]; Bold FP7 ITN project [238821]; VICI of the
Netherlands Organization for Scientific Research [918.56.611]
FX Contract grant sponsors: H.S. is an MRC PhD fellow; P.G. is a Wellcome
Trust Senior Research Fellow in Clinical Sciences (WT095662MA); P.G. and
B.B. are supported by Bold FP7 ITN project-238821; R.G. and J.K. were
supported by VICI grant 918.56.611 of the Netherlands Organization for
Scientific Research awarded to J.K.
NR 28
TC 24
Z9 28
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD DEC
PY 2012
VL 33
IS 12
BP 1656
EP 1664
DI 10.1002/humu.22155
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 035UP
UT WOS:000310975900007
PM 22753090
ER
PT J
AU Mittag, F
Buchel, F
Saad, M
Jahn, A
Schulte, C
Bochdanovits, Z
Simon-Sanchez, J
Nalls, MA
Keller, M
Hernandez, DG
Gibbs, JR
Lesage, S
Brice, A
Heutink, P
Martinez, M
Wood, NW
Hardy, J
Singleton, AB
Zell, A
Gasser, T
Sharma, M
AF Mittag, Florian
Buechel, Finja
Saad, Mohamad
Jahn, Andreas
Schulte, Claudia
Bochdanovits, Zoltan
Simon-Sanchez, Javier
Nalls, Mike A.
Keller, Margaux
Hernandez, Dena G.
Gibbs, J. Raphael
Lesage, Suzanne
Brice, Alexis
Heutink, Peter
Martinez, Maria
Wood, Nicholas W.
Hardy, John
Singleton, Andrew B.
Zell, Andreas
Gasser, Thomas
Sharma, Manu
CA Int Parkinson's Dis Genomics Conso
TI Use of support vector machines for disease risk prediction in
genome-wide association studies: Concerns and opportunities
SO HUMAN MUTATION
LA English
DT Article
DE genome-wide association studies; disease risk prediction; machine
learning; support vector machines; Parkinson disease
ID COMPLEX DISEASES; COMMON DISEASES; PARKINSONS-DISEASE; HERITABILITY;
METAANALYSIS; POPULATION; VARIANTS; GENES; LOCI
AB The success of genome-wide association studies (GWAS) in deciphering the genetic architecture of complex diseases has fueled the expectations whether the individual risk can also be quantified based on the genetic architecture. So far, disease risk prediction based on top-validated single-nucleotide polymorphisms (SNPs) showed little predictive value. Here, we applied a support vector machine (SVM) to Parkinson disease (PD) and type 1 diabetes (T1D), to show that apart from magnitude of effect size of risk variants, heritability of the disease also plays an important role in disease risk prediction. Furthermore, we performed a simulation study to show the role of uncommon (frequency 15%) as well as rare variants (frequency <1%) in disease etiology of complex diseases. Using a cross-validation model, we were able to achieve predictions with an area under the receiver operating characteristic curve (AUC) of similar to 0.88 for T1D, highlighting the strong heritable component (similar to 90%). This is in contrast to PD, where we were unable to achieve a satisfactory prediction (AUC similar to 0.56; heritability similar to 38%). Our simulations showed that simultaneous inclusion of uncommon and rare variants in GWAS would eventually lead to feasible disease risk prediction for complex diseases such as PD. The used software is available at http://www.ra.cs.uni-tuebingen.de/software/MACLEAPS/. Hum Mutat 33:17081718, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Mittag, Florian; Buechel, Finja; Jahn, Andreas; Zell, Andreas] Univ Tubingen, Ctr Bioinformat Tuebingen ZBIT, D-72076 Tubingen, Germany.
[Saad, Mohamad; Martinez, Maria] Ctr Physiopathol Toulouse Purpan, INSERM, UMR 1043, Toulouse, France.
[Saad, Mohamad; Martinez, Maria] Univ Toulouse 3, Dept Sci Vivant, F-31062 Toulouse, France.
[Schulte, Claudia; Gasser, Thomas; Sharma, Manu] Univ Tubingen, Dept Neurodegenerat Dis, Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany.
[Schulte, Claudia; Gasser, Thomas; Sharma, Manu] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany.
[Bochdanovits, Zoltan; Simon-Sanchez, Javier; Heutink, Peter] Vrije Univ Amsterdam, Sect Med Genom, Dept Clin Genet, Med Ctr, Amsterdam, Netherlands.
[Nalls, Mike A.; Keller, Margaux; Hernandez, Dena G.; Gibbs, J. Raphael; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Keller, Margaux] Temple Univ, Dept Biol Anthropol, Philadelphia, PA 19122 USA.
[Hernandez, Dena G.; Gibbs, J. Raphael; Wood, Nicholas W.; Hardy, John] UCL, Inst Neurol, Dept Mol Neurosci, London, England.
[Lesage, Suzanne; Brice, Alexis] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, UMR S975, Paris, France.
[Brice, Alexis] Hop La Pitie Salpetriere, AP HP, Dept Genet & Cytogenet, Paris, France.
[Lesage, Suzanne; Brice, Alexis] INSERM, UMR CRicm S975, Paris, France.
[Lesage, Suzanne; Brice, Alexis] CNRS, UMR 7225, Paris, France.
RP Sharma, M (reprint author), Univ Tubingen, Dept Neurol, Hertie Inst Clin Brain Res, Hoppe Seyler Str 3, D-72076 Tubingen, Germany.
EM manu.sharma@uni-tuebingen.de
RI Traynor, Bryan/G-5690-2010; Guerreiro, Rita/A-1327-2011; Hardy,
John/C-2451-2009; Bras, Jose/A-1428-2011; Charlesworth,
Gavin/B-5895-2011; Singleton, Andrew/C-3010-2009; O'Sullivan,
Sean/C-9333-2012; Deuschl, Gunther/A-7986-2010; lambert,
jean-charles/F-8787-2013; Trabzuni, Daniah/C-4034-2012; Wood,
Nicholas/C-2505-2009; van de Warrenburg, Bart/D-1935-2010; Martinez,
Maria/B-3111-2013; corvol, jean-christophe/I-6387-2012;
OI O'Sullivan, Sean/0000-0002-0583-7956; Trabzuni,
Daniah/0000-0003-4826-9570; Wood, Nicholas/0000-0002-9500-3348;
Martinez, Maria/0000-0003-2180-4537; corvol,
jean-christophe/0000-0001-7325-0199; Schulte,
Claudia/0000-0003-4006-1265; Stefansson, Hreinn/0000-0002-9331-6666;
Bhatia, Kailash/0000-0001-8185-286X
FU National Institute on Aging; National Institute of Neurological
Disorders and Stroke; National Institute of Environmental Health
Sciences; National Human Genome Research Institute of the National
Institutes of Health; Department of Health and Human Services
[Z01-AG000949-02, Z01-ES101986]; Human subjects protocol [2003-077]; US
Department of Defense [W81XWH-09-2-0128]; National Institutes of Health
[NS057105, RR024992]; American Parkinson disease Association (APDA);
Barnes Jewish Hospital Foundation; Greater St Louis Chapter of the APDA;
Hersenstichting Nederland; Neuroscience Campus Amsterdam; section of
medical genomics, the Prinses Beatrix Fonds; Michael J. Fox foundation;
KORA (Cooperative Research in the Region of Augsburg) research platform;
Forschungszentrum fur Umwelt und Gesundheit; German Federal Ministry of
Education, Science, Research, and Technology; State of Bavaria; German
National Genome Network [01GS08134]; German Federal Ministry of
Education and Research [NGFN 01GR0468, PopGen]; Initiative and
Networking Fund of the Helmholtz Association [01EW0908]; French National
Agency of Research [ANR-08-MNP-012]; Wellcome Trust [076113, 085475]
FX Contract grant sponsors: Intramural Research Programs of the National
Institute on Aging; National Institute of Neurological Disorders and
Stroke; National Institute of Environmental Health Sciences; National
Human Genome Research Institute of the National Institutes of Health;
Department of Health and Human Services (project numbers Z01-AG000949-02
and Z01-ES101986); Human subjects protocol 2003-077; US Department of
Defense (award number W81XWH-09-2-0128); National Institutes of Health
(grants NS057105 and RR024992); American Parkinson disease Association
(APDA); Barnes Jewish Hospital Foundation; Greater St Louis Chapter of
the APDA; Hersenstichting Nederland; Neuroscience Campus Amsterdam; the
section of medical genomics, the Prinses Beatrix Fonds; and the Michael
J. Fox foundation; the KORA (Cooperative Research in the Region of
Augsburg) research platform was started and nanced by the
Forschungszentrum fur Umwelt und Gesundheit, which is funded by the
German Federal Ministry of Education, Science, Research, and Technology
and by the State of Bavaria; German National Genome Network (NGFNplus
number 01GS08134, German Ministry for Education and Research); German
Federal Ministry of Education and Research (NGFN 01GR0468, PopGen);
Initiative and Networking Fund of the Helmholtz Association (01EW0908 in
the frame of ERA-NET NEURON); French National Agency of Research
(ANR-08-MNP-012).; This study utilized the high-performance
computational capabilities of the Biowulf Linux cluster at the National
Institutes of Health, Bethesda, Md. (http://biowulf.nih.gov). We used
DNA panels, samples, and clinical data from the National Institute of
Neurological Disorders and Stroke Human Genetics Resource Center DNA and
Cell Line Repository. People who contributed samples are acknowledged in
descriptions of every panel on the repository website. We thank the
French Parkinson's Disease Genetics Study Group: Y Agid, M Anheim, A-M
Bonnet, M Borg, A Brice, E Broussolle, J-C Corvol, P Damier, A Destee, A
Durr, F Durif, S Klebe, E Lohmann, M Martinez, P Pollak, O Rascol, F
Tison, C Tranchant, M Verin, F Viallet, and M Vidailhet. We also thank
the members of the French 3C Consortium: A Alperovitch, C Berr, C
Tzourio, and P Amouyel for allowing us to use part of the 3C cohort, and
D Zelenika for support in generating the genome-wide molecular data.
This study makes use of data generated by the Wellcome Trust
Case-Control Consortium. A full list of the investigators who
contributed to the generation of the data is available from
www.wtccc.org.uk. Funding for the project was provided by the Wellcome
Trust under award 076113 and 085475.
NR 32
TC 13
Z9 17
U1 1
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD DEC
PY 2012
VL 33
IS 12
BP 1708
EP 1718
DI 10.1002/humu.22161
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 035UP
UT WOS:000310975900012
PM 22777693
ER
PT J
AU Jennings, BL
Estes, AM
Anderson, LJ
Fang, XR
Yaghini, FA
Fan, Z
Gonzalez, FJ
Campbell, WB
Malik, KU
AF Jennings, Brett L.
Estes, Anne M.
Anderson, Larry J.
Fang, Xiao R.
Yaghini, Fariborz A.
Fan, Zheng
Gonzalez, Frank J.
Campbell, William B.
Malik, Kafait U.
TI Cytochrome P450 1B1 Gene Disruption Minimizes Deoxycorticosterone
Acetate-Salt-Induced Hypertension and Associated Cardiac Dysfunction and
Renal Damage in Mice
SO HYPERTENSION
LA English
DT Article
DE deoxycorticosterone acetate-salt; cytochrome P450 1B1; hypertension;
oxidative stress; cardiac dysfunction; renal fibrosis; inflammation
ID II-INDUCED HYPERTENSION; VASCULAR SMOOTH-MUSCLE; ACTIVATED
PROTEIN-KINASE; NITRIC-OXIDE SYNTHASE; CYTOSOLIC PHOSPHOLIPASE A(2);
ARACHIDONIC-ACID RELEASE; ANGIOTENSIN-II; BLOOD-PRESSURE; OXIDATIVE
STRESS; DEPENDENT HYPERTENSION
AB Previously, we showed that the cytochrome P450 1B1 inhibitor 2,3',4,5'-tetramethoxystilbene reversed deoxycorticosterone acetate (DOCA)-salt-induced hypertension and minimized endothelial and renal dysfunction in the rat. This study was conducted to test the hypothesis that cytochrome P450 1B1 contributes to cardiac dysfunction, and renal damage and inflammation associated with DOCA-salt-induced hypertension, via increased production of reactive oxygen species and modulation of neurohumoral factors and signaling molecules. DOCA-salt increased systolic blood pressure, cardiac and renal cytochrome P450 1B1 activity, and plasma levels of catecholamines, vasopressin, and endothelin-1 in wild-type (Cyp1b1(+/+)) mice that were minimized in Cyp1b1(-/-) mice. Cardiac function, assessed by echocardiography, showed that DOCA-salt increased the thickness of the left ventricular posterior and anterior walls during diastole, the left ventricular internal diameter, and end-diastolic and end-systolic volume in Cyp1b1(+/+) but not in Cyp1b1(-/-) mice; stroke volume was not altered in either genotype. DOCA-salt increased renal vascular resistance and caused vascular hypertrophy and renal fibrosis, increased renal infiltration of macrophages and T lymphocytes, caused proteinuria, increased cardiac and renal nicotinamide adenine dinucleotide phosphate-oxidase activity, caused production of reactive oxygen species, and increased activities of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, and cellular-Src; these were all reduced in DOCA-salt-treated Cyp1b1(-/-) mice. Renal and cardiac levels of eicosanoids were not altered in either genotype of mice. These data suggest that, in DOCA-salt hypertension in mice, cytochrome P450 1B1 plays a pivotal role in cardiovascular dysfunction, renal damage, and inflammation, and increased levels of catecholamines, vasopressin, and endothelin-1, consequent to generation of reactive oxygen species and activation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, and cellular-Src independent of eicosanoids. (Hypertension. 2012;60:1510-1516.)
C1 [Jennings, Brett L.; Estes, Anne M.; Anderson, Larry J.; Fang, Xiao R.; Yaghini, Fariborz A.; Malik, Kafait U.] Univ Tennessee, Ctr Hlth Sci, Coll Med, Dept Pharmacol, Memphis, TN 38163 USA.
[Fan, Zheng] Univ Tennessee, Ctr Hlth Sci, Coll Med, Dept Physiol, Memphis, TN 38163 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
[Campbell, William B.] Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA.
RP Malik, KU (reprint author), Univ Tennessee, Ctr Hlth Sci, Coll Med, Dept Pharmacol, 874 Union Ave, Memphis, TN 38163 USA.
EM kmalik@uthsc.edu
FU National Institutes of Health-National Heart, Lung, and Blood Institute
[R01-HL-19134-37, R01-HL-103673]; American Society of Pharmacology and
Experimental Therapeutics
FX This work was supported by the National Institutes of Health-National
Heart, Lung, and Blood Institute grants R01-HL-19134-37 (K.U. Malik) and
R01-HL-103673 (W.B. Campbell). L.J. Anderson was supported by a summer
student fellowship from the American Society of Pharmacology and
Experimental Therapeutics.
NR 71
TC 9
Z9 9
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD DEC
PY 2012
VL 60
IS 6
BP 1510
EP U349
DI 10.1161/HYPERTENSIONAHA.112.202606
PG 28
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 037LK
UT WOS:000311105900033
PM 23108654
ER
PT J
AU Durum, S
Hixon, J
Li, WQ
Felber, B
Anver, M
Stewart, C
Shen, W
McLean, M
Rottiers, P
Steidler, L
Hanson, M
AF Durum, Scott
Hixon, Julie
Li, Wenqing
Felber, Barbara
Anver, Miriam
Stewart, Charles
Shen, Wei
McLean, Mairi
Rottiers, Pieter
Steidler, Lothar
Hanson, Miranda
TI Mucosal Delivery of IL-27 Attenuates Murine Enterocolitis via T
Cell-Derived IL-10
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Meeting Abstract
CT Crohn's-and-Colitis-Foundation's-National-Clinical-and-Research
Conference on Advances in Inflammatory Bowel Diseases
CY DEC 13-15, 2012
CL Hollywood, FL
SP Crohns & Colitis Fdn, Natl Clin & Res
C1 [Durum, Scott; Hixon, Julie; Li, Wenqing; Felber, Barbara; Anver, Miriam; Stewart, Charles; Shen, Wei; McLean, Mairi; Hanson, Miranda] NCI, NIH, Frederick, MD 21701 USA.
[Rottiers, Pieter; Steidler, Lothar] ActoGeniX, Zwijnaared, NA, Belgium.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1078-0998
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD DEC
PY 2012
VL 18
SU 1
BP S85
EP S86
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 038KC
UT WOS:000311172600210
ER
PT J
AU Durum, S
Hixon, J
Li, WQ
Felber, B
Anver, M
Stewart, C
Shen, W
McLean, M
Rottiers, P
Steidler, L
Hanson, M
AF Durum, Scott
Hixon, Julie
Li, Wenqing
Felber, Barbara
Anver, Miriam
Stewart, Charles
Shen, Wei
McLean, Mairi
Rottiers, Pieter
Steidler, Lothar
Hanson, Miranda
TI Mucosal Delivery of IL-27 Attenuates Murine Enterocolitis via T
Cell-Derived IL-10
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Meeting Abstract
CT Crohn's-and-Colitis-Foundation's-National-Clinical-and-Research
Conference on Advances in Inflammatory Bowel Diseases
CY DEC 13-15, 2012
CL Hollywood, FL
SP Crohns & Colitis Fdn, Natl Clin & Res
C1 [Durum, Scott; Hixon, Julie; Li, Wenqing; Felber, Barbara; Anver, Miriam; Stewart, Charles; Shen, Wei; McLean, Mairi; Hanson, Miranda] NCI, NIH, Frederick, MD 21701 USA.
[Rottiers, Pieter; Steidler, Lothar] ActoGeniX, Zwijnaarde, Belgium.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1078-0998
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD DEC
PY 2012
VL 18
SU 1
BP S12
EP S13
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 038KC
UT WOS:000311172600032
ER
PT J
AU Shao, BM
Munford, RS
Kitchens, R
Varley, AW
AF Shao, Baomei
Munford, Robert S.
Kitchens, Richard
Varley, Alan W.
TI Hepatic uptake and deacylation of the LPS in bloodborne LPS-lipoprotein
complexes
SO INNATE IMMUNITY
LA English
DT Article
DE LPS; acyloxyacyl hydrolase; HDL; endotoxin; Kupffer cell
ID HIGH-DENSITY LIPOPROTEIN; LIPOPOLYSACCHARIDE-BINDING-PROTEIN; ALCOHOLIC
LIVER-DISEASE; BACTERIAL LIPOPOLYSACCHARIDE; CELLULAR-DISTRIBUTION;
ALKALINE-PHOSPHATASE; PLASMA-LIPOPROTEINS; PARENCHYMAL-CELLS; KUPFFER
CELLS; MOUSE-LIVER
AB Much evidence indicates that bacterial LPS (endotoxin) is removed from the bloodstream mainly by the liver, yet the hepatic uptake mechanisms remain uncertain and controversial. In plasma, LPS can be either 'free' (as aggregates, bacterial membrane fragments or loosely bound to albumin, CD14, or other proteins) or 'bound' (complexed with lipoproteins). Whereas most free LPS is taken up by Kupffer cells (KCs), lipoprotein-bound LPS has seemed to be cleared principally by hepatocytes. Here, we compared the liver's ability to take up and deacylate free LPS aggregates and the LPS in preformed LPS-high density lipoprotein (HDL) complexes. In mice examined from 1 h to 7 d after a small amount of fluorescent (FITC-)LPS was injected into a lateral tail vein, we found FITC-LPS almost entirely within, or adjacent to, KCs. As expected, FITC-LPS complexed with HDL (FITC-LPS-HDL) disappeared more slowly from the circulation and a smaller fraction of the injected dose of FITC-LPS was found in the liver. Unexpectedly, the FITC-LPS injected as FITC-LPS-HDL complexes was also found within sinusoids, adjacent to, or within, KCs. In other experiments, we found that both free and HDL-bound radiolabeled LPS underwent enzymatic deacylation by acyloxyacyl hydrolase (AOAH), the LPS-inactivating enzyme that is principally produced within the liver by KCs. Our observations suggest that KCs and AOAH play important roles in clearing and catabolizing both free LPS and the LPS in circulating LPS-HDL complexes.
C1 [Shao, Baomei; Munford, Robert S.; Kitchens, Richard; Varley, Alan W.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Infect Dis, Dallas, TX 75390 USA.
[Munford, Robert S.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Varley, AW (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Infect Dis, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM alan.varley@UTSouthwestern.edu
FU National Institutes of Health from the National Institute of Allergy and
Infectious Diseases [AI-018188, AI-045896]; Jan and Henri Bromberg Chair
in Internal Medicine (UT-Southwestern); Division of Intramural Research,
NIAID, NIH
FX This work was supported by National Institutes of Health grants
[AI-018188] and [AI-045896] from the National Institute of Allergy and
Infectious Diseases; the Jan and Henri Bromberg Chair in Internal
Medicine (UT-Southwestern); and, in part, by the Division of Intramural
Research, NIAID, NIH.
NR 46
TC 14
Z9 16
U1 1
U2 4
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1753-4259
J9 INNATE IMMUN-LONDON
JI Innate Immun.
PD DEC
PY 2012
VL 18
IS 6
BP 825
EP 833
DI 10.1177/1753425912442431
PG 9
WC Biochemistry & Molecular Biology; Immunology; Medicine, Research &
Experimental; Microbiology
SC Biochemistry & Molecular Biology; Immunology; Research & Experimental
Medicine; Microbiology
GA 040OY
UT WOS:000311333400005
PM 22441700
ER
PT J
AU Haring, R
Xanthakis, V
Coviello, A
Sullivan, L
Bhasin, S
Wallaschofski, H
Murabito, JM
Vasan, RS
AF Haring, R.
Xanthakis, V.
Coviello, A.
Sullivan, L.
Bhasin, S.
Wallaschofski, H.
Murabito, J. M.
Vasan, R. S.
TI Clinical correlates of sex steroids and gonadotropins in men over the
late adulthood: the Framingham Heart Study
SO INTERNATIONAL JOURNAL OF ANDROLOGY
LA English
DT Article
DE ageing male; Framingham Heart Study; gonadotropins; sex steroids;
testosterone
ID HORMONE-BINDING GLOBULIN; SERUM TESTOSTERONE LEVELS; MIDDLE-AGED MEN;
POPULATION-BASED COHORT; LIFE-STYLE FACTORS; CARDIOVASCULAR-DISEASE;
OLDER MEN; DEHYDROEPIANDROSTERONE-SULFATE; METABOLIC SYNDROME;
RISK-FACTORS
AB Low serum concentrations of sex steroids and gonadotropins in men have been associated with increased cardiometabolic risk and mortality, but the clinical correlates of these hormones in men over late adulthood are less clearly understood. We analysed up to five serial measurements of total testosterone (TT), dehydroepiandrosterone sulphate (DHEAS), follicle stimulating hormone (FSH), luteinizing hormone (LH) and total estradiol (EST) in older men in the original cohort of the Framingham Heart Study to determine the short- (2-years; 1,165 person-observations in 528 individuals) and long-term (up to 10-years follow-up; 2520 person-observations in 835 individuals with mean baseline age: 71.2 years) clinical correlates of these sex steroids and gonadotropins using multilevel modelling and Generalized Estimating Equations. Age, body mass index and pre-existing type 2 diabetes were inversely related to long-term TT concentrations, whereas higher systolic blood pressure showed a positive association. Furthermore, age and pre-existing cardiovascular disease (CVD) were inversely associated and HDL cholesterol concentrations positively associated with long-term DHEAS concentrations respectively. Analyses of short-term changes revealed age was inversely related to DHEAS, but positively related to FSH and LH concentrations. Our community-based study identified modifiable correlates of decreasing TT and DHEAS concentrations in elderly men, suggesting that maintenance of a low CVD risk factor burden may mitigate the age-related decline of these hormones over the late adulthood.
C1 [Haring, R.; Wallaschofski, H.] Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany.
[Haring, R.; Xanthakis, V.; Coviello, A.; Murabito, J. M.; Vasan, R. S.] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
[Haring, R.; Xanthakis, V.; Coviello, A.; Murabito, J. M.; Vasan, R. S.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Xanthakis, V.; Sullivan, L.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA.
[Coviello, A.; Bhasin, S.] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
[Xanthakis, V.; Murabito, J. M.; Vasan, R. S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Haring, R (reprint author), Univ Med Greifswald, Inst Clin Chem & Lab Med, Ferdinand Sauerbruch Str, D-17475 Greifswald, Germany.
EM robin.haring@uni-greifswald.de; vasan@bu.edu
OI Murabito, Joanne/0000-0002-0192-7516; Ramachandran,
Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149
FU National Heart Blood and Lung Institute [N01-HC-25195]
FX This work was supported by the National Heart Blood and Lung Institute
(contract N01-HC-25195).
NR 49
TC 13
Z9 13
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-6263
EI 1365-2605
J9 INT J ANDROL
JI Int. J. Androl.
PD DEC
PY 2012
VL 35
IS 6
BP 775
EP 782
DI 10.1111/j.1365-2605.2012.01285.x
PG 8
WC Andrology
SC Endocrinology & Metabolism
GA 041XM
UT WOS:000311435200002
PM 22640232
ER
PT J
AU Villasenor, A
Ballard-Barbash, R
Baumgartner, K
Baumgartner, R
Bernstein, L
McTiernan, A
Neuhouser, ML
AF Villasenor, Adriana
Ballard-Barbash, Rachel
Baumgartner, Kathy
Baumgartner, Richard
Bernstein, Leslie
McTiernan, Anne
Neuhouser, Marian L.
TI Prevalence and prognostic effect of sarcopenia in breast cancer
survivors: the HEAL Study
SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE
LA English
DT Article
DE Sarcopenia; Appendicular lean mass; Mortality; Breast cancer survivor
ID RANDOMIZED CONTROLLED-TRIAL; X-RAY ABSORPTIOMETRY; BODY-SURFACE AREA;
MUSCLE MASS; ALTERNATIVE DEFINITIONS; FUNCTIONAL IMPAIRMENT;
CHEMOTHERAPY TOXICITY; WOMEN; OBESITY; OLDER
AB Purpose This study aimed to determine the prevalence of sarcopenia and examine whether sarcopenia was associated with overall and breast-cancer-specific mortality in a cohort of women diagnosed with breast cancer (stages I-IIIA).
Methods A total of 471 breast cancer patients from western Washington State and New Mexico who participated in the prospective Health, Eating, Activity, and Lifestyle Study were included in this study. Appendicular lean mass was measured using dual X-ray absorptiometry scans at study inception, on average, 12 months after diagnosis. Sarcopenia was defined as two standard deviations below the young healthy adult female mean of appendicular lean mass divided by height squared (< 5.45 kg/m(2)). Total and breast-cancer-specific mortality data were obtained from Surveillance Epidemiology and End Results registries. Multivariable Cox proportional hazard models assessed the associations between sarcopenia and mortality.
Results Median follow-up was 9.2 years; 75 women were classified as sarcopenic, and among 92 deaths, 46 were attributed to breast cancer. In multivariable models that included age, race-ethnicity/study site, treatment type, comorbidities, waist circumference, and total body fat percentage, sarcopenia was independently associated with overall mortality (hazard ratio (HR) = 2.86; 95 % CI, 1.67-4.89). Sarcopenic women had increased risk of breast-cancer-specific mortality, although the association was not statistically significant (HR = 1.95, 95 % CI, 0.87-4.35).
Conclusion Sarcopenia is associated with an increased risk of overall mortality in breast cancer survivors and may be associated with breast-cancer-specific mortality. The development of effective interventions to maintain and/or increase skeletal muscle mass to improve prognosis in breast cancer survivors warrants further study.
Implications for Cancer Survivors Such interventions may help breast cancer patients live longer.
C1 [Villasenor, Adriana; Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, Seattle, WA 98109 USA.
[Villasenor, Adriana; McTiernan, Anne; Neuhouser, Marian L.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA.
[Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Baumgartner, Kathy; Baumgartner, Richard] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA 91010 USA.
[McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98109 USA.
RP Villasenor, A (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA.
EM avillase@fhcrc.org
FU National Cancer Institute [NO1-CN-75036-20, NO1-CN-05228, NO1-PC-67010,
U54-CA116847, R25-CA094880]; National Institutes of Health
[MO1-RR-0037]; University of New Mexico [NCRR MO1-RR-0997]
FX The authors would like to thank Anita Ambs and Todd Gibson for their
continued assistance and support, as well as the HEAL participants for
their ongoing dedication to this study. This study was supported through
National Cancer Institute contracts NO1-CN-75036-20, NO1-CN-05228,
NO1-PC-67010, U54-CA116847, and training grant R25-CA094880. A portion
of this work was conducted through the Clinical Research Center at the
University of Washington and support by the National Institutes of
Health grant MO1-RR-0037 and University of New Mexico grant, NCRR
MO1-RR-0997.
NR 55
TC 41
Z9 44
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1932-2259
J9 J CANCER SURVIV
JI J. Cancer Surviv.-Res. Pract.
PD DEC
PY 2012
VL 6
IS 4
BP 398
EP 406
DI 10.1007/s11764-012-0234-x
PG 9
WC Oncology; Social Sciences, Biomedical
SC Oncology; Biomedical Social Sciences
GA 043HX
UT WOS:000311534600006
PM 23054848
ER
PT J
AU Yabroff, KR
Dowling, E
Rodriguez, J
Ekwueme, DU
Meissner, H
Soni, A
Lerro, C
Willis, G
Forsythe, LP
Borowski, L
Virgo, KS
AF Yabroff, K. Robin
Dowling, Emily
Rodriguez, Juan
Ekwueme, Donatus U.
Meissner, Helen
Soni, Anita
Lerro, Catherine
Willis, Gordon
Forsythe, Laura P.
Borowski, Laurel
Virgo, Katherine S.
TI The Medical Expenditure Panel Survey (MEPS) Experiences with Cancer
Survivorship Supplement
SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE
LA English
DT Article
DE Cost of illness; Health care expenditures; Burden of illness; Neoplasms;
SEER-Medicare; NHIS; MEPS
ID HEALTH-CARE COSTS; UNITED-STATES; BREAST-CANCER; LESS-THAN-65 YEARS;
ECONOMIC BURDEN; POPULATION; TIME; AGE
AB Introduction The prevalence of cancer survivorship in the USA is expected to increase in the future because the US population is increasing in size and is aging and because survival following diagnosis is improving for many types of cancer. Medical care costs associated with cancer are also projected to increase dramatically. However, currently available data for estimating medical care costs and other important aspects of the burden of cancer, including time spent receiving medical care, productivity loss due to morbidity for patients and their families, and financial hardship, are limited, particularly in the population under the age of 65.
Methods We describe selected publicly available data sources for estimating the burden of cancer in the USA and a new collaborative effort to improve the quality of these data: the nationally representative Medical Expenditure Panel Survey (MEPS) Experiences with Cancer Survivorship Supplement.
Conclusions Data from this effort can be used to address key gaps in cancer survivorship research related to medical care costs, employment patterns, financial hardship, and other aspects of the burden of illness for cancer survivors and their families.
Implications for cancer survivors Research using the MEPS Experiences with Cancer Survivorship Supplement can inform efforts by health care policy makers, healthcare systems, providers, and employers to improve the cancer survivorship experience in the USA.
C1 [Yabroff, K. Robin] NCI, Hlth Serv & Econ Branch, Appl Res Program, Bethesda, MD 20892 USA.
[Yabroff, K. Robin; Dowling, Emily; Willis, Gordon; Forsythe, Laura P.; Borowski, Laurel] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Dowling, Emily] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Rodriguez, Juan; Ekwueme, Donatus U.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
[Soni, Anita] Agcy Healthcare Res & Qual, Ctr Financing Access & Cost Trends, Rockville, MD USA.
[Lerro, Catherine; Virgo, Katherine S.] Amer Canc Soc, Hlth Serv, Res Program, Intramural Res Dept,Natl Home Off, Atlanta, GA 30329 USA.
RP Yabroff, KR (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA.
EM yabroffr@mail.nih.gov
OI Yabroff, K. Robin/0000-0003-0644-5572
FU NCI; CDC; National Institutes of Health Office of Behavioral and Social
Sciences Research; ACS; AHRQ; Westat
FX The authors wish to thank Cathy Bradley, Pamela Farley Short, Patricia
Ganz, and Michael Feuerstein for comments on an early version of the
MEPS Experiences with Cancer questionnaire; Martha Stapleton and
Stephanie Beauvais of Westat for their detailed cognitive testing report
describing responses in cancer survivors to the MEPS Experiences with
Cancer questionnaire; and Stephanie Nutt and Ruth Rechis of LIVESTRONG,
Neetu Chawla of the NCI for comments on an earlier version of the
manuscript, and Timothy McNeel of IMS, Inc for programming assistance
with the 2009 MEPS. Funding for the MEPS Experiences with Cancer
Supplement was provided by the NCI, the CDC, the National Institutes of
Health Office of Behavioral and Social Sciences Research, and the ACS
and supported by the AHRQ and Westat.
NR 40
TC 15
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U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1932-2259
J9 J CANCER SURVIV
JI J. Cancer Surviv.-Res. Pract.
PD DEC
PY 2012
VL 6
IS 4
BP 407
EP 419
DI 10.1007/s11764-012-0221-2
PG 13
WC Oncology; Social Sciences, Biomedical
SC Oncology; Biomedical Social Sciences
GA 043HX
UT WOS:000311534600007
PM 23011572
ER
PT J
AU Miao, N
Lu, XW
O'Grady, NP
Yanjanin, N
Porter, FD
Quezado, ZMN
AF Miao, Ning
Lu, Xiaowei
O'Grady, Naomi P.
Yanjanin, Nicole
Porter, Forbes D.
Quezado, Zenaide M. N.
TI Niemann-Pick Disease Type C: Implications for Sedation and Anesthesia
for Diagnostic Procedures
SO JOURNAL OF CHILD NEUROLOGY
LA English
DT Article
DE neurodegeneration; anesthesia; Niemann-Pick disease type C; cholesterol
ID EPILEPTIFORM EEG; SEVOFLURANE; MIGLUSTAT; ONSET
AB Niemann-Pick disease type C, an autosomal recessive lysosomal storage disorder, can present with severe visceral and neurologic involvement and is associated with a significant decrease in life expectancy. As little is known about anesthetic considerations of this disease, we examined the perianesthetic course of patients with Niemann-Pick disease type C. Thirty-two patients with Niemann-Pick disease type C, median age 6.9 years (1.8-33 years), underwent 64 general anesthetics for diagnostic procedures. Perianesthetic morbidity included need for tracheal reintubation, pneumonitis, hypothermia, and seizure. Therefore, Niemann-Pick disease type C-associated neurologic and visceral involvement might have anesthetic implications that neurologists and pediatricians should be aware of and consider discussing with parents, guardians, and the patient's care team when procedures requiring anesthesia are planned. Furthermore, it is important for delivery of safe anesthesia that there is communication among care team members so that all involved understand the disease manifestation spectrum.
C1 [Quezado, Zenaide M. N.] NIH, Dept Perioperat Med, Ctr Clin, Sheikh Zayed Inst Pediat Surg Innovat,Childrens N, Washington, DC 20010 USA.
[O'Grady, Naomi P.] NIH, Dept Crit Care Med, Ctr Clin, Washington, DC 20010 USA.
[Yanjanin, Nicole; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Dysmorphol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Quezado, ZMN (reprint author), NIH, Dept Perioperat Med, Ctr Clin, Sheikh Zayed Inst Pediat Surg Innovat,Childrens N, 10 Ctr Dr,MSC 1512,111 Michigan Ave NW, Washington, DC 20010 USA.
EM zquezado@childrensnational.org
RI Quezado, Zenaide/O-4860-2016
OI Quezado, Zenaide/0000-0001-9793-4368
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institutes of Health Clinical Center, National
Institutes of Health; Office of Rare Diseases; National Institutes of
Health Clinical Center; Ara Parseghian Medical Research Foundation; Dana
Angels Research Trust
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
supported by the intramural research program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development and the
National Institutes of Health Clinical Center, National Institutes of
Health. The work was also supported by a Bench to Bedside award from the
Office of Rare Diseases and National Institutes of Health Clinical
Center and grants from the Ara Parseghian Medical Research Foundation
and Dana Angels Research Trust (Nicole Yanjanin).
NR 23
TC 4
Z9 4
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0883-0738
J9 J CHILD NEUROL
JI J. Child Neurol.
PD DEC
PY 2012
VL 27
IS 12
BP 1541
EP 1546
DI 10.1177/0883073812437243
PG 6
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 043AU
UT WOS:000311515900007
PM 22378675
ER
PT J
AU Gonzalez, P
Cortes, B
Quint, W
Kreimer, AR
Porras, C
Rodriguez, AC
Jimenez, S
Herrero, R
Struijk, L
Hildesheim, A
Melchers, W
AF Gonzalez, Paula
Cortes, Bernal
Quint, Wim
Kreimer, Aimee R.
Porras, Carolina
Rodriguez, Ana Cecilia
Jimenez, Silvia
Herrero, Rolando
Struijk, Linda
Hildesheim, Allan
Melchers, Willem
TI Evaluation of the FTA Carrier Device for Human Papillomavirus Testing in
Developing Countries
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID DRIED BLOOD SPOTS; CERVICAL-CANCER; ELUTE CARTRIDGE; BROAD-SPECTRUM;
LARGE-SCALE; PCR; DNA; HPV; MEASLES; RISK
AB Liquid-based methods for the collection, transportation, and storage of cervical cells are cumbersome and expensive and involve laborious DNA extraction. An FTA cartridge is a solid carrier device, easier to handle and allowing simple DNA elution for human papillomavirus (HPV) testing. HPV-DNA results from cervical specimens collected in PreservCyt medium (Hologic, Inc.) and the indicating FTA elute cartridge were compared in an area where transportation and storage may affect the performance of the test. Cervical cells from 319 young adult women enrolled in the Costa Rica Vaccine Trial were collected by a nurse using a Cervex brush (Roberts), which was placed on the FTA cartridge and subsequently rinsed in 20 ml of PreservCyt medium. Two 0.5-ml PreservCyt aliquots were frozen for HPV-PCR testing; the FTA cartridges were kept at room temperature. HPV-DNA detection and typing was performed using SPF10 PCR/DEIA (DNA enzyme immunoassay detection of amplimers)/LiPA(25) system. The percent agreement, agreement among positives, and kappas were estimated. Positivity was higher for FTA compared to PreservCyt specimens (54.5% versus 45.8%, P < 0.001). For oncogenic types, the overall agreement was 0.92, the agreement between positives was 0.74, and the kappa was 0.79. For individual HPV types, the overall agreement ranged from 0.97 to 1.00. We did not observe reduced cytology adequacy when specimen collection for cytology was preceded by FTA collection for HPV testing. HPV-DNA detection from FTA cartridges is broadly comparable to detection from PC medium. The higher HPV detection observed for FTA-collected specimens should be explored further. FTA cartridges could provide a simpler and more cost-effective method for cervical cell collection, storage, and transportation for HPV-DNA detection in research settings in developing countries.
C1 [Gonzalez, Paula; Cortes, Bernal; Porras, Carolina; Rodriguez, Ana Cecilia; Jimenez, Silvia] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, Guanacaste, Costa Rica.
[Gonzalez, Paula; Herrero, Rolando] Int Agcy Res Canc, Prevent & Implementat Grp, F-69372 Lyon, France.
[Kreimer, Aimee R.; Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Quint, Wim; Struijk, Linda] DDL Diagnost Lab, Rijswijk, Netherlands.
[Melchers, Willem] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, NL-6525 ED Nijmegen, Netherlands.
RP Gonzalez, P (reprint author), Fdn INCIENSA, Proyecto Epidemiol Guanacaste, Guanacaste, Costa Rica.
EM pgonzalez@proyectoguanacaste.org
RI Hildesheim, Allan/B-9760-2015; Kreimer, Aimee/H-1687-2015; Melchers,
Willem/C-8819-2015
OI Hildesheim, Allan/0000-0003-0257-2363; Melchers,
Willem/0000-0002-5446-2230
FU National Institutes of Health (NIH) Office of Research on Women's Health
[NCI N01-CP-11005]
FX The Costa Rican Vaccine Trial is a longstanding collaboration between
investigators in Costa Rica and the NCI. The trial is sponsored and
funded by NCI N01-CP-11005 with support from the National Institutes of
Health (NIH) Office of Research on Women's Health and conducted in
agreement with the Ministry of Health of Costa Rica. The NCI and Costa
Rica investigators are responsible for the design and conduct of the
study, the collection, management, analysis, and interpretation of the
data, and the preparation of the manuscript.
NR 31
TC 10
Z9 10
U1 1
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD DEC
PY 2012
VL 50
IS 12
BP 3870
EP 3876
DI 10.1128/JCM.01698-12
PG 7
WC Microbiology
SC Microbiology
GA 038ZE
UT WOS:000311211800009
PM 22993174
ER
PT J
AU Keating, SM
Hanson, D
Lebedeva, M
Laeyendecker, O
Ali-Napo, NL
Owen, SM
Stramer, SL
Moore, RD
Norris, PJ
Busch, MP
AF Keating, Sheila M.
Hanson, Debra
Lebedeva, Mila
Laeyendecker, Oliver
Ali-Napo, N'Ko L.
Owen, S. Michele
Stramer, Susan L.
Moore, Richard D.
Norris, Philip J.
Busch, Michael P.
TI Lower-Sensitivity and Avidity Modifications of the Vitros Anti-HIV 1+2
Assay for Detection of Recent HIV Infections and Incidence Estimation
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENZYME-IMMUNOASSAY; ANTIRETROVIRAL
THERAPY; TESTING STRATEGY; SEROCONVERSION; CHALLENGES; SUBTYPES; COHORT;
LOAD
AB Recent-infection testing assays/algorithms (RITAs) have been developed to exploit the titer and avidity of HIV antibody evolution following seroconversion for incidence estimation. The Vitros Anti-HIV 1+2 assay (Ortho-Clinical Diagnostics) was approved by the FDA to detect HIV-1 and HIV-2 infections. We developed a less-sensitive (LS) and an avidity-modified version of this assay to detect recent HIV infection. Seroconversion panels (80 subjects, 416 samples) were tested to calculate the mean duration of recent infection (MDR) for these assays. A panel from known long-term (2+ years) HIV-infected subjects on highly active antiretroviral therapy (HAART) (n = 134) and subjects with low CD4 counts (AIDS patients [n = 140]) was used to measure the false-recent rate (FRR) of the assays. Using a signal-to-cutoff ratio of 20 and the LS-Vitros assay gave a RITA MDR of 215 days (95% confidence interval [95% CI], +/-65 days) and using an avidity index (AI) of 0.6 gave an MDR of 170 days (+/-44 days), while a combination of the two assays yielded a MDR of 146 days (+/-38.6) and an FRR of 8%. Misclassifying subjects with known long-term infection as recently infected occurred in 14% of AIDS patients and 29% (95% CI, 22, 38) of HAART subjects and 3% (95% CI, 0.8, 7.2) and 42% (95% CI, 33, 51), respectively, for the LS- and avidity-modified Vitros assays, with a misclassification rate of 15% (95% CI, 11, 20) overall using a dual-assay algorithm. Both modified Vitros assays can be used to estimate the length of time since seroconversion and in calculations for HIV incidence. Like other RITAs, they are subject to high FRR in subjects on HAART or with AIDS.
C1 [Keating, Sheila M.; Lebedeva, Mila; Norris, Philip J.; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA.
[Keating, Sheila M.; Norris, Philip J.; Busch, Michael P.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hanson, Debra; Owen, S. Michele] CDC, Atlanta, GA 30333 USA.
[Laeyendecker, Oliver] NIAID, Baltimore, MD USA.
[Laeyendecker, Oliver; Moore, Richard D.] Johns Hopkins Med Ctr, Baltimore, MD USA.
[Ali-Napo, N'Ko L.] Wadsworth Ctr, New York State Dept Hlth, Albany, NY USA.
[Ali-Napo, N'Ko L.] Univ Albany, Albany, NY USA.
[Stramer, Susan L.] Amer Red Cross, Gaithersburg, MD USA.
RP Keating, SM (reprint author), Blood Syst Res Inst, San Francisco, CA USA.
EM Skeating@bloodsystems.org
RI Keating, Sheila/B-1652-2013; Laeyendecker, Oliver/B-9331-2009;
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU HIV Prevention Trials Network (HPTN); National Institute of Allergy and
Infectious Diseases (NIAID); National Institute on Drug Abuse; National
Institute of Mental Health; Office of AIDS Research, of the NIH, DHHS
[U01-AI46745, U01-AI48054, U01-AI068613, UM1-AI068613, NIH R01 DA11602,
R01 AA16893]; Division of Intramural Research, NIAID; NIH
FX This work was supported by the HIV Prevention Trials Network (HPTN)
sponsored by the National Institute of Allergy and Infectious Diseases
(NIAID), National Institute on Drug Abuse, National Institute of Mental
Health, and Office of AIDS Research, of the NIH, DHHS (U01-AI46745,
U01-AI48054, U01-AI068613, UM1-AI068613, NIH R01 DA11602, and R01
AA16893). Additional support was provided by the Division of Intramural
Research, NIAID, NIH and NIH intramural funding.
NR 27
TC 20
Z9 20
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD DEC
PY 2012
VL 50
IS 12
BP 3968
EP 3976
DI 10.1128/JCM.01454-12
PG 9
WC Microbiology
SC Microbiology
GA 038ZE
UT WOS:000311211800024
PM 23035182
ER
PT J
AU Engeli, S
Bluher, M
Jumpertz, R
Wiesner, T
Wirtz, H
Bosse-Henck, A
Stumvoll, M
Batkai, S
Pacher, P
Harvey-White, J
Kunos, G
Jordan, J
AF Engeli, Stefan
Blueher, Matthias
Jumpertz, Reiner
Wiesner, Tobias
Wirtz, Hubertus
Bosse-Henck, Andrea
Stumvoll, Michael
Batkai, Sandor
Pacher, Pal
Harvey-White, Judy
Kunos, George
Jordan, Jens
TI Circulating anandamide and blood pressure in patients with obstructive
sleep apnea
SO JOURNAL OF HYPERTENSION
LA English
DT Article
DE anandamide; endocannabinoid system; hypertension; obesity; sleep apnea;
sympathetic nervous system
ID ENDOCANNABINOID SYSTEM; CARDIOVASCULAR-DISEASE; CARDIOMETABOLIC RISK;
OBESITY; DYSREGULATION; ADIPOSE; HUMANS; MODELS; CELLS; MICE
AB Objective: Obstructive sleep apnea chronically increases blood pressure through sympathetic nervous system activation. In animals, hypertension and sympathetic activity are restrained by cannabinoid receptor activation. Therefore, we hypothesized that increased blood pressure in patients with obstructive sleep apnea is associated with increased circulating endocannabinoid concentrations.
Methods: Arterial oxygen saturation and apnea/hypopnea episodes were recorded in 29 patients with normal glucose tolerance, 26 patients with type 2 diabetes mellitus, and 21 patients obese subjects without sleep apnea. We determined seated blood pressure, insulin, glucose, and high-sensitive C-reactive protein in the morning, and insulin sensitivity by euglycemic-hyperinsulinemic clamp the next day. Anandamide, the sum of 1-arachidonoylglycerol and 2-arachidonoylglycerol, and oleoylethanolamide were measured in plasma by liquid chromatography-tandem mass spectrometry.
Results: Endocannabinoid concentrations in sleep apnea patients were increased compared to obese individuals without disordered nocturnal breathing. Correction for variables of obesity and insulin resistance almost completely abrogated this difference in endocannabinoids. Anandamide strongly correlated with blood pressure in sleep apnea patients (r = 0.60 for SBP and r = 0.58 for DBP, P < 0.001). In multivariate regression analysis, anandamide was a stronger determinant of blood pressure than sleep apnea severity, obesity, insulin resistance, and inflammation.
Conclusion: Obstructive sleep apnea patients show positive correlations between blood pressure and venous anandamide concentrations independent of confounding factors. Our data suggest a previously not recognized role of the endocannabinoid system for blood pressure regulation in patients with high risk for hypertension and cardiovascular disease.
C1 [Engeli, Stefan; Jordan, Jens] Hannover Med Sch, Inst Clin Pharmacol, D-30625 Hannover, Germany.
[Blueher, Matthias; Wiesner, Tobias; Wirtz, Hubertus; Bosse-Henck, Andrea; Stumvoll, Michael] Univ Leipzig, Dept Med, Leipzig, Germany.
[Jumpertz, Reiner] Charite, Clin Endocrinol Diabet & Nutr, Expt & Clin Res Ctr, D-13353 Berlin, Germany.
[Batkai, Sandor] Hannover Med Sch, Inst Mol & Translat Therapeut Strategies, D-30625 Hannover, Germany.
[Pacher, Pal; Harvey-White, Judy; Kunos, George] NIAAA, Lab Physiol Studies, Bethesda, MD USA.
RP Engeli, S (reprint author), Hannover Med Sch, Inst Clin Pharmacol, Carl Neuberg Str 1, D-30625 Hannover, Germany.
EM engeli.stefan@mh-hannover.de
RI Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014
OI Pacher, Pal/0000-0001-7036-8108;
FU Alexander von Humboldt Foundation in Bonn, Germany; German Competence
Network for Obesity; Federal Ministry of Education and Research
[01GI0829, 01Gl0830]
FX S.B. was a fellowship recipient of the Alexander von Humboldt Foundation
in Bonn, Germany, from August 2009 to August 2010.; This work was
supported by the German Competence Network for Obesity funded by the
Federal Ministry of Education and Research (grant 01GI0829 to M. B. and
grant 01Gl0830 to S.E.).
NR 27
TC 8
Z9 8
U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0263-6352
J9 J HYPERTENS
JI J. Hypertens.
PD DEC
PY 2012
VL 30
IS 12
BP 2345
EP 2351
DI 10.1097/HJH.0b013e3283591595
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 039VA
UT WOS:000311273700015
PM 23032139
ER
PT J
AU Jaacks, LM
Oza-Frank, R
D'Agostino, R
Dolan, LM
Dabelea, D
Lawrence, JM
Pihoker, C
O'Connor, MR
Linder, B
Imperatore, G
Seid, M
Narayan, KMV
Mayer-Davis, EJ
AF Jaacks, Lindsay M.
Oza-Frank, Reena
D'Agostino, Ralph, Jr.
Dolan, Lawrence M.
Dabelea, Dana
Lawrence, Jean M.
Pihoker, Catherine
O'Connor, M. Rebecca
Linder, Barbara
Imperatore, Giuseppina
Seid, Michael
Narayan, K. M. Venkat
Mayer-Davis, Elizabeth J.
TI Migration Status in Relation to Clinical Characteristics and Barriers to
Care Among Youth with Diabetes in the US
SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH
LA English
DT Article
DE Diabetes; Youth; Migration; US
ID GLYCEMIC CONTROL; RISK-FACTORS; PREVALENCE; IMMIGRANT; MELLITUS; HEALTH;
CHILDREN; SEARCH; TYPE-1; ACCULTURATION
AB Migration status and the accompanying diversity in culture, foods and family norms, may be an important consideration for practitioners providing individualized care to treat and prevent complications among youth with diabetes. Approximately 20 % of youth in the US have a parts per thousand yen1 foreign-born parent. However, the proportion and characteristics of youth with diabetes and a parts per thousand yen1 foreign-born parent have yet to be described. Study participants (n = 3,086) were from SEARCH for Diabetes in Youth, a prospective multi-center study in the US. Primary outcomes of interest included HbA1c, body mass index and barriers to care. Multivariable analyses were carried out using logistic regression and analysis of covariance. Approximately 17 % of participants with type 1 diabetes (T1D) and 22 % with type 2 diabetes (T2D) had a parts per thousand yen1 foreign-born parent. Youth with T1D and a parts per thousand yen1 foreign-born parent were less likely to have poor glycemic control [adjusted odds ratio (OR) (95 % confidence interval): 0.70 (0.53, 0.94)]. Among youth with T2D, those with a parts per thousand yen1 foreign-born parent had lower odds of obesity [adjusted OR (95 % CI): 0.35 (0.17, 0.70)]. This is the first study to estimate the proportion and characteristics of youth with diabetes exposed to migration in the US. Research into potential mechanisms underlying the observed protective effects is warranted.
C1 [Jaacks, Lindsay M.; Mayer-Davis, Elizabeth J.] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.
[Oza-Frank, Reena] Ohio State Univ, Dept Pediat, Res Inst, Nationwide Childrens Hosp, Columbus, OH 43210 USA.
[D'Agostino, Ralph, Jr.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat, Winston Salem, NC USA.
[Dolan, Lawrence M.; Seid, Michael] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Dabelea, Dana] Univ Colorado, Dept Epidemiol, Denver, CO 80202 USA.
[Lawrence, Jean M.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA.
[Pihoker, Catherine; O'Connor, M. Rebecca] Seattle Childrens Hosp, Seattle, WA USA.
[Linder, Barbara] NIDDK, NIH, Bethesda, MD USA.
[Imperatore, Giuseppina] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Narayan, K. M. Venkat] Emory Univ, Hubert Dept Global Hlth, Atlanta, GA 30322 USA.
[Mayer-Davis, Elizabeth J.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
RP Mayer-Davis, EJ (reprint author), Univ N Carolina, Dept Nutr, 2211 McGavran Greenberg Hall,135 Dauer Dr,Campus, Chapel Hill, NC 27599 USA.
EM mayerdav@email.unc.edu
RI Narayan, K.M. Venkat /J-9819-2012; Dagostino Jr, Ralph/C-4060-2017
OI Narayan, K.M. Venkat /0000-0001-8621-5405; Dagostino Jr,
Ralph/0000-0002-3550-8395
FU HSRD VA [HIR 10-001]; NCCDPHP CDC HHS [DP-05-069, DP-10-001, U01
DP000244, U01 DP000245, U01 DP000246, U01 DP000247, U01 DP000248, U01
DP000250, U01 DP000254, U18 DP002708, U18 DP002709, U18 DP002710, U18
DP002714]; NCRR NIH HHS [1UL1RR026314-01, M01 RR000037, M01 RR000069,
M01 RR00069, M01RR00037, UL1 RR025014, UL1 RR026314, UL1 RR029882,
UL1RR029882]; NIDDK NIH HHS [P30 DK057516, P30 DK57516]; PHS HHS [00097]
NR 34
TC 3
Z9 3
U1 2
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1912
J9 J IMMIGR MINOR HEALT
JI J. Immigr. Minor. Health
PD DEC
PY 2012
VL 14
IS 6
BP 949
EP 958
DI 10.1007/s10903-012-9617-3
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 036MM
UT WOS:000311030400007
PM 22481308
ER
PT J
AU Watts, DH
Mofenson, LM
AF Watts, D. Heather
Mofenson, Lynne M.
TI Antiretrovirals in Pregnancy: A Note of Caution
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID HIV-INFECTED WOMEN; TO-CHILD TRANSMISSION; LOW-BIRTH-WEIGHT; PRETERM
DELIVERY; INCREASED RISK; PREMATURE DELIVERY; UNITED-KINGDOM; THERAPY;
OUTCOMES; DRUGS
C1 [Watts, D. Heather; Mofenson, Lynne M.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA.
RP Watts, DH (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, 6100 Execut Blvd,Room 4B11, Bethesda, MD 20892 USA.
EM wattsh@mail.nih.gov
OI Mofenson, Lynne/0000-0002-2818-9808
NR 26
TC 10
Z9 10
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 DEC 1
PY 2012
VL 206
IS 11
BP 1639
EP 1641
DI 10.1093/infdis/jis581
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 035SK
UT WOS:000310968700003
PM 23066163
ER
PT J
AU Hobbs, CV
Voza, T
De La Vega, P
Vanvliet, J
Conteh, S
Penzak, SR
Fay, MP
Anders, N
Ilmet, T
Li, YH
Borkowsky, W
Krzych, U
Duffy, PE
Sinnis, P
AF Hobbs, Charlotte V.
Voza, Tatiana
De La Vega, Patricia
Vanvliet, Jillian
Conteh, Solomon
Penzak, Scott R.
Fay, Michael P.
Anders, Nicole
Ilmet, Tiina
Li, Yonghua
Borkowsky, William
Krzych, Urszula
Duffy, Patrick E.
Sinnis, Photini
TI HIV Nonnucleoside Reverse Transcriptase Inhibitors and
Trimethoprim-Sulfamethoxazole Inhibit Plasmodium Liver Stages
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID EXO-ERYTHROCYTIC STAGES; HUMAN HEPATOCYTE LINE; HUMAN HEPATIC CELLS;
MALARIA PARASITES; FALCIPARUM; EFAVIRENZ; MICE; EXPRESSION; NEVIRAPINE;
PHARMACOKINETICS
AB Background. Although nonnucleoside reverse transcriptase inhibitors (NNRTIs) are usually part of first-line treatment regimens for human immunodeficiency virus (HIV), their activity on Plasmodium liver stages remains unexplored. Additionally, trimethoprim-sulfamethoxazole (TMP-SMX), used for opportunistic infection prophylaxis in HIV-exposed infants and HIV-infected patients, reduces clinical episodes of malaria; however, TMP-SMX effect on Plasmodium liver stages requires further study.
Methods. We characterized NNRTI and TMP-SMX effects on Plasmodium liver stages in vivo using Plasmodium yoelii. On the basis of these results, we conducted in vitro studies assessing TMP-SMX effects on the rodent parasites P. yoelii and Plasmodium berghei and on the human malaria parasite Plasmodium falciparum.
Results. Our data showed NNRTI treatment modestly reduced P. yoelii liver stage parasite burden and minimally extended prepatent period. TMP-SMX administration significantly reduced liver stage parasite burden, preventing development of patent parasitemia in vivo. TMP-SMX inhibited development of rodent and P. falciparum liver stage parasites in vitro.
Conclusions. NNRTIs modestly affect liver stage Plasmodium parasites, whereas TMP-SMX prevents patent parasitemia. Because drugs that inhibit liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. Understanding HIV drug effects on Plasmodium liver stages will aid in optimizing treatment regimens for HIV-exposed and HIV-infected infected patients in malaria-endemic areas.
C1 [Hobbs, Charlotte V.; Vanvliet, Jillian; Conteh, Solomon; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA.
[Voza, Tatiana] CUNY, Dept Biol Sci, New York City Coll Technol, Brooklyn, NY USA.
[De La Vega, Patricia; Krzych, Urszula] Walter Reed Army Inst Res, Dept Cellular Immunol, Malaria Vaccine Branch, Silver Spring, MD USA.
[Penzak, Scott R.] NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA.
[Fay, Michael P.] NIAID, NIH, Biostat Res Branch, Rockville, MD 20852 USA.
[Anders, Nicole] Johns Hopkins Sch Med, Dept Med, Div Clin Pharmacol, Baltimore, MD USA.
[Hobbs, Charlotte V.; Li, Yonghua; Borkowsky, William] NYU, Dept Pediat, Div Infect Dis & Immunol, Sch Med, New York, NY 10016 USA.
[Sinnis, Photini] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Voza, Tatiana; Sinnis, Photini] NYU, Dept Med Parasitol, New York, NY USA.
RP Hobbs, CV (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA.
EM charlotte.hobbs@nih.gov
OI Fay, Michael P./0000-0002-8643-9625
FU New York University; NIH [R01 AI056840]; NIH Division of Intramural
Research; US Army Medical Research and Materiel Command
FX This work was funded by the New York University Global Public Health
Research Challenge Fund (P. S. and C. H.), NIH R01 AI056840 (P. S.), the
NIH Division of Intramural Research, and the US Army Medical Research
and Materiel Command.
NR 49
TC 9
Z9 9
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD DEC 1
PY 2012
VL 206
IS 11
BP 1706
EP 1714
DI 10.1093/infdis/jis602
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 035SK
UT WOS:000310968700012
PM 23125449
ER
PT J
AU Grant, PM
Komarow, L
Lederman, MM
Pahwa, S
Zolopa, AR
Andersen, J
Asmuth, DM
Devaraj, S
Pollard, RB
Richterman, A
Kanthikeel, S
Sereti, I
AF Grant, Philip M.
Komarow, Lauren
Lederman, Michael M.
Pahwa, Savita
Zolopa, Andrew R.
Andersen, Janet
Asmuth, David M.
Devaraj, Sridevi
Pollard, Richard B.
Richterman, Aaron
Kanthikeel, Sudheesh
Sereti, Irini
TI Elevated Interleukin 8 and T-Helper 1 and T-Helper 17 Cytokine Levels
Prior to Antiretroviral Therapy in Participants Who Developed Immune
Reconstitution Inflammatory Syndrome During ACTG A5164
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID INFECTED PATIENTS; RESTORATION DISEASE; RISK-FACTORS; MYCOBACTERIAL
LYMPHADENITIS; CRYPTOCOCCAL MENINGITIS; CELL-ACTIVATION; HIV PATIENTS;
TUBERCULOSIS; INITIATION; BIOMARKERS
AB Background. Immune reconstitution inflammatory syndrome (IRIS) reflects an aberrant immune response that can develop in human immunodeficiency virus-infected patients initiating antiretroviral therapy (ART). Its pathogenesis remains unclear.
Methods. We performed a nested case-control study using specimens from ACTG A5164. We compared plasma biomarkers and T-cell subsets in 19 IRIS and 39 control participants at study entry, ART initiation, and IRIS and used conditional logistic regression to develop IRIS predictive models. We evaluated the effect of corticosteroids on biomarker levels.
Results. Eleven and 8 participants developed paradoxical and unmasking IRIS, respectively, none while still receiving corticosteroids. Compared to controls, cases displayed elevations at study entry in interleukin (IL) 8, T-helper (Th) 1 (IL-2, interferon [IFN]-gamma, tumor necrosis factor [TNF]) and Th17 (IL-17) cytokine levels that persisted through ART initiation and IRIS. In logistic regression, baseline higher IFN-gamma and TNF were strong predictors of IRIS. Participants who received corticosteroids and later developed IRIS had marked increases in IL-6, IL-8, and IFN-gamma at the time of IRIS. T-cell activation markers did not differ in cases and controls prior to ART but were increased in cases at the time of IRIS.
Conclusions. Increased IL-8, Th1, and Th17 cytokine levels in IRIS patients precede ART initiation and could help identify patient populations at higher risk for IRIS.
C1 [Grant, Philip M.; Zolopa, Andrew R.] Stanford Univ, Div Infect Dis, Stanford, CA 94305 USA.
[Komarow, Lauren; Andersen, Janet] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Lederman, Michael M.] Case Western Reserve Univ, Div Infect Dis, Cleveland, OH 44106 USA.
[Pahwa, Savita; Kanthikeel, Sudheesh] Univ Miami, Dept Microbiol & Immunol, Coral Gables, FL 33124 USA.
[Asmuth, David M.; Pollard, Richard B.] Univ Calif Davis, Dept Med Microbiol & Immunol, Div Infect Dis, Sacramento, CA 95817 USA.
[Devaraj, Sridevi] Baylor Univ, Div Pathol & Immunol, Houston, TX 77030 USA.
[Richterman, Aaron; Sereti, Irini] NIAID, NIH, Bethesda, MD 20892 USA.
RP Grant, PM (reprint author), Div Infect Dis & Geog Med, 300 Pasteur Dr,Room S-101, Stanford, CA 94305 USA.
EM pmgrant@stanford.edu
FU AIDS Clinical Trials Group; National Institute of Allergy and Infectious
Diseases [AI38858, AI68636, AI6863]
FX This work was supported in part by the AIDS Clinical Trials Group funded
by the National Institute of Allergy and Infectious Diseases (AI38858,
AI68636, and AI6863). I. S. was supported by the Intramural Research
Program of the National Institute of Allergy and Infectious Diseases.
NR 34
TC 24
Z9 25
U1 0
U2 4
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 DEC 1
PY 2012
VL 206
IS 11
BP 1715
EP 1723
DI 10.1093/infdis/jis604
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 035SK
UT WOS:000310968700013
PM 23002445
ER
PT J
AU Sun, G
Luo, T
Yang, CG
Dong, XR
Li, J
Zhu, YQ
Zheng, HJ
Tian, WD
Wang, SY
Barry, CE
Mei, J
Gao, Q
AF Sun, Gang
Luo, Tao
Yang, Chongguang
Dong, Xinran
Li, Jing
Zhu, Yongqiang
Zheng, Huajun
Tian, Weidong
Wang, Shengyue
Barry, Clifton E., III
Mei, Jian
Gao, Qian
TI Dynamic Population Changes in Mycobacterium tuberculosis During
Acquisition and Fixation of Drug Resistance in Patients
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID CLONAL INTERFERENCE; SEQUENCING DATA; SOUTH-AFRICA; MUTATIONS;
EVOLUTION; STRAINS; FITNESS; SHANGHAI; CHINA; ASSAY
AB Background. Drug-resistant tuberculosis poses a growing challenge to global public health. However, the diversity and dynamics of the bacterial population during acquisition of drug resistance have yet to be carefully examined.
Methods. Whole-genome sequencing was performed on 7 serial Mycobacterium tuberculosis (M. tuberculosis) populations from 3 patients during different stages in the development of drug resistance. The population diversity was assessed by the number and frequencies of unfixed mutations in each sample.
Results. For each bacterial population, 8-41 unfixed mutations were monitored by the fraction of single-nucleotide polymorphisms at specific loci. Among them, as many as 4 to 5 resistance-conferring mutations were transiently detected in the same single sputum, but ultimately only a single type of mutant was fixed. In addition, we identified 14 potential compensatory mutations that occurred during or after the emergence of resistance-conferring mutations.
Conclusions. M. tuberculosis population within patients exhibited considerable genetic diversity, which underwent selections for most fit resistant mutant. These findings have important implications and emphasize the need for early diagnosis of tuberculosis to decrease the chance of evolving highly fit drug-resistant strains.
C1 [Gao, Qian] Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Inst Biomed Sci, Shanghai 200032, Peoples R China.
[Sun, Gang; Luo, Tao; Yang, Chongguang; Gao, Qian] Fudan Univ, Inst Med Microbiol, Shanghai 200032, Peoples R China.
[Dong, Xinran; Tian, Weidong] Fudan Univ, Sch Life Sci, Inst Biostat, Shanghai 200032, Peoples R China.
[Li, Jing; Mei, Jian] Shanghai Municipal Ctr Dis Control & Prevent, Dept TB Control, Shanghai, Peoples R China.
[Zhu, Yongqiang; Zheng, Huajun; Wang, Shengyue] Chinese Natl Human Genome Ctr Shanghai, Shanghai MOST Key Lab Hlth & Dis Gen, Shanghai, Peoples R China.
[Barry, Clifton E., III] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA.
RP Gao, Q (reprint author), Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Inst Biomed Sci, 138 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China.
EM qgao99@yahoo.com
RI Barry, III, Clifton/H-3839-2012;
OI Yang, Chongguang/0000-0001-8109-4974
FU Ministry of Science and Technology, China [2010DFA34440]; Intramural
Research Division of National Institute of Allergy and Infectious
Diseases (NIAID), National Institutes of Health (NIH); NIH [D43TW007887]
FX This work was supported by the grant of International Cooperation
Project of Ministry of Science and Technology, China (2010DFA34440), and
partially supported by the Intramural Research Division of National
Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH) and NIH grant D43TW007887.
NR 50
TC 69
Z9 74
U1 11
U2 28
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 DEC 1
PY 2012
VL 206
IS 11
BP 1724
EP 1733
DI 10.1093/infdis/jis601
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 035SK
UT WOS:000310968700014
PM 22984115
ER
PT J
AU Resnik, DB
Ness, E
AF Resnik, David B.
Ness, Elizabeth
TI Participants' responsibilities in clinical research
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
ID ANTIRETROVIRAL THERAPY; PUBLIC-HEALTH; INALIENABLE RIGHT; RESEARCH
ETHICS; TRIALS; WITHDRAW; TUBERCULOSIS; INFECTION; ADHERENCE; DUTY
AB Discussions on the ethics and regulation of clinical research have a great deal to say about the responsibilities of investigators, sponsors, research institutions and institutional review boards, but very little about the responsibilities of research participants. In this article, we discuss the responsibilities of participants in clinical research. We argue that competent adult participants are responsible for complying with study requirements and fulfilling other obligations they undertake when they make an informed choice to enrol in a study. These responsibilities are based on duties related to promise-keeping, avoiding harm to one's self or others, beneficence and reciprocity. Investigators and research staff should inform participants about their responsibilities during the consent process, and should stress the importance of fulfilling study requirements. They should address any impediments to compliance, and they may provide participants with financial incentives for meeting study requirements. In very rare cases, coercive measures may be justified to prevent immanent harm to others resulting from non-compliance with study requirements.
C1 [Resnik, David B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Ness, Elizabeth] NCI, NIH, Bethesda, MD 20892 USA.
RP Resnik, DB (reprint author), NIEHS, NIH, 111 Alexander Dr,POB 12233,CU 03,Mail Drop CU 108, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES102646-04, ZIA ES102646-03]
NR 39
TC 5
Z9 5
U1 1
U2 10
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
J9 J MED ETHICS
JI J. Med. Ethics
PD DEC
PY 2012
VL 38
IS 12
BP 746
EP 750
DI 10.1136/medethics-2011-100319
PG 5
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 042RO
UT WOS:000311488900011
PM 22822200
ER
PT J
AU Lu, J
Ksendzovsky, A
Yang, CZ
Mehta, GU
Yong, RL
Weil, RJ
Park, DM
Mushlin, HM
Fang, XP
Balgley, BM
Lee, DH
Lee, CS
Lonser, RR
Zhuang, ZP
AF Lu, Jie
Ksendzovsky, Alexander
Yang, Chunzhang
Mehta, Gautam U.
Yong, Raymund L.
Weil, Robert J.
Park, Deric M.
Mushlin, Harry M.
Fang, Xueping
Balgley, Brian M.
Lee, Dae-Hee
Lee, Cheng S.
Lonser, Russell R.
Zhuang, Zhengping
TI CNTF receptor subunit alpha as a marker for glioma tumor-initiating
cells and tumor grade
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE ciliary neurotrophic factor receptor subunit-alpha; glioma;
tumor-initiating cell; oncology; mouse
ID CILIARY NEUROTROPHIC FACTOR; CANCER STEM-CELLS;
AMYOTROPHIC-LATERAL-SCLEROSIS; CENTRAL-NERVOUS-SYSTEM; ERYTHROPOIETIN
RECEPTOR; MALIGNANT GLIOMAS; BRAIN-TUMORS; DIFFERENTIATION; EXPRESSION;
PATHWAY
AB Object. Tumor-initiating cells are uniquely resilient to current treatment modalities and play an important role in tumor resistance and recurrence. The lack of specific tumor-initiating cell markers to identify and target these cells presents a major obstacle to effective directed therapy.
Methods. To identify tumor-initiating cell markers in primary brain tumors, the authors compared the proteomes of glioma tumor-initiating cells to their differentiated progeny using a novel, nongel/shotgun-based, multidimensional liquid-chromatography protein separation technique. An in vivo xenograft model was used to demonstrate the tumorigenic and stem cell properties of these cells. Western blot and immunofluorescence analyses were used to confirm findings of upregulated ciliary neurotrophic factor receptor subunit-alpha (CNTFR alpha) in undifferentiated tumor-initiating cells and gliomas of increasing tumor grade. Sequencing of the CNTFR alpha coding regions was performed for mutation analysis. Finally, antibody-dependent cell-mediated cytotoxicity was used to establish the role of CNTFR alpha as a potential immunotherapeutic target.
Results. Ciliary neurotrophic factor receptor subunit-alpha expression was increased in tumor-initiating cells and was decreased in the cells' differentiated progeny, and expression levels increased with glioma grade. Mutations of CNTFR alpha are not common in gliomas. Functional studies using CNTF treatment in glioma tumor-initiating cells showed induction of differentiation through the CNTFR alpha pathway. Treatment with anti-CNTFR alpha antibody resulted in increased antibody-dependent cell-mediated cytotoxicity in CNTFR alpha expressing DAOY cells but not in cell lines that lack CNTFR alpha.
Conclusions. These data indicate that CNTFR alpha plays a role in the formation or maintenance of tumor-initiating cells in gliomas, is a marker that correlates with histological grade, may underlie treatment resistance in some cases, and is a potential therapeutic target. (http://thejns.org/doi/abs/10.3171/2012.9.JNS1212)
C1 [Lu, Jie; Ksendzovsky, Alexander; Yang, Chunzhang; Mehta, Gautam U.; Yong, Raymund L.; Mushlin, Harry M.; Lonser, Russell R.; Zhuang, Zhengping] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Fang, Xueping; Balgley, Brian M.; Lee, Cheng S.] Calibrant Biosyst, Gaithersburg, MD USA.
[Weil, Robert J.] Cleveland Clin, Neurol Inst, Dept Neurosurg, Rose Ella Burkhardt Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA.
[Park, Deric M.; Lee, Dae-Hee] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA.
RP Lonser, RR (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bldg 10,Room 3D20, Bethesda, MD 20892 USA.
EM lonserr@ninds.nih.gov
RI Park, Deric/C-5675-2013;
OI Balgley, Brian/0000-0002-3509-4567
FU Neuro-Oncology Center at the Cleveland Clinic Foundation
FX The Melvin Burkhardt Chair in Neurosurgical Oncology and the Karen
Colina Wilson research endowment within the Burkhardt Brain Tumor and
Neuro-Oncology Center at the Cleveland Clinic Foundation provided
partial support and funding. Dr. Bagley has ownership in Bioproximity,
LLC.
NR 46
TC 5
Z9 5
U1 1
U2 5
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD DEC
PY 2012
VL 117
IS 6
BP 1022
EP 1031
DI 10.3171/2012.9.JNS1212
PG 10
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 042IC
UT WOS:000311463900007
PM 23061382
ER
PT J
AU Nduom, EK
Walbridge, S
Lonser, RR
AF Nduom, Edjah K.
Walbridge, Stuart
Lonser, Russell R.
TI Comparison of pulsed versus continuous convective flow for central
nervous system tissue perfusion Laboratory investigation
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE pulsatile flow; continuous flow; convection-enhanced delivery; drug
delivery; nervous system; Macaca mulatta
ID MALIGNANT BRAIN-TUMORS; ENHANCED DELIVERY; RECURRENT GLIOBLASTOMA;
PARKINSON-DISEASE; TARGETED TOXIN; PHASE-II; INFUSION; MACROMOLECULES;
INHIBITOR; ACCURACY
AB Object. Although pulsatile and continuous infusion paradigms have been described for convective delivery of drugs, the effectiveness and properties of each flow paradigm are unknown. To determine the effectiveness and properties of pulsatile and continuous convective infusion paradigms, the authors compared these convective flow methods in the gray and white matter of primates.
Methods. Six primates (Macaca mulatta) underwent convective infusion of Gd-DPTA (5 mM) into the cerebral gray matter (thalamus) or white matter (frontal lobe) using pulsed (intermittent pulses of 15 mu l/min) or continuous (1 mu l/min) convective flow.
Results were assessed by clinical MRI and histological analyses. Results. Distribution of Gd-DTPA infusate in gray and white matter by pulsed and continuous flow was clearly identified using MRI, which revealed that both convective flow methods demonstrated an increase in the volume of distribution (Vd) with increasing volume of infusion (Vi) in the surrounding gray and white matter. Although the mean (+/- SD) gray matter Vd:Vi ratio for the pulsed infusions (4.2 +/- 0.5) was significantly lower than the mean Vd:Vi ratio for continuous infusions (5.4 +/- 0.5; a 22% difference [P = 0.0006]), the difference between pulsed (3.8 +/- 0.4) and continuous (4.3 +/- 1.2) infusions in white matter was not significantly different (p = 0.3). Pulsed infusions were associated with more leakback (12.3% +/- 6.4% of Vi) than continuous infusions (3.9% +/- 7.8%), although this difference was not significant (p = 0.2). All animals tolerated the infusions and there was no histological evidence of tissue injury at the infusion sites.
Conclusions. Although pulsed and continuous infusion flow paradigms can be safely and effectively used for convective delivery into both gray and white matter, continuous infusion is associated with a higher Vd:Vi ratio than pulsatile infusion in gray matter. High rates of infusion (15 mu l/min) can be used to deliver infusate without any significant leakback and without any clinical or histological evidence of injury. (http ://thejns.org/doi/abs/10.3171/2012.9.JNS12506)
C1 [Nduom, Edjah K.; Walbridge, Stuart; Lonser, Russell R.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Nduom, Edjah K.] Emory Univ, Dept Neurol Surg, Atlanta, GA 30322 USA.
RP Lonser, RR (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 3D20, Bethesda, MD 20892 USA.
EM lonserr@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke at the National
Institutes of Health
FX This work was supported by the intramural program of the National
Institute of Neurological Disorders and Stroke at the National
Institutes of Health.
NR 19
TC 5
Z9 5
U1 0
U2 1
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD DEC
PY 2012
VL 117
IS 6
BP 1150
EP 1154
DI 10.3171/2012.9.JNS12506
PG 5
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 042IC
UT WOS:000311463900024
PM 23061389
ER
PT J
AU Winer, KK
Rothenberg, ME
Guimond, J
Handwerger, S
Boxer, LA
Grave, G
Devaskar, SU
Castle, VP
AF Winer, Karen K.
Rothenberg, Marc E.
Guimond, Jennifer
Handwerger, Stuart
Boxer, Laurence A.
Grave, Gilman
Devaskar, Sherin U.
Castle, Valerie P.
TI The Child Health Research Centers: Twenty-One Years of Promoting the
Development of Pediatrician Scientists from 1990-2011
SO JOURNAL OF PEDIATRICS
LA English
DT Editorial Material
ID WILL
C1 [Winer, Karen K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Endocrinol Nutr & Growth Branch, Bethesda, MD 20892 USA.
[Rothenberg, Marc E.; Handwerger, Stuart] Univ Cincinnati, Med Ctr, Cincinnati Childrens Hosp, Cincinnati, OH 45267 USA.
[Boxer, Laurence A.; Castle, Valerie P.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Devaskar, Sherin U.] Univ Calif Los Angeles, Los Angeles, CA USA.
RP Winer, KK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Endocrinol Nutr & Growth Branch, Bldg 6100,Room 4B11, Bethesda, MD 20892 USA.
EM winerk@exchange.nih.gov
OI Guimond, Jennifer/0000-0002-8887-5885
NR 7
TC 4
Z9 4
U1 0
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 DEC
PY 2012
VL 161
IS 6
BP 975
EP U17
DI 10.1016/j.jpeds.2012.09.001
PG 3
WC Pediatrics
SC Pediatrics
GA 040TZ
UT WOS:000311348400001
PM 23171484
ER
PT J
AU Wren, TAL
Shepherd, JA
Kalkwarf, HJ
Zemel, BS
Lappe, JM
Oberfield, S
Dorey, FJ
Winer, KK
Gilsanz, V
AF Wren, Tishya A. L.
Shepherd, John A.
Kalkwarf, Heidi J.
Zemel, Babette S.
Lappe, Joan M.
Oberfield, Sharon
Dorey, Frederick J.
Winer, Karen K.
Gilsanz, Vicente
TI Racial Disparity in Fracture Risk between White and Nonwhite Children in
the United States
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID BONE-MINERAL DENSITY; FOREARM FRACTURES; PHYSICAL-ACTIVITY; DISTAL
RADIUS; GROWTH; CHILDHOOD; MASS; EPIDEMIOLOGY; ASSOCIATION; COHORT
AB Objectives To examine risk factors for fracture in a racially diverse cohort of healthy children in the US.
Study design A total of 1470 healthy children, aged 6-17 years, underwent yearly evaluations of height, weight, body mass index, skeletal age, sexual maturation, calcium intake, physical activity levels, and dual-energy x-ray absorptiometry (DXA) bone and fat measurements for up to 6 years. Fracture information was obtained at each annual visit, and risk factors for fracture were examined using the time-dependent Cox proportional hazards model.
Results The overall fracture incidence was 0.034 fracture per person-year with 212 children reporting a total of 257 fractures. Being white (hazard ratio [HR] = 2.1), being male (HR = 1.8), and having skeletal age of 10-14 years (HR = 2.2) were the strongest risk factors for fracture (all P <= .001). Increased sports participation (HR = 1.4), lower body fat percentage (HR = 0.97), and previous fracture in white girls (HR = 2.1) were also significant risk factors (all P <= .04). Overall, fracture risk decreased with higher DXA z scores, except in white boys, who had increased fracture risk with higher DXA z scores (HR = 1.7, P < .001).
Conclusions Boys and girls of European descent had double the fracture risk of children from other backgrounds, suggesting that the genetic predisposition to fractures seen in elderly adults also manifests in children. (J Pediatr 2012;161:1035-40).
C1 [Wren, Tishya A. L.; Dorey, Frederick J.; Gilsanz, Vicente] Childrens Hosp Los Angeles, Dept Orthopaed Surg, Los Angeles, CA 90027 USA.
[Wren, Tishya A. L.; Dorey, Frederick J.; Gilsanz, Vicente] Childrens Hosp Los Angeles, Dept Radiol, Los Angeles, CA 90027 USA.
[Shepherd, John A.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA.
[Kalkwarf, Heidi J.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH USA.
[Zemel, Babette S.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Lappe, Joan M.] Creighton Univ, Dept Med, Omaha, NE 68178 USA.
[Oberfield, Sharon] Columbia Univ, Dept Pediat, New York, NY 10027 USA.
[Winer, Karen K.] NICHHD, Bethesda, MD 20892 USA.
RP Wren, TAL (reprint author), Childrens Hosp Los Angeles, Dept Orthopaed Surg, 4650 Sunset Blvd,MS 69, Los Angeles, CA 90027 USA.
EM twren@chla.usc.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [NO1-HD-1-3228, NO1-HD-1-3329, NO1-HD-1-3330, NO1-HD-1-3331,
NO1-HD-1-3332, NO1-HD-13333]
FX Supported by Eunice Kennedy Shriver National Institute of Child Health
and Human Development (NO1-HD-1-3228, NO1-HD-1-3329, NO1-HD-1-3330,
NO1-HD-1-3331, NO1-HD-1-3332, and NO1-HD-13333). The authors declare no
conflicts of interest.
NR 28
TC 22
Z9 23
U1 0
U2 2
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 DEC
PY 2012
VL 161
IS 6
BP 1035
EP U90
DI 10.1016/j.jpeds.2012.07.054
PG 8
WC Pediatrics
SC Pediatrics
GA 040TZ
UT WOS:000311348400015
PM 22974572
ER
PT J
AU Newman, JE
Bann, CM
Vohr, BR
Dusick, AM
Higgins, RD
AF Newman, Jamie E.
Bann, Carla M.
Vohr, Betty R.
Dusick, Anna M.
Higgins, Rosemary D.
CA Eunice Kennedy Shriver Natl Inst
TI Improving the Neonatal Research Network Annual Certification for
Neurologic Examination of the 18-22 Month Child
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID GROSS MOTOR FUNCTION; CEREBRAL-PALSY; RELIABILITY; SYSTEM; SCORES
AB Objective To describe the Neonatal Research Network's efforts to improve the certification process for the Follow-Up Study neurologic exam and to evaluate inter-rater agreement before and after two annual training workshops.
Study design The Neonatal Research Network Follow-Up Study is a multi-center observational study that has examined more than 11 500 infants from 1998-2010 and born <= 26 weeks gestational age at 18-22 months corrected age for neurodevelopmental outcome. The percentages of examiners who agreed with the Gold Standard examiner on 4 neurodevelopmental outcomes on the initial training video and a test video were calculated. Consistency among examiners was assessed with the first-order agreement coefficient statistic.
Results Improvements in agreement among examiners occurred between 2009 and 2010 and between initial training and test. Examiner agreement with the Gold Standard during the initial training was 83%-91% in 2009 and 89%-99% in 2010. Examiner agreement on the workshop test video increased from 2009-2010 with agreement reaching 100% for all four neurodevelopmental outcomes examined in 2010. First-order agreement coefficient values for the four neurodevelopmental outcomes on the training videos ranged from 0.64-0.82 in 2009 and 0.77-0.97 in 2010.
Conclusions We demonstrate the importance of annual certification and the benefits of evaluation and revision of certification protocols to achieve high levels of confidence in neurodevelopmental study outcomes for multi-center networks. (J Pediatr 2012;161:1041-6).
C1 [Newman, Jamie E.; Bann, Carla M.] RTI Int, Dept Stat & Epidemiol, Res Triangle Pk, NC 27709 USA.
[Vohr, Betty R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Dusick, Anna M.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Newman, JE (reprint author), RTI Int, Dept Stat & Epidemiol, 3040 Cornwallis Rd, Res Triangle Pk, NC 27709 USA.
EM newman@rti.org
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD)
FX The National Institutes of Health and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD)
provided grant support for the Neonatal Research Network's (NRN)
Follow-Up Study. Data collected at participating sites of the NICHD NRN
were transmitted to RTI International, the data coordinating center for
the network, which stored, managed, and analyzed the data for this
study. J.N.'s time was supported by the NICHD Neonatal Research Network,
as the Data Coordinating Center coordinator for the Follow-Up Study. The
authors declare no conflicts of interest.
NR 19
TC 5
Z9 5
U1 1
U2 4
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 DEC
PY 2012
VL 161
IS 6
BP 1041
EP U98
DI 10.1016/j.jpeds.2012.05.048
PG 8
WC Pediatrics
SC Pediatrics
GA 040TZ
UT WOS:000311348400016
PM 22748517
ER
PT J
AU Horkay, F
AF Horkay, Ferenc
TI Interactions of cartilage extracellular matrix macromolecules
SO JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS
LA English
DT Article
DE aggrecan; biopolymers; cartilage; hyaluronic acid; osmotic pressure;
small-angle neutron scattering; self-assembly
ID ARTICULAR-CARTILAGE; SCATTERING; HYDROGELS; SAMPLES; REPAIR; TISSUE
AB Articular cartilage is a low-friction, load-bearing tissue located at joint surfaces. The extracellular matrix (ECM) of cartilage consists of a fibrous collagen network, which is prestressed by the osmotic swelling pressure exerted by negatively charged proteoglycan (PG) aggregates embedded in the collagen network. The major PG is the bottlebrush-shaped aggrecan, which forms complexes with linear hyaluronic acid (HA) chains. We quantify microscopic and macroscopic changes resulting from self-assembly between aggrecan and HA using a complementary set of physical measurements to determine structure and interactions by combining scattering techniques, including small-angle X-ray scattering, small-angle neutron scattering, and dynamic light scattering with macroscopic osmotic pressure measurements. It is demonstrated that the osmotic pressure that defines the load-bearing ability of cartilage is primarily governed by the main macromolecular components (aggrecan and collagen) of the ECM. Knowledge of the interactions between the macromolecular components of cartilage ECM is essential to understand biological function and to develop successful tissue engineering strategies for cartilage repair. (c) 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA.
RP Horkay, F (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, 13 South Dr, Bethesda, MD 20892 USA.
EM horkay@helix.nih.gov
FU Intramural Research Program of the NICHD, NIH; National Institute of
Standards and Technology, U.S. Department of Commerce; National Science
Foundation [DMR-0944772]
FX This research was supported by the Intramural Research Program of the
NICHD, NIH. We acknowledge the support of the National Institute of
Standards and Technology, U.S. Department of Commerce, in providing the
neutron research facilities used in this work. This work utilized
facilities supported in part by the National Science Foundation under
Agreement No. DMR-0944772. The author gratefully acknowledges the help
and consultation of Dr. Boualem Hammouda (NIST) with the SANS
experiment.
NR 21
TC 6
Z9 7
U1 3
U2 28
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-6266
J9 J POLYM SCI POL PHYS
JI J. Polym. Sci. Pt. B-Polym. Phys.
PD DEC 1
PY 2012
VL 50
IS 24
BP 1699
EP 1705
DI 10.1002/polb.23191
PG 7
WC Polymer Science
SC Polymer Science
GA 037BG
UT WOS:000311075400005
PM 23997426
ER
PT J
AU Kemp, AD
Harding, CC
Cabral, WA
Marini, JC
Wallace, JM
AF Kemp, Arika D.
Harding, Chad C.
Cabral, Wayne A.
Marini, Joan C.
Wallace, Joseph M.
TI Effects of tissue hydration on nanoscale structural morphology and
mechanics of individual Type I collagen fibrils in the Brtl mouse model
of Osteogenesis Imperfecta
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE AFM; Ultrastructure; Genotype/phenotype; D-periodic spacing; Modulus;
Energy
ID ATOMIC-FORCE MICROSCOPY; ELASTIC-MODULUS; MORPHOMETRIC-ANALYSIS;
ESTROGEN DEPLETION; MOLECULAR PACKING; MINERALIZATION; RESOLUTION;
MUTATIONS; STRENGTH; PEPTIDE
AB Type I collagen is the most abundant protein in mammals, and is a vital part of the extracellular matrix for numerous tissues. Despite collagen's importance, little is known about its nanoscale morphology in tissues and how morphology relates to mechanical function. This study probes nanoscale structure and mechanical properties of collagen as a function of disease in native hydrated tendons. Wild type tendon and tendon from the Brtl/+ mouse model of Osteogenesis Imperfecta were investigated. An atomic force microscope (AFM) was used to image and indent minimally-processed collagen fibrils in hydrated and dehydrated conditions. AFM was used because of the ability to keep biological tissues as close to their native in situ conditions as possible. The study demonstrated phenotypic difference in Brtl/+ fibril morphology and mechanics in hydrated tendon which became more compelling upon dehydration. Dried tendons had a significant downward shift in fibril D-periodic spacing versus a shift up in wet tendons. Nanoscale changes in morphology in dry samples were accompanied by significant increases in modulus and adhesion force and decreased indentation depth. A minimal mechanical phenotype existed in hydrated samples, possibly due to water masking structural defects within the diseased fibrils. This study demonstrates that collagen nanoscale morphology and mechanics are impacted in Brtl/+ tendons, and that the phenotype can be modulated by the presence or absence of water. Dehydration causes artifacts in biological samples which require water and this factor must be considered for studies at any length scale in collagen-based tissues, especially when characterizing disease-induced differences. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Kemp, Arika D.; Harding, Chad C.; Wallace, Joseph M.] Indiana Univ Purdue Univ, Dept Biomed Engn, Indianapolis, IN 46202 USA.
[Cabral, Wayne A.; Marini, Joan C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA.
RP Wallace, JM (reprint author), Indiana Univ Purdue Univ, Dept Biomed Engn, 723 W Michigan St,SL220D, Indianapolis, IN 46202 USA.
EM jmwalla@iupui.edu
RI Wallace, Joseph/G-7906-2012
FU IUPUI; NICHD
FX This work was partially supported by IUPUI Departmental Funds (JMW). JCM
is supported by NICHD Intramural Funding.
NR 45
TC 18
Z9 18
U1 3
U2 29
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD DEC
PY 2012
VL 180
IS 3
BP 428
EP 438
DI 10.1016/j.jsb.2012.09.012
PG 11
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 042KV
UT WOS:000311471000005
PM 23041293
ER
PT J
AU Shaikh, Q
Kamal, AK
AF Shaikh, Quratulain
Kamal, Ayeesha Kamran
TI Can telemedicine improve stroke outcomes?
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Kamal, Ayeesha Kamran] Aga Khan Univ Hosp, Stroke Serv & Vasc Fellowship Program, Int Cerebrovasc Translat Clin Res Training Progra, Karachi, Pakistan.
Aga Khan Univ Hosp, Fogarty Int Ctr, Karachi, Pakistan.
Aga Khan Univ Hosp, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan.
RP Kamal, AK (reprint author), Aga Khan Univ Hosp, Stroke Serv & Vasc Fellowship Program, Int Cerebrovasc Translat Clin Res Training Progra, Karachi, Pakistan.
EM ayeesha.kamal@aku.edu
OI Shaikh, Quratulain/0000-0001-6106-2713
FU FIC NIH HHS [D43TW008660, D43 TW008660]
NR 4
TC 0
Z9 0
U1 0
U2 3
PU PAKISTAN MEDICAL ASSOC
PI KARACHI
PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN
SN 0030-9982
J9 J PAK MED ASSOC
JI J. Pak. Med. Assoc.
PD DEC
PY 2012
VL 62
IS 12
BP 1352
EP 1353
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 042JQ
UT WOS:000311467900024
PM 23866493
ER
PT J
AU Ricketts, CJ
Shuch, B
Vocke, CD
Metwalli, AR
Bratslavsky, G
Middelton, L
Yang, YF
Wei, MH
Pautler, SE
Peterson, J
Stolle, CA
Zbar, B
Merino, MJ
Schmidt, LS
Pinto, PA
Srinivasan, R
Pacak, K
Linehan, WM
AF Ricketts, Christopher J.
Shuch, Brian
Vocke, Cathy D.
Metwalli, Adam R.
Bratslavsky, Gennady
Middelton, Lindsay
Yang, Youfeng
Wei, Ming-Hui
Pautler, Stephen E.
Peterson, James
Stolle, Catherine A.
Zbar, Berton
Merino, Maria J.
Schmidt, Laura S.
Pinto, Peter A.
Srinivasan, Ramaprasad
Pacak, Karel
Linehan, W. Marston
TI Succinate Dehydrogenase Kidney Cancer: An Aggressive Example of the
Warburg Effect in Cancer
SO JOURNAL OF UROLOGY
LA English
DT Article
DE kidney; carcinoma; renal cell; succinate dehydrogenase; germline
mutation; citric acid cycle
ID RENAL-CELL CARCINOMA; GERMLINE MUTATIONS; HEREDITARY LEIOMYOMATOSIS; B
GENE; PARAGANGLIOMA; SDHB; PHEOCHROMOCYTOMA; TUMORS; VARIANTS; TYPE-3
AB Purpose: Recently, a new renal cell cancer syndrome has been linked to germline mutation of multiple subunits (SDHB/C/D) of the Krebs cycle enzyme, succinate dehydrogenase. We report our experience with the diagnosis, evaluation and treatment of this novel form of hereditary kidney cancer.
Materials and Methods: Patients with suspected hereditary kidney cancer were enrolled on a National Cancer Institute institutional review board approved protocol to study inherited forms of kidney cancer. Individuals from families with germline SDHB, SDHC and SDHD mutations, and kidney cancer underwent comprehensive clinical and genetic evaluation.
Results: A total of 14 patients from 12 SDHB mutation families were evaluated. Patients presented with renal cell cancer at an early age (33 years, range 15 to 62), metastatic kidney cancer developed in 4 and some families had no manifestation other than kidney tumors. An additional family with 6 individuals found to have clear cell renal cell cancer that presented at a young average age (47 years, range 40 to 53) was identified with a germline SDHC mutation (R133X) Metastatic disease developed in 2 of these family members. A patient with a history of carotid body paragangliomas and an aggressive form of kidney cancer was evaluated from a family with a germline SDHD mutation.
Conclusions: SDH mutation associated renal cell carcinoma can be an aggressive type of kidney cancer, especially in younger individuals. Although detection and management of early tumors is most often associated with a good outcome, based on our initial experience with these patients and our long-term experience with hereditary leiomyomatosis and renal cell carcinoma, we recommend careful surveillance of patients at risk for SDH mutation associated renal cell carcinoma and wide surgical excision of renal tumors.
C1 [Ricketts, Christopher J.; Shuch, Brian; Vocke, Cathy D.; Metwalli, Adam R.; Bratslavsky, Gennady; Middelton, Lindsay; Yang, Youfeng; Wei, Ming-Hui; Peterson, James; Zbar, Berton; Schmidt, Laura S.; Pinto, Peter A.; Srinivasan, Ramaprasad; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Schmidt, Laura S.] SAIC Frederick Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Pautler, Stephen E.] Univ Western Ontario, Dept Oncol, London, ON, Canada.
[Pautler, Stephen E.] Univ Western Ontario, Dept Urol, London, ON, Canada.
[Stolle, Catherine A.] Childrens Hosp Philadelphia, Mol Genet Lab, Dept Pathol & Lab Med, Abramson Res Ctr, Philadelphia, PA 19104 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bldg 10 CRC Room 1-5940, Bethesda, MD 20892 USA.
EM WML@nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; federal funds
from the Frederick National Laboratory for Cancer Research, National
Institutes of Health [HHSN261200800001E]
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research and
federal funds from the Frederick National Laboratory for Cancer
Research, National Institutes of Health under Contract
HHSN261200800001E.
NR 30
TC 58
Z9 62
U1 1
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD DEC
PY 2012
VL 188
IS 6
BP 2063
EP 2071
DI 10.1016/j.juro.2012.08.030
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 043WM
UT WOS:000311581400011
PM 23083876
ER
PT J
AU Singer, EA
Vourganti, S
Lin, KY
Gupta, GN
Pinto, PA
Rastinehad, AR
Linehan, WM
Bratslavsky, G
AF Singer, Eric A.
Vourganti, Srinivas
Lin, Kelly Y.
Gupta, Gopal N.
Pinto, Peter A.
Rastinehad, Ardeshir R.
Linehan, W. Marston
Bratslavsky, Gennady
TI Outcomes of Patients with Surgically Treated Bilateral Renal Masses and
a Minimum of 10 Years of Followup
SO JOURNAL OF UROLOGY
LA English
DT Article
DE kidney; carcinoma, renal cell; nephrectomy; reoperation; genetic
diseases; inborn
ID PARENCHYMAL SPARING SURGERY; CHRONIC KIDNEY-DISEASE; CELL CARCINOMA;
PARTIAL NEPHRECTOMY; RADICAL NEPHRECTOMY; LINDAU-DISEASE; TUMOR SIZE;
FEASIBILITY; CANCER; EXPERIENCE
AB Purpose: Nephron sparing surgery has been advocated for patients with bilateral renal masses but long-term functional and oncological outcomes are lacking. We report the outcomes of patients with bilateral renal masses and a minimum 10-year followup.
Materials and Methods: Patients with bilateral renal masses evaluated at our institution who were treated with initial surgery at least 10 years ago and underwent interventions on each renal unit were included in the analysis. Collected data included demographics, hereditary diagnosis, number of renal interventions, renal function and mortality status. Overall and renal cell carcinoma specific survival was assessed. Comparisons were made of renal function and overall survival between groups with 2 renal units and a surgically solitary kidney.
Results: A total of 128 patients met study inclusion criteria. Median followup in our cohort was 16 years (mean 17, range 10 to 49). The median number of surgical interventions was 3 (range 2 to 10). Of the patients 87 (68%) required repeat interventions on the ipsilateral renal unit at last followup with a median of 6.2 years (range 0.7 to 21) between interventions. Overall and renal cell cancer specific survival was 88% and 97%, respectively. Six patients (4.7%) ultimately underwent bilateral nephrectomy. Although renal function was better preserved in patients with 2 kidneys (70 vs 53 ml/minute/1.73 m(2), p = 0.0002), there was no difference in overall survival between those with bilateral kidneys or a surgically solitary kidney.
Conclusions: At a minimum 10-year followup after initial surgery, nephron sparing surgery allowed for excellent oncological and functional outcomes. Despite the need for repeat surgical interventions, nephron sparing surgery enabled dialysis to be avoided in more than 95% of patients.
C1 [Bratslavsky, Gennady] State Univ New York Upstate Med Univ, Dept Urol, Syracuse, NY 13210 USA.
[Singer, Eric A.; Vourganti, Srinivas; Lin, Kelly Y.; Gupta, Gopal N.; Pinto, Peter A.; Rastinehad, Ardeshir R.; Linehan, W. Marston; Bratslavsky, Gennady] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Bratslavsky, G (reprint author), State Univ New York Upstate Med Univ, Dept Urol, Syracuse, NY 13210 USA.
EM bratslag@upstate.edu
FU National Institutes of Health, NCI, Center for Cancer Research; National
Institutes of Health; Pfizer, Inc.; Clinical Research Training Program
FX Supported by the Intramural Research Program of the National Institutes
of Health, NCI, Center for Cancer Research and the Clinical Research
Training Program, supported jointly by the National Institutes of Health
and Pfizer, Inc., via a Pfizer, Inc. grant to the Foundation for the
National Institute of Health.
NR 30
TC 7
Z9 7
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD DEC
PY 2012
VL 188
IS 6
BP 2084
EP 2088
DI 10.1016/j.juro.2012.08.038
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 043WM
UT WOS:000311581400014
PM 23083858
ER
PT J
AU Vourganti, S
Rastinehad, A
Yerram, NK
Nix, J
Volkin, D
Hoang, A
Turkbey, B
Gupta, GN
Kruecker, J
Linehan, WM
Choyke, PL
Wood, BJ
Pinto, PA
AF Vourganti, Srinivas
Rastinehad, Ardeshir
Yerram, Nitin K.
Nix, Jeffrey
Volkin, Dmitry
Hoang, An
Turkbey, Baris
Gupta, Gopal N.
Kruecker, Jochen
Linehan, W. Marston
Choyke, Peter L.
Wood, Bradford J.
Pinto, Peter A.
TI Multiparametric Magnetic Resonance Imaging and Ultrasound Fusion Biopsy
Detect Prostate Cancer in Patients with Prior Negative Transrectal
Ultrasound Biopsies
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostatic neoplasms; biopsy
ID REPEAT BIOPSY; SATURATION BIOPSY; NEEDLE-BIOPSY; POPULATION; MEN
AB Purpose: Patients with negative transrectal ultrasound biopsies and a persistent clinical suspicion are at risk for occult but significant prostate cancer. The ability of multiparametric magnetic resonance imaging/ultrasound fusion biopsy to detect these occult prostate lesions may make it an effective tool in this challenging scenario.
Materials and Methods: Between March 2007 and November 2011 all men underwent prostate 3 T endorectal coil magnetic resonance imaging. All concerning lesions were targeted with magnetic resonance imaging/ultrasound fusion biopsy. In addition, all patients underwent standard 12-core transrectal ultrasound biopsy. Men with 1 or more negative systematic prostate biopsies were included in our cohort.
Results: Of the 195 men with previous negative biopsies, 73 (37%) were found to have cancer using the magnetic resonance imaging/ultrasound fusion biopsy combined with 12-core transrectal ultrasound biopsy. High grade cancer (Gleason score 8+) was discovered in 21 men (11%), all of whom had disease detected with magnetic resonance imaging/ultrasound fusion biopsy. However, standard transrectal ultrasound biopsy missed 12 of these high grade cancers (55%). Pathological upgrading occurred in 28 men (38.9%) as a result of magnetic resonance imaging/ultrasound fusion targeting vs standard transrectal ultrasound biopsy. The diagnostic yield of combined magnetic resonance imaging/ultrasound fusion platform was unrelated to the number of previous negative biopsies and persisted despite increasing the number of previous biopsy sessions. On multivariate analysis only prostate specific antigen density and magnetic resonance imaging suspicion level remained significant predictors of cancer.
Conclusions: Multiparametric magnetic resonance imaging with a magnetic resonance imaging/ultrasound fusion biopsy platform is a novel diagnostic tool for detecting prostate cancer and may be ideally suited for patients with negative transrectal ultrasound biopsies in the face of a persistent clinical suspicion for cancer.
C1 [Vourganti, Srinivas; Rastinehad, Ardeshir; Yerram, Nitin K.; Nix, Jeffrey; Volkin, Dmitry; Hoang, An; Gupta, Gopal N.; Linehan, W. Marston; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Wood, Bradford J.; Pinto, Peter A.] NCI, Ctr Intervent Oncol, Dept Radiol & Imaging Sci, NIH, Bethesda, MD 20892 USA.
[Kruecker, Jochen] Philips Res N Amer, Briarcliff Manor, NY USA.
RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC 1210,Bldg 10,CRC,Room 2W-5940, Bethesda, MD 20892 USA.
EM pintop@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
FX Supported by the Intramural Research Program of the National Cancer
Institute, National Institutes of Health.
NR 18
TC 116
Z9 120
U1 2
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD DEC
PY 2012
VL 188
IS 6
BP 2152
EP 2157
DI 10.1016/j.juro.2012.08.025
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 043WM
UT WOS:000311581400034
PM 23083875
ER
PT J
AU Albo, ME
Litman, HJ
Richter, HE
Lemack, GE
Sirls, LT
Chai, TC
Norton, P
Kraus, SR
Zyczynski, H
Kenton, K
Gormley, EA
Kusek, JW
AF Albo, Michael E.
Litman, Heather J.
Richter, Holly E.
Lemack, Gary E.
Sirls, Larry T.
Chai, Toby C.
Norton, Peggy
Kraus, Stephen R.
Zyczynski, Halina
Kenton, Kimberly
Gormley, E. Ann
Kusek, John W.
CA Urinary Incontinence Treatment
TI Treatment Success of Retropubic and Transobturator Mid Urethral Slings
at 24 Months
SO JOURNAL OF UROLOGY
LA English
DT Article
DE urinary incontinence, stress; suburethral slings; treatment outcome
ID STRESS URINARY-INCONTINENCE; FREE VAGINAL TAPE; IMPACT; COLPOSUSPENSION;
COMPLICATIONS; METAANALYSIS; TRIALS; WOMEN
AB Purpose: Longer term comparative efficacy information regarding transobturator and retropubic mid urethral slings is needed. We report 24-month continence rates, complications and symptom outcomes from a randomized equivalence trial.
Materials and Methods: Primary outcomes were objective (negative stress test, negative pad test and no re-treatment for stress urinary incontinence) and subjective (no self-report of stress urinary incontinence symptoms, no leakage episodes on 3-day bladder diary and no re-treatment for stress urinary incontinence) success at 24 months. The predetermined equivalence margin was +/- 12%.
Results: Of 597 randomized participants 516 (86.4%) were assessed. Objective success rates for retropubic and transobturator mid urethral slings were 77.3% and 72.3%, respectively (95% CI for difference of 5.1% was -2.0, 12.1), and subjective success rates were 55.7% and 48.3%, respectively (CI for difference of 7.4% was -0.7, 15.5). Neither objective nor subjective success rates met the prespecified criteria for equivalence. Patient satisfaction (retropubic 86.3% vs transobturator 88.1%, p = 0.58), frequency of de novo urgency incontinence (retropubic 0% vs transobturator 0.3%, p = 0.99) and occurrence of mesh exposure (retropubic 4.4% vs transobturator 2.7%, p = 0.26) were not significantly different. The retropubic mid urethral sling group had higher rates of voiding dysfunction requiring surgery (3.0% vs 0%, p = 0.002) and urinary tract infections (17.1% vs 10.7%, p = 0.025), whereas the transobturator group had more neurological symptoms (9.7% vs 5.4%, p = 0.045).
Conclusions: Objective success rates met the criteria for equivalence at 12 months but no longer met these criteria at 24 months. Subjective success rates remained inconclusive for equivalence. Patient satisfaction remained high and symptom severity remained markedly improved. Continued surveillance is important in women undergoing mid urethral sling surgery.
C1 [Albo, Michael E.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Litman, Heather J.] New England Res Inst, Watertown, MA 02172 USA.
[Richter, Holly E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Lemack, Gary E.] Univ Texas Dallas, Dallas, TX 75230 USA.
[Kraus, Stephen R.] Univ Texas San Antonio, San Antonio, TX USA.
[Sirls, Larry T.] William Beaumont Hosp, Royal Oak, MI 48072 USA.
[Chai, Toby C.] Univ Maryland, Baltimore, MD 21201 USA.
[Kusek, John W.] NIDDK, Bethesda, MD USA.
[Norton, Peggy] Univ Utah, Salt Lake City, UT USA.
[Zyczynski, Halina] Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA.
[Kenton, Kimberly] Loyola Univ, Chicago, IL 60611 USA.
[Gormley, E. Ann] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
RP Albo, ME (reprint author), Univ Calif San Diego, San Diego Hlth Syst, Div Urol, 9350 Campus Point Dr,Ste 2A,MC 0974, San Diego, CA 92037 USA.
EM malbo@ucsd.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases [U01
DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01
DK60380, U01 DK60393, U01 DK60395, U01 DK60397, U01 DK60401]; National
Institute of Child Health and Human Development; Office of Research in
Women's Health
FX Supported by cooperative agreements from the National Institute of
Diabetes and Digestive and Kidney Diseases U01 DK58225, U01 DK58229, U01
DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01 DK60393, U01
DK60395, U01 DK60397 and U01 DK60401, and by the National Institute of
Child Health and Human Development, and the Office of Research in
Women's Health.
NR 20
TC 29
Z9 29
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD DEC
PY 2012
VL 188
IS 6
BP 2281
EP 2287
DI 10.1016/j.juro.2012.07.103
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 043WM
UT WOS:000311581400096
PM 23083653
ER
PT J
AU van der Zanden, LFM
Galesloot, TE
Feitz, WFJ
Brouwers, MM
Shi, M
Knoers, NVAM
Franke, B
Roeleveld, N
van Rooij, IALM
AF van der Zanden, Loes F. M.
Galesloot, Tessel E.
Feitz, Wout F. J.
Brouwers, Marijn M.
Shi, Min
Knoers, Nine V. A. M.
Franke, Barbara
Roeleveld, Nel
van Rooij, Iris A. L. M.
TI Exploration of Gene-Environment Interactions, Maternal Effects and
Parent of Origin Effects in the Etiology of Hypospadias
SO JOURNAL OF UROLOGY
LA English
DT Article
DE gene-environment interaction; genetic association studies; hypospadias
ID TRIADS; RISK; DISEASE
AB Purpose: Hypospadias is a common congenital malformation of the male external genitalia. Association studies for single nucleotide polymorphisms in genes encoding steroid 5alpha-reductase, estrogen receptors 1 and 2, and activating transcription factor 3 have been equivocal. We examined whether nonreplication of findings for 4 single nucleotide polymorphisms in these genes could be due to interaction with environmental exposures.
Materials and Methods: We genotyped 712 Dutch hypospadias case-parent triads for the 4 single nucleotide polymorphisms, used questionnaire information to determine exposures and performed association tests using the log-linear approach. We studied gene-environment interactions for the 4 single nucleotide polymorphisms with exposure to estrogens, cytokines or cigarette smoke, multiple birth, being born small for gestational age, maternal hypertension or pre-eclampsia, high body mass index or primiparity. In addition, the presence of maternal genetic and parent of origin effects was tested.
Results: Gene-environment interactions were identified for rs523349 in SRD5A2 with estrogen exposure and maternal hypertension or preeclampsia, as well as for rs11119982 in ATF3 with exposure to cytokines. Both single nucleotide polymorphisms seemed to influence hypospadias risk only in exposed cases. For rs6932902 in ESR1 only maternally derived alleles appeared to increase hypospadias risk in offspring.
Conclusions: Interactions between genetic and environmental factors may help to explain nonreplication in genetic studies of hypospadias.
C1 [van der Zanden, Loes F. M.; Galesloot, Tessel E.; Brouwers, Marijn M.; Roeleveld, Nel; van Rooij, Iris A. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6500 HB Nijmegen, Netherlands.
[van der Zanden, Loes F. M.; Knoers, Nine V. A. M.; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands.
[Feitz, Wout F. J.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6500 HB Nijmegen, Netherlands.
[Brouwers, Marijn M.] Radboud Univ Nijmegen, Med Ctr, Fdn Prenatal Screening Nijmegen Region, NL-6500 HB Nijmegen, Netherlands.
[Knoers, Nine V. A. M.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[Shi, Min] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP van der Zanden, LFM (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, Internal Postal Code 133,POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM L.vanderZanden@ebh.umcn.nl
RI Franke, Barbara/D-4836-2009; Feitz, W.F.J./H-8028-2014; Galesloot,
Tessel/P-6667-2015; Roeleveld, Nel/B-4242-2008; Rooij, van,
Iris/A-5705-2014; van der Zanden, Loes/M-4795-2015
OI Franke, Barbara/0000-0003-4375-6572; Roeleveld, Nel/0000-0002-3390-4466;
Rooij, van, Iris/0000-0002-9519-966X; van der Zanden,
Loes/0000-0003-3914-7491
FU National Institutes of Health, National Institute of Environmental
Health Sciences
FX Supported by Intramural Research Program of National Institutes of
Health, National Institute of Environmental Health Sciences.
NR 29
TC 13
Z9 13
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD DEC
PY 2012
VL 188
IS 6
BP 2354
EP 2360
DI 10.1016/j.juro.2012.08.033
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 043WM
UT WOS:000311581400131
PM 23088992
ER
PT J
AU Carlson, JM
Brumme, CJ
Martin, E
Listgarten, J
Brockman, MA
Le, AQ
Chui, CKS
Cotton, LA
Knapp, DJHF
Riddler, SA
Haubrich, R
Nelson, G
Pfeifer, N
DeZiel, CE
Heckerman, D
Apps, R
Carrington, M
Mallal, S
Harrigan, PR
John, M
Brumme, ZL
AF Carlson, Jonathan M.
Brumme, Chanson J.
Martin, Eric
Listgarten, Jennifer
Brockman, Mark A.
Le, Anh Q.
Chui, Celia K. S.
Cotton, Laura A.
Knapp, David J. H. F.
Riddler, Sharon A.
Haubrich, Richard
Nelson, George
Pfeifer, Nico
DeZiel, Charles E.
Heckerman, David
Apps, Richard
Carrington, Mary
Mallal, Simon
Harrigan, P. Richard
John, Mina
Brumme, Zabrina L.
CA Int HIV Adaptation Collaborative
TI Correlates of Protective Cellular Immunity Revealed by Analysis of
Population-Level Immune Escape Pathways in HIV-1
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD8(+) T-CELLS; CLASS-I MOLECULES; VIRAL
LOAD; SELECTION PRESSURE; LYMPHOCYTE RESPONSES; HLA ALLELES; DISEASE
PROGRESSION; PRIMARY INFECTION; PEPTIDE BINDING
AB HLA class I-associated polymorphisms identified at the population level mark viral sites under immune pressure by individual HLA alleles. As such, analysis of their distribution, frequency, location, statistical strength, sequence conservation, and other properties offers a unique perspective from which to identify correlates of protective cellular immunity. We analyzed HLA-associated HIV-1 subtype B polymorphisms in 1,888 treatment-naive, chronically infected individuals using phylogenetically informed methods and identified characteristics of HLA-associated immune pressures that differentiate protective and nonprotective alleles. Over 2,100 HLA-associated HIV-1 polymorphisms were identified, approximately one-third of which occurred inside or within 3 residues of an optimally defined cytotoxic T-lymphocyte (CTL) epitope. Differential CTL escape patterns between closely related HLA alleles were common and increased with greater evolutionary distance between allele group members. Among 9-mer epitopes, mutations at HLA-specific anchor residues represented the most frequently detected escape type: these occurred nearly 2-fold more frequently than expected by chance and were computationally predicted to reduce peptide-HLA binding nearly 10-fold on average. Characteristics associated with protective HLA alleles (defined using hazard ratios for progression to AIDS from natural history cohorts) included the potential to mount broad immune selection pressures across all HIV-1 proteins except Nef, the tendency to drive multisite and/or anchor residue escape mutations within known CTL epitopes, and the ability to strongly select mutations in conserved regions within HIV's structural and functional proteins. Thus, the factors defining protective cellular immune responses may be more complex than simply targeting conserved viral regions. The results provide new information to guide vaccine design and immunogenicity studies.
C1 [Brumme, Chanson J.; Brockman, Mark A.; Chui, Celia K. S.; Knapp, David J. H. F.; Harrigan, P. Richard; Brumme, Zabrina L.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
[Carlson, Jonathan M.; Listgarten, Jennifer; Pfeifer, Nico; DeZiel, Charles E.; Heckerman, David] Microsoft Res, Los Angeles, CA USA.
[Martin, Eric; Brockman, Mark A.; Le, Anh Q.; Cotton, Laura A.; Brumme, Zabrina L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada.
[Riddler, Sharon A.] Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA USA.
[Haubrich, Richard] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Nelson, George] SAIC Frederick Inc, Basic Res Program, Ctr Canc Res Genet Core, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Apps, Richard; Carrington, Mary] SAIC Frederick Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Apps, Richard; Carrington, Mary] Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Charlestown, MA USA.
[Mallal, Simon; John, Mina] Murdoch Univ, Ctr Clin Immunol & Biomed Stat, Inst Immunol & Infect Dis, Murdoch, WA 6150, Australia.
[Mallal, Simon; John, Mina] Royal Perth Hosp, Dept Clin Immunol, Perth, WA 6001, Australia.
RP Brumme, ZL (reprint author), British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
EM carlson@microsoft.com; zbrumme@sfu.ca
RI Pfeifer, Nico/G-1559-2016;
OI Knapp, David/0000-0002-2161-9959; Pfeifer, Nico/0000-0002-4647-8566;
Brumme, Chanson/0000-0003-2722-5288; Brockman, Mark/0000-0001-6432-1426
FU Canadian Institutes for Health Research (CIHR) [MOP-93536, HOP-115700];
NIAID [AI27670, AI36214, AI064086]; Frederick National Laboratory for
Cancer Research [HHSN261200800001E]; Intramural Research Program of the
NIH; Frederick National Lab; Center for Cancer Research; Vanier Canada
Graduate Scholarship from the CIHR; Master's Scholarship from the
Canadian Association of HIV Research and Abbott Virology; CIHR New
Investigator Award; Michael Smith Foundation for Health Research;
Northwestern University [AI 069471]; University of Minnesota [AI 27661];
Vanderbilt University [AI-069439]; Indiana University [AI25859,
MO1RR000750]; University of Miami School of Medicine [AI069477];
University of Cincinnati [AI-069513]; University of Alabama [1 U01
AI069452-01, M01 RR-00032]; University of Southern California [AI27673];
Cornell CTU [AI069419-01, CTSC RR024996]; Ohio State University
[AI069474]; University of Rochester [AI69411, 5-MO1 RR00044]; Univeristy
of North Carolina-Chapel Hill [AI50410, AI69423-01, RR00046]; University
of Pittsburgh [AI69494-01]; Duke University Medical Center
[1U01-AI069484]; Harvard/BMC CTU [AI069472, AI060354, RR02635]; Durban
International CTU [UOIA138858]; Case Western Reserve University [AI
069501]; University of Pennsylvania, Philadelphia [AI 69467-01,
5-P30-AI-045008-07]; Colorado ACTU [AI069450, RR00051]; University of
Texas Medical Branch-Galveston [AI32782]; Johns Hopkins University
[AI-69465, RR-00052]; University of California, Los Angeles [AI069424];
University of California, Davis Medical Center [AI38858-09S1];
University of Maryland, Institute of Human Virology [AI069447-01];
Washington University in St. Louis [AI069495]; University of California,
San Francisco [AI069502-01]; Stanford University [AI069556]; University
of California, San Diego [AI069432]; Beth Israel Medical Center
[AI46370]; New York University/New York City Health and Hospitals Corp.
at Bellevue Hospital Center [AI069532, M01-RR00096]; Miriam Hospital
[AI69472]; University of Texas Southwestern Medical Center at Dallas
[AI046376-05]; University of Hawaii at Manoa and Queen's Medical Center
[AI34853]; University of Washington, Seattle [AI069434]; [AI068636];
[RR024975]
FX This work was supported by operating grants from the Canadian Institutes
for Health Research (CIHR) (MOP-93536 and HOP-115700) to Z.L.B./M.A.B.
In addition this project has been funded in part by NIAID grants
AI27670, AI36214, and AI064086 to University of California, San Diego
(UCSD; R. Haubrich) and in whole or in part with federal funds from the
Frederick National Laboratory for Cancer Research, under contract number
HHSN261200800001E. This Research was supported in part by the Intramural
Research Program of the NIH, Frederick National Lab, Center for Cancer
Research. C.J.B. is supported by a Vanier Canada Graduate Scholarship
from the CIHR. E. M. is supported by a Master's Scholarship from the
Canadian Association of HIV Research and Abbott Virology. M. A. B. holds
a Canada Research Chair, Tier 2, in Viral Pathogenesis and Immunity.
J.M.C., J.L., N.P., C. E. D., and D. H. are employees of Microsoft
Corporation. Z.L.B. is the recipient of a CIHR New Investigator Award
and a scholar award from the Michael Smith Foundation for Health
Research. The ACTG Human DNA Repository is supported by grants AI068636
and RR024975. The following is a list of ACTG sites that participated in
both A5142 and A5128 protocols, along with their grant numbers:
Northwestern University (sites 2701, 2702, and 2705), Clinical Trials
Unit (CTU) grant AI 069471; University of Minnesota (sites 1501, 1504,
and 1505), CTU grant AI 27661; Vanderbilt University (site 3652), CTU
grant AI-069439; Indiana University (sites 2601 and 2603), CTU grant
AI25859 and GCRC grant MO1RR000750; University of Miami School of
Medicine (site 901), CTU grant AI069477; University of Cincinnati (site
2401), CTU grant AI-069513; University of Alabama (sites 5801 and 5802),
CTU grant 1 U01 AI069452-01 and GCRC grant M01 RR-00032; University of
Southern California (site 1201), CTU grant AI27673; Cornell CTU (site
30329, 7803, and 7804), CTU grants AI069419-01 and CTSC RR024996; The
Ohio State University (Site 2301), CTU grant AI069474; University of
Rochester (sites 1101, 1102, 1107, and 1108), CTU grant AI69411 and GCRC
grant 5-MO1 RR00044; Univeristy of North Carolina-Chapel Hill (site
3201), CFAR grant AI50410, CTU grant AI69423-01, and GCRC grant RR00046;
University of Pittsburgh (site 1001 and 1008), CTU grant AI69494-01;
Duke University Medical Center (site 1601), CTU grant 1U01-AI069484;
Harvard/BMC CTU (sites 103, 104, and 107), CTU grant AI069472, CFAR
grant AI060354, and GCRC grant RR02635; Durban International CTU (site
11201), grant UOIA138858; Case Western Reserve University (sites 2501,
2503, and 2508), CTU grant AI 069501; University of Pennsylvania,
Philadelphia (sites 6201 and 6206), CTU grant AI 69467-01 and CFAR grant
5-P30-AI-045008-07; Colorado ACTU (site 6101), CTU grant AI069450 and
GCRC grant RR00051; University of Texas Medical Branch-Galveston (site
6301), CTU grant AI32782; Johns Hopkins University (site 201), CTU grant
AI-69465 and GCRC grant RR-00052; University of California, Los Angeles
(sites 601 and 603), CTU grant AI069424; University of California, Davis
Medical Center (site 3852), CTU grant AI38858-09S1; University of
Maryland, Institute of Human Virology (site 4651), CTU grant
AI069447-01; Washington University in St.; Louis (site 2101), CTU grant
AI069495; University of California, San Francisco (site 801), CTU grant
AI069502-01; Stanford University (sites 501, 505, and 506), CTU grant
AI069556; University of California, San Diego (site 701), grant
AI069432; Beth Israel Medical Center (site 2851), CTU grant AI46370; New
York University/New York City Health and Hospitals Corp. at Bellevue
Hospital Center (site 401), CTU grant AI069532 and GCRC grant
M01-RR00096; The Miriam Hospital (site 2951), CTU grant AI69472;
University of Texas Southwestern Medical Center at Dallas (site 3751),
CTU grant AI046376-05; University of Hawaii at Manoa and Queen's Medical
Center (site 5201), CTU grant AI34853; University of Washington, Seattle
(site 1401), CTU grant AI069434.
NR 124
TC 42
Z9 44
U1 2
U2 10
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 DEC
PY 2012
VL 86
IS 24
BP 13202
EP 13216
DI 10.1128/JVI.01998-12
PG 15
WC Virology
SC Virology
GA 040DC
UT WOS:000311299600006
PM 23055555
ER
PT J
AU Page, C
Goicochea, L
Matthews, K
Zhang, Y
Klover, P
Holtzman, MJ
Hennighausen, L
Frieman, M
AF Page, Carly
Goicochea, Lindsay
Matthews, Krystal
Zhang, Yong
Klover, Peter
Holtzman, Michael J.
Hennighausen, Lothar
Frieman, Matthew
TI Induction of Alternatively Activated Macrophages Enhances Pathogenesis
during Severe Acute Respiratory Syndrome Coronavirus Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IDIOPATHIC PULMONARY-FIBROSIS; INNATE IMMUNE-RESPONSE; TARGETED
DISRUPTION; DISTRESS-SYNDROME; MEDICAL PROGRESS; VIRAL-INFECTION; LIVER
FIBROSIS; AIRWAY DISEASE; STAT1 FUNCTION; LUNG FIBROSIS
AB Infection with severe acute respiratory syndrome coronavirus (SARS-CoV) causes acute lung injury (ALI) that often leads to severe lung disease. A mouse model of acute SARS-CoV infection has been helpful in understanding the host response to infection; however, there are still unanswered questions concerning SARS-CoV pathogenesis. We have shown that STAT1 plays an important role in the severity of SARS-CoV pathogenesis and that it is independent of the role of STAT1 in interferon signaling. Mice lacking STAT1 have greater weight loss, severe lung pathology with pre-pulmonary-fibrosis-like lesions, and an altered immune response following infection with SARS-CoV. We hypothesized that STAT1 plays a role in the polarization of the immune response, specifically in macrophages, resulting in a worsened outcome. To test this, we created bone marrow chimeras and cell-type-specific knockouts of STAT1 to identify which cell type(s) is critical to protection from severe lung disease after SARS-CoV infection. Bone marrow chimera experiments demonstrated that hematopoietic cells are responsible for the pathogenesis in STAT1(-/-) mice, and because of an induction of alternatively activated (AA) macrophages after infection, we hypothesized that the AA macrophages were critical for disease severity. Mice with STAT1 in either monocytes and macrophages (LysM/STAT1) or ciliated lung epithelial cells (FoxJ1/STAT1) deleted were created. Following infection, LysM/STAT1 mice display severe lung pathology, while FoxJ1/STAT1 mice display normal lung pathology. We hypothesized that AA macrophages were responsible for this STAT1-dependent pathology and therefore created STAT1/STAT6(-/-) double-knockout mice. STAT6 is essential for the development of AA macrophages. Infection of the double-knockout mice displayed a lack of lung disease and prefibrotic lesions, suggesting that AA macrophage production may be the cause of STAT1-dependent lung disease. We propose that the control of AA macrophages by STAT1 is critical to regulating immune pathologies and for protection from long-term progression to fibrotic lung disease in a mouse model of SARS-CoV infection.
C1 [Page, Carly; Matthews, Krystal; Frieman, Matthew] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Goicochea, Lindsay] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Zhang, Yong; Holtzman, Michael J.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Klover, Peter; Hennighausen, Lothar] NIH, Lab Genet & Physiol, Bethesda, MD 20892 USA.
[Holtzman, Michael J.] Washington Univ, Sch Med, Dept Cell Biol, St Louis, MO 63110 USA.
RP Frieman, M (reprint author), Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
EM mfrieman@som.umaryland.edu
FU NIAID/NIH [R01AI095569-01, T32AI007540]
FX This work was supported by NIAID/NIH grant R01AI095569-01 (M. F.) and
NIAID/NIH grant T32AI007540 (C.P.).
NR 79
TC 16
Z9 16
U1 1
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD DEC
PY 2012
VL 86
IS 24
BP 13334
EP 13349
DI 10.1128/JVI.01689-12
PG 16
WC Virology
SC Virology
GA 040DC
UT WOS:000311299600018
PM 23015710
ER
PT J
AU Aoki, M
Danish, ML
Aoki-Ogata, H
Amano, M
Ide, K
Das, D
Koh, Y
Mitsuya, H
AF Aoki, Manabu
Danish, Matthew L.
Aoki-Ogata, Hiromi
Amano, Masayuki
Ide, Kazuhiko
Das, Debananda
Koh, Yasuhiro
Mitsuya, Hiroaki
TI Loss of the Protease Dimerization Inhibition Activity of Tipranavir
(TPV) and Its Association with the Acquisition of Resistance to TPV by
HIV-1
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VITRO; REDUCED SUSCEPTIBILITY;
VIROLOGICAL RESPONSE; ANTIVIRAL ACTIVITY; VIRAL INFECTIVITY; INFECTED
PATIENTS; DRUG-SENSITIVITY; CLEAVAGE SITES; MUTATIONS
AB Tipranavir (TPV), a protease inhibitor (PI) inhibiting the enzymatic activity and dimerization of HIV-1 protease, exerts potent activity against multi-PI-resistant HIV-1 isolates. When a mixture of 11 multi-PI-resistant (but TPV-sensitive) clinical isolates (HIV11MIX), which included HIVB and HIVC, was selected against TPV, HIV11MIX rapidly (by 10 passages [HIV11MIXP10]) acquired high-level TPV resistance and replicated at high concentrations of TPV. HIV11MIXP10 contained various amino acid substitutions, including I54V and V82T. The intermolecular FRET-based HIV-1 expression assay revealed that TPV's dimerization inhibition activity against cloned HIVB (cHIV(B)) was substantially compromised. The introduction of I54V/V82T into wild-type cHIV(NL4-3) (cHIV(NL4-3I54V/V82T)) did not block TPV's dimerization inhibition or confer TPV resistance. However, the introduction of I54V/V82T into cHIV(B) (cHIV(B)(I54V/V82T)) compromised TPV's dimerization inhibition and cHIV(B)(I54V/V82T) proved to be significantly TPV resistant. L24M was responsible for TPV resistance with the cHIV(C) genetic background. The introduction of L24M into cHIV(NL4-3) (cHIV(NL4-3L24M)) interfered with TPV's dimerization inhibition, while L24M increased HIV-1's susceptibility to TPV with the HIVNL4-3 genetic background. When selected with TPV, cHIV(NL4-3I54V/V82T) most readily developed TPV resistance and acquired E34D, which compromised TPV's dimerization inhibition with the HIVNL4-3 genetic background. The present data demonstrate that certain amino acid substitutions compromise TPV's dimerization inhibition and confer TPV resistance, although the loss of TPV's dimerization inhibition is not always associated with significantly increased TPV resistance. The findings that TPV's dimerization inhibition is compromised with one or two amino acid substitutions may explain at least in part why the genetic barrier of TPV against HIV-1's development of TPV resistance is relatively low compared to that of darunavir.
C1 [Aoki, Manabu; Danish, Matthew L.; Aoki-Ogata, Hiromi; Amano, Masayuki; Ide, Kazuhiko; Koh, Yasuhiro; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Infect Dis, Kumamoto, Japan.
[Aoki, Manabu; Danish, Matthew L.; Aoki-Ogata, Hiromi; Amano, Masayuki; Ide, Kazuhiko; Koh, Yasuhiro; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Hematol, Kumamoto, Japan.
[Aoki, Manabu] Kumamoto Hlth Sci Univ, Dept Med Technol, Kumamoto, Japan.
[Das, Debananda; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
RP Mitsuya, H (reprint author), Kumamoto Univ, Grad Sch Med Sci, Dept Infect Dis, Kumamoto, Japan.
EM hmitsuya@helix.nih.gov
RI Amano, Masayuki/N-7407-2016
OI Amano, Masayuki/0000-0003-0516-9502
FU Monbu-Kagakusho; Ministry of Health, Welfare, and Labor of Japan;
Monbu-Kagakusho [78, 21790527]; Intramural Research Program of Center
for Cancer Research, National Cancer Institute, National Institutes of
Health
FX This work was supported in part by a grant for global education and a
research center aiming at the control of AIDS (Global Center of
Excellence supported by Monbu-Kagakusho), a grant for the promotion of
AIDS research from the Ministry of Health, Welfare, and Labor of Japan,
a grant to the Cooperative Research Project on Clinical and
Epidemiological Studies of Emerging and Re-Emerging Infectious Diseases
(Renkei Jigyo no. 78, Kumamoto University) of Monbu-Kagakusho, and a
Grant-in-Aid for Young Scientists (B) (grant 21790527) of
Monbu-Kagakusho and in part by the Intramural Research Program of Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 41
TC 7
Z9 7
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD DEC
PY 2012
VL 86
IS 24
BP 13384
EP 13396
DI 10.1128/JVI.07234-11
PG 13
WC Virology
SC Virology
GA 040DC
UT WOS:000311299600022
PM 23015723
ER
PT J
AU Kajihara, M
Marzi, A
Nakayama, E
Noda, T
Kuroda, M
Manzoor, R
Matsuno, K
Feldmann, H
Yoshida, R
Kawaoka, Y
Takada, A
AF Kajihara, Masahiro
Marzi, Andrea
Nakayama, Eri
Noda, Takeshi
Kuroda, Makoto
Manzoor, Rashid
Matsuno, Keita
Feldmann, Heinz
Yoshida, Reiko
Kawaoka, Yoshihiro
Takada, Ayato
TI Inhibition of Marburg Virus Budding by Nonneutralizing Antibodies to the
Envelope Glycoprotein
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID EBOLA-VIRUS; MONOCLONAL-ANTIBODIES; ANTIGENIC MODULATION;
INFECTED-CELLS; MEASLES-VIRUS; NEUTRALIZING ANTIBODIES; MATRIX PROTEIN;
VP40; PARTICLES; RELEASE
AB The envelope glycoprotein (GP) of Marburg virus (MARV) and Ebola virus (EBOV) is responsible for virus entry into host cells and is known as the only target of neutralizing antibodies. While knowledge about EBOV-neutralizing antibodies and the mechanism for the neutralization of infectivity is being accumulated gradually, little is known about antibodies that can efficiently regulate MARV infectivity. Here we show that MARV GP-specific monoclonal antibodies AGP127-8 (IgG1) and MGP72-17 (IgM), which do not inhibit the GP-mediated entry of MARV into host cells, drastically reduced the budding and release of progeny viruses from infected cells. These antibodies similarly inhibited the formation of virus-like particles (VLPs) consisting of GP, the viral matrix protein, and nucleoprotein, whereas the Fab fragment of AGP127-8 showed no inhibitory effect. Morphological analyses revealed that filamentous VLPs were bunched on the surface of VLP-producing cells cultured in the presence of the antibodies. These results demonstrate a novel mechanism of the antibody-mediated inhibition of MARV budding, in which antibodies arrest unformed virus particles on the cell surface. Our data lead to the idea that such antibodies, like classical neutralizing antibodies, contribute to protective immunity against MARV and that the "classical" neutralizing activity is not the only indicator of a protective antibody that may be available for prophylactic and therapeutic use.
C1 [Kajihara, Masahiro; Nakayama, Eri; Kuroda, Makoto; Manzoor, Rashid; Matsuno, Keita; Yoshida, Reiko; Takada, Ayato] Hokkaido Univ, Res Ctr Zoonosis Control, Div Global Epidemiol, Sapporo, Hokkaido, Japan.
[Marzi, Andrea; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Noda, Takeshi; Kawaoka, Yoshihiro] Univ Tokyo, Inst Med Sci, Div Virol, Dept Microbiol & Immunol, Tokyo, Japan.
[Kawaoka, Yoshihiro] Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Tokyo, Japan.
[Kawaoka, Yoshihiro] ERATO Infect Induced Host Responses Project, Saitama, Japan.
[Kawaoka, Yoshihiro] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA.
[Takada, Ayato] Univ Zambia, Sch Vet Med, Lusaka, Zambia.
RP Takada, A (reprint author), Hokkaido Univ, Res Ctr Zoonosis Control, Div Global Epidemiol, Sapporo, Hokkaido, Japan.
EM atakada@czc.hokudai.ac.jp
RI Takada, Ayato/A-6679-2012; YOSHIDA, Reiko/F-6883-2012
FU Japan Initiative for Global Research Network on Infectious Diseases
(J-GRID); Global COE Program; Ministry of Education, Culture, Sports,
Science and Technology (MEXT); ERATO (Japan Science and Technology
Agency); National Institute of Allergy and Infectious Disease Public
Health Service; Ministry of Health, Labour and Welfare of Japan;
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Japan Initiative for Global Research
Network on Infectious Diseases (J-GRID); the Global COE Program; a
grant-in-aid from the Ministry of Education, Culture, Sports, Science
and Technology (MEXT); ERATO (Japan Science and Technology Agency); and
National Institute of Allergy and Infectious Disease Public Health
Service research grants. Funding was also provided by a grant-in-aid
from the Ministry of Health, Labour and Welfare of Japan and by the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 53
TC 16
Z9 18
U1 2
U2 17
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 DEC
PY 2012
VL 86
IS 24
BP 13467
EP 13474
DI 10.1128/JVI.01896-12
PG 8
WC Virology
SC Virology
GA 040DC
UT WOS:000311299600029
PM 23035224
ER
PT J
AU Dang, Q
Whitted, S
Goeken, RM
Brenchley, JM
Matsuda, K
Brown, CR
Lafont, BAP
Starost, MF
Iyengar, R
Plishka, RJ
Buckler-White, A
Hirsch, VM
AF Dang, Que
Whitted, Sonya
Goeken, Robert M.
Brenchley, Jason M.
Matsuda, Kenta
Brown, Charles R.
Lafont, Bernard A. P.
Starost, Matthew F.
Iyengar, Ranjini
Plishka, Ronald J.
Buckler-White, Alicia
Hirsch, Vanessa M.
TI Development of Neurological Disease Is Associated with Increased Immune
Activation in Simian Immunodeficiency Virus-Infected Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CD8(+) T-CELLS; MICROBIAL TRANSLOCATION; HIV-1 INFECTION; CD4(+); AIDS;
ENCEPHALITIS; PATHOGENESIS; DEMENTIA; ABSENCE; COUNT
AB Simian immunodeficiency virus (SIV) infection of macaques can result in central nervous system disorders, such as meningitis and encephalitis. We studied 10 animals inoculated with brain-derived virus from animals with SIV encephalitis. Over half of the macaques developed SIV-induced neurologic disease. Elevated levels of systemic immune activation were observed to correlate with viral RNA in the cerebral spinal fluid but not with plasma viral load, consistent with a role for SIV in the pathogenesis of neurologic disease.
C1 [Dang, Que; Whitted, Sonya; Goeken, Robert M.; Brenchley, Jason M.; Matsuda, Kenta; Brown, Charles R.; Lafont, Bernard A. P.; Iyengar, Ranjini; Plishka, Ronald J.; Buckler-White, Alicia; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Starost, Matthew F.] NIAID, Div Vet Resources, NIH, Bethesda, MD 20892 USA.
RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM vhirsch@niaid.nih.gov
RI Lafont, Bernard/B-7236-2014
FU Intramural Research Program of NIAID, NIH; Division of Intramural
Research, NIAID, NIH
FX We thank Heather Cronise-Santis, Joanna Swerczek, and Richard Herbert of
the NIH Animal Center for expert animal care. This work was supported by
the Intramural Research Program of NIAID, NIH.; This research is
supported by the Division of Intramural Research, NIAID, NIH.
NR 14
TC 7
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
J9 J VIROL
JI J. Virol.
PD DEC
PY 2012
VL 86
IS 24
BP 13795
EP 13799
DI 10.1128/JVI.02174-12
PG 5
WC Virology
SC Virology
GA 040DC
UT WOS:000311299600064
PM 23035225
ER
PT J
AU Groseth, A
Matsuno, K
Dahlstrom, E
Anzick, SL
Porcella, SF
Ebihara, H
AF Groseth, Allison
Matsuno, Keita
Dahlstrom, Eric
Anzick, Sarah L.
Porcella, Stephen F.
Ebihara, Hideki
TI Complete Genome Sequencing of Four Geographically Diverse Strains of
Batai Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID REASSORTMENT; DISEASE
AB Batai virus (BATV) is a widely distributed but poorly studied member of the Orthobunyavirus genus in the family Bunyaviridae and is of particular interest as a known participant in natural reassortment events. Both research and surveillance efforts on this and other related viruses have been hampered by the lack of available full-length sequence data covering all three genomic segments. Here, we report the complete genome sequence of four BATV strains (MM2222, Chittoor/IG-20217, UgMP-6830, and MS50) isolated from various geographical locations. Based on these data, we have determined that strain MS50 is in fact unrelated to BATV and likely represents as a novel genotype in the genus Orthobunyavirus.
C1 [Groseth, Allison; Matsuno, Keita; Ebihara, Hideki] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Dahlstrom, Eric; Anzick, Sarah L.; Porcella, Stephen F.] NIAID, RML Genom Unit, Res Technol Branch, NIH, Hamilton, MT USA.
RP Ebihara, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
EM ebiharah@niaid.nih.gov
FU Intramural Research Program of the NIH
FX This work was supported by the Intramural Research Program of the NIH.
NR 6
TC 8
Z9 9
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD DEC
PY 2012
VL 86
IS 24
BP 13844
EP 13845
DI 10.1128/JVI.02641-12
PG 2
WC Virology
SC Virology
GA 040DC
UT WOS:000311299600089
PM 23166251
ER
PT J
AU Groseth, A
Weisend, C
Ebihara, H
AF Groseth, Allison
Weisend, Carla
Ebihara, Hideki
TI Complete Genome Sequencing of Mosquito and Human Isolates of Ngari Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HEMORRHAGIC-FEVER; REASSORTANT; BUNYAVIRUS; OUTBREAKS; AFRICA; BATAI
AB Ngari virus (NRIV) is a recently described, naturally occurring reassortant between two other orthobunyaviruses, Bunyamwera virus (BUNV) and Batai virus (BATV). Intriguingly, this reassortment was associated with the acquisition of heightened virulence, although the molecular basis for this is not understood. Here we report the first complete genome sequences of Ngari virus. We include five isolates from various geographical locations, as well as samples isolated from both mosquitos and human cases. Based on an analysis of these sequence data, NRIVs are clearly genetically distinct from all known BUNV and BATV strains but are very closely related to one another regardless of their source.
C1 [Groseth, Allison; Weisend, Carla; Ebihara, Hideki] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
RP Ebihara, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
EM ebiharah@niaid.nih.gov
FU Intramural Research Program of the NIH
FX This work was supported by the Intramural Research Program of the NIH.
NR 7
TC 4
Z9 4
U1 2
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD DEC
PY 2012
VL 86
IS 24
BP 13846
EP 13847
DI 10.1128/JVI.02644-12
PG 2
WC Virology
SC Virology
GA 040DC
UT WOS:000311299600090
PM 23166252
ER
PT J
AU Barzilai, N
Ferrucci, L
AF Barzilai, Nir
Ferrucci, Luigi
TI Insulin Resistance and Aging: A Cause or a Protective Response?
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Editorial Material
ID LIFE-SPAN; ENDOCRINE REGULATION; CALORIE RESTRICTION; RATS; MICE;
GLUCOSE; FAT
C1 [Barzilai, Nir] Albert Einstein Coll Med, Inst Aging Res, Bronx, NY 10461 USA.
[Barzilai, Nir] Albert Einstein Coll Med, Dept Med, Diabet Res & Training Ctr, Bronx, NY 10461 USA.
[Barzilai, Nir] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA.
[Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
RP Barzilai, N (reprint author), Albert Einstein Coll Med, Inst Aging Res, 1300 Morris Pk Ave,Belfer Bld 701, Bronx, NY 10461 USA.
EM Nir.Barzilai@einstein.yu.edu
FU Intramural NIH HHS; NIA NIH HHS [P01 AG 021654, P30AG038072, R01AG
618381]
NR 22
TC 19
Z9 19
U1 0
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD DEC
PY 2012
VL 67
IS 12
BP 1329
EP 1331
DI 10.1093/gerona/gls145
PG 3
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 040ES
UT WOS:000311305000009
PM 22859390
ER
PT J
AU Peron, EP
Zheng, Y
Perera, S
Newman, AB
Resnick, NM
Shorr, RI
Bauer, DC
Simonsick, EM
Gray, SL
Hanlon, JT
Ruby, CM
AF Peron, Emily P.
Zheng, Yan
Perera, Subashan
Newman, Anne B.
Resnick, Neil M.
Shorr, Ronald I.
Bauer, Douglas C.
Simonsick, Eleanor M.
Gray, Shelly L.
Hanlon, Joseph T.
Ruby, Christine M.
CA Hlth Aging Body Composition Hlth
TI Antihypertensive Drug Class Use and Differential Risk of Urinary
Incontinence in Community-Dwelling Older Women
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
ID BODY-COMPOSITION; MEDICATION USE; RANDOMIZED-TRIAL; ELDERLY-WOMEN;
HYPERTENSION; HEALTH; THERAPY; ADULTS; HYDRALAZINE; PREVENTION
AB Background. Medication use is a potentially reversible cause of urinary incontinence (UI). The objective of this longitudinal cohort study was to evaluate whether self-reported UI in community-dwelling older women is associated with the use of different classes of antihypertensive agents.
Methods. The sample consisted of 959 black and white women aged 7281 years without baseline (Year 1) UI from the Health, Aging, and Body Composition Study. Use of any antihypertensive from 10 drug classes (ie, alpha blockers [central], alpha blockers [peripheral], angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, beta blockers, calcium channel blockers, diuretics [loop], diuretics [potassium-sparing], diuretics [thiazide], and vasodilators) was determined during Year 3 in-person interviews. The number of unique antihypertensive agents used and the standardized daily dosage were also examined. Self-reported UI, operationally defined as leaking urine at least weekly during the previous 12 months, was assessed at Year 4 visits.
Results. A total of 197 women (20.5%) reported UI at Year 4. Although any antihypertensive use, number of agents used, and standardized daily dosage at Year 3 were not associated with UI at Year 4, use of one particular drug class-peripheral alpha blockers (ie, doxazosin, prazosin, and terazosin)-was associated with fourfold greater odds of UI (adjusted odds ratio = 4.47; 95% confidence interval = 1.79-11.21; p = .0014). Further, in post hoc analyses, these odds nearly doubled in those also taking loop diuretics (adjusted odds ratio = 8.81; 95% confidence interval = 1.78-43.53; p = .0076).
Conclusion. In community-dwelling older women, peripheral alpha blocker use was associated with UI, and the odds nearly doubled when used with loop diuretics.
C1 [Peron, Emily P.] Virginia Commonwealth Univ, Sch Pharm, Dept Pharmacotherapy & Outcomes Sci, Richmond, VA 23298 USA.
[Zheng, Yan; Perera, Subashan; Newman, Anne B.; Resnick, Neil M.; Hanlon, Joseph T.; Ruby, Christine M.] Univ Penn, Sch Med, Dept Geriatr Med, Philadelphia, PA 19104 USA.
[Newman, Anne B.; Hanlon, Joseph T.] Univ Penn, Grad Sch Publ Hlth, Dept Epidemiol, Philadelphia, PA 19104 USA.
[Shorr, Ronald I.] N Florida S Georgia Vet Affairs Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Gainesville, FL USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Sch Med, Dept Med Gen Internal Med, San Francisco, CA USA.
[Simonsick, Eleanor M.] Johns Hopkins Univ, Sch Med, Dept Geriatr Med, Baltimore, MD USA.
[Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Gray, Shelly L.] Univ Washington, Sch Pharm, Dept Pharm, Seattle, WA 98195 USA.
[Hanlon, Joseph T.] Pittsburgh Vet Affairs Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Hanlon, Joseph T.] Pittsburgh Vet Affairs Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
[Hanlon, Joseph T.; Ruby, Christine M.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15260 USA.
RP Peron, EP (reprint author), Virginia Commonwealth Univ, Sch Pharm, Dept Pharmacotherapy & Outcomes Sci, 410 N 12th St,POB 980533, Richmond, VA 23298 USA.
EM epperon@vcu.edu
RI Perera, Subashan/D-7603-2014; Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU Intramural Research Project of the National Institutes of Health;
National Institute on Aging (NIA) [N01-AG-62101, N01-AG-62103,
N01-AG-62106]; NIA [R01-AG-028050, P30-AG-024827, T32-AG-021885,
R01-AG-027017, K07-AG-033174, R56-AG-027017, R01-AG-034056]; NINR
[R01-NR-012459]; Agency for Healthcare Research and Quality
[R01-HS-017695, R01-HS-018721, K12-HS-019461]
FX This research was supported by the Intramural Research Project of the
National Institutes of Health; National Institute on Aging (NIA)
Contracts N01-AG-62101, N01-AG-62103, and N01-AG-62106; NIA grants
R01-AG-028050, P30-AG-024827, T32-AG-021885, R01-AG-027017,
K07-AG-033174, R56-AG-027017, and R01-AG-034056; NINR grant
R01-NR-012459; and Agency for Healthcare Research and Quality grants
(R01-HS-017695, R01-HS-018721, and K12-HS-019461).
NR 38
TC 8
Z9 8
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD DEC
PY 2012
VL 67
IS 12
BP 1373
EP 1378
DI 10.1093/gerona/gls177
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 040ES
UT WOS:000311305000016
PM 22972942
ER
PT J
AU Sanders, JL
Boudreau, RM
Penninx, BW
Simonsick, EM
Kritchevsky, SB
Satterfield, S
Harris, TB
Bauer, DC
Newman, AB
AF Sanders, Jason L.
Boudreau, Robert M.
Penninx, Brenda W.
Simonsick, Eleanor M.
Kritchevsky, Stephen B.
Satterfield, Suzanne
Harris, Tamara B.
Bauer, Douglas C.
Newman, Anne B.
CA Hlth ABC Study
TI Association of a Modified Physiologic Index With Mortality and Incident
Disability: The Health, Aging, and Body Composition Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Aging; Index; Mortality; Disability; Longevity
ID OLDER-ADULTS; CARDIOVASCULAR HEALTH; CYSTATIN-C; DEPRESSION; MARKERS;
DISEASE; RISK
AB Background. Indexes constructed from components may identify individuals who age well across systems. We studied the associations of a Modified Physiologic Index (systolic blood pressure, forced vital capacity, Digit Symbol Substitution Test score, serum cystatin-C, serum fasting glucose) with mortality and incident disability.
Methods. Data are from the Health, Aging, and Body Composition study on 2,737 persons (51.2% women, 40.3% black) aged 70-79 years at baseline and followed on average 9.3 (2.9) years. Components were graded 0 (healthiest), 1 (middle), or 2 (unhealthiest) by tertile or clinical cutpoints and summed to calculate a continuous index score (range 0-10). We used multivariate Cox proportional hazards regression to calculate risk of death or disability and determined accuracy predicting death using the area under the curve.
Results. Mortality was 19% greater per index unit (p < .05). Those with highest index scores (scores 7-10) had 3.53-fold greater mortality than those with lowest scores (scores 0-2). The unadjusted index (c-statistic = 0.656, 95% CI 0.636-0.677, p < .0001) predicted death better than age (c-statistic = 0.591, 95% CI 0.568-0.613, p < .0001; for comparison, p < .0001). The index attenuated the age association with mortality by 33%. A model including age and the index did not predict death better than the index alone (c-statistic = 0.671). Prediction was improved with the addition of other markers of health (c-statistic = 0.710, 95% CI 0.689-0.730). The index was associated with incident disability (adjusted hazard ratio per index unit = 1.04, 95% CI 1.01-1.07).
Conclusions. A simple index of available physiologic measurements was associated with mortality and incident disability and may prove useful for identifying persons who age well across systems.
C1 [Sanders, Jason L.; Boudreau, Robert M.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Sanders, Jason L.] Univ Pittsburgh, Sch Med, Med Scientist Training Program, Pittsburgh, PA 15213 USA.
[Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Simonsick, Eleanor M.] Johns Hopkins Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD USA.
[Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Wake Forest Univ Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Sanders, JL (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Bellefield Profess Bldg,4th Floor,130 N Belllefie, Pittsburgh, PA 15213 USA.
EM sanders.jason@medstudent.pitt.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187;
Kritchevsky, Stephen/0000-0003-3336-6781
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; NIA [R01-AG028050]; NINR [R01-NR012459]; NIH, National
Institute on Aging; National Research Service Award from the National
Institute on Aging [1F30-AG038093-01]
FX This research was supported by National Institute on Aging (NIA)
Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant
R01-AG028050, and NINR grant R01-NR012459. This research was supported
in part by the Intramural Research Program of the NIH, National
Institute on Aging. JLS is supported by a National Research Service
Award from the National Institute on Aging (1F30-AG038093-01).
NR 24
TC 7
Z9 7
U1 0
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD DEC
PY 2012
VL 67
IS 12
BP 1439
EP +
DI 10.1093/gerona/gls123
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 040ES
UT WOS:000311305000001
PM 22546961
ER
PT J
AU Karesh, WB
Dobson, A
Lloyd-Smith, JO
Lubroth, J
Dixon, MA
Bennett, M
Aldrich, S
Harrington, T
Formenty, P
Loh, EH
Machalaba, CC
Thomas, MJ
Heymann, DL
AF Karesh, William B.
Dobson, Andy
Lloyd-Smith, James O.
Lubroth, Juan
Dixon, Matthew A.
Bennett, Malcolm
Aldrich, Stephen
Harrington, Todd
Formenty, Pierre
Loh, Elizabeth H.
Machalaba, Catherine C.
Thomas, Mathew Jason
Heymann, David L.
TI Zoonoses 1 Ecology of zoonoses: natural and unnatural histories
SO LANCET
LA English
DT Article
ID EMERGING INFECTIOUS-DISEASES; ANTIBIOTIC-RESISTANCE; HUMAN HEALTH;
COMPETITIVE-EXCLUSION; ESCHERICHIA-COLI; GLOBAL TRENDS; EMERGENCE;
DYNAMICS; POPULATIONS; WILDLIFE
AB More than 60% of human infectious diseases are caused by pathogens shared with wild or domestic animals. Zoonotic disease organisms include those that are endemic in human populations or enzootic in animal populations with frequent cross-species transmission to people. Some of these diseases have only emerged recently. Together, these organisms are responsible for a substantial burden of disease, with endemic and enzootic zoonoses causing about a billion cases of illness in people and millions of deaths every year. Emerging zoonoses are a growing threat to global health and have caused hundreds of billions of US dollars of economic damage in the past 20 years. We aimed to review how zoonotic diseases result from natural pathogen ecology, and how other circumstances, such as animal production, extraction of natural resources, and antimicrobial application change the dynamics of disease exposure to human beings. In view of present anthropogenic trends, a more effective approach to zoonotic disease prevention and control will require a broad view of medicine that emphasises evidence-based decision making and integrates ecological and evolutionary principles of animal, human, and environmental factors. This broad view is essential for the successful development of policies and practices that reduce probability of future zoonotic emergence, targeted surveillance and strategic prevention, and engagement of partners outside the medical community to help improve health outcomes and reduce disease threats.
C1 [Karesh, William B.; Loh, Elizabeth H.; Machalaba, Catherine C.] EcoHlth Alliance, New York, NY 10001 USA.
[Karesh, William B.] IUCN Species Survival Commiss, Wildlife Hlth Specialist Grp, Gland, Switzerland.
[Karesh, William B.] World Org Anim Hlth Working Grp Wildlife Dis, Paris, France.
[Dobson, Andy] Princeton Univ, Princeton, NJ 08544 USA.
[Dobson, Andy] Santa Fe Inst, Santa Fe, NM 87501 USA.
[Lloyd-Smith, James O.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Lubroth, Juan] Food & Agr Org UN, Anim Hlth Serv, Rome, Italy.
[Dixon, Matthew A.; Heymann, David L.] Chatham House Ctr Global Hlth Secur, London, England.
[Bennett, Malcolm] Univ Liverpool, Inst Infect & Global Hlth, Sch Vet Sci, Leahurst, Neston, England.
[Aldrich, Stephen; Harrington, Todd] Bioecon Res Associates Bioera, Stockbridge, VT USA.
[Formenty, Pierre] WHO, Strategies Epidem & Emerging Dis Pandem & Epidem, CH-1211 Geneva, Switzerland.
[Thomas, Mathew Jason] US Dept HHS, Int Influenza Unit, Off Global Affairs, Washington, DC 20201 USA.
[Heymann, David L.] London Sch Hyg & Trop Med, London WC1, England.
RP Karesh, WB (reprint author), EcoHlth Alliance, 460 W 34th St, New York, NY 10001 USA.
EM karesh@ecohealthalliance.org
RI Lloyd-Smith, James/K-4080-2012
OI Lloyd-Smith, James/0000-0001-7941-502X
FU US Agency for International Development (USAID) Emerging Pandemic
Threats programme PREDICT; US National Science Foundation [EF-0928690];
De Logi Chair in Biological Sciences; Research and Policy for Infectious
Disease Dynamics programme of the Science and Technology Directorate;
Department of Homeland Security; Fogarty International Center, National
Institutes of Health
FX WBK, EL, and CM were funded by the US Agency for International
Development (USAID) Emerging Pandemic Threats programme PREDICT. Support
for economic assessments provided by SA and TH was provided by the
Public Health Agency of Canada and the Canadian Ministry of Health.
JOL-S is supported by US National Science Foundation grant EF-0928690,
the De Logi Chair in Biological Sciences, and the Research and Policy
for Infectious Disease Dynamics programme of the Science and Technology
Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health. We thank James
Newcomb, Robert Carlson, and Alex Thiermann for their input, and the
anonymous reviewers for their detailed critiques and valuable
suggestions. The contents are the responsibility of the authors and do
not necessarily reflect the views of the governments of the USA, UK, or
Canada.
NR 77
TC 114
Z9 117
U1 11
U2 146
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD DEC 1
PY 2012
VL 380
IS 9857
BP 1936
EP 1945
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 046IK
UT WOS:000311758500030
PM 23200502
ER
PT J
AU Tomei, S
Adams, S
Uccellini, L
Bedognetti, D
De Giorgi, V
Erdenebileg, N
Ascierto, ML
Reinboth, J
Liu, QZ
Bevilacqua, G
Wang, E
Mazzanti, C
Marincola, FM
AF Tomei, Sara
Adams, Sharon
Uccellini, Lorenzo
Bedognetti, Davide
De Giorgi, Valeria
Erdenebileg, Narnygerel
Ascierto, Maria Libera
Reinboth, Jennifer
Liu, Qiuzhen
Bevilacqua, Generoso
Wang, Ena
Mazzanti, Chiara
Marincola, Francesco M.
TI Association between HRAS rs12628 and rs112587690 polymorphisms with the
risk of melanoma in the North American population
SO MEDICAL ONCOLOGY
LA English
DT Article
DE HRAS; Polymorphism; Melanoma; rs12628; rs112587690
ID BREAST-CANCER; P21 PROTEIN; RAS-GENE; MUTATIONS; CELLS; GDP; GTP
AB HRAS belongs to the RAS genes superfamily. RAS genes are important players in several human tumors and the single-nucleotide polymorphism rs12628 has been shown to contribute to the risk of bladder, colon, gastrointestinal, oral, and thyroid carcinoma. We hypothesized that this SNP may affect the risk of cutaneous melanoma as well. HRAS gene contains a polymorphic region (rs112587690), a repeated hexanucleotide -GGGCCT- located in intron 1. Three alleles of this region, P1, P2, and P3, have been identified that contain two, three, and four repeats of the hexanucleotide, respectively. We investigated the clinical impact of these polymorphisms in a case-control study. A total of 141 melanoma patients and 118 healthy donors from the North America Caucasian population were screened for rs12628 and rs112587690 polymorphisms. Genotypes were assessed by capillary sequencing or fragment analysis, respectively, and rs12628 CC and rs112587690 P1P1 genotypes significantly associated with increased melanoma risk (OR = 3.83, p = 0.003; OR = 11.3, p = 0.033, respectively), while rs112587690 P1P3 frequency resulted significantly higher in the control group (OR = 0.5, p = 0.017). These results suggest that rs12628 C homozygosis may be considered a potential risk factor for melanoma development in the North American population possibly through the linkage to rs112587690.
C1 [Tomei, Sara; Uccellini, Lorenzo; Bedognetti, Davide; De Giorgi, Valeria; Erdenebileg, Narnygerel; Ascierto, Maria Libera; Reinboth, Jennifer; Liu, Qiuzhen; Wang, Ena; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Tomei, Sara; Uccellini, Lorenzo; Bedognetti, Davide; De Giorgi, Valeria; Erdenebileg, Narnygerel; Ascierto, Maria Libera; Reinboth, Jennifer; Liu, Qiuzhen; Wang, Ena; Marincola, Francesco M.] Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA.
[Tomei, Sara; Bevilacqua, Generoso; Mazzanti, Chiara] Univ Pisa, Sect Mol Pathol, Div Surg Mol & Ultrastruct Pathol, I-56100 Pisa, Italy.
[Tomei, Sara; Bevilacqua, Generoso; Mazzanti, Chiara] Pisa Univ Hosp, I-56100 Pisa, Italy.
[Adams, Sharon] NIH, HLA Lab, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Uccellini, Lorenzo] Univ Milan, L Sacco Hosp, Inst Infect & Trop Dis, Milan, Italy.
[Ascierto, Maria Libera] Univ Genoa, Ctr Excellence Biomed Res, Genoa, Italy.
[Ascierto, Maria Libera] Fdn G Pascale, Natl Canc Inst, Naples, Italy.
[Reinboth, Jennifer] Univ Wurzburg, Dept Biochem, Bioctr, Wurzburg, Germany.
[Reinboth, Jennifer] San Diego Sci Ctr, Genelux Corp, San Diego, CA USA.
RP Tomei, S (reprint author), NIH, IDIS, Dept Transfus Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM tomeis@mail.nih.gov
RI De Giorgi, Valeria/D-4582-2017;
OI Bedognetti, Davide/0000-0002-5857-773X
FU Intramural NIH HHS [Z01 CL002118-02]
NR 20
TC 4
Z9 4
U1 0
U2 4
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1357-0560
J9 MED ONCOL
JI Med. Oncol.
PD DEC
PY 2012
VL 29
IS 5
BP 3456
EP 3461
DI 10.1007/s12032-012-0255-3
PG 6
WC Oncology
SC Oncology
GA 043AE
UT WOS:000311513800065
PM 22618666
ER
PT J
AU Warolin, J
Carrico, AR
Whitaker, LE
Wang, L
Chen, KY
Acra, S
Buchowski, MS
AF Warolin, Joshua
Carrico, Amanda R.
Whitaker, Lauren E.
Wang, Li
Chen, Kong Y.
Acra, Sari
Buchowski, Maciej S.
TI Effect of BMI on Prediction of Accelerometry-Based Energy Expenditure in
Youth
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE ENERGY PREDICTION; ADIPOSITY; ACTICAL; ACTIGRAPH; RT3
ID PHYSICAL-ACTIVITY; ACTIVITY MONITORS; ADOLESCENT GIRLS; CHILDREN;
VALIDATION; CALIBRATION; RT3; ACTIGRAPH; VALIDITY; ADULTS
AB WAROLIN, J., A. R. CARRICO, L. E. WHITAKER, L. WANG, K. Y. CHEN, S. ACRA, and M. S. BUCHOWSKI. Effect of BMI on Prediction of Accelerometry-Based Energy Expenditure in Youth. Med. Sci. Sports Exerc., Vol. 44, No. 12, pp. 2428-2435, 2012. Purpose: The objective of this study is to determine the effect of body mass index (BMI) on level of agreement between six previously established prediction equations for three commonly used accelerometers to predict summary measures of energy expenditure (EE) in youth. Methods: One hundred and thirty-one youth between the ages of 10-17 yr and BMI from 15 to 44 kg.m(-2) were outfitted with hip-worn ActiGraph GT1M (Pensacola, FL), Actical (MiniMiter/Respironics, Bend, OR), and RT3 (StayHealthy, Monrovia, CA) accelerometers and spent approximately 24 h in a whole-room indirect calorimeter while performing structured and self-selected activities. Five commonly used regression and one propriety equations for each device were used to predict the minute-to-minute EE (normalized to METs), daily physical activity level (PAL), and time spent in sedentary, light, moderate, and vigorous physical activity intensity categories. The calculated values were compared with criterion measurements obtained from the room calorimeter. Results: All predictive equations, except RT3, significantly over-or underpredicted daily PAL (P < 0.001), with large discrepancies observed in the estimate of sedentary and light activity. Discrepancies between actual and estimated PAL ranged from 0.05 to 0.68. In addition, BMI represented a modifier for two ActiGraph predictive equations (AG1 and AG2), affecting the accuracy of physical activity-related EE predictions. Conclusion: ActiGraph (AG3) and the RT3 closely predicted overall PAL (within 4.2% and 6.8%, respectively) as a group. When adjusting for age, sex, and ethnicity, Actical (AC1 and AC2) and ActiGraph (AG3) were not influenced by BMI. However, a gap between some hip-worn accelerometer predictive and regression equations was demonstrated compared with both criterion measurement and each other, which poses a potential difficulty for interstudy (e.g., different accelerometers) and intrastudy (e.g., BMI and adiposity) comparisons.
C1 [Warolin, Joshua; Acra, Sari] Vanderbilt Univ, Div Gastroenterol, Dept Pediat, Med Ctr, Nashville, TN 37232 USA.
[Carrico, Amanda R.] Vanderbilt Univ, Climate Change Res Network, Vanderbilt Inst Energy & Environm, Nashville, TN 37232 USA.
[Whitaker, Lauren E.; Buchowski, Maciej S.] Vanderbilt Univ, Dept Med, Med Ctr, Div Gastroenterol, Nashville, TN 37232 USA.
[Wang, Li] Vanderbilt Univ, Dept Biostat, Med Ctr, Nashville, TN 37232 USA.
[Chen, Kong Y.] NIDDKD, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
RP Buchowski, MS (reprint author), Vanderbilt Univ, Div Gastroenterol Hepatol & Nutr, Dept Med, Med Ctr,Med Ctr N, 1161 21st Ave S,Room A4103, Nashville, TN 37232 USA.
EM maciej.buchowski@vanderbilt.edu
OI Chen, Kong/0000-0002-0306-1904; Buchowski, Maciej/0000-0002-0566-1743
FU National Institutes of Health [RO1HL082988, DK20593]; Vanderbilt CTSA
grant [UL1 RR024975]; Vanderbilt Diabetes Research and Training Center
FX This work was supported by grants from the National Institutes of
Health, RO1HL082988, Vanderbilt CTSA grant UL1 RR024975, and Vanderbilt
Diabetes Research and Training Center supported by the National
Institutes of Health grant DK20593.
NR 44
TC 1
Z9 1
U1 2
U2 10
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 DEC
PY 2012
VL 44
IS 12
BP 2428
EP 2435
DI 10.1249/MSS.0b013e318267b8f1
PG 8
WC Sport Sciences
SC Sport Sciences
GA 040GQ
UT WOS:000311310600022
PM 22776880
ER
PT J
AU Lin, PY
Mischoulon, D
Freeman, MP
Matsuoka, Y
Hibbeln, J
Belmaker, RH
Su, KP
AF Lin, P-Y
Mischoulon, D.
Freeman, M. P.
Matsuoka, Y.
Hibbeln, J.
Belmaker, R. H.
Su, K-P
TI Are omega-3 fatty acids antidepressants or just mood-improving agents?
The effect depends upon diagnosis, supplement preparation, and severity
of depression
SO MOLECULAR PSYCHIATRY
LA English
DT Letter
ID EICOSAPENTAENOIC ACID; DOUBLE-BLIND; METAANALYSIS; TRIALS; EPA
C1 [Lin, P-Y] Kaohsiung Chang Gung Mem Hosp, Dept Psychiat, Kaohsiung, Taiwan.
[Lin, P-Y] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan.
[Mischoulon, D.; Freeman, M. P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Mischoulon, D.; Freeman, M. P.] Harvard Univ, Sch Med, Boston, MA USA.
[Matsuoka, Y.] Natl Ctr Neurol & Psychiat, Dept Psychiat, Tokyo, Japan.
[Hibbeln, J.] NIAAA, NIH, Sect Nutr Neurosci, Bethesda, MD USA.
[Belmaker, R. H.] Ben Gurion Univ Negev, Dept Psychiat, IL-84105 Beer Sheva, Israel.
[Su, K-P] China Med Univ, Grad Inst Neural & Cognit Sci, Taichung, Taiwan.
[Su, K-P] China Med Univ Hosp, Dept Psychiat, Taichung, Taiwan.
RP Lin, PY (reprint author), Kaohsiung Chang Gung Mem Hosp, Dept Psychiat, Kaohsiung, Taiwan.
EM cobolsu@gmail.com
FU Intramural NIH HHS [ZIA AA000115-12]
NR 9
TC 41
Z9 41
U1 0
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD DEC
PY 2012
VL 17
IS 12
BP 1161
EP 1163
DI 10.1038/mp.2012.111
PG 3
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 041UB
UT WOS:000311425600007
PM 22824812
ER
PT J
AU Kapur, S
Phillips, AG
Insel, TR
AF Kapur, S.
Phillips, A. G.
Insel, T. R.
TI Why has it taken so long for biological psychiatry to develop clinical
tests and what to do about it?
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE clinical tests; diagnosis; stratified medicine; stratified psychiatry
ID BREAST-CANCER; SCHIZOPHRENIA; SCIENCE; CLASSIFICATION; METAANALYSIS;
DIMENSIONS; DEPRESSION; BIOMARKERS; DISORDERS; SPECTRUM
AB Patients with mental disorders show many biological abnormalities which distinguish them from normal volunteers; however, few of these have led to tests with clinical utility. Several reasons contribute to this delay: lack of a biological 'gold standard' definition of psychiatric illnesses; a profusion of statistically significant, but minimally differentiating, biological findings; approximate replications' of these findings in a way that neither confirms nor refutes them; and a focus on comparing prototypical patients to healthy controls which generates differentiations with limited clinical applicability. Overcoming these hurdles will require a new approach. Rather than seek biomedical tests that can 'diagnose' DSM-defined disorders, the field should focus on identifying biologically homogenous subtypes that cut across phenotypic diagnosis-thereby sidestepping the issue of a gold standard. To ensure clinical relevance and applicability, the field needs to focus on clinically meaningful differences between relevant clinical populations, rather than hypothesis-rejection versus normal controls. Validating these new biomarker-defined subtypes will require longitudinal studies with standardized measures which can be shared and compared across studies-thereby overcoming the problem of significance chasing and approximate replications. Such biological tests, and the subtypes they define, will provide a natural basis for a 'stratified psychiatry' that will improve clinical outcomes across conventional diagnostic boundaries.
C1 [Kapur, S.] Kings Coll London, Inst Psychiat, London SE5 8AF, England.
[Phillips, A. G.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada.
[Phillips, A. G.] CIHR Inst Neurosci Mental Hlth & Addict, Vancouver, BC, Canada.
[Insel, T. R.] NIMH, Bethesda, MD 20892 USA.
RP Kapur, S (reprint author), Kings Coll London, Inst Psychiat, London SE5 8AF, England.
EM shitij.kapur@kcl.ac.uk
OI Kapur, Shitij/0000-0002-2231-2924
FU GSK; MRC [G0701748/1]; Innovative Medicines Initiative (IMI) grant
NEWMEDS [N8 115008]; National Institute for Health Research (NIHR)
Mental Health Biomedical Research Centre at South London; Maudsley NHS
Foundation Trust; King's College London
FX SK has received grant support from GSK and has served as consultant
and/or speaker for AstraZeneca, Bioline, BMS-Otsuka, Eli Lilly, Janssen
(J&J), Lundbeck, NeuroSearch, Pfizer, Roche, Servier and Solvay Wyeth.
AGP serves on the Board of Allon Therapeutics Inc., and holds shares in
this corporation. TI has no financial interests to disclose.; We would
like to thank Dr Bruce Cuthbert for his useful comments on an earlier
version of this manuscript. SK's research related to the article is
supported by G0701748/1 from the MRC and the Innovative Medicines
Initiative (IMI) grant NEWMEDS, under Grant Agreement N8 115008. SK
received salary support from the National Institute for Health Research
(NIHR) Mental Health Biomedical Research Centre at South London and
Maudsley NHS Foundation Trust and King's College London.
NR 58
TC 251
Z9 252
U1 8
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD DEC
PY 2012
VL 17
IS 12
BP 1174
EP 1179
DI 10.1038/mp.2012.105
PG 6
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 041UB
UT WOS:000311425600010
PM 22869033
ER
PT J
AU Rapoport, JL
Giedd, JN
Gogtay, N
AF Rapoport, J. L.
Giedd, J. N.
Gogtay, N.
TI Neurodevelopmental model of schizophrenia: update 2012
SO MOLECULAR PSYCHIATRY
LA English
DT Review
DE CNV; genetics; imaging; neurodevelopment; schizophrenia; placenta
ID CHILDHOOD-ONSET SCHIZOPHRENIA; GRAPH-THEORETICAL ANALYSIS; PLURIPOTENT
STEM-CELLS; WHITE-MATTER; BRAIN-DEVELOPMENT; HIGH-RISK;
PSYCHIATRIC-DISORDERS; NONPSYCHOTIC SIBLINGS; PSYCHOTIC-DISORDERS;
PREFRONTAL CORTEX
AB The neurodevelopmental model of schizophrenia, which posits that the illness is the end state of abnormal neurodevelopmental processes that started years before the illness onset, is widely accepted, and has long been dominant for childhood-onset neuropsychiatric disorders. This selective review updates our 2005 review of recent studies that have impacted, or have the greatest potential to modify or extend, the neurodevelopmental model of schizophrenia. Longitudinal whole-population studies support a dimensional, rather than categorical, concept of psychosis. New studies suggest that placental pathology could be a key measure in future prenatal high-risk studies. Both common and rare genetic variants have proved surprisingly diagnostically nonspecific, and copy number variants (CNVs) associated with schizophrenia are often also associated with autism, epilepsy and intellectual deficiency. Large post-mortem gene expression studies and prospective developmental multi-modal brain imaging studies are providing critical data for future clinical and high-risk developmental brain studies. Whether there can be greater molecular specificity for phenotypic characterization is a subject of current intense study and debate, as is the possibility of neuronal phenotyping using human pluripotent-inducible stem cells. Biological nonspecificity, such as in timing or nature of early brain development, carries the possibility of new targets for broad preventive treatments. Molecular Psychiatry (2012) 17, 1228-1238; doi:10.1038/mp.2012.23; published online 10 April 2012
C1 [Rapoport, J. L.; Giedd, J. N.; Gogtay, N.] NIMH, NIH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Rapoport, JL (reprint author), NIMH, NIH, Child Psychiat Branch, 10 Ctr Dr,Rm 3N202-MSC 1600, Bethesda, MD 20892 USA.
EM rapoporj@mail.nih.gov
RI Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978
FU Intramural NIH HHS [Z99 MH999999]
NR 130
TC 186
Z9 189
U1 12
U2 113
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD DEC
PY 2012
VL 17
IS 12
BP 1228
EP 1238
DI 10.1038/mp.2012.23
PG 11
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 041UB
UT WOS:000311425600015
PM 22488257
ER
PT J
AU Junttila, IS
Creusot, RJ
Moraga, I
Bates, DL
Wong, MT
Alonso, MN
Suhoski, MM
Lupardus, P
Meier-Schellersheim, M
Engleman, EG
Utz, PJ
Fathman, CG
Paul, WE
Garcia, KC
AF Junttila, Ilkka S.
Creusot, Remi J.
Moraga, Ignacio
Bates, Darren L.
Wong, Michael T.
Alonso, Michael N.
Suhoski, Megan M.
Lupardus, Patrick
Meier-Schellersheim, Martin
Engleman, Edgar G.
Utz, Paul J.
Fathman, C. Garrison
Paul, William E.
Garcia, K. Christopher
TI Redirecting cell-type specific cytokine responses with engineered
interleukin-4 superkines
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID IL-4 RECEPTOR; NOD MICE; BINDING; EXPRESSION; COMPLEX; DIFFERENTIATION;
MECHANISMS; INTERFACE; SYSTEM; ALLOWS
AB Cytokines dimerize their receptors, with the binding of the 'second chain' triggering signaling. In the interleukin (IL)-4 and IL-13 system, different cell types express varying numbers of alternative second receptor chains (gamma c or IL-13R alpha 1), forming functionally distinct type I or type II complexes. We manipulated the affinity and specificity of second chain recruitment by human IL-4. A type I receptor-selective IL-4 'superkine' with 3,700-fold higher affinity for gamma c was three- to ten-fold more potent than wild-type IL-4. Conversely, a variant with high affinity for IL-13R alpha 1 more potently activated cells expressing the type II receptor and induced differentiation of dendritic cells from monocytes, implicating the type II receptor in this process. Superkines showed signaling advantages on cells with lower second chain numbers. Comparative transcriptional analysis reveals that the superkines induce largely redundant gene expression profiles. Variable second chain numbers can be exploited to redirect cytokines toward distinct cell subsets and elicit new actions, potentially improving the selectivity of cytokine therapy.
C1 [Moraga, Ignacio; Bates, Darren L.; Lupardus, Patrick; Garcia, K. Christopher] Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA.
[Junttila, Ilkka S.; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Junttila, Ilkka S.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Junttila, Ilkka S.] Fimlab Labs, Tampere, Finland.
[Creusot, Remi J.; Wong, Michael T.; Utz, Paul J.; Fathman, C. Garrison] Stanford Univ, Dept Med, Sch Med, Div Rheumatol & Immunol, Stanford, CA 94305 USA.
[Moraga, Ignacio; Bates, Darren L.; Lupardus, Patrick; Garcia, K. Christopher] Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA.
[Moraga, Ignacio; Bates, Darren L.; Lupardus, Patrick; Garcia, K. Christopher] Stanford Univ, Dept Biol Struct, Sch Med, Stanford, CA 94305 USA.
[Moraga, Ignacio; Bates, Darren L.; Lupardus, Patrick; Garcia, K. Christopher] Stanford Univ, Program Immunol, Sch Med, Stanford, CA 94305 USA.
[Alonso, Michael N.; Suhoski, Megan M.; Engleman, Edgar G.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Meier-Schellersheim, Martin] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Garcia, KC (reprint author), Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA.
EM kcgarcia@stanford.edu
FU US National Institute of Allergy and Infectious Diseases Division of
Intramural Research; Finnish Medical Foundation; Sigrid Juselius
Foundation; Howard Hughes Medical Institute; US National Institutes of
Health (NIH) [RO1-AI51321]; NIH [UO1-DK078123]; Stanford Immunology
Program Training Grant
FX The authors thank J. Gregorio and K. Weiskopf for assistance and the
Stanford Human Immune Monitoring Center. This work was supported by US
National Institute of Allergy and Infectious Diseases Division of
Intramural Research (I. S. J. and W. E. P.), the Finnish Medical
Foundation, the Sigrid Juselius Foundation (I. S. J.), the Howard Hughes
Medical Institute (K. C. G.), the US National Institutes of Health (NIH)
RO1-AI51321 (K. C. G.) and NIH UO1-DK078123 (C. G. F.) and the Stanford
Immunology Program Training Grant (D.L.B.).
NR 31
TC 23
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U1 1
U2 11
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 DEC
PY 2012
VL 8
IS 12
BP 990
EP 998
DI 10.1038/NCHEMBIO.1096
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 042SL
UT WOS:000311491200014
PM 23103943
ER
PT J
AU Lee, EQ
Kuhn, J
Lamborn, KR
Abrey, L
DeAngelis, LM
Lieberman, F
Robins, HI
Chang, SM
Yung, WKA
Drappatz, J
Mehta, MP
Levin, VA
Aldape, K
Dancey, JE
Wright, JJ
Prados, MD
Cloughesy, TF
Gilbert, MR
Wen, PY
AF Lee, Eudocia Q.
Kuhn, John
Lamborn, Kathleen R.
Abrey, Lauren
DeAngelis, Lisa M.
Lieberman, Frank
Robins, H. Ian
Chang, Susan M.
Yung, W. K. Alfred
Drappatz, Jan
Mehta, Minesh P.
Levin, Victor A.
Aldape, Kenneth
Dancey, Janet E.
Wright, John J.
Prados, Michael D.
Cloughesy, Timothy F.
Gilbert, Mark R.
Wen, Patrick Y.
TI Phase I/II study of sorafenib in combination with temsirolimus for
recurrent glioblastoma or gliosarcoma: North American Brain Tumor
Consortium study 05-02
SO NEURO-ONCOLOGY
LA English
DT Article
DE anaplastic glioma; glioblastoma; malignant glioma; sorafenib;
temsirolimus
ID ANTITUMOR-ACTIVITY; MALIGNANT GLIOMA; CCI-779; MULTIFORME; RAPAMYCIN;
TRIAL; RADIOTHERAPY; TEMOZOLOMIDE; CARCINOMA; AKT
AB The activity of single-agent targeted molecular therapies in glioblastoma has been limited to date. The North American Brain Tumor Consortium examined the safety, pharmacokinetics, and efficacy of combination therapy with sorafenib, a small molecule inhibitor of Raf, vascular endothelial growth factor receptor 2, and platelet-derived growth factor receptor, and temsirolimus (CCI-779), an inhibitor of mammalian target of rapamycin. This was a phase I/II study. The phase I component used a standard 3 3 dose escalation scheme to determine the safety and tolerability of this combination therapy. The phase II component used a 2-stage design; the primary endpoint was 6-month progression-free survival (PFS6) rate. Thirteen patients enrolled in the phase I component. The maximum tolerated dosage (MTD) for combination therapy was sorafenib 800 mg daily and temsirolimus 25 mg once weekly. At the MTD, grade 3 thrombocytopenia was the dose-limiting toxicity. Eighteen patients were treated in the phase II component. At interim analysis, the study was terminated and did not proceed to the second stage. No patients remained progression free at 6 months. Median PFS was 8 weeks. The toxicity of this combination therapy resulted in a maximum tolerated dose of temsirolimus that was only one-tenth of the single-agent dose. Minimal activity in recurrent glioblastoma multiforme was seen at the MTD of the 2 combined agents.
C1 [Lee, Eudocia Q.; Kuhn, John; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA.
[Kuhn, John] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA.
[Abrey, Lauren; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA.
[Drappatz, Jan] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
[Robins, H. Ian] Univ Wisconsin, Madison, WI USA.
Northwestern Univ, Chicago, IL 60611 USA.
[Yung, W. K. Alfred; Levin, Victor A.; Aldape, Kenneth; Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Dancey, Janet E.; Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Cloughesy, Timothy F.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA.
RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave,SW 430, Boston, MA 02215 USA.
EM pwen@partners.org
RI Gilbert, Mark/J-7494-2016;
OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713
FU NIH [U01 CA062399]; Astrazeneca; Pfizer; Amgen; Esai; Sanofi-Aventis;
Genentech; Genzyme; Novartis; Medimmune; Vascular Biogenics
FX This study was sponsored by NIH grant number U01 CA062399.; Kenneth
Aldape-Speaker: Merck; Grant funding: Astrazeneca. Lauren Abrey-now
employed by Roche. Janet Dancey-Research Support from Pfizer. Lisa
DeAngelis-Consultant: Genentech, Pharmacokinesis. Eudocia Q.
Lee-Consultant: Novartis, Genentech. Royalties: UpToDate, DEMOS
Publishers. Minesh Mehta-Consultant: Abbott, Bayer,
Bristol-Meyers-Squibb, Elekta, Merck, Novartis, Quark, Tomotherapy, US
Oncology, Vertex; Stock Options: Accuray, Colby, Pharmacyclics,
Procertus, Stemina; Data Safety Monitoring Boards: Apogenix Protocol
Data Review: Adnexus; Board of Directors: Pharmacyclics; Medical
Advisory Boards: Colby, Stemina, Procertus; Speaker: GRACE Foundation,
MCM, Medscape, Merck, priME Oncology, Strategic Edge, WebMD; Patents:
WARF/Procertus, Royalties: DEMOS Publishers. Patrick Wen-Consultant:
Novartis, Merck. Paid Speaker: Merck. Research Support: Amgen,
AstraZeneca, Esai, Sanofi-Aventis, Genentech, Genzyme, Novartis,
Medimmune, Vascular Biogenics, Royalties: UpToDate, DEMOS Publishers.
All remaining authors-no disclosures.
NR 28
TC 42
Z9 43
U1 2
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD DEC
PY 2012
VL 14
IS 12
BP 1511
EP 1518
DI 10.1093/neuonc/nos264
PG 8
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 040HP
UT WOS:000311313600011
PM 23099651
ER
PT J
AU Kreisl, TN
McNeill, KA
Sul, J
Iwamoto, FM
Shih, J
Fine, HA
AF Kreisl, Teri N.
McNeill, Katharine A.
Sul, Joohee
Iwamoto, Fabio M.
Shih, Joanna
Fine, Howard A.
TI A phase I/II trial of vandetanib for patients with recurrent malignant
glioma
SO NEURO-ONCOLOGY
LA English
DT Article
DE angiogenesis; EGFR; glioma; vandetanib; VEGFR
ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER;
BEVACIZUMAB PLUS IRINOTECAN; GLIOBLASTOMA-MULTIFORME; II TRIAL;
TUMOR-GROWTH; ERLOTINIB; ZD6474; TEMOZOLOMIDE
AB Vandetanib is a once-daily multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor2, epidermal growth factor receptor, and the rearranged-during-transfection oncogene. A phase I trial was conducted to describe the pharmacokinetics of vandetanib in patients with recurrent glioma on enzyme-inducing anti-epileptic drugs (EIAEDs) and to identify the maximum tolerated dose (MTD) in this population. A phase II trial evaluated the efficacy of vandetanib in patients with recurrent malignant glioma not on EIAEDs as measured by 6-month progression-free survival (PFS6). In the phase I trial, 15 patients were treated with vandetanib at doses of 300, 400, and 500 mg/day, in a standard dose-escalation design. The MTD in patients on EIAEDs was 400 mg/day, and steady-state levels were similar to those measured in patients not on EIAEDs. Dose-limiting toxicities were prolonged QTc and thromboembolism. Thirty-two patients with recurrent glioblastoma multiforme (GBM) and 32 patients with recurrent anaplastic gliomas (AGs) were treated in the phase II trial, at a dosage of 300 mg/day on 28-day cycles. Six patients (4 GBM, 2 AG) had radiographic response. PFS6 was 6.5 in the GBM arm and 7.0 in the AG arm. Median overall survival was 6.3 months in the GBM arm and 7.6 months in the AG arm. Seizures were an unexpected toxicity of therapy. Vandetanib did not have significant activity in unselected patients with recurrent malignant glioma.
C1 [Kreisl, Teri N.; McNeill, Katharine A.; Iwamoto, Fabio M.; Shih, Joanna; Fine, Howard A.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA.
[Sul, Joohee] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Kreisl, TN (reprint author), NCI, Neurooncol Branch, NIH, 9030 Old Georgetown Rd,Bloch Bldg 82,Room 225, Bethesda, MD 20892 USA.
EM kreislt@mail.nih.gov
FU National Cancer Institute (NCI) Intramural Research Program
FX This work was supported by the National Cancer Institute (NCI)
Intramural Research Program.
NR 35
TC 32
Z9 32
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD DEC
PY 2012
VL 14
IS 12
BP 1519
EP 1526
DI 10.1093/neuonc/nos265
PG 8
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 040HP
UT WOS:000311313600012
PM 23099652
ER
PT J
AU Thanos, PK
Subrize, M
Delis, F
Cooney, RN
Culnan, D
Sun, MJ
Wang, GJ
Volkow, ND
Hajnal, A
AF Thanos, Panayotis K.
Subrize, Mike
Delis, Foteini
Cooney, Robert N.
Culnan, Derek
Sun, Mingjie
Wang, Gene-Jack
Volkow, Nora D.
Hajnal, Andras
TI Gastric Bypass Increases Ethanol and Water Consumption in Diet-Induced
Obese Rats
SO OBESITY SURGERY
LA English
DT Article
DE Alcohol; Ethanol abuse; High-fat diet; Roux-en-Y; Bariatric; Gastric
bypass
ID BARIATRIC SURGERY; WEIGHT-LOSS; MATERNAL SEPARATION; DOPAMINE-RECEPTORS;
WISTAR RATS; FOLLOW-UP; GHRELIN; DEPRIVATION; PHASES; MODEL
AB Background Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment for morbid obesity. Increased alcohol abuse after RYGB resulted in recommendations to exclude patients with alcohol abuse histories from RYGB. The purpose of our study was to examine the effects of a RYGB on ethanol intake in diet-induced obese rats (high-fat diet).
Methods The animals underwent RYGB and were habituated along with their sham-operated obese controls and with lean rats to increasing concentrations of ethanol in a two-bottle choice paradigm.
Results RYGB rats' daily consumption of ethanol averaged 2 g/kg at 2 % habituation and 3.8 g/kg at 4 % habituation, twice as much as sham-operated obese controls and 50 % more than normal-diet lean controls. Obese controls drank on average 1 g/kg of ethanol (2 and 4 %), significantly less (50 %) than lean controls did. RYGB rats when given higher ethanol concentrations (6 and 8 %) or no ethanol drank significantly more water than lean and obese controls did (66 and 100 %, respectively), and their enhanced total fluid intake was associated with increased food intake, which was significantly higher than in lean (66 % more calories; food + alcohol) and obese controls (44 % more calories). The lower alcohol intake in the obese controls than in the lean rats suggests that obesity may interfere with alcohol's rewarding effects and RYGB may remove this protective effect.
Conclusions The overall enhancement of consummatory behaviors (both ethanol and water) suggests that RYGB may facilitate alcohol consumption, which in vulnerable individuals could lead to abuse and addiction.
C1 [Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, Lab Neuroimaging, Intramural Program, NIH, Bethesda, MD USA.
[Thanos, Panayotis K.; Subrize, Mike; Delis, Foteini; Wang, Gene-Jack] Brookhaven Natl Lab, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
[Sun, Mingjie; Hajnal, Andras] Penn State Univ, Dept Neural & Behav Sci, University Pk, PA 16802 USA.
[Cooney, Robert N.; Culnan, Derek; Sun, Mingjie; Hajnal, Andras] Penn State Univ, Dept Surg, University Pk, PA 16802 USA.
RP Thanos, PK (reprint author), NIAAA, Lab Neuroimaging, Intramural Program, NIH, Bethesda, MD USA.
EM thanos@bnl.gov
OI Hajnal, Andras/0000-0001-7297-7134
FU NIAAA [AA 11034, AA07574, AA07611, DK080899]; SULI program
FX This work was supported by the NIAAA (AA 11034 & AA07574, AA07611)
DK080899 (AH).; We thank the SULI program for partial support of Mike
Subrize.
NR 33
TC 23
Z9 23
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0960-8923
J9 OBES SURG
JI Obes. Surg.
PD DEC
PY 2012
VL 22
IS 12
BP 1884
EP 1892
DI 10.1007/s11695-012-0749-2
PG 9
WC Surgery
SC Surgery
GA 042YV
UT WOS:000311509800013
PM 22976430
ER
PT J
AU Karami, S
Lan, Q
Rothman, N
Stewart, PA
Lee, KM
Vermeulen, R
Moore, LE
AF Karami, Sara
Lan, Qing
Rothman, Nathaniel
Stewart, Patricia A.
Lee, Kyoung-Mu
Vermeulen, Roel
Moore, Lee E.
TI Occupational trichloroethylene exposure and kidney cancer risk: a
meta-analysis
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Review
ID RENAL-CELL CARCINOMA; AIRCRAFT MANUFACTURING WORKERS;
EXTENDED-FOLLOW-UP; EPIDEMIOLOGIC EVIDENCE; HYDROCARBON EXPOSURES;
AEROSPACE WORKERS; ORGANIC-SOLVENTS; PUBLICATION BIAS; MORTALITY; COHORT
AB Objectives Inconsistent epidemiological findings, debate over interpretation, and extrapolation of findings from animal studies to humans have produced uncertainty surrounding the carcinogenicity of trichloroethylene (TCE) exposure in occupational settings. We updated meta-analyses of published case-control and cohort studies exploring occupational TCE exposure and kidney cancer risk, incorporating new analytical results from three recently published cohort studies and a case-control study.
Methods PubMed MEDLINE was searched for studies published from 1950 to 2011 assessing occupational exposure to chlorinated solvents, degreasers or TCE. All cohort (N=15) and case-control (N=13) studies included in analyses were stratified by assessment of occupational exposure to TCE specifically and to any chlorinated solvent.
Results Significantly elevated summary estimates were observed for cohort studies (relative risk (RR) 1.26, 95% CI 1.02 to 1.56; p heterogeneity=0.65), case-control studies (OR 1.35, 95% CI 1.17 to 1.57; p heterogeneity=0.41), and cohort and case-control studies combined (RR 1.32, 95% CI 1.17 to 1.50, p heterogeneity=0.63) that specifically assessed TCE exposure after excluding outlier studies that contributed to heterogeneity. Non-significantly elevated summary estimates were generally observed for studies of workers exposed to chlorinated solvents but who were not assessed for TCE specifically.
Conclusions Regardless of study design, significant and stronger estimates were only observed in studies specifically assessing occupational exposure to TCE. Estimates were lower in studies assessing occupational exposure to chlorinated solvents. This updated meta-analysis supports an association between occupational TCE exposure and kidney cancer and provides evidence that exposure misclassification may weaken estimates assessing exposure to the broader class of chlorinated solvents.
C1 [Karami, Sara; Lan, Qing; Rothman, Nathaniel; Moore, Lee E.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
[Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA.
[Lee, Kyoung-Mu] Korea Natl Open Univ, Dept Environm Hlth, Seoul, South Korea.
[Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
RP Moore, LE (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 6120 Executive Blvd,EPS 8102, Rockville, MD 20852 USA.
EM moorele@mail.nih.gov
RI Vermeulen, Roel/F-8037-2011
OI Vermeulen, Roel/0000-0003-4082-8163
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute
FX This study was supported by the Intramural Research Program of the
National Institutes of Health and the National Cancer Institute.
NR 61
TC 17
Z9 18
U1 3
U2 26
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
EI 1470-7926
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD DEC
PY 2012
VL 69
IS 12
BP 858
EP 867
DI 10.1136/oemed-2012-100932
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 037LQ
UT WOS:000311106600002
PM 23000822
ER
PT J
AU Marsh, AA
Yu, HH
Pine, DS
Gorodetsky, EK
Goldman, D
Blair, RJR
AF Marsh, Abigail A.
Yu, Henry H.
Pine, Daniel S.
Gorodetsky, Elena K.
Goldman, David
Blair, R. J. R.
TI The influence of oxytocin administration on responses to infant faces
and potential moderation by OXTR genotype
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Oxytocin; OXTR; Parental; Faces; Affiliation
ID RECEPTOR GENE OXTR; MATERNAL-BEHAVIOR; AFFILIATIVE BEHAVIOR; SOCIAL
ATTACHMENT; HUMANS; EXPRESSION; BRAIN; RAT; VASOPRESSIN; REACTIVITY
AB Oxytocin is a neuropeptide that is associated with increases in social affiliative behaviors, particularly toward infants. However, no previous study has investigated healthy adults' responses to infant faces following oxytocin administration. In addition, given that preliminary evidence suggests that a single-nucleotide polymorphism of the oxytocin receptor (OXTR) gene, rs53576, may influence behaviors associated with parental sensitivity, we assessed whether such responses vary according to OXTR rs53576 genotype.
The present study assessed the effects of intranasally administered oxytocin and OXTR genotype on human adults' preferences for infant faces.
A double-blind, between-groups design was used, with 57 genotyped volunteers randomly assigned to receive intranasally administered oxytocin or placebo. Fifty minutes following the administration of oxytocin or placebo, participants viewed infants' and adults' faces showing neutral expressions and assessed how appealing they found each face.
Infants' faces were more strongly preferred following oxytocin inhalation relative to placebo. When participants were separated according to genotype, this effect was only observed for participants homozygous for the rs53576G allele. Parallel effects were not seen for adults' faces.
The present results are consistent with the hypothesis that acute oxytocin administration increases sensitivity to reward-relevant features of infants and/or reduces sensitivity to their aversive properties. The results are also consistent with suggestions of more efficient oxytocinergic function in rs53576G homozygotes.
C1 [Marsh, Abigail A.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA.
[Marsh, Abigail A.; Yu, Henry H.; Pine, Daniel S.; Blair, R. J. R.] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA.
[Gorodetsky, Elena K.; Goldman, David] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA.
RP Marsh, AA (reprint author), NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA.
EM aam72@georgetown.edu
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU Intramural Research Program of the NIH/NIMH
FX This research was supported by the Intramural Research Program of the
NIH/NIMH. The authors would like to thank Andy Speer, Samantha Crowe,
Nanette Schell, David Fink, Adriana Pavletic, and Judith Starling for
their assistance in conducting this research.
NR 54
TC 33
Z9 33
U1 0
U2 20
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD DEC
PY 2012
VL 224
IS 4
BP 469
EP 476
DI 10.1007/s00213-012-2775-0
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 042ZA
UT WOS:000311510300001
PM 22763666
ER
PT J
AU Theberge, FRM
Pickens, CL
Goldart, E
Fanous, S
Hope, BT
Liu, QR
Shaham, Y
AF Theberge, Florence R. M.
Pickens, Charles L.
Goldart, Evan
Fanous, Sanya
Hope, Bruce T.
Liu, Qing-Rong
Shaham, Yavin
TI Association of time-dependent changes in mu opioid receptor mRNA, but
not BDNF, TrkB, or MeCP2 mRNA and protein expression in the rat nucleus
accumbens with incubation of heroin craving
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE BDNF; Extinction; MeCP2; mu opioid receptor; Heroin self-administration;
Relapse; Withdrawal; Incubation of drug craving; Naloxone
ID MEDIAL PREFRONTAL CORTEX; MESOLIMBIC DOPAMINE SYSTEM; CONTEXT-INDUCED
REINSTATEMENT; VENTRAL TEGMENTAL AREA; GENE-EXPRESSION; COCAINE-SEEKING;
NEUROTROPHIC FACTOR; DRUG-SEEKING; INTRAVENOUS HEROIN; INDUCED RELAPSE
AB Responding to heroin cues progressively increases after cessation of heroin self-administration (incubation of heroin craving). We investigated whether this incubation is associated with time-dependent changes in brain-derived neurotrophic factor (BDNF) and methyl-CpG binding protein 2 (MeCP2) signaling and mu opioid receptor (MOR) expression in nucleus accumbens (NAc), dorsal striatum (DS), and medial prefrontal cortex (mPFC). We also investigated the effect of the preferential MOR antagonist naloxone on cue-induced heroin seeking during abstinence.
We trained rats to self-administer heroin or saline for 9-10 days and then dissected the NAc, DS, and mPFC at different abstinence days and measured mRNA and protein levels of BDNF, TrkB, and MeCP2, as well as MOR mRNA (Oprm1). In other groups, we assessed cue-induced heroin seeking in extinction tests after 1, 11, and 30 abstinence days, and naloxone's (0-1.0 mg/kg) effect on extinction responding after 1 and 15 days.
Cue-induced heroin seeking progressively increased or incubated during abstinence. This incubation was not associated with changes in BDNF, TrkB, or MeCP2 mRNA or protein levels in NAc, DS, or mPFC; additionally, no molecular changes were observed after extinction tests on day 11. In NAc, but not DS or mPFC, MOR mRNA decreased on abstinence day 1 and returned to basal levels over time. Naloxone significantly decreased cue-induced heroin seeking after 15 abstinence days but not 1 day.
Results suggest a role of MOR in incubation of heroin craving. As previous studies implicated NAc BDNF in incubation of cocaine craving, our data suggest that different mechanisms contribute to incubation of heroin versus cocaine craving.
C1 [Theberge, Florence R. M.; Pickens, Charles L.; Goldart, Evan; Fanous, Sanya; Hope, Bruce T.; Liu, Qing-Rong; Shaham, Yavin] NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA.
RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM Yshaham@intra.nida.nih.gov
RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014; Liu,
Qing-Rong/A-3059-2012
OI Hope, Bruce/0000-0001-5804-7061; Liu, Qing-Rong/0000-0001-8477-6452
FU National Institute on Drug Abuse's Intramural Research Program
FX Research was supported by the National Institute on Drug Abuse's
Intramural Research Program. We thank Xingyu Hou for helping with the
molecular assays and Brittany Navarre and Anna Stern for helping with
the intravenous surgeries. We also thank Dr. Anne E. West (Duke
University) for helpful comments on the molecular aspects of our work.
The authors declare that they do not have any conflicts of interest
(financial or otherwise) related to the data presented in this
manuscript.
NR 68
TC 19
Z9 20
U1 0
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD DEC
PY 2012
VL 224
IS 4
BP 559
EP 571
DI 10.1007/s00213-012-2784-z
PG 13
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 042ZA
UT WOS:000311510300009
PM 22790874
ER
PT J
AU Abd-Elmoniem, KZ
Gharib, AM
Pettigrew, RI
AF Abd-Elmoniem, Khaled Z.
Gharib, Ahmed M.
Pettigrew, Roderic I.
TI Coronary Vessel Wall 3-T MR Imaging with Time-resolved Acquisition of
Phase-Sensitive Dual Inversion-Recovery (TRAPD) Technique: Initial
Results in Patients with Risk Factors for Coronary Artery Disease
SO RADIOLOGY
LA English
DT Article
ID HEART-RATE-VARIABILITY; NAVIGATOR CORRECTION; MYOCARDIAL MOTION; CARDIAC
MOTION; ANGIOGRAPHY; TRACKING; ATHEROSCLEROSIS; IMPACT; RESOLUTION;
QUALITY
AB Purpose: To develop a technique for time-resolved acquisition of phase-sensitive dual-inversion recovery (TRAPD) coronary vessel wall magnetic resonance (MR) images, to investigate the success rate in coronary wall imaging compared with that of single-frame imaging, and to assess vessel wall thickness in healthy subjects and subjects with risk factors for coronary artery disease (CAD).
Materials and Methods: Thirty-eight subjects (12 healthy subjects, 26 subjects with at least one CAD risk factor) provided informed consent for participation in this institutional review board-approved and HIPAA-compliant study. The TRAPD coronary vessel wall imaging sequence was developed and validated with a flow phantom. Time-resolved coronary artery wall images at three to five cine phases were obtained in all subjects. Qualitative and quantitative comparisons were made between TRAPD and conventional single-image wall measurements. Measurement reproducibility also was assessed. Statistical analysis was performed for all comparisons.
Results: The TRAPD sequence successfully restored the negative polarity of lumen signal and enhanced lumen wall contrast on the cine images of the flow phantom and in all subjects. Use of three to five frames increased the success rate of acquiring at least one image of good to excellent quality from 76% in single-image acquisitions to 95% with the TRAPD sequence. The difference in vessel wall thickness between healthy subjects and subjects with CAD risk factors was significant (P < .05) with the TRAPD sequence (1.07 vs 1.46 mm, respectively; 36% increase) compared with single-frame dual inversion-recovery imaging (1.24 vs 1.55 mm, respectively; 25% increase). Intraobserver, interobserver, and interexamination agreement for wall thickness measurement were 0.98, 0.97, and 0.92, respectively.
Conclusion: TRAPD imaging of coronary arteries improved arterial wall visualization and quantitative assessment by increasing the success rate of obtaining good-to excellent-quality images and sections orthogonal to the longitudinal axis of the vessel. This also resulted in vessel wall thickness measurements that show a more distinct difference between healthy subjects and those with CAD risk factors. (C) RSNA, 2012
C1 [Abd-Elmoniem, Khaled Z.; Gharib, Ahmed M.; Pettigrew, Roderic I.] NIDDKD, Biomed & Metab Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Pettigrew, Roderic I.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
RP Abd-Elmoniem, KZ (reprint author), NIDDKD, Biomed & Metab Imaging Branch, NIH, 10 Ctr Dr,Bldg 10,Room 3-5340, Bethesda, MD 20892 USA.
EM abdelmoniemkz@mail.nih.gov
RI Gharib, Ahmed/O-2629-2016; Abd-Elmoniem, Khaled/B-9289-2008
OI Gharib, Ahmed/0000-0002-2476-481X; Abd-Elmoniem,
Khaled/0000-0002-1001-1702
NR 34
TC 6
Z9 7
U1 0
U2 1
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD DEC
PY 2012
VL 265
IS 3
BP 715
EP 723
DI 10.1148/radiol.12120068
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 041SA
UT WOS:000311420300008
PM 23047838
ER
PT J
AU Sibley, CT
Noureldin, RA
Gai, N
Nacif, MS
Liu, ST
Turkbey, EB
Mudd, JO
van der Geest, RJ
Lima, JAC
Halushka, MK
Bluemke, DA
AF Sibley, Christopher T.
Noureldin, Radwa A.
Gai, Neville
Nacif, Marcelo Souto
Liu, Songtao
Turkbey, Evrim B.
Mudd, James O.
van der Geest, Rob J.
Lima, Joao A. C.
Halushka, Marc K.
Bluemke, David A.
TI T1 Mapping in Cardiomyopathy at Cardiac MR: Comparison with
Endomyocardial Biopsy
SO RADIOLOGY
LA English
DT Article
ID CARDIOVASCULAR MAGNETIC-RESONANCE; DIFFUSE MYOCARDIAL FIBROSIS;
HYPERTROPHIC CARDIOMYOPATHY; LOOK-LOCKER; HEART-FAILURE; ISCHEMIC
CARDIOMYOPATHY; DILATED CARDIOMYOPATHY; INTERSTITIAL FIBROSIS;
INFARCTION; ENHANCEMENT
AB Purpose: To determine the utility of cardiac magnetic resonance (MR) T1 mapping for quantification of diffuse myocardial fibrosis compared with the standard of endomyocardial biopsy.
Materials and Methods: This HIPAA-compliant study was approved by the institutional review board. Cardiomyopathy patients were retrospectively identified who had undergone endomyocardial biopsy and cardiac MR at one institution during a 5-year period. Forty-seven patients (53% male; mean age, 46.8 years) had undergone diagnostic cardiac MR and endomyocardial biopsy. Thirteen healthy volunteers (54% male; mean age, 38.1 years) underwent cardiac MR as a reference. Myocardial T1 mapping was performed 10.7 minutes +/- 2.7 (standard deviation) after bolus injection of 0.2 mmol/kg gadolinium chelate by using an inversion-recovery Look-Locker sequence on a 1.5-T MR imager. Late gadolinium enhancement was assessed by using gradient-echo inversion-recovery sequences. Cardiac MR results were the consensus of two radiologists who were blinded to histopathologic findings. Endomyocardial biopsy fibrosis was quantitatively measured by using automated image analysis software with digital images of specimens stained with Masson trichrome. Histopathologic findings were reported by two pathologists blinded to cardiac MR findings. Statistical analyses included Mann-Whitney U test, analysis of variance, and linear regression.
Results: Median myocardial fibrosis was 8.5% (interquartile range, 5.7-14.4). T1 times were greater in control subjects than in patients without and in patients with evident late gadolinium enhancement (466 msec +/- 14, 406 msec +/- 59, and 303 msec +/- 53, respectively; P < .001). T1 time and histologic fibrosis were inversely correlated (r = -0.57; 95% confidence interval: -0.74, -0.34; P < .0001). The area under the curve for myocardial T1 time to detect fibrosis of greater than 5% was 0.84 at a cutoff of 383 msec.
Conclusion: Cardiac MR with T1 mapping can provide noninvasive evidence of diffuse myocardial fibrosis in patients referred for evaluation of cardiomyopathy. (C) RSNA, 2012
C1 [Sibley, Christopher T.; Noureldin, Radwa A.; Gai, Neville; Nacif, Marcelo Souto; Liu, Songtao; Turkbey, Evrim B.; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Dept Radiol & Imaging Sci, Ctr Clin, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Nacif, Marcelo Souto; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[Halushka, Marc K.] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Cardiovasc Pathol, Baltimore, MD 21205 USA.
[Mudd, James O.] Oregon Hlth & Sci Univ, Dept Med, Div Cardiol, Portland, OR 97201 USA.
[van der Geest, Rob J.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
RP Bluemke, DA (reprint author), Natl Inst Biomed Imaging & Bioengn, Dept Radiol & Imaging Sci, Ctr Clin, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,Bldg 10,MSC 1182, Bethesda, MD 20892 USA.
EM bluemked@nih.gov
RI Sibley, Christopher/C-9900-2013; van der Geest, Rob/J-8193-2015;
OI van der Geest, Rob/0000-0002-9084-5597; Halushka,
Marc/0000-0002-7112-7389; Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health Intramural Research Program; National
Institutes of Health Clinical Center
FX This research was supported by the National Institutes of Health
Intramural Research Program.; We gratefully acknowledge the
contributions of Charles Steenbergen, MD, PhD, for his expertise in
cardiovascular pathology. This study was wholly funded by the intramural
research program of the National Institutes of Health Clinical Center.
NR 35
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U2 11
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD DEC
PY 2012
VL 265
IS 3
BP 724
EP 732
DI 10.1148/radiol.12112721
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 041SA
UT WOS:000311420300009
PM 23091172
ER
PT J
AU Sati, P
George, IC
Shea, CD
Gaitan, MI
Reich, DS
AF Sati, Pascal
George, Ilena C.
Shea, Colin D.
Gaitan, Maria I.
Reich, Daniel S.
TI FLAIR(star): A Combined MR Contrast Technique for Visualizing White
Matter Lesions and Parenchymal Veins
SO RADIOLOGY
LA English
DT Article
ID MULTIPLE-SCLEROSIS; MS LESIONS; IN-VIVO; VENOGRAPHY; IRON
AB Purpose: To evaluate a magnetic resonance (MR) imaging contrast technique, called FLAIR(star), that combines the advantages of T2-weighted fluid-attenuated inversion recovery (FLAIR) contrast and T2(star)-weighted contrast on a single image for assessment of white matter (WM) diseases such as multiple sclerosis (MS).
Materials and Methods: This prospective pilot study was HIPAA compliant and institutional review board approved. Ten patients with clinically definite MS (eight men, two women; mean age, 41 years) provided informed consent and underwent 3.0-T MR imaging. Images from a T2-weighted FLAIR sequence were combined with images from a T2(star)-weighted segmented echo-planar imaging sequence performed during contrast material injection, yielding high-isotropic-resolution (0.55 x 0.55 x 0.55 mm(3)) FLAIR(star) images. Qualitative assessment was performed for image quality, lesion conspicuity, and vein conspicuity. Contrast-to-noise ratio (CNR) was calculated to compare normal-appearing WM (NAWM) with cerebrospinal fluid, lesions, and veins. To evaluate the differences in CNR among imaging modalities, a bootstrap procedure clustered on subjects was used, together with paired t tests.
Results: High-quality FLAIR(star) images of the brain were produced at 3.0 T, yielding conspicuous lesions and veins. Lesion-to-NAWM and NAWM-to-vein CNR values were significantly higher for FLAIR(star) images than for T2-weighted FLAIR images (P < .0001). Findings on FLAIR(star) images included intralesional veins for lesions located throughout the brain and a hypointense rim around some WM lesions.
Conclusion: High-isotropic-resolution FLAIR(star) images obtained at 3.0 T yield high contrast for WM lesions and parenchymal veins, making it well suited to investigate the relationship between WM abnormalities and veins in a clinical setting. (C) RSNA, 2012
C1 [Sati, Pascal; George, Ilena C.; Shea, Colin D.; Gaitan, Maria I.; Reich, Daniel S.] Natl Inst Neurol Disorders & Stroke, Translat Neuroradiol Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Reich, Daniel S.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
RP Sati, P (reprint author), Natl Inst Neurol Disorders & Stroke, Translat Neuroradiol Unit, Neuroimmunol Branch, NIH, 9000 Rockville Pike,Bldg 10-5C205, Bethesda, MD 20892 USA.
EM satip@ninds.nih.gov
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke; NIH Clinical Center
FX The authors acknowledge the Intramural Research Program of the National
Institute of Neurological Disorders and Stroke and the NIH Clinical
Center for support. The authors thank Dr John Butman and Dr David
Thomasson for insightful discussions, Roger Stone and the NIH Clinical
Center Radiology technologists for their work in acquiring the data, the
Neuroimmunology Branch clinical group for coordinating recruitment and
evaluation of patients, Dr John Ostuni from the NINDS image processing
facility, and Dr Joseph Frank for access to a research imager for
initial development of the technique. Finally, the authors thank Dr
Tianxia Wu and Elizabeth Sweeney for their help and advice with the
statistical methods.
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PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD DEC
PY 2012
VL 265
IS 3
BP 926
EP 932
DI 10.1148/radiol.12120208
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 041SA
UT WOS:000311420300031
PM 23074257
ER
PT J
AU Ishkaraeva-Yakovleva, VV
Fedorova, OV
Solodovnikova, NG
Frolova, EV
Bzhelyansky, AM
Emelyanov, IV
Adair, CD
Zazerskaya, IE
Bagrov, AY
AF Ishkaraeva-Yakovleva, Valentina V.
Fedorova, Olga V.
Solodovnikova, Nelly G.
Frolova, Elena V.
Bzhelyansky, Anton M.
Emelyanov, Igor V.
Adair, C. David
Zazerskaya, Irina E.
Bagrov, Alexei Y.
TI DigiFab Interacts With Endogenous Cardiotonic Steroids and Reverses
Preeclampsia-Induced Na/K-ATPase Inhibition
SO REPRODUCTIVE SCIENCES
LA English
DT Article
DE preeclampsia; cardiotonic steroids; Na/K-ATPase; immunotherapy;
monoclonal antibody; digibind; DigiFab; marinobufagenin
ID LOWERS BLOOD-PRESSURE; IMMUNOREACTIVE SUBSTANCE; PREGNANT RATS;
ANTIBODY; MARINOBUFAGENIN; IMMUNOGLOBULIN; DIGITALIS; ECLAMPSIA
AB Elevated levels of endogenous Na/K-ATPase (NKA) inhibitors, cardiotonic steroids (CTSs) including marinobufagenin (MBG), contribute to pathogenesis of preeclampsia (PE) and represent a target for immunoneutralization by Digibind (Ovine Digoxin Immune Antibody, Glaxo-Smith Kline). Because Digibind is no longer commercially available, we studied whether DigiFab (BTG International Ltd, UK) can substitute Digibind for immunoneutralization of CTS in patients with PE. We compared DigiFab, Digibind, and anti-MBG monoclonal antibody (mAb) with respect to their ability to interact with CTS in PE plasma and to restore NKA activity in erythrocytes from patients with PE. Using immunoassays based on DigiFab, Digibind, and anti-MBG mAb, we studied the elution profile of CTS following high-performance liquid chromatography (HPLC) fractionation of PE plasma. Totally, 7 patients with mild PE (28 +/- 2 years; gestational age, 39 +/- 0.5 weeks; blood pressure 156 +/- 5/94 +/- 2 mm Hg) and 6 normotensive pregnant participants (28 +/- 1 years; gestational age, 39 +/- 0.4 weeks; blood pressure 111 +/- 2/73 +/- 2 mm Hg) were enrolled. Preeclampsia was associated with a substantial inhibition of erythrocyte NKA (1.47 +/- 0.17 vs 2.65 +/- 0.16 mu mol Pi/mL per h in control group, P < .001). Ex vivo, at 10 mu g/mL concentration, which is consistent with the clinical dosing of Digibind administered previously in PE, DigiFab and Digibind as well as anti-MBG mAb (0.5 mu g/mL) restored erythrocyte NKA activity. Following HPLC fractionation of pooled PE and control plasma, PE-associated increase in CTS material was detected by Digibind (176 vs 75 pmoles), DigiFab (221 vs 70 pmoles), and anti-MBG mAb (1056 vs 421 pmoles). Therefore, because DigiFab interacts with CTS from PE plasma and reverses PE-induced NKA inhibition, it can substitute Digibind for immunoneutralization of CTS in patients with PE.
C1 [Fedorova, Olga V.; Bzhelyansky, Anton M.; Bagrov, Alexei Y.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Ishkaraeva-Yakovleva, Valentina V.; Solodovnikova, Nelly G.; Emelyanov, Igor V.; Zazerskaya, Irina E.] Almazov Heart Blood & Endocrinol Ctr, Inst Neonatol & Heart & Vessels, Lab Reprod & Womens Hlth, St Petersburg, Russia.
[Frolova, Elena V.] IM Sechenov Evolutionary Physiol & Biochem Inst, Pharmacol Lab, St Petersburg 194223, Russia.
[Adair, C. David] Univ Tennessee, Dept Obstet & Gynecol, Chattanooga, TN USA.
RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM BagrovA@mail.nih.gov
RI Bzhelyansky, Anton/J-8302-2014
OI Bzhelyansky, Anton/0000-0001-6184-9284
FU Intramural Research Program, National Institute on Aging, National
Institutes of Health; Ministry of Science and Education of Russian
Federation [14.740.11.0928]; Glenveigh Pharmaceuticals, Chattanooga,
Tennessee
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: Intramural
Research Program, National Institute on Aging, National Institutes of
Health (OVF and AYB), by a grant from Ministry of Science and Education
of Russian Federation Nr. 14.740.11.0928, and by Glenveigh
Pharmaceuticals (CDA), Chattanooga, Tennessee.
NR 30
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U1 2
U2 10
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD DEC
PY 2012
VL 19
IS 12
BP 1260
EP 1267
DI 10.1177/1933719112447124
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 033KV
UT WOS:000310795900003
PM 22649120
ER
PT J
AU Ding, D
Scott, NM
Thompson, EE
Chaiworapongsa, T
Torres, R
Billstrand, C
Murray, K
Dexheimer, PJ
Ismail, M
Kay, H
Levy, S
Romero, R
Lindheimer, MD
Nicolae, DL
Ober, C
AF Ding, David
Scott, Nicole M.
Thompson, Emma E.
Chaiworapongsa, Tinnakorn
Torres, Raul
Billstrand, Christine
Murray, Kathleen
Dexheimer, Phillip J.
Ismail, Mahmoud
Kay, Helen
Levy, Shawn
Romero, Roberto
Lindheimer, Marshall D.
Nicolae, Dan L.
Ober, Carole
TI Increased Protein-Coding Mutations in the Mitochondrial Genome of
African American Women With Preeclampsia
SO REPRODUCTIVE SCIENCES
LA English
DT Article
DE preeclampsia; mtDNA; African American women; oxidative phosphorylation
ID OXIDATIVE STRESS; HUMAN-EVOLUTION; PLACENTAL MITOCHONDRIA; SOLUBLE
ENDOGLIN; UNITED-STATES; GROWTH-FACTOR; DNA VARIATION; MTDNA GENOME;
COMMON-CAUSE; PREGNANCY
AB Preeclampsia occurs more frequently in women of African ancestry. The cause of this hypertensive complication is unclear, but placental oxidative stress may play a role. Because mitochondria are the major sites of oxidative phosphorylation, we hypothesized that placentas of preeclamptic pregnancies harbor mitochondrial DNA (mtDNA) mutations. Next-generation sequencing of placental mtDNA in African American preeclamptics (N = 30) and controls (N = 38) from Chicago revealed significant excesses in preeclamptics of nonsynonymous substitutions in protein-coding genes and mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 5 gene and an increase in the substitution rate (P = .0001). Moreover, 88% of preeclamptics and 53% of controls carried at least one nonsynonymous substitution (P = .005; odds ratio [OR] = 6.36, 95% confidence interval [CI]: 1.5-39.1). These results were not replicated in a sample of African American preeclamptics (N = 162) and controls (N = 171) from Detroit. Differences in study design and heterogeneity may account for this lack of replication. Nonsynonymous substitutions in mtDNA may be risk factors for preeclampsia in some African American women, but additional studies are required to establish this relationship.
C1 [Ding, David; Ismail, Mahmoud; Kay, Helen; Lindheimer, Marshall D.; Ober, Carole] Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA.
[Scott, Nicole M.; Thompson, Emma E.; Torres, Raul; Billstrand, Christine; Murray, Kathleen; Nicolae, Dan L.; Ober, Carole] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Dexheimer, Phillip J.; Levy, Shawn] HudsonAlpha Inst Biotechnol, Huntsville, AL USA.
[Chaiworapongsa, Tinnakorn; Romero, Roberto] NICHD, Perinatal Res Branch, NIH, DHHS, Bethesda, MD USA.
[Chaiworapongsa, Tinnakorn; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Lindheimer, Marshall D.; Nicolae, Dan L.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Nicolae, Dan L.] Univ Chicago, Dept Stat, Chicago, IL 60637 USA.
RP Scott, NM (reprint author), Univ Chicago, Dept Obstet & Gynecol, 920 E 58th St,CLSC 425, Chicago, IL 60637 USA.
EM nicolescott1@gmail.com
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS; Preeclampsia Foundation; Stanley W. Marion
Family's Maternal-Fetal Medicine Fellow Research Grant; National
Institutes of Health [R01 HD21244, P01 HD49480, UL1 RR024999]; Institute
Translational Medicine at the University of Chicago
FX We acknowledge the Chicago Lying-In Women's Board and the Departments of
OB/GYN and Pediatrics for supporting the CLIPP Biobank, and the
University of Chicago Institute of Medicine CTSA for core services. This
research was supported, in part, by the Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.; The
author(s) disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: Preeclampsia
Foundation Vision Grant and Stanley W. Marion Family's Maternal-Fetal
Medicine Fellow Research Grant to DD, National Institutes of Health
grants R01 HD21244 and P01 HD49480 to CO, and UL1 RR024999 to the
Institute Translational Medicine at the University of Chicago.
NR 54
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U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD DEC
PY 2012
VL 19
IS 12
BP 1343
EP 1351
DI 10.1177/1933719112450337
PG 9
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 033KV
UT WOS:000310795900012
PM 22902742
ER
PT J
AU Racovan, M
Walitt, B
Collins, CE
Pettinger, M
Parks, CG
Shikany, JM
Wactawski-Wende, J
Manson, JE
Moreland, L
Wright, N
Jackson, R
Howard, BV
AF Racovan, Marius
Walitt, Brian
Collins, Christopher E.
Pettinger, Mary
Parks, Christine G.
Shikany, James M.
Wactawski-Wende, Jean
Manson, JoAnn E.
Moreland, Larry
Wright, Nicole
Jackson, Rebecca
Howard, Barbara V.
TI Calcium and vitamin D supplementation and incident rheumatoid arthritis:
the Women's Health Initiative Calcium plus Vitamin D trial
SO RHEUMATOLOGY INTERNATIONAL
LA English
DT Article
DE Calcium; Vitamin D; Clinical trial; Rheumatoid arthritis; Postmenopause
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; RISK; CANCER; COHORT
AB To determine whether calcium plus vitamin D supplementation (CaD) affects incidence of rheumatoid arthritis (RA). Participants enrolled in the Women's Health Initiative CaD trial (n = 36,282) were randomized to 1,000 mg calcium carbonate plus 400 IU of vitamin D-3 daily or to placebo. Incident RA cases were identified via self-report and validated rheumatic medication use. Cox proportional hazards models were used to compare RA incidence in the treatment versus placebo groups. The analysis included 32,435 women without the history of RA, of which 163 incident RA cases were identified over an average of 5.1 years. No significant differences in demographics, total personal vitamin D intake [P = 0.36], or solar irradiance [P = 0.68] were seen between the groups. In intention-to-treat analyses, no differences were observed in RA incidence [HR 1.04, 95% CI 0.76, 1.41]. No significant modifying effects were seen for stratum of age, solar irradiance, or total vitamin D intake, overall or when adjusted for adherence. Significant effect modifications were seen between CaD and total vitamin D intake and CaD and solar irradiance that suggest increased RA incidence with high vitamin D exposure. CaD supplementation did not demonstrate a significant effect on RA incidence in postmenopausal women. Modifying effects between CaD and both solar irradiance and dietary vitamin D intake are suggestive that multiple high vitamin D exposures may increase RA incidence. Further research is needed to fully explore the benefits and possible adverse effects of vitamin D supplementation on RA.
C1 [Racovan, Marius; Walitt, Brian; Collins, Christopher E.] Washington Hosp Ctr, Washington, DC 20010 USA.
[Pettinger, Mary] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Parks, Christine G.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Shikany, James M.] Univ Alabama Birmingham, Birmingham, AL USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Buffalo, NY 14260 USA.
[Manson, JoAnn E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Moreland, Larry] Univ Pittsburgh, Pittsburgh, PA USA.
[Wright, Nicole] Univ Arizona, Tucson, AZ USA.
[Jackson, Rebecca] Ohio State Univ, Columbus, OH 43210 USA.
[Howard, Barbara V.] MedStar Hlth Res Inst, Hyattsville, MD USA.
RP Walitt, B (reprint author), Washington Hosp Ctr, 110 Irving St, Washington, DC 20010 USA.
EM Brian.t.walitt@medstar.net
OI Parks, Christine/0000-0002-5734-3456
NR 32
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U1 0
U2 9
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0172-8172
J9 RHEUMATOL INT
JI Rheumatol. Int.
PD DEC
PY 2012
VL 32
IS 12
BP 3823
EP 3830
DI 10.1007/s00296-011-2268-1
PG 8
WC Rheumatology
SC Rheumatology
GA 043AS
UT WOS:000311515600017
PM 22190273
ER
PT J
AU Knowles, EEM
Weiser, M
David, AS
Dickinson, D
Glahn, D
Gold, J
Davidson, M
Reichenberg, A
AF Knowles, Emma E. M.
Weiser, Mark
David, Anthony S.
Dickinson, Dwight
Glahn, David
Gold, James
Davidson, Michael
Reichenberg, Abraham
TI Dedifferentiation and substitute strategy: Deconstructing the
processing-speed impairment in schizophrenia
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; Cognition; Processing speed; Dedifferentiation;
Confirmatory factor modelling
ID VERBAL FLUENCY; DIGIT SYMBOL; PREFRONTAL CORTEX; HEALTHY CONTROLS;
MEMORY; TRAIL; PERFORMANCE; DEFICITS; INDIVIDUALS; ACTIVATION
AB Background: Recent research has identified impairment in processing speed, measured by the digit-symbol substitution task, as central to the cognitive deficit in schizophrenia. However, the underlying cognitive correlates of this impairment remain unknown.
Methods: A sample of cases (N = 125) meeting DSM-IV criteria for schizophrenia and a sample of community controls (N = 272) from the same geographical area completed a set of putative measures of processing-speed ability to which we implemented confirmatory factor and structural regression modelling in order to elucidate the latent structure of processing speed. Next, we tested the degree to which the structural and relational portions of the model were equal across groups.
Results: Processing-speed ability was best defined, in both controls and cases (chi(2) = 38.59(26), p = 0.053), as a multidimensional cognitive ability consisting of three latent factors comprising: psychomotor speed, sequencing and shifting, and verbal fluency. However, cases exhibited dedifferentiation (i.e., markedly stronger inter-correlations between factors; chi(2) = 59.94(29), pb<.01) and a reliance on an alternative ensemble of cognitive operations to controls when completing the digit-symbol substitution task.
Conclusion: Dedifferentiation of processing-speed ability in schizophrenia and subsequent overreliance on alternative (and possibly less than optimal) cognitive operations underlies the marked deficit observed on the digit-symbol substitution task. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Knowles, Emma E. M.] Inst Living, Olin Neuropsychiat Res Ctr, Hartford, CT 06106 USA.
[Knowles, Emma E. M.; Glahn, David] Yale Univ, Hartford, CT USA.
[Knowles, Emma E. M.; David, Anthony S.; Reichenberg, Abraham] Kings Coll London, Inst Psychiat, Dept Psychosis Studies, London WC2R 2LS, England.
[Weiser, Mark; Davidson, Michael] Sheba Med Ctr, Ramat Gan, Israel.
[Dickinson, Dwight] NIMH, Clin Brain Disorders Branch & Genes, Cognit & Psychosis Program, NIH, Bethesda, MD USA.
[Gold, James] Univ Maryland, Baltimore Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD USA.
RP Knowles, EEM (reprint author), Inst Living, Olin Neuropsychiat Res Ctr, 200 Retreat Ave,Whitehall Bldg, Hartford, CT 06106 USA.
EM emma.knowles@yale.edu
RI David, Anthony/C-1315-2011
OI David, Anthony/0000-0003-0967-774X
FU NIMH [MH066105]; UK Department of Health via the National Institute for
Health Research (NIHR) Specialist Biomedical Research Centre for Mental
Health; Institute of Psychiatry at King's College London
FX This research was supported by the NIMH grant MH066105, and by the UK
Department of Health via the National Institute for Health Research
(NIHR) Specialist Biomedical Research Centre for Mental Health award to
South London and Maudsley NHS Foundation Trust (SLaM) and the Institute
of Psychiatry at King's College London. Dr. Dickinson is supported by
the NIMH Intramural Research Program.
NR 50
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U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD DEC
PY 2012
VL 142
IS 1-3
BP 129
EP 136
DI 10.1016/j.schres.2012.08.020
PG 8
WC Psychiatry
SC Psychiatry
GA 039CR
UT WOS:000311220900020
PM 23084540
ER
PT J
AU Li, M
Wang, Y
Zheng, XB
Ikeda, M
Iwata, N
Luo, XJ
Chong, SA
Lee, J
Rietschel, M
Zhang, FY
Muller-Myhsok, B
Cichon, S
Weinberger, DR
Mattheisen, M
Schulze, TG
Martin, NG
Mitchell, PB
Schofield, PR
Liu, JJ
Su, B
AF Li, Ming
Wang, Yi
Zheng, Xue-bin
Ikeda, Masashi
Iwata, Nakao
Luo, Xiong-jian
Chong, Siow-Ann
Lee, Jimmy
Rietschel, Marcella
Zhang, Fengyu
Mueller-Myhsok, Bertram
Cichon, Sven
Weinberger, Daniel R.
Mattheisen, Manuel
Schulze, Thomas G.
Martin, Nicholas G.
Mitchell, Philip B.
Schofield, Peter R.
Liu, Jian-jun
Su, Bing
CA MooDS Consortium
TI Meta-analysis and brain imaging data support the involvement of VRK2
(rs2312147) in schizophrenia susceptibility
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE VRK2; Schizophrenia; Asian populations; MRI; Brain imaging analysis
ID COMMON VARIANTS; BIPOLAR DISORDER; CONFERRING RISK; HAN CHINESE;
ASSOCIATION; ZNF804A
AB Recent genome-wide association studies have reported a set of schizophrenia susceptibility genes, but many of them await further replications in additional samples. Here we analyzed 5 genome-wide supported variants in a Han Chinese sample, and the variant rs2312147 at VRK2 showed significant association, which was confirmed in the meta-analysis combining multiple Asian and European samples (P=3.17x10(-4), N=7498). Rs2312147 is also associated with brain structure in healthy subjects, including the total brain volume and the white matter volume. Gene expression analyses indicated an up-regulation of VRK2 in schizophrenia patients. Our data provide further evidence for the contribution of VRK2 to schizophrenia. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Li, Ming; Wang, Yi; Luo, Xiong-jian; Su, Bing] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China.
[Zheng, Xue-bin; Liu, Jian-jun] ASTAR, Genome Inst Singapore, Singapore, Singapore.
[Ikeda, Masashi; Iwata, Nakao] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan.
[Chong, Siow-Ann; Lee, Jimmy] Inst Mental Hlth, Singapore, Singapore.
[Rietschel, Marcella] Univ Heidelberg, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-68159 Mannheim, Germany.
[Rietschel, Marcella] Univ Bonn, Dept Psychiat, D-53127 Bonn, Germany.
[Zhang, Fengyu; Weinberger, Daniel R.] NIMH, Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Cichon, Sven] Struct & Funct Org Brain, Res Ctr Juelich, INM 1, D-52425 Julich, Germany.
[Cichon, Sven; Mattheisen, Manuel] Univ Bonn, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany.
[Cichon, Sven; Mattheisen, Manuel] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany.
[Schulze, Thomas G.] Univ Gottingen, Univ Med Ctr, Dept Psychiat & Psychotherapy, Sect Psychiat Genet, D-37075 Gottingen, Germany.
[Martin, Nicholas G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Mitchell, Philip B.] Univ New S Wales, Sch Psychiat, Sydney, NSW 2052, Australia.
[Schofield, Peter R.] Univ New S Wales, Sydney, NSW 2031, Australia.
[Schofield, Peter R.] Neurosci Res Australia, Sydney, NSW 2031, Australia.
[Li, Ming] Chinese Acad Sci, Grad Univ, Beijing, Peoples R China.
RP Su, B (reprint author), Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, 32 E Jiao Chang Rd, Kunming 650223, Yunnan, Peoples R China.
EM sub@mail.kiz.ac.cn
RI Schumacher, Johannes/F-4970-2015; Muller-Myhsok, Bertram/A-3289-2013;
Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon,
Sven/B-9618-2014; Li, Ming/K-7455-2013; Mattheisen, Manuel/B-4949-2012
OI Schumacher, Johannes/0000-0001-9217-6457; Lee,
Jimmy/0000-0002-7724-7445; Mitchell, Philip/0000-0002-7954-5235; Martin,
Nicholas/0000-0003-4069-8020; Cichon, Sven/0000-0002-9475-086X; Cichon,
Sven/0000-0002-9475-086X; Li, Ming/0000-0002-8197-6552; Mattheisen,
Manuel/0000-0002-8442-493X
FU National 973 project of China [2011CBA00401]; National Natural Science
Foundation of China [31237068]; National Medical Research Council
Translational and Clinical Research Flagship Program
[NMRC/TCR/003/2008]; German Federal Ministry of Education and Research
(BMBF), within National Genome Research Network (NGFN); Integrated
Genome Research Network (IG) MooDS [01GS08144, 01GS08147]; Australian
NHMRC program [510135]
FX This work was supported by grants from the National 973 project of China
(grant number, 2011CBA00401), the National Natural Science Foundation of
China (31237068), the National Medical Research Council Translational
and Clinical Research Flagship Program (grant number,
NMRC/TCR/003/2008), the German Federal Ministry of Education and
Research (BMBF), within the context of the National Genome Research
Network (NGFN), and the Integrated Genome Research Network (IG) MooDS
(grant 01GS08144 to S.C, grant 01GS08147 to M.R.). Recruitment of the
Australian BDP sample was supported by the Australian NHMRC program
(grant number 510135).
NR 27
TC 22
Z9 22
U1 1
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD DEC
PY 2012
VL 142
IS 1-3
BP 200
EP 205
DI 10.1016/j.schres.2012.10.008
PG 6
WC Psychiatry
SC Psychiatry
GA 039CR
UT WOS:000311220900030
PM 23102693
ER
PT J
AU Moran, LV
Sampath, H
Stein, EA
Hong, LE
AF Moran, Lauren V.
Sampath, Hemalatha
Stein, Elliot A.
Hong, L. Elliot
TI Insular and anterior cingulate circuits in smokers with schizophrenia
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Resting state functional connectivity; Schizophrenia; Smoking; Nicotine;
Insula; Anterior cingulate
ID FUNCTIONAL CONNECTIVITY; NICOTINE DEPENDENCE; BRAIN-FUNCTION; SMOKING;
ADDICTION; CORTEX; ASSOCIATION; METAANALYSIS; CIGARETTE; SINGLE
AB Schizophrenia (SZ) is associated with high rates of smoking. We previously found that resting state functional connectivity (rsFC) between the dorsal anterior cingulate (dACC) and striatum is independently associated with nicotine addiction and psychiatric illness. Since the insula is implicated in nicotine dependence, we hypothesized that SZ smokers will have greater dysfunction in smoking-related insular and dACC circuits than normal control smokers (NC) independent of smoking severity, consistent with an inherent disease-related weakening of smoking-related circuits. Nicotine challenge was used to demonstrate that decreased rsFC in identified circuits reflects addiction trait and is not affected by pharmacological state. Twenty-four NC smokers and 20 smokers with SZ matched on nicotine addiction severity participated in a resting state fMRI study and were scanned during two separate sessions while receiving a placebo or nicotine patch, in a randomized, cross-over design. Using individualized, anatomically defined anterior and posterior insula and dACC as regions of interest (ROI), whole brain rsFC was performed using each ROI as a seed. Significant negative correlations between smoking severity and rsFC between insula, dACC and striatum were found for both groups. Furthermore, smokers with SZ demonstrated additive reductions in circuit strength between the dACC and insula compared to NC smokers independent of smoking severity. Nicotine challenge did not significantly alter rsFC in insula-dACC-striatal circuits. Reduced rsFC strength between the insula, dACC and striatum is associated with nicotine addiction severity in both non-psychiatrically ill and in SZ smokers. Decreased insula-dACC rsFC may index overlapping circuitry associated with smoking and SZ. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Moran, Lauren V.; Sampath, Hemalatha; Hong, L. Elliot] Univ Maryland, Maryland Psychiat Res Ctr, Dept Psychiat, Sch Med, Baltimore, MD 21228 USA.
[Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD USA.
RP Moran, LV (reprint author), Univ Maryland, Maryland Psychiat Res Ctr, Dept Psychiat, Sch Med, POB 21247, Baltimore, MD 21228 USA.
EM lmoran@mprc.umaryland.edu
FU National Institutes of Health [R01DA027680, R01MH085646, T32MH067533];
Maryland Cigarette Restitution Fund Program; NIDA Intramural Research
Program, NIH
FX Financial support was received from National Institutes of Health grants
R01DA027680, R01MH085646, T32MH067533, and a grant from the Maryland
Cigarette Restitution Fund Program. This research was also supported by
the NIDA Intramural Research Program, NIH.
NR 36
TC 7
Z9 7
U1 2
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD DEC
PY 2012
VL 142
IS 1-3
BP 223
EP 229
DI 10.1016/j.schres.2012.08.033
PG 7
WC Psychiatry
SC Psychiatry
GA 039CR
UT WOS:000311220900034
PM 23021898
ER
PT J
AU Rollins, N
Mahy, M
Becquet, R
Kuhn, L
Creek, T
Mofenson, L
AF Rollins, Nigel
Mahy, Mary
Becquet, Renaud
Kuhn, Louise
Creek, Tracy
Mofenson, Lynne
TI Estimates of peripartum and postnatal mother-to-child transmission
probabilities of HIV for use in Spectrum and other population-based
models
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SINGLE-DOSE NEVIRAPINE; RANDOMIZED
CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; BREAST-FED CHILDREN;
COTE-DIVOIRE; DOUBLE-BLIND; ANTIRETROVIRAL THERAPY; INFANT TRANSMISSION;
PROSPECTIVE COHORT
AB Background The Global Plan Towards the Elimination of New HIV Infections among Children and Keeping Their Mothers Alive aims to reduce by 2015 the number of new infections in children, in 22 priority countries, by at least 90% from 2009 levels. Mathematical models, such as Spectrum, are used to estimate national and global trends of the number of infants infected through mother-to-child transmission (MTCT). However, other modelling exercises have also examined MTCT under different settings. MTCT probabilities applied in models to populations that are assumed to receive antiretroviral interventions need to reflect the most current risk estimates.
Methods The UNAIDS Reference Group on Estimates, Modelling and Projections held a consultation to review data on MTCT probabilities. Published literature, recent conferences and data from personal communications with principle investigators were reviewed. Based on available data, peripartum and postnatal transmission probabilities were estimated for different antiretroviral drug regimens and maternal CD4 levels including for women with incident infection.
Results Incident infections occurring during pregnancy are estimated to be associated with a 30% probability of MTCT; incident infections during breast feeding lead to a 28% probability of postnatal MTCT. The 2010 WHO recommended regimens (Options A or B) are estimated to be associated with a 2% peripartum transmission probability and 0.2% transmission probability per month of breast feeding. Peripartum and postnatal transmission probabilities were lowest for women who were taking antiretroviral therapy before the pregnancy namely 0.5% peripartum and 0.16% per month of breast feeding, respectively.
Discussion These updated probabilities of HIV transmission (applied to Spectrum in April 2011) will be used to estimate new child HIV infections and track progress towards the 2015 targets of the Global Plan.
C1 [Rollins, Nigel] WHO, Dept Maternal Newborn Child & Adolescent Hlth, CH-1211 Geneva, Switzerland.
[Rollins, Nigel] Univ KwaZulu Natal, Dept Paediat, Durban, South Africa.
[Mahy, Mary] Joint United Nations Programme HIV AIDS UNAIDS, Dept Evidence Innovat & Policy, Geneva, Switzerland.
[Becquet, Renaud] Ctr Rech Epidemiol & Biostat, Dept INSERM, U897, Bordeaux, France.
[Becquet, Renaud] Univ Bordeaux 2, ISPED, F-33076 Bordeaux, France.
[Kuhn, Louise] Columbia Univ, Gertrude H Sergievsky Ctr, Coll Phys & Surg, New York, NY 10027 USA.
[Creek, Tracy] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Mofenson, Lynne] NICHHD, Ctr Res Mothers & Children, NIH, Rockville, MD USA.
RP Rollins, N (reprint author), WHO, Dept Maternal Newborn Child & Adolescent Hlth, Ave Appia 20, CH-1211 Geneva, Switzerland.
EM rollinsn@who.int
RI Becquet, Renaud/F-4837-2013
OI Becquet, Renaud/0000-0003-3277-0985
NR 51
TC 21
Z9 22
U1 1
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD DEC
PY 2012
VL 88
SU 2
BP I44
EP I51
DI 10.1136/sextrans-2012-050709
PG 8
WC Infectious Diseases
SC Infectious Diseases
GA 040QM
UT WOS:000311338000007
PM 23172345
ER
PT J
AU Kawasaki, R
Xie, J
Cheung, N
Lamoureux, E
Klein, R
Klein, BEK
Frances, M
Sharrett, AR
Shea, S
Wong, TY
AF Kawasaki, Ryo
Xie, Jing
Cheung, Ning
Lamoureux, Ecosse
Klein, Ronald
Klein, Barbara E. K.
Frances, Mary
Sharrett, A. Richey
Shea, Steven
Wong, Tien Y.
TI Retinal Microvascular Signs and Risk of Stroke The Multi-Ethnic Study of
Atherosclerosis (MESA)
SO STROKE
LA English
DT Article
DE retinal vessel; microvascular network; retinopathy; stroke
ID CORONARY-ARTERY CALCIFICATION; CARDIOVASCULAR HEALTH; VESSEL DIAMETERS;
CEREBROVASCULAR-DISEASE; CEREBRAL INFARCTION; INCIDENT STROKE; OLDER
PERSONS; ABNORMALITIES; COMMUNITIES; RETINOPATHY
AB Background and Purpose-Small-vessel disease contributes to the pathophysiology of stroke, and retinal microvascular signs have been linked to the risk of stroke. We examined the relationship of retinal signs with incident stroke in a multiethnic cohort.
Methods-The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study that enrolled participants without clinical cardiovascular diseases from 6 US communities between 2000 and 2002. Of the participants, 4849 (71.2%) had fundus photography performed in 2002 to 2004. Retinopathy and retinal vessel caliber were assessed from retinal images. Stroke risk factors including high-sensitivity C-reactive protein, carotid artery intima-media thickness, and coronary artery calcium were measured using standardized protocols. Incident stroke was confirmed from medical record review and death certificates.
Results-After 6 years of follow-up, there were 62 incident strokes. Narrower retinal arteriolar caliber was associated with increased risk of stroke after adjusting for conventional cardiovascular risk factors (adjusted incidence rate ratio, 2.83; 95% CI, 1.34-5.95; P=0.006; adjusted hazard ratio, 3.01; 95% CI, 1.29-6.99; P=0.011). Retinopathy in persons without diabetes was associated with increased risk of stroke (adjusted adjusted incidence rate ratio, 2.96; 95% CI, 1.50-5.84; P=0.002; adjusted hazard ratio, 3.07; 95% CI, 1.17-8.09; P=0.023). These associations remained significant after adjusting for high-sensitivity C-reactive protein, carotid intima-media thickness, or coronary artery calcium.
Conclusions-Narrower retinal arteriolar caliber and retinopathy in nondiabetic persons were associated with increased risk of stroke in this relatively healthy multiethnic cohort independent of traditional risk factors and measures of atherosclerosis. The association between narrower retinal arteriolar caliber and stroke warrants further investigation. (Stroke. 2012; 43: 3245-3251.)
C1 [Kawasaki, Ryo; Xie, Jing; Cheung, Ning; Lamoureux, Ecosse; Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, Melbourne, Vic 3002, Australia.
[Kawasaki, Ryo; Klein, Barbara E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Frances, Mary] NEI, US NIH, Bethesda, MD 20892 USA.
[Sharrett, A. Richey] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Shea, Steven] Columbia Univ, Dept Med, New York, NY USA.
[Shea, Steven] Columbia Univ, Dept Epidemiol, New York, NY USA.
[Wong, Tien Y.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, 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 [N01-HC-95159, N01-HC-95169];
National Center for Research Resources (NCRR) [UL1-RR-024156,
UL1-RR-025005]
FX This research was supported by contracts N01-HC-95159 through
N01-HC-95169 from the National Heart, Lung, and Blood Institute and by
grants UL1-RR-024156 and UL1-RR-025005 from National Center for Research
Resources (NCRR).
NR 31
TC 25
Z9 26
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD DEC
PY 2012
VL 43
IS 12
BP 3245
EP 3251
DI 10.1161/STROKEAHA.112.673335
PG 7
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 042UU
UT WOS:000311497600026
PM 23111439
ER
PT J
AU Wendell, CR
Waldstein, SR
Ferrucci, L
O'Brien, RJ
Strait, JB
Zonderman, AB
AF Wendell, Carrington R.
Waldstein, Shari R.
Ferrucci, Luigi
O'Brien, Richard J.
Strait, James B.
Zonderman, Alan B.
TI Carotid Atherosclerosis and Prospective Risk of Dementia
SO STROKE
LA English
DT Article
DE Alzheimer disease; atherosclerosis; dementia; intimal medial thickness
ID INTIMA-MEDIA THICKNESS; ALZHEIMERS-DISEASE; COGNITIVE DECLINE;
APOLIPOPROTEIN-E; ROTTERDAM; HEALTH
AB Background and Purpose-Although vascular risk factors have been implicated in the development of all-cause dementia and Alzheimer disease (AD), few studies have examined the association between subclinical atherosclerosis and prospective risk of dementia.
Methods-Participants from the Baltimore Longitudinal Study of Aging (n=364; age, 60-95 years; median age, 73; 60% male; 82% white) underwent initial carotid atherosclerosis assessment and subsequently were assessed for dementia and AD annually for up to 14 years (median, 7.0). Cox proportional hazards models predicting all-cause dementia and AD were adjusted for age, sex, race, education, blood pressure, cholesterol, cardiovascular disease, diabetes mellitus, and smoking.
Results-Sixty participants developed dementia, with 53 diagnosed as AD. Raw rates of future dementia and AD among individuals initially in the upper quintile of carotid intimal medial thickness or with bilateral carotid plaque were generally double the rates of individuals with intimal medial thickness in the lower quintiles or no plaque at baseline. Adjusted proportional hazards models revealed >2.5-fold increased risk of dementia and AD among individuals in the upper quintile of carotid intimal medial thickness, and approximately 2.0-fold increased risk of dementia among individuals with bilateral plaque.
Conclusions-Multiple measures of carotid atherosclerosis are associated with prospective risk of dementia. Individuals in the upper quintile of carotid intimal medial thickness or bilateral carotid plaque were at greatest risk. These findings underscore the possibility that early intervention to reduce atherosclerosis may help delay or prevent onset of dementia and AD. (Stroke. 2012; 43: 3319-3324.)
C1 [Wendell, Carrington R.; Ferrucci, Luigi; Strait, James B.; Zonderman, Alan B.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Wendell, Carrington R.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA.
[O'Brien, Richard J.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Waldstein, Shari R.] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21201 USA.
[Waldstein, Shari R.] Univ Maryland, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Baltimore, MD 21201 USA.
[Waldstein, Shari R.] Baltimore VA Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA.
[Waldstein, Shari R.] Baltimore VA Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA.
RP O'Brien, RJ (reprint author), NIA, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM cwendell@jhmi.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institute on Aging Intramural Research Program, National
Institutes of Health
FX This research was supported by the National Institute on Aging
Intramural Research Program, National Institutes of Health.
NR 23
TC 29
Z9 32
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD DEC
PY 2012
VL 43
IS 12
BP 3319
EP 3324
DI 10.1161/STROKEAHA.112.672527
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 042UU
UT WOS:000311497600037
PM 23103489
ER
PT J
AU Cyphert, JM
Nyska, A
Mahoney, RK
Schladweiler, MC
Kodavanti, UP
Gavett, SH
AF Cyphert, Jaime M.
Nyska, Abraham
Mahoney, Ron K.
Schladweiler, Mette C.
Kodavanti, Urmila P.
Gavett, Stephen H.
TI Sumas Mountain Chrysotile Induces Greater Lung Fibrosis in Fischer 344
Rats Than Libby Amphibole, El Dorado Tremolite, and Ontario
Ferroactinolite
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE Libby amphibole; El Dorado; Sumas Mountain; cleavage fragments; fibrosis
ID NATURALLY-OCCURRING ASBESTOS; TERM INHALATION EXPOSURE; ENVIRONMENTAL
EXPOSURE; CLEAVAGE FRAGMENTS; INTRATRACHEAL INSTILLATION; PATHOLOGICAL
RESPONSE; ANATOLIAN VILLAGE; MESOTHELIOMA; VERMICULITE; MONTANA
AB The physical properties of different types of asbestos may strongly affect health outcomes in exposed individuals. This study was designed to provide understanding of the comparative toxicity of naturally occurring asbestos (NOA) fibers including Libby amphibole (LA), Sumas Mountain chrysotile (SM), El Dorado tremolite (ED), and Ontario ferroactinolite (ON) cleavage fragments. Rat-respirable fractions (PM2.5) were prepared by water elutriation. Surface area was greater for SM (64.1 m(2)/g) than all other samples (range: 14.116.2 m(2)/g), whereas mean lengths and aspect ratios (ARs) for LA and SM were comparable and greater than ED and ON. Samples were delivered via a single intratracheal (IT) instillation at doses of 0.5 and 1.5mg/rat. One day post-IT instillation, low-dose NOA exposure resulted in a 3- to 4-fold increase in bronchoalveolar lavage fluid (BALF) cellularity compared with dispersion media (DM) controls, whereas high-dose exposure had a more severe effect on lung inflammation which varied by source. Although inducing less neutrophilic inflammation than ON and ED, exposure to either LA or SM resulted in a greater degree of acute lung injury. Three months post-IT instillation, most BALF parameters had returned to control levels, whereas the development of fibrosis persisted and was greatest in SM-exposed rats (SM > LA > ON > ED). These data demonstrate that fiber length and higher AR are directly correlated with the severity of fibrosis and that, in the rat, exposure to SM is more fibrogenic than LA which suggests that there may be cause for concern for people at risk of being exposed to NOA from the Sumas Mountain landslide.
C1 [Cyphert, Jaime M.; Schladweiler, Mette C.; Kodavanti, Urmila P.; Gavett, Stephen H.] US EPA, EPHD, NHEERL, Res Triangle Pk, NC 27711 USA.
[Cyphert, Jaime M.] UNC Sch Med, Curriculum Toxicol, Chapel Hill, NC 27599 USA.
[Nyska, Abraham] Tel Aviv Univ, Sackler Sch Med, IL-36576 Timrat, Israel.
[Nyska, Abraham] NIEHS, NIH, Res Triangle Pk, NC 27711 USA.
[Mahoney, Ron K.] EMSL Analyt Inc, Libby, MT 59923 USA.
RP Gavett, SH (reprint author), US EPA, EPHD, NHEERL, Mail Drop B105-02,109 TW Alexander Dr, Res Triangle Pk, NC 27711 USA.
EM gavett.stephen@epa.gov
FU U.S. Environmental Protection Agency/University of North Carolina [CR
833237, 83515201-0]; U.S. Environmental Protection Agency (Region 8);
U.S. Environmental Protection Agency (Office of Solid Waste and
Emergency Response)
FX U.S. Environmental Protection Agency/University of North Carolina
Toxicology Research Program Training Agreement (CR 833237; 83515201-0 to
J.M.C.); U.S. Environmental Protection Agency (Region 8 and Office of
Solid Waste and Emergency Response).
NR 56
TC 8
Z9 8
U1 0
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD DEC
PY 2012
VL 130
IS 2
BP 405
EP 415
DI 10.1093/toxsci/kfs249
PG 11
WC Toxicology
SC Toxicology
GA 040FN
UT WOS:000311307600018
PM 22903825
ER
PT J
AU Liebschner, D
Brzezinski, K
Dauter, M
Dauter, Z
Nowak, M
Kur, J
Olszewski, M
AF Liebschner, Dorothee
Brzezinski, Krzysztof
Dauter, Miroslawa
Dauter, Zbigniew
Nowak, Marta
Kur, Jozef
Olszewski, Marcin
TI Dimeric structure of the N-terminal domain of PriB protein from
Thermoanaerobacter tengcongensis solved ab initio
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
ID X-RAY-STRUCTURE; REPLICATION RESTART PRIMOSOME; PYROCOCCUS-ABYSSI
RUBREDOXIN; DNA-BINDING PROTEINS; CRYSTAL-STRUCTURE;
ULTRAHIGH-RESOLUTION; ATOMIC-RESOLUTION; ESCHERICHIA-COLI; DATA-BANK;
THERMUS-AQUATICUS
AB PriB is one of the components of the bacterial primosome, which catalyzes the reactivation of stalled replication forks at sites of DNA damage. The N-terminal domain of the PriB protein from the thermophilic bacterium Thermoanaerobacter tengcongensis (TtePriB) was expressed and its crystal structure was solved at the atomic resolution of 1.09 angstrom by direct methods. The protein chain, which encompasses the first 104 residues of the full 220-residue protein, adopts the characteristic oligonucleotide/oligosaccharide-binding (OB) structure consisting of a five-stranded beta-barrel filled with hydrophobic residues and equipped with four loops extending from the barrel. In the crystal two protomers dimerize, forming a six-stranded antiparallel beta-sheet. The structure of the N-terminal OB domain of T. tengcongensis shows significant differences compared with mesophile PriBs. While in all other known structures of PriB a dimer is formed by two identical OB domains in separate chains, TtePriB contains two consecutive OB domains in one chain. However, sequence comparison of both the N-terminal and the C-terminal domains of TtePriB suggests that they have analogous structures and that the natural protein possesses a structure similar to a dimer of two N-terminal domains.
C1 [Liebschner, Dorothee; Brzezinski, Krzysztof; Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA.
[Brzezinski, Krzysztof] Univ Bialystok, Inst Chem, PL-15399 Bialystok, Poland.
[Dauter, Miroslawa] Argonne Natl Lab, SAIC Frederick Inc, Basic Res Program, Argonne, IL 60439 USA.
[Nowak, Marta; Kur, Jozef; Olszewski, Marcin] Gdansk Univ Technol, Dept Microbiol, PL-80952 Gdansk, Poland.
RP Dauter, Z (reprint author), NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA.
EM dauter@anl.gov; molszewski@pg.gda.pl
FU National Cancer Institute, National Institutes of Health [NO1-CO-12400];
NIH, National Cancer Institute, Center for Cancer Research; Polish State
Committee for Scientific Research [N302 116636, N302 439439]; US
Department of Energy, Office of Science, Office of Basic Energy Sciences
[W-31-109-Eng-38]
FX This work was supported in part with Federal funds from the National
Cancer Institute, National Institutes of Health contract No.
NO1-CO-12400, the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research and Polish State Committee
for Scientific Research grants No. N302 116636 and N302 439439. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does the
mention of trade names, commercial products or organizations imply
endorsement by the US Government. Diffraction data were collected on the
SER-CAT beamline 22-ID at the Advanced Photon Source, Argonne National
Laboratory. Use of the Advanced Photon Source was supported by the US
Department of Energy, Office of Science, Office of Basic Energy Sciences
under Contract No. W-31-109-Eng-38.
NR 55
TC 1
Z9 1
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0907-4449
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Biol. Crystallogr.
PD DEC
PY 2012
VL 68
BP 1680
EP 1689
DI 10.1107/S0907444912041637
PN 12
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 037IR
UT WOS:000311097200010
PM 23151633
ER
PT J
AU Denny, SS
Morhardt, D
Gaul, JE
Lester, P
Andersen, G
Higgins, PJ
Nee, L
AF Denny, Sharon S.
Morhardt, Darby
Gaul, J. Elise
Lester, Paul
Andersen, Gail
Higgins, Paul J.
Nee, Linda
TI Caring for Children of Parents With Frontotemporal Degeneration: A
Report of the AFTD Task Force on Families With Children
SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS
LA English
DT Article
DE frontotemporal degeneration; caregivers; children and teens; children's
bereavement; young onset dementia
ID YOUNG ONSET DEMENTIA; CHILDHOOD BEREAVEMENT; GRIEF; DEATH; CAREGIVERS;
CARERS; BURDEN; IMPACT
AB The Association for Frontotemporal Degeneration (AFTD) organized a 7-person Task Force on Families With Children to explore the concerns of families when a parent of young children or teens is diagnosed with FTD. This report summarizes the findings of the task force and highlights the need for additional attention to this topic. The task force conducted a review of related literature and existing resources and compiled issues identified by spouses/partners, teens, and adult children within an affected family. The project confirmed a significant lack of information and support for parents caring for a spouse with FTD and for their children. Recommendations include developing resources and strategies that promote comprehensive family support, including those that build resiliency in the well parent and the children, and strengthen the changing family unit. Avenues for additional research in this area of need in the FTD community are suggested.
C1 [Denny, Sharon S.] Assoc Frontotemporal Degenerat, Philadelphia, PA 19087 USA.
[Morhardt, Darby] Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA.
[Gaul, J. Elise] Ctr Grieving Children, Philadelphia, PA USA.
[Lester, Paul; Andersen, Gail] AFTD Parents Support Grp, Philadelphia, PA USA.
[Higgins, Paul J.] Keller Independent Sch Dist, Keller, TX USA.
[Nee, Linda] Natl Inst Neurol Disorders & Stroke, Family Studies Unit, Bethesda, MD USA.
RP Denny, SS (reprint author), Assoc Frontotemporal Degenerat, Radnor Stn 2,Suite 320,290 King Prussia Rd, Philadelphia, PA 19087 USA.
EM sdenny@theaftd.org
NR 23
TC 2
Z9 2
U1 2
U2 13
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1533-3175
J9 AM J ALZHEIMERS DIS
JI Am. J. Alzheimers Dis. Other Dement.
PD DEC
PY 2012
VL 27
IS 8
BP 568
EP 578
DI 10.1177/1533317512459791
PG 11
WC Geriatrics & Gerontology; Clinical Neurology
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 034LX
UT WOS:000310876100004
PM 23038712
ER
PT J
AU Rosenthal, J
Jessup, C
Felknor, S
Humble, M
Bader, F
Bridbord, K
AF Rosenthal, Joshua
Jessup, Christine
Felknor, Sarah
Humble, Michael
Bader, Farah
Bridbord, Kenneth
TI International environmental and occupational health: From individual
scientists to networked science Hubs
SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
LA English
DT Article
DE environmental health; occupational health; research training; global
health
ID EXPOSURE
AB For the past 16 years, the International Training and Research in Environmental and Occupational Health program (ITREOH) has supported projects that link U.S. academic scientists with scientists from low- and middle-income countries in diverse research and research training activities. Twenty-two projects of varied duration have conducted training to enhance the research capabilities of scientists at 75 institutions in 43 countries in Asia, Africa, Eastern Europe, and Latin America, and have built productive research relationships between these scientists and their U.S. partners. ITREOH investigators and their trainees have produced publications that have advanced basic sciences, developed methods, informed policy outcomes, and built institutional capacity. Today, the changing nature of the health sciences calls for a more strategic approach. Data-rich team science requires greater capacity for information technology and knowledge synthesis at the local institution. More robust systems for ethical review and administrative support are necessary to advance population-based research. Sustainability of institutional research capability depends on linkages to multiple national and international partners. In this context, the Fogarty International Center, the National Institute of Environmental Sciences and the National Institute for Occupational Safety and Health, have reengineered the ITREOH program to support and catalyze a multi-national network of regional hubs for Global Environmental and Occupational Health Sciences (GEOHealth). We anticipate that these networked science hubs will build upon previous investments by the ITREOH program and will serve to advance locally and internationally important health science, train and attract first-class scientists, and provide critical evidence to guide policy discussions. Am. J. Ind. Med. 55:10691077, 2012. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Rosenthal, Joshua; Jessup, Christine; Bader, Farah; Bridbord, Kenneth] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Felknor, Sarah] NIOSH, Bethesda, MD USA.
[Humble, Michael] NIEHS, Bethesda, MD USA.
RP Rosenthal, J (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM joshua.rosenthal@nih.gov
FU Intramural CDC HHS [CC999999]; Intramural NIH HHS [Z99 TW999999]
NR 23
TC 2
Z9 2
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0271-3586
J9 AM J IND MED
JI Am. J. Ind. Med.
PD DEC
PY 2012
VL 55
IS 12
SI SI
BP 1069
EP 1077
DI 10.1002/ajim.22130
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 033NX
UT WOS:000310805600001
PM 23109132
ER
PT J
AU Reddy, P
Naidoo, RN
Robins, TG
Mentz, G
Li, HL
London, SJ
Batterman, S
AF Reddy, Poovendhree
Naidoo, Rajen N.
Robins, Thomas G.
Mentz, Graciela
Li, Huiling
London, Stephanie J.
Batterman, Stuart
TI GSTM1 and GSTP1 gene variants and the effect of air pollutants on lung
function measures in South African children
SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
LA English
DT Article
DE air pollutants; asthma; child respiratory health; gene-environment
interaction
ID S-TRANSFERASE P1; RESPIRATORY HEALTH; CHILDHOOD ASTHMA; POLLUTION; RISK;
SUSCEPTIBILITY; POLYMORPHISM; POPULATION; EXPOSURE
AB Background Several genes are associated with an increased susceptibility to asthma, which may be exacerbated by ambient air pollution. These genes include GSTM1 (glutathione-S-transferase M1 gene) and GSTP1 (glutathione-S-transferase P1 gene), which may modulate the response to epithelial oxidative changes caused by air pollutant exposure. This study evaluated fluctuations in the forced expiratory volume in one second (FEV1) in relation to lagged daily averages of ambient air pollutants (SO2, NO2, NO, and PM10) while considering genotype as an effect modifier. Methods A longitudinal cohort of 129 schoolchildren of African descent from Durban, South Africa was assessed. GSTM1 (null vs. present genotype) and GSTP1 (Ile105Val; AA???AG/GG) genotypes were determined using standard techniques. SO2, NO2, NO, and PM10 were measured continuously over a year using validated methods. The outcome was intraday variability in FEV1. Data were collected daily over a 3-week period in each of four seasons (20042005). Results Among the children tested, 27% had the GSTM1 null genotype and 81% carried the GSTP1 G allele. Approximately 26 out 104 children (25%) showed evidence of bronchial hyperreactivity, 13% reported having symptoms in keeping with persistent asthma, and a further 25% reported symptoms of mild intermittent asthma. PM10 and SO2 levels were moderately high relative to international guidelines. Neither GSTM1 nor GSTP1 genotypes alone were significantly associated with FEV1 intraday variability. In models not including genotype, FEV1 variability was statistically significantly associated only with NO2 for 5-day lags (% change in intraday variability in FEV1 per interquartile range?=?1.59, CI 0.58, 2.61). The GSTP1 genotype modified the effect of 3 days prior 24-hr average PM10 and increased FEV1 variability. A similar pattern was observed for lagged 3 day SO2 exposure (P interaction?= 9.0%, after adjustment for age, sex, race, BMI, serum albumin, years of dialysis, serum creatinine, 12 comorbid conditions, insulin use, hemoglobin, LDL cholesterol, country, and study phase. Diabetes medications were prescribed for 35% of patients with A(1c) <6% and not prescribed for 29% of those with A(1c) >= 9%.
CONCLUSIONS-A(1c) levels strongly predicted mortality in hemodialysis patients with type 1 or type 2 diabetes. Mortality increased as A(1c) moved further from 7-7.9%; thus, target A(1c) in hemodialysis patients may encompass values higher than those recommended by current guidelines. Modifying glucose-lowering medicines for dialysis patients to target A(1c) levels within this range may be a modifiable practice to improve outcomes.
C1 [Ramirez, Sylvia Paz B.; Mccullough, Keith P.; Thumma, Jyothi R.; Morgenstern, Hal; Pisoni, Ronald L.; Port, Fritz K.; Robinson, Bruce M.] Arbor Res Collaborat Hlth, Ann Arbor, MI USA.
[Nelson, Robert G.] NIDDKD, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Inaba, Masaaki] Osaka City Univ, Osaka 558, Japan.
[Jacobson, Stefan H.] Karolinska Inst, Danderyd Univ Hosp, Dept Nephrol, Stockholm, Sweden.
[Vanholder, Raymond] Univ Ghent, Ghent Univ Hosp, Nephrol Div, B-9000 Ghent, Belgium.
RP Ramirez, SPB (reprint author), Arbor Res Collaborat Hlth, Ann Arbor, MI USA.
EM sylvia.ramirez@arborresearch.org
FU Amgen; Kyowa Hakko Kirin; Sanofi Renal; Abbott; Baxter; Vifor Fresenius
Renal Pharma
FX The DOPPS is administered by Arbor Research Collaborative for Health and
is supported by scientific research grants from Amgen (since 1996),
Kyowa Hakko Kirin (since 1999, in Japan), Sanofi Renal (since 2009),
Abbott (since 2009), Baxter (since 2011), and Vifor Fresenius Renal
Pharma (since 2011), without restrictions on publications. No other
potential conflicts of interest relevant to this article were reported.
NR 25
TC 27
Z9 28
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD DEC
PY 2012
VL 35
IS 12
BP 2527
EP 2532
DI 10.2337/dc12-0573
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 041UF
UT WOS:000311426000036
PM 22912431
ER
PT J
AU Sacks, DB
AF Sacks, David B.
TI Measurement of Hemoglobin A(1c) A new twist on the path to harmony
SO DIABETES CARE
LA English
DT Review
ID ESTIMATED AVERAGE GLUCOSE; GLYCATED HEMOGLOBIN; WORLDWIDE
STANDARDIZATION; CONSENSUS STATEMENT; DIABETES-MELLITUS; PROGRESS
REPORT; BLOCKING GROUP; NORMAL ADULT; HUMAN BLOOD; A1C ASSAY
C1 NIH, Dept Lab Med, Bethesda, MD 20892 USA.
RP Sacks, DB (reprint author), NIH, Dept Lab Med, Bldg 10, Bethesda, MD 20892 USA.
EM sacksdb@mail.nih.gov
OI Sacks, David/0000-0003-3100-0735
FU National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institutes of Health.
NR 49
TC 36
Z9 38
U1 1
U2 8
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD DEC
PY 2012
VL 35
IS 12
BP 2674
EP 2680
DI 10.2337/dc12-1348
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 041UF
UT WOS:000311426000060
PM 23173136
ER
PT J
AU Hammer, MB
El Euch-Fayache, G
Nehdi, H
Saidi, D
Nasri, A
Nabli, F
Bouhlal, Y
Maamouri-Hicheri, W
Hentati, F
Amouri, R
AF Hammer, Monia Benhamed
El Euch-Fayache, Ghada
Nehdi, Houda
Saidi, Dalel
Nasri, Amira
Nabli, Fatma
Bouhlal, Yosr
Maamouri-Hicheri, Wieme
Hentati, Faycal
Amouri, Rim
TI Clinical and Molecular Findings of Ataxia With Oculomotor Apraxia Type 2
(AOA2) in 5 Tunisian Families
SO DIAGNOSTIC MOLECULAR PATHOLOGY
LA English
DT Article
DE AOA2; SETX; mutation; ataxia; Tunisian
ID MUTATIONS; SENATAXIN; HELICASE; ONSET; GENE
AB Ataxia with oculomotor apraxia type 2 (AOA2) is a recently described autosomal recessive cerebellar ataxia caused by mutations in the SETX gene. It is a rare monogenic disease characterized by progressive cerebellar ataxia, oculomotor apraxia, axonal sensorimotor neuropathy, and an elevated serum alpha-fetoprotein level. To date, > 100 AOA2 patients have been described and 75 different mutations in the SETX gene have been identified. We report here the clinical and genetic findings of 13 AOA2 patients from 5 unrelated Tunisian consanguineous families. DNA was collected from probands and available family members, and the 24 SETX exons were screened by direct sequencing. Four different homozygous SETX gene mutations were identified. The missense mutation 915G > T [W305C] has been described previously in Algeria. The 3 other SETX mutations are novel, including a missense mutation c.7231C > T [R 2380 W], a nonsense mutation c.6475 C > T [R2098X], and a deletion c.7180-7183delAAAA [D2332fsX2343]. More extensive screening by molecular genetic analysis of SETX in patients with Friedreich ataxia-like phenotype may show that AOA2 is more common in Tunisia than previously thought.
C1 [Hammer, Monia Benhamed] NIA, NIH, Bethesda, MD 20892 USA.
[El Euch-Fayache, Ghada; Nehdi, Houda; Saidi, Dalel; Nasri, Amira; Nabli, Fatma; Bouhlal, Yosr; Maamouri-Hicheri, Wieme; Hentati, Faycal; Amouri, Rim] Natl Inst Neurol, Dept Mol Neurobiol & Neuropathol, Tunis, Tunisia.
RP Hammer, MB (reprint author), NIA, NIH, 35 Convent Dr,Room 1A1010, Bethesda, MD 20892 USA.
EM benhamadm@mail.nih.gov
NR 18
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Z9 5
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1052-9551
J9 DIAGN MOL PATHOL
JI Diagn. Mol. Pathol.
PD DEC
PY 2012
VL 21
IS 4
BP 241
EP 245
DI 10.1097/PDM.0b013e318257ad9a
PG 5
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Pathology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Pathology
GA 039CW
UT WOS:000311221400007
PM 23111195
ER
PT J
AU Tamura, D
Khan, SG
Merideth, M
DiGiovanna, JJ
Tucker, MA
Goldstein, AM
Oh, KS
Ueda, T
Boyle, J
Sarihan, M
Kraemer, KH
AF Tamura, Deborah
Khan, Sikandar G.
Merideth, Melissa
DiGiovanna, John J.
Tucker, Margaret A.
Goldstein, Alisa M.
Oh, Kyu-Seon
Ueda, Takahiro
Boyle, Jennifer
Sarihan, Mansi
Kraemer, Kenneth H.
TI Effect of mutations in XPD(ERCC2) on pregnancy and prenatal development
in mothers of patients with trichothiodystrophy or xeroderma pigmentosum
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE DNA repair; pre-eclampsia; transcription factor IIH
ID FACIO-SKELETAL SYNDROME; COCKAYNE-SYNDROME; XPD MUTATIONS; DNA-REPAIR;
NEUROLOGIC ABNORMALITIES; GENE; PHOTOSENSITIVITY; DISORDER; DISEASES;
CANCER
AB The XPD(ERCC2) gene encodes a DNA helicase involved in DNA repair and transcription. Patients with mutations in XPD may have different autosomal recessive phenotypes including trichothiodystrophy (TTD) or xeroderma pigmentosum (XP). TTD patients have sulfur-deficient, brittle hair, short stature and developmental delay. In contrast, XP patients have freckle-like pigmentation and a greatly increased risk of sun-induced skin cancers. Mothers of TTD patients have been reported to have a high frequency of pregnancy and neonatal complications. We performed a molecular epidemiological study of 15 mothers of 17 TTD patients and 13 mothers of 17 XP patients, all with XPD mutations. We found that 94% (16/17) of the TTD pregnancies had pre-term delivery, pre-eclampsia, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, prematurity or low birth weight. None of the 17 XP pregnancies had these complications (P<0.001). As mutations in XPD may have differential effects on DNA repair and transcription, these observations should provide insights into the role of XPD in human pregnancy and fetal development. European Journal of Human Genetics (2012) 20, 1308-1310; doi:10.1038/ejhg.2012.90; published online 23 May 2012
C1 [Tamura, Deborah; Khan, Sikandar G.; DiGiovanna, John J.; Oh, Kyu-Seon; Ueda, Takahiro; Boyle, Jennifer; Sarihan, Mansi; Kraemer, Kenneth H.] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Merideth, Melissa] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Merideth, Melissa] Intramural Off Rare Dis, Bethesda, MD USA.
[Tucker, Margaret A.; Goldstein, Alisa M.] NCI, Genet Epidemiol Branch, DCEG, Bethesda, MD 20892 USA.
[Sarihan, Mansi] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Kraemer, KH (reprint author), NCI, Dermatol Branch, Ctr Canc Res, Bldg 37,Room 4002,MSC 4258, Bethesda, MD 20892 USA.
EM kraemerk@nih.gov
RI Tucker, Margaret/B-4297-2015
FU Center for Cancer Research, National Cancer Institute, NIH, Bethesda,
MD, USA; Division of Cancer Epidemiology and Genetics, National Cancer
Institute, NIH, Bethesda, MD, USA; NIH; Pfizer, Inc.
FX This work was supported by the intramural research program of the Center
for Cancer Research and the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, NIH, Bethesda, MD, USA. Ms Sarihan
was supported by the Clinical Research Training Program, a
public-private partnership supported jointly by the NIH and Pfizer, Inc.
(via a grant to the Foundation for NIH from Pfizer, Inc.).
NR 27
TC 5
Z9 6
U1 2
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 DEC
PY 2012
VL 20
IS 12
BP 1308
EP 1310
DI 10.1038/ejhg.2012.90
PG 3
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 038GT
UT WOS:000311163900016
PM 22617342
ER
PT J
AU O'hUigin, C
AF O'hUigin, Colm
TI The research of W.E. Mayer (1953-2012): a spectrum of immune systems
SO IMMUNOGENETICS
LA English
DT Review
DE Major histocompatibility complex; Adaptive immune system; Trans-species;
Polymorphism; Vertebrate evolution
ID MAJOR HISTOCOMPATIBILITY-COMPLEX; LYMPHOCYTE-LIKE CELLS; HLA-DRB GENES;
CLASS-I GENES; CICHLID FISHES; SEA LAMPREY; POLYMORPHISM; EVOLUTION;
IDENTIFICATION; ORIGIN
AB Over a period of some 20 years, Werner Eugen Mayer played a significant role in establishing a framework for molecular studies of Mhc genes in multiple vertebrates. His work largely concerned gene isolation, sequencing, and related bioinformatic analyses both for the Mhc and for immune system genes of about 200 species, ranging from apes, monkeys, rodents, and marsupials, through to birds, bony fishes, and lampreys. In addition to his exploration of diverse Mhc genes, Werner is remembered for playing a critical role in the development of two important insights into the evolution of immune systems. His was among the first published DNA sequence-based descriptions of trans-species evolution of Mhc alleles, including the first description of the long-lived polymorphisms shared by humans and chimpanzees. This research opened the way for using Mhc polymorphisms in demographic analyses. The second important insight in which he played a prominent role involved the characterization of immune cells and their expressed genes in the lamprey, a jawless vertebrate. His findings helped to indicate the considerable degree to which extant immune mechanisms were co-opted in the creation of the adaptive immune system of jawed vertebrates.
C1 SAIC Frederick Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP O'hUigin, C (reprint author), SAIC Frederick Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM ohuiginc@mail.nih.gov
NR 41
TC 0
Z9 0
U1 0
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0093-7711
J9 IMMUNOGENETICS
JI Immunogenetics
PD DEC
PY 2012
VL 64
IS 12
BP 849
EP 854
DI 10.1007/s00251-012-0654-9
PG 6
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 036KT
UT WOS:000311025500001
PM 23053060
ER
PT J
AU Hicks, CW
Sweeney, DA
Danner, RL
Eichacker, PQ
Suffredini, AF
Feng, J
Sun, JF
Moriyama, B
Wesley, R
Behrend, EN
Solomon, SB
Natanson, C
AF Hicks, Caitlin W.
Sweeney, Daniel A.
Danner, Robert L.
Eichacker, Peter Q.
Suffredini, Anthony F.
Feng, Jing
Sun, Junfeng
Moriyama, Brad
Wesley, Robert
Behrend, Ellen N.
Solomon, Steven B.
Natanson, Charles
TI Beneficial effects of stress-dose corticosteroid therapy in canines
depend on the severity of staphylococcal pneumonia
SO INTENSIVE CARE MEDICINE
LA English
DT Article
DE Shock: experimental studies; SIRS/sepsis: experimental studies;
Antimicrobial agents; Cardiopulmonary resuscitation; Host defenses
against pathogens; Pulmonary nosocomial infections
ID HYPERDYNAMIC SEPTIC SHOCK; BACTERIAL CLEARANCE; HYDROCORTISONE THERAPY;
EXPERIMENTAL SEPSIS; CYTOKINE LEVELS; DOUBLE-BLIND; METAANALYSIS;
MORTALITY; EFFICACY; METHYLPREDNISOLONE
AB The effects of stress-dose corticosteroid therapy were studied in a canine staphylococcal pneumonia model of septic shock.
Immediately following intrabronchial bacterial challenge, purpose-bred beagles were treated with stress doses of desoxycorticosterone (DOC), a mineralocorticoid agonist, and dexamethasone (DEX), a glucocorticoid agonist, or with placebo for 96 h. Oxacillin (30 mg/kg every 8 h) was started 4 h after infection onset. Bacterial dose was titrated to achieve 80-90 % lethality (n = 20) using an adaptive design; additional animals (n = 18) were investigated using the highest bacterial dose.
Initial analysis of all animals (n = 38) demonstrated that the effects of DOC + DEX were significantly altered by bacterial dose (p = 0.04). The treatment effects of DOC + DEX were different in animals administered high or relatively lower bacterial doses in terms of survival (p = 0.05), shock reversal (p = 0.02), interleukin-6 levels (p = 0.02), and temperature (p = 0.01). DOC + DEX significantly improved the above parameters (p a parts per thousand currency sign 0.03 for all) and lung injury scores (p = 0.02) after high-dose bacterial challenges, but not after lower challenges (p = not significant for all). Oxacillin trough levels were below the minimum inhibitory concentration of the infecting organism, and DOC + DEX increased the frequency of persistent staphylococcal bacteremia (odds ratio 3.09; 95 % confidence interval 1.05-9.11; p = 0.04).
Stress-dose corticosteroids were only beneficial in cases of sepsis with high risk for death and even short courses may interfere with host mechanisms of bacterial clearance.
C1 [Hicks, Caitlin W.; Danner, Robert L.; Eichacker, Peter Q.; Suffredini, Anthony F.; Feng, Jing; Sun, Junfeng; Solomon, Steven B.; Natanson, Charles] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Hicks, Caitlin W.] Johns Hopkins Univ Hosp, Dept Gen Surg, Baltimore, MD 21287 USA.
[Hicks, Caitlin W.] NIH, Res Scholars Program, Howard Hughes Med Inst, Chevy Chase, MD USA.
[Sweeney, Daniel A.] Washington Hosp, Med Intensivist Program, Fremont, CA 94538 USA.
[Moriyama, Brad] NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA.
[Wesley, Robert] NIH, Off Deputy Director Clin Care, Ctr Clin, Bethesda, MD 20892 USA.
[Behrend, Ellen N.] Auburn Univ, Coll Vet Med, Dept Clin Sci, Auburn, AL 36849 USA.
RP Hicks, CW (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 9000 Rockville Pike,Bldg 10,Room 2C145, Bethesda, MD 20892 USA.
EM cmh@jhmi.edu
OI Hicks, Caitlin/0000-0001-7638-1936
FU Intramural NIH HHS [ZIA CL008074-10, ZIA CL008060-11]
NR 40
TC 9
Z9 9
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0342-4642
J9 INTENS CARE MED
JI Intensive Care Med.
PD DEC
PY 2012
VL 38
IS 12
BP 2063
EP 2071
DI 10.1007/s00134-012-2735-5
PG 9
WC Critical Care Medicine
SC General & Internal Medicine
GA 036KU
UT WOS:000311025600019
PM 23111805
ER
PT J
AU Jasny, E
Geer, S
Frank, I
Vagenas, P
Aravantinou, M
Salazar, AM
Lifson, JD
Piatak, M
Gettie, A
Blanchard, JL
Robbiani, M
AF Jasny, Edith
Geer, Suzanne
Frank, Ines
Vagenas, Panagiotis
Aravantinou, Meropi
Salazar, Andres M.
Lifson, Jeffrey D.
Piatak, Michael, Jr.
Gettie, Agegnehu
Blanchard, James L.
Robbiani, Melissa
TI Characterization of Peripheral and Mucosal Immune Responses In Rhesus
Macaques on Long-Term Tenofovir and Emtricitabine Combination
Antiretroviral Therapy
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE antiretroviral therapy; mucosal immunity; peripheral immunity; SIV
ID SIMIAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; SIV INFECTION;
HIV-INFECTION; DENDRITIC CELLS; REVERSE-TRANSCRIPTASE; DISOPROXIL
FUMARATE; DISEASE PROGRESSION; INFANT MACAQUES; PATHOGENIC SIV
AB Background: The goal of antiretroviral therapy (ART) is to suppress virus replication to limit immune system damage. Some have proposed combining ART with immune therapies to boost antiviral immunity. For this to be successful, ART must not impair physiological immune function.
Methods: We studied the impact of ART (tenofovir and emtricitabine) on systemic and mucosal immunity in uninfected and simian immunodeficiency (SIV)-infected Chinese rhesus macaques. Subcutaneous ART was initiated 2 weeks after tonsillar inoculation with SIVmac239.
Results: There was no evidence of immune dysregulation as a result of ART in either infected or uninfected animals. Early virus-induced alterations in circulating immune cell populations (decreased central memory T cells and myeloid dendritic cells) were detected, but normalized shortly after ART initiation. ART-treated animals showed marginal SIV-specific T-cell responses during treatment, which increased after ART discontinuation. Elevated expression of CXCL10 in oral, rectal, and blood samples and APOBEC3G mRNA in oral and rectal tissues was observed during acute infection and was down regulated after starting ART. ART did not impact the ability of the animals to respond to tonsillar application of polyICLC with increased CXCL10 expression in oral fluids and CD80 expression on blood myeloid dendritic cells.
Conclusion: Early initiation of ART prevented virus-induced damage and did not impede mucosal or systemic immune functions.
C1 [Jasny, Edith; Geer, Suzanne; Frank, Ines; Vagenas, Panagiotis; Aravantinou, Meropi; Robbiani, Melissa] Populat Council, Ctr Biomed Res, HIV & AIDS Program, New York, NY 10065 USA.
[Salazar, Andres M.] Oncovir, Washington, DC USA.
[Lifson, Jeffrey D.; Piatak, Michael, Jr.] NCI, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA.
[Gettie, Agegnehu] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA.
[Blanchard, James L.] Tulane Univ, Tulane Natl Primate Res Ctr, Covington, LA USA.
RP Robbiani, M (reprint author), Populat Council, Ctr Biomed Res, HIV & AIDS Program, 1230 York Ave, New York, NY 10065 USA.
EM mrobbiani@popcouncil.org
RI Vagenas, Panagiotis/H-7850-2013
OI Vagenas, Panagiotis/0000-0003-2107-0377
FU National Institutes of Health (NIH) National Institute of Dental and
Craniofacial Research [DE018293]; National Cancer Institute, NIH
[HHSN261200800001E]; NIH [1G20RR016930-01, 1G20RR018397-01,
1G20RR019628-01, 1G20RR013466-01, 1G20RR019607-01, 1G20RR21381,
1G20RR22760, 1CO6RR012112-01]; [RR000164]
FX Supported by the National Institutes of Health (NIH) National Institute
of Dental and Craniofacial Research Grant DE018293 and in part with
federal funds from the National Cancer Institute, NIH, under Contract
No. HHSN261200800001E. Partial support was provided to the Tulane
National Primate Research Center by base Grant RR000164 and NIH
construction Grants 1G20RR016930-01, 1G20RR018397-01, 1G20RR019628-01,
1G20RR013466-01, 1G20RR019607-01, 1G20RR21381, 1G20RR22760, and
1CO6RR012112-01. M. Robbiani is a 2002 Elizabeth Glaser Scientist.
NR 65
TC 4
Z9 4
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD DEC 1
PY 2012
VL 61
IS 4
BP 425
EP 435
DI 10.1097/QAI.0b013e318266be53
PG 11
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 037DU
UT WOS:000311083200007
PM 22820802
ER
PT J
AU Penazzato, M
Crowley, S
Mofenson, L
Franceschetto, G
Nannyonga, MM
Mazza, A
Giaquinto, C
AF Penazzato, Martina
Crowley, Siobhan
Mofenson, Lynne
Franceschetto, Genny
Nannyonga, Maria-Musoke
Mazza, Antonio
Giaquinto, Carlo
TI Programmatic Impact of the Evolution of WHO Pediatric Antiretroviral
Treatment Guidelines for Resource-Limited Countries (Tukula Fenna
Project, Uganda)
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE pediatrics; infants; guidelines; ART initiation; children;
antiretroviral therapy
ID MORTALITY; CHILDREN; THERAPY
AB Background: World Health Organization (WHO) recommendations for the initiation of antiretroviral therapy (ART) in children were revised in 2010, but the programmatic impact has had limited study.
Methods: We used a cohort of 985 Ugandan children followed since 2003 by the Tukula Fenna project to model the differential impact of the 2006, 2008, and 2010 WHO pediatric ART inititation criteria on the proportion of children eligible for ART at enrollment and over time.
Results: Using the WHO 2006, 2008, and 2010 ART criteria, 40%, 57%, and 66% of children, respectively, would have been eligible for ART at enrollment and 76%, 84%, and 88% 2 years later. Evaluating the entire cohort followed for 6 years using the 2006, 2008, and 2010 guidelines, the proportion in need of ART was found to be 70%, 82%, and 87%, respectively. Between 2006 and 2008, the proportions of eligible children starting ART within 6 and 12 months were 39% and 50%, respectively; after this, the proportions starting within 6 and 12 months were 50% and 52%. Before 2008, the most common criterion met in children who did not start ART was WHO clinical stage (odds ratio = 2.0, CI 95% = 1.2 to 3.2); after the 2008 recommendations, the most common eligibility criterion in children who did not start ART was age <12 months (odds ratio = 10.5, CI 95% = 3.8 to 31.1).
Conclusions: An overall increase of 17% (from 70% to 87%) in children in need of ART was observed in our cohort comparing the 2006 and 2010 guidelines; this increase was primarily driven by the introduction of universal treatment for infants <12 months in 2008.
C1 [Penazzato, Martina; Franceschetto, Genny; Giaquinto, Carlo] Univ Padua, Dept Paediat, Padua, Italy.
[Penazzato, Martina] MRC, Clin Trial Unit, London, England.
[Crowley, Siobhan] UNICEF S Africa, Hlth & Nutr Unit, Pretoria, South Africa.
[Mofenson, Lynne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Mat AIDS PAMA Branch, NIH, Bethesda, MD USA.
[Nannyonga, Maria-Musoke] St Raphael St Francis Nsambya Hosp, Nsambya Home Care, Kampala, Uganda.
[Mazza, Antonio] Santa Chiara Hosp, Dept Paediat, Trento, Italy.
RP Penazzato, M (reprint author), Univ Padua, Dept Paediat, Via Giustiniani 3, Padua, Italy.
EM martina.penazzato@gmail.com
OI Mofenson, Lynne/0000-0002-2818-9808
NR 9
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD DEC 1
PY 2012
VL 61
IS 4
BP 522
EP 525
DI 10.1097/QAI.0b013e31826f369d
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 037DU
UT WOS:000311083200020
PM 22932320
ER
PT J
AU Abeykoon, AH
Chao, CC
Wang, GH
Gucek, M
Yang, DCH
Ching, WM
AF Abeykoon, Amila H.
Chao, Chien-Chung
Wang, Guanghui
Gucek, Marjan
Yang, David C. H.
Ching, Wei-Mei
TI Two Protein Lysine Methyltransferases Methylate Outer Membrane Protein B
from Rickettsia
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID STRUCTURE PREDICTION; PROWAZEKII; ROMPB; INFECTION; VIRULENCE; INVASION;
STRAINS; CONORII; SERVER; CELLS
AB Rickettsia prowazekii, the etiologic agent of epidemic typhus, is a potential biological threat agent. Its outer membrane protein B (OmpB) is an immunodominant antigen and plays roles as protective envelope and as adhesins. The observation of the correlation between methylation of lysine residues in rickettsial OmpB and bacterial virulence has suggested the importance of an enzymatic system for the methylation of OmpB. However, no rickettsial lysine methyltransferase has been characterized. Bioinformatic analysis of genomic DNA sequences of Rickettsia identified putative lysine methyltransferases. The genes of the potential methyltransferases were synthesized, cloned, and expressed in Escherichia coli, and expressed proteins were purified by nickel-nitrilotriacetic acid (Ni-NTA) affinity chromatography. The methyltransferase activities of the purified proteins were analyzed by methyl incorporation of radioactively labeled S-adenosylmethionine into recombinant fragments of OmpB. Two putative recombinant methyltransferases (rRP789 and rRP027-028) methylated recombinant OmpB fragments. The specific activity of rRP789 is 10- to 30-fold higher than that of rRP027-028. Western blot analysis using specific antibodies against trimethyl lysine showed that both rRP789 and rRP027-028 catalyzed trimethylation of recombinant OmpB fragments. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis showed that rRP789 catalyzed mono-, di-, and trimethylation of lysine, while rRP027-028 catalyzed exclusively trimethylation. To our knowledge, rRP789 and rRP027-028 are the first biochemically characterized lysine methyltransferases of outer membrane proteins from Gram-negative bacteria. The production and characterization of rickettsial lysine methyltransferases provide new tools to investigate the mechanism of methylation of OmpB, effects of methylation on the structure and function of OmpB, and development of methylated OmpB-based diagnostic assays and vaccine candidates.
C1 [Abeykoon, Amila H.; Yang, David C. H.] Georgetown Univ, Dept Chem, Washington, DC 20057 USA.
[Chao, Chien-Chung; Ching, Wei-Mei] USN, Med Res Ctr, Infect Dis Directorate, Viral & Rickettsial Dis Dept, Silver Spring, MD USA.
[Wang, Guanghui; Gucek, Marjan] NHLBI, Prote Core Facil, Bethesda, MD 20892 USA.
RP Yang, DCH (reprint author), Georgetown Univ, Dept Chem, Washington, DC 20057 USA.
EM yangdc@georgetown.edu
RI Yang, David/A-7294-2009
FU Naval Medical Logistic Command award [N62645, 6000.RAD1.J.A0310]
FX The work was supported by Naval Medical Logistic Command award N62645
(to Georgetown University) and work unit number (WUN) 6000.RAD1.J.A0310
(to NMRC). C.-C. C. and W.-M. C. are employees of the U. S. Government.
This work was prepared as part of official duties.
NR 38
TC 10
Z9 10
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD DEC
PY 2012
VL 194
IS 23
BP 6410
EP 6418
DI 10.1128/JB.01379-12
PG 9
WC Microbiology
SC Microbiology
GA 035DV
UT WOS:000310924300007
PM 23002218
ER
PT J
AU Ramaswamy, M
Siegel, RM
AF Ramaswamy, Madhu
Siegel, Richard M.
TI Autoimmunity: Twenty Years in the Fas Lane
SO JOURNAL OF IMMUNOLOGY
LA English
DT Editorial Material
ID PROGRAMMED CELL-DEATH; FAMILY MEMBER BIM; LYMPHOPROLIFERATIVE SYNDROME;
SIGNALING COMPLEX; INDUCED APOPTOSIS; T-CELLS; SYSTEMIC AUTOIMMUNITY;
LYMPHOCYTE APOPTOSIS; GENE-MUTATIONS; CD95
C1 [Ramaswamy, Madhu; Siegel, Richard M.] NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
RP Siegel, RM (reprint author), NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bldg 10,Room 9N238, Bethesda, MD 20892 USA.
EM rsiegel@nih.gov
FU Intramural NIH HHS [Z01 AR041133-06, Z99 AR999999]
NR 62
TC 3
Z9 3
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD DEC 1
PY 2012
VL 189
IS 11
BP 5097
EP 5100
DI 10.4049/jimmunol.1202833
PG 4
WC Immunology
SC Immunology
GA 039ZJ
UT WOS:000311287600002
PM 23169861
ER
PT J
AU Watanabe-Fukunaga, R
Brannan, CI
Copeland, NG
Jenkins, NA
Nagata, S
AF Watanabe-Fukunaga, Rie
Brannan, Camilynn I.
Copeland, Neal G.
Jenkins, Nancy A.
Nagata, Shigekazu
TI Lymphoproliferation disorder in mice explained by defects in fas antigen
that mediates apoptosis (Reprinted from Nature, vol 356, pg 314-317,
1992)
SO JOURNAL OF IMMUNOLOGY
LA English
DT Reprint
ID TUMOR-NECROSIS-FACTOR; B-CELL DEFECT; LPR LPR MICE; T-CELLS; SYSTEMIC
AUTOIMMUNITY; GENE; RECEPTOR; GLD; LYMPHADENOPATHY; EXPRESSION
AB Fas antigen is a cell-surface protein that mediates apoptosis. It is expressed in various tissues including the thymus and has structural homology with a number of cell-surface receptors, including tumour necrosis factor receptor and nerve growth factor receptor. Mice carrying the lymphoproliferation (lpr) mutation have defects in the Fas antigen gene. The lpr mice develop lymphadenopathy and suffer from a systemic lupus erythematosus-like autoimmune disease, indicating an important role for Fas antigen in the negative selection of autoreactive T cells in the thymus.
C1 [Watanabe-Fukunaga, Rie; Nagata, Shigekazu] Osaka Biosci Inst, Suita, Osaka 565, Japan.
[Brannan, Camilynn I.; Copeland, Neal G.; Jenkins, Nancy A.] NCI, Mammalian Genet Lab, ABL, Basic Res Program,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA.
RP Nagata, S (reprint author), Osaka Biosci Inst, 6-2-4 Furuedai, Suita, Osaka 565, Japan.
NR 35
TC 0
Z9 0
U1 0
U2 12
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD DEC 1
PY 2012
VL 189
IS 11
BP 5101
EP 5104
PG 4
WC Immunology
SC Immunology
GA 039ZJ
UT WOS:000311287600003
PM 23169862
ER
PT J
AU Cunnington, AJ
Njie, M
Correa, S
Takem, EN
Riley, EM
Walther, M
AF Cunnington, Aubrey J.
Njie, Madi
Correa, Simon
Takem, Ebako N.
Riley, Eleanor M.
Walther, Michael
TI Prolonged Neutrophil Dysfunction after Plasmodium falciparum Malaria Is
Related to Hemolysis and Heme Oxygenase-1 Induction
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CHRONIC GRANULOMATOUS-DISEASE; SALMONELLA INFECTION; OXIDATIVE BURST;
KENYAN CHILDREN; NONTYPHOIDAL SALMONELLA; HUMAN MONOCYTES;
FLOW-CYTOMETRY; NADPH OXIDASE; WHOLE-BLOOD; SUSCEPTIBILITY
AB It is not known why people are more susceptible to bacterial infections such as nontyphoid Salmonella during and after a malaria infection, but in mice, malarial hemolysis impairs resistance to nontyphoid Salmonella by impairing the neutrophil oxidative burst. This acquired neutrophil dysfunction is a consequence of induction of the cytoprotective, heme-degrading enzyme heme oxygenase-1 (HO-1) in neutrophil progenitors in bone marrow. In this study, we assessed whether neutrophil dysfunction occurs in humans with malaria and how this relates to hemolysis. We evaluated neutrophil function in 58 Gambian children with Plasmodium falciparum malaria [55 (95%) with uncomplicated disease] and examined associations with erythrocyte count, haptoglobin, hemopexin, plasma heme, expression of receptors for heme uptake, and HO-1 induction. Malaria caused the appearance of a dominant population of neutrophils with reduced oxidative burst activity, which gradually normalized over 8 wk of follow-up. The degree of neutrophil impairment correlated significantly with markers of hemolysis and HO-1 induction. HO-1 expression was increased in blood during acute malaria, but at a cellular level HO-1 expression was modulated by changes in surface expression of the haptoglobin receptor (CD163). These findings demonstrate that neutrophil dysfunction occurs in P. falciparum malaria and support the relevance of the mechanistic studies in mice. Furthermore, they suggest the presence of a regulatory pathway to limit HO-1 induction by hemolysis in the context of infection and indicate new targets for therapeutic intervention to abrogate the susceptibility to bacterial infection in the context of hemolysis in humans. The Journal of Immunology, 2012, 189: 5336-5346.
C1 [Cunnington, Aubrey J.; Riley, Eleanor M.] Univ London London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Immunol & Infect, London WC1E 7HT, England.
[Cunnington, Aubrey J.; Njie, Madi; Correa, Simon; Takem, Ebako N.; Walther, Michael] MRC Labs, Banjul, Gambia.
[Walther, Michael] NIAID, Immune Regulat Sect, Lab Malaria Immunol & Vaccinol, Div Intramural Res,NIH, Rockville, MD USA.
RP Cunnington, AJ (reprint author), Univ London London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Immunol & Infect, Keppel St, London WC1E 7HT, England.
EM aubrey.cunnington@lshtm.ac.uk
RI Riley, Eleanor/C-8960-2013;
OI Riley, Eleanor/0000-0003-3447-3570; Cunnington,
Aubrey/0000-0002-1305-3529
FU Medical Research Council (U.K.) [G0701427]; Medical Research Council
FX This work was supported by a clinical research training fellowship from
the Medical Research Council (U.K.) (G0701427 to A.J.C.) and by Medical
Research Council Institute funding to the Medical Research Council
Laboratories, Gambia.
NR 67
TC 37
Z9 37
U1 0
U2 6
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD DEC 1
PY 2012
VL 189
IS 11
BP 5336
EP 5346
DI 10.4049/jimmunol.1201028
PG 11
WC Immunology
SC Immunology
GA 039ZJ
UT WOS:000311287600030
PM 23100518
ER
PT J
AU Dunleavy, K
AF Dunleavy, Kieron
TI Advancing therapeutics in human immunodeficiency virus-associated
lymphoma: where to go from here?
SO LEUKEMIA & LYMPHOMA
LA English
DT Editorial Material
ID NON-HODGKIN-LYMPHOMA; B-CELL LYMPHOMA; RITUXIMAB; CHEMOTHERAPY; TRIAL;
EPOCH; CHOP
C1 NCI, Metab Branch, Bethesda, MD 20892 USA.
RP Dunleavy, K (reprint author), NCI, Metab Branch, Bldg 10,Room 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dunleavk@mail.nih.gov
NR 14
TC 0
Z9 0
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 DEC
PY 2012
VL 53
IS 12
BP 2333
EP 2334
DI 10.3109/10428194.2012.712691
PG 2
WC Oncology; Hematology
SC Oncology; Hematology
GA 032IJ
UT WOS:000310709000002
PM 22897732
ER
PT J
AU Tong, HY
Hu, C
Zhuang, ZP
Wang, LJ
Jin, J
AF Tong, Hongyan
Hu, Chao
Zhuang, Zhengping
Wang, Lijun
Jin, Jie
TI Hypoxia-inducible factor-1 alpha expression indicates poor prognosis in
myelodysplastic syndromes
SO LEUKEMIA & LYMPHOMA
LA English
DT Article
DE Myelodysplastic syndromes; hypoxia; hypoxia-inducible factor-1 alpha;
immunohistochemistry
ID WORLD-HEALTH-ORGANIZATION; ACUTE MYELOID-LEUKEMIA; FACTOR 1-ALPHA;
GENE-EXPRESSION; CANCER; METHYLATION; RESISTANCE; HIF-1; CLASSIFICATION;
CHEMOTHERAPY
AB Myelodysplastic syndromes (MDS), which are clonal bone marrow malignancies characterized by ineffective hematopoiesis, incorporate a variety of disorders and have variable prognosis. Although the International Prognostic Scoring System (IPSS) provides a clinical model for risk stratification of patients with primary MDS, notable variability in prognosis is still observed within the same IPSS category. Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is associated with an adverse prognosis in patients with solid tumors and some hematological malignancies. However, the relationship between HIF-1 alpha and clinical outcomes of patients with MDS is unknown. We examined HIF-1 alpha by immunohistochemistry in bone marrow specimens from 81 patients with MDS. Results showed that the expression rate of HIF-1 alpha was 49.4% (40/81). Multivariate analysis including age, bone marrow blast percentage, cytogenetics, hemoglobin, white blood cell count and IPSS score demonstrated that HIF-1 alpha (p = 0.049, HR = 2.704) was an independent prognostic indicator for MDS. Furthermore, the expression of HIF-1 alpha was correlated with poor overall survival (p < 0.001) and disease progression (p = 0.004). In addition, correlation analysis revealed that the expression of HIF-1 alpha was associated with bone marrow blast percentage (p < 0.001, r = 0.510), hemoglobin count (p < 0.001, r = -0.649) and cytogenetics (p = 0.009, r = 0.287). We also found that decitabine achieved a better therapeutic effect compared to traditional chemotherapy in HIF-1 alpha positive patients. In conclusion, these results suggest that HIF-1 alpha is a vital biomarker for predicting the progression and prognosis of MDS.
C1 [Tong, Hongyan; Hu, Chao; Jin, Jie] Zhejiang Univ, Dept Hematol, Affiliated Hosp 1, Coll Med, Hangzhou 310003, Zhejiang, Peoples R China.
[Wang, Lijun] Zhejiang Univ, Dept Pathol, Affiliated Hosp 1, Coll Med, Hangzhou 310003, Zhejiang, Peoples R China.
[Tong, Hongyan; Hu, Chao; Jin, Jie] Zhejiang Univ, Inst Hematol, Hangzhou 310003, Zhejiang, Peoples R China.
[Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Tong, HY (reprint author), Zhejiang Univ, Dept Hematol, Affiliated Hosp 1, Coll Med, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China.
EM hongyantong@yahoo.com.cn
FU National Natural Science Foundation of China [30870914]; Medical
Scientific Research Foundation of Zhejiang Province [2009B046]
FX This research was supported by grants from the National Natural Science
Foundation of China (No. 30870914) and Medical Scientific Research
Foundation of Zhejiang Province (No. 2009B046), and also assistance from
the Case Management Center and Pathology Department of the First
Affiliated Hospital, College of Medicine, Zhejiang University.
NR 34
TC 11
Z9 13
U1 0
U2 10
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 DEC
PY 2012
VL 53
IS 12
BP 2412
EP 2418
DI 10.3109/10428194.2012.696637
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA 032IJ
UT WOS:000310709000015
PM 22632108
ER
PT J
AU Ahmed, S
Berzon, RA
Revicki, DA
Lenderking, WR
Moinpour, CM
Basch, E
Reeve, BB
Wu, AW
AF Ahmed, Sara
Berzon, Richard A.
Revicki, Dennis A.
Lenderking, William R.
Moinpour, Carol M.
Basch, Ethan
Reeve, Bryce B.
Wu, Albert W.
CA Int Soc Quality Life Res
TI The Use of Patient-reported Outcomes (PRO) Within Comparative
Effectiveness Research Implications for Clinical Practice and Health
Care Policy
SO MEDICAL CARE
LA English
DT Article
DE patient-reported outcome; comparative effectiveness research; clinical
care; health policy
ID QUALITY-OF-LIFE; MCGILL PAIN QUESTIONNAIRE; PREFERENCE-BASED MEASURE;
WELL-BEING SCALE; SURVEY MOS-HIV; LOW-BACK-PAIN; MEDICAL OUTCOMES;
UTILITIES INDEX; BREAST-CANCER; METHODOLOGICAL QUALITY
AB Background: The goal of comparative effectiveness research (CER) is to explain the differential benefits and harms of alternate methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. To inform decision making, information from the patient's perspective that reflects outcomes that patients care about are needed and can be collected rigorously using appropriate patient-reported outcomes (PRO). It can be challenging to select the most appropriate PRO measure given the proliferation of such questionnaires over the past 20 years.
Objective: In this paper, we discuss the value of PROs within CER, types of measures that are likely to be useful in the CER context, PRO instrument selection, and key challenges associated with using PROs in CER.
Methods: We delineate important considerations for defining the CER context, selecting the appropriate measures, and for the analysis and interpretation of PRO data. Emerging changes that may facilitate CER using PROs as an outcome are also reviewed including implementation of electronic and personal health records, hospital and population-based registries, and the use of PROs in national monitoring initiatives. The potential benefits of linking the information derived from PRO endpoints in CER to decision making is also reviewed.
Conclusions: The recommendations presented for incorporating PROs in CER are intended to provide a guide to researchers, clinicians, and policy makers to ensure that information derived from PROs is applicable and interpretable for a given CER context. In turn, CER will provide information that is necessary for clinicians, patients, and families to make informed care decisions.
C1 [Ahmed, Sara] McGill Univ, Fac Med, Sch Phys & Occupat Therapy, Ctr Rech Interdisciplinaire Readaptat,Hlth Ctr, Montreal, PQ H3G 1Y5, Canada.
[Berzon, Richard A.] Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD USA.
[Revicki, Dennis A.] United BioSource Corp, Hlth Outcomes Res, Bethesda, MD USA.
[Lenderking, William R.] United BioSource Corp, Ctr Hlth Outcomes Res, Lexington, MA USA.
[Moinpour, Carol M.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98104 USA.
[Basch, Ethan] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Reeve, Bryce B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Reeve, Bryce B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA.
[Wu, Albert W.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Ahmed, S (reprint author), McGill Univ, Fac Med, Sch Phys & Occupat Therapy, Ctr Rech Interdisciplinaire Readaptat,Hlth Ctr, 3654 Prom Sir William Osler, Montreal, PQ H3G 1Y5, Canada.
EM sara.ahmed@mcgill.ca
FU Fonds de la Recherche en Sante du Quebec (FRSQ) research career award
FX S. Ahmed is supported by a Fonds de la Recherche en Sante du Quebec
(FRSQ) research career award.
NR 124
TC 72
Z9 72
U1 10
U2 46
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7079
EI 1537-1948
J9 MED CARE
JI Med. Care
PD DEC
PY 2012
VL 50
IS 12
BP 1060
EP 1070
DI 10.1097/MLR.0b013e318268aaff
PG 11
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 037LU
UT WOS:000311107300008
PM 22922434
ER
PT J
AU Philip, S
Machado, JP
Maldonado, E
Vasconcelos, V
O'Brien, SJ
Johnson, WE
Antunes, A
AF Philip, Siby
Machado, Joao Paulo
Maldonado, Emanuel
Vasconcelos, Vitor
O'Brien, Stephen J.
Johnson, Warren E.
Antunes, Agostinho
TI Fish Lateral Line Innovation: Insights into the Evolutionary Genomic
Dynamics of a Unique Mechanosensory Organ
SO MOLECULAR BIOLOGY AND EVOLUTION
LA English
DT Article
DE lateral line; teleost; adaptive evolution; positive selection
ID MAXIMUM-LIKELIHOOD PHYLOGENIES; RAY-FINNED FISHES; POSITIVE SELECTION;
DUPLICATE GENES; NUCLEOTIDE SUBSTITUTION; VERTEBRATE CHROMOSOMES;
MOLECULAR EVOLUTION; SIGNAL-TRANSDUCTION; SEQUENCE ALIGNMENT;
MITOCHONDRIAL-DNA
AB The mechanosensory lateral line, found only in fishes and amphibians, is an important sense organ associated with aquatic life. Lateral line patterns differ among teleost, the most diverse vertebrate taxa, hypothetically in response to selective pressures from different aquatic habitats. In this article, we conduct evolutionary genomic analyses of 34 genes associated with lateral line system development in teleosts to elucidate the significance of contrasting evolutionary rates and changes in the protein coding sequences. We find that duplicated copies of these genes are preferentially retained in the teleost genomes and that episodic events of positive selection have occurred in 22 of the 30 postduplication branches. In general, teleost genes evolved at a faster rate relative to their tetrapod counterparts, and the mutation rates of 26 of the 34 genes differed among teleosts and tetrapods. We conclude that following whole genome duplication, evolutionary rates and episodic events of positive selection on the lateral line system development genes might have been one of the factors favoring the subsequent adaptive radiation of teleosts into diverse habitats. These results provide the foundation for further detailed explorations into lateral line system genes and the evolution of diverse phenotypes and adaptations.
C1 [Philip, Siby; Machado, Joao Paulo; Maldonado, Emanuel; Vasconcelos, Vitor; Antunes, Agostinho] Univ Porto, Ctr Interdisciplinar Invest Marinha & Ambiental, CIMAR CIIMAR, P-4100 Oporto, Portugal.
[Philip, Siby; Vasconcelos, Vitor; Antunes, Agostinho] Univ Porto, Fac Ciencias, Dept Biol, P-4100 Oporto, Portugal.
[Machado, Joao Paulo] Univ Porto, ICBAS, P-4100 Oporto, Portugal.
[O'Brien, Stephen J.; Johnson, Warren E.; Antunes, Agostinho] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
[O'Brien, Stephen J.] St Petersburg State Univ, Theodosius Dobzhansky Ctr Genome Bioinformat, St Petersburg, Russia.
RP Antunes, A (reprint author), Univ Porto, Ctr Interdisciplinar Invest Marinha & Ambiental, CIMAR CIIMAR, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
EM aantunes@ciimar.up.pt
RI Vasconcelos, Vitor/A-8933-2008; Scientific output, CIIMAR/E-5122-2012;
Johnson, Warren/D-4149-2016;
OI Antunes, Agostinho/0000-0002-1328-1732; Maldonado,
Emanuel/0000-0002-0084-6116; Vasconcelos, Vitor/0000-0003-3585-2417;
Scientific output, CIIMAR/0000-0001-6270-2153; Johnson,
Warren/0000-0002-5954-186X; O'Brien, Stephen J./0000-0001-7353-8301
FU Portuguese Foundation for Science and Technology (FCT)
[SFRH/BD/47938/2008, SFRH/BD/65245/2009]; Intramural Research Program of
the National Institutes of Health, National Cancer Institute;
[PTDC/AAC-AMB/104983/2008 (FCOMP-01-0124-FEDER-008610)
PTDC/AAC-AMB/121301/2010 (FCOMP-01-0124-FEDER-019490)]
FX The authors thank two anonymous reviewers for constructive comments on
an earlier version of this manuscript. They also thank Osnat Penn for
advice on the use of RASERv2.0 (to S. P.), Hua Ying and Gavin Huttley
for advice on the PyCogent Ensembl query interface (to S. P.), and
Rajeev Raghavan for critical reading and suggestions on the manuscript.
The authors acknowledge the Portuguese Foundation for Science and
Technology (FCT) for financial support to S. P. (SFRH/BD/47938/2008) and
J.P.M. (SFRH/BD/65245/2009) and the projects PTDC/AAC-AMB/104983/2008
(FCOMP-01-0124-FEDER-008610) and PTDC/AAC-AMB/121301/2010
(FCOMP-01-0124-FEDER-019490) to A. A. This research received support by
the Intramural Research Program of the National Institutes of Health,
National Cancer Institute to W.E.J. and S.J.O.
NR 89
TC 6
Z9 6
U1 3
U2 28
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0737-4038
J9 MOL BIOL EVOL
JI Mol. Biol. Evol.
PD DEC
PY 2012
VL 29
IS 12
BP 3887
EP 3898
DI 10.1093/molbev/mss194
PG 12
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA 035SW
UT WOS:000310970000023
PM 22844072
ER
PT J
AU Guo, N
Lang, LX
Gao, HK
Niu, G
Kiesewetter, DO
Xie, QG
Chen, XY
AF Guo, Ning
Lang, Lixin
Gao, Haokao
Niu, Gang
Kiesewetter, Dale O.
Xie, Qingguo
Chen, Xiaoyuan
TI Quantitative Analysis and Parametric Imaging of F-18-Labeled Monomeric
and Dimeric RGD Peptides Using Compartment Model
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Article
DE Positron emission tomography; Kinetic modeling; Quantitative analysis;
RGD peptide; Integrin
ID INTEGRIN ALPHA(V)BETA(3) EXPRESSION; POSITRON-EMISSION-TOMOGRAPHY;
SMALL-ANIMAL PET; ALPHA-V-BETA-3 EXPRESSION; CANCER-PATIENTS; IN-VIVO;
RADIOSYNTHESIS; F-18-FPPRGD2; BINDING; AGENT
AB Purpose: Non-invasive PET imaging with radiolabeled RGD peptides for alpha(v)beta(3) integrin targeting has become an important tool for tumor diagnosis and treatment monitoring in both pre-clinical and clinical studies. To better understand the molecular process and tracer pharmacokinetics, we introduced kinetic modeling in the investigation of F-18-labeled RGD peptide monomer F-18-FP-c(RGDyK) (denoted as F-18-FPRGD) and dimer F-18-FP-PEG3-E[c(RGDyK)](2) (denoted as F-18-FPPRGD2).
Procedures: MDA-MB-435 tumor-bearing mice underwent 60 min dynamic PET scans following the injection of either F-18-FPRGD or F-18-FPPRGD2. Blocking studies with pre-injection of a blocking mass dose were performed for both monomeric and dimeric RGD groups. F-18-FPRAD (RAD) was used as a negative control. Kinetic parameters (K-1, k(2), k(3), k(4)) of a three-compartment model were fitted to the dynamic data to allow quantitative comparisons between the monomeric and dimeric RGD peptides.
Results: Dimeric RGD peptide tracer showed significantly higher binding potential (Bp(ND)=k(3)/k(4), 5.87 +/- 0.31) than that of the monomeric analog (2.75 +/- 0.48, p = 0.0022, n = 4/group). The Bp(ND) values showed a significantly greater ratio (dimer/monomer 2.1) than the difference in %ID/g uptake measured from static images (dimer/monomer 1.5, p = 0.0045). Significant decrease in Bp(ND) was found in the blocked groups compared with the unblocked ones (dimer p = 0.00024, monomer p = 0.005, n = 4/group). Similarly, the RAD control group showed the lowest Bp(ND) value among all the test groups, as the RAD peptide does not bind to integrin alpha(v)beta(3). Volume of distribution (V-T = K-1/k(2)(1 + k (3)/k (4))) could be separated into non-specific (V-ND = K (1)/k (2)) and specific (V-S = K-1 k(3)/(k(2) k(4))) components. Specific distribution volume (V-S) was the dominant component of V (T) in the unblocked groups and decreased in the blocked groups. Unblocked RGD dimer also showed higher V (S) than that of the monomer (dimer V-S = 2.38 +/- 0.15, monomer V-S = 0.90 +/- 0.17, p = 0.0013, n = 4/group), well correlated with Bp(ND) calculations. Little difference in V (ND) was found among all groups. Moreover, parametric maps allowed quantitative analysis at voxel level and provided higher tumor-to-background contrast for Bp(ND) maps than the static images. Tumor heterogeneity in kinetic parameters was found in parametric images, which could not be clearly identified in static intensity images.
Conclusions: The pharmacokinetics of both monomeric and dimeric RGD peptide tracers was compared, and the RGD dimers showed significantly higher binding affinity than the monomeric analogs. Kinetic parameters were demonstrated to be valuable for separating specific and non-specific binding and may allow more sensitive and detailed quantification than simple standardized uptake value analysis.
C1 [Guo, Ning; Xie, Qingguo] Huazhong Univ Sci & Technol, Dept Biomed Engn, Wuhan 430074, Hubei, Peoples R China.
[Guo, Ning; Xie, Qingguo] Wuhan Natl Lab Optoelect, Wuhan, Hubei, Peoples R China.
[Guo, Ning; Lang, Lixin; Gao, Haokao; Niu, Gang; Kiesewetter, Dale O.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
RP Xie, QG (reprint author), Huazhong Univ Sci & Technol, Dept Biomed Engn, 505 Bldg D11,1037 Luoyu Rd, Wuhan 430074, Hubei, Peoples R China.
EM qgxie@mail.hust.edu.cn; shawn.chen@nih.gov
FU Intramural Research Program of the National Institute of Biomedical
Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH);
International Cooperative Program of the National Science Foundation of
China (NSFC) [81028009]; NSFC [60972099, 61027006]; China Scholarship
Council (CSC)
FX This work was supported in part, by the Intramural Research Program of
the National Institute of Biomedical Imaging and Bioengineering (NIBIB),
National Institutes of Health (NIH), the International Cooperative
Program of the National Science Foundation of China (NSFC) (81028009),
and NSFC Grants (60972099, 61027006). NG was partially sponsored by the
China Scholarship Council (CSC).
NR 34
TC 15
Z9 15
U1 0
U2 20
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD DEC
PY 2012
VL 14
IS 6
BP 743
EP 752
DI 10.1007/s11307-012-0541-7
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 034LA
UT WOS:000310873400010
PM 22437879
ER
PT J
AU Hu, S
Kiesewetter, DO
Zhu, L
Guo, N
Gao, HK
Liu, G
Hida, N
Lang, LX
Niu, G
Chen, XY
AF Hu, Shuo
Kiesewetter, Dale O.
Zhu, Lei
Guo, Ning
Gao, Haokao
Liu, Gang
Hida, Naoki
Lang, Lixin
Niu, Gang
Chen, Xiaoyuan
TI Longitudinal PET Imaging of Doxorubicin-Induced Cell Death with
F-18-Annexin V
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Article
DE F-18-Annexin V; Doxorubicin; Apoptosis; PET; Chemotherapy
ID IN-VIVO DETECTION; TC-99M ANNEXIN-V; TUMOR RESPONSE; APOPTOSIS;
EXPRESSION; AGENT; CARCINOMA; CHEMOTHERAPY; CANCER; HEAD
AB Purpose: This study aims to apply longitudinal positron emission tomography (PET) imaging with (18) F-Annexin V to visualize and evaluate cell death induced by doxorubicin in a human head and neck squamous cell cancer UM-SCC-22B tumor xenograft model.
Procedures: In vitro toxicity of doxorubicin to UM-SCC-22B cells was determined by a colorimetric assay. Recombinant human Annexin V protein was expressed and purified. The protein was labeled with fluorescein isothiocyanate for fluorescence staining and (18) F for PET imaging. Established UM-SCC-22B tumors in nude mice were treated with two doses of doxorubicin (10 mg/kg each dose) with 1 day interval. Longitudinal (18) F-Annexin V PET was performed at 6 h, 24 h, 3 days, and 7 days after the treatment started. Following PET imaging, direct tissue biodistribution study was performed to confirm the accuracy of PET quantification.
Results: Two doses of doxorubicin effectively inhibited the growth of UM-SCC-22B tumors by inducing cell death including apoptosis. The cell death was clearly visualized by (18) F-Annexin V PET. The peak tumor uptake, which was observed at day 3 after treatment started, was significantly higher than that in the untreated tumors (1.56 +/- 0.23 vs. 0.89 +/- 0.31%ID/g, p < 0.05). Moreover, the tumor uptake could be blocked by co-injection of excess amount of unlabeled Annexin V protein. At day 7 after treatment, the tumor uptake of (18) F-Annexin had returned to baseline level.
Conclusions: (18) F-Annexin V PET imaging is sensitive enough to allow visualization of doxorubicin-induced cell death in UM-SCC-22B xenograft model. The longitudinal imaging with (18) F-Annexin will be helpful to monitor early response to chemotherapeutic anti-cancer drugs.
C1 [Hu, Shuo; Kiesewetter, Dale O.; Zhu, Lei; Guo, Ning; Gao, Haokao; Liu, Gang; Hida, Naoki; Lang, Lixin; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Hu, Shuo] Cent S Univ, Dept Nucl Med, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China.
[Liu, Gang] N Sichuan Med Coll, Affiliated Hosp, Sichuan Key Lab Med Imaging, Dept Radiol, Nanchong 637007, Peoples R China.
RP Niu, G (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, 9 Mem Dr,9-1W111, Bethesda, MD 20892 USA.
EM niug@mail.nih.gov; shawn.chen@nih.gov
RI Zhu, Lei/P-9786-2016
OI Zhu, Lei/0000-0002-1820-4795
FU Intramural Research Program of the National Institute of Biomedical
Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH);
International Cooperative Program of the National Science Foundation of
China (NSFC) [81028009]
FX This project was supported by the Intramural Research Program of the
National Institute of Biomedical Imaging and Bioengineering (NIBIB),
National Institutes of Health (NIH), and the International Cooperative
Program of the National Science Foundation of China (NSFC) (81028009).
NR 35
TC 22
Z9 23
U1 5
U2 28
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD DEC
PY 2012
VL 14
IS 6
BP 762
EP 770
DI 10.1007/s11307-012-0551-5
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 034LA
UT WOS:000310873400012
PM 22392643
ER
PT J
AU Pillai, AD
Nguitragool, W
Lyko, B
Dolinta, K
Butler, MM
Nguyen, ST
Peet, NP
Bowlin, TL
Desai, SA
AF Pillai, Ajay D.
Nguitragool, Wang
Lyko, Brian
Dolinta, Keithlee
Butler, Michelle M.
Nguyen, Son T.
Peet, Norton P.
Bowlin, Terry L.
Desai, Sanjay A.
TI Solute Restriction Reveals an Essential Role for clag3-Associated
Channels in Malaria Parasite Nutrient Acquisition
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID SURFACE ANION CHANNEL; INFECTED HUMAN ERYTHROCYTES; RED-BLOOD-CELLS;
PLASMODIUM-FALCIPARUM CLONES; HIGH-THROUGHPUT SCREEN; ANTIGENIC
VARIATION; HOST ERYTHROCYTE; PERMEABILITY PATHWAYS; GENES; GROWTH
AB The plasmodial surface anion channel (PSAC) increases erythrocyte permeability to many solutes in malaria but has uncertain physiological significance. We used a PSAC inhibitor with different efficacies against channels from two Plasmodium falciparum parasite lines and found concordant effects on transport and in vitro parasite growth when external nutrient concentrations were reduced. Linkage analysis using this growth inhibition phenotype in the Dd2 x HB3 genetic cross mapped the clag3 genomic locus, consistent with a role for two clag3 genes in PSAC-mediated transport. Altered inhibitor efficacy, achieved through allelic exchange or expression switching between the clag3 genes, indicated that the inhibitor kills para-sites through direct action on PSAC. In a parasite unable to undergo expression switching, the inhibitor selected for ectopic homologous recombination between the clag3 genes to increase the diversity of available channel isoforms. Broad-spectrum inhibitors, which presumably interact with conserved sites on the channel, also exhibited improved efficacy with nutrient restriction. These findings indicate that PSAC functions in nutrient acquisition for intracellular parasites. Although key questions regarding the channel and its biological role remain, antimalarial drug development targeting PSAC should be pursued.
C1 [Pillai, Ajay D.; Nguitragool, Wang; Lyko, Brian; Dolinta, Keithlee; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Butler, Michelle M.; Nguyen, Son T.; Peet, Norton P.; Bowlin, Terry L.] Microbiotix Inc, Worcester, MA USA.
RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3W-01, Rockville, MD 20852 USA.
EM sdesai@niaid.nih.gov
FU Medicines for Malaria Venture; National Institutes of Health, National
Institute of Allergy and Infectious Diseases
FX This research was supported by the Medicines for Malaria Venture and the
Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases. A.D.P. and S.A.D.
are named inventors on provisional patent applications describing some
of the PSAC inhibitors reported in this article. M.M.B., S.T.N., N.P.P.,
and T.L.B. are employees and shareholders of Microbiotix, Inc., which
has obtained a license to develop PSAC inhibitors as antimalarial drugs.
NR 59
TC 31
Z9 31
U1 0
U2 5
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD DEC
PY 2012
VL 82
IS 6
BP 1104
EP 1114
DI 10.1124/mol.112.081224
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 037WP
UT WOS:000311137500010
PM 22949525
ER
PT J
AU Ombrello, MJ
Kastner, DL
Milner, JD
AF Ombrello, Michael J.
Kastner, Daniel L.
Milner, Joshua D.
TI HOIL and water: the two faces of HOIL-1 deficiency
SO NATURE IMMUNOLOGY
LA English
DT News Item
ID AUTOINFLAMMATORY DISEASE; IMMUNODEFICIENCY; PLCG2
AB Autoinflammation and immunodeficiency are rare in humans, but the rate of discovery of these conditions has increased. Three patients have now been characterized in whom deficiency in HOIL-1, a component of the LUBAC complex, leads to these conditions.
C1 [Ombrello, Michael J.; Kastner, Daniel L.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Milner, Joshua D.] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA.
RP Ombrello, MJ (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
EM ombrellomj@mail.nih.gov; kastnerd@arb.niams.nih.gov
NR 10
TC 8
Z9 8
U1 0
U2 4
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 DEC
PY 2012
VL 13
IS 12
BP 1133
EP 1135
DI 10.1038/ni.2471
PG 3
WC Immunology
SC Immunology
GA 039BN
UT WOS:000311217900002
PM 23160206
ER
PT J
AU Ring, AM
Lin, JX
Feng, D
Mitra, S
Rickert, M
Bowman, GR
Pande, VS
Li, P
Moraga, I
Spolski, R
Ozkan, E
Leonard, WJ
Garcia, KC
AF Ring, Aaron M.
Lin, Jian-Xin
Feng, Dan
Mitra, Suman
Rickert, Mathias
Bowman, Gregory R.
Pande, Vijay S.
Li, Peng
Moraga, Ignacio
Spolski, Rosanne
Oezkan, Engin
Leonard, Warren J.
Garcia, K. Christopher
TI Mechanistic and structural insight into the functional dichotomy between
IL-2 and IL-15
SO NATURE IMMUNOLOGY
LA English
DT Article
ID ALPHA-RECEPTOR; DIFFERENTIAL REGULATION; MOLECULAR SIMULATION; FAMILY
CYTOKINES; CELL-SURVIVAL; T-CELLS; INTERLEUKIN-2; BINDING; KINETICS;
COMPLEX
AB Interleukin 15 (IL-15) and IL-2 have distinct immunological functions even though both signal through the receptor subunit IL-2R beta and the common gamma-chain (gamma(c)). Here we found that in the structure of the IL-15-IL-15R alpha-IL-2R beta-gamma(c) quaternary complex, IL-15 binds to IL-2R beta and gamma(c) in a heterodimer nearly indistinguishable from that of the IL-2-IL-2R alpha-IL-2R beta-gamma(c) complex, despite their different receptor-binding chemistries. IL-15R alpha substantially increased the affinity of IL-15 for IL-2R beta, and this allostery was required for IL-15 trans signaling. Consistent with their identical IL-2R beta-gamma(c) dimer geometries, IL-2 and IL-15 showed similar signaling properties in lymphocytes, with any differences resulting from disparate receptor affinities. Thus, IL-15 and IL-2 induced similar signals, and the cytokine specificity of IL-2R alpha versus IL-15R alpha determined cellular responsiveness. Our results provide new insights for the development of specific immunotherapeutics based on IL-15 or IL-2.
C1 [Ring, Aaron M.; Feng, Dan; Rickert, Mathias; Moraga, Ignacio; Oezkan, Engin; Garcia, K. Christopher] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
[Ring, Aaron M.; Feng, Dan; Rickert, Mathias; Moraga, Ignacio; Oezkan, Engin; Garcia, K. Christopher] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
[Ring, Aaron M.; Feng, Dan; Rickert, Mathias; Moraga, Ignacio; Oezkan, Engin; Garcia, K. Christopher] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
[Mitra, Suman; Li, Peng; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Bowman, Gregory R.; Pande, Vijay S.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
RP Garcia, KC (reprint author), Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
EM kcgarcia@stanford.edu
FU US National Institutes of Health [R01 AI51321, R01 GM062868]; National
Research Service Award [NIH-F30DK094541]; American Recovery and
Reinvestment Act [MRI-R2]; Division of Intramural Research of the
National Heart, Lung and Blood Institute (US National Institutes of
Health); Stanford Medical Scientist Training Program [NIH-GM07365];
Howard Hughes Medical Institute
FX We thank E. Long, M. Rubinstein and members of the Leonard and Garcia
laboratories for advice and discussions; and N. Goriatcheva, D. Waghray
and S. Fischer for technical assistance. Supported by the US National
Institutes of Health (R01 AI51321 to K.C.G.; R01 GM062868 to V.S.P.; and
National Research Service Award NIH-F30DK094541 to A.M.R.), the American
Recovery and Reinvestment Act of 2009 (Public Law 111-5; MRI-R2 to
V.S.P.), the Division of Intramural Research of the National Heart, Lung
and Blood Institute (US National Institutes of Health; W.J.L., J.-X.L.,
P.L., S.M. and R.S.), the Stanford Medical Scientist Training Program
(NIH-GM07365 to A.M.R.) and the Howard Hughes Medical Institute
(K.C.G.).
NR 50
TC 68
Z9 69
U1 3
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD DEC
PY 2012
VL 13
IS 12
BP 1187
EP +
DI 10.1038/ni.2449
PG 11
WC Immunology
SC Immunology
GA 039BN
UT WOS:000311217900012
PM 23104097
ER
PT J
AU Subrahmanyam, R
Du, HS
Ivanova, I
Chakraborty, T
Ji, YH
Zhang, Y
Alt, FW
Schatz, DG
Sen, RJ
AF Subrahmanyam, Ramesh
Du, Hansen
Ivanova, Irina
Chakraborty, Tirtha
Ji, Yanhong
Zhang, Yu
Alt, Frederick W.
Schatz, David G.
Sen, Ranjan
TI Localized epigenetic changes induced by D-H recombination restricts
recombinase to DJ(H) junctions
SO NATURE IMMUNOLOGY
LA English
DT Article
ID CHAIN GENE LOCUS; V(D)J RECOMBINATION; V-H; PLANT HOMEODOMAIN;
REARRANGEMENT; ACTIVATION; LYSINE-4; SEGMENTS; MICE; PAX5
AB Genes encoding immunoglobulin heavy chains (Igh) are assembled by rearrangement of variable (V-H), diversity (D-H) and joining (J(H)) gene segments. Three critical constraints govern V-H recombination. These include timing (V-H recombination follows D-H recombination), precision (V-H gene segments recombine only to DJ(H) junctions) and allele specificity (V-H recombination is restricted to DJ(H)-recombined alleles). Here we provide a model for these universal features of V-H recombination. Analyses of DJ(H)-recombined alleles showed that DJ(H) junctions were selectively epigenetically marked, became nuclease sensitive and bound RAG recombinase proteins, which thereby permitted D-H-associated recombination signal sequences to initiate the second step of Igh gene assembly. We propose that V-H recombination is precise, because these changes did not extend to germline D-H segments located 5' of the DJ(H) junction.
C1 [Subrahmanyam, Ramesh; Du, Hansen; Ivanova, Irina; Chakraborty, Tirtha; Sen, Ranjan] NIA, US NIH, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
[Ji, Yanhong; Schatz, David G.] Yale Med Sch, Dept Immunobiol, Howard Hughes Med Inst, New Haven, CT USA.
[Zhang, Yu; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Zhang, Yu; Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst,Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
RP Sen, RJ (reprint author), NIA, US NIH, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
EM senranja@grc.nia.nih.gov
RI Subrahmanyam, Ramesh/K-5503-2012; Schatz, David/A-6748-2013
OI Schatz, David/0000-0002-5669-1176
FU Intramural Research Program of the National Institute on Aging (US
National Institutes of Health) [AI20047, AI32524]; Howard Hughes Medical
Institute
FX Supported by the Intramural Research Program of the National Institute
on Aging (US National Institutes of Health; AI20047 to F.W.A., and
AI32524 to D.G.S.) and the Howard Hughes Medical Institute (F.W.A. and
D.G.S.).
NR 39
TC 17
Z9 17
U1 1
U2 11
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 DEC
PY 2012
VL 13
IS 12
BP 1205
EP +
DI 10.1038/ni.2447
PG 9
WC Immunology
SC Immunology
GA 039BN
UT WOS:000311217900014
PM 23104096
ER
PT J
AU Villapol, S
Yaszemski, AK
Logan, TT
Sanchez-Lemus, E
Saavedra, JM
Symes, AJ
AF Villapol, Sonia
Yaszemski, Alexandra K.
Logan, Trevor T.
Sanchez-Lemus, Enrique
Saavedra, Juan M.
Symes, Aviva J.
TI Candesartan, an Angiotensin II AT(1)-Receptor Blocker and PPAR-gamma
Agonist, Reduces Lesion Volume and Improves Motor and Memory Function
After Traumatic Brain Injury in Mice
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE traumatic brain injury; candesartan; TGF beta; inflammation;
neuroprotection; PPAR gamma
ID SPONTANEOUSLY HYPERTENSIVE-RATS; ACTIVATED-RECEPTOR-GAMMA;
CEREBRAL-BLOOD-FLOW; TRANSFORMING GROWTH FACTOR-BETA(1); INNATE
IMMUNE-RESPONSE; TYPE-1 RECEPTOR; MICROGLIAL ACTIVATION; VASCULAR
INFLAMMATION; OXIDATIVE STRESS; EPITHELIAL-CELLS
AB Traumatic brain injury (TBI) results in complex pathological reactions, the initial lesion worsened by secondary inflammation and edema. Angiotensin II (Ang II) is produced in the brain and Ang II receptor type 1 (AT(1)R) overstimulation produces vasoconstriction and inflammation. Ang II receptor blockers (ARBs) are neuroprotective in models of stroke but little is known of their effect when administered in TBI models. We therefore performed controlled cortical impact (CCI) injury on mice to investigate whether the ARB candesartan would mitigate any effects of TBI. We administered candesartan or vehicle to mice 5 h before CCI injury. Candesartan treatment reduced the lesion volume after CCI injury by approximately 50%, decreased the number of dying neurons, lessened the number of activated microglial cells, protected cerebral blood flow (CBF), and reduced the expression of the cytokine TGF beta 1 while increasing expression of TGF beta 3. Candesartan-treated mice also showed better motor skills on the rotarod 3 days after injury, and improved performance in the Morris water maze 4 weeks after injury. These results indicate that candesartan is neuroprotective, reducing neuronal injury, decreasing lesion volume and microglial activation, protecting CBF and improving functional behavior in a mouse model of TBI. Co-treatment with a peroxisome proliferator-activated receptor-gamma (PPAR gamma) antagonist significantly reduced some of the beneficial effects of candesartan after CCI, suggesting that PPAR gamma activation may contribute to part or to all of the neuroprotective effect of candesartan. Overall, our data suggest that ARBs with dual AT(1)R-blocking and PPAR gamma activation properties may have therapeutic value in treating TBI. Neuropsychopharmacology (2012) 37, 2817-2829; doi: 10.1038/npp.2012.152; published online 15 August 2012
C1 [Villapol, Sonia; Yaszemski, Alexandra K.; Logan, Trevor T.; Symes, Aviva J.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA.
[Villapol, Sonia; Yaszemski, Alexandra K.; Logan, Trevor T.; Symes, Aviva J.] Ctr Neurosci & Regenerat Med, Bethesda, MD USA.
[Sanchez-Lemus, Enrique; Saavedra, Juan M.] NIMH, Pharmacol Sect, Div Intramural Res Programs, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
RP Symes, AJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pharmacol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM aviva.symes@usuhs.edu
RI Symes, Aviva/S-7471-2016
OI Symes, Aviva/0000-0003-2557-9939
FU Center for Neuroscience and Regenerative Medicine (CNRM); CNRM
postdoctoral fellowship; Division of Intramural Research Programs,
National Institute of Mental Health, National Institutes of Health
FX This study was supported by a pilot award from the Center for
Neuroscience and Regenerative Medicine (CNRM) grant (AJS). SV is
supported by a CNRM postdoctoral fellowship. JMS and ESL are supported
by the Division of Intramural Research Programs, National Institute of
Mental Health, National Institutes of Health. We thank Laura Tucker, Oz
Malkesman, and Amanda Fu from the CNRM pre-clinical core facility for
expert advice, Dr Tim ONeil for his assistance with blood pressure
measurements. We are grateful to members of the Symes and Saavedra
laboratories for their helpful comments and suggestions. The opinions
and assertions contained herein are the private opinions of the authors
and are not to be construed as reflecting the views of the Uniformed
Services University of the Health Sciences or the US Department of
Defense.
NR 82
TC 23
Z9 24
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2012
VL 37
IS 13
BP 2817
EP 2829
DI 10.1038/npp.2012.152
PG 13
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 037GT
UT WOS:000311090900009
PM 22892395
ER
PT J
AU Wang, B
You, ZB
Wise, RA
AF Wang, Bin
You, Zhi-Bing
Wise, Roy A.
TI Heroin Self-Administration Experience Establishes Control of Ventral
Tegmental Glutamate Release by Stress and Environmental Stimuli
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE heroin; self-administration; extinction; reinstatement; ventral
tegmental area; glutamate
ID NUCLEUS-ACCUMBENS SHELL; DOPAMINE NEURONS; COCAINE-SEEKING; INDUCED
RELAPSE; DRUG-SEEKING; AREA; REWARD; RAT; RECEPTORS; REINSTATEMENT
AB Heroin and cocaine have very different unconditioned receptor-mediated actions; however, in the brain circuitry of drug-reward and motivation, the two drugs establish common conditioned consequences. A single experience with either drug can change the sensitivity of ventral tegmental area (VTA) dopamine neurons to glutamatergic input. In the case of cocaine, repeated intravenous self-administration establishes de novo VTA glutamate release and dopaminergic activation in response to conditioned stimuli and mild footshock stress. Here we determined whether repeated self-administration of heroin would establish similar glutamate release and dopaminergic activation. Although self-administration of heroin itself did not cause VTA glutamate release, conditioned glutamate release was seen when rats expecting rewarding heroin were given nonrewarding saline in its place. Mild footshock stress also caused glutamate release in heroin-trained animals. In each case, the VTA glutamate release was accompanied by elevations in VTA dopamine levels, indicative of dopaminergic activation. In each case, infusion of the ionotropic glutamate antagonist kynurenic acid blocked the VTA dopamine release associated with VTA glutamate elevation. Although glutamate levels in the extinction and reinstatement tests were similar to those reported in cocaine studies, the effects of heroin self-administration itself were quite different from what has been seen during cocaine self-administration. Neuropsychopharmacology (2012) 37, 2863-2869; doi:10.1038/npp.2012.167; published online 5 September 2012
C1 [Wang, Bin; You, Zhi-Bing; Wise, Roy A.] NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
RP Wise, RA (reprint author), NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM rwise@intra.nida.nih.gov
FU Intramural Research Program, National Institute on Drug Abuse
FX This study was supported by the Intramural Research Program, National
Institute on Drug Abuse.
NR 37
TC 9
Z9 11
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2012
VL 37
IS 13
BP 2863
EP 2869
DI 10.1038/npp.2012.167
PG 7
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 037GT
UT WOS:000311090900014
PM 22948979
ER
PT J
AU Brady, LS
AF Brady, Linda S.
TI Stephen G Holtzman Obituary
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Biographical-Item
C1 NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA.
RP Brady, LS (reprint author), NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA.
EM lbrady@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2012
VL 37
IS 13
BP 2881
EP 2882
DI 10.1038/npp.2012.159
PG 2
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 037GT
UT WOS:000311090900016
ER
PT J
AU Bonci, A
AF Bonci, Antonello
TI Toni S Shippenberg Obituary
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Biographical-Item
C1 Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA.
RP Bonci, A (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA.
EM antonello.bonci@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2012
VL 37
IS 13
BP 2889
EP 2889
DI 10.1038/npp.2012.199
PG 1
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 037GT
UT WOS:000311090900022
ER
PT J
AU Haigentz, M
Kim, M
Sarta, C
Lin, J
Keresztes, RS
Culliney, B
Gaba, AG
Smith, RV
Shapiro, GI
Chirieac, LR
Mariadason, JM
Belbin, TJ
Greally, JM
Wright, JJ
Haddad, RI
AF Haigentz, Missak, Jr.
Kim, Mimi
Sarta, Catherine
Lin, Juan
Keresztes, Roger S.
Culliney, Bruce
Gaba, Anu G.
Smith, Richard V.
Shapiro, Geoffrey I.
Chirieac, Lucian R.
Mariadason, John M.
Belbin, Thomas J.
Greally, John M.
Wright, John J.
Haddad, Robert I.
TI Phase II trial of the histone deacetylase inhibitor romidepsin in
patients with recurrent/metastatic head and neck cancer
SO ORAL ONCOLOGY
LA English
DT Article
DE Romidepsin; Head and neck cancer; Squamous cell carcinoma; Histone
deacetylase (HDAC) inhibitors; Phase II trial
ID SQUAMOUS-CELL CARCINOMA; SUBEROYLANILIDE HYDROXAMIC ACID;
SOUTHWEST-ONCOLOGY-GROUP; DEPSIPEPTIDE FK228; PROSTATE-CANCER;
METASTATIC HEAD; BREAST-CANCER; COLON-CANCER; OPEN-LABEL; RECURRENT
AB Objectives: Patients with advanced squamous cell carcinoma of the head and neck (SCCHN) have limited treatment options. Inhibition of histone deacetylases (HDACs) represents a novel therapeutic approach warranting additional investigation in solid tumors.
Methods: A phase II trial of single agent romidepsin, an HDAC inhibitor, was performed in 14 patients with SCCHN who provided consent for pre- and post-therapy samples of accessible tumor, blood and uninvolved oral mucosa. Romidepsin was administered at 13 mg/m(2) as a 4-h intravenous infusion on days 1, 8 and 15 of 28 day cycles, with response assessment by RECIST every 8 weeks.
Results: Objective responses were not observed, although 2 heavily pretreated patients had brief clinical disease stabilization. Observed toxicities were expected, including frequent severe fatigue. Immunohistochemical analysis of 7 pre- and post-treatment tumor pairs demonstrated induction of p21(Waf1/Cip1) characteristic of HDAC inhibition, as well as decreased Ki67 staining. Exploratory microarray analyses of mucosal and tumor samples detected changes in gene expression following romidepsin treatment that were most commonly associated with regulation of transcription, cell cycle control, signal transduction, and electron transport. Treatment with romidepsin did not alter the extent of DNA methylation of candidate gene loci (including CDH1 and hMLH1) in SCCHN tumors.
Conclusions: Single agent romidepsin has limited activity for the treatment of SCCHN but can effectively achieve tumor-associated HDAC inhibition. Although tolerability of romidepsin in this setting may be limiting, further evaluation of other HDAC inhibitors in combination with active therapies may be justified. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Haigentz, Missak, Jr.; Gaba, Anu G.; Mariadason, John M.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Oncol, Bronx, NY 10467 USA.
[Haigentz, Missak, Jr.; Sarta, Catherine; Smith, Richard V.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Otorhinolaryngol Head & Neck Surg, Bronx, NY 10467 USA.
[Kim, Mimi; Lin, Juan] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Div Biostat, Bronx, NY 10467 USA.
[Keresztes, Roger S.] Weill Cornell Med Coll, Dept Med, Div Hematol & Med Oncol, New York, NY USA.
[Culliney, Bruce] Beth Israel Deaconess Med Ctr, Dept Med, Div Oncol, New York, NY 10003 USA.
[Shapiro, Geoffrey I.; Haddad, Robert I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Shapiro, Geoffrey I.; Chirieac, Lucian R.; Haddad, Robert I.] Harvard Univ, Sch Med, Boston, MA USA.
[Shapiro, Geoffrey I.; Haddad, Robert I.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Belbin, Thomas J.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.
[Greally, John M.] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA.
[Wright, John J.] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Rockville, MD USA.
RP Haigentz, M (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Oncol, 111 E 210th St,Hofheimer Room 100, Bronx, NY 10467 USA.
EM mhaigent@montefiore.org
RI Mariadason, John/N-2003-2013
FU American Society of Clinical Oncology Career Development Award; NIH
[R21-CA110342, U01-CA062490, N01-CM-62204]
FX This study was supported by the American Society of Clinical Oncology
Career Development Award and NIH Grant R21-CA110342 (M. H.),
U01-CA062490, and N01-CM-62204.
NR 44
TC 19
Z9 19
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1368-8375
J9 ORAL ONCOL
JI Oral Oncol.
PD DEC
PY 2012
VL 48
IS 12
BP 1281
EP 1288
DI 10.1016/j.oraloncology.2012.05.024
PG 8
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA 038BW
UT WOS:000311151200014
PM 22748449
ER
PT J
AU Webb, SM
Vollrath-Smith, FR
Shin, R
Jhou, TC
Xu, SP
Ikemoto, S
AF Webb, Sierra M.
Vollrath-Smith, Fiori R.
Shin, Rick
Jhou, Thomas C.
Xu, Shengping
Ikemoto, Satoshi
TI Rewarding and incentive motivational effects of excitatory amino acid
receptor antagonists into the median raphe and adjacent regions of the
rat
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Intracranial self-administration; Visual sensation seeking;
Reinforcement; Glutamate; Superior central raphe nucleus; Oral pontine
reticular nucleus
ID VENTRAL TEGMENTAL AREA; CONDITIONED PLACE PREFERENCE;
SELF-ADMINISTRATION PARADIGM; PRIMARY REINFORCEMENT; OLFACTORY TUBERCLE;
SEROTONIN NEURONS; NUCLEUS-ACCUMBENS; GABA(B) RECEPTORS; MIDBRAIN RAPHE;
BRAIN
AB The motivational process that regulates approach behavior toward salient distal stimuli (i.e., incentive motivation) plays a key role in voluntary behavior and motivational disorders such as addiction. This process may be mediated by many neurotransmitter systems and a network of many brain structures, including the median and dorsal raphe regions (MR and DR, respectively).
We sought to examine whether the blockade of excitatory amino acid receptors in the MR and DR is rewarding, using intracranial self-administration, and whether the self-administration effect can be explained by drug's effectiveness to enhance incentive motivation, using a visual sensation seeking procedure.
Rats learned to self-administer the AMPA receptor antagonist ZK 200775 into the vicinity of the MR, DR, or medial oral pontine reticular regions, but not the ventral tegmental area. The NMDA receptor antagonist AP5 was also self-administered into the MR, while it was not readily self-administered into other regions. When ZK 200775 was noncontingently administered into the MR, rats markedly increased approach responses rewarded by brief illumination of a light stimulus. In addition, contingent administration of ZK 200775 into the MR induced a conditioning effect on approach responses.
Rats self-administer excitatory amino acid receptor antagonists into the MR and adjacent regions. Self-administration effect of AMPA receptor antagonists into the MR can be largely explained by the manipulation's properties to invigorate ongoing approach behavior and induces conditioned approach. Glutamatergic afferents to the median raphe and adjacent regions appear to tonically suppress incentive-motivational processes.
C1 [Webb, Sierra M.; Vollrath-Smith, Fiori R.; Shin, Rick; Jhou, Thomas C.; Xu, Shengping; Ikemoto, Satoshi] NIDA, Behav Neurosci Branch, NIH, US Dept HHS, Baltimore, MD 21224 USA.
RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Branch, NIH, US Dept HHS, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM satoshi.ikemoto@nih.gov
OI Ikemoto, Satoshi/0000-0002-0732-7386
FU National Institute on Drug Abuse, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute on Drug Abuse, National Institutes of Health. We
would like to thank Drs. Anton Ilango and Dong Wang for their comments
on earlier versions of the manuscript.
NR 61
TC 5
Z9 5
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD DEC
PY 2012
VL 224
IS 3
BP 401
EP 412
DI 10.1007/s00213-012-2759-0
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 036AO
UT WOS:000310998900005
PM 22752328
ER
PT J
AU Milaneschi, Y
Bandinelli, S
Penninx, BW
Corsi, AM
Lauretani, F
Vazzana, R
Semba, RD
Guralnik, JM
Ferrucci, L
AF Milaneschi, Yuri
Bandinelli, Stefania
Penninx, Brenda W.
Corsi, Anna Maria
Lauretani, Fabrizio
Vazzana, Rosamaria
Semba, Richard D.
Guralnik, Jack M.
Ferrucci, Luigi
TI The relationship between plasma carotenoids and depressive symptoms in
older persons
SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Carotenoids; antioxidants; depression; inflammation; aging
ID MEDITERRANEAN-STYLE DIET; LOW SERUM CAROTENOIDS; LATE-LIFE DEPRESSION;
HOMOCYSTEINE LEVELS; METABOLIC SYNDROME; MAJOR DEPRESSION; GREEK
POPULATION; RANDOMIZED-TRIAL; WOMENS HEALTH; RISK-FACTORS
AB Objectives. We examined the cross-sectional and longitudinal relationship between plasma carotenoids and depressive symptoms over a 6-year follow-up in older persons. Methods. This research is part of the InCHIANTI Study, a prospective population-based study of older persons in Tuscany, Italy. The sample for this analysis included 958 women and men aged 65 years and older. Plasma total carotenoids were assessed at baseline. Depressive symptoms were assessed at baseline and at the 3- and 6-year follow-up using the Center for Epidemiological Studies-Depression Scale (CES-D). Depressed mood was defined as CES-D >= 20. Results. At baseline, higher total carotenoids level were associated with lower probability of depressed mood (OR = 0.82, 95% CI = 0.68-0.99, P = 0.04) after adjustment for sociodemographic, health and inflammation. After the exclusion of participants with baseline depressed mood and use of antidepressants, higher total carotenoids level were associated with lower risk of incident depressed mood (OR = 0.72, 95% CI = 0.52-0.99, P = 0.04) at 6-year follow-up, after adjustment for confounders plus baseline CES-D. Inflammatory marker Interleukin-1 receptor antagonist partially mediated this association. Conclusions. Low plasma concentrations of carotenoids are associated with depressive symptoms and predict the development of new depressive symptoms in older persons. Understanding the mechanism of this association may reveal potential targets for prevention and treatment.
C1 [Milaneschi, Yuri] Harbor Hosp Ctr, Natl Inst Aging, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21225 USA.
[Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy.
[Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands.
[Corsi, Anna Maria; Lauretani, Fabrizio] Tuscany Hlth Reg Agcy, Florence, Italy.
[Vazzana, Rosamaria] Univ G DAnnunzio Chieti, Lab Clin Epidemiol, Dept Med & Sci Aging, Chieti, Italy.
[Semba, Richard D.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
[Guralnik, Jack M.] Natl Inst Aging, Lab Epidemiol Demog & Biometry, Bethesda, MD USA.
RP Milaneschi, Y (reprint author), Harbor Hosp Ctr, Natl Inst Aging, Longitudinal Studies Sect, Clin Res Branch, Room NM540,3001 S Hanover St, Baltimore, MD 21225 USA.
EM milaneschiy@mail.nih.gov
FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute
on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111,
N01-AG-5-0002]; National Institute on Aging, National Institutes of
Health; NIA [R01 AG027012]
FX The InCHIANTI study baseline (1998-2000) was supported as a "targeted
project " (ICS110.1/RF97.71) by the Italian Ministry of Health and in
part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and
263 MD 821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the
U.S. National Institute on Aging (Contracts: N.1-AG-1-1 and
N.1-AG-1-2111); the InCHIANTI Follow-ups 2 and 3 studies (2004-2010)
were financed by the U.S. National Institute on Aging (Contract:
N01-AG-5-0002); supported in part by the Intramural research program of
the National Institute on Aging, National Institutes of Health. This
work was supported also by NIA Grant R01 AG027012. None of the
sponsoring institutions interfered with the collection, analysis,
presentation, or interpretation of the data reported herein.
NR 67
TC 9
Z9 9
U1 4
U2 10
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1562-2975
EI 1814-1412
J9 WORLD J BIOL PSYCHIA
JI World J. Biol. Psychiatry
PD DEC
PY 2012
VL 13
IS 8
BP 588
EP 598
DI 10.3109/15622975.2011.597876
PG 11
WC Psychiatry
SC Psychiatry
GA 036ON
UT WOS:000311037300005
PM 21929378
ER
PT J
AU Mathews, JM
Zhan, Q
Etheridge, AS
Patel, PR
Black, SR
Banks, TT
Fennell, TR
Snyder, RW
Burgess, JP
Warren, SD
Surh, I
Waidyanatha, S
AF Mathews, James M.
Zhan, Qiao
Etheridge, Amy S.
Patel, Purvi R.
Black, Sherry R.
Banks, Troy T.
Fennell, Timothy R.
Snyder, Rodney W.
Burgess, Jason P.
Warren, Stephen D.
Surh, Inok
Waidyanatha, Suramya
TI Metabolism and disposition of 2-methoxy-4-nitroaniline in male and
female Harlan Sprague Dawley rats and B6C3F(1)/N mice
SO XENOBIOTICA
LA English
DT Article
DE 2-Methoxy-4-nitroaniline; DNA binding; hepatocytes; dermal absorption;
oral absorption
ID MALE F344 RAT; INDUCTION; INVIVO
AB 1. The disposition of 2-Methoxy-4-nitroaniline (MNA) was investigated in male and female Harlan Sprague Dawley rats and B6C3F(1)/N mice following oral, intravenous, and dermal exposure to [C-14] MNA at 2, 15, or 150 mg/kg. Clearance of MNA was investigated in male and female rat, mouse, and human hepatocytes.
2. MNA was cleared slowly in hepatocytes from rat (t(1/2) = 152-424 min) and human (t(1/2) = 118-403 min) but faster in mouse (t(1/2) = 70-106 min).
3. MNA was well-absorbed in rats and mice following oral administration and eliminated chiefly in urine (rats, 75-79%; mice, 55-68%) 72 h post dosing. Less than 1% of the radioactivity remained in tissues at 72 h. MNA was poorly absorbed following dermal application in rats (5.5%) and mice (10%) over 24 h.
4. The major pathway of metabolism of MNA was via hydroxylation of the phenyl ring to form 6-hydroxy MNA; major metabolites detected were sulfate and glucuronide conjugates of 6-hydroxy MNA.
5. Following oral administration, the percent of total radioactivity bound in tissues bound was highest in liver (43%) and red blood cells (30%), whereas the radioactivity bound to DNA was highest in cecum (160 pmol/mg DNA).
C1 [Surh, Inok; Waidyanatha, Suramya] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Mathews, James M.; Zhan, Qiao; Etheridge, Amy S.; Patel, Purvi R.; Black, Sherry R.; Banks, Troy T.; Fennell, Timothy R.; Snyder, Rodney W.; Burgess, Jason P.; Warren, Stephen D.] RTI Int, Res Triangle Pk, NC USA.
RP Waidyanatha, S (reprint author), NIEHS, Natl Toxicol Program, POB 12233,MD K2-07, Res Triangle Pk, NC 27709 USA.
EM waidyanathas@niehs.nih.gov
RI Fennell, Tim/D-9936-2013
FU National Toxicology Program, National Institute of EnvironmentalHealth
Sciences, National Institutes of Health, U.S. Department of Health and
Human Services [N01-ES-75563 (HHSN29120077563)]
FX The authors are grateful to Drs Michael J Sanders and Helen Cunny for
their review of this manuscript, and Ms. Kathy Ancheta for her
assistance in preparation of the manuscript. This work was performed for
the National Toxicology Program, National Institute of
EnvironmentalHealth Sciences, National Institutes of Health, U.S.
Department of Health and Human Services, under contract No. N01-ES-75563
(HHSN29120077563). This article may be the work product of an employee
or group of employees of the National Institute of Environmental Health
Sciences (NIEHS), National Institute of Health (NIH), however, the
statements, opinions, or conclusions contained therein do not
necessarily represent the statements, opinions, or conclusions of NIEHS,
NIH, or the United States government.
NR 23
TC 0
Z9 0
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0049-8254
J9 XENOBIOTICA
JI Xenobiotica
PD DEC
PY 2012
VL 42
IS 12
BP 1213
EP 1224
DI 10.3109/00498254.2012.697211
PG 12
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 033PS
UT WOS:000310810900007
PM 22725680
ER
PT J
AU Karnaukhova, E
Krupnikova, SS
Rajabi, M
Alayash, AI
AF Karnaukhova, Elena
Krupnikova, Sonia Silinsky
Rajabi, Mohsen
Alayash, Abdu I.
TI Heme binding to human alpha-1 proteinase inhibitor
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Article
DE Alpha-1 proteinase inhibitor; Heme; Protoporphyrin; Bilirubin; Circular
dichroism; Surface plasmon resonance
ID HUMAN-SERUM-ALBUMIN; HIGH-RESOLUTION; SECONDARY STRUCTURE;
ALPHA(1)-ANTITRYPSIN; BILIRUBIN; VARIABILITY; RESONANCE; KINETICS;
ISOFORMS; DISEASE
AB Background: Heme is a unique prosthetic group of various hemoproteins that perform diverse biological functions: however, in its free form heme is intrinsically toxic in vivo. Due to its potential toxicity, heme binding to plasma proteins is an important safety issue in regard to protein therapeutics derived from human blood. While heme binding by hemopexin, albumin and alpha(1)-microglobulin has been extensively studied, the role of other plasma proteins remains largely unknown.
Methods: We examined two acute-phase plasma proteins, haptoglobin (Hp) and alpha-1 proteinase inhibitor (alpha(1)-PI) for possible interactions with heme and bilirubin (BR), the final product of heme degradation, using various techniques: UV/Vis spectroscopy, fluorescence, circular dichroism (CD), and surface plasmon resonance (SPR).
Results: According to our data, Hp exhibits a very weak association with both heme and BR; alpha(1)-PI's affinity to BR is also very low. However, alpha(1)-PI's affinity to heme (K-D 2.0 x 10(-8) M) is of the same order of magnitude as that of albumin (1.26x10(-8) M). The data for alpha(1)-PI binding with protoporphyrin IX (PPIX) suggest that the elimination of the iron atom from the porphyrin structure results in almost 350-fold lower affinity (K-D 6.93 x 10(-6) M), thus indicating that iron is essential for the heme coordination with the alpha(1)-PI.
Conclusions: This work demonstrates for the first time that human alpha(1)-PI is a heme binding protein with an affinity to heme comparable to that of albumin.
General significance: Our data may have important implications for safety and efficacy of plasma protein therapeutics. Published by Elsevier B.V.
C1 [Karnaukhova, Elena; Krupnikova, Sonia Silinsky; Rajabi, Mohsen; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Karnaukhova, E (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, 8800 Rockville Pike,NIH Bldg 29,Room 300, Bethesda, MD 20892 USA.
EM elena.karnaukhova@fda.hhs.gov
FU Oak Ridge Institute for Science and Education (ORISE)
FX The authors are thankful to Drs. Todd Mollan and Christine Harman
(Center for Biologics Evaluation and Research, FDA) for critical reading
of the manuscript and helpful comments. MR and SSK are grateful to the
Oak Ridge Institute for Science and Education (ORISE) for fellowship.
NR 46
TC 5
Z9 5
U1 3
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4165
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD DEC
PY 2012
VL 1820
IS 12
BP 2020
EP 2029
DI 10.1016/j.bbagen.2012.09.012
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 036CM
UT WOS:000311004000020
PM 23000493
ER
PT J
AU Veiga, AS
Sinthuvanich, C
Gaspar, D
Franquelim, HG
Castanho, MARB
Schneider, JP
AF Veiga, Ana Salome
Sinthuvanich, Chomdao
Gaspar, Diana
Franquelim, Henri G.
Castanho, Miguel A. R. B.
Schneider, Joel P.
TI Arginine-rich self-assembling peptides as potent antibacterial gels
SO BIOMATERIALS
LA English
DT Article
DE Peptide; Self-assembly; Hydrogel; Antibacterial; Syringe delivery
ID PSEUDOMONAS-AERUGINOSA; ANTIMICROBIAL SURFACES; LIPID-COMPOSITION;
EPIDEMIOLOGY; HYDROGEL; DEFENSINS; INFECTIONS; RELEASE
AB Hydrogel materials that display inherent activity against bacteria can be used to directly treat accessible wounds to prevent or kill existing infection. Hydrogels composed of self-assembling beta-hairpin peptides. having a high content of arginine, were found to be extremely effective at killing both gram-positive and gram-negative bacteria, including multi-drug resistant Pseudomonas aeruginosa. No added antibacterial agents are necessary to realize activity. Using self-assembling peptides for material construction allows facile structure-activity relationships to be determined since changes in peptide sequence at the monomer level are directly transposed to the bulk material's antibacterial properties. SAR studies show that arginine content largely influences the hydrogel's antibacterial activity, and influences their bulk rheological properties. These studies culminated in an optimized gel, composed of the peptide PEP6R ((VKVRVRVRVPPTRVRVRVKN)-P-D). PEP6R gels prepared at 1.5 wt % or higher concentration, demonstrate high potency against bacteria, but are cytocompatible toward human erythrocytes as well as mammalian mesenchymal stem cells. Rheological studies indicate that the gel is moderately stiff and displays shear-thin recovery behavior, allowing its delivery via simple syringe. Published by Elsevier Ltd.
C1 [Veiga, Ana Salome; Sinthuvanich, Chomdao; Schneider, Joel P.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
[Veiga, Ana Salome; Gaspar, Diana; Franquelim, Henri G.; Castanho, Miguel A. R. B.] Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal.
[Sinthuvanich, Chomdao] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
RP Schneider, JP (reprint author), NCI, Biol Chem Lab, Frederick, MD 21702 USA.
EM joel.schneider@nih.gov
RI Schneider, Joel/N-2610-2014; Gaspar, Diana/M-9562-2015;
OI Gaspar, Diana/0000-0002-9602-567X; Veiga, Ana
Salome/0000-0002-9892-2243; Castanho, Miguel/0000-0001-7891-7562
FU Marie Curie International Outgoing Fellowship within the 7th European
Community Framework Programme [PIOF-GA-2009-235154]; Fundacao para a
Ciencia e a Tecnologia (Ministerio da Educacao e Ciencia, Portugal)
[SFRH/BPD/43931/2008]; Office of the Higher Education Commission,
Ministry of Education, Thailand; Fundacao para a Ciencia e a Tecnologia
(Ministerio da Educacdo e Ciencia, Portugal) [SFRH/BPD/73500/2010];
Intramural Research Program of the National Cancer Institute of the
National Institutes of Health; Fundacao para a Ciencia e Tecnologia
(FCT-MCTES, Portugal) [PTDC/SAU-BEB/099142/2008]
FX This work was supported by a Marie Curie International Outgoing
Fellowship within the 7th European Community Framework Programme awarded
to Ana Salome Veiga (PIOF-GA-2009-235154). ASV also acknowledges
Fundacao para a Ciencia e a Tecnologia (Ministerio da Educacao e
Ciencia, Portugal) for Fellowship SFRH/BPD/43931/2008. This work is
partially supported by a graduate fellowship awarded to Chomdao
Sinthuvanich through the Strategic Scholarship for Frontier Research
Network (SFR) from the Office of the Higher Education Commission,
Ministry of Education, Thailand. Diana Gaspar acknowledges Fundacao para
a Ciencia e a Tecnologia (Ministerio da Educacdo e Ciencia, Portugal)
for Fellowship SFRH/BPD/73500/2010. This work was also supported by the
Intramural Research Program of the National Cancer Institute of the
National Institutes of Health. We thank Fundacao para a Ciencia e
Tecnologia (FCT-MCTES, Portugal) for funding - PTDC/SAU-BEB/099142/2008.
We acknowledge Dr. M.C. Branco for helpful discussions.
NR 33
TC 62
Z9 65
U1 14
U2 158
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 DEC
PY 2012
VL 33
IS 35
BP 8907
EP 8916
DI 10.1016/j.biomaterials.2012.08.046
PG 10
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 032MC
UT WOS:000310721900001
PM 22995710
ER
PT J
AU Ahsan, MJ
Govindasamy, J
Khalilullah, H
Mohan, G
Stables, JP
Pannecouque, C
De Clercq, E
AF Ahsan, Mohamed Jawed
Govindasamy, Jeyabalan
Khalilullah, Habibullah
Mohan, Govind
Stables, James P.
Pannecouque, Christophe
De Clercq, Eric
TI POMA analyses as new efficient bioinformatics' platform to predict and
optimise bioactivity of synthesized
3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide
analogues
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Pyrazolines; Tautomerism; Petra/Osiris/Molinspiration/ALOGPS 2.1
program; Anti-HIV; Antibacterial; Antifungal; Anticonvulsant
ID ANTIMYCOBACTERIAL EVALUATION; PYRAZOLINE DERIVATIVES; COLORIMETRIC
ASSAY; INHIBITORS; PERMEABILITY; DESIGN; QSAR
AB A series of 43, 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues (D01-D43) were analysed using Petra, Osiris, Molinspiration and ALOGPS (POMA) to identify pharmacophore, toxicity prediction, lipophilicity and bioactivity. All the compounds were evaluated for anti-HIV activity. 3-(4-Chlorophenyl)-N-(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D07) was found to be the most active with IC50 > 4.83 mu M and CC50 4.83 mu M. 3-(4-Fluorophenyl)-6,7-dimethoxy-3a, 4-dihydro-3H-indeno[1,2-c]pyrazole-2-carbothioamide (D41) was found to be the most active compound against bacterial strains with MIC of 4 mu g/ml, comparable to the standard drug ciprofloxacin while 3-(4-methoxyphenyl)-6,7-dimethoxy-3a, 4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D38) was found to be the most active compound against fungal strains with MIC 2-4 mu g/ml, however less active than standard fluconazole. Toxicities prediction by Osiris were well supported and experimentally verified with exception of some compounds. In anticonvulsant screening, 3-(4-fluorophenyl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D09) showed maximum activity showing 100% (4/4, 0.25-0.5 h) and 75% (3/4, 1.0 h) protection against minimal clonic seizure test without any toxicity. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Ahsan, Mohamed Jawed; Govindasamy, Jeyabalan; Khalilullah, Habibullah] New Drug Discovery Res, Alwar Pharm Coll, Dept Med Chem, Alwar 301030, Rajasthan, India.
[Ahsan, Mohamed Jawed; Mohan, Govind] Nims Univ, Nims Inst Pharm, Dept Pharmaceut Chem, Jaipur 303121, Rajasthan, India.
[Stables, James P.] NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA.
[Pannecouque, Christophe; De Clercq, Eric] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium.
RP Ahsan, MJ (reprint author), New Drug Discovery Res, Alwar Pharm Coll, Dept Med Chem, Alwar 301030, Rajasthan, India.
EM jawedpharma@gmail.com
OI Ahsan, Mohamed Jawed/0000-0002-6919-5489; Khalilullah,
Habibullah/0000-0002-7401-6254
NR 27
TC 5
Z9 5
U1 0
U2 12
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 DEC 1
PY 2012
VL 22
IS 23
BP 7029
EP 7035
DI 10.1016/j.bmcl.2012.09.108
PG 7
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 030PR
UT WOS:000310583100006
PM 23099090
ER
PT J
AU Aschrafi, A
Kar, AN
Natera-Naranjo, O
MacGibeny, MA
Gioio, AE
Kaplan, BB
AF Aschrafi, Armaz
Kar, Amar N.
Natera-Naranjo, Orlangie
MacGibeny, Margaret A.
Gioio, Anthony E.
Kaplan, Barry B.
TI MicroRNA-338 regulates the axonal expression of multiple nuclear-encoded
mitochondrial mRNAs encoding subunits of the oxidative phosphorylation
machinery
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Article
DE Axonal protein synthesis; ATP synthesis; Reactive oxygen species;
Neurite outgrowth; Sympathetic neurons
ID NERVE GROWTH-FACTOR; SYMPATHETIC NEURONS; PROTEIN-SYNTHESIS;
LOCAL-CONTROL; COMPLEX; SYNAPSE; STRESS; IV; IDENTIFICATION; TRANSLATION
AB MicroRNAs (miRNAs) constitute a novel class of small, non-coding RNAs that act as post-transcriptional regulators of gene expression. Remarkably, it has been shown that these small molecules can coordinately regulate multiple genes coding for proteins with related cellular functions. Previously, we reported that brain-specific miR-338 modulates the axonal expression of cytochrome c oxidase IV (COXIV), a nuclear-encoded mitochondrial protein that plays a key role in oxidative phosphorylation and axonal function. Here, we report that ATP synthase (ATP5G1), like COXIV mRNA, contains a putative miR-338 binding site, and that modulation of miR-338 levels in the axon results in alterations in both COXIV and ATP5G1 expression. Importantly, miR-338 modulation of local COXIV and ATP5G1 expression has a marked effect on axonal ROS levels, as well as axonal growth. These findings point to a mechanism by which miR-338 modulates local energy metabolism through the coordinate regulation of the expression of multiple nuclear-encoded mitochondrial mRNAs in the axon.
C1 [Aschrafi, Armaz; Kar, Amar N.; Natera-Naranjo, Orlangie; MacGibeny, Margaret A.; Gioio, Anthony E.; Kaplan, Barry B.] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Kaplan, BB (reprint author), NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM kaplanb@mail.nih.gov
RI Aschrafi, Armaz/E-2202-2012;
OI Kar, Amar/0000-0003-2380-7504
FU Division of Intramural Research Programs of the National Institute of
Mental Health
FX This work was supported by the Division of Intramural Research Programs
of the National Institute of Mental Health. We thank Ms. Sanah Vohra for
her invaluable technical assistance.
NR 52
TC 21
Z9 21
U1 0
U2 11
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD DEC
PY 2012
VL 69
IS 23
BP 4017
EP 4027
DI 10.1007/s00018-012-1064-8
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 034JF
UT WOS:000310868200012
PM 22773120
ER
PT J
AU Signore, C
AF Signore, Caroline
TI VBAC: What Does the Evidence Show?
SO CLINICAL OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE vaginal birth after cesarean; trial of labor after cesarean; morbidity;
mortality; maternal outcomes; neonatal outcomes
ID ATTEMPTING VAGINAL BIRTH; REPEAT CESAREAN DELIVERY; UTERINE RUPTURE;
MATERNAL MORBIDITY; UNITED-STATES; SECTION; LABOR; RISK; TRIAL; TERM
AB Declining rates of vaginal birth after cesarean (VBAC) are contributing to rising total cesarean delivery rates. The reasons behind the decreased utilization of VBAC are complex, but concerns about the safety of a trial of labor after cesarean are often cited. This manuscript will present a summary of existing evidence on maternal and fetal/neonatal outcomes associated with trial of labor after cesarean/VBAC, and highlight findings from recent contributions to this literature.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Hlth & Human Serv, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA.
RP Signore, C (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Hlth & Human Serv, Pregnancy & Perinatol Branch, NIH, 6100 Execut Blvd,Room 4B03,MSC 7510, Bethesda, MD 20892 USA.
EM signorec@mail.nih.gov
RI wechie, winnie/M-4550-2013
NR 39
TC 6
Z9 6
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-9201
J9 CLIN OBSTET GYNECOL
JI Clin. Obstet. Gynecol.
PD DEC
PY 2012
VL 55
IS 4
BP 961
EP 968
DI 10.1097/GRF.0b013e318263c55d
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 029RQ
UT WOS:000310513700013
PM 23090465
ER
PT J
AU Jones, RB
Reeves, D
Martinez, CS
AF Jones, Roy B.
Reeves, Dianne
Martinez, Charles S.
TI Overview of Electronic Data Sharing: Why, How, and Impact
SO CURRENT ONCOLOGY REPORTS
LA English
DT Article
DE Informatics; Data sharing; Data standards; Database; BRIDG; SCTOD;
Electronic medical records; Outcomes
AB Electronic data sharing is a critical, but underappreciated, requirement for modern medical informatics systems. This capability is facilitated by acquisition of structured clinical data, but optimized only if this data is stored and transmitted using standardized representations. Most electronic medical record and clinical trials management systems are poorly suited for data sharing. In the near future, sharing clinical outcome data is likely to become very important, so these capabilities must be improved. In this article, basic concepts of electronic data sharing are reviewed and their use illustrated in a data-sharing project developed to support Hematopoietic Cell Transplantation reporting to a national database.
C1 [Jones, Roy B.; Martinez, Charles S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Reeves, Dianne] NCI, Informat Operat Branch, Rockville, MD 20852 USA.
RP Jones, RB (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM rbjones@mdanderson.org; dianne.reeves@nih.gov; cmart@mdanderson.org
NR 1
TC 3
Z9 3
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3790
J9 CURR ONCOL REP
JI Curr. Oncol. Rep.
PD DEC
PY 2012
VL 14
IS 6
BP 486
EP 493
DI 10.1007/s11912-012-0271-7
PG 8
WC Oncology
SC Oncology
GA 032HQ
UT WOS:000310706700004
PM 22976780
ER
PT J
AU Fleisher, TA
Oliveira, JB
AF Fleisher, Thomas A.
Oliveira, Joao Bosco
TI Monogenic defects in lymphocyte apoptosis
SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Review
DE ALPS; apoptosis; FAS; RALD; RAS
ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; BONE-MARROW-TRANSPLANTATION;
SOMATIC FAS MUTATIONS; SYNDROME ALPS; T-CELLS; CLINICAL-MANIFESTATIONS;
MYCOPHENOLATE-MOFETIL; ONCOGENE PROTEIN; GENE-MUTATIONS; DISEASE
AB Purpose of review
The recognition that apoptosis - programmed cell death - is an important mechanism in immune homeostasis has led to the identification of human disorders associated with defects in the critical control mechanism.
Recent findings
Patients have been identified with defects affecting the extrinsic apoptotic pathway mediated by the protein receptor FAS which results in the autoimmune lymphoproliferative syndrome and more recently in defects affecting the intrinsic apoptotic pathway mediated by RAS proteins resulting in the RAS-associated autoimmune leukoproliferative disorder. This review summarizes the immunopathogenesis, clinical features and diagnostic approaches to these human disorders.
Summary
Apoptotic pathways are critical in the maintenance of leukocyte homeostasis, and genetic defects impacting these can result in clinical disease manifested as expansion of selected leukocyte populations, autoimmunity, increased risk for malignancy and in some situations defects in host defense.
C1 [Fleisher, Thomas A.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Fleisher, TA (reprint author), NIH, Dept Lab Med, Ctr Clin, Bldg 10,Room 2C410, Bethesda, MD 20892 USA.
EM tfleishe@mail.nih.gov
OI Oliveira, Joao/0000-0001-9388-8173
FU Intramural Research Program of the NIH
FX The research was supported by the Intramural Research Program of the
NIH.
NR 55
TC 7
Z9 7
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-4050
J9 CURR OPIN ALLERGY CL
JI Curr. Opin. Allergy Clin. Immunol.
PD DEC
PY 2012
VL 12
IS 6
BP 609
EP 615
DI 10.1097/ACI.0b013e3283588da0
PG 7
WC Allergy; Immunology
SC Allergy; Immunology
GA 029TY
UT WOS:000310520100006
PM 22918222
ER
PT J
AU Jacques, BE
Puligilla, C
Weichert, RM
Ferrer-Vaquer, A
Hadjantonakis, AK
Kelley, MW
Dabdoub, A
AF Jacques, Bonnie E.
Puligilla, Chandrakala
Weichert, Rachel M.
Ferrer-Vaquer, Anna
Hadjantonakis, Anna-Katerina
Kelley, Matthew W.
Dabdoub, Alain
TI A dual function for canonical Wnt/beta-catenin signaling in the
developing mammalian cochlea
SO DEVELOPMENT
LA English
DT Article
DE Mouse; beta-catenin; Hair cells; Proliferation; Sox2; Cyclin D1
ID MOUSE INNER-EAR; BETA-CATENIN; HAIR-CELLS; EXPRESSION PATTERNS;
MOLECULAR-MECHANISM; MULTIPLE ROLES; OTIC PLACODE; STEM-CELLS; WNT;
PATHWAY
AB The canonical Wnt/beta-catenin signaling pathway is known to play crucial roles in organogenesis by regulating both proliferation and differentiation. In the inner ear, this pathway has been shown to regulate the size of the otic placode from which the cochlea will arise; however, direct activity of canonical Wnt signaling as well as its function during cochlear mechanosensory hair cell development had yet to be identified. Using TCF/Lef:H2B-GFP reporter mice and transfection of an independent TCF/Lef reporter construct, we describe the pattern of canonical Wnt activity in the developing mouse cochlea. We show that prior to terminal mitosis, canonical Wnt activity is high in early prosensory cells from which hair cells and support cells will differentiate, and activity becomes reduced as development progresses. Using an in vitro model we demonstrate that Wnt/beta-catenin signaling regulates both proliferation and hair cell differentiation within the developing cochlear duct. Inhibition of Wnt/beta-catenin signaling blocks proliferation during early mitotic phases of development and inhibits hair cell formation in the differentiating organ of Corti. Conversely, activation increases the number of hair cells that differentiate and induces proliferation in prosensory cells, causing an expansion of the Sox2-positive prosensory domain. We further demonstrate that the induced proliferation of Sox2-positive cells may be mediated by the cell cycle regulator cyclin D1. Lastly, we provide evidence that the mitotic Sox2-positive cells are competent to differentiate into hair cells. Combined, our data suggest that Wnt/beta-catenin signaling has a dual function in cochlear development, regulating both proliferation and hair cell differentiation.
C1 [Jacques, Bonnie E.; Weichert, Rachel M.; Dabdoub, Alain] Univ Calif San Diego, Sch Med, Dept Surg, Div Otolaryngol, La Jolla, CA 92093 USA.
[Puligilla, Chandrakala; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, NIH, Cochlear Dev Lab, Bethesda, MD 20892 USA.
[Ferrer-Vaquer, Anna; Hadjantonakis, Anna-Katerina] Sloan Kettering Inst, Dev Biol Program, New York, NY 10065 USA.
RP Jacques, BE (reprint author), Univ Calif San Diego, Sch Med, Dept Surg, Div Otolaryngol, La Jolla, CA 92093 USA.
EM bjacques@ucsd.edu; adabdoub@sri.utoronto.ca
FU Specialized Support Grant [P30 CA23100]; Deafness Research Foundation
Grant; National Institutes of Health [R01DC011104]
FX Images were generated at the UCSD Cancer Center Microscopy Facility
funded by Specialized Support Grant [P30 CA23100]. This work was funded
by a Deafness Research Foundation Grant and a grant from the National
Institutes of Health [R01DC011104] to A.D. Deposited in PMC for release
after 12 months.
NR 67
TC 50
Z9 54
U1 1
U2 12
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD DEC 1
PY 2012
VL 139
IS 23
BP 4395
EP 4404
DI 10.1242/dev.080358
PG 10
WC Developmental Biology
SC Developmental Biology
GA 033FT
UT WOS:000310780300012
PM 23132246
ER
PT J
AU Zhang, B
Suarez-Jimenez, B
Hathaway, A
Waters, C
Vaughan, K
Noble, PL
Fox, NA
Suomi, SJ
Pine, DS
Nelson, EE
AF Zhang, Bo
Suarez-Jimenez, Benjamin
Hathaway, Amanda
Waters, Carlos
Vaughan, Kelli
Noble, Pamela L.
Fox, Nathan A.
Suomi, Stephen J.
Pine, Daniel S.
Nelson, Eric E.
TI Developmental changes of rhesus monkeys in response to separation from
the mother
SO DEVELOPMENTAL PSYCHOBIOLOGY
LA English
DT Article
DE infant; separation; anxiety; attachment
ID ULTRASONIC VOCALIZATION; INDIVIDUAL-DIFFERENCES; BEHAVIORAL-INHIBITION;
DEFENSIVE BEHAVIORS; ANXIETY DISORDERS; MACACA-MULATTA; ATTACHMENT;
VARIABLES; INFANTS; RATS
AB The development of separation response behaviors in infant rhesus macaques across the first 6 months of life was assessed. Seventeen infants underwent a neonatal assessment at 7, 14, 21, and 30 days of age which included a brief period of social isolation. At 3 and 6 months of age these same monkeys and four additional subjects were again subjected to a period of brief social isolation and also exposed to a novel environment with their sedated mother. Results indicate a developmental increase followed by a steady decline in the frequency of separation vocalizations. A modest relationship between early-infancy locomotor profiles and separation responses was also observed at several time points suggesting a possible relationship between these measures. However, stable inter-individual measures of separation distress did not emerge until late in the infantile period. This could suggest that high levels of maternal contact-seeking behavior early in infancy are context specific and not a reliable index of enduring temperament. (c) 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 798807, 2012
C1 [Zhang, Bo; Pine, Daniel S.; Nelson, Eric E.] NIMH, Sect Dev Affect Neurosci, Bethesda, MD 20892 USA.
[Suarez-Jimenez, Benjamin; Hathaway, Amanda; Waters, Carlos; Vaughan, Kelli; Noble, Pamela L.] NIMH, Nonhuman Primate Core, Bethesda, MD 20892 USA.
[Fox, Nathan A.] Univ Maryland, Dept Human Dev, Bethesda, MD USA.
[Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, Bethesda, MD 20892 USA.
RP Nelson, EE (reprint author), NIMH, Sect Dev Affect Neurosci, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM nelsone@mail.nih.gov
RI Nelson, Eric/B-8980-2008;
OI Nelson, Eric/0000-0002-3376-2453; Vaughan, Kelli/0000-0001-5274-582X
FU National Institutes of Health, NIMH
FX The work presented here was supported entirely by the intramural
research program of the National Institutes of Health, NIMH. The authors
wish to thank the veterinary and animal care staff of the NIH animal
facility in Poolesville.
NR 50
TC 3
Z9 3
U1 3
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0012-1630
J9 DEV PSYCHOBIOL
JI Dev. Psychobiol.
PD DEC
PY 2012
VL 54
IS 8
BP 798
EP 807
DI 10.1002/dev.21000
PG 10
WC Developmental Biology; Psychology
SC Developmental Biology; Psychology
GA 033LN
UT WOS:000310798000003
PM 22213455
ER
PT J
AU Waisertreiger, ISR
Liston, VG
Menezes, MR
Kim, HM
Lobachev, KS
Stepchenkova, EI
Tahirov, TH
Rogozin, IB
Pavlov, YI
AF Waisertreiger, Irina S. -R.
Liston, Victoria G.
Menezes, Miriam R.
Kim, Hyun-Min
Lobachev, Kirill S.
Stepchenkova, Elena I.
Tahirov, Tahir H.
Rogozin, Igor B.
Pavlov, Youri I.
TI Modulation of mutagenesis in eukaryotes by DNA replication fork dynamics
and quality of nucleotide pools
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Review
DE DNA polymerases; nucleotide pools; mutagenesis; Okazaki fragments
ID INOSINE TRIPHOSPHATE PYROPHOSPHATASE; BASE ANALOG
6-N-HYDROXYLAMINOPURINE; YEAST SACCHAROMYCES-CEREVISIAE; POLYMERASE
ALPHA-PRIMASE; HUMAN MISMATCH REPAIR; CELL NUCLEAR ANTIGEN;
STRAND-BREAK-REPAIR; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; OKAZAKI
FRAGMENT MATURATION; DAMAGE-INDUCED MUTAGENESIS
AB The rate of mutations in eukaryotes depends on a plethora of factors and is not immediately derived from the fidelity of DNA polymerases (Pols). Replication of chromosomes containing the anti-parallel strands of duplex DNA occurs through the copying of leading and lagging strand templates by a trio of Pols alpha, delta and epsilon, with the assistance of Pol xi and Y-family Pols at difficult DNA template structures or sites of DNA damage. The parameters of the synthesis at a given location are dictated by the quality and quantity of nucleotides in the pools, replication fork architecture, transcription status, regulation of Pol switches, and structure of chromatin. The result of these transactions is a subject of survey and editing by DNA repair. Environ. Mol. Mutagen., 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Waisertreiger, Irina S. -R.; Liston, Victoria G.; Menezes, Miriam R.; Stepchenkova, Elena I.; Tahirov, Tahir H.; Pavlov, Youri I.] Univ Nebraska, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68182 USA.
[Kim, Hyun-Min; Lobachev, Kirill S.] Georgia Inst Technol, Sch Biol, Dept Bil, Atlanta, GA 30332 USA.
[Kim, Hyun-Min; Lobachev, Kirill S.] Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA.
[Stepchenkova, Elena I.] Vavilov Inst Gen Genet, St Petersburg Branch, Lab Modeling Human Dis, St Petersburg 199034, Russia.
[Stepchenkova, Elena I.; Pavlov, Youri I.] St Petersburg Univ, Dept Genet, St Petersburg 199034, Russia.
[Rogozin, Igor B.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Rogozin, Igor B.] Russian Acad Sci, Inst Cytol & Genet, Mutagenesis Sect, Novosibirsk 630090, Russia.
RP Pavlov, YI (reprint author), Univ Nebraska, Eppley Inst Res Canc & Allied Dis, ESH 7009,986805 Nebraska Med Ctr, Omaha, NE 68182 USA.
EM ypavlov@unmc.edu
RI Stepchenkova, Elena/F-9931-2014
OI Stepchenkova, Elena/0000-0002-5854-8701
FU UNMC Eppley Cancer Center seed grants; NIGMS [R01GM082923]; NCI
[CA129925]; Smoking Disease Research Program DHHS [2011-27]; Russian
federal program "Innovation scientific personnel" [14.740.11.0916];
NIGMS/NIH [R01GM0825950]; NSF [MCB-0818122]; National Library of
Medicine at the National Institutes of Health/DHHS; National Center for
Research Resources [5P20RR016469]; National Institute for General
Medical Science (NIGMS) [8P20GM103427]
FX Grant sponsor: UNMC Eppley Cancer Center seed grants; Grant sponsor:
NIGMS; Grant Number R01GM082923 (to THT); Grant sponsor: NCI; Grant
Number CA129925 (to YIP); Grant sponsor: Smoking Disease Research
Program DHHS; Grant Number 2011-27; Grant sponsor: Russian federal
program "Innovation scientific personnel," State contract 14.740.11.0916
(to YIP); Grant sponsor: NIGMS/NIH (K. S. L. laboratory); Grant Number
R01GM0825950; Grant sponsor: NSF; Grant Number MCB-0818122; Grant
sponsor: National Library of Medicine at the National Institutes of
Health/DHHS (Intramural Research Program, to IBR); Grant sponsor:
National Center for Research Resources; Grant Number 5P20RR016469; Grant
sponsor: National Institute for General Medical Science (NIGMS); Grant
Number 8P20GM103427.
NR 317
TC 11
Z9 11
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD DEC
PY 2012
VL 53
IS 9
BP 699
EP 724
DI 10.1002/em.21735
PG 26
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 033LG
UT WOS:000310797100005
PM 23055184
ER
PT J
AU Stone, JE
Lujan, SA
Kunkel, TA
AF Stone, Jana E.
Lujan, Scott A.
Kunkel, Thomas A.
TI DNA polymerase zeta generates clustered mutations during bypass of
endogenous DNA lesions in Saccharomyces cerevisiae
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Article
DE spontaneous mutagenesis; nucleotide excision repair; error-prone DNA
synthesis; translesion synthesis; multiple mutations
ID THYMINE-THYMINE DIMER; DEPENDENT TRANSLESION SYNTHESIS; REV1 PROTEIN;
POL-ZETA; ACCESSORY PROTEINS; GENE DISRUPTION; HUMAN CANCERS; YEAST;
ETA; REPLICATION
AB Multiple sequence changes that are simultaneously introduced in a single DNA transaction have a higher probability of altering gene function than do single base substitutions. DNA polymerase zeta (Pol xi) has been shown to introduce such clustered mutations under specific selective and/or DNA damage-producing conditions. In this study, a forward mutation assay was used to determine the specificity of spontaneous mutations generated in Saccharomyces cerevisiae when either wild-type Pol xi or a mutator Pol xi variant (rev3-L979F) bypasses endogenous lesions. Mutagenesis in strains proficient for nucleotide excision repair (NER) was compared to mutagenesis in NER-deficient strains that retain unrepaired endogenous DNA lesions in the genome. Compared to NER-proficient strains, NER-deficient rad14 Delta strains have elevated mutation rates that depend on Pol xi. Rates are most strongly elevated for tandem base pair substitutions and clusters of multiple, closely spaced mutations. Both types of mutations depend on Pol xi, but not on Pol eta. Rates of each are further elevated in yeast strains bearing the rev3-979F allele. The results indicate that when Pol xi performs mutagenic bypass of endogenous, helix-distorting lesions, it catalyzes a short track of processive, error-prone synthesis. We discuss the implications of this unique catalytic property of Pol xi to its evolutionary conservation and possibly to multistage carcinogenesis.Environ. Mol. Mutagen., 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Kunkel, Thomas A.] NIEHS, Genet Mol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Kunkel, TA (reprint author), NIEHS, Genet Mol Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
FU Division of Intramural Research of the National Institute of
Environmental Health Sciences, National Institutes of Health [Z01
ES065070]
FX Grant sponsor: Division of Intramural Research of the National Institute
of Environmental Health Sciences, National Institutes of Health; Grant
number: Project Z01 ES065070.
NR 48
TC 18
Z9 18
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD DEC
PY 2012
VL 53
IS 9
BP 777
EP 786
DI 10.1002/em.21728
PG 10
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 033LG
UT WOS:000310797100010
PM 22965922
ER
PT J
AU Klabunde, CN
Willis, GB
McLeod, CC
Dillman, DA
Johnson, TP
Greene, SM
Brown, ML
AF Klabunde, Carrie N.
Willis, Gordon B.
McLeod, Caroline C.
Dillman, Don A.
Johnson, Timothy P.
Greene, Sarah M.
Brown, Martin L.
TI Improving the Quality of Surveys of Physicians and Medical Groups: A
Research Agenda
SO EVALUATION & THE HEALTH PROFESSIONS
LA English
DT Article
DE survey research; health care provider; physicians; medical groups;
health; services research
ID SURVEY RESPONSE RATES; MAIL SURVEY; RANDOMIZED-TRIAL; MONETARY
INCENTIVES; POSTAL SURVEY; INTERNET; WEB; QUESTIONNAIRES; PEDIATRICIANS;
TECHNOLOGY
AB Because health care providers have a central role in implementing guidelines, health care reform, and new standards of care and technologies, surveying them about their practices and perspectives is vital for health services and policy research. In November 2010, the National Cancer Institute convened a workshop to review and discuss current methodologies in designing and fielding large-scale surveys of physicians and medical groups. This report summarizes key issues and future directions for four topic areas addressed in the workshop: sample frames for surveying physicians and medical groups; points of contact and response modes; response incentives; and questionnaire design and burden. Recommendations were made for improving sample frame databases, optimizing mixed-mode surveys, and studying use of incentives with gatekeepers and in medical group settings. There is particular need for empirical assessment of factors that motivate or impede participation of physicians, other types of clinicians, and medical groups in survey research.
C1 [Klabunde, Carrie N.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA.
[McLeod, Caroline C.] NOVA Res Co, Bethesda, MD USA.
[Dillman, Don A.] Washington State Univ, Social & Econ Sci Res Ctr, Pullman, WA 99164 USA.
[Johnson, Timothy P.] Univ Illinois, Survey Res Lab, Chicago, IL USA.
[Greene, Sarah M.] Grp Hlth Res Inst, Seattle, WA USA.
RP Klabunde, CN (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, EPN 4005,6130 Execut Blvd, Bethesda, MD 20892 USA.
EM KlabundC@mail.nih.gov
NR 59
TC 29
Z9 29
U1 2
U2 17
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0163-2787
J9 EVAL HEALTH PROF
JI Eval. Health Prof.
PD DEC
PY 2012
VL 35
IS 4
BP 477
EP 506
DI 10.1177/0163278712458283
PG 30
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 032BU
UT WOS:000310687700007
PM 22947596
ER
PT J
AU Hueber, W
Sands, BE
Lewitzky, S
Vandemeulebroecke, M
Reinisch, W
Higgins, PDR
Wehkamp, J
Feagan, BG
Yao, MD
Karczewski, M
Karczewski, J
Pezous, N
Bek, S
Bruin, G
Mellgard, B
Berger, C
Londei, M
Bertolino, AP
Tougas, G
Travis, SPL
AF Hueber, Wolfgang
Sands, Bruce E.
Lewitzky, Steve
Vandemeulebroecke, Marc
Reinisch, Walter
Higgins, Peter D. R.
Wehkamp, Jan
Feagan, Brian G.
Yao, Michael D.
Karczewski, Marek
Karczewski, Jacek
Pezous, Nicole
Bek, Stephan
Bruin, Gerard
Mellgard, Bjoern
Berger, Claudia
Londei, Marco
Bertolino, Arthur P.
Tougas, Gervais
Travis, Simon P. L.
CA Secukinumab Crohns Dis Study Grp
TI Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to
severe Crohn's disease: unexpected results of a randomised, double-blind
placebo-controlled trial
SO GUT
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; CHRONIC MUCOCUTANEOUS CANDIDIASIS;
GENOME-WIDE ASSOCIATION; NECROSIS-FACTOR; SUSCEPTIBILITY LOCI;
CERTOLIZUMAB PEGOL; CLINICAL-RESPONSE; COLITIS; IMMUNITY; IL-23
AB Objective The authors tested whether the anti-interleukin (IL)-17A monoclonal antibody secukinumab was safe and effective for the treatment of active Crohn's disease.
Design In a double-blind, randomised, placebo-controlled proof-of-concept study, 59 patients with moderate to severe Crohn's disease (Crohn's Disease Activity Index (CDAI) >= 220 to <= 450) were assigned in a 2:1 ratio to 2x10 mg/kg intravenous secukinumab or placebo. The primary end point, addressed by Bayesian statistics augmented with historical placebo information, was the probability that secukinumab reduces the CDAI by >= 50 points more than placebo at week 6. Ancillary analyses explored associations of 35 candidate genetic polymorphisms and faecal calprotectin response.
Results 59 patients (39 secukinumab, 20 placebo, mean baseline CDAI 307 and 301, respectively) were recruited. 18/59 (31%) patients discontinued prematurely (12/39 (31%) secukinumab, 6/20 (30%) placebo), 10/59 (17%) due to insufficient therapeutic effect (8/39 (21%) secukinumab, 2/20 (10%) placebo). Fourteen serious adverse events occurred in 10 patients (seven secukinumab, three placebo); 20 infections, including four local fungal infections, were seen on secukinumab versus none on placebo. Primary end point analysis estimated <0.1% probability (Delta CDAI (SD) = 33.9 (19.7), 95% credible interval -4.9 to 72.9) that secukinumab reduces CDAI by >= 50 points more than placebo. Secondary area under the curve analysis (weeks 4-10) showed a significant difference (mean Delta CDAI=49; 95% CI (2 to 96), p=0.043) in favour of placebo. Post hoc subgroup analysis showed that unfavourable responses on secukinumab were driven by patients with elevated inflammatory markers (CRP >= 10 mg/l and/or faecal calprotectin >= 200 ng/ml; mean Delta CDAI=62; 95% CI (-1 to 125), p=0.054 in favour of placebo). Absence of the minor allele of tumour necrosis factor-like ligand 1A was strongly associated with lack of response measured by baseline-adjusted changes in calprotectin at week 6 (p=0.00035 Bonferroni-corrected).
Conclusions Blockade of IL-17A was ineffective and higher rates of adverse events were noted compared with placebo.
C1 [Hueber, Wolfgang; Bek, Stephan; Bruin, Gerard; Mellgard, Bjoern; Berger, Claudia; Bertolino, Arthur P.] Novartis Inst BioMed Res, Basel, Switzerland.
[Sands, Bruce E.] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Lewitzky, Steve] Novartis Inst BioMed Res, Cambridge, MA USA.
[Vandemeulebroecke, Marc; Pezous, Nicole; Tougas, Gervais] Novartis Pharmaceut, Basel, Switzerland.
[Reinisch, Walter] Med Univ Vienna, Vienna, Austria.
[Higgins, Peter D. R.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Wehkamp, Jan] IKB Robert Bosch Krankenhaus, Stuttgart, Germany.
[Feagan, Brian G.] Univ Western Ontario, Robarts Res Inst, London, ON, Canada.
[Yao, Michael D.] NIH, Bethesda, MD 20892 USA.
[Karczewski, Marek; Karczewski, Jacek] Solumed Res Unit, Poznan, Poland.
[Londei, Marco] Novartis Res Fdn, Novartis Genom Inst, San Diego, CA USA.
[Travis, Simon P. L.] Univ Oxford, Nuffield Dept Expt Med, Translat Gastroenterol Unit, Oxford, England.
RP Hueber, W (reprint author), Novartis Inst BioMed Res, Basel, Switzerland.
EM wolfgang.hueber@novartis.com
RI Karczewski, Jacek/G-3399-2011; Wehkamp, Jan/B-7319-2011; Feagan,
Brian/M-4283-2015; Higgins, Peter/A-3511-2009;
OI Higgins, Peter/0000-0003-1602-4341; Wehkamp, Jan/0000-0001-6788-841X
FU Novartis Pharma AG, Basel, Switzerland
FX Novartis Pharma AG, Basel, Switzerland funded this study. External
advisors (B Feagan, P D R Higgins, M and J Karczewski, W Reinisch, B
Sands, S Travis, J Wehkamp, M Yao) together with the NIBR clinical team
supervised the study and assisted with data interpretation.
Investigators (see also Acknowledgements) gathered data and Novartis
staff entered them into the clinical database. Novartis statisticians
and programmers together with Covance statisticians did the analyses,
and advisory committee members together with Novartis experts prepared
this manuscript. The corresponding author had full access to all data
and had final responsibility for the decision to submit for publication.
NR 39
TC 308
Z9 317
U1 2
U2 28
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
J9 GUT
JI Gut
PD DEC
PY 2012
VL 61
IS 12
BP 1693
EP 1700
DI 10.1136/gutjnl-2011-301668
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 035DB
UT WOS:000310922000008
PM 22595313
ER
PT J
AU Rajaraman, P
Melin, BS
Wang, ZM
McKean-Cowdin, R
Michaud, DS
Wang, SS
Bondy, M
Houlston, R
Jenkins, RB
Wrensch, M
Yeager, M
Ahlbom, A
Albanes, D
Andersson, U
Freeman, LEB
Buring, JE
Butler, MA
Braganza, M
Carreon, T
Feychting, M
Fleming, SJ
Gapstur, SM
Gaziano, JM
Giles, GG
Hallmans, G
Henriksson, R
Hoffman-Bolton, J
Inskip, PD
Johansen, C
Kitahara, CM
Lathrop, M
Liu, CW
Le Marchand, L
Linet, MS
Lonn, S
Peters, U
Purdue, MP
Rothman, N
Ruder, AM
Sanson, M
Sesso, HD
Severi, G
Shu, XO
Simon, M
Stampfer, M
Stevens, VL
Visvanathan, K
White, E
Wolk, A
Zeleniuch-Jacquotte, A
Zheng, W
Decker, P
Enciso-Mora, V
Fridley, B
Gao, YT
Kosel, M
Lachance, DH
Lau, C
Rice, T
Swerdlow, A
Wiemels, JL
Wiencke, JK
Shete, S
Xiang, YB
Xiao, YY
Hoover, RN
Fraumeni, JF
Chatterjee, N
Hartge, P
Chanock, SJ
AF Rajaraman, Preetha
Melin, Beatrice S.
Wang, Zhaoming
McKean-Cowdin, Roberta
Michaud, Dominique S.
Wang, Sophia S.
Bondy, Melissa
Houlston, Richard
Jenkins, Robert B.
Wrensch, Margaret
Yeager, Meredith
Ahlbom, Anders
Albanes, Demetrius
Andersson, Ulrika
Freeman, Laura E. Beane
Buring, Julie E.
Butler, Mary Ann
Braganza, Melissa
Carreon, Tania
Feychting, Maria
Fleming, Sarah J.
Gapstur, Susan M.
Gaziano, J. Michael
Giles, Graham G.
Hallmans, Goran
Henriksson, Roger
Hoffman-Bolton, Judith
Inskip, Peter D.
Johansen, Christoffer
Kitahara, Cari M.
Lathrop, Mark
Liu, Chenwei
Le Marchand, Loic
Linet, Martha S.
Lonn, Stefan
Peters, Ulrike
Purdue, Mark P.
Rothman, Nathaniel
Ruder, Avima M.
Sanson, Marc
Sesso, Howard D.
Severi, Gianluca
Shu, Xiao-Ou
Simon, Matthias
Stampfer, Meir
Stevens, Victoria L.
Visvanathan, Kala
White, Emily
Wolk, Alicja
Zeleniuch-Jacquotte, Anne
Zheng, Wei
Decker, Paul
Enciso-Mora, Victor
Fridley, Brooke
Gao, Yu-Tang
Kosel, Matthew
Lachance, Daniel H.
Lau, Ching
Rice, Terri
Swerdlow, Anthony
Wiemels, Joseph L.
Wiencke, John K.
Shete, Sanjay
Xiang, Yong-Bing
Xiao, Yuanyuan
Hoover, Robert N.
Fraumeni, Joseph F., Jr.
Chatterjee, Nilanjan
Hartge, Patricia
Chanock, Stephen J.
TI Genome-wide association study of glioma and meta-analysis
SO HUMAN GENETICS
LA English
DT Article
ID HIGH-GRADE GLIOMA; NERVOUS-SYSTEM; 1ST-DEGREE RELATIVES; BRAIN-TUMORS;
CANCER; RISK; SUSCEPTIBILITY; ALLELES; VARIANTS; ALLERGY
AB Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.
C1 [Rajaraman, Preetha] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Rajaraman, Preetha; Wang, Zhaoming; Yeager, Meredith; Albanes, Demetrius; Freeman, Laura E. Beane; Braganza, Melissa; Inskip, Peter D.; Kitahara, Cari M.; Linet, Martha S.; Purdue, Mark P.; Rothman, Nathaniel; Hartge, Patricia; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Melin, Beatrice S.; Andersson, Ulrika; Henriksson, Roger] Umea Univ, Dept Radiat Sci, Umea, Sweden.
[Wang, Zhaoming; Yeager, Meredith; Liu, Chenwei; Chanock, Stephen J.] NCI, Core Genotyping Facil, SAIC Frederick Inc, Gaithersburg, MD USA.
[McKean-Cowdin, Roberta] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Michaud, Dominique S.] Brown Univ, Div Biol & Med, Dept Epidemiol, Providence, RI 02912 USA.
[Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Wang, Sophia S.] City Hope Natl Med Ctr, Div Canc Etiol, Dept Populat Sci, Duarte, CA USA.
[Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[Bondy, Melissa; Lau, Ching] Baylor Coll Med, Houston, TX 77030 USA.
[Houlston, Richard; Enciso-Mora, Victor; Swerdlow, Anthony] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
[Jenkins, Robert B.; Decker, Paul; Fridley, Brooke; Kosel, Matthew; Lachance, Daniel H.] Mayo Clin, Rochester, MN USA.
[Wrensch, Margaret; Rice, Terri; Wiemels, Joseph L.; Wiencke, John K.; Xiao, Yuanyuan] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Ahlbom, Anders; Feychting, Maria; Lonn, Stefan] Karolinska Inst, Inst Environm Med, Div Epidemiol, S-10401 Stockholm, Sweden.
[Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MA USA.
[Butler, Mary Ann; Carreon, Tania; Ruder, Avima M.] Ctr Dis Control & Prevent, Natl Inst Occupat Safety & Hlth, Cincinnati, OH USA.
[Fleming, Sarah J.] Univ Leeds, Div Biostat, Leeds, W Yorkshire, England.
[Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol, Res & Informat Ctr, Geriatr Res Educ & Clin Ctr, Boston, MA USA.
[Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med Nutr Res, Umea, Sweden.
[Hoffman-Bolton, Judith; Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Johansen, Christoffer] Danish Canc Soc, Res Ctr, Unit Survivorship, Copenhagen, Denmark.
[Lathrop, Mark] IG CEA, Ctr Natl Genotypage, Evry, France.
[Lathrop, Mark] Fdn Jean Dauset CEPH, Paris, France.
[Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96822 USA.
[Lonn, Stefan] AstraZeneca Nord, Dept Med, Sodertalje, Sweden.
[Peters, Ulrike; White, Emily] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Peters, Ulrike; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Sanson, Marc] APHP, GH Pitie Salpetriere, Serv Neurol Mazarin, Paris, France.
[Sanson, Marc] CRICM, UMR INSERM UPMC 975, Paris, France.
[Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Simon, Matthias] Neurochirurg Univklin, Bonn, Germany.
[Stampfer, Meir] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Visvanathan, Kala] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Wolk, Alicja] Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, S-10401 Stockholm, Sweden.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Div Epidemiol, Dept Environm Med, New York, NY USA.
[Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Sch Med, Shanghai Canc Inst, Dept Epidemiol,Renji Hosp, Shanghai 200030, Peoples R China.
[Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England.
[Shete, Sanjay] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Orlando, TX USA.
RP Rajaraman, P (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM rajarama@mail.nih.gov
RI Simon, Matthias/F-3046-2014; Michaud, Dominique/I-5231-2014; Rice,
Terri/J-6071-2014; Albanes, Demetrius/B-9749-2015; Fridley,
Brooke/D-8315-2015; Purdue, Mark/C-9228-2016; Kitahara, Cari/R-8267-2016
OI Giles, Graham/0000-0003-4946-9099; Fleming, Sarah/0000-0002-7655-4806;
Fridley, Brooke/0000-0001-7739-7956; Zeleniuch-Jacquotte,
Anne/0000-0001-9350-1303; Houlston, Richard/0000-0002-5268-0242; Purdue,
Mark/0000-0003-1177-3108;
FU NCI, NIH, Department of Health and Human Services; NCI, NIH [1-CO-12400]
FX This research was supported by intramural funds from the NCI, NIH,
Department of Health and Human Services, and has been funded in whole or
in part with federal funds from the NCI, NIH, under contract
N01-CO-12400. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the US government. We are indebted to
the scientific and field efforts of Michelle Brotzman (Westat), Laurie
Burdette, Peter Hui (IMS), Annelie Landgren, Leah Mechanic, Lisa Newman
(RTI), Aurelie Vogt, Tim Sheehy, Mitchel Berger, Susan Chang, Mike
Prados, Tarik Tihan, Ivan Smirnov, and Lucie McCoy.
NR 30
TC 88
Z9 89
U1 3
U2 42
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD DEC
PY 2012
VL 131
IS 12
BP 1877
EP 1888
DI 10.1007/s00439-012-1212-0
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 034JU
UT WOS:000310869700008
PM 22886559
ER
PT J
AU Chen, WY
Xu, Z
Nishitani, M
Van Ryzin, C
McDonnell, NB
Merke, DP
AF Chen, Wuyan
Xu, Zhi
Nishitani, Miki
Van Ryzin, Carol
McDonnell, Nazli B.
Merke, Deborah P.
TI Complement component 4 copy number variation and CYP21A2 genotype
associations in patients with congenital adrenal hyperplasia due to
21-hydroxylase deficiency
SO HUMAN GENETICS
LA English
DT Article
ID RP-C4-CYP21-TNX RCCX MODULES; MAJOR HISTOCOMPATIBILITY COMPLEX;
HIGH-FREQUENCY; GENE MUTATION; 2 PARTS; C4; POPULATIONS; IMMUNOLOGY;
DIVERSITY; VARIANTS
AB Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of cortisol biosynthesis caused by CYP21A2 mutations. An increase in gene copy number variation (CNV) exists at the CYP21A2 locus. CNV of C4, a neighboring gene that encodes complement component 4, is associated with autoimmune disease susceptibility. In this study, we performed comprehensive genetic analysis of the RP-C4-CYP21-TNX (RCCX) region in 127 unrelated 21-OHD patients (100 classic, 27 nonclassic). C4 copy number was determined by Southern blot. C4 CNV and serum C4 levels were evaluated in relation to CYP21A2 mutations and relevant phenotypes. We found that the most common CYP21A2 mutation associated with the nonclassic form of CAH, V281L, was associated with high C4 copy number (p = 7.13 x 10(-16)). Large CYP21A2 deletion, a common mutation associated with the classic form of CAH, was associated with low C4 copy number (p = 1.61 x 10(-14)). Monomodular RCCX with a short C4 gene, a risk factor for autoimmune disease, was significantly less frequent in CAH patients compared to population estimates (2.8 vs. 10.6 %; p = 1.08 x 10(-4)). In conclusion, CAH patients have increased C4 CNV, with mutation-specific associations that may be protective for autoimmune disease. The study of CYP21A2 in relation to neighboring genes provides insight into the genetics of CNV hotspots, an important determinant of human health.
C1 [Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet PDEGEN, NIH, Bethesda, MD USA.
[Chen, Wuyan; Xu, Zhi; McDonnell, Nazli B.] NIA, Clin Invest Lab, Baltimore, MD 21224 USA.
[Nishitani, Miki; Van Ryzin, Carol; Merke, Deborah P.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[McDonnell, Nazli B.] NIA, Clin Res Branch, NIH, Baltimore, MD USA.
RP Merke, DP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet PDEGEN, NIH, Bethesda, MD USA.
EM wuyanchen.nia@gmail.com; dmerke@nih.gov
RI Xu, Zhi/I-2546-2012
FU Intramural Research Programs of the The Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD); National
Institutes of Health Clinical Center; National Institute of Aging (NIA);
Congenital Adrenal Hyperplasia Research, Education and Support (CARES)
Foundation
FX We are grateful to the patients for their participation in this study.
We are indebted to Dr. Chack-Yung Yu (Department of Pediatrics, The Ohio
State University, Columbus, OH, USA) for providing probes for Southern
blot and valuable discussion of the genetics of the RCCX module. We want
to thank NIA Core Laboratory staff for DNA extraction and sample
processing, and Ms. Tina Roberson for administrative assistance. This
work was supported (in part) by the Intramural Research Programs of the
The Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), the National Institutes of Health Clinical Center,
and the National Institute of Aging (NIA) and (in part) by The
Congenital Adrenal Hyperplasia Research, Education and Support (CARES)
Foundation. Dr. Merke is a Commissioned Officer in the United States
Public Health Service.
NR 24
TC 2
Z9 6
U1 2
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD DEC
PY 2012
VL 131
IS 12
BP 1889
EP 1894
DI 10.1007/s00439-012-1217-8
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 034JU
UT WOS:000310869700009
PM 22886582
ER
PT J
AU Little, MP
Kleinerman, RA
Stovall, M
Smith, SA
Mabuchi, K
AF Little, Mark P.
Kleinerman, Ruth A.
Stovall, Marilyn
Smith, Susan A.
Mabuchi, Kiyohiko
TI Analysis of Dose Response for Circulatory Disease After Radiotherapy for
Benign Disease
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Circulatory disease; Ischemic heart disease; Stroke; Peptic ulcer;
Benign disease
ID ATOMIC-BOMB SURVIVORS; LONG-TERM MORTALITY; BREAST-CANCER; HODGKIN
LYMPHOMA; CHILDHOOD-CANCER; INCREASED RISK; HEART-DISEASE; PEPTIC-ULCER;
RADIATION; STROKE
AB Purpose: To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure.
Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease).
Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy(-1) of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy(-1) of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups.
Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure. (C) 2012 Elsevier Inc.
C1 [Little, Mark P.; Kleinerman, Ruth A.; Mabuchi, Kiyohiko] NCI, Radiat Epidemiol Branch, Rockville, MD 20852 USA.
[Stovall, Marilyn; Smith, Susan A.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
RP Little, MP (reprint author), NCI, Radiat Epidemiol Branch, Execut Plaza S,6120 Execut Blvd,MSC 7238, Rockville, MD 20852 USA.
EM mark.little@nih.gov
OI Kleinerman, Ruth/0000-0001-7415-2478; Little, Mark/0000-0003-0980-7567
FU National Institutes of Health, the National Cancer Institute, Division
of Cancer Epidemiology and Genetics
FX The authors are grateful for the detailed and helpful comments of the
three referees. This work was supported by the Intramural Research
Program of the National Institutes of Health, the National Cancer
Institute, Division of Cancer Epidemiology and Genetics.
NR 25
TC 11
Z9 12
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD DEC 1
PY 2012
VL 84
IS 5
BP 1101
EP 1109
DI 10.1016/j.ijrobp.2012.01.053
PG 9
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 037GH
UT WOS:000311089700023
PM 22494591
ER
PT J
AU Cooper, JS
Zhang, Q
Pajak, TF
Forastiere, AA
Jacobs, J
Saxman, SB
Kish, JA
Kim, HE
Cmelak, AJ
Rotman, M
Lustig, R
Ensley, JF
Thorstad, W
Schultz, CJ
Yom, SS
Ang, KK
AF Cooper, Jay S.
Zhang, Qiang
Pajak, Thomas F.
Forastiere, Arlene A.
Jacobs, John
Saxman, Scott B.
Kish, Julie A.
Kim, Harold E.
Cmelak, Anthony J.
Rotman, Marvin
Lustig, Robert
Ensley, John F.
Thorstad, Wade
Schultz, Christopher J.
Yom, Sue S.
Ang, K. Kian
TI Long-term Follow-up of the RTOG 9501/Intergroup Phase III Trial:
Postoperative Concurrent Radiation Therapy and Chemotherapy in High-Risk
Squamous Cell Carcinoma of the Head and Neck
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID LOCALLY ADVANCED HEAD; RANDOMIZED-TRIAL; CONCOMITANT CHEMOTHERAPY;
CANCER; CHEMORADIOTHERAPY; RADIOTHERAPY; IRRADIATION
AB Purpose: Previous analysis of this Intergroup trial demonstrated that with a median follow-up among surviving patients of 45.9 months, the concurrent postoperative administration of cisplatin and radiation therapy improved local-regional control and disease-free survival of patients who had high-risk resectable head-and-neck carcinomas. With a minimum of 10 years of follow-up potentially now available for all patients, these results are updated here to examine long-term outcomes.
Methods and Materials: A total of 410 analyzable patients who had high-risk resected head-and-neck cancers were prospectively randomized to receive either radiation therapy (RT: 60 Gy in 6 weeks) or identical RT plus cisplatin, 100 mg/m 2 i.v. on days 1, 22, and 43 (RT vertical bar CT).
Results: At 10 years, the local-regional failure rates were 28.8% vs 22.3% (P=.10), disease-free survival was 19.1% vs 20.1% (P=.25), and overall survival was 27.0% vs 29.1% (P=.31) for patients treated by RT vs RT + CT, respectively. In the unplanned subset analysis limited to patients who had microscopically involved resection margins and/or extracapsular spread of disease, local-regional failure occurred in 33.1% vs 21.0% (P=.02), disease-free survival was 12.3% vs 18.4% (P=.05), and overall survival was 19.6% vs 27.1% (P=.07), respectively.
Conclusion: At a median follow-up of 9.4 years for surviving patients, no significant differences in outcome were observed in the analysis of all randomized eligible patients. However, analysis of the subgroup of patients who had either microscopically involved resection margins and/or extracapsular spread of disease showed improved local-regional control and disease-free survival with concurrent administration of chemotherapy. The remaining subgroup of patients who were enrolled only because they had tumor in 2 or more lymph nodes did not benefit from the addition of CT to RT. (C) 2012 Elsevier Inc.
C1 [Cooper, Jay S.] Maimonides Canc Ctr, New York, NY 11220 USA.
[Zhang, Qiang; Pajak, Thomas F.] Radiat Therapy Oncol Grp Stat Ctr, Philadelphia, PA USA.
[Forastiere, Arlene A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
[Jacobs, John; Ensley, John F.] Wayne State Univ, Barbara Ann Karmanos Comprehens Canc Ctr, Detroit, MI USA.
[Saxman, Scott B.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Kish, Julie A.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Kim, Harold E.] Wayne State Univ, Med Ctr, Detroit, MI 48202 USA.
[Cmelak, Anthony J.] Vanderbilt Canc Ctr, Nashville, TN USA.
[Rotman, Marvin] SUNY Hlth Ctr Brooklyn, Brooklyn, NY USA.
[Lustig, Robert] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Thorstad, Wade] Washington Univ, St Louis, MO USA.
[Schultz, Christopher J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Yom, Sue S.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Ang, K. Kian] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Cooper, JS (reprint author), Maimonides Canc Ctr, 6300 8th Ave Brooklyn, New York, NY 11220 USA.
EM jcooper@maimonidesmed.org
OI Yom, Sue/0000-0002-0779-7476
FU RTOG [U10 CA21661]; CCOP [U10 CA37422]; National Cancer Institute (NCI)
[U10 CA32115]
FX Supported by RTOG grant U10 CA21661, CCOP grant U10 CA37422, and Stat
grant U10 CA32115 from the National Cancer Institute (NCI). This
manuscript's contents are solely the responsibility of the authors and
do not necessarily represent the official views of the National Cancer
Institute.
NR 18
TC 85
Z9 89
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD DEC 1
PY 2012
VL 84
IS 5
BP 1198
EP 1205
DI 10.1016/j.ijrobp.2012.05.008
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 037GH
UT WOS:000311089700037
PM 22749632
ER
PT J
AU Cantilena, L
Kahn, R
Duncan, CC
Li, SH
Anderson, A
Elkashef, A
AF Cantilena, Louis
Kahn, Roberta
Duncan, Connie C.
Li, Shou-Hua
Anderson, Ann
Elkashef, Ahmed
TI Safety of Atomoxetine in Combination With Intravenous Cocaine in
Cocaine-Experienced Participants
SO JOURNAL OF ADDICTION MEDICINE
LA English
DT Article
DE atomoxetine; cocaine; cognitive; interaction; pharmacokinetics; safety
ID ATTENTION DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY
DISORDER; SPONTANEOUSLY HYPERTENSIVE-RAT; PREFRONTAL CORTEX;
METHYLPHENIDATE; NOREPINEPHRINE; TOLERABILITY; MAINTENANCE; WITHDRAWAL;
DOPAMINE
AB Objectives: Atomoxetine has been considered as an agonist replacement therapy for cocaine. We investigated the safety of the interaction of atomoxetine with cocaine and also whether cognitive function was affected by atomoxetine during short-term administration.
Methods: In a double-blind placebo-controlled inpatient study of 20 cocaine-dependent volunteers, participants received atomoxetine 80 mg daily followed by 100 mg daily for 5 days each. On the fourth and fifth day at each dose, cocaine (20 and 40 mg) was infused intravenously in sequential daily sessions.
Results: Preinfusion mean systolic pressures showed a small but statistically significant difference between placebo and both doses of atomoxetine. Preinfusion mean diastolic pressures were significant between placebo and atomoxetine 80 mg only. The diastolic pressure response to 40 mg cocaine was statistically significant only between the 80- and 100-mg atomoxetine doses. All electrocardiogram parameters were unchanged. Visual Analog Scale (VAS) scores for "bad effect" in the atomoxetine group were significantly higher at baseline, then declined, and for "likely to use" declined with atomoxetine treatment. On the Addiction Research Center Inventory, the atomoxetine group scored significantly lower on amphetamine, euphoria, and energy subscales (P < 0.0001). Other VAS descriptors, Brief Substance Craving Scale, Profile of Moods State, and Brief Psychiatric Rating Scale showed no differences. Atomoxetine did not affect cocaine pharmacokinetics. In tests of working memory, sustained attention, cognitive flexibility, and decision-making, atomoxetine improved performance on the visual n-back task. There were no differences in any pharmacokinetic parameters for cocaine with atomoxetine.
Conclusions: Atomoxetine was tolerated safely by all participants. Certain cognitive improvements and a dampening effect on VAS scores after cocaine were observed, but should be weighed against small but significant differences in hemodynamic responses after atomoxetine.
C1 [Kahn, Roberta; Li, Shou-Hua; Anderson, Ann; Elkashef, Ahmed] NIDA, Med Clin Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA.
[Cantilena, Louis] Uniformed Serv Univ Hlth Sci, Div Clin Pharmacol & Med Toxicol, Bethesda, MD 20814 USA.
[Duncan, Connie C.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA.
RP Li, SH (reprint author), NIDA, Med Clin Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA.
EM SLi1@nida.nih.gov
FU NIDA [HU0001-04-1-0006, N01DA-05-8864, N01DA-7-8870, N01DA-3-8829];
Henry M Jackson Foundation for the Advancement of Military Medicine
[HU0001-04-1-0006]
FX Supported by grant/cooperative agreement HU0001-04-1-0006 between the
NIDA and the Henry M Jackson Foundation for the Advancement of Military
Medicine. Data management, pharmacokinetic analysis and plasma drug
analyses were supported by NIDA contracts N01DA-05-8864, N01DA-7-8870
and N01DA-3-8829, respectively.
NR 25
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1932-0620
J9 J ADDICT MED
JI J. Addict. Med.
PD DEC
PY 2012
VL 6
IS 4
BP 265
EP 273
DI 10.1097/ADM.0b013e31826b767f
PG 9
WC Substance Abuse
SC Substance Abuse
GA 033II
UT WOS:000310787200005
PM 22987022
ER
PT J
AU Sutin, AR
Milaneschi, Y
Cannas, A
Ferrucci, L
Uda, M
Schlessinger, D
Zonderman, AB
Terracciano, A
AF Sutin, Angelina R.
Milaneschi, Yuri
Cannas, Alessandra
Ferrucci, Luigi
Uda, Manuela
Schlessinger, David
Zonderman, Alan B.
Terracciano, Antonio
TI Impulsivity-related traits are associated with higher white blood cell
counts
SO JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Personality; Impulsivity; White blood cells; Inflammation; Neuroticism;
Conscientiousness
ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; PERSONALITY MEASURES;
MORTALITY; SMOKING; OBESITY; IMMUNE; PREDICTORS; HEALTH; ATHEROSCLEROSIS
AB A chronically elevated white blood cell (WBC) count is a risk factor for morbidity and mortality. The present research tests whether facets of impulsivity-impulsiveness, excitement-seeking, self-discipline, and deliberation-are associated with chronically elevated WBC counts. Community-dwelling participants (N = 5,652) from Sardinia, Italy, completed a standard personality questionnaire and provided blood samples concurrently and again 3 years later. Higher scores on impulsivity, in particular impulsiveness and excitement-seeking, were related to higher total WBC counts and higher lymphocyte counts at both time points. Impulsiveness was a predictor of chronic inflammation: for every standard deviation difference in this trait, there was an almost 25% higher risk of elevated WBC counts at both time points (OR = 1.23, 95% CI = 1.10-1.38). These associations were mediated, in part, by smoking and body mass index. The findings demonstrate that links between psychological processes and immunity are not limited to acute stressors; stable personality dispositions are associated with a chronic inflammatory state.
C1 [Sutin, Angelina R.; Milaneschi, Yuri; Ferrucci, Luigi; Schlessinger, David; Zonderman, Alan B.; Terracciano, Antonio] NIA, NIH, DHHS, Baltimore, MD 21224 USA.
[Cannas, Alessandra; Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, Monserrato, Italy.
RP Sutin, AR (reprint author), NIA, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sutina@mail.nih.gov
RI terracciano, antonio/B-1884-2008;
OI Zonderman, Alan B/0000-0002-6523-4778
FU Intramural NIH HHS [ZIA AG000197-03, Z99 AG999999, ZIA AG000197-04]
NR 44
TC 8
Z9 8
U1 0
U2 17
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0160-7715
J9 J BEHAV MED
JI J. Behav. Med.
PD DEC
PY 2012
VL 35
IS 6
BP 616
EP 623
DI 10.1007/s10865-011-9390-0
PG 8
WC Psychology, Clinical
SC Psychology
GA 034TC
UT WOS:000310894800005
PM 22190235
ER
PT J
AU Kovalchik, SA
AF Kovalchik, Stephanie A.
TI Survey finds that most meta-analysts do not attempt to collect
individual patient data
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE Effect modification; Individual patient data; Meta-analysis;
Meta-regression; Randomized controlled trial; Subgroup analysis
ID RANDOMIZED-TRIALS; DATA METAANALYSIS; CLINICAL-TRIALS; LEVEL; REGRESSION
AB Objective: To characterize current efforts and outcomes of individual patient data (IPD) collection among meta-analysts of randomized controlled clinical trials.
Study Design and Setting: Corresponding authors of meta-analyses of randomized controlled trials in general medicine with a binary endpoint were sent an e-mail survey inquiring about their efforts to obtain IPD. Descriptive statistics of each meta-analysis were extracted to evaluate their association with data seeking.
Results: Only 22 (4.2%) of the sampled meta-analyses included IPD. Of the 360 authors surveyed, 256 (71%) reported not seeking IPD: 48% thought that the undertaking would be too difficult, 30% thought that it was not necessary for their main analysis, 25% did not have sufficient time or resources, and 22% never considered it. Seeking IPD was not significantly associated with any trial characteristic examined, including whether subgroup analyses were performed. Authors who sought IPD obtained a median of two data sets (interquartile range = 0-5). Unsuccessful contact (43%), refusal without explanation (21%), and lost or inaccessible data (20%) were the most common reasons why trial data could not be obtained.
Conclusion: The infrequency of attempts made by meta-analysts to obtain participant data is an important contributor to the rarity of IPD meta-analyses. Published by Elsevier Inc.
C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Kovalchik, SA (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8047, Rockville, MD 20852 USA.
EM kovalchiksa@mail.nih.gov
FU intramural research program of the National Institutes of
Health/National Cancer Institute
FX This research was supported by the intramural research program of the
National Institutes of Health/National Cancer Institute. The author has
no conflicts of interest to declare.
NR 20
TC 3
Z9 3
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0895-4356
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD DEC
PY 2012
VL 65
IS 12
BP 1296
EP 1299
DI 10.1016/j.jclinepi.2012.07.010
PG 4
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 031VA
UT WOS:000310669400012
PM 22981246
ER
PT J
AU Peterson, PG
Pak, SK
Nguyen, B
Jacobs, G
Folio, L
AF Peterson, P. Gabriel
Pak, Sung K.
Binh Nguyen
Jacobs, Genevieve
Folio, Les
TI Extreme Compression for Extreme Conditions: Pilot Study to Identify
Optimal Compression of CT Images Using MPEG-4 Video Compression
SO JOURNAL OF DIGITAL IMAGING
LA English
DT Article
DE Compression; MPEG4; Universal trauma window; Combat trauma
ID WAVELET COMPRESSION; IRREVERSIBLE COMPRESSION; COMPUTED-TOMOGRAPHY;
RADIOGRAPHS; SYSTEM
AB This study aims to evaluate the utility of compressed computed tomography (CT) studies (to expedite transmission) using Motion Pictures Experts Group, Layer 4 (MPEG-4) movie formatting in combat hospitals when guiding major treatment regimens. This retrospective analysis was approved by Walter Reed Army Medical Center institutional review board with a waiver for the informed consent requirement. Twenty-five CT chest, abdomen, and pelvis exams were converted from Digital Imaging and Communications in Medicine to MPEG-4 movie format at various compression ratios. Three board-certified radiologists reviewed various levels of compression on emergent CT findings on 25 combat casualties and compared with the interpretation of the original series. A Universal Trauma Window was selected at -200 HU level and 1,500 HU width, then compressed at three lossy levels. Sensitivities and specificities for each reviewer were calculated along with 95 % confidence intervals using the method of general estimating equations. The compression ratios compared were 171:1, 86:1, and 41:1 with combined sensitivities of 90 % (95 % confidence interval, 79-95), 94 % (87-97), and 100 % (93-100), respectively. Combined specificities were 100 % (85-100), 100 % (85-100), and 96 % (78-99), respectively. The introduction of CT in combat hospitals with increasing detectors and image data in recent military operations has increased the need for effective teleradiology; mandating compression technology. Image compression is currently used to transmit images from combat hospital to tertiary care centers with subspecialists and our study demonstrates MPEG-4 technology as a reasonable means of achieving such compression.
C1 [Jacobs, Genevieve; Folio, Les] NIH, Bethesda, MD 20892 USA.
[Peterson, P. Gabriel; Pak, Sung K.; Binh Nguyen] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA.
RP Jacobs, G (reprint author), NIH, 9000 Rockville Pike,Bldg 10, Bethesda, MD 20892 USA.
EM jacobs@vt.edu
NR 19
TC 4
Z9 4
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0897-1889
J9 J DIGIT IMAGING
JI J. Digit. Imaging
PD DEC
PY 2012
VL 25
IS 6
BP 764
EP 770
DI 10.1007/s10278-012-9500-8
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 033QF
UT WOS:000310812400009
PM 22722754
ER
PT J
AU Matsubara, T
Tanaka, N
Sato, M
Kang, DW
Krausz, KW
Flanders, KC
Ikeda, K
Luecke, H
Wakefield, LM
Gonzalez, FJ
AF Matsubara, Tsutomu
Tanaka, Naoki
Sato, Misako
Kang, Dong Wook
Krausz, Kristopher W.
Flanders, Kathleen C.
Ikeda, Kazuo
Luecke, Hans
Wakefield, Lalage M.
Gonzalez, Frank J.
TI TGF-beta-SMAD3 signaling mediates hepatic bile acid and phospholipid
metabolism following lithocholic acid-induced liver injury
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE cholestasis; hepatitis; transforming growth factor; MAD homolog
ID ACTIVATED RECEPTOR-ALPHA; CHOLESTEROL 7-ALPHA-HYDROXYLASE GENE;
FARNESOID-X-RECEPTOR; SALT EXPORT PUMP; NECROSIS-FACTOR-ALPHA; NUCLEAR
RECEPTORS; HYDROXYSTEROID SULFOTRANSFERASE; TARGETED DISRUPTION;
PROTECTIVE ROLE; UP-REGULATION
AB Transforming growth factor-beta (TGF beta) is activated as a result of liver injury, such as cholestasis. However, its influence on endogenous metabolism is not known. This study demonstrated that TGF beta regulates hepatic phospholipid and bile acid homeostasis through MAD homolog 3 (SMAD3) activation as revealed by lithocholic acid-induced experimental intrahepatic cholestasis. Lithocholic acid (LCA) induced expression of TGFB1 and the receptors TGFBR1 and TGFBR2 in the liver. In addition, immunohistochemistry revealed higher TGF beta expression around the portal vein after LCA exposure and diminished SMAD3 phosphorylation in hepatocytes from Smad3-null mice. Serum metabolomics indicated increased bile acids and decreased lysophosphatidylcholine (LPC) after LCA exposure. Interestingly, in Smad3-null mice, the metabolic alteration was attenuated. LCA-induced lysophosphatidylcholine acyltransferase 4 (LPCAT4) and organic solute transporter beta (OST beta) expression were markedly decreased in Smad3-null mice, whereas TGF beta induced LPCAT4 and OST beta expression in primary mouse hepatocytes. In addition, introduction of SMAD3 enhanced the TGF beta-induced LPCAT4 and OST beta expression in the human hepatocellular carcinoma cell line HepG2. In conclusion, considering that Smad3-null mice showed attenuated serum ALP activity, a diagnostic indicator of cholangiocyte injury, these results strongly support the view that TGF beta-SMAD3 signaling mediates an alteration in phospholipid and bile acid metabolism following hepatic inflammation with the biliary injury. -Matsubara, T., N. Tanaka, M. Sato, D.W. Kang, K.W. Krausz, K.C. Flanders, K. Ikeda, H. Luecke, L.M. Wakefield, and F.J. Gonzalez. TGF-beta-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury. J. Lipid Res. 2012. 53: 2698-2707.
C1 [Matsubara, Tsutomu; Tanaka, Naoki; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Sato, Misako; Flanders, Kathleen C.; Wakefield, Lalage M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Matsubara, Tsutomu; Ikeda, Kazuo] Osaka City Univ, Dept Anat & Regenerat Biol, Osaka 558, Japan.
[Kang, Dong Wook; Luecke, Hans] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM fjgonz@helix.nih.gov
FU National Cancer Institute Intramural Research Program, Center for Cancer
Research, National Institutes of Health; Japan Society for the Promotion
of Science
FX This work was supported by the National Cancer Institute Intramural
Research Program, Center for Cancer Research, National Institutes of
Health. Its contents are solely the responsibility of the authors and do
not necessarily represent the official views of the National Institutes
of Health.; The authors thank John Buckley and Linda Byrd (National
Cancer Institute) for technical assistance. T.M. was supported by a
fellowship from the Japan Society for the Promotion of Science.
NR 56
TC 9
Z9 11
U1 1
U2 22
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
J9 J LIPID RES
JI J. Lipid Res.
PD DEC
PY 2012
VL 53
IS 12
BP 2698
EP 2707
DI 10.1194/jlr.M031773
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 034XA
UT WOS:000310905000018
PM 23034213
ER
PT J
AU Srivastava, S
Kashiwaya, Y
Chen, XS
Geiger, JD
Pawlosky, R
Veech, RL
AF Srivastava, Shireesh
Kashiwaya, Yoshihiro
Chen, Xuesong
Geiger, Jonathan D.
Pawlosky, Robert
Veech, Richard L.
TI Microwave irradiation decreases ATP, increases free [Mg2+], and alters
in vivo intracellular reactions in rat brain
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE anoxic changes; biochemical thermodynamics; freeze blowing; intermediate
metabolites; neurotransmitters; phosphorylation potential
ID INTERMEDIARY METABOLISM; ENERGY; HYDROLYSIS; ADENOSINE; ETHANOL;
ENZYMES; BINDING
AB Rapid inactivation of metabolism is essential for accurately determining the concentrations of metabolic intermediates in the in vivo state. We compared a broad spectrum of energetic intermediate metabolites and neurotransmitters in brains obtained by microwave irradiation to those obtained by freeze blowing, the most rapid method of extracting and freezing rat brain. The concentrations of many intermediates, cytosolic free NAD(P)+/NAD(P)H ratios, as well as neurotransmitters were not affected by the microwave procedure. However, the brain concentrations of ATP were about 30% lower, whereas those of ADP, AMP, and GDP were higher in the microwave-irradiated compared with the freeze-blown brains. In addition, the hydrolysis of approximately 1 mu mol/g of ATP, a major in vivo Mg2+-binding site, was related to approximately five-fold increase in free [Mg2+] (0.53 +/- 0.07 mM in freeze blown vs. 2.91 mM +/- 0.48 mM in microwaved brains), as determined from the ratio [citrate]/[isocitrate]. Consequently, many intracellular properties, such as the phosphorylation potential and the ?G' of ATP hydrolysis were significantly altered in microwaved tissue. The determinations of some glycolytic and TCA cycle metabolites, the phosphorylation potential, and the ?G' of ATP hydrolysis do not represent the in vivo state when using microwave-fixed brain tissue.
C1 [Veech, Richard L.] NIAAA, Lab Metab Control, NIH, DHHS, Bethesda, MD 20892 USA.
[Chen, Xuesong; Geiger, Jonathan D.] Univ N Dakota, Dept Pharmacol, Grand Forks, ND 58201 USA.
[Chen, Xuesong; Geiger, Jonathan D.] Univ N Dakota, Dept Physiol, Grand Forks, ND 58201 USA.
[Chen, Xuesong; Geiger, Jonathan D.] Univ N Dakota, Dept Therapeut, Grand Forks, ND 58201 USA.
RP Veech, RL (reprint author), NIAAA, Lab Metab Control, NIH, DHHS, 5625 Fishers Lane,Rm 2S-28, Bethesda, MD 20892 USA.
EM rveech@mail.nih.gov
FU NCRR; NIH [2P20RR017699]; NINDS [R01NS065957]
FX The authors would like to thank Professor Eric Murphy for the use of the
microwave apparatus. This publication was made possible by grants to JDG
from the NCRR, a component of the NIH (2P20RR017699), and from NINDS
(R01NS065957). The authors have no conflict of interest to report.
NR 24
TC 6
Z9 6
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD DEC
PY 2012
VL 123
IS 5
BP 668
EP 675
DI 10.1111/jnc.12026
PG 8
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 033OQ
UT WOS:000310807800004
PM 23013291
ER
PT J
AU Ridnour, LA
Dhanapal, S
Hoos, M
Wilson, J
Lee, J
Cheng, RYS
Brueggemann, EE
Hines, HB
Wilcock, DM
Vitek, MP
Wink, DA
Colton, CA
AF Ridnour, Lisa A.
Dhanapal, Sneha
Hoos, Michael
Wilson, Joan
Lee, Jennifer
Cheng, Robert Y. S.
Brueggemann, Ernst E.
Hines, Harry B.
Wilcock, Donna M.
Vitek, Michael P.
Wink, David A.
Colton, Carol A.
TI Nitric oxide-mediated regulation of beta-amyloid clearance via
alterations of MMP-9/TIMP-1
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE amyloid; immunity; matrix metalloproteinase-9 (MMP-9); microglia; nitric
oxide (NOS2); tissue inhibitor of metalloproteinase-1 (TIMP-1)
ID MATRIX-METALLOPROTEINASE EXPRESSION; CENTRAL-NERVOUS-SYSTEM;
ALZHEIMERS-DISEASE; GELATINASE-B; MATRIX-METALLOPROTEINASE-9 EXPRESSION;
COGNITIVE IMPAIRMENT; CULTURED MICROGLIA; DEGRADING ENZYMES; PRECURSOR
PROTEIN; HUMAN MACROPHAGES
AB Fibrillar amyloid plaques are largely composed of amyloid-beta (A beta) peptides that are metabolized into products, including A beta 1-16, by proteases including matrix metalloproteinase 9 (MMP-9). The balance between production and degradation of A beta proteins is critical to amyloid accumulation and resulting disease. Regulation of MMP-9 and its endogenous inhibitor tissue inhibitor of metalloproteinase (TIMP)-1 by nitric oxide (NO) has been shown. We hypothesize that nitric oxide synthase (NOS2) protects against Alzheimer's disease pathology by increasing amyloid clearance through NO regulation of MMP-9/TIMP-1 balance. We show NO-mediated increased MMP-9/TIMP-1 ratios enhanced the degradation of fibrillar A beta in vitro, which was abolished when silenced for MMP-9 protein translation. The in vivo relationship between MMP-9, NO and A beta degradation was examined by comparing an Alzheimer's disease mouse model that expresses NOS2 with a model lacking NOS2. To quantitate MMP-9 mediated changes, we generated an antibody recognizing the A beta 1-16 fragment, and used mass spectrometry multi-reaction monitoring assay for detection of immunoprecipitated A beta 1-16 peptides. A beta 1-16 levels decreased in brain lysates lacking NOS2 when compared with strains that express human amyloid precursor protein on the NOS2 background. TIMP-1 increased in the APPSwDI/NOS2-/- mice with decreased MMP activity and increased amyloid burden, thereby supporting roles for NO in the regulation of MMP/TIMP balance and plaque clearance.
C1 [Hoos, Michael; Wilson, Joan; Lee, Jennifer; Wilcock, Donna M.; Vitek, Michael P.; Colton, Carol A.] Duke Univ, Sch Med, Div Neurol, Durham, NC 27709 USA.
[Ridnour, Lisa A.; Dhanapal, Sneha; Cheng, Robert Y. S.; Wink, David A.] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Brueggemann, Ernst E.; Hines, Harry B.] USAMRID, Integrated Div Toxicol, Ft Detrick, MD USA.
RP Colton, CA (reprint author), Duke Univ, Sch Med, Div Neurol, Durham, NC 27709 USA.
EM Carol.Colton@duke.edu
RI Wilcock, Donna/J-7517-2016
FU NIH [AG031845]; National Institutes of Health, National Cancer
Institute, and Center for Cancer Research
FX This work was funded in part by an NIH grant (AG031845) awarded to CAC.
The authors thank the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, and Center for Cancer
Research who have supported this work.
NR 67
TC 23
Z9 25
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD DEC
PY 2012
VL 123
IS 5
BP 736
EP 749
DI 10.1111/jnc.12028
PG 14
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 033OQ
UT WOS:000310807800010
PM 23016931
ER
PT J
AU Newland, PK
Thomas, FP
Riley, M
Flick, LH
Fearing, A
AF Newland, Pamela K.
Thomas, Florian P.
Riley, Marguerite
Flick, Louise H.
Fearing, Arleen
TI The Use of Focus Groups to Characterize Symptoms in Persons With
Multiple Sclerosis
SO JOURNAL OF NEUROSCIENCE NURSING
LA English
DT Article
DE focus groups; multiple sclerosis; qualitative research; symptoms
ID QUALITY-OF-LIFE; ACUTE MYOCARDIAL-INFARCTION; COGNITIVE IMPAIRMENT;
PAIN; FATIGUE; WOMEN; DEPRESSION; CLUSTERS; HEAT
AB Multiple sclerosis is a chronic neurological disease with a myriad of symptoms. Because most work has been quantitative, it is important to capture symptoms as described by patients who experience them, using a qualitative approach. The purpose of our study was to describe and identify symptoms, with emphasis on co-occurrence, using focus groups. Three focus groups were conducted (N = 16) with relapsing-remitting multiple sclerosis patients. Common symptoms, described as both singular and co-occurring, were problems with balance, cognition, vision, and heat intolerance. These findings augment past characterizations of symptoms experienced in persons with relapsing-remitting multiple sclerosis and provide evidence for future studies.
C1 [Newland, Pamela K.] Natl Inst Nursing Res NRSA, NIH, Edwardsville, IL USA.
[Newland, Pamela K.; Riley, Marguerite; Fearing, Arleen] So Illinois Univ, Edwardsville, IL 62026 USA.
[Thomas, Florian P.] St Louis Univ, Dept Neurol & Psychiat, St Louis, MO 63103 USA.
[Thomas, Florian P.] St Louis Univ, Natl MS Soc Multiple Sclerosis Ctr, St Louis, MO 63103 USA.
[Flick, Louise H.] St Louis Univ, Sch Publ Hlth, St Louis, MO 63103 USA.
RP Newland, PK (reprint author), Natl Inst Nursing Res NRSA, NIH, Edwardsville, IL USA.
EM pnewlan@siue.edu
FU NINR NIH HHS [F32 NR012389]
NR 33
TC 2
Z9 2
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0888-0395
J9 J NEUROSCI NURS
JI J. Neurosci. Nurs.
PD DEC
PY 2012
VL 44
IS 6
BP 351
EP 357
DI 10.1097/JNN.0b013e318268308b
PG 7
WC Clinical Neurology; Nursing
SC Neurosciences & Neurology; Nursing
GA 032YF
UT WOS:000310756000008
PM 23124125
ER
PT J
AU Kohli, A
Zhang, X
Yang, J
Russell, RS
Donnelly, RP
Sheikh, F
Sherman, A
Young, H
Imamichi, T
Lempicki, RA
Masur, H
Kottilil, S
AF Kohli, A.
Zhang, X.
Yang, J.
Russell, R. S.
Donnelly, R. P.
Sheikh, F.
Sherman, A.
Young, H.
Imamichi, T.
Lempicki, R. A.
Masur, H.
Kottilil, S.
TI Distinct and overlapping genomic profiles and antiviral effects of
Interferon-lambda and -alpha on HCV-infected and noninfected hepatoma
cells
SO JOURNAL OF VIRAL HEPATITIS
LA English
DT Article
DE hepatitis C; Huh7.5 cells; IFN-alpha; IL28B; JFH-1
ID HEPATITIS-C VIRUS; NONSTRUCTURAL 5A PROTEIN; SIGNAL-TRANSDUCTION;
GENETIC-VARIATION; PLUS RIBAVIRIN; IL28B; REPLICATION; CLEARANCE;
CULTURE
AB Recently, several SNPs in the region of the IL28B (IFN-lambda) gene have been associated with spontaneous clearance of hepatitis C virus (HCV) and enhanced cure rates for IFN-alfa-based therapies, suggesting a potential correlation between IFN-lambda and the ability to clear HCV. To understand the mechanism of IFN-lambda s as compared to IFN-alpha s antiviral activity, we performed a comprehensive analysis of their anti-HCV effects, whole genome transcriptome profiling with validation, and signalling of IFN-alpha and IFN-lambda using J6/JFH-1 and Huh7.5 cells in vitro. IFN-lambda and IFN-alpha exhibited comparable anti-HCV activity and gene expression profiles in Huh7.5 cells. While the majority of genes induced by IFN-alpha and IFN-lambda were similar, IFN-lambda exhibits profound, but delayed kinetics of IFN-stimulated genes (ISG) induction, while IFN-alpha induced more rapid induction of ISGs. Furthermore, the increased induction of ISG expression by IFN-lambda correlated with up-regulation of IFN-lambda receptor (IL-28RA) expression and more prolonged activation of the Jak-STAT signalling pathway. The findings from our comparative analysis of IFN-alpha and IFN-lambda in HCV-infected and noninfected cells support the clinical use of IFN-lambda as a potential alternative to IFN-alpha in the treatment of chronic hepatitis C.
C1 [Kohli, A.; Zhang, X.; Sherman, A.; Kottilil, S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Yang, J.; Imamichi, T.; Lempicki, R. A.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Russell, R. S.] Mem Univ Newfoundland, Fac Med, St John, NF, Canada.
[Donnelly, R. P.; Sheikh, F.] US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
[Young, H.] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Masur, H.] NIH, CCMD, CC, Bethesda, MD 20892 USA.
RP Kohli, A (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10 Magnuson Clin Ctr,Room 11N204,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kohlia@niaid.nih.gov
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
FU NIH [National Institute of Allergy and Infectious Diseases]; NIH
[National Cancer Institute]; U.S. Food and Drug Administration
FX This research was supported in whole by the Intramural Research Program
of the NIH, [National Institute of Allergy and Infectious Diseases and
National Cancer Institute and the U.S. Food and Drug Administration].
The content of this publication does not necessarily reflect the views
or policies of the U. S. Department of Health and Human Services, or
does mention of any trade names, commercial products or organizations
imply endorsement by the U. S. Government. Some of the data in this
manuscript were presented in an oral presentation at the American
Association for Liver Disease Meeting, Oct 2010, Boston, MA. The authors
do not have commercial ownership or other association that might pose a
conflict of interest.
NR 23
TC 20
Z9 22
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1352-0504
J9 J VIRAL HEPATITIS
JI J. Viral Hepatitis
PD DEC
PY 2012
VL 19
IS 12
BP 843
EP 853
DI 10.1111/j.1365-2893.2012.01610.x
PG 11
WC Gastroenterology & Hepatology; Infectious Diseases; Virology
SC Gastroenterology & Hepatology; Infectious Diseases; Virology
GA 030WE
UT WOS:000310600000003
PM 23121362
ER
PT J
AU Boltz, VF
Ambrose, Z
Kearney, MF
Shao, W
KewalRamani, VN
Maldarelli, F
Mellors, JW
Coffin, JM
AF Boltz, Valerie F.
Ambrose, Zandrea
Kearney, Mary F.
Shao, Wei
KewalRamani, Vineet N.
Maldarelli, Frank
Mellors, John W.
Coffin, John M.
TI Ultrasensitive Allele-Specific PCR Reveals Rare Preexisting
Drug-Resistant Variants and a Large Replicating Virus Population in
Macaques Infected with a Simian Immunodeficiency Virus Containing Human
Immunodeficiency Virus Reverse Transcriptase
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ANTIRETROVIRAL THERAPY; IN-VIVO; HIV-1; TYPE-1; NEVIRAPINE; MUTATIONS;
FITNESS; POLYMORPHISM; PERSISTENCE; EVOLUTION
AB It has been proposed that most drug-resistant mutants, resulting from a single-nucleotide change, exist at low frequency in human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) populations in vivo prior to the initiation of antiretroviral therapy (ART). To test this hypothesis and to investigate the emergence of resistant mutants with drug selection, we developed a new ultrasensitive allele-specific PCR (UsASP) assay, which can detect drug resistance mutations at a frequency of >= 0.001% of the virus population. We applied this assay to plasma samples obtained from macaques infected with an SIV variant containing HIV-1 reverse transcriptase (RT) (RT-simian-human immunodeficiency [SHIV](mne)), before and after they were exposed to a short course of efavirenz (EFV) monotherapy. We detected RT inhibitor (RTI) resistance mutations K65R and M184I but not K103N in 2 of 2 RT-SHIV-infected macaques prior to EFV exposure. After three doses over 4 days of EFV monotherapy, 103N mutations (AAC and AAT) rapidly emerged and increased in the population to levels of similar to 20%, indicating that they were present prior to EFV exposure. The rapid increase of 103N mutations from < 0.001% to 20% of the viral population indicates that the replicating virus population size in RT-SHIV-infected macaques must be 106 or more infected cells per replication cycle.
C1 [Boltz, Valerie F.; Kearney, Mary F.; KewalRamani, Vineet N.; Maldarelli, Frank] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Ambrose, Zandrea; Mellors, John W.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA.
[Shao, Wei] SAIC Frederick, Adv Biomed Comp Ctr, Frederick, MD USA.
[Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
RP Boltz, VF (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
EM boltzv@mail.nih.gov
FU National Cancer Institute's Intramural Center for Cancer Research; NIH
R01 grant [AI080290]; FM Kirby Foundation
FX Funding for this research was provided by the National Cancer
Institute's Intramural Center for Cancer Research, which supports the
HIV Drug Resistance Program, and NIH R01 grant AI080290 (to Z.A.).
J.M.C. was a research professor of the American Cancer Society with
support from the FM Kirby Foundation.
NR 34
TC 12
Z9 12
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD DEC
PY 2012
VL 86
IS 23
BP 12525
EP 12530
DI 10.1128/JVI.01963-12
PG 6
WC Virology
SC Virology
GA 030QN
UT WOS:000310585300006
PM 22933296
ER
PT J
AU Demberg, T
Brocca-Cofano, E
Xiao, P
Venzon, D
Vargas-Inchaustegui, D
Lee, EM
Kalisz, I
Kalyanaraman, VS
DiPasquale, J
McKinnon, K
Robert-Guroff, M
AF Demberg, Thorsten
Brocca-Cofano, Egidio
Xiao, Peng
Venzon, David
Vargas-Inchaustegui, Diego
Lee, Eun Mi
Kalisz, Irene
Kalyanaraman, V. S.
DiPasquale, Janet
McKinnon, Katherine
Robert-Guroff, Marjorie
TI Dynamics of Memory B-Cell Populations in Blood, Lymph Nodes, and Bone
Marrow during Antiretroviral Therapy and Envelope Boosting in Simian
Immunodeficiency Virus SIVmac251-Infected Rhesus Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HIV-INFECTED INDIVIDUALS; SOLUBLE CD27; T-CELLS; DISEASE PROGRESSION;
1-INFECTED PATIENTS; IMMUNE ACTIVATION; SIV INFECTION; EXPRESSION;
IMMUNIZATION; RESPONSES
AB Human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection causes B-cell dysregulation and the loss of memory B cells in peripheral blood mononuclear cells (PBMC). These effects are not completely reversed by antiretroviral treatment (ART). To further elucidate B-cell changes during chronic SIV infection and treatment, we investigated memory B-cell subpopulations and plasma cells/plasmablasts (PC/PB) in blood, bone marrow, and lymph nodes of rhesus macaques during ART and upon release from ART. Macaques previously immunized with SIV recombinants and the gp120 protein were included to assess the effects of prior vaccination. ART was administered for 11 weeks, with or without gp120 boosting at week 9. Nave and resting, activated, and tissue-like memory B cells and PC/PB were evaluated by flow cytometry. Antibody-secreting cells (ASC) and serum antibody titers were assessed. No lasting changes in B-cell memory subpopulations occurred in bone marrow and lymph nodes, but significant decreases in numbers of activated memory B cells and increases in numbers of tissue-like memory B cells persisted in PBMC. Macaque PC/PB were found to be either CD27(+) or CD27(-) and therefore were defined as CD19(+) CD38(hi) CD138(+). The numbers of these PC/PB were transiently increased in both PBMC and bone marrow following gp120 boosting of the unvaccinated and vaccinated macaque groups. Similarly, ASC numbers in PBMC and bone marrow of the two macaque groups also transiently increased following envelope boosting. Nevertheless, serum binding titers against SIVgp120 remained unchanged. Thus, even during chronic SIV infection, B cells respond to antigen, but long-term memory does not develop, perhaps due to germinal center destruction. Earlier and/or prolonged treatment to allow the generation of virus-specific long-term memory B cells should benefit ART/therapeutic vaccination regimens.
C1 [Demberg, Thorsten; Brocca-Cofano, Egidio; Xiao, Peng; Vargas-Inchaustegui, Diego; DiPasquale, Janet; McKinnon, Katherine; Robert-Guroff, Marjorie] NCI, Vaccine Branch, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Lee, Eun Mi; Kalisz, Irene; Kalyanaraman, V. S.] Adv BioSci Labs Inc, Rockville, MD USA.
RP Robert-Guroff, M (reprint author), NCI, Vaccine Branch, Bethesda, MD 20892 USA.
EM guroffm@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health
National Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Institutes of Health National Cancer Institute.
NR 66
TC 33
Z9 33
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 DEC
PY 2012
VL 86
IS 23
BP 12591
EP 12604
DI 10.1128/JVI.00298-12
PG 14
WC Virology
SC Virology
GA 030QN
UT WOS:000310585300013
PM 22973034
ER
PT J
AU Wang, KN
Kappel, JD
Canders, C
Davila, WF
Sayre, D
Chavez, M
Pesnicak, L
Cohen, JI
AF Wang, Kening
Kappel, Justin D.
Canders, Caleb
Davila, Wilmer F.
Sayre, Dean
Chavez, Mayra
Pesnicak, Lesley
Cohen, Jeffrey I.
TI A Herpes Simplex Virus 2 Glycoprotein D Mutant Generated by Bacterial
Artificial Chromosome Mutagenesis Is Severely Impaired for Infecting
Neuronal Cells and Infects Only Vero Cells Expressing Exogenous HVEM
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LATENCY-ASSOCIATED TRANSCRIPT; HUMAN RECEPTOR HVEA; LONG UNIQUE REGION;
GENITAL HERPES; ESCHERICHIA-COLI; IN-VIVO; SPONTANEOUS REACTIVATION;
VECTOR SEQUENCES; GENETIC-ANALYSIS; GENOME SEQUENCE
AB We constructed a herpes simplex virus 2 (HSV-2) bacterial artificial chromosome (BAC) clone, bHSV2-BAC38, which contains full-length HSV-2 inserted into a BAC vector. Unlike previously reported HSV-2 BAC clones, the virus genome inserted into this BAC clone has no known gene disruptions. Virus derived from the BAC clone had a wild-type phenotype for growth in vitro and for acute infection, latency, and reactivation in mice. HVEM, expressed on epithelial cells and lymphocytes, and nectin-1, expressed on neurons and epithelial cells, are the two principal receptors used by HSV to enter cells. We used the HSV-2 BAC clone to construct an HSV-2 glycoprotein D mutant (HSV2-gD27) with point mutations in amino acids 215, 222, and 223, which are critical for the interaction of gD with nectin-1. HSV2-gD27 infected cells expressing HVEM, including a human epithelial cell line. However, the virus lost the ability to infect cells expressing only nectin-1, including neuronal cell lines, and did not infect ganglia in mice. Surprisingly, we found that HSV2-gD27 could not infect Vero cells unless we transduced the cells with a retrovirus expressing HVEM. High-level expression of HVEM in Vero cells also resulted in increased syncytia and enhanced cell-to-cell spread in cells infected with wild-type HSV-2. The inability of the HSV2-gD27 mutant to infect neuronal cells in vitro or sensory ganglia in mice after intramuscular inoculation suggests that this HSV-2 mutant might be an attractive candidate for a live attenuated HSV-2 vaccine.
C1 [Wang, Kening; Kappel, Justin D.; Canders, Caleb; Davila, Wilmer F.; Sayre, Dean; Chavez, Mayra; Pesnicak, Lesley; Cohen, Jeffrey I.] NIAID, Med Virol Sect, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Wang, KN (reprint author), NIAID, Med Virol Sect, Infect Dis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kwang@niaid.nih.gov
FU intramural research program of the National Institute of Allergy and
Infectious Diseases
FX This research was supported by the intramural research program of the
National Institute of Allergy and Infectious Diseases.
NR 66
TC 13
Z9 15
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD DEC
PY 2012
VL 86
IS 23
BP 12891
EP 12902
DI 10.1128/JVI.01055-12
PG 12
WC Virology
SC Virology
GA 030QN
UT WOS:000310585300039
PM 22993162
ER
PT J
AU O'Carroll, IP
Crist, RM
Mirro, J
Harvin, D
Soheilian, F
Kamata, A
Nagashima, K
Rein, A
AF O'Carroll, Ina P.
Crist, Rachael M.
Mirro, Jane
Harvin, Demetria
Soheilian, Ferri
Kamata, Anne
Nagashima, Kunio
Rein, Alan
TI Functional Redundancy in HIV-1 Viral Particle Assembly
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ROUS-SARCOMA-VIRUS; MURINE
LEUKEMIA-VIRUS; IN-VITRO; NUCLEOCAPSID PROTEIN; MEMBRANE-BINDING; GAG;
DOMAIN; RNA; DIMERIZATION
AB Expression of a retroviral Gag protein in mammalian cells leads to the assembly of virus particles. In vitro, recombinant Gag proteins are soluble but assemble into virus-like particles (VLPs) upon addition of nucleic acid. We have proposed that Gag undergoes a conformational change when it is at a high local concentration and that this change is an essential prerequisite for particle assembly; perhaps one way that this condition can be fulfilled is by the cooperative binding of Gag molecules to nucleic acid. We have now characterized the assembly in human cells of HIV-1 Gag molecules with a variety of defects, including (i) inability to bind to the plasma membrane, (ii) near-total inability of their capsid domains to engage in dimeric interaction, and (iii) drastically compromised ability to bind RNA. We find that Gag molecules with any one of these defects still retain some ability to assemble into roughly spherical objects with roughly correct radius of curvature. However, combination of any two of the defects completely destroys this capability. The results suggest that these three functions are somewhat redundant with respect to their contribution to particle assembly. We suggest that they are alternative mechanisms for the initial concentration of Gag molecules; under our experimental conditions, any two of the three is sufficient to lead to some semblance of correct assembly.
C1 [O'Carroll, Ina P.; Crist, Rachael M.; Mirro, Jane; Harvin, Demetria; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Soheilian, Ferri; Kamata, Anne; Nagashima, Kunio] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Adv Technol Program, Frederick, MD USA.
RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
EM reina@mail.nih.gov
RI Crist, Rachael/K-7603-2012
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; NIH Intramural AIDS Targeted Antiviral
Program; 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, in part
by the NIH Intramural AIDS Targeted Antiviral Program, and in part with
federal funds from the National Cancer Institute, National Institutes of
Health, under contract HHSN26120080001E.
NR 34
TC 15
Z9 15
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD DEC
PY 2012
VL 86
IS 23
BP 12991
EP 12996
DI 10.1128/JVI.06287-11
PG 6
WC Virology
SC Virology
GA 030QN
UT WOS:000310585300048
PM 22993163
ER
PT J
AU Pilkington, GR
Majerciak, V
Bear, J
Uranishi, H
Zheng, ZM
Felber, BK
AF Pilkington, Guy R.
Majerciak, Vladimir
Bear, Jenifer
Uranishi, Hiroaki
Zheng, Zhi-Ming
Felber, Barbara K.
TI Kaposi's Sarcoma-Associated Herpesvirus ORF57 Is Not a Bona Fide Export
Factor
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MESSENGER-RNA EXPORT; REGULATORY PROTEIN; 5' END; VIRUS; EXPRESSION;
PATHWAY; ELEMENT; STABILITY; TRANSPORT; INTERACTS
AB Kaposi's sarcoma-associated herpesvirus (KSHV [human herpesvirus 8; HHV-8]) open reading frame 57 (ORF57) is a viral early protein participating in posttranscriptional regulatory events, such as splicing, RNA stabilization, and protein expression. Recent data suggest that ORF57 recruits the transcription and export (TREX) complex to viral RNA and exports these transcripts to the cytoplasm. In this study, we show that although ORF57 promotes expression of a selection of KSHV viral intronless RNAs, it is not a bona fide export factor.
C1 [Pilkington, Guy R.; Bear, Jenifer; Felber, Barbara K.] Frederick Natl Lab Canc Res, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD USA.
[Majerciak, Vladimir; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Uranishi, Hiroaki] Frederick Natl Lab Canc Res, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD USA.
RP Felber, BK (reprint author), Frederick Natl Lab Canc Res, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD USA.
EM felberb@mail.nih.gov
FU Intramural Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research
FX This work was supported in part by the Intramural Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 32
TC 8
Z9 8
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 DEC
PY 2012
VL 86
IS 23
BP 13089
EP 13094
DI 10.1128/JVI.00606-12
PG 6
WC Virology
SC Virology
GA 030QN
UT WOS:000310585300059
PM 22993146
ER
PT J
AU Ma, X
Li, J
Zhang, F
AF Ma, X.
Li, J.
Zhang, F.
TI Intranasal Co-delivery with the Mouse Zona Pellucida 3 and GM-CSF
Expressing Constructs Enhances Humoral Immune Responses and
Contraception in Mice
SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID DNA VACCINE; AUTOIMMUNE-DISEASE; DENDRITIC CELLS; IN-VITRO; ZP3;
IMMUNIZATION; OVARY; INFERTILITY; MECHANISMS; ANTIBODIES
AB Granulocytemonocyte colony-stimulating factor (GM-CSF) regulates the function of antigen-presenting cells (APCs) and has been broadly used as the adjuvant. Here, we tested whether intranasal delivery of GM-CSF can improve the contraception of mouse zona pellucida 3 (mZP3) DNA vaccine. Our results showed that co-administration of GM-CSF and mZP3 DNA vaccine increased the levels of secretory IgA (sIgA) and IgG antibodies in vaginal washes and serum, respectively. Co-administration enhanced Th2 responses through improving the maturation of dendritic cells. Importantly, GM-CSF significantly reduced the fertility rate and mean litter size induced by mZP3 DNA vaccine alone without interfering the normal follicular development. These data suggest that GM-CSF could be used as adjuvant to develop immunocontraceptive vaccine.
C1 [Li, J.] Ctr Canc Res, Human Retrovirus Sect, Vaccine Branch, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Ma, X.; Zhang, F.] Xinjiang Univ, Coll Life Sci & Technol, Xinjiang Key Lab Biol Resources & Genet Engn, Urumqi 830046, Peoples R China.
RP Li, J (reprint author), Ctr Canc Res, Human Retrovirus Sect, Vaccine Branch, Frederick Natl Lab Canc Res, 1050 Boyles St,Bldg 535,Room 226, Frederick, MD 21702 USA.
EM jinyao.li@nih.gov; zfcxju@xju.edu.cn
FU National Natural Science Foundation of China [30760136]
FX This work was supported by the National Natural Science Foundation of
China (No. 30760136) to FCZ, We would like to thank Dr. Ailian Zhang,
Dr. Yixian Tu and Zibirnisa Kadir for their assistance in this work.
NR 31
TC 4
Z9 5
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-9475
J9 SCAND J IMMUNOL
JI Scand. J. Immunol.
PD DEC
PY 2012
VL 76
IS 6
BP 521
EP 527
DI 10.1111/j.1365-3083.2012.02765.x
PG 7
WC Immunology
SC Immunology
GA 034LB
UT WOS:000310873500001
PM 22924630
ER
PT J
AU Remaley, AT
AF Remaley, Alan T.
TI Comment
SO ACTA BIOQUIMICA CLINICA LATINOAMERICANA
LA Spanish
DT Editorial Material
C1 NIH, Dept Lab Med, Bethesda, MD 20892 USA.
RP Remaley, AT (reprint author), NIH, Dept Lab Med, Bldg 10,Rm 2C-433, Bethesda, MD 20892 USA.
EM aremaley@cc.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 0
PU FEDERACION BIOQUIMICA PROVINCIA BUENOS AIRES
PI LA PLATA, BUENOS AIRES
PA CALLE 6, NO. 1344, 1900 LA PLATA, BUENOS AIRES, ARGENTINA
SN 0325-2957
EI 1851-6114
J9 ACTA BIOQUIM CLIN L
JI Acta Bioquim. Clin. Latinoam.
PD DEC
PY 2012
VL 46
IS 4
BP 699
EP 700
PG 2
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA V33PY
UT WOS:000209031900018
ER
PT J
AU Sacks, DB
Arnold, M
Bakris, GL
Bruns, DE
Horvath, AR
Kirkman, MS
Lernmark, A
Metzger, BE
Nathan, DM
AF Sacks, David B.
Arnold, Mark
Bakris, George L.
Bruns, David E.
Horvath, Andrea Rita
Kirkman, M. Sue
Lernmark, Ake
Metzger, Boyd E.
Nathan, David M.
TI Clinical Laboratory Practice Guides Instructions and recommendations for
the diagnosis and management of diabetes mellitus Chapters 7 to 13
SO ACTA BIOQUIMICA CLINICA LATINOAMERICANA
LA Spanish
DT Article
C1 [Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
[Arnold, Mark] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA.
[Bakris, George L.] Univ Chicago, Dept Med, Hypertens Dis Unit, Sect Endocrinol Diabet & Metab, Chicago, IL 60637 USA.
[Bruns, David E.] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA.
[Horvath, Andrea Rita] Univ Sydney, Screening & Test Evaluat Program, Sch Publ Hlth, SEALS Dept Clin Chem,Prince Wales Hosp, Sydney, NSW 2006, Australia.
[Kirkman, M. Sue] Amer Diabet Assoc, Alexandria, VA USA.
[Lernmark, Ake] Lund Univ, Dept Clin Sci, CRC, Skane Univ Hosp Malmo, Malmo, Sweden.
[Metzger, Boyd E.] Northwestern Univ, Feinberg Sch Med, Div Endocrinol, Chicago, IL 60611 USA.
[Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Nathan, David M.] Harvard Univ, Sch Med, Ctr Diabet, Boston, MA USA.
[Nathan, David M.] Univ Toronto, Toronto, ON M5S 1A1, Canada.
RP Sacks, DB (reprint author), NIH, Dept Lab Med, Bldg 10, Bethesda, MD 20892 USA.
OI Sacks, David/0000-0003-3100-0735
NR 380
TC 0
Z9 0
U1 0
U2 1
PU FEDERACION BIOQUIMICA PROVINCIA BUENOS AIRES
PI LA PLATA, BUENOS AIRES
PA CALLE 6, NO. 1344, 1900 LA PLATA, BUENOS AIRES, ARGENTINA
SN 0325-2957
EI 1851-6114
J9 ACTA BIOQUIM CLIN L
JI Acta Bioquim. Clin. Latinoam.
PD DEC
PY 2012
VL 46
IS 4
BP 701
EP 741
PG 41
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA V33PY
UT WOS:000209031900019
ER
PT J
AU Dackiewicz, N
Viteritti, L
Marciano, B
Bailez, M
Merino, P
Bortolato, D
Jaichenko, A
Seminara, R
Amarilla, A
AF Dackiewicz, Nora
Viteritti, Laura
Marciano, Beatriz
Bailez, Marcela
Merino, Patricia
Bortolato, Diana
Jaichenko, Andre
Seminara, Rodolfo
Amarilla, Analia
TI Achievements and challenges in implementing the surgical checklist in a
Pediatric Hospital
SO ARCHIVOS ARGENTINOS DE PEDIATRIA
LA Spanish
DT Article
DE surgical checklist; patient safety in OR
ID SAFETY CHECKLIST; CULTURE
AB Patient safety in the operating room is a topic of universal concern. Several studies support the existence of a high percentage of complications and a high mortality rate in surgical procedures (0.5 to 5%). The World Health Organization (WHO) has proposed the implementation of surgical check list in order to improve patient safety in the operating room.
In Hospital Garrahan, 9600 surgeries and surgical anesthesia for more than 8000 studies and other invasive procedures are performed per year. WHO checklist adaptation and implementation was considered an institutional priority. We describe difficulties and solutions in implementing the surgical checklist. Surgical team involvement in project planning and development was essential.
C1 [Marciano, Beatriz] NIH, Bethesda, MD USA.
EM noradack@gmail.com
NR 19
TC 2
Z9 3
U1 1
U2 3
PU SOC ARGENTINA PEDIATRIA
PI CAP FED BUENO AIRES
PA AV COLONEL DIAZ 1971-75-C1425DQF, CAP FED BUENO AIRES, 00000, ARGENTINA
SN 0325-0075
EI 1668-3501
J9 ARCH ARGENT PEDIATR
JI Arch. Argent. Pediatr.
PD DEC
PY 2012
VL 110
IS 6
BP 503
EP 508
DI 10.5546/aap.2012.503
PG 6
WC Pediatrics
SC Pediatrics
GA 246TY
UT WOS:000326563200015
PM 23224308
ER
PT J
AU Soliman, AS
Schairer, C
AF Soliman, Amr S.
Schairer, Catherine
TI Considerations in setting up and conducting epidemiologic studies of
cancer in middle- and low-income countries: the experience of a
case-control study of inflammatory breast cancer in North Africa in the
past 10 years
SO CANCER MEDICINE
LA English
DT Article
DE Breast cancer; Egypt; epidemiology; field methods; Morocco; North
Africa; Tunisia
AB This article illustrates some issues we faced during our experience in conducting an epidemiologic case-control study of inflammatory breast cancer in North Africa. We expect that some of the questions we had to ask in order to address these issues might be helpful to others in setting up epidemiologic studies in developing regions. We describe our experience from different angles including the use of multiple sites to achieve adequate sample size, standardizing diagnosis of disease, identifying cancer cases at the time of diagnosis, control selection procedures, logistics of study implementation, questionnaire development and interviewing, biologic specimens, and procedures for protection of human subjects. We have developed a brief checklist to summarize important issues for conducting future epidemiologic studies in these or similar low- or middle-income countries.
C1 [Soliman, Amr S.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Schairer, Catherine] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
RP Soliman, AS (reprint author), Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Epidemiol, 984395 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM amr.soliman@unmc.edu
FU National Cancer Institute [R25 CA112383]; AVON Foundation [N012091];
Office of International Affairs of the National Cancer Institute;
National Cancer Institute Intramural Research Program
FX This work was supported, in part, by grant R25 CA112383 from the
National Cancer Institute, grant N012091 from the AVON Foundation, the
Office of International Affairs of the National Cancer Institute, and
the National Cancer Institute Intramural Research Program.
NR 45
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2045-7634
J9 CANCER MED-US
JI Cancer Med.
PD DEC
PY 2012
VL 1
IS 3
BP 338
EP 349
DI 10.1002/cam4.36
PG 12
WC Oncology
SC Oncology
GA V36KG
UT WOS:000209210400006
PM 23342283
ER
PT J
AU Lee, S
Young, DR
Pratt, CA
Jobe, JB
Chae, SE
McMurray, RG
Johnson, CC
Going, SB
Elder, JP
Stevens, J
AF Lee, Sunmin
Young, Deborah Rohm
Pratt, Charlotte A.
Jobe, Jared B.
Chae, Soo Eun
McMurray, Robert G.
Johnson, Carolyn C.
Going, Scott B.
Elder, John P.
Stevens, June
TI Effects of Parents' Employment Status on Changes in Body Mass Index and
Percent Body Fat in Adolescent Girls
SO CHILDHOOD OBESITY
LA English
DT Article
AB Background: Parents' employment status is frequently cited as a possible predictor of child weight status. Despite the importance of the topic, only a few studies have been conducted. No longitudinal studies have been conducted in the United States.
Methods: A cohort of 1201 girls from the Trial of Activity for Adolescent Girls was used. Height, weight, and percent body fat (PBF) were measured at the 6th and 8th grades. Parents' employment status (measured at 6th grade) was categorized into working full time (reference), part time, unemployed, working or staying at home, and don't know. Mixed-model regression was used to reflect the hierarchical design of our study and adjusted for age, race, parents' education level, free or reduced-price school lunch status, and living arrangement.
Results: Girls whose mothers worked part time or stayed at home had a decreased risk of excess weight gain [relative risk (RR) = 0.94, 95% confidence interval (CI) 0.88, 1.00; RR = 0.89, 95% CI 0.79, 1.00, respectively] compared to girls whose mothers worked full time. Girls whose fathers were unemployed had a moderately increased risk of excess weight gain (RR = 1.13, 95% CI 1.00, 1.26) compared to girls whose fathers worked full time. Having an unemployed mother or part-time or stay-at-home father was not associated with excess weight gain. Parents' employment status was not associated with excess PBF gain.
Conclusions: Our findings suggest that the availability of the mother has a greater influence on the weight of the daughter than the availability of the father. There is a need for a better understanding of how parents' employment status influences excess weight gain in adolescent girls.
C1 [Lee, Sunmin] Univ Maryland, Sch Publ Hlth, Dept Epidemiol & Biostat, College Pk, MD 20742 USA.
[Young, Deborah Rohm] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA.
[Pratt, Charlotte A.; Jobe, Jared B.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA.
[Chae, Soo Eun] Korean Educ Dev Inst, Seoul, South Korea.
[McMurray, Robert G.] Univ N Carolina, Dept Exercise & Sport Sci, Chapel Hill, NC USA.
[Johnson, Carolyn C.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Community Hlth Sci, New Orleans, LA USA.
[Going, Scott B.] Univ Arizona, Dept Physiol & Nutr Sci, Tucson, AZ USA.
[Elder, John P.] San Diego State Univ, Div Hlth Promot & Behav Sci, San Diego, CA 92182 USA.
[Stevens, June] Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA.
[Stevens, June] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
RP Lee, S (reprint author), Univ Maryland, Sch Publ Hlth, Dept Epidemiol & Biostat, 2234C SPH Bldg, College Pk, MD 20742 USA.
EM sunmin@umd.edu
RI Lee, Sunmin/C-9262-2011
FU National Heart, Lung, and Blood Institute at the National Institutes of
Health [U01 HL-066845, HL66852, HL-066853, HL-066855, HL-066856,
HL-066857, HL-066858]
FX This work was supported by the National Heart, Lung, and Blood Institute
at the National Institutes of Health (U01 HL-066845, HL66852, HL-066853,
HL-066855, HL-066856, HL-066857, and HL-066858).
NR 29
TC 1
Z9 1
U1 1
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2153-2168
EI 2153-2176
J9 CHILD OBES
JI Child Obes.
PD DEC
PY 2012
VL 8
IS 6
BP 526
EP 532
DI 10.1089/chi.2011.0087
PG 7
WC Pediatrics
SC Pediatrics
GA V32JL
UT WOS:000208947400004
PM 23181918
ER
PT J
AU Binford, MC
Kahana, SY
Altice, FL
AF Binford, Meredith Camp
Kahana, Shoshana Y.
Altice, Frederick L.
TI A Systematic Review of Antiretroviral Adherence Interventions for
HIV-Infected People Who Use Drugs
SO CURRENT HIV/AIDS REPORTS
LA English
DT Review
DE Antiretroviral therapy; Intervention. Adherence; Persons who use drugs
(PWUDs); HIV and drug use; Combination antiretroviral therapy (cART);
Viral load. HIV treatment outcomes; Antiretroviral adherence
interventions; Behavioral aspects of HIV management; Substance abuse
AB HIV-infected persons who use drugs (PWUDs) are particularly vulnerable for suboptimal combination antiretroviral therapy (cART) adherence. A systematic review of interventions to improve cART adherence and virologic outcomes among HIV-infected PWUDs was conducted. Among the 45 eligible studies, randomized controlled trials suggested directly administered antiretroviral therapy, medication- assisted therapy ( MAT), contingency management, and multi- component, nurse- delivered interventions provided significant improved short- term adherence and virologic outcomes, but these effects were not sustained after intervention cessation. Cohort and prospective studies suggested short- term increased cART adherence with MAT. More conclusive data regarding the efficacy on cART adherence and HIV treatment outcomes using cognitive behavioral therapy, motivational interviewing, peer- driven interventions and the integration of MAT into HIV clinical care are warranted. Of great concern was the virtual lack of interventions with sustained post- intervention adherence and virologic benefits. Future research directions, including the development of interventions that promote long- term improvements in adherence and virologic outcomes, are discussed.
C1 [Binford, Meredith Camp; Altice, Frederick L.] Yale Univ, Sch Med, AIDS Program, Infect Dis Sect, New Haven, CT 06510 USA.
[Altice, Frederick L.] Yale Univ, Sch Publ Hlth, New Haven, CT 06510 USA.
[Kahana, Shoshana Y.] NIDA, Bethesda, MD 20892 USA.
RP Altice, FL (reprint author), Yale Univ, Sch Med, AIDS Program, Infect Dis Sect, 135 Coll St,Suite 323, New Haven, CT 06510 USA.
EM frederick.altice@yale.edu
FU National Institutes on Drug Abuse for career development [K24 DA017072]
FX The authors would like to acknowledge Paula Dellamura and Kathleen R.
Hamill for their editorial assistance in the preparation of this
manuscript and all study authors who responded to inquiries about
relevant papers. We would also like to thank the National Institutes on
Drug Abuse for career development support (K24 DA017072 for FLA). The
views and opinions expressed in this report are those of the authors and
should not be construed to represent the views of the National
Institutes on Drug Abuse or any of the sponsoring organizations,
agencies, or the U. S. government.
NR 91
TC 40
Z9 41
U1 4
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1548-3568
EI 1548-3576
J9 CURR HIV-AIDS REP
JI Curr. Hiv/Aids Rep.
PD DEC
PY 2012
VL 9
IS 4
BP 287
EP 312
DI 10.1007/s11904-012-0134-8
PG 26
WC Infectious Diseases
SC Infectious Diseases
GA V32TV
UT WOS:000208974400001
PM 22936463
ER
PT J
AU Kurland, BF
Johnson, LL
Diehr, PH
AF Kurland, Brenda F.
Johnson, Laura L.
Diehr, Paula H.
TI Accommodation of missing data in supportive and palliative care clinical
trials
SO CURRENT OPINION IN SUPPORTIVE AND PALLIATIVE CARE
LA English
DT Review
DE clinical trials; missing data; truncation because of death
AB Purpose of review Clinical trials to evaluate the supportive and palliative care treatments have some different missing data concerns than the other clinical trials. This study reviews the literature on missing data as it may apply to these trials.
Recent findings Prevention of missing data through study design and conduct is a recent area of focus. Missing data can be minimized by simplifying trial participation for patients, their caregivers, and trialists. Run-in periods with active drug or collecting data from observer (proxy) respondents may complicate a trial but may be used to address some specific concerns. Many analyses can accommodate data missing because of nonresponse by multiple imputation, using carefully chosen imputation models. Analysis of trials evaluating end-of-life care should distinguish between missing data and truncation because of death.
Summary Likely patterns for missing data should be discussed when planning a clinical trial, as modifications to trial design can minimize missing data while still addressing study aims. Many statistical analysis methods are available to accommodate missing data, but robustness of study conclusions to assumptions about mechanisms underlying the missingness should be evaluated by sensitivity analyses.
C1 [Kurland, Brenda F.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98019 USA.
[Johnson, Laura L.] NIH, Natl Ctr Complementary & Alternat Med, Seattle, WA USA.
[Diehr, Paula H.] Univ Washington, Seattle, WA 98195 USA.
RP Kurland, BF (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D5-360, Seattle, WA 98019 USA.
EM bkurland@fhcrc.org
OI Kurland, Brenda/0000-0002-5669-0595
FU National Center for Complementary and Alternative Medicine, National
Institutes of Health [1P50CA138293-01]
FX Funding disclosures: 1P50CA138293-01. This research was supported in
part by the National Center for Complementary and Alternative Medicine,
National Institutes of Health.
NR 36
TC 3
Z9 3
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1751-4258
EI 1751-4266
J9 CURR OPIN SUPPORT PA
JI Curr. Opin Support Palliat. Car.
PD DEC
PY 2012
VL 6
IS 4
BP 465
EP 470
DI 10.1097/SPC.0b013e328358441d
PG 6
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA V32OT
UT WOS:000208961200009
PM 23042422
ER
PT J
AU Lodato, JE
Aziz, N
Bennett, RE
Abernethy, AP
Kutner, JS
AF Lodato, Jordan E.
Aziz, Noreen
Bennett, Rachael E.
Abernethy, Amy P.
Kutner, Jean S.
TI Achieving palliative care research efficiency through defining and
benchmarking performance metrics
SO CURRENT OPINION IN SUPPORTIVE AND PALLIATIVE CARE
LA English
DT Review
DE clinical trials; operating procedures; palliative care; performance
metrics; process mapping
AB Purpose of review Research efficiency is gaining increasing attention in the research enterprise, including palliative care research. The importance of generating meaningful findings and translating these scientific advances to improved patient care creates urgency in the field to address well documented system inefficiencies. The Palliative Care Research Cooperative Group (PCRC) provides useful examples for ensuring research efficiency in palliative care.
Recent findings Literature on maximizing research efficiency focuses on the importance of clearly delineated process maps, working instructions, and standard operating procedures in creating synchronicity in expectations across research sites. Examples from the PCRC support these objectives and suggest that early creation and employment of performance metrics aligned with these processes are essential to generate clear expectations and identify benchmarks. These benchmarks are critical in effective monitoring and ultimately the generation of high-quality findings that are translatable to clinical populations. Prioritization of measurable goals and tasks to ensure that activities align with programmatic aims is critical.
Summary Examples from the PCRC affirm and expand the existing literature on research efficiency, providing a palliative care focus. Operating procedures, performance metrics, prioritization, and monitoring for success should all be informed by and inform the process map to achieve maximum research efficiency.
C1 [Lodato, Jordan E.; Abernethy, Amy P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Duke Ctr Learning Healthcare, Durham, NC 27710 USA.
[Lodato, Jordan E.; Abernethy, Amy P.] Duke Univ, Med Ctr, Duke Canc Inst, Duke Canc Care Res Program, Durham, NC 27710 USA.
[Aziz, Noreen] NINR, NIH, Bethesda, MD 20892 USA.
[Bennett, Rachael E.; Kutner, Jean S.] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Aurora, CO USA.
[Abernethy, Amy P.] Duke Univ, Med Ctr, Dept Med, Div Med Oncol, Durham, NC 27710 USA.
[Abernethy, Amy P.] Flinders Univ S Australia, Dept Palliat & Support Serv, Adelaide, SA 5001, Australia.
RP Lodato, JE (reprint author), Duke Univ, Med Ctr, Box 3436, Durham, NC 27710 USA.
EM jordan.lodato@duke.edu
OI Abernethy, Amy/0000-0001-6930-8722
FU US National Institutes of Health; US Agency for Healthcare Research and
Quality; Robert Wood Johnson Foundation; Biovex; DARA; Helsinn; MiCo;
Pfizer; Novartis
FX Dr A.P.A. has research funding from the US National Institutes of
Health, US Agency for Healthcare Research and Quality, Robert Wood
Johnson Foundation, Biovex, DARA, Helsinn, MiCo and Pfizer; these funds
are all distributed to Duke University Medical Center to support
research including salary support for Dr A. P. A.. In the last 2 years,
she has had nominal consulting agreements with, or received honoraria
from (15O] PET-CBF data, and Stathis Kanterakis and Drew Parker at
Penn for assistance with statistical analysis. We are grateful to the
BLSA participants and staff for their dedication to these studies.
NR 63
TC 19
Z9 20
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD DEC
PY 2012
VL 33
IS 12
BP 2733
EP 2745
DI 10.1016/j.neurobiolaging.2012.01.010
PG 13
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 025OJ
UT WOS:000310200000002
PM 22365049
ER
PT J
AU Qiu, CX
Cotch, MF
Sigurdsson, S
Eiriksdottir, G
Jonasson, F
Klein, R
Klein, BEK
Harris, TB
van Buchem, MA
Gudnason, V
Launer, LJ
AF Qiu, Chengxuan
Cotch, Mary Frances
Sigurdsson, Sigurdur
Eiriksdottir, Gudny
Jonasson, Fridbert
Klein, Ronald
Klein, Barbara E. K.
Harris, Tamara B.
van Buchem, Mark A.
Gudnason, Vilmundur
Launer, Lenore J.
TI Cerebral microbleeds and age-related macular degeneration: the
AGES-Reykjavik Study
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Age-related macular degeneration; Cerebral microbleeds; Amyloid-beta;
The AGES-Reykjavik Study
AB We test the hypothesis that cerebral microbleeds (CMB) and age-related macular degeneration (AMD), both linked to amyloid-beta deposition, are correlated. This study includes 4205 participants (mean age 76.2; 57.8% women) in the Age, Gene/Environment Susceptibility (AGES)Reykjavik Study (2002-2006). CMB were assessed from magnetic resonance images, and AMD was assessed using digital retinal images. Data were analyzed with multinomial logistic models controlling for major confounders. Evidence of CMB was detected in 476 persons (272 with strict lobar CMB and 204 with nonlobar CMB). AMD was detected in 1098 persons (869 with early AMD, 140 with exudative AMD, and 89 with pure geographic atrophy). Early and exudative AMD were not associated with CMB. The adjusted odds ratio of pure geographic atrophy was 1.62 (95% confidence interval 0.93-2.82, p = 0.089) for having any CMB, 1.43 (0.66-3.06, p = 0.363) for strict lobar CMB, and 1.85 (0.89-3.87, p = 0.100) for nonlobar CMB. This study provides no evidence that amyloid deposits in the brain and AMD are correlated. However, the suggestive association of geographic atrophy with CMB warrants further investigation. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Qiu, Chengxuan] Stockholm Univ, Karolinska Inst, Aging Res Ctr, SE-11330 Stockholm, Sweden.
[Qiu, Chengxuan; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Jonasson, Fridbert; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Jonasson, Fridbert] Natl Univ Hosp Reykjavik, Dept Ophthalmol, Reykjavik, Iceland.
[Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
RP Qiu, CX (reprint author), Stockholm Univ, Karolinska Inst, Aging Res Ctr, Gavlegatan 16, SE-11330 Stockholm, Sweden.
EM chengxuan.qiu@ki.se; launerl@nia.nih.gov
RI Gudnason, Vilmundur/K-6885-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Cotch, Mary
Frances/0000-0002-2046-4350; Qiu, Chengxuan/0000-0003-1922-4912; Klein,
Ronald/0000-0002-4428-6237
FU NIH [N01-AG-12100]; National Institute on Aging; National Eye Institute,
USA [ZIAEY000401]; Icelandic Heart Association; Icelandic Parliament,
Iceland; Swedish Council for Working Life and Social Research; Swedish
Research Council for Medical Research; Karolinska Institutet, Sweden
FX The AGES-Reykjavik Study was funded by NIH contract N01-AG-12100, the
Intramural Research Program of the National Institute on Aging, and the
National Eye Institute (ZIAEY000401), USA, and by the Icelandic Heart
Association and the Icelandic Parliament, Iceland. We thank all the
participants of the AGES-Reykjavik Study and the clinic staff at the
Icelandic Heart Association for their invaluable contribution. C. Q. is
supported by grants from the Swedish Council for Working Life and Social
Research, the Swedish Research Council for Medical Research, and
Karolinska Institutet, Sweden.
NR 3
TC 2
Z9 2
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD DEC
PY 2012
VL 33
IS 12
BP 2935
EP 2937
DI 10.1016/j.neurobiolaging.2012.01.012
PG 3
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 025OJ
UT WOS:000310200000019
PM 22382405
ER
PT J
AU Raney, R
Meza, J
Barr, F
Breneman, J
Hawkins, D
Hayes-Jordan, A
Huh, W
Meyer, W
Parham, D
Walterhouse, D
Anderson, J
AF Raney, Richard
Meza, Jane
Barr, Frederick
Breneman, John
Hawkins, Douglas
Hayes-Jordan, Andrea
Huh, Winston
Meyer, William
Parham, David
Walterhouse, David
Anderson, James
CA Childrens Oncology Grp
TI RESULTS OF THE IRSG D9602 LOW-RISK PROTOCOL FOR 35 PATIENTS WITH
ALVEOLAR RHABDOMYOSARCOMA (ARMS), 1997-1999
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Raney, Richard] UT MD Anderson Canc Ctr, Austin, TX USA.
[Anderson, James] Univ Nebraska Sch Med, Coll Publ Hlth, Omaha, NE USA.
[Barr, Frederick] NIH, Chevy Chase, MD USA.
[Breneman, John] Univ Cincinnati, Med Ctr, Barrett Canc Ctr, Cincinnati, OH 45267 USA.
[Hawkins, Douglas] Childrens Hosp & Reg Med Ctr, Seattle, WA USA.
[Huh, Winston] UT MD Anderson Canc Ctr, Houston, TX USA.
[Parham, David] Univ Oklahoma Hlth Sci Ctr, Oklahoma City, OK USA.
[Walterhouse, David] Childrens Mem Med Ctr, Chicago, IL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD DEC
PY 2012
VL 59
IS 6
SI SI
BP 991
EP 991
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 019QL
UT WOS:000309754300102
ER
PT J
AU Kroesen, M
Nierkens, S
Den Brok, M
Boon, L
Orentas, R
Hoogerbrugge, P
Adema, G
AF Kroesen, Michiel
Nierkens, Stefan
Den Brok, Martijn
Boon, Louis
Orentas, Rimas
Hoogerbrugge, Peter
Adema, Gosse
TI THE TH-MYCN MOUSE MODEL FOR IMMUNOTHERAPEUTICAL STUDIES INTO
NEUROBLASTOMA
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Kroesen, Michiel; Den Brok, Martijn; Hoogerbrugge, Peter; Adema, Gosse] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Nierkens, Stefan] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Boon, Louis] Bioceros, Utrecht, Netherlands.
[Orentas, Rimas] NCI, NIH, Washington, WA USA.
RI den Brok, Martijn/O-1054-2013; Adema, G.J./H-8007-2014; Hoogerbrugge,
Peter/H-8049-2014
NR 2
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD DEC
PY 2012
VL 59
IS 6
SI SI
BP 1055
EP 1055
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 019QL
UT WOS:000309754300361
ER
PT J
AU Kendall, G
Little, MP
Wakeford, R
Bunch, KJ
Miles, JCH
Vincent, TJ
Meara, JR
Murphy, MFG
AF Kendall, Gerry
Little, Mark P.
Wakeford, Richard
Bunch, Kathryn J.
Miles, Jon C. H.
Vincent, Timothy J.
Meara, Jill R.
Murphy, Michael F. G.
TI A RECORD-BASED CASE-CONTROL STUDY OF NATURAL BACKGROUND RADIATION AND
THE INCIDENCE OF CHILDHOOD CANCER IN GREAT BRITAIN
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Kendall, Gerry; Bunch, Kathryn J.; Vincent, Timothy J.; Murphy, Michael F. G.] Univ Oxford, Childhood Canc Res Grp, Oxford, England.
[Little, Mark P.] NCI, Radiat Epidemiol Branch, DHHS, NIH,Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Wakeford, Richard] Univ Mancheser, Dalton Nucl Inst, Manchester, Lancs, England.
[Miles, Jon C. H.; Meara, Jill R.] Hlth Protect Agcy, Didcot, Oxon, England.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD DEC
PY 2012
VL 59
IS 6
SI SI
BP 1096
EP 1096
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 019QL
UT WOS:000309754300535
ER
PT J
AU Cho, YM
Kim, YS
Kang, MJ
Farrar, WL
Hurt, EM
AF Cho, Yong Mee
Kim, Young Seok
Kang, Mun Jung
Farrar, William L.
Hurt, Elaine M.
TI Long-Term Recovery of Irradiated Prostate Cancer Increases Cancer Stem
Cells
SO PROSTATE
LA English
DT Article
DE prostate cancer; cancer stem cells; radiotherapy; resistance
ID PROGNOSTIC VALUE; IDENTIFICATION; RADIATION; TUMOR; CARCINOMA; SURVIVAL;
THERAPY; CD44
AB BACKGROUND. Despite improvements in treatment, prostate cancer (PC) remains the second-leading cause of cancer death in men. Radiotherapy is among the first-line treatments for PC, but a significant number of patients relapse. Recent evidence supports the idea that PC is initiated by a subset of cells, termed cancer stem cells (CSCs). CSCs have also been implicated in radioresistance in various malignancies, but their role in PC has not yet been investigated.
METHODS. We compared the relative radiosensitivity of isolated CSCs to the total population of their corresponding cell lines, and examined the relative numbers of CSCs in irradiated cell lines following long-term recovery and in recurrent human PC.
RESULTS. Here, we show that while irradiation does not immediately favor increased survival of CSCs, irradiated PC cell lines showed an increase in CSC properties with long-term recovery. These data suggest that, although CSCs are initially damaged by radiation, they possess a greater capacity for recovery and regrowth.
CONCLUSIONS. The combination of radiotherapy with a CSC-targeted therapeutic strategy may prevent tumor recurrence. Prostate 72: 1746-1756, 2012. (C) 2012 Wiley Periodicals, Inc.
C1 [Cho, Yong Mee; Farrar, William L.; Hurt, Elaine M.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Frederick, MD 21701 USA.
[Cho, Yong Mee; Kang, Mun Jung] Univ Ulsan, Coll Med, Dept Pathol, Asan Med Ctr, Seoul, South Korea.
[Kim, Young Seok] Univ Ulsan, Coll Med, Dept Radiat Oncol, Asan Med Ctr, Seoul, South Korea.
RP Hurt, EM (reprint author), Medimmune Inc, 1 MedImmune Way, Gaithersburg, MD 20878 USA.
EM hurte@medimmune.com
FU NCI; NIH [N01-CO-12400]; Intramural Research Fund; National Research
Foundation of Korea (NRF) [2010-0013063]
FX Grant sponsor: NCI; Grant sponsor: NIH N01-CO-12400; Grant sponsor:
Intramural Research Fund; Grant sponsor: National Research Foundation of
Korea (NRF) 2010-0013063.
NR 36
TC 13
Z9 15
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-4137
EI 1097-0045
J9 PROSTATE
JI Prostate
PD DEC
PY 2012
VL 72
IS 16
BP 1746
EP 1756
DI 10.1002/pros.22527
PG 11
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 029ID
UT WOS:000310487200006
PM 22513891
ER
PT J
AU Zhang, T
Ploetz, EA
Nagy, M
Doyle, SM
Wickner, S
Smith, PE
Zolkiewski, M
AF Zhang, Ting
Ploetz, Elizabeth A.
Nagy, Maria
Doyle, Shannon M.
Wickner, Sue
Smith, Paul E.
Zolkiewski, Michal
TI Flexible connection of the N-terminal domain in ClpB modulates substrate
binding and the aggregate reactivation efficiency
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Article
DE molecular chaperone; AAA plus ATPase; protein aggregation; aggregate
reactivation; conformational fluctuations
ID ESCHERICHIA-COLI; CHAPERONE ACTIVITY; PROTEIN DISAGGREGATION;
CRYSTAL-STRUCTURE; ATPASE ACTIVITY; HSP104; THERMOTOLERANCE;
OLIGOMERIZATION; DYNAMICS; MODELS
AB ClpB reactivates aggregated proteins in cooperation with DnaK/J. The ClpB monomer contains two nucleotide-binding domains (D1, D2), a coiled-coil domain, and an N-terminal domain attached to D1 with a 17-residue-long unstructured linker containing a Gly-Gly motif. The ClpB-mediated protein disaggregation is linked to translocation of substrates through the central channel in the hexameric ClpB, but the events preceding the translocation are poorly understood. The N-terminal domains form a ring surrounding the entrance to the channel and contribute to the aggregate binding. It was suggested that the N-terminal domain's mobility that is maintained by the unstructured linker might control the efficiency of aggregate reactivation. We produced seven variants of ClpB with modified sequence of the N-terminal linker. To increase the linker's conformational flexibility, we inserted up to four Gly next to the GG motif. To decrease the linker's flexibility, we deleted the GG motif and converted it into GP and PP. We found that none of the linker modifications inhibited the basal ClpB ATPase activity or its capability to form oligomers. However, the modified linker ClpB variants showed lower reactivation rates for aggregated glucose-6-phosphate dehydrogenase and firefly luciferase and a lower aggregate-binding efficiency than wt ClpB. We conclude that the linker does not merely connect the N-terminal domain, but it supports the chaperone activity of ClpB by contributing to the efficiency of aggregate binding and disaggregation. Moreover, our results suggest that selective pressure on the linker sequence may be crucial for maintaining the optimal efficiency of aggregate reactivation by ClpB.
C1 [Zhang, Ting; Nagy, Maria; Zolkiewski, Michal] Kansas State Univ, Dept Biochem, Manhattan, KS 66506 USA.
[Ploetz, Elizabeth A.; Smith, Paul E.] Kansas State Univ, Dept Chem, Manhattan, KS 66506 USA.
[Doyle, Shannon M.; Wickner, Sue] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Zolkiewski, M (reprint author), Kansas State Univ, Dept Biochem, 141 Chalmers Hall, Manhattan, KS 66506 USA.
EM michalz@ksu.edu
FU National Institutes of Health [R01GM079277]; Kansas Agricultural
Experiment Station [12-234-J]; KSU NSF GK-12 [NSF DGE-0841414]; NSF GRF
[NSF DGE-0750823]; Terry C. Johnson Center for Basic Cancer Research;
Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research
FX Grant sponsor: National Institutes of Health; Grant number: R01GM079277;
Grant sponsor: Kansas Agricultural Experiment Station; Contribution:
12-234-J; Grant sponsor: KSU NSF GK-12; Grant number: NSF DGE-0841414;
Grant sponsor: NSF GRF; Grant number: NSF DGE-0750823; Grant sponsors:
Terry C. Johnson Center for Basic Cancer Research; the Intramural
Research Program of the NIH; National Cancer Institute; Center for
Cancer Research
NR 48
TC 9
Z9 9
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-3585
J9 PROTEINS
JI Proteins
PD DEC
PY 2012
VL 80
IS 12
BP 2758
EP 2768
DI 10.1002/prot.24159
PG 11
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 030EP
UT WOS:000310552400010
PM 22890624
ER
PT J
AU Hoskins, LM
Greene, MH
AF Hoskins, Lindsey M.
Greene, Mark H.
TI Anticipatory Loss and Early Mastectomy for Young Female BRCA1/2 Mutation
Carriers
SO QUALITATIVE HEALTH RESEARCH
LA English
DT Article
DE cancer, breast; cancer, genetics; cancer, psychosocial aspects;
genetics; grounded theory; interviews; semistructured; young adults
ID BILATERAL PROPHYLACTIC MASTECTOMY; QUALITY-OF-LIFE; OVARIAN-CANCER RISK;
BREAST-CANCER; HEREDITARY BREAST; WOMEN; PREDISPOSITION; IDENTIFICATION;
SATISFACTION; METAANALYSIS
AB Young women who carry BRCA1/2 mutations face difficult decisions in managing their hereditary breast/ovarian cancer risk. Through this National Cancer Institute study, we sought to understand the process by which some young women choose risk-reducing bilateral mastectomy (RRBM) instead of alternative risk-management options. Data indicate that electing to undergo RRBM, although difficult, is experienced as a way to sidestep potentially devastating outcomes, such as stressful and costly high-risk screening, chemotherapy or radiation, or putting loved ones through the challenges of a cancer diagnosis. The decision to pursue RRBM is often the product of screening fatigue, encouragement from loved ones, and/or a sense of urgency to put one's high-risk period behind one. By understanding how young carriers make decisions about surgical risk reduction, providers can better guide, counsel, and support patients in the important tasks surrounding this life-changing medical decision, thereby helping to increase the duration and quality of their lives.
C1 [Hoskins, Lindsey M.; Greene, Mark H.] NCI, Clin Genet Branch, DCEG, NIH,USDHHS, Rockville, MD 20852 USA.
RP Hoskins, LM (reprint author), NCI, Clin Genet Branch, DCEG, NIH,USDHHS, 6120 Execut Blvd,EPS 7021, Rockville, MD 20852 USA.
EM hoskinsl@mail.nih.gov
FU Intramural NIH HHS; NCI NIH HHS [N02-CP-65504]
NR 44
TC 10
Z9 10
U1 0
U2 17
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1049-7323
J9 QUAL HEALTH RES
JI Qual. Health Res.
PD DEC
PY 2012
VL 22
IS 12
SI SI
BP 1633
EP 1646
DI 10.1177/1049732312458182
PG 14
WC Information Science & Library Science; Social Sciences,
Interdisciplinary; Social Sciences, Biomedical
SC Information Science & Library Science; Social Sciences - Other Topics;
Biomedical Social Sciences
GA 027TX
UT WOS:000310377700003
PM 22927701
ER
PT J
AU Franco, R
Cidlowski, JA
AF Franco, Rodrigo
Cidlowski, John A.
TI Glutathione Efflux and Cell Death
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID MITOCHONDRIAL PERMEABILITY TRANSITION; MULTIDRUG-RESISTANCE PROTEIN-1;
NECROSIS-FACTOR-ALPHA; FAS-INDUCED APOPTOSIS; RECEPTOR-MEDIATED
APOPTOSIS; S-NITROSOTHIOL FORMATION; HUMAN PROMONOCYTIC CELLS;
TNF-INDUCED APOPTOSIS; CYTOCHROME-C RELEASE; KAPPA-B ACTIVATION
AB Significance: Glutathione (GSH) depletion is a central signaling event that regulates the activation of cell death pathways. GSH depletion is often taken as a marker of oxidative stress and thus, as a consequence of its antioxidant properties scavenging reactive species of both oxygen and nitrogen (ROS/RNS). Recent Advances: There is increasing evidence demonstrating that GSH loss is an active phenomenon regulating the redox signaling events modulating cell death activation and progression. Critical Issues: In this work, we review the role of GSH depletion by its efflux, as an important event regulating alterations in the cellular redox balance during cell death independent from oxidative stress and ROS/RNS formation. We discuss the mechanisms involved in GSH efflux during cell death progression and the redox signaling events by which GSH depletion regulates the activation of the cell death machinery. Future Directions: The evidence summarized here clearly places GSH transport as a central mechanism mediating redox signaling during cell death progression. Future studies should be directed toward identifying the molecular identity of GSH transporters mediating GSH extrusion during cell death, and addressing the lack of sensitive approaches to quantify GSH efflux. Antioxid. Redox Signal. 17, 1694-1713.
C1 [Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Franco, Rodrigo] Univ Nebraska, Redox Biol Ctr, Sch Vet Med & Biomed Sci, Lincoln, NE 68583 USA.
RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM rfrancocruz2@unl.edu; cidlows1@mail.nih.gov
RI Franco, Rodrigo/D-9470-2013
OI Franco, Rodrigo/0000-0003-3241-8615
FU Intramural Research Program of the NIH/National Institute of
Environmental Health Sciences [1Z01ES090079]; Centers of Biomedical
Research Excellence (COBRE) [P20RR17675]; Research Council and the Life
Sciences Grant Program of the University of Nebraska-Lincoln
FX This work was supported by the Intramural Research Program of the
NIH/National Institute of Environmental Health Sciences 1Z01ES090079
(J.A.C.), P20RR17675 Centers of Biomedical Research Excellence (COBRE),
and an Interdisciplinary Grant from the Research Council and the Life
Sciences Grant Program of the University of Nebraska-Lincoln (R.F).
NR 258
TC 45
Z9 47
U1 2
U2 32
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD DEC
PY 2012
VL 17
IS 12
BP 1694
EP 1713
DI 10.1089/ars.2012.4553
PG 20
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 023UJ
UT WOS:000310061100004
PM 22656858
ER
PT J
AU Marino, N
Nakayama, J
Collins, JW
Steeg, PS
AF Marino, Natascia
Nakayama, Joji
Collins, Joshua W.
Steeg, Patricia S.
TI Insights into the biology and prevention of tumor metastasis provided by
the Nm23 metastasis suppressor gene
SO CANCER AND METASTASIS REVIEWS
LA English
DT Review
DE Nm23; Metastasis suppressor; Therapeutics; Histidine protein kinase;
Metastasis; NDPK; NME
ID NM23/NUCLEOSIDE DIPHOSPHATE-KINASE; PRIMARY CUTANEOUS MELANOMA; HUMAN
BREAST-CARCINOMA; CELL LUNG-CANCER; AUTONOMOUS LETHAL MUTATION;
ENDOTHELIAL GROWTH-FACTOR; HETEROTRIMERIC G-PROTEIN; LYMPH-NODE
METASTASIS; ACID RECEPTOR EDG2; HEPATOCELLULAR-CARCINOMA
AB Metastatic disease is the major cause of death among cancer patients. A class of genes, named metastasis suppressors, has been described to specifically regulate the metastatic process. The metastasis suppressor genes are downregulated in the metastatic lesion compared to the primary tumor. In this review, we describe the body of research surrounding the first metastasis suppressor identified, Nm23. Nm23 overexpression in aggressive cancer cell lines reduced their metastatic potential in vivo with no significant reduction in primary tumor size. A complex mechanism of anti-metastatic action is unfolding involving several known Nm23 enzymatic activities (nucleotide diphosphate kinase, histidine kinase, and 3'aEuro"5' exonuclease), protein-protein interactions, and downstream gene regulation properties. Translational approaches involving Nm23 have progressed to the clinic. The upregulation of Nm23 expression by medroxyprogesterone acetate has been tested in a phase II trial. Other approaches with significant preclinical success include gene therapy using traditional or nanoparticle delivery, and cell permeable Nm23 protein. Recently, based on the inverse correlation of Nm23 and LPA1 expression, a LPA1 inhibitor has been shown to both inhibit metastasis and induce metastatic dormancy.
C1 [Marino, Natascia; Nakayama, Joji; Collins, Joshua W.; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Marino, N (reprint author), NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, 37 Convent Dr,Room 1122, Bethesda, MD 20892 USA.
EM marinon@mail.nih.gov
FU Intramural Program of National Cancer Institute
FX This research was supported by the Intramural Program of National Cancer
Institute.
NR 128
TC 26
Z9 29
U1 3
U2 29
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-7659
J9 CANCER METAST REV
JI Cancer Metastasis Rev.
PD DEC
PY 2012
VL 31
IS 3-4
SI SI
BP 593
EP 603
DI 10.1007/s10555-012-9374-8
PG 11
WC Oncology
SC Oncology
GA 021CV
UT WOS:000309863800016
PM 22706779
ER
PT J
AU Crea, F
Fornaro, L
Bocci, G
Sun, L
Farrar, WL
Falcone, A
Danesi, R
AF Crea, Francesco
Fornaro, Lorenzo
Bocci, Guido
Sun, Lei
Farrar, William L.
Falcone, Alfredo
Danesi, Romano
TI EZH2 inhibition: targeting the crossroad of tumor invasion and
angiogenesis
SO CANCER AND METASTASIS REVIEWS
LA English
DT Review
DE EZH2; Metastasis; Angiogenesis; DZNeP; Polycomb
ID HISTONE METHYLTRANSFERASE EZH2; CANCER CELL-LINES; BREAST-CANCER;
GENE-EXPRESSION; PROSTATE-CANCER; STEM-CELLS; NEOADJUVANT CHEMOTHERAPY;
MESENCHYMAL TRANSITION; ANTITUMOR-ACTIVITY; COLORECTAL-CANCER
AB Tumor angiogenesis and metastatic spreading are two highly interconnected phenomena, which contribute to cancer-associated deaths. Thus, the identification of novel strategies to target angiogenesis and metastatic spreading is crucial. Polycomb genes are a set of epigenetic effectors, structured in multimeric repressive complexes. EZH2 is the catalytic subunit of Polycomb repressive complex 2 (PRC2), which methylates histone H3 lysine 27, thereby silencing several tumor-suppressor genes. EZH2 is essential for cancer stem cell self-renewal. Interestingly, cancer stem cells are thought to be the seeds of metastatic spreading and are able to differentiate into tumor-associated endothelial cells. Pre-clinical studies showed that EZH2 is able to silence several anti-metastatic genes ( e.g., E-cadherin and tissue inhibitors of metalloproteinases), thereby favoring cell invasion and anchorage-independent growth. In addition, EZH2 seems to play a crucial role in the regulation of tumor angiogenesis. High EZH2 expression predicts poor prognosis, high grade, and high stage in several cancer types. Recently, a small molecule inhibitor of PRC2 (DZNeP) demonstrated promising anti-tumor activity, both in vitro and in vivo. Interestingly, DZNeP was able to inhibit cancer cell invasion and tumor angiogenesis in prostate and brain cancers, respectively. At tumor-inhibiting doses, DZNeP is not harmful for non-transformed cells. In the present manuscript, we review current evidence supporting a role of EZH2 in metastatic spreading and tumor angiogenesis. Using Oncomine datasets, we show that DZNeP targets are specifically silenced in some metastatic cancers, and some of them may inhibit angiogenesis. Based on this evidence, we propose the development of EZH2 inhibitors as anti-angiogenic and anti-metastatic therapy.
C1 [Crea, Francesco; Bocci, Guido; Danesi, Romano] Univ Pisa, Div Pharmacol, Dept Internal Med, I-56126 Pisa, Italy.
[Fornaro, Lorenzo; Falcone, Alfredo] Univ Pisa, Div Med Oncol Transplants & New Technol Med, Dept Oncol, I-56126 Pisa, Italy.
[Fornaro, Lorenzo] Scuola Super Studi Univ & Perfezionamento St Anna, Inst Life Sci, I-56127 Pisa, Italy.
[Bocci, Guido] Ist Toscano Tumori, I-50139 Florence, Italy.
[Sun, Lei; Farrar, William L.] Frederick Natl Lab Canc Res, Canc Stem Cell Sect, Lab Canc Prevent, Frederick, MD USA.
RP Bocci, G (reprint author), Univ Pisa, Div Pharmacol, Dept Internal Med, Via Roma 55, I-56126 Pisa, Italy.
EM guido.bocci@med.unipi.it
RI Crea, Francesco /I-8383-2015; Sun, Lei/J-9943-2015;
OI Fornaro, Lorenzo/0000-0002-0187-5904; Crea,
Francesco/0000-0002-4903-2973
FU AIRC (Associazione Italiana per la Ricerca sul Cancro); MIUR-PRIN
[20084TASKL_004]
FX This work has been supported, in part, by AIRC (Associazione Italiana
per la Ricerca sul Cancro) to Guido Bocci and by MIUR-PRIN2008 project
20084TASKL_004: "Epigenetic manipulation and reversal of resistance to
irinotecan in human colorectal cancer cell lines" to Romano Danesi.
NR 86
TC 67
Z9 70
U1 3
U2 51
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-7659
J9 CANCER METAST REV
JI Cancer Metastasis Rev.
PD DEC
PY 2012
VL 31
IS 3-4
SI SI
BP 753
EP 761
DI 10.1007/s10555-012-9387-3
PG 9
WC Oncology
SC Oncology
GA 021CV
UT WOS:000309863800029
PM 22711031
ER
PT J
AU Liles, BD
Newman, E
LaGasse, LL
Derauf, C
Shah, R
Smith, LM
Arria, AM
Huestis, MA
Haning, W
Strauss, A
DellaGrotta, S
Dansereau, LM
Neal, C
Lester, BM
AF Liles, Brandi D.
Newman, Elana
LaGasse, Linda L.
Derauf, Chris
Shah, Rizwan
Smith, Lynne M.
Arria, Amelia M.
Huestis, Marilyn A.
Haning, William
Strauss, Arthur
DellaGrotta, Sheri
Dansereau, Lynne M.
Neal, Charles
Lester, Barry M.
TI Perceived Child Behavior Problems, Parenting Stress, and Maternal
Depressive Symptoms Among Prenatal Methamphetamine Users
SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT
LA English
DT Article
DE Parenting stress; Prenatal drug exposure; Methamphetamine; Child
behavior problems; Maternal depression
ID LIFE-STYLE; COCAINE EXPOSURE; SUBSTANCE USE; INVENTORY-II; INFANT
DEVELOPMENT; PSYCHOMETRIC CHARACTERISTICS; DRUG-USERS; PREGNANCY;
MOTHERS; ENVIRONMENT
AB The present study was designed to examine parenting stress, maternal depressive symptoms, and perceived child behavior problems among mothers who used methamphetamine (MA) during pregnancy. Participants were a subsample (n = 212; 75 exposed, 137 comparison) of biological mothers who had continuous custody of their child from birth to 36 months. The subsample was drawn from a larger, ongoing longitudinal study on the effects of prenatal methamphetamine exposure (n = 412; 204 exposed, 208 comparison) (Arria et al in Matern Child Health J 10:293-302 2006). Mothers who used MA during pregnancy reported more parenting stress and more depressive symptoms than a matched comparison group. There were no differences between groups on perceived child behavior problems. In a hierarchical linear model, depressive symptoms, and perceived child behavior problems, but not MA exposure, were statistically significant predictors of parenting stress. Screening for potential parenting problems among mothers with a history of substance abuse is warranted. Parenting interventions targeting depressive symptoms, parenting stress, and child behavior problems are needed for this population.
C1 [Liles, Brandi D.; Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA.
[LaGasse, Linda L.; DellaGrotta, Sheri; Dansereau, Lynne M.; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Ctr Study Children Risk, Warren Alpert Med Sch, Providence, RI USA.
[Derauf, Chris] Mayo Clin, Dept Pediat & Adolescent Med, Rochester, MN USA.
[Shah, Rizwan] Blank Hosp, Reg Child Protect Ctr Iowa Hlth, Des Moines, IA USA.
[Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Harbor UCLA Med Ctr, LABioMed Inst, Los Angeles, CA 90095 USA.
[Arria, Amelia M.] Univ Maryland Sch Publ Hlth, Ctr Young Adult Hlth & Dev, College Pk, MD USA.
[Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Haning, William; Neal, Charles] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.
[Strauss, Arthur] MCHLB, Long Beach, CA USA.
RP Liles, BD (reprint author), Univ Tulsa, Dept Psychol, 800 S Tucker Dr, Tulsa, OK 74104 USA.
EM brandi-sebourn@utulsa.edu; elana-newman@utulsa.edu
OI Arria, Amelia/0000-0002-6360-9265
FU Intramural NIH HHS [ZIA DA000433-10, ZIA DA000433-11]; NCATS NIH HHS
[UL1 TR000124]; NCRR NIH HHS [P20 RR011091, 3M01 RR 00425, M01 RR000425,
P20 RR 11091]; NIDA NIH HHS [R01 DA014948, R01DA014948]
NR 66
TC 7
Z9 8
U1 2
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-398X
J9 CHILD PSYCHIAT HUM D
JI Child Psychiat. Hum. Dev.
PD DEC
PY 2012
VL 43
IS 6
BP 943
EP 957
DI 10.1007/s10578-012-0305-2
PG 15
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 021DS
UT WOS:000309866100008
PM 22552952
ER
PT J
AU Aka, P
Kawira, E
Masalu, N
Emmanuel, B
Brubaker, G
Magatti, J
Mbulaiteye, SM
AF Aka, Peter
Kawira, Esther
Masalu, Nestory
Emmanuel, Benjamin
Brubaker, Glen
Magatti, Josiah
Mbulaiteye, Sam M.
TI Incidence and trends in Burkitt lymphoma in northern Tanzania from 2000
to 2009
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE Burkitt lymphoma; epidemiology; Epstein-Bar virus; malaria; Tanzania
ID EPSTEIN-BARR-VIRUS; SICK INDIVIDUALS; UNITED-STATES; MALARIA; UGANDA;
CHILDHOOD; CANCER; RISK; MALIGNANCIES; POPULATIONS
AB Introduction Burkitt lymphoma (BL) is endemic in parts of Tanzania, but there is scant country or region level data about burden and trends of BL in Tanzania over the past three decades. Here, we update baseline epidemiology of BL in northern Tanzania using recent data. Procedure Data for childhood BL diagnosed at six hospitals in Mara and Mwanza regions in northern Tanzania during 2000-2009 were compiled. Age, sex, and regional patterns were analyzed. Crude incidence rates of BL were calculated by sex, anatomic site, geographical region, and calendar year. Results Among 944 cases, 549 (58%) were male (male/female case ratio 1.4:1). Among those with known anatomic site (92%), facial only tumors represented a large proportion of tumors in boys than girls (50% vs. 36%, P?= 30) is higher in non-Hispanic blacks than in non-Hispanic whites, the relation of BMI to total mortality in non-Hispanic blacks is not well defined.
Purpose: We investigated the association between BMI and total mortality in 16,471 non-Hispanic blacks in the NIH-AARP Diet and Health Study, a prospective cohort of adults aged 50-71 years.
Methods: During an average of 13 years of follow-up, 2,609 deaths were identified using the Social Security Administration Death Master File and the National Death Index. Cox proportional hazard models were used to estimate relative risks and two-sided 95% confidence intervals (CI), adjusting for potential confounders.
Results: Among individuals with no history of cancer or heart disease at baseline and had a BMI of 20 or greater, the relative risk for total death was 1.12 (95% CI: 1.05, 1.19, for a 5-unit increase in BMI) in men and 1.09 (95% CI: 1.03, 1.15) in women. Among never smokers with no history of cancer or heart disease at baseline, relative risks for total death for BMI 25-< 30, 30-< 35, 35-< 40, and 40-50, compared with BMI 20-< 25, were 1.27 (95% CI: 0.91, 1.78), 1.56 (95% CI: 1.07, 2.28), 2.48 (95% CI: 1.53, 4.05), and 2.80 (95% CI: 1.46, 5.39), respectively, in men and 0.78 (95% CI: 0.59, 1.04), 1.17 (95% CI: 0.88, 1.57), 1.35 (95% CI: 0.96, 1.90), and 1.93 (95% CI: 1.33, 2.81), respectively, in women.
Conclusions: Our findings suggest that overweight is related to an increased risk of death in black men, but not in black women, while obesity is related to an increased risk of death in both black men and women. A large pooled analysis of existing studies is needed to systematically evaluate the association between a wide range of BMIs and total mortality in blacks.
C1 [Park, Yikyung; Hartge, Patricia; Moore, Steven C.; Kitahara, Cari M.; de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Park, Y (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
EM yikyung.park@nih.gov
RI Kitahara, Cari/R-8267-2016; Moore, Steven/D-8760-2016;
OI Moore, Steven/0000-0002-8169-1661; Park, Yikyung/0000-0002-6281-489X
FU National Cancer Institute, United States National Institutes of Health
FX The study was supported by the Intramural Research Program of the
National Cancer Institute, United States 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 4
Z9 4
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 NOV 27
PY 2012
VL 7
IS 11
AR e50091
DI 10.1371/journal.pone.0050091
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048BS
UT WOS:000311885800047
PM 23209650
ER
PT J
AU Poliakov, E
Gubin, AN
Stearn, O
Li, Y
Campos, MM
Gentleman, S
Rogozin, IB
Redmond, TM
AF Poliakov, Eugenia
Gubin, Alexander N.
Stearn, Olivia
Li, Yan
Campos, Maria Mercedes
Gentleman, Susan
Rogozin, Igor B.
Redmond, T. Michael
TI Origin and Evolution of Retinoid Isomerization Machinery in Vertebrate
Visual Cycle: Hint from Jawless Vertebrates
SO PLOS ONE
LA English
DT Article
ID LONG-BRANCH ATTRACTION; LAMPREY PETROMYZON-MARINUS; CIONA-INTESTINALIS;
SWISS-MODEL; PROTEIN SEQUENCES; DUPLICATED GENES; IN-VIVO; RPE65;
ESTERS; ISOMEROHYDROLASE
AB In order to maintain visual sensitivity at all light levels, the vertebrate eye possesses a mechanism to regenerate the visual pigment chromophore 11-cis retinal in the dark enzymatically, unlike in all other taxa, which rely on photoisomerization. This mechanism is termed the visual cycle and is localized to the retinal pigment epithelium (RPE), a support layer of the neural retina. Speculation has long revolved around whether more primitive chordates, such as tunicates and cephalochordates, anticipated this feature. The two key enzymes of the visual cycle are RPE65, the visual cycle all-trans retinyl ester isomerohydrolase, and lecithin: retinol acyltransferase (LRAT), which generates RPE65's substrate. We hypothesized that the origin of the vertebrate visual cycle is directly connected to an ancestral carotenoid oxygenase acquiring a new retinyl ester isomerohydrolase function. Our phylogenetic analyses of the RPE65/BCMO and N1pC/P60 (LRAT) superfamilies show that neither RPE65 nor LRAT orthologs occur in tunicates (Ciona) or cephalochordates (Branchiostoma), but occur in Petromyzon marinus (Sea Lamprey), a jawless vertebrate. The closest homologs to RPE65 in Ciona and Branchiostoma lacked predicted functionally diverged residues found in all authentic RPE65s, but lamprey RPE65 contained all of them. We cloned RPE65 and LRATb cDNAs from lamprey RPE and demonstrated appropriate enzymatic activities. We show that Ciona beta-carotene monooxygenase a (BCMOa) (previously annotated as an RPE65) has carotenoid oxygenase cleavage activity but not RPE65 activity. We verified the presence of RPE65 in lamprey RPE by immunofluorescence microscopy, immunoblot and mass spectrometry. On the basis of these data we conclude that the crucial transition from the typical carotenoid double bond cleavage functionality (BCMO) to the isomerohydrolase functionality (RPE65), coupled with the origin of LRAT, occurred subsequent to divergence of the more primitive chordates (tunicates, etc.) in the last common ancestor of the jawless and jawed vertebrates.
C1 [Poliakov, Eugenia; Gubin, Alexander N.; Stearn, Olivia; Li, Yan; Gentleman, Susan; Redmond, T. Michael] NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Campos, Maria Mercedes] NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA.
[Rogozin, Igor B.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA.
RP Redmond, TM (reprint author), NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM redmondd@helix.nih.gov
OI Redmond, T. Michael/0000-0002-1813-5291
FU National Institutes of Health Intramural Research Program of the
National Eye Institute; National Library of Medicine at the National
Institutes of Health (US Department Health and Human Services)
FX This research was supported by the National Institutes of Health
Intramural Research Program of the National Eye Institute and the
Intramural Research Program of the National Library of Medicine at the
National Institutes of Health (US Department Health and Human Services).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 68
TC 14
Z9 14
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 27
PY 2012
VL 7
IS 11
AR e49975
DI 10.1371/journal.pone.0049975
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048BS
UT WOS:000311885800037
PM 23209628
ER
PT J
AU Li, YP
Ramirez, S
Jensen, SB
Purcell, RH
Gottwein, JM
Bukh, J
AF Li, Yi-Ping
Ramirez, Santseharay
Jensen, Sanne B.
Purcell, Robert H.
Gottwein, Judith M.
Bukh, Jens
TI Highly efficient full-length hepatitis C virus genotype 1 (strain TN)
infectious culture system
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID NONSTRUCTURAL PROTEIN 4B; HUMAN HEPATOMA-CELLS; IN-VITRO;
FULMINANT-HEPATITIS; REPLICATION; MUTATIONS; RNA; 3A; CHIMPANZEES;
GENOME
AB Chronic infection with hepatitis C virus (HCV) is an important cause of end stage liver disease worldwide. In the United States, most HCV-related disease is associated with genotype 1 infection, which remains difficult to treat. Drug and vaccine development was hampered by inability to culture patient isolates representing HCV genotypes 1-7 and subtypes; only a recombinant 2a genome (strain JFH1) spontaneously replicated in vitro. Recently, we identified three mutations F1464L/A1672S/D2979G (LSG) in the nonstructural (NS) proteins, essential for development of full-length HCV 2a (J6) and 2b (J8) culture systems in Huh7.5 cells. Here, we developed a highly efficient genotype 1a (strain TN) full-length culture system. We initially found that the LSG substitutions conferred viability to an intergenotypic recombinant composed of TN 5' untranslated region (5'UTR)-NS5A and JFH1 NS5B-3'UTR; recovered viruses acquired two adaptive mutations located in NS3 and NS4B. Introduction of these changes into a replication-deficient TN full-length genome, harboring LSG, permitted efficient HCV production. Additional identified NS4B and NS5B mutations fully adapted the TN full-length virus. Thus, a TN genome with 8 changes (designated TN cell-culture derived, TNcc) replicated efficiently and released infectious particles of similar to 5 log(10) focus-forming units per mL; passaged TNcc did not require additional changes. IFN-alpha and directly acting antivirals targeting the HCV protease, NS5A, and NS5B, each inhibited full-length TN infection dose-dependently. Given the unique importance of genotype 1 for pathogenesis, this infectious 1a culture system represents an important advance in HCV research. The approach used and the mutations identified might permit culture development for other HCV isolates, thus facilitating vaccine development and personalized treatment.
C1 [Purcell, Robert H.; Bukh, Jens] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Li, Yi-Ping; Ramirez, Santseharay; Jensen, Sanne B.; Gottwein, Judith M.; Bukh, Jens] Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis Program C, DK-2650 Hvidovre, Denmark.
[Li, Yi-Ping; Ramirez, Santseharay; Jensen, Sanne B.; Gottwein, Judith M.; Bukh, Jens] Copenhagen Univ Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark.
[Li, Yi-Ping; Ramirez, Santseharay; Jensen, Sanne B.; Gottwein, Judith M.; Bukh, Jens] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, DK-2200 Copenhagen N, Denmark.
RP Purcell, RH (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM RPURCELL@niaid.nih.gov; jbukh@sund.ku.dk
RI Ramirez, Santseharay/R-9257-2016; Brun Jensen, Sanne/G-2673-2016
OI Ramirez, Santseharay/0000-0003-3699-1814; Brun Jensen,
Sanne/0000-0002-2852-934X
FU Lundbeck Foundation; Danish Cancer Society; Novo Nordisk Foundation; A.
P. Moller og Hustru Chastine Mc-Kinney Mollers Fondation; Danish Council
for Independent Research-Medical Sciences; National Institute of Allergy
and Infectious Diseases, National Institutes of Health
FX We thank L. S. Mikkelsen for technical assistance, A. L. Sorensen and L.
Ghanem for general laboratory support, J. O. Nielsen and O. Andersen for
providing valuable support (all from Copenhagen University Hospital,
Hvidovre), and C. M. Rice (Rockefeller University, New York) and T.
Wakita (National Institute of Infectious Diseases, Tokyo) for providing
reagents. This study was supported by research grants from the Lundbeck
Foundation (J. G. M. and J. B.), the Danish Cancer Society (J. M. G. and
J. B.), the Novo Nordisk Foundation (Y.-P.L., J.M.G., and J.B.), the A.
P. Moller og Hustru Chastine Mc-Kinney Mollers Fondation (J. B.), the
Danish Council for Independent Research-Medical Sciences (Y.-P.L., S.
R., and J. B.), and in part by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health (R. H. P.). S. R. is the recipient of an individual
postdoctoral stipend from the Danish Council for Independent
Research-Medical Sciences.
NR 52
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PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 27
PY 2012
VL 109
IS 48
BP 19757
EP 19762
DI 10.1073/pnas.1218260109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053ZN
UT WOS:000312313900054
PM 23151512
ER
PT J
AU Shingai, M
Donau, OK
Schmidt, SD
Gautam, R
Plishka, RJ
Buckler-White, A
Sadjadpour, R
Lee, WR
LaBranche, CC
Montefiori, DC
Mascola, JR
Nishimura, Y
Martin, MA
AF Shingai, Masashi
Donau, Olivia K.
Schmidt, Stephen D.
Gautam, Rajeev
Plishka, Ronald J.
Buckler-White, Alicia
Sadjadpour, Reza
Lee, Wendy R.
LaBranche, Celia C.
Montefiori, David C.
Mascola, John R.
Nishimura, Yoshiaki
Martin, Malcolm A.
TI Most rhesus macaques infected with the CCR5-tropic SHIVAD8 generate
cross-reactive antibodies that neutralize multiple HIV-1 strains
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RAPID DEVELOPMENT; TYPE-1 INFECTION;
CELLS; MONKEYS; VACCINE; ISOLATE; BROAD; SERA; PATHOGENICITY
AB The induction of broadly reacting neutralizing antibodies has been a major goal of HIV vaccine research. Characterization of a pathogenic CCR5 (R5)-tropic SIV/HIV chimeric virus (SHIV) molecular clone (SHIVAD8-EO) revealed that eight of eight infected animals developed cross-reactive neutralizing antibodies (NAbs) directed against an envelope glycoprotein derived from the heterologous HIV-1(DH12) strain. A panel of plasmas, collected from monkeys inoculated with either molecularly cloned or uncloned SHIVAD8 stocks, exhibited cross-neutralization against multiple tier 1 and tier 2 HIV-1 clade B isolates. One SHIVAD8-infected animal also developed NAbs against clades A and C HIV-1 strains. In this particular infected macaque, the cross-reacting anti-HIV-1 NAbs produced between weeks 7 and 13 were directed against a neutralization-sensitive virus strain, whereas neutralizing activities emerging at weeks 41-51 targeted more neutralization-resistant HIV-1 isolates. These results indicate that the SHIVAD8 macaque model represents a potentially valuable experimental system for investigating B-cell maturation and the induction of cross-reactive NAbs directed against multiple HIV-1 strains.
C1 [Shingai, Masashi; Donau, Olivia K.; Gautam, Rajeev; Plishka, Ronald J.; Buckler-White, Alicia; Sadjadpour, Reza; Lee, Wendy R.; Nishimura, Yoshiaki; Martin, Malcolm A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Schmidt, Stephen D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[LaBranche, Celia C.; Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mmartin@niaid.nih.gov
RI Schmidt, Stephen/B-5398-2012
FU Aine McKnight through the Bill and Melinda Gates Foundation's
Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody Vaccine
Immune Monitoring Consortium [38619]; Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX We thank Keiko Tomioka, Robin Kruthers, and Ranjini Iyengar for
determining plasma viral RNA loads and Boris Skopets and Rahel Petros
for diligently assisting in the maintenance of animals and assisting
with procedures. We are indebted to the National Institutes of Health
AIDS Research and Reference Reagent Program for providing AMD3100 and to
Julie Strizki and Shering Plough for providing AD101. Plasma samples for
determining the neutralization phenotype of virus stocks were provided
by Aine McKnight through the Bill and Melinda Gates Foundation's
Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody Vaccine
Immune Monitoring Consortium (Grant 38619). This work was supported by
the Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 37
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PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 27
PY 2012
VL 109
IS 48
BP 19769
EP 19774
DI 10.1073/pnas.1217443109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053ZN
UT WOS:000312313900056
PM 23129652
ER
PT J
AU Omsland, A
Sager, J
Nair, V
Sturdevant, DE
Hackstadt, T
AF Omsland, Anders
Sager, Janet
Nair, Vinod
Sturdevant, Daniel E.
Hackstadt, Ted
TI Developmental stage-specific metabolic and transcriptional activity of
Chlamydia trachomatis in an axenic medium
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE metabolism; transcription; intracellular parasite
ID OUTER-MEMBRANE PROTEIN; COXIELLA-BURNETII; ADENOSINE-TRIPHOSPHATE;
INCLUSION; PSITTACI; CYCLE; DIFFERENTIATION; TRAFFICKING; TRANSPORT;
GLUCOSE
AB Chlamydia trachomatis is among the most clinically significant human pathogens, yet their obligate intracellular nature places severe restrictions upon research. Chlamydiae undergo a biphasic developmental cycle characterized by an infectious cell type known as an elementary body (EB) and an intracellular replicative form called a reticulate body (RB). EBs have historically been described as metabolically dormant. A cell-free (axenic) culture system was developed, which showed high levels of metabolic and biosynthetic activity from both EBs and RBs, although the requirements differed for each. EBs preferentially used glucose-6-phosphate as an energy source, whereas RBs required ATP. Both developmental forms showed increased activity when incubated under microaerobic conditions. Incorporation of isotopically labeled amino acids into proteins from both developmental forms indicated unique expression profiles, which were confirmed by genome-wide transcriptional analysis. The described axenic culture system will greatly enhance biochemical and physiological analyses of chlamydiae.
C1 [Omsland, Anders; Sager, Janet; Hackstadt, Ted] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Hamilton, MT 59840 USA.
[Nair, Vinod] NIAID, Electron Microscopy Unit, Hamilton, MT 59840 USA.
[Sturdevant, Daniel E.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Hamilton, MT 59840 USA.
EM thackstadt@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases
FX We thank A. Whitney and F. DeLeo for advice and assistance with RNA
processing and K. Virtaneva, K. Kanakabandi, and S. F. Porcella for
technical help with optimization of sample preparation for the
transcription microarray analysis. Additional electron microscopy by E.
R. Fischer and B. Hansen is also appreciated. This work was supported by
the Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases.
NR 36
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PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 27
PY 2012
VL 109
IS 48
BP 19781
EP 19785
DI 10.1073/pnas.1212831109
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053ZN
UT WOS:000312313900058
PM 23129646
ER
PT J
AU Raznahan, A
Greenstein, D
Lee, NR
Clasen, LS
Giedd, JN
AF Raznahan, Armin
Greenstein, Deanna
Lee, Nancy Raitano
Clasen, Liv S.
Giedd, Jay N.
TI Reply to Segal: Are relationships between birth weight and intelligence
quotient variation within twin pairs modulated by patterns of handedness
discordance?
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Letter
C1 [Raznahan, Armin; Greenstein, Deanna; Lee, Nancy Raitano; Clasen, Liv S.; Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Raznahan, A (reprint author), NIMH, Child Psychiat Branch, Bldg 10, Bethesda, MD 20892 USA.
EM raznahana@mail.nih.gov
RI Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Lee,
Nancy/0000-0002-6663-0713
NR 3
TC 0
Z9 0
U1 0
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 27
PY 2012
VL 109
IS 48
BP E3294
EP E3294
DI 10.1073/pnas.1214891109
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053ZN
UT WOS:000312313900006
ER
PT J
AU de Azua, IR
Gautam, D
Jain, S
Guettier, JM
Wess, J
AF de Azua, Inigo Ruiz
Gautam, Dinesh
Jain, Shalini
Guettier, Jean-Marc
Wess, Juergen
TI Critical metabolic roles of beta-cell M-3 muscarinic acetylcholine
receptors
SO LIFE SCIENCES
LA English
DT Article; Proceedings Paper
CT 3rd International Symposium on Non-Neuronal Acetylcholine
CY AUG 24-26, 2011
CL Univ Groningen, Groningen, NETHERLANDS
HO Univ Groningen
DE Acetylcholine; Beta cell; Insulin; Muscarinic receptor; Transgenic mice;
Type 2 diabetes
ID PROTEIN-COUPLED RECEPTORS; INSULIN-RELEASE; RGS PROTEINS; IN-VIVO;
GLUCOSE-HOMEOSTASIS; MECHANISMS; SECRETION; MICE; STIMULATION;
ACTIVATION
AB Muscarinic acetylcholine (ACh) receptors (mAChRs: M-1-M-5) regulate the activity of an extraordinarily large number of important physiological processes. We and others previously demonstrated that pancreatic beta-cells are endowed with M-3 mAChFts which are linked to G proteins of the G(q) family. The activation of these receptors by ACh or other muscarinic agonists leads to the augmentation of glucose-induced insulin release via multiple mechanisms. Interestingly, in humans, ACh acting on human beta-cell mAChRs is released from adjacent alpha-cells which express both choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (vAChT), indicative of the presence of a non-neuronal cholinergic system in human pancreatic islets. In order to shed light on the physiological roles of beta-cell M-3 receptors, we recently generated and analyzed various mutant mouse models. Specifically, we carded out studies with mice which overexpressed M-3 receptors or mutant M-3 receptors in pancreatic beta-cells or which selectively lacked M-3 receptors or M-3-receptor-associated proteins in pancreatic beta-cells. Our findings indicate that beta-cell M-3 receptors play a key role in maintaining proper insulin release and whole body glucose homeostasis and that strategies aimed at enhancing signaling through beta-cell M-3 receptors may prove useful to improve beta-cell function for the treatment of type 2 diabetes (T2D). Published by Elsevier Inc.
C1 [de Azua, Inigo Ruiz; Gautam, Dinesh; Jain, Shalini; Guettier, Jean-Marc; Wess, Juergen] NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Wess, J (reprint author), NIH NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, Bldg 8A,Room B1A-05,8 Ctr Dr,MSC 0810, Bethesda, MD 20892 USA.
EM jwess@helix.nih.gov
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U1 1
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0024-3205
J9 LIFE SCI
JI Life Sci.
PD NOV 27
PY 2012
VL 91
IS 21-22
SI SI
BP 986
EP 991
DI 10.1016/j.lfs.2012.04.010
PG 6
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 051IL
UT WOS:000312119700005
ER
PT J
AU Skjaerven, R
Wilcox, AJ
Klungsoyr, K
Irgens, LM
Vikse, BE
Vatten, LJ
Lie, RT
AF Skjaerven, Rolv
Wilcox, Allen J.
Klungsoyr, Kari
Irgens, Lorentz M.
Vikse, Bjorn Egil
Vatten, Lars J.
Lie, Rolv Terje
TI Cardiovascular mortality after pre-eclampsia in one child mothers:
prospective, population based cohort study
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID ISCHEMIC-HEART-DISEASE; LONG-TERM MORTALITY; RISK-FACTORS; PREGNANCY
COMPLICATIONS; LATER LIFE; RETROSPECTIVE COHORT; INSULIN-RESISTANCE;
MATERNAL RISK; BIRTH-WEIGHT; WOMEN
AB Objective To assess the association of pre-eclampsia with later cardiovascular death in mothers according to their lifetime number of pregnancies, and particularly after only one child.
Design Prospective, population based cohort study.
Setting Medical Birth Registry of Norway.
Participants We followed 836 147 Norwegian women with a first singleton birth between 1967 and 2002 for cardiovascular mortality through linkage to the national Cause of Death Registry. About 23 000 women died by 2009, of whom 3891 died from cardiovascular causes. Associations between pre-eclampsia and cardiovascular death were assessed by hazard ratios, estimated by Cox regression analyses. Hazard ratios were adjusted for maternal education (three categories), maternal age at first birth, and year of first birth
Results The rate of cardiovascular mortality among women with preterm pre-eclampsia was 9.2% after having only one child, falling to 1.1% for those with two or more children. With term pre-eclampsia, the rates were 2.8% and 1.1%, respectively. Women with pre-eclampsia in their first pregnancy had higher rates of cardiovascular death than those who did not have the condition at first birth (adjusted hazard ratio 1.6 (95% confidence interval 1.4 to 2.0) after term pre-eclampsia; 3.7 (2.7 to 4.8) after preterm pre-eclampsia). Among women with only one lifetime pregnancy, the increase in risk of cardiovascular death was higher than for those with two or more children (3.4 (2.6 to 4.6) after term pre-eclampsia; 9.4 (6.5 to 13.7) after preterm pre-eclampsia). The risk of cardiovascular death was only moderately elevated among women with pre-eclamptic first pregnancies who went on to have additional children (1.5 (1.2 to 2.0) after term pre-eclampsia; 2.4 (1.5 to 3.9) after preterm pre-eclampsia). There was little evidence of additional risk after recurrent pre-eclampsia. All cause mortality for women with two or more lifetime births, who had pre-eclampsia in first pregnancy, was not elevated, even with preterm pre-eclampsia in first pregnancy (1.1 (0.87 to 1.14)).
Conclusions Cardiovascular death in women with pre-eclampsia in their first pregnancy is concentrated mainly in women with no additional births. This association might be due to health problems that discourage or prevent further pregnancies rather than to pre-eclampsia itself. As a screening criterion for cardiovascular disease risk, pre-eclampsia is a strong predictor primarily among women with only one child-particularly with preterm pre-eclampsia.
C1 [Skjaerven, Rolv; Klungsoyr, Kari; Irgens, Lorentz M.; Lie, Rolv Terje] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
[Skjaerven, Rolv; Klungsoyr, Kari; Irgens, Lorentz M.; Lie, Rolv Terje] Natl Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway.
[Wilcox, Allen J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Vikse, Bjorn Egil] Univ Bergen, Inst Med, Bergen, Norway.
[Vikse, Bjorn Egil] Haukeland Hosp, Dept Med, N-5021 Bergen, Norway.
[Vatten, Lars J.] Norwegian Univ Sci & Technol, Dept Publ Hlth, N-7034 Trondheim, Norway.
RP Skjaerven, R (reprint author), Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
EM rolv.skjaerven@smis.uib.no
OI Wilcox, Allen/0000-0002-3376-1311
FU Norwegian Research Council; National Institute of Environmental Health
Sciences, National Institute of Health; National Institute of
Environmental Health Sciences
FX The study has been supported by grants from the Norwegian Research
Council and by the Intramural Research Program of the National Institute
of Environmental Health Sciences, National Institute of Health. The
authors' institutions had no role in the design and conduct of the
study; the collection, management, analysis, and interpretation of the
data; or the preparation, review, or approval of the manuscript.; All
authors have completed the Unified Competing Interest form at
www.icmje.org/coi_disclosure.pdf (available on request from the
corresponding author) and declare: support from the Norwegian Research
Council and the National Institute of Environmental Health Sciences; no
financial relationships with any organisations that might have an
interest in the submitted work in the previous three years, no other
relationships or activities that could appear to have influenced the
submitted work
NR 46
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PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BRIT MED J
JI Br. Med. J.
PD NOV 27
PY 2012
VL 345
AR e7677
DI 10.1136/bmj.e7677
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 048FM
UT WOS:000311895700002
PM 23186909
ER
PT J
AU Singh, AK
Seavey, CN
Corcoran, PC
Hoyt, RF
Lewis, B
Thomas, ML
Eckhaus, MA
Ayares, D
Horvath, KA
Mohiuddin, MM
AF Singh, A. K.
Seavey, C. N.
Corcoran, P. C.
Hoyt, R. F.
Lewis, B.
Thomas, M. L.
Eckhaus, M. A.
Ayares, D.
Horvath, K. A.
Mohiuddin, M. M.
TI Anti CD154 Mediated Co-Stimulation Blockade in a Pig to Baboon Cardiac
Xenotransplantation Model: A Possible Role of T Regulatory Cells
Induction in Long Term Graft Survival
SO TRANSPLANTATION
LA English
DT Meeting Abstract
C1 [Singh, A. K.; Seavey, C. N.; Corcoran, P. C.; Horvath, K. A.; Mohiuddin, M. M.] NHLBI, NIH, CSRP, Bethesda, MD 20892 USA.
[Hoyt, R. F.] NHLBI, NIH, LAMS, Bethesda, MD 20892 USA.
[Lewis, B.; Thomas, M. L.; Eckhaus, M. A.] NIH, ORS, DVR, Bethesda, MD 20892 USA.
[Ayares, D.] Revivicor Inc, Blacksburg, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD NOV 27
PY 2012
VL 94
IS 10
SU S
MA 862
BP 68
EP 68
PG 1
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA V45WJ
UT WOS:000209846400125
ER
PT J
AU Mohiuddin, MM
Singh, AK
Corcoran, PC
Thomas, ML
Eckhaus, MA
Lewis, B
Hoyt, RF
Ayares, D
Reimann, KA
Horvath, KA
AF Mohiuddin, M. M.
Singh, A. K.
Corcoran, P. C.
Thomas, M. L.
Eckhaus, M. A.
Lewis, B.
Hoyt, R. F.
Ayares, D.
Reimann, K. A.
Horvath, K. A.
TI B Cell Depletion Along with Co-Stimulation Blockade by Anti CD40 (Clone
2C10) Extends Graft Survival Significantly in a Heterotopic Cardiac
Xenotransplantation Model
SO TRANSPLANTATION
LA English
DT Meeting Abstract
C1 [Mohiuddin, M. M.; Singh, A. K.; Corcoran, P. C.; Horvath, K. A.] NHLBI, NIH, CSRP, Bethesda, MD 20892 USA.
[Thomas, M. L.; Eckhaus, M. A.; Lewis, B.] NIH, ORS, DVR, Bethesda, MD 20892 USA.
[Hoyt, R. F.] NHLBI, NIH, LAMS, Bethesda, MD 20892 USA.
[Ayares, D.] Revivicor Inc, Blacksburg, VA USA.
[Reimann, K. A.] Beth Israel Deaconess Med Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD NOV 27
PY 2012
VL 94
IS 10
SU S
MA 453
BP 70
EP 70
PG 1
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA V45WJ
UT WOS:000209846400129
ER
PT J
AU Zhou, Y
Wang, S
Yu, Z
Hoyt, RF
Horvath, KA
Singh, AK
AF Zhou, Y.
Wang, S.
Yu, Z.
Hoyt, R. F., Jr.
Horvath, K. A.
Singh, A. K.
TI Allogeneic Transplantation of Induced Pluripotent Stem Cells in a
Porcine Model of Chronic Myocardial Ischemia Failed to Stimulate Myocyte
Differentiation
SO TRANSPLANTATION
LA English
DT Meeting Abstract
C1 [Zhou, Y.; Wang, S.; Yu, Z.; Hoyt, R. F., Jr.; Horvath, K. A.; Singh, A. K.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD NOV 27
PY 2012
VL 94
IS 10
SU S
MA 1649
BP 1014
EP 1014
PG 1
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA V45WJ
UT WOS:000209846404149
ER
PT J
AU Wehby, GL
Goco, N
Moretti-Ferreira, D
Felix, T
Richieri-Costa, A
Padovani, C
Queiros, F
Guimaraes, CVN
Pereira, GR
Litavecz, S
Hartwell, T
Chakraborty, H
Javois, L
Murray, JC
AF Wehby, George L.
Goco, Norman
Moretti-Ferreira, Danilo
Felix, Temis
Richieri-Costa, Antonio
Padovani, Carla
Queiros, Fernanda
Nova Guimaraes, Camilla Vila
Pereira, Guimaraes Rui
Litavecz, Steve
Hartwell, Tyler
Chakraborty, Hrishikesh
Javois, Lorette
Murray, Jeffrey C.
TI Oral cleft prevention program (OCPP)
SO BMC PEDIATRICS
LA English
DT Article
DE Oral clefts; Cleft lip; Cleft palate; Craniofacial anomalies; Congenital
anomalies; Birth defects; Folic acid; Vitamins; Prevention
ID NEURAL-TUBE DEFECTS; MATERNAL CIGARETTE-SMOKING; GROWTH-FACTOR-ALPHA;
FOLIC-ACID FORTIFICATION; GENE-ENVIRONMENT INTERACTION; FOLATE CARRIER
A80G; CASE-PARENT TRIADS; OROFACIAL CLEFTS; BIRTH-DEFECTS;
METHYLENETETRAHYDROFOLATE REDUCTASE
AB Background: Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted.
Methods/design: This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings.
Discussion: The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women.
C1 [Wehby, George L.; Murray, Jeffrey C.] Univ Iowa, Iowa City, IA 52242 USA.
[Moretti-Ferreira, Danilo] Sao Paulo State Univ, Biosci Inst, Genet Counseling Serv, Botucatu, SP, Brazil.
[Richieri-Costa, Antonio] Hosp Reabilitacao Anomalias Craniofaciais, Bauru, SP, Brazil.
[Felix, Temis] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.
[Padovani, Carla; Queiros, Fernanda; Nova Guimaraes, Camilla Vila] Hosp Santo Antonio Centrinho Obras Sociais Irma D, Salvador, BA, Brazil.
[Pereira, Guimaraes Rui] Inst Materno Infantil Prof Fernando Figueira, Recife, PE, Brazil.
[Litavecz, Steve; Hartwell, Tyler; Chakraborty, Hrishikesh] RTI Int, Durham, NC USA.
[Javois, Lorette] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Murray, JC (reprint author), Univ Iowa, Iowa City, IA 52242 USA.
EM jeff-murray@uiowa.edu
RI Richieri-Costa, Antonio/B-2514-2013; Felix, Temis/B-8073-2010;
Moretti-Ferreira, Danilo/F-9565-2012;
OI Felix, Temis/0000-0002-8401-6821; Moretti-Ferreira,
Danilo/0000-0002-9256-7623
FU NIH/NICHD, Global Network for Women's and Children's Health Research
[U01HD040561]; NIH/NIDCR [U01 DE017958]
FX This work has been funded by NIH/NICHD grant U01HD040561 awarded as part
of the Global Network for Women's and Children's Health Research and by
NIH/NIDCR grant U01 DE017958. The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Institutes of Health.
NR 127
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U1 1
U2 20
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2431
J9 BMC PEDIATR
JI BMC Pediatr.
PD NOV 26
PY 2012
VL 12
AR 184
DI 10.1186/1471-2431-12-184
PG 33
WC Pediatrics
SC Pediatrics
GA 064LQ
UT WOS:000313076900001
PM 23181832
ER
PT J
AU Cukras, C
Gaasterland, T
Lee, P
Gudiseva, HV
Chavali, VRM
Pullakhandam, R
Maranhao, B
Edsall, L
Soares, S
Reddy, GB
Sieving, PA
Ayyagari, R
AF Cukras, Catherine
Gaasterland, Terry
Lee, Pauline
Gudiseva, Harini V.
Chavali, Venkata R. M.
Pullakhandam, Raghu
Maranhao, Bruno
Edsall, Lee
Soares, Sandra
Reddy, G. Bhanuprakash
Sieving, Paul A.
Ayyagari, Radha
TI Exome Analysis Identified a Novel Mutation in the RBP4 Gene in a
Consanguineous Pedigree with Retinal Dystrophy and Developmental
Abnormalities
SO PLOS ONE
LA English
DT Article
ID BINDING-PROTEIN; VITAMIN-A; NIGHT BLINDNESS; SERUM RETINOL;
TRANSTHYRETIN; PLASMA; DEFICIENCY; COLOBOMA; THERAPY; DEFECT
AB Retinitis Pigmentosa (RP) is a common form of retinal degeneration characterized by photoreceptor degeneration and retinal pigment epithelium (RPE) atrophy causing loss of visual field and acuities. Exome sequencing identified a novel homozygous splice site variant (c.111+1G>A) in the gene encoding retinol binding protein 4 (RBP4). This change segregated with early onset, progressive, and severe autosomal recessive retinitis pigmentosa (arRP) in an eight member consanguineous pedigree of European ancestry. Additionally, one patient exhibited developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. The second patient developed acne from young age and extending into the 5th decade. Both patients had undetectable levels of RBP4 in the serum suggesting that this mutation led to either mRNA or protein instability resulting in a null phenotype. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. Circulating transthyretin levels were normal. This study identifies the RBP4 splice site change as the cause of RP in this pedigree. The presence of developmental abnormalities and severe acne in patients with retinal degeneration may indicate the involvement of genes that regulate vitamin A absorption, transport and metabolism.
C1 [Gudiseva, Harini V.; Chavali, Venkata R. M.; Maranhao, Bruno; Ayyagari, Radha] Univ Calif San Diego, Shiley Eye Ctr, La Jolla, CA 92093 USA.
[Cukras, Catherine; Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
[Gaasterland, Terry; Edsall, Lee; Soares, Sandra] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
[Gaasterland, Terry; Edsall, Lee; Soares, Sandra] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
[Lee, Pauline] Scripps Res Inst, La Jolla, CA 92037 USA.
[Pullakhandam, Raghu; Reddy, G. Bhanuprakash] Natl Inst Nutr, Hyderabad, AP, India.
[Sieving, Paul A.] NIDCD, NIH, Bethesda, MD USA.
RP Ayyagari, R (reprint author), Univ Calif San Diego, Shiley Eye Ctr, La Jolla, CA 92093 USA.
EM rayyagari@ucsd.edu
OI Edsall, Lee Elizabeth/0000-0002-0326-2829; Reddy, G.
Bhanuprakash/0000-0003-4787-3944
FU NIH; National Institutes of Health [EY013198, EY021237, EY022306,
EY020678]; Department of Biotechnology:Indo-US Vision Research Program;
Department of Science & Technology, Government of India; Foundation
Fighting Blindness USA; Research to Prevent Blindness
FX This work was supported by grants from the Department of
Biotechnology:Indo-US Vision Research Program, Department of Science &
Technology, Government of India, Foundation Fighting Blindness USA,
Research to Prevent Blindness, the NIH Intramural Research Program,
National Institutes of Health grants EY013198, EY021237, EY022306 and
EY020678. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 27
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U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 26
PY 2012
VL 7
IS 11
AR e50205
DI 10.1371/journal.pone.0050205
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048RI
UT WOS:000311929800065
PM 23189188
ER
PT J
AU Gaur, R
Strebel, K
AF Gaur, Ritu
Strebel, Klaus
TI Insights into the Dual Activity of SIVmac239 Vif against Human and
African Green Monkey APOBEC3G
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SINGLE AMINO-ACID; HIV-1 REVERSE
TRANSCRIPTION; VIRION INFECTIVITY FACTOR; TYPE-1 VIF; CYTIDINE
DEAMINASES; CBF-BETA; I VIF; DNA; PROTEIN
AB Human immunodeficiency virus type 1 (HIV-1) Vif is essential for viral evasion of the host antiviral protein APOBEC3G (APO3G). The Vif protein from a distantly related African green monkey (Agm) simian immunodeficiency virus (SIVagm) is unable to suppress the antiviral activity of human APO3G but is active against Agm APO3G. SIVmac Vif on the other hand, possesses antiviral activity against both human and Agm APO3G. In this study, we were interested in mapping domains in SIVmac Vif that are responsible for its dual activity against human and Agm APO3G. We constructed a series of Vif chimeras by swapping domains in SIVmac Vif with equivalent regions from SIVagm Vif and determined their activity against human and Agm APO3G. We found that replacing any region in SIVmac Vif by corresponding fragments from SIVagm Vif only moderately reduced the activity of the chimeras against Agm APO3G but in all cases resulted in a severe loss of activity against human APO3G. These results suggest that the domains in SIVmac Vif required for targeting human and Agm APO3G are distinct and cannot be defined as linear amino acid motifs but rather appear to depend on the overall structure of full-length SIVmac Vif.
C1 [Gaur, Ritu] S Asian Univ, Fac Life Sci & Biotechnol, New Delhi, India.
[Strebel, Klaus] NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bethesda, MD 20892 USA.
RP Gaur, R (reprint author), S Asian Univ, Fac Life Sci & Biotechnol, New Delhi, India.
EM rgaur@sau.ac.in
FU South Asian University; Department of Biotechnology, Government of
India; National Institute of Allergy and Infectious Disease, National
Institutes of Health, USA
FX The work was partly supported by the Intramural Research Funding of
South Asian University and Department of Biotechnology, Government of
India to RG and Intramural Research Program of the National Institute of
Allergy and Infectious Disease, National Institutes of Health, USA. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 60
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U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 26
PY 2012
VL 7
IS 11
AR e48850
DI 10.1371/journal.pone.0048850
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048RI
UT WOS:000311929800014
PM 23189135
ER
PT J
AU Prasad, V
Rho, J
Cifu, A
AF Prasad, Vinay
Rho, Jason
Cifu, Adam
TI Freedom to Innovate: The Perils of Centralized Medical Research reply
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
ID APROTININ
C1 [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Rho, Jason] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Cifu, Adam] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,Ste 10-12N226, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov
NR 5
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U1 0
U2 0
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 NOV 26
PY 2012
VL 172
IS 21
BP 1693
EP 1693
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 042ZY
UT WOS:000311513000030
ER
PT J
AU Schaap-Nutt, A
Liesman, R
Bartlett, EJ
Scull, MA
Collins, PL
Pickles, RJ
Schmidt, AC
AF Schaap-Nutt, Anne
Liesman, Rachael
Bartlett, Emmalene J.
Scull, Margaret A.
Collins, Peter L.
Pickles, Raymond J.
Schmidt, Alexander C.
TI Human parainfluenza virus serotypes differ in their kinetics of
replication and cytokine secretion in human tracheobronchial airway
epithelium
SO VIROLOGY
LA English
DT Article
DE Human parainfluenza virus; Human airway epithelium; Cytokines;
Chemokines; Interferon; Pathogenesis
ID RESPIRATORY SYNCYTIAL VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; VACCINE
CANDIDATES; NONHUMAN-PRIMATES; IMMUNE-RESPONSE; WILD-TYPE;
HEMAGGLUTININ-NEURAMINIDASE; INTERFERON-PRODUCTION; CELL
TRANSPLANTATION; CHEMOKINE RESPONSES
AB Human parainfluenza viruses (PIVs) cause acute respiratory illness in children, the elderly, and immunocompromised patients. PIV3 is a common cause of bronchiolitis and pneumonia, whereas PIV1 and 2 are frequent causes of upper respiratory tract illness and croup. To assess how PIV1, 2, and 3 differ with regard to replication and induction of type I interferons, interleukin-6, and relevant chemokines, we infected primary human airway epithelium (HAE) cultures from the same tissue donors and examined replication kinetics and cytokine secretion. PIV1 replicated to high titer yet did not induce cytokine secretion until late in infection, while PIV2 replicated less efficiently but induced an early cytokine peak. PIV3 replicated to high titer but induced a slower rise in cytokine secretion. The T cell chemoattractants CXCL10 and CXCL11 were the most abundant chemokines induced. Differences in replication and cytokine secretion might explain some of the differences in PIV serotype-specific pathogenesis and epidemiology. Published by Elsevier Inc.
C1 [Schaap-Nutt, Anne; Bartlett, Emmalene J.; Collins, Peter L.; Schmidt, Alexander C.] NIAID, Infect Dis Lab, RNA Viruses Sect, NIH, Bethesda, MD 20892 USA.
[Liesman, Rachael; Scull, Margaret A.; Pickles, Raymond J.] Univ N Carolina, Cyst Fibrosis Pulmonary Res & Treatment Ctr, Chapel Hill, NC 27599 USA.
[Liesman, Rachael; Scull, Margaret A.; Pickles, Raymond J.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
RP Schmidt, AC (reprint author), NIAID, Infect Dis Lab, RNA Viruses Sect, NIH, 50 S Dr,Room 6515,MSC 8007, Bethesda, MD 20892 USA.
EM as337y@gmail.com
FU National Institutes of Health [R01 HL77844, 5-T32-AI007419]; Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases at the National Institutes of Health
FX This work was supported by the National Institutes of Health (Grant no.
R01 HL77844 to R.J.P. and 5-T32-AI007419) and the Intramural Research
Program of the National Institute of Allergy and Infectious Diseases at
the National Institutes of Health. The views expressed in this report
are the personal opinions of the authors and are not the official
opinion of the National Institutes of Health or the Department of Health
and Human Services. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 65
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U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD NOV 25
PY 2012
VL 433
IS 2
BP 320
EP 328
DI 10.1016/j.virol.2012.08.027
PG 9
WC Virology
SC Virology
GA 024FS
UT WOS:000310095700005
PM 22959894
ER
PT J
AU Handisurya, A
Day, PM
Thompson, CD
Buck, CB
Kwak, K
Roden, RBS
Lowy, DR
Schiller, JT
AF Handisurya, Alessandra
Day, Patricia M.
Thompson, Cynthia D.
Buck, Christopher B.
Kwak, Kihyuck
Roden, Richard B. S.
Lowy, Douglas R.
Schiller, John T.
TI Murine skin and vaginal mucosa are similarly susceptible to infection by
pseudovirions of different papillomavirus classifications and species
SO VIROLOGY
LA English
DT Article
DE Papillomavirus; Pseudovirions; Murine model; Skin infection; Tissue
tropism; Murine papillomavirus; In vivo imaging
ID UPSTREAM REGULATORY REGION; CROSS-NEUTRALIZING EPITOPE; SQUAMOUS-CELL
CARCINOMAS; RABBIT PAPILLOMAVIRUS; HEPARAN-SULFATE; BINDING; SURFACE;
VIRUS; HPV; PROTECTION
AB Depending upon viral genotype, productive papillomavirus infection and disease display preferential tropism for cutaneous or mucosal stratified squamous epithelia, although the mechanisms are unclear. To investigate papillomavirus entry tropism, we used reporter pseudovirions based on various cutaneous and mucosal papillomavirus species, including the recently identified murine papillomavirus. Pseudovirus transduction of BALB/c mice was examined using an improved murine skin infection protocol and a previously developed cervicovaginal challenge model. In the skin, HPV5, HPV6, HPV16, BPV1 and Mu5PV1 pseudovirions preferentially transduced keratinocytes at sites of trauma, similar to the genital tract. Skin infection, visualized by in vivo imaging using a luciferase reporter gene, peaked between days 2-3 and rapidly diminished for all pseudovirion types. Murine cutaneous and genital tissues were similarily permissive for pseudovirions of HPV types 5, 6, 8, 16, 18, 26, 44, 45, 51, 58 and animal papillomaviruses BPV1 and Mu5PV1, implying that papillomavirus' tissue and host tropism is governed primarily by post-entry regulatory events in the mouse. Published by Elsevier Inc.
C1 [Handisurya, Alessandra; Day, Patricia M.; Thompson, Cynthia D.; Buck, Christopher B.; Lowy, Douglas R.; Schiller, John T.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Handisurya, Alessandra] Med Univ Vienna, Dept Dermatol, Div Immunol Allergy & Infect Dis, A-1090 Vienna, Austria.
[Kwak, Kihyuck; Roden, Richard B. S.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21287 USA.
RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM schillej@mail.nih.gov
OI Buck, Christopher/0000-0003-3165-8094
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; Austrian Science
Fund FWF [J3012-B13]; Public Health Service [CA133749, CA118790, P50
CA098252]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research and the Austrian Science Fund FWF (Erwin Schroedinger
Fellowship project no.: J3012-B13 to AH) and Public Health Service
grants CA133749, CA118790 and P50 CA098252.
NR 35
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U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD NOV 25
PY 2012
VL 433
IS 2
BP 385
EP 394
DI 10.1016/j.virol.2012.08.035
PG 10
WC Virology
SC Virology
GA 024FS
UT WOS:000310095700012
PM 22985477
ER
PT J
AU Bengali, Z
Satheshkumar, PS
Moss, B
AF Bengali, Zain
Satheshkumar, P. S.
Moss, Bernard
TI Orthopoxvirus species and strain differences in cell entry
SO VIROLOGY
LA English
DT Article
DE Vaccinia virus; Cowpox virus; Monkeypox virus; Endocytosis; Fusion;
Bafilomycin A1
ID INTRACELLULAR MATURE VIRION; SURFACE HEPARAN-SULFATE; VACCINIA VIRUS
ENTRY; A-TYPE INCLUSIONS; MEMBRANE-PROTEIN; FUSION COMPLEX; ESSENTIAL
COMPONENT; VIRAL MEMBRANE; POXVIRUS ENTRY; A27 PROTEINS
AB Vaccinia virus (VACV) enters cells by a low pH endosomal route or by direct fusion with the plasma membrane. We previously found differences in entry properties of several VACV strains: entry of WR was enhanced by low pH, reduced by bafilomycin A1 and relatively unaffected by heparin, whereas entry of IHD-J, Copenhagen and Elstree were oppositely affected. Since binding and entry modes may have been selected by specific conditions of in vitro propagation, we now examined the properties of three distinct, recently isolated cowpox viruses and a monkeypox virus as well as additional VACV and cowpox virus strains. The recent isolates were more similar to WR than to other VACV strains, underscoring the biological importance of endosomal entry by orthopoxviruses. Sequence comparisons, gene deletions and gene swapping experiments indicated that viral determinants, other than or in addition to the A26 and A25 "fusion-suppressor" proteins, impact entry properties. Published by Elsevier Inc.
C1 [Bengali, Zain; Satheshkumar, P. S.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
FU DIR, NIAID, NIH
FX We thank Scott Sammons of the Centers for Disease Control and Prevention
for providing IHD-J genome sequences, David Pickup of Duke University
for antibody to the CPXV ATI protein, Catherine Cotter for help with
cell culture, Jeffery Americo for conducting the MPXV experiments under
BSL-3 conditions, and Robin Kastenmeyer and Andrea Weisberg for
unpublished information regarding ATI formation by CPXV isolates.
Research funds were provided by the DIR, NIAID, NIH.
NR 49
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U1 0
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD NOV 25
PY 2012
VL 433
IS 2
BP 506
EP 512
DI 10.1016/j.virol.2012.08.044
PG 7
WC Virology
SC Virology
GA 024FS
UT WOS:000310095700025
PM 22999097
ER
PT J
AU Shugart, YY
Zhu, Y
Guo, W
Xiong, MM
AF Shugart, Yin Yao
Zhu, Yun
Guo, Wei
Xiong, Momiao
TI Weighted pedigree-based statistics for testing the association of rare
variants
SO BMC GENOMICS
LA English
DT Article
DE Pedigree; Next-generation sequencing; GWAS; Rare Variants; Collapsing
ID COMPLEX TRAITS; DISEASE; COMMON; ARCHITECTURE; INDIVIDUALS; HYPERTROPHY
AB Background: With the advent of next-generation sequencing (NGS) technologies, researchers are now generating a deluge of data on high dimensional genomic variations, whose analysis is likely to reveal rare variants involved in the complex etiology of disease. Standing in the way of such discoveries, however, is the fact that statistics for rare variants are currently designed for use with population-based data. In this paper, we introduce a pedigree-based statistic specifically designed to test for rare variants in family-based data. The additional power of pedigree-based statistics stems from the fact that while rare variants related to diseases or traits of interest occur only infrequently in populations, in families with multiple affected individuals, such variants are enriched. Note that while the proposed statistic can be applied with and without statistical weighting, our simulations show that its power increases when weighting (WSS and VT) are applied.
Results: Our working hypothesis was that, since rare variants are concentrated in families with multiple affected individuals, pedigree-based statistics should detect rare variants more powerfully than population-based statistics. To evaluate how well our new pedigree-based statistics perform in association studies, we develop a general framework for sequence-based association studies capable of handling data from pedigrees of various types and also from unrelated individuals. In short, we developed a procedure for transforming population-based statistics into tests for family-based associations. Furthermore, we modify two existing tests, the weighted sum-square test and the variable-threshold test, and apply both to our family-based collapsing methods. We demonstrate that the new family-based tests are more powerful than corresponding population-based test and they generate a reasonable type I error rate.
To demonstrate feasibility, we apply the newly developed tests to a pedigree-based GWAS data set from the Framingham Heart Study (FHS). FHS-GWAS data contain approximately 5000 uncommon variants with frequencies less than 0.05. Potential association findings in these data demonstrate the feasibility of the software PB-STAR (note, PB-STAR is now freely available to the public).
Conclusion: Our tests show that when analyzing for rare variants, a pedigree-based design is more powerful than a population-based case-control design. We further demonstrate that a pedigree-based statistic's power to detect rare variants increases in direct relation to the proportion of affected individuals within the pedigree.
C1 [Shugart, Yin Yao; Guo, Wei] NIMH, Unit Stat Genom, Div Intramural Div Program, NIH, Bethesda, MD 20892 USA.
[Zhu, Yun; Xiong, Momiao] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Biostat, Houston, TX 77225 USA.
[Xiong, Momiao] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77225 USA.
RP Xiong, MM (reprint author), Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Biostat, Houston, TX 77225 USA.
EM Momiao.Xiong@uth.tmc.edu
RI Zhu, Yun/N-3403-2014
OI Zhu, Yun/0000-0002-9500-5415
FU National Institutes of Health [1R01AR057120 - 01, 1R01HL106034-01,
1U01HG005728-01]; Intramural Research Program at the National Institute
of Mental Health; National Heart, Lung, and Blood Institute (NHLBI);
Boston University [N01-HC-25195]; NHLBI [N02-HL-64278]
FX MM. Xiong and Y. Zhu were supported by Grants 1R01AR057120 - 01,
1R01HL106034-01, and 1U01HG005728-01 from the National Institutes of
Health. YY. Shugart and W. Guo were supported by the Intramural Research
Program at the National Institute of Mental Health.; The views expressed
in this presentation do not necessarily represent the views of the NIMH,
NIH, HHS, or the United States Government.; The Framingham Heart Study
is conducted and supported by the National Heart, Lung, and Blood
Institute (NHLBI) in collaboration with Boston University (Contract No.
N01-HC-25195). This manuscript was not prepared in collaboration with
investigators of the Framingham Heart Study and does not necessarily
reflect the opinions or views of the Framingham Heart Study, Boston
University, or NHLBI. Funding for SHARe genotyping was provided by NHLBI
Contract N02-HL-64278.
NR 25
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U1 0
U2 6
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 NOV 24
PY 2012
VL 13
AR 667
DI 10.1186/1471-2164-13-667
PG 16
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 085ZF
UT WOS:000314652100001
PM 23176082
ER
PT J
AU Khozoie, C
Borland, MG
Zhu, BK
Baek, S
John, S
Hager, GL
Shah, YM
Gonzalez, FJ
Peters, JM
AF Khozoie, Combiz
Borland, Michael G.
Zhu, Bokai
Baek, Songjoon
John, Sam
Hager, Gordon L.
Shah, Yatrik M.
Gonzalez, Frank J.
Peters, Jeffrey M.
TI Analysis of the peroxisome proliferator-activated receptor-beta/delta
(PPAR beta/delta) cistrome reveals novel co-regulatory role of ATF4
SO BMC GENOMICS
LA English
DT Article
DE Peroxisome proliferator-activated receptor-beta/delta; Gene expression;
Keratinocytes
ID LARGE GENE LISTS; TRANSCRIPTIONAL REGULATION; GLUCOCORTICOID-RECEPTOR;
CELL-PROLIFERATION; LIGAND ACTIVATION; DIFFERENTIATION; PROTEIN;
CARCINOGENESIS; KERATINOCYTES; EXPRESSION
AB Background: The present study coupled expression profiling with chromatin immunoprecipitation sequencing (ChIP-seq) to examine peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta)-dependent regulation of gene expression in mouse keratinocytes, a cell type that expresses PPAR beta/delta in high concentration.
Results: Microarray analysis elucidated eight different types of regulation that modulated PPAR beta/delta-dependent gene expression of 612 genes ranging from repression or activation without an exogenous ligand, repression or activation with an exogenous ligand, or a combination of these effects. Bioinformatic analysis of ChIP-seq data demonstrated promoter occupancy of PPAR beta/delta for some of these genes, and also identified the presence of other transcription factor binding sites in close proximity to PPAR beta/delta bound to chromatin. For some types of regulation, ATF4 is required for ligand-dependent induction of PPAR beta/delta target genes.
Conclusions: PPAR beta/delta regulates constitutive expression of genes in keratinocytes, thus suggesting the presence of one or more endogenous ligands. The diversity in the types of gene regulation carried out by PPAR beta/delta is consistent with dynamic binding and interactions with chromatin and indicates the presence of complex regulatory networks in cells expressing high levels of this nuclear receptor such as keratinocytes. Results from these studies are the first to demonstrate that differences in DNA binding of other transcription factors can directly influence the transcriptional activity of PPAR beta/delta.
C1 [Khozoie, Combiz; Borland, Michael G.; Zhu, Bokai; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Khozoie, Combiz; Borland, Michael G.; Zhu, Bokai; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Baek, Songjoon; John, Sam; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA.
[Shah, Yatrik M.; Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
EM jmp21@psu.edu
FU National Institutes of Health [CA124533, CA126826, CA141029, CA140369,
AA018863]; National Cancer Institute Intramural Research Program
[ZIABC005561, ZIABC005562, ZIABC005708]
FX The authors gratefully acknowledge the National Cancer Institute's
Center for Cancer Research Sequencing Facility for performing the ChIP
sequencing, and Drs. Pallavi Devchand and Walter Wahli for providing the
pSG5-mouse PPAR beta/delta construct. Supported by the National
Institutes of Health (CA124533, CA126826, CA141029, CA140369, AA018863)
J.M.P., and the National Cancer Institute Intramural Research Program
(ZIABC005561, ZIABC005562, ZIABC005708) F.J.G.
NR 60
TC 13
Z9 14
U1 0
U2 6
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 NOV 24
PY 2012
VL 13
AR 665
DI 10.1186/1471-2164-13-665
PG 19
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 085YY
UT WOS:000314651400001
PM 23176727
ER
PT J
AU Umhau, JC
Trandem, K
Shah, M
George, DT
AF Umhau, John C.
Trandem, Karysse
Shah, Mohsin
George, David T.
TI The physician's unique role in preventing violence: a neglected
opportunity?
SO BMC MEDICINE
LA English
DT Editorial Material
DE aggression; alcoholism; psychopharmacology; violence; domestic abuse;
prevention; neurobiology; treatment; domestic violence
ID BORDERLINE PERSONALITY-DISORDER; INTERMITTENT EXPLOSIVE DISORDER;
TREATING ALCOHOL DEPENDENCE; PLACEBO-CONTROLLED TRIAL; YOUNG-ADULT
PRISONERS; DOMESTIC VIOLENCE; DOUBLE-BLIND; AGGRESSIVE-BEHAVIOR; CONDUCT
DISORDER; IMPULSIVE AGGRESSION
AB Background: Episodes of explosive rage and violence comprise a symptom complex which can have a devastating effect on a person's life. In the community this behavior is seen as workplace violence, domestic abuse and road rage, while in the clinical setting, this behavior is rarely mentioned by patients, despite evidence that it can signify an important biological disorder that may afflict more than three percent of the population.
Discussion: Patients are often reluctant to seek help for episodic attacks of rage, especially attacks which are accompanied by physical violence. Although, in the past, clinicians have had few treatment options to offer, recent neuroscience advances have created new possibilities to understand and help patients with this neglected problem. No formal medical guidelines for treating violence exist; however, many patients can be helped by diagnosis, referral and treatment. Treatment can include pharmaceuticals and nutrients, as well as referral for anger management or behavioral therapy.
Summary: The astute clinician has an opportunity to positively impact an important problem through the diagnosis and treatment of patients with symptoms of intermittent explosive disorder.
C1 [Umhau, John C.; George, David T.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Trandem, Karysse] Grand Itasca Clin & Hosp, Dept Obstet & Gynecol, Grand Rapids, MN 55744 USA.
[Shah, Mohsin] Univ Hlth Sci, CMH Lahore Med Coll, Coll Med, Lahore 54000, Punjab, Pakistan.
RP Umhau, JC (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,Bldg 10 CRC Hatfield Ctr,Room 1-5330, Bethesda, MD 20892 USA.
EM umhau@jhu.edu
OI Shah, Mohsin /0000-0002-3450-4843
NR 133
TC 2
Z9 3
U1 4
U2 21
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD NOV 23
PY 2012
VL 10
AR 146
DI 10.1186/1741-7015-10-146
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 064DW
UT WOS:000313052300001
PM 23177023
ER
PT J
AU Crooks, DR
Jeong, SY
Tong, WH
Ghosh, MC
Olivierre, H
Haller, RG
Rouault, TA
AF Crooks, Daniel R.
Jeong, Suh Young
Tong, Wing-Hang
Ghosh, Manik C.
Olivierre, Hayden
Haller, Ronald G.
Rouault, Tracey A.
TI Tissue Specificity of a Human Mitochondrial Disease
DIFFERENTIATION-ENHANCED MIS-SPLICING OF THE Fe-S SCAFFOLD GENE ISCU
RENDERS PATIENT CELLS MORE SENSITIVE TO OXIDATIVE STRESS IN ISCU
MYOPATHY
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SULFUR CLUSTER BIOGENESIS; SUCCINATE-DEHYDROGENASE; LACTIC-ACIDOSIS;
PAROXYSMAL MYOGLOBINURIA; ACONITASE DEFICIENCY; HEREDITARY MYOPATHY;
IRON HOMEOSTASIS; MAMMALIAN-CELLS; INTRON MUTATION; SKELETAL-MUSCLE
AB Iron-sulfur (Fe-S) cluster cofactors are formed on the scaffold protein ISCU. ISCU myopathy is a disease caused by an intronic mutation that leads to abnormally spliced ISCU mRNA. We found that two predominant mis-spliced ISCU mRNAs produce a truncated and short-lived ISCU protein product in multiple patient cell types. Expression of the muscle-specific transcription factor MyoD further diminished normal splicing of ISCU mRNA in patient myoblasts, demonstrating that the process of muscle differentiation enhances the loss of normal ISCU mRNA splicing. ISCU protein was nearly undetectable in patient skeletal muscle, but was higher in patient myoblasts, fibroblasts, and lymphoblasts. We next treated patient cells with pro-oxidants to mimic the oxidative stress associated with muscle activity. Brief hydrogen peroxide treatment or incubation in an enriched oxygen atmosphere led to a marked further reduction of ISCU protein levels, which could be prevented by pretreatment with the antioxidant ascorbate. Thus, we conclude that skeletal muscle differentiation of patient cells causes a higher degree of abnormal ISCU splicing and that oxidative stress resulting from skeletal muscle work destabilizes the small amounts of normal ISCU protein generated in patient skeletal muscles.
C1 [Crooks, Daniel R.] Georgetown Univ, Dept Biochem Mol & Cellular Biol, Med Ctr, Washington, DC 20057 USA.
[Crooks, Daniel R.; Jeong, Suh Young; Tong, Wing-Hang; Ghosh, Manik C.; Olivierre, Hayden; Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, NIH, Bethesda, MD 20892 USA.
[Haller, Ronald G.] Texas Hlth Presbyterian Hosp, Neuromuscular Ctr, Inst Exercise & Environm Med, Dallas, TX 75231 USA.
[Haller, Ronald G.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA.
[Haller, Ronald G.] N Texas VA Med Ctr, Div Neurol, Dallas, TX 75216 USA.
RP Rouault, TA (reprint author), Bldg 18T,Rm 101,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rouault@helix.nih.gov
OI Jeong, Suh Young/0000-0002-6376-7001
FU National Institutes of Health through the NICHD Intramural Research
Program; NIAMS [R01 AR050597]; Veterans Affairs Merit Review
FX This work was supported, in whole or in part, by the National Institutes
of Health through the NICHD Intramural Research Program (to T. A. R.)
and NIAMS Grant R01 AR050597 (to R. G. H.). This work was also supported
by a Veterans Affairs Merit Review (to R. G. H.).
NR 48
TC 15
Z9 16
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 NOV 23
PY 2012
VL 287
IS 48
BP 40119
EP 40130
DI 10.1074/jbc.M112.418889
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 042CM
UT WOS:000311448800003
PM 23035118
ER
PT J
AU Yang, T
Jian, W
Luo, Y
Fu, XQ
Noguchi, C
Bungert, J
Huang, SM
Qiu, Y
AF Yang, Tao
Jian, Wei
Luo, Yi
Fu, Xueqi
Noguchi, Constance
Bungert, Joerg
Huang, Suming
Qiu, Yi
TI Acetylation of Histone Deacetylase 1 Regulates NuRD Corepressor Complex
Activity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TRANSCRIPTION FACTOR GATA-1; LOCUS-CONTROL REGION; BETA-GLOBIN LOCUS;
ERYTHROID-DIFFERENTIATION; CELL-DIFFERENTIATION; CHROMATIN OCCUPANCY;
GENE-EXPRESSION; DEPENDENT REGULATION; DISTINCT FUNCTIONS;
LEUKEMIC-CELLS
AB Histone deacetylases (HDACs) play important roles in regulating cell proliferation and differentiation. The HDAC1-containing NuRD complex is generally considered as a corepressor complex and is required for GATA-1-mediated repression. However, recent studies also show that the NuRD complex is involved in GATA-1-mediated gene activation. We tested whether the GATA-1-associated NuRD complex loses its deacetylase activity and commits the GATA-1 complex to become an activator during erythropoiesis. We found that GATA-1-associated deacetylase activity gradually decreased upon induction of erythroid differentiation. GATA-1-associated HDAC1 is increasingly acetylated after differentiation. It has been demonstrated earlier that acetylated HDAC1 has no deacetylase activity. Indeed, overexpression of an HDAC1 mutant, which mimics acetylated HDAC1, promotes GATA-1-mediated transcription and erythroid differentiation. Furthermore, during erythroid differentiation, acetylated HDAC1 recruitment is increased at GATA-1-activated genes, whereas it is significantly decreased at GATA-1-repressed genes. Interestingly, deacetylase activity is not required for Mi2 remodeling activity, suggesting that remodeling activity may be required for both activation and repression. Thus, our data suggest that NuRD can function as a coactivator or repressor and that acetylated HDAC1 converts the NuRD complex from a repressor to an activator during GATA-1-directed erythroid differentiation.
C1 [Yang, Tao; Jian, Wei; Luo, Yi; Qiu, Yi] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL 32610 USA.
[Bungert, Joerg; Huang, Suming] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA.
[Yang, Tao; Fu, Xueqi] Jilin Univ, Coll Life Sci, Changchun 130023, Peoples R China.
[Noguchi, Constance] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
RP Qiu, Y (reprint author), 2033 Mowry Rd,Rm 356, Gainesville, FL 32610 USA.
EM qiuy@ufl.edu
RI cheng, yong/I-4270-2012
FU National Institutes of Health [R01 HL095674, R01 HL091929,
R01091929-01A1S1, R01 DK 83389, R01 DK 52356]; Florida Bankhead Coley
Research Foundation; NIDDK, National Institutes of Health
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01 HL095674 (to Y. Q.); R01 HL091929,
R01091929-01A1S1-the American Recovery and Reinvestment Act
Administrative Supplement, and R01 HL 090589 (to S. H.); and R01 DK
83389 and R01 DK 52356 (to J. B.). This work was also supported by a
grant from the Florida Bankhead Coley Research Foundation (to Y. Q.).
Supported by the Intramural Research programs, NIDDK, National
Institutes of Health.
NR 71
TC 12
Z9 14
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 23
PY 2012
VL 287
IS 48
BP 40279
EP 40291
DI 10.1074/jbc.M112.349704
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 042CM
UT WOS:000311448800020
PM 23014989
ER
PT J
AU Muller, JR
Waldmann, TA
Kruhlak, MJ
Dubois, S
AF Mueller, Juergen R.
Waldmann, Thomas A.
Kruhlak, Michael J.
Dubois, Sigrid
TI Paracrine and Transpresentation Functions of IL-15 Are Mediated by
Diverse Splice Versions of IL-15R alpha in Human Monocytes and Dendritic
Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID RECEPTOR-ALPHA-CHAIN; MARROW-DERIVED CELLS; NATURAL-KILLER; TRANS
PRESENTATION; CUTTING EDGE; NK CELLS; T-CELLS; EXPRESSION;
INTERLEUKIN-15; GLYCOSYLATION
AB Species-specific differences of post-translational modifications suggested the existence of human IL-15R alpha isoforms. We identified eight new isoforms that are predicted to modify the intracellular C termini of IL-15R alpha, and another N-terminal exon "Ex2A" that was consistently present in all but one of the C-terminal isoforms. Ex2A encodes a 49-amino acid domain that allowed the transfer of IL-15/IL-15R alpha complex to the cell surface but prevented its cleavage from cell membranes and its secretion thus facilitating the transpresentation of IL-15 as part of the immunological synapse. The Ex2A domain also affected the O-glycosylation of IL-15R alpha that explained the species-specific differences. The Ex2A domain appeared to be removed from major IL-15R alpha species during protein maturation, but both Ex2A and IL-15R alpha appeared on the surface of monocytic cells upon activation. The membrane-associated form of the only C-terminal isoform that lacked Ex2A (IC3) was retained inside the cell, but soluble IL-15/IL-15R alpha complexes were readily released from cells that expressed IL-15/IL-15R alpha-IC3 thus limiting this IL-15/IL-15R alpha isoform to act as a secreted molecule. These data suggest that splice versions of IL-15R alpha determine the range of IL-15 activities.
C1 [Mueller, Juergen R.; Waldmann, Thomas A.; Dubois, Sigrid] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
[Kruhlak, Michael J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Dubois, S (reprint author), NCI, Metab Branch, NIH, Bldg 10,Rm 4B47,10 Ctr Dr, Bethesda, MD 20892 USA.
EM duboiss@mail.nih.gov
FU NCI, National Institutes of Health
FX This work was supported by the intramural research program of the NCI,
National Institutes of Health.
NR 35
TC 10
Z9 11
U1 0
U2 8
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 NOV 23
PY 2012
VL 287
IS 48
BP 40328
EP 40338
DI 10.1074/jbc.M112.378612
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 042CM
UT WOS:000311448800024
PM 23074221
ER
PT J
AU Munoz, MC
Laulier, C
Gunn, A
Cheng, A
Robbiani, DF
Nussenzweig, A
Stark, JM
AF Munoz, Meilen C.
Laulier, Corentin
Gunn, Amanda
Cheng, Anita
Robbiani, Davide F.
Nussenzweig, Andre
Stark, Jeremy M.
TI Ring Finger Nuclear Factor RNF168 Is Important for Defects in Homologous
Recombination Caused by Loss of the Breast Cancer Susceptibility Factor
BRCA1
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DOUBLE-STRAND BREAKS; CLASS SWITCH RECOMBINATION; MAMMALIAN-CELLS;
DNA-DAMAGE; DIRECTED REPAIR; IONIZING-RADIATION; GENOMIC STABILITY; END
RESECTION; GENE BRCA1; 53BP1
AB The RING finger nuclear factor RNF168 is required for recruitment of several DNA damage response factors to double strand breaks (DSBs), including 53BP1 and BRCA1. Because 53BP1 and BRCA1 function antagonistically during the DSB repair pathway homologous recombination (HR), the influence of RNF168 on HR has been unclear. We report that RNF168 depletion causes an elevated frequency of two distinct HR pathways (homology-directed repair and single strand annealing), suppresses defects in HR caused by BRCA1 silencing, but does not suppress HR defects caused by disruption of CtIP, RAD50, BRCA2, or RAD51. Furthermore, RNF168-depleted cells can form ionizing radiation-induced foci of the recombinase RAD51 without forming BRCA1 ionizing radiation-induced foci, indicating that this loss of BRCA1 recruitment to DSBs does not reflect a loss of function during HR. Additionally, we find that RNF168 and 53BP1 have a similar influence on HR. We suggest that RNF168 is important for HR defects caused by BRCA1 loss.
C1 [Munoz, Meilen C.; Laulier, Corentin; Gunn, Amanda; Cheng, Anita; Stark, Jeremy M.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Radiat Biol, Duarte, CA 91010 USA.
[Munoz, Meilen C.; Gunn, Amanda; Stark, Jeremy M.] City Hope Natl Med Ctr, Beckman Res Inst, Irell & Manella Grad Sch Biol Sci, Duarte, CA 91010 USA.
[Robbiani, Davide F.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
[Nussenzweig, Andre] NCI, Lab Genome Integr, Bethesda, MD 20892 USA.
RP Stark, JM (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Dept Radiat Biol, 1500 E Duarte Rd, Duarte, CA 91010 USA.
EM jstark@coh.org
FU National Institutes of Health [RO1CA120954]; Marsha Rivkin Center for
Ovarian Cancer Research; University of California [181B-0046]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant RO1CA120954 (to J. M. S.). This work was also supported by
the Marsha Rivkin Center for Ovarian Cancer Research and by Regents of
the University of California Breast Cancer Research Program Grant
181B-0046 (to J. M. S.).
NR 56
TC 16
Z9 16
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 NOV 23
PY 2012
VL 287
IS 48
BP 40618
EP 40628
DI 10.1074/jbc.M112.410951
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 042CM
UT WOS:000311448800051
PM 23055523
ER
PT J
AU Suntharalingam, A
Abisambra, JF
O'Leary, JC
Koren, J
Zhang, B
Joe, MK
Blair, LJ
Hill, SE
Jinwal, UK
Cockman, M
Duerfeldt, AS
Tomarev, S
Blagg, BSJ
Lieberman, RL
Dickey, CA
AF Suntharalingam, Amirthaa
Abisambra, Jose F.
O'Leary, John C., III
Koren, John, III
Zhang, Bo
Joe, Myung Kuk
Blair, Laura J.
Hill, Shannon E.
Jinwal, Umesh K.
Cockman, Matthew
Duerfeldt, Adam S.
Tomarev, Stanislav
Blagg, Brian S. J.
Lieberman, Raquel L.
Dickey, Chad A.
TI Glucose-regulated Protein 94 Triage of Mutant Myocilin through
Endoplasmic Reticulum-associated Degradation Subverts a More Efficient
Autophagic Clearance Mechanism
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; TRABECULAR MESHWORK CELLS; CHAPERONE-MEDIATED
AUTOPHAGY; OLFACTOMEDIN-HOMOLOGY DOMAIN; TIGR/MYOCILIN PROTEIN;
RETINITIS-PIGMENTOSA; CHEMICAL CHAPERONE; POINT MUTANTS; MOUSE MODEL; ER
STRESS
AB Clearance of misfolded proteins in the endoplasmic reticulum (ER) is traditionally handled by ER-associated degradation (ERAD), a process that requires retro-translocation and ubiquitination mediated by a luminal chaperone network. Here we investigated whether the secreted, glaucoma-associated protein myocilin was processed by this pathway. Myocilin is typically transported through the ER/Golgi network, but inherited mutations in myocilin lead to its misfolding and aggregation within trabecular meshwork cells, and ultimately, ER stress-induced cell death. Using targeted knockdown strategies, we determined that glucose-regulated protein 94 (Grp94), the ER equivalent of heat shock protein 90 (Hsp90), specifically recognizes mutant myocilin, triaging it through ERAD. The addition of mutant myocilin to the short list of Grp94 clients strengthens the hypothesis that beta-strand secondary structure drives client association with Grp94. Interestingly, the ERAD pathway is incapable of efficiently handling the removal of mutant myocilin, but when Grp94 is depleted, degradation of mutant myocilin is shunted away from ERAD toward a more robust clearance pathway for aggregation-prone proteins, the autophagy system. Thus ERAD inefficiency for distinct aggregation-prone proteins can be subverted by manipulating ER chaperones, leading to more effective clearance by the autophagic/lysosomal pathway. General Hsp90 inhibitors and a selective Grp94 inhibitor also facilitate clearance of mutant myocilin, suggesting that therapeutic approaches aimed at inhibiting Grp94 could be beneficial for patients suffering from some cases of myocilin glaucoma.
C1 [Suntharalingam, Amirthaa; Abisambra, Jose F.; O'Leary, John C., III; Koren, John, III; Zhang, Bo; Blair, Laura J.; Cockman, Matthew; Dickey, Chad A.] Univ S Florida, Dept Mol Med, Tampa, FL 33613 USA.
[Suntharalingam, Amirthaa; Abisambra, Jose F.; O'Leary, John C., III; Koren, John, III; Zhang, Bo; Blair, Laura J.; Cockman, Matthew; Dickey, Chad A.] Univ S Florida, Byrd Alzheimers Res Inst, Tampa, FL 33613 USA.
[Jinwal, Umesh K.] Univ S Florida, Coll Pharm, Tampa, FL 33613 USA.
[Joe, Myung Kuk; Tomarev, Stanislav] NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Hill, Shannon E.; Lieberman, Raquel L.] Georgia Inst Technol, Sch Chem & Biochem, Atlanta, GA 30332 USA.
[Duerfeldt, Adam S.; Blagg, Brian S. J.] Univ Kansas, Dept Med Chem, Lawrence, KS 66049 USA.
RP Dickey, CA (reprint author), Univ S Florida, Dept Mol Med, Tampa, FL 33613 USA.
EM cdickey@health.usf.edu
FU National Institutes of Health [R00AG031291, R01NS073899, R01EY021205];
American Health Assistance Foundation
FX This work was supported, in whole or in part, by the National Institutes
of Health Grants R00AG031291 (to C. A. D.), R01NS073899 (to C. A. D.),
and R01EY021205 (to R. L. L.). This work was also supported by the
American Health Assistance Foundation.
NR 65
TC 24
Z9 26
U1 1
U2 11
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 NOV 23
PY 2012
VL 287
IS 48
BP 40661
EP 40669
DI 10.1074/jbc.M112.384800
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 042CM
UT WOS:000311448800055
PM 23035116
ER
PT J
AU Schneider, EH
Weaver, JD
Gaur, SS
Tripathi, BK
Jesaitis, AJ
Zelenka, PS
Gao, JL
Murphy, PM
AF Schneider, Erich H.
Weaver, Joseph D.
Gaur, Sonia S.
Tripathi, Brajendra K.
Jesaitis, Algirdas J.
Zelenka, Peggy S.
Gao, Ji-Liang
Murphy, Philip M.
TI The Leukocyte Chemotactic Receptor FPR1 Is Functionally Expressed on
Human Lens Epithelial Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FORMYL PEPTIDE RECEPTOR; N-FORMYLPEPTIDE RECEPTOR; MESENCHYMAL
STEM-CELLS; CHEMOATTRACTANT RECEPTORS; HUMAN NEUTROPHIL; G-PROTEIN;
BINDING; LIGAND; ACTIVATION; FAMILY
AB Formyl peptide receptor 1 (FPR1) is a G protein-coupled chemoattractant receptor expressed mainly on leukocytes. Surprisingly, aging Fpr1(-/-) mice develop spontaneous lens degeneration without inflammation or infection (J.-L. Gao et al., manuscript in preparation). Therefore, we hypothesized that FPR1 is functionally expressed directly on lens epithelial cells, the only cell type in the lens. Consistent with this, the human fetal lens epithelial cell line FHL 124 expressed FPR1 FPR1 mRNA and was strongly FPR1 protein-positive by Western blot and FACS. Competition binding using FPR1 ligands N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys (Nle = Norleucine), formylmethionylleucylphenylalanine, and peptide W revealed the same profile for FHL 124 cells, neutrophils, and FPR1-transfected HEK 293 cells. Saturation binding with fluorescein-labeled N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys revealed similar to 2500 specific binding sites on FHL-124 cells (K-D similar to 0.5 nM) versus similar to 40,000 sites on neutrophils (K-D = 3.2 nM). Moreover, formylmethionylleucylphenylalanine induced pertussis toxin-sensitive Ca2+ flux in FHL 124 cells, consistent with classic G(i)-mediated FPR1 signaling. FHL 124 cell FPR1 was atypical in that it resisted agonist-induced internalization. Expression of FPR1 was additionally supported by detection of the intact full-length open reading frame in sequenced cDNA from FHL 124 cells. Thus, FHL-124 cells express functional FPR1, which is consistent with a direct functional role for FPR1 in the lens, as suggested by the phenotype of Fpr1 knock-out mice.
C1 [Schneider, Erich H.; Weaver, Joseph D.; Gaur, Sonia S.; Gao, Ji-Liang; Murphy, Philip M.] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Tripathi, Brajendra K.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Jesaitis, Algirdas J.] Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA.
[Zelenka, Peggy S.] NEI, Sect Cellular Differentiat, Lab Mol & Dev Biol, NIH, Rockville, MD 20892 USA.
RP Murphy, PM (reprint author), NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bldg 10,Rm 11N113,10 Ctr Dr, Bethesda, MD 20892 USA.
EM pmm@nih.gov
RI Schneider, Erich/B-9051-2016
OI Schneider, Erich/0000-0002-7905-4276
FU Division of Intramural Research of the NIAID, National Institutes of
Health; German Research Foundation Grant [SCHN 1192/1-1]; Public Health
Service Grant [R01 AI22735]; Helmsley Senior Investigator Award from the
Crohn and Colitis Foundation
FX This work was supported, in whole or in part, by the Division of
Intramural Research of the NIAID, National Institutes of Health. This
work was also supported by German Research Foundation Grant SCHN
1192/1-1 (to E. H. S.).; Supported by Public Health Service Grant R01
AI22735 and a Helmsley Senior Investigator Award from the Crohn and
Colitis Foundation.
NR 44
TC 4
Z9 4
U1 0
U2 11
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 NOV 23
PY 2012
VL 287
IS 48
BP 40779
EP 40792
DI 10.1074/jbc.M112.411181
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 042CM
UT WOS:000311448800066
PM 23012360
ER
PT J
AU Fleischhacker, SE
Rodriguez, DA
Evenson, KR
Henley, A
Gizlice, Z
Soto, D
Ramachandran, G
AF Fleischhacker, Sheila E.
Rodriguez, Daniel A.
Evenson, Kelly R.
Henley, Amanda
Gizlice, Ziya
Soto, Dolly
Ramachandran, Gowri
TI Evidence for validity of five secondary data sources for enumerating
retail food outlets in seven American Indian Communities in North
Carolina
SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
LA English
DT Article
DE Food environment; Measurement; Ground-truth; Secondary data; Validity;
American Indian; Rurality; Global Positioning Systems (GPS); Geographic
Information Systems (GIS)
ID NUTRITION ENVIRONMENT MEASURES; AVAILABILITY; RESTAURANTS; OBESITY;
ACCESS; COST; DISPARITIES; PREVALENCE; VALIDATION; DATABASES
AB Background: Most studies on the local food environment have used secondary sources to describe the food environment, such as government food registries or commercial listings (e.g., Reference USA). Most of the studies exploring evidence for validity of secondary retail food data have used on-site verification and have not conducted analysis by data source (e.g., sensitivity of Reference USA) or by food outlet type (e.g., sensitivity of Reference USA for convenience stores). Few studies have explored the food environment in American Indian communities. To advance the science on measuring the food environment, we conducted direct, on-site observations of a wide range of food outlets in multiple American Indian communities, without a list guiding the field observations, and then compared our findings to several types of secondary data.
Methods: Food outlets located within seven State Designated Tribal Statistical Areas in North Carolina (NC) were gathered from online Yellow Pages, Reference USA, Dun & Bradstreet, local health departments, and the NC Department of Agriculture and Consumer Services. All TIGER/Line 2009 roads (>1,500 miles) were driven in six of the more rural tribal areas and, for the largest tribe, all roads in two of its cities were driven. Sensitivity, positive predictive value, concordance, and kappa statistics were calculated to compare secondary data sources to primary data.
Results: 699 food outlets were identified during primary data collection. Match rate for primary data and secondary data differed by type of food outlet observed, with the highest match rates found for grocery stores (97%), general merchandise stores (96%), and restaurants (91%). Reference USA exhibited almost perfect sensitivity (0.89). Local health department data had substantial sensitivity (0.66) and was almost perfect when focusing only on restaurants (0.91). Positive predictive value was substantial for Reference USA (0.67) and moderate for local health department data (0.49). Evidence for validity was comparatively lower for Dun & Bradstreet, online Yellow Pages, and the NC Department of Agriculture.
Conclusions: Secondary data sources both over- and under-represented the food environment; they were particularly problematic for identifying convenience stores and specialty markets. More attention is needed to improve the validity of existing data sources, especially for rural local food environments.
C1 [Fleischhacker, Sheila E.] NIH, Div Nutr Res Coordinat, US Dept HHS, Bethesda, MD 20892 USA.
[Rodriguez, Daniel A.] Coll Arts & Sci, Dept City & Reg Planning, Chapel Hill, NC 27514 USA.
[Evenson, Kelly R.] Bank Amer Ctr, Dept Epidemiol, Gillings Sch Global Publ Hlth, Ctr Hlth Promot & Dis Prevent, Chapel Hill, NC 27514 USA.
[Henley, Amanda] Walter Royal Davis Lib, Reference Dept, Chapel Hill, NC 27514 USA.
[Gizlice, Ziya] Ctr Hlth Promot & Dis Prevent, Biostat Support Unit, Chapel Hill, NC 27599 USA.
[Soto, Dolly] Ctr Hlth Promot & Dis Prevent, Chapel Hill, NC 27514 USA.
RP Fleischhacker, SE (reprint author), NIH, Div Nutr Res Coordinat, US Dept HHS, 2 Democracy Plaza,Room 635,6707 Democracy Blvd,MS, Bethesda, MD 20892 USA.
EM Sheila.fleischhacker@nih.gov
FU Coharie Tribe; Haliwa-Saponi Indian Tribe; Lumbee Tribe of North
Carolina; Meherrin Indian Tribe; Occaneechi Band of the Saponi Nation;
Sappony; Waccamaw Siouan Tribe; Healthy Eating Research; Robert Wood
Johnson Foundation (RWJF) [66958]; National Institutes of Health (NIH)
UNC Interdisciplinary Obesity Training [T 32 MH75854-03]
FX This project would not have been possible without the support from
Coharie Tribe, Haliwa-Saponi Indian Tribe, Lumbee Tribe of North
Carolina, Meherrin Indian Tribe, Occaneechi Band of the Saponi Nation,
Sappony, and Waccamaw Siouan Tribe. We acknowledge the NC Commission of
Indian Affairs. Joseph Sharkey provided invaluable guidance throughout
data collection and manuscript preparation. Research assistance was
provided by Ashley McPhail, Amy Ries, and John Scott-Richardson. We
acknowledge the resources provided by Carianne Jenkins while working at
the US Census Bureau, Melanie Moore of the NC Department of Agriculture
and Consumer Services, and 21 NC County Health Departments. Support for
this project was provided by Healthy Eating Research, a national program
of the Robert Wood Johnson Foundation (RWJF), ID # 66958 and a National
Institutes of Health (NIH) UNC Interdisciplinary Obesity Training Grant,
ID # T 32 MH75854-03. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
RWJF or NIH.
NR 50
TC 14
Z9 14
U1 1
U2 16
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5868
J9 INT J BEHAV NUTR PHY
JI Int. J. Behav. Nutr. Phys. Act.
PD NOV 22
PY 2012
VL 9
AR 137
DI 10.1186/1479-5868-9-137
PG 14
WC Nutrition & Dietetics; Physiology
SC Nutrition & Dietetics; Physiology
GA 076HT
UT WOS:000313947900001
PM 23173781
ER
PT J
AU Hofmann, JN
Liao, LM
Pollak, MN
Wang, Y
Pfeiffer, RM
Baris, D
Andreotti, G
Lan, Q
Landgren, O
Rothman, N
Purdue, MP
AF Hofmann, Jonathan N.
Liao, Linda M.
Pollak, Michael N.
Wang, Ye
Pfeiffer, Ruth M.
Baris, Dalsu
Andreotti, Gabriella
Lan, Qing
Landgren, Ola
Rothman, Nathaniel
Purdue, Mark P.
TI A prospective study of circulating adipokine levels and risk of multiple
myeloma
SO BLOOD
LA English
DT Article
ID CANCER SCREENING TRIAL; GROWTH-FACTOR; UNDETERMINED SIGNIFICANCE;
MONOCLONAL GAMMOPATHY; ADIPOSE-TISSUE; ADIPONECTIN; OBESITY; ACTIVATION;
EXPRESSION; PROSTATE
AB It has been hypothesized that the observed excess risk of multiple myeloma (MM) among obese persons could be the result of altered circulating levels of adipokines, polypeptide hormones with pro- and anti-inflammatory properties secreted by adipose tissue. We investigated whether circulating levels of leptin, total adiponectin, and high molecular weight adiponectin are associated with subsequent MM risk among 174 MM patients and 348 controls within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Inverse associations with MM were observed for total adiponectin (highest quartile vs lowest: odds ratio = 0.49; 95% CI = 0.26-0.93, P-trend = .03) and high molecular weight adiponectin (0.44; 0.23-0.85, P-trend = .01). These associations remained after restricting to MM patients diagnosed similar to 8 years or more after blood collection. Leptin levels were not associated with MM risk. The results of this study, to our knowledge the first prospective investigation of circulating adipokines and MM, suggest that adiponectin may play an important role in obesity-related myelomagenesis. (Blood. 2012;120(22):4418-4420)
C1 [Hofmann, Jonathan N.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Pollak, Michael N.; Wang, Ye] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.
[Landgren, Ola] NCI, Multiple Myeloma Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Hofmann, JN (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA.
EM hofmannjn@mail.nih.gov
RI Purdue, Mark/C-9228-2016;
OI Purdue, Mark/0000-0003-1177-3108; Liao, Linda/0000-0002-1923-5294
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics; Division of Cancer Prevention, National Cancer Institute,
National Institutes of Health, Department of Health and Human Services
FX This work was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics and by contracts from the
Division of Cancer Prevention, National Cancer Institute, National
Institutes of Health, Department of Health and Human Services.
NR 20
TC 20
Z9 20
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD NOV 22
PY 2012
VL 120
IS 22
BP 4418
EP 4420
DI 10.1182/blood-2012-06-438606
PG 3
WC Hematology
SC Hematology
GA 064YK
UT WOS:000313111300024
PM 23007407
ER
PT J
AU Jumbo-Lucioni, P
Bu, S
Harbison, ST
Slaughter, JC
Mackay, TFC
Moellering, DR
De Luca, M
AF Jumbo-Lucioni, Patricia
Bu, Su
Harbison, Susan T.
Slaughter, Juanita C.
Mackay, Trudy F. C.
Moellering, Douglas R.
De Luca, Maria
TI Nuclear genomic control of naturally occurring variation in
mitochondrial function in Drosophila melanogaster
SO BMC GENOMICS
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; BROWN ADIPOSE-TISSUE;
OXIDATIVE-PHOSPHORYLATION; SIGNAL-TRANSDUCTION; ELECTRON-TRANSPORT;
PROTON CONDUCTANCE; INSULIN-RESISTANCE; ENERGY-METABOLISM;
GENETIC-VARIATION; SYSTEMS GENETICS
AB Background: Mitochondria are organelles found in nearly all eukaryotic cells that play a crucial role in cellular survival and function. Mitochondrial function is under the control of nuclear and mitochondrial genomes. While the latter has been the focus of most genetic research, we remain largely ignorant about the nuclear-encoded genomic control of inter-individual variability in mitochondrial function. Here, we used Drosophila melanogaster as our model organism to address this question.
Results: We quantified mitochondrial state 3 and state 4 respiration rates and P:O ratio in mitochondria isolated from the thoraces of 40 sequenced inbred lines of the Drosophila Genetic Reference Panel. We found significant within-population genetic variability for all mitochondrial traits. Hence, we performed genome-wide association mapping and identified 141 single nucleotide polymorphisms (SNPs) associated with differences in mitochondrial respiration and efficiency (P <= 1 x 10(-5)). Gene-centered regression models showed that 2-3 SNPs can explain 31, 13, and 18% of the phenotypic variation in state 3, state 4, and P: O ratio, respectively. Most of the genes tagged by the SNPs are involved in organ development, second messenger-mediated signaling pathways, and cytoskeleton remodeling. One of these genes, sallimus (s/s), encodes a component of the muscle sarcomere. We confirmed the direct effect of s/s on mitochondrial respiration using two viable mutants and their coisogenic wild-type strain. Furthermore, correlation network analysis revealed that s/s functions as a transcriptional hub in a co-regulated module associated with mitochondrial respiration and is connected to CG7834, which is predicted to encode a protein with mitochondrial electron transfer flavoprotein activity. This latter finding was also verified in the s/s mutants.
Conclusions: Our results provide novel insights into the genetic factors regulating natural variation in mitochondrial function in D. melanogaster. The integrative genomic approach used in our study allowed us to identify s/s as a novel hub gene responsible for the regulation of mitochondrial respiration in muscle sarcomere and to provide evidence that s/s might act via the electron transfer flavoprotein/ubiquinone oxidoreductase complex.
C1 [Jumbo-Lucioni, Patricia; Bu, Su; Slaughter, Juanita C.; Moellering, Douglas R.; De Luca, Maria] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Harbison, Susan T.] NHLBI, Lab Syst Genet, Bethesda, MD 20892 USA.
[Mackay, Trudy F. C.] N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA.
RP Moellering, DR (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
EM dmoellering@uab.edu; mdeluca2@uab.edu
RI Harbison, Susan/P-2577-2016;
OI Harbison, Susan/0000-0001-7233-0947; De Luca, Maria/0000-0001-6345-7508
FU BARB Core/Diabetes Research Training Center NIDDK [P60 DK079626];
Diabetes Research Training Center; NIH [R01 GM45146, R01 DK084219]
FX We thank Michelle Moses Chambers for help with Drosophila husbandry
procedures. We also thank Dr. David Rand and an anonymous reviewer for
proving insightful comments on the manuscript. We are enormously
grateful to Dr. Carlos Krumdieck for designing and making available the
motorized micro-mortar used for the mitochondrial assays. This study was
supported by a BARB Core/Diabetes Research Training Center NIDDK Grant
P60 DK079626, Diabetes Research Training Center Pilot Feasibility grant
to DRM, and NIH Grants R01 GM45146 to TFCM and R01 DK084219 to MD.
NR 90
TC 6
Z9 6
U1 1
U2 24
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 NOV 22
PY 2012
VL 13
AR 659
DI 10.1186/1471-2164-13-659
PG 15
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 059XF
UT WOS:000312738200001
PM 23171078
ER
PT J
AU Corso-Diaz, X
Borrie, AE
Bonaguro, R
Schuetz, JM
Rosenberg, T
Jensen, H
Brooks, BP
MacDonald, IM
Pasutto, F
Walter, MA
Gronskov, K
Brooks-Wilson, A
Simpson, EM
AF Corso-Diaz, Ximena
Borrie, Adrienne E.
Bonaguro, Russell
Schuetz, Johanna M.
Rosenberg, Thomas
Jensen, Hanne
Brooks, Brian P.
MacDonald, Ian M.
Pasutto, Francesca
Walter, Michael A.
Gronskov, Karen
Brooks-Wilson, Angela
Simpson, Elizabeth M.
TI Absence of NR2E1 mutations in patients with aniridia
SO MOLECULAR VISION
LA English
DT Article
ID NUCLEAR RECEPTOR TLX; PETERS PLUS SYNDROME; S-CONE-SYNDROME; RETINOIC
ACID; PAX6 MUTATIONS; OPTIC CUP; GENE; EYE; MALFORMATIONS; TAILLESS
AB Purpose: Nuclear receptor 2E1 (NR2E1) is a transcription factor with many roles during eye development and thus may be responsible for the occurrence of certain congenital eye disorders in humans. To test this hypothesis, we screened NR2E1 for candidate mutations in patients with aniridia and other congenital ocular malformations (anterior segment dysgenesis, congenital optic nerve malformation, and microphthalmia).
Methods: The NR2E1 coding region, 5' and 3' untranslated regions (UTRs), exon flanking regions including consensus splice sites, and six evolutionarily conserved non-coding candidate regulatory regions were analyzed by sequencing 58 probands with aniridia of whom 42 were negative for PAX6 mutations. Nineteen probands with anterior segment dysgenesis, one proband with optic nerve malformation, and two probands with microphthalmia were also sequenced. The control population comprised 376 healthy individuals. All sequences were analyzed against the GenBank sequence AL078596.8 for NR2E1. In addition, the coding region and flanking intronic sequences of FOXE3, FOXC1, PITX2, CYP1B1, PAX6, and B3GALTL were sequenced in one patient and his relatives.
Results: Sequencing analysis showed 17 NR2E1 variants including two novel rare non-coding variants (g.-1507G>A, g.14258C>T), and one novel rare coding variant (p.Arg274Gly). The latter was present in a male diagnosed with Peters' anomaly who subsequently was found to have a known causative mutation for Peters' plus syndrome in B3GALTL (c.660+1G>A). In addition, the NR2E1 novel rare variant Arg274Gly was present in the unaffected mother of the patient but absent in 746 control chromosomes.
Conclusions: We eliminated a major role for NR2E1 regulatory and coding mutations in aniridia and found a novel rare coding variant in NR2E1. In addition, we found no coding region variation in the control population for NR2E1, which further supports its previously reported high level of conservation and low genetic diversity. Future NR2E1 studies in ocular disease groups such as those involving retinal and optic nerve abnormalities should be undertaken to determine whether NR2E1 plays a role in these conditions.
C1 [Corso-Diaz, Ximena; Borrie, Adrienne E.; Bonaguro, Russell; Simpson, Elizabeth M.] Univ British Columbia, Child & Family Res Inst, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada.
[Corso-Diaz, Ximena; Simpson, Elizabeth M.] Univ British Columbia, Grad Program Genet, Vancouver, BC V5Z 4H4, Canada.
[Borrie, Adrienne E.; Schuetz, Johanna M.; Brooks-Wilson, Angela; Simpson, Elizabeth M.] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 4H4, Canada.
[Schuetz, Johanna M.; Brooks-Wilson, Angela] BC Canc Agcy, Canadas Michael Smiths Genome Sci Ctr, Vancouver, BC, Canada.
[Rosenberg, Thomas; Jensen, Hanne] Kennedy Ctr, Natl Eye Clin Visually Impaired, Glostrup, Denmark.
[Jensen, Hanne] Univ Copenhagen, Glostrup Hosp, Dept Ophthalmol, Glostrup, Denmark.
[Brooks, Brian P.] NEI, NIH, Bethesda, MD 20892 USA.
[MacDonald, Ian M.] Univ Alberta, Dept Ophthalmol, Edmonton, AB, Canada.
[Pasutto, Francesca] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany.
[Walter, Michael A.] Univ Alberta, Dept Med Genet, Edmonton, AB, Canada.
[Gronskov, Karen] Rigshosp, Ctr Appl Human Mol Genet, Kennedy Ctr, Glostrup, Denmark.
[Gronskov, Karen] Univ Copenhagen, Fac Hlth Sci, Inst Cellular & Mol Med, Copenhagen, Denmark.
[Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
[Simpson, Elizabeth M.] Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 4H4, Canada.
RP Simpson, EM (reprint author), Univ British Columbia, Child & Family Res Inst, Ctr Mol Med & Therapeut, 980 W 28th Ave, Vancouver, BC V5Z 4H4, Canada.
EM simpson@cmmt.ubc.ca
RI Brooks-Wilson, Angela/E-9399-2012;
OI Brooks-Wilson, Angela/0000-0003-1009-6408; MacDonald,
Ian/0000-0001-7472-8385
FU Sharon Stewart Aniridia Research Award
FX The authors thank Dr. Veronica Van Heyningen (Human Genet. Unit, Med.
Res. Council, Edinburgh, UK) for providing DNA samples, and Dr. Valerie
Anne Wallace (Faculty of Medicine, University of Ottawa, ON, Canada) for
providing training to AB. Importantly, the authors also thank the
patients and their families for the kind donation of their time and DNA.
This work was funded by a Sharon Stewart Aniridia Research Award to EMS.
The authors indicate no financial conflict of interest.
NR 59
TC 3
Z9 3
U1 0
U2 3
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD NOV 22
PY 2012
VL 18
IS 283-86
BP 2770
EP 2782
PG 13
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 053AL
UT WOS:000312241700002
PM 23213277
ER
PT J
AU Lynch, PA
Grimm, U
Thomas, MB
Read, AF
AF Lynch, Penelope A.
Grimm, Uwe
Thomas, Matthew B.
Read, Andrew F.
TI Prospective malaria control using entomopathogenic fungi: comparative
evaluation of impact on transmission and selection for resistance
SO MALARIA JOURNAL
LA English
DT Article
ID ANOPHELES-GAMBIAE; METARHIZIUM-ANISOPLIAE; INSECTICIDE RESISTANCE;
SCORPION NEUROTOXIN; BEAUVERIA-BASSIANA; BIOCONTROL AGENTS; MOSQUITOS;
INFECTION; MODEL; PARASITES
AB Background: Chemical insecticides against adult mosquitoes are a key element in most malaria management programmes, but their efficacy is threatened by the evolution of insecticide-resistant mosquitoes. By killing only older mosquitoes, entomopathogenic fungi can in principle significantly impact parasite transmission while imposing much less selection for resistance. Here an assessment is made as to which of the wide range of possible virulence characteristics for fungal biopesticides best realise this potential.
Methods: With mathematical models that capture relevant timings and survival probabilities within successive feeding cycles, transmission and resistance-management metrics are used to compare susceptible and resistant mosquitoes exposed to no intervention, to conventional instant-kill interventions, and to delayed-action biopesticides with a wide range of virulence characteristics.
Results: Fungal biopesticides that generate high rates of mortality at around the time mosquitoes first become able to transmit the malaria parasite offer potential for large reductions in transmission while imposing low fitness costs. The best combinations of control and resistance management are generally accessed at high levels of coverage. Strains which have high virulence in malaria-infected mosquitoes but lower virulence in malaria-free mosquitoes offer the ultimate benefit in terms of minimizing selection pressure whilst maximizing impact on transmission. Exploiting this phenotype should be a target for product development. For indoor residual spray programmes, biopesticides may offer substantial advantages over the widely used pyrethroid-based insecticides. Not only do fungal biopesticides provide substantial resistance management gains in the long term, they may also provide greater reductions in transmission before resistance has evolved. This is because fungal spores do not have contact irritancy, reducing the chances that a blood-fed mosquito can survive an encounter and thus live long enough to transmit malaria.
Conclusions: Delayed-action products, such as fungal biopesticides, have the potential to achieve reductions in transmission comparable with those achieved with existing instant-kill insecticides, and to sustain this control for substantially longer once resistant alleles arise. Given the current insecticide resistance crisis, efforts should continue to fully explore the operational feasibility of this alternative approach.
C1 [Thomas, Matthew B.; Read, Andrew F.] Penn State Univ, Dept Entomol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Read, Andrew F.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Read, Andrew F.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
EM pennymath@lynch-fm.demon.co.uk
RI Grimm, Uwe/E-5351-2010;
OI Grimm, Uwe/0000-0001-5492-7467; Lynch, Penelope/0000-0002-0486-8507
FU National Institute for Allergy and Infectious Disease [R21 AI088094]
FX We thank S Blanford for beautiful survival curves, members of the
Research and Policy in Infectious Disease Dynamics Program of the
Science and Technology Directorate, Department of Homeland Security and
the Fogarty International Center, National Institutes of Health for
discussion, and T Ayerst for patience, encouragement and support. This
work was supported by a grant (R21 AI088094) from the National Institute
for Allergy and Infectious Disease.
NR 44
TC 10
Z9 12
U1 2
U2 45
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD NOV 22
PY 2012
VL 11
AR 383
DI 10.1186/1475-2875-11-383
PG 15
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 050XW
UT WOS:000312089200001
PM 23171286
ER
PT J
AU Ouyang, WM
Liao, W
Luo, CT
Yin, N
Huse, M
Kim, MV
Peng, M
Chan, P
Ma, Q
Mo, YF
Meijer, D
Zhao, KJ
Rudensky, AY
Atwal, G
Zhang, MQ
Li, MO
AF Ouyang, Weiming
Liao, Will
Luo, Chong T.
Yin, Na
Huse, Morgan
Kim, Myoungjoo V.
Peng, Min
Chan, Pamela
Ma, Qian
Mo, Yifan
Meijer, Dies
Zhao, Keji
Rudensky, Alexander Y.
Atwal, Gurinder
Zhang, Michael Q.
Li, Ming O.
TI Novel Foxo1-dependent transcriptional programs control T-reg cell
function
SO NATURE
LA English
DT Article
ID FOXP3 EXPRESSION; GENE-EXPRESSION; TARGET GENES; DIFFERENTIATION; FOXO1;
TOOL; AKT; MECHANISMS; INDUCTION; PROFILES
AB Regulatory T (T-reg) cells, characterized by expression of the transcription factor forkhead box P3 (Foxp3), maintain immune homeostasis by suppressing self-destructive immune responses(1-4). Foxp3 operates as a late-acting differentiation factor controlling T-reg cell homeostasis and function(5), whereas the early T-reg-cell-lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors(6-10). However, whether Foxo proteins act beyond the T-reg-cell-commitment stage to control T-reg cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of T-reg cell function. T-reg cells express high amounts of Foxo1 and display reduced T-cell-receptor-induced Akt activation, Foxo1 phosphorylation and Foxo1 nuclear exclusion. Mice with T-reg-cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to that seen in Foxp3-deficient mice, but without the loss of T-reg cells. Genome-wide analysis of Foxo1 binding sites reveals similar to 300 Foxo1-bound target genes, including the pro-inflammatory cytokine Ifng, that do not seem to be directly regulated by Foxp3. These findings show that the evolutionarily ancient Akt-Foxo1 signalling module controls a novel genetic program indispensable for T-reg cell function.
C1 [Ouyang, Weiming; Luo, Chong T.; Yin, Na; Huse, Morgan; Kim, Myoungjoo V.; Peng, Min; Chan, Pamela; Ma, Qian; Rudensky, Alexander Y.; Li, Ming O.] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA.
[Liao, Will; Mo, Yifan; Atwal, Gurinder] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
[Liao, Will; Mo, Yifan] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA.
[Luo, Chong T.] Mem Sloan Kettering Canc Ctr, Louis V Gerstner Jr Grad Sch Biomed Sci, New York, NY 10065 USA.
[Meijer, Dies] Erasmus Univ, Med Ctr, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands.
[Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA.
[Zhang, Michael Q.] Univ Texas Dallas, Ctr Syst Biol, Dept Mol & Cell Biol, Richardson, TX 75080 USA.
[Zhang, Michael Q.] Tsinghua Univ, TNLIST, Ctr Synthet & Syst Biol, Bioinformat Div, Beijing 100084, Peoples R China.
RP Li, MO (reprint author), Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA.
EM mzhang@cshl.edu; lim@mskcc.org
OI Luo, Chong/0000-0002-3477-5969
FU Starr Cancer Consortium [13-A123]; Rita Allen Foundation; National Bio
Resource Project (NBRPC) [2012CB316503]; National Institutes of Health
[HG001696]
FX We thank R. Flavell for the Foxp3-IRES-RFP mouse strain, K. Rajewsky and
C. Xiao for the Rosa26 targeting vector and T. Unterman for the
HA-hFoxo1(AAA) construct. This work was supported by the Starr Cancer
Consortium (13-A123 to M.O.L., M.Q.Z. and G. A.), the Rita Allen
Foundation (M.O.L.), National Bio Resource Project (NBRPC) (2012CB316503
to M.Q.Z.) and National Institutes of Health (HG001696 to M.Q.Z.).
NR 44
TC 116
Z9 118
U1 6
U2 41
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 NOV 22
PY 2012
VL 491
IS 7425
BP 554
EP +
DI 10.1038/nature11581
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800043
PM 23135404
ER
EF