FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Rajesh, M
Mukhopadhyay, P
Batkai, S
Patel, V
Saito, K
Matsumoto, S
Kashiwaya, Y
Horvath, B
Mukhopadhyay, B
Becker, L
Hasko, G
Liaudet, L
Wink, DA
Veves, A
Mechoulam, R
Pacher, P
AF Rajesh, Mohanraj
Mukhopadhyay, Partha
Batkai, Sandor
Patel, Vivek
Saito, Keita
Matsumoto, Shingo
Kashiwaya, Yoshihiro
Horvath, Bela
Mukhopadhyay, Bani
Becker, Lauren
Hasko, Gyoergy
Liaudet, Lucas
Wink, David A.
Veves, Aristidis
Mechoulam, Raphael
Pacher, Pal
TI Cannabidiol Attenuates Cardiac Dysfunction, Oxidative Stress, Fibrosis,
and Inflammatory and Cell Death Signaling Pathways in Diabetic
Cardiomyopathy
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE cannabinoids; diabetic complications; inflammation; oxidative stress
ID NF-KAPPA-B; ENDOCANNABINOID SYSTEM; MITOCHONDRIAL; PROTECTS; DISEASE;
METALLOTHIONEIN; CANNABINOIDS; CONSTITUENT; INHIBITION; ANTAGONISM
AB Objectives In this study, we have investigated the effects of cannabidiol (CBD) on myocardial dysfunction, inflammation, oxidative/nitrative stress, cell death, and interrelated signaling pathways, using a mouse model of type I diabetic cardiomyopathy and primary human cardiomyocytes exposed to high glucose.
Background Cannabidiol, the most abundant nonpsychoactive constituent of Cannabis sativa (marijuana) plant, exerts anti-inflammatory effects in various disease models and alleviates pain and spasticity associated with multiple sclerosis in humans.
Methods Left ventricular function was measured by the pressure-volume system. Oxidative stress, cell death, and fibrosis markers were evaluated by molecular biology/biochemical techniques, electron spin resonance spectroscopy, and flow cytometry.
Results Diabetic cardiomyopathy was characterized by declined diastolic and systolic myocardial performance associated with increased oxidative-nitrative stress, nuclear factor-kappa B and mitogen-activated protein kinase (c-Jun N-terminal kinase, p-38, p38 alpha) activation, enhanced expression of adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1), tumor necrosis factor-alpha, markers of fibrosis (transforming growth factor-beta, connective tissue growth factor, fibronectin, collagen-1, matrix metalloproteinase-2 and -9), enhanced cell death (caspase 3/7 and poly[adenosine diphosphate-ribose] polymerase activity, chromatin fragmentation, and terminal deoxynucleotidyl transferase dUTP nick end labeling), and diminished Akt phosphorylation. Remarkably, CBD attenuated myocardial dysfunction, cardiac fibrosis, oxidative/nitrative stress, inflammation, cell death, and interrelated signaling pathways. Furthermore, CBD also attenuated the high glucose-induced increased reactive oxygen species generation, nuclear factor-kappa B activation, and cell death in primary human cardiomyocytes.
Conclusions Collectively, these results coupled with the excellent safety and tolerability profile of CBD in humans, strongly suggest that it may have great therapeutic potential in the treatment of diabetic complications, and perhaps other cardiovascular disorders, by attenuating oxidative/nitrative stress, inflammation, cell death and fibrosis. (J Am Coll Cardiol 2010;56:2115-25) (C) 2010 by the American College of Cardiology Foundation
C1 [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
[Kashiwaya, Yoshihiro] NIAAA, Lab Metab Control, NIH, Bethesda, MD 20892 USA.
[Saito, Keita; Matsumoto, Shingo; Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
[Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA.
[Liaudet, Lucas] Univ Lausanne Hosp, Dept Intens Care Med, Lausanne, Switzerland.
[Veves, Aristidis] Harvard Univ, Sch Med, Microcirculat Lab, Boston, MA USA.
[Veves, Aristidis] Harvard Univ, Beth Israel Deaconess Med Ctr, Joslin Beth Israel Deaconess Foot Ctr, Sch Med, Boston, MA 02215 USA.
[Mechoulam, Raphael] Hebrew Univ Jerusalem, Dept Med Chem & Nat Prod, Fac Med, Jerusalem, Israel.
RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA.
EM pacher@mail.nih.gov
RI Horvath, Bela/A-7368-2009; Batkai, Sandor/G-3889-2010; MUKHOPADHYAY,
PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014;
Liaudet, Lucas/E-1322-2017
OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher,
Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930
FU NIH/NIAAA; NIDA [DA9789]; Hungarian Research Council (EU) [MB08 80238];
Novartis
FX This study was supported by the Intramural Research Program of the
NIH/NIAAA (to Dr. Pacher) and NIDA Grant DA9789 (to Dr. Mechoulam). Dr.
Horvath is a recipient of a Hungarian Research Council Scientific
Research Fund Fellowship (NKTH OTKA EU, MB08 80238). Dr. Veves receives
funding from Novartis for an investigator-initiated research grant,
unrelated to this study. Dr. Mechoulam is a consultant for GW
Pharmaceuticals, United Kingdom, which is not involved in this
publication and is unaware of it. All other authors have reported that
they have no relationships to disclose.
NR 33
TC 101
Z9 105
U1 4
U2 38
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD DEC 14
PY 2010
VL 56
IS 25
BP 2115
EP 2125
DI 10.1016/j.jacc.2010.07.033
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 691MI
UT WOS:000285084000011
PM 21144973
ER
PT J
AU Qiu, C
Cotch, MF
Sigurdsson, S
Jonsson, PV
Jonsdottir, MK
Sveinbjornsdottir, S
Eiriksdottir, G
Klein, R
Harris, TB
van Buchem, MA
Gudnason, V
Launer, LJ
AF Qiu, C.
Cotch, M. F.
Sigurdsson, S.
Jonsson, P. V.
Jonsdottir, M. K.
Sveinbjornsdottir, S.
Eiriksdottir, G.
Klein, R.
Harris, T. B.
van Buchem, M. A.
Gudnason, V.
Launer, L. J.
TI Cerebral microbleeds, retinopathy, and dementia The AGES-Reykjavik Study
SO NEUROLOGY
LA English
DT Article
ID GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK; RETINAL MICROVASCULAR
ABNORMALITIES; WHITE-MATTER LESIONS; COGNITIVE IMPAIRMENT;
CARDIOVASCULAR HEALTH; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA;
ROTTERDAM-SCAN; PREVALENCE; DECLINE
AB Objective: To determine whether microvascular damage, indicated by cerebral microbleeds (CMBs) and retinal microvascular signs, is associated with cognitive function and dementia in older persons.
Methods: This is a cross-sectional study of 3,906 participants (mean age 76 years; 58% women) in the AGES-Reykjavik Study (2002-2006). We assessed CMBs on MRI and retinal microvascular signs on digital retinal images. Composite Z scores of memory, processing speed, and executive function were derived from a battery of neurocognitive tests. Dementia and subtypes were diagnosed following international criteria. Regression models were used to relate cognitive Z scores and dementia to CMBs and retinal microvascular signs, adjusting for demographics, cardiovascular factors, and brain ischemic lesions.
Results: People with multiple (>= 2) CMBs had lower Z scores on tests of processing speed (beta-coefficient -0.16; 95% confidence interval -0.26 to -0.05) and executive function (-0.14; -0.24 to -0.04); results were strongest for having multiple CMBs located in the deep hemispheric or infratentorial areas. The odds ratio of vascular dementia was 2.32 (95% confidence interval 1.02 to 5.25) for multiple CMBs and 1.95 (1.04 to 3.62) for retinopathy. Having both CMBs and retinopathy, compared to having neither, was significantly associated with markedly slower processing speed (-0.25; -0.37 to -0.12), poorer executive function (-0.19; -0.31 to -0.07), and an increased odds ratio of vascular dementia (3.10; 1.11 to 8.62).
Conclusion: Having multiple CMBs or concomitant CMBs and retinopathy is associated with a profile of vascular cognitive impairment. These findings suggest that microvascular damage, as indicated by CMBs and retinopathy lesions, has functional consequences in older men and women living in the community. Neurology (R) 2010;75:2221-2228
C1 [Qiu, C.] Karolinska Inst, Aging Res Ctr, Dept Neurobiol Care Sci & Soc, S-11330 Stockholm, Sweden.
[Qiu, C.; Harris, T. B.; Launer, L. J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Cotch, M. F.] NEI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
[Sigurdsson, S.; Jonsson, P. V.; Jonsdottir, M. K.; Eiriksdottir, G.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland.
[Jonsson, P. V.; Jonsdottir, M. K.; Sveinbjornsdottir, S.] Landspitali Univ Hosp, Reykjavik, Iceland.
[Jonsson, P. V.; Gudnason, V.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Jonsdottir, M. K.] Univ Iceland, Fac Psychol, Reykjavik, Iceland.
[Klein, R.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol, Madison, WI USA.
[van Buchem, M. A.] Leiden Univ, Dept Radiol, Med Ctr, Leiden, Netherlands.
RP Qiu, C (reprint author), Karolinska Inst, Aging Res Ctr, Dept Neurobiol Care Sci & Soc, Gavlegatan 16, S-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
FU NIH [N01-AG-12100, ZIAEY000401, NEI 2 U10 EY006594-21A1, NEI 1 R01
HL6997, NEI 1 R01 EY016379, 1 R01 DK073217-01]; National Institute on
Aging; National Eye Institute [ZIAEY000401]; NIH, USA; Icelandic Heart
Association; Icelandic Parliament, Iceland; Swedish Council for Working
Life and Social Research for the Future Leaders on Ageing Research in
Europe (FLARE) [2007-1728, 2009-1934]; Swedish Research Council
[K2008-69X-20821-01-3]
FX Study funding: The AGES-Reykjavik Study was funded by NIH contract
N01-AG-12100, the Intramural Research Program of the National Institute
on Aging, the National Eye Institute (ZIAEY000401), NIH, USA, and the
Icelandic Heart Association and the Icelandic Parliament, Iceland.; Dr.
Qiu serves as an Associate Editor for the Journal of Alzheimer's Disease
and receives research support from the Swedish Council for Working Life
and Social Research for the Future Leaders on Ageing Research in Europe
(FLARE) Program (2007-1728 and 2009-1934) and the Swedish Research
Council (K2008-69X-20821-01-3 [PI]). Dr. Cotch receives research support
from the Intramural Research Program of the NIH (ZIAEY000401). S.
Sigurdsson, Dr. Jonsson, Dr. Jonsdottir, Dr. Sveinbjornsdottir, and G.
Eiriksdottir report no disclosures. Dr. Klein serves on a scientific
advisory board for AstraZeneca; serves on the editorial board of
Ophthalmology; has served/serves as a consultant for Pfizer Inc., Eli
Lilly and Company, Novartis, Genentech Inc., CoMentis, Inc., Allergan,
Inc., and Merck Serono; and has received/receives research support from
the NIH (NEI 2 U10 EY006594-21A1 [PI], NEI 1 R01 HL6997 [PI], NEI 1 R01
EY016379 [PI], 1 R01 DK073217-01 [PI], and N01-AG-12100 [PI]). Dr.
Harris serves on the editorial boards of the Journal of Gerontology:
Medical Sciences, Age and Nutrition, and Ageing: Clinical and Geriatric
Science. Dr. van Buchem reports no disclosures. Dr. Gudnason receives
research support from the NIH (N01-AG-12100 [PI]) and the Icelandic
Heart Association. Dr. Launer reports no disclosures.
NR 40
TC 80
Z9 85
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD DEC 14
PY 2010
VL 75
IS 24
BP 2221
EP 2228
DI 10.1212/WNL.0b013e3182020349
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 694JJ
UT WOS:000285292700016
PM 21172845
ER
PT J
AU Gill, DK
Huang, YD
Levine, GL
Sambor, A
Carter, DK
Sato, A
Kopycinski, J
Hayes, P
Hahn, B
Birungi, J
Tarragona-Fiol, T
Wan, H
Randles, M
Cooper, AR
Ssemaganda, A
Clark, L
Kaleebu, P
Self, SG
Koup, R
Wood, B
McElrath, MJ
Cox, JH
Hural, J
Gilmour, J
AF Gill, Dilbinder K.
Huang, Yunda
Levine, Gail L.
Sambor, Anna
Carter, Donald K.
Sato, Alicia
Kopycinski, Jakub
Hayes, Peter
Hahn, Bridget
Birungi, Josephine
Tarragona-Fiol, Tony
Wan, Hong
Randles, Mark
Cooper, Andrew Raxworthy
Ssemaganda, Aloysius
Clark, Lorna
Kaleebu, Pontiano
Self, Steven G.
Koup, Richard
Wood, Blake
McElrath, M. Juliana
Cox, Josephine H.
Hural, John
Gilmour, Jill
TI Equivalence of ELISpot Assays Demonstrated between Major HIV Network
Laboratories
SO PLOS ONE
LA English
DT Article
ID VACCINE TRIALS; CELL; IMMUNITY; PROFICIENCY; RESPONSES; ENTERPRISE;
CANCER; PANEL
AB Background: The Comprehensive T Cell Vaccine Immune Monitoring Consortium (CTC-VIMC) was created to provide standardized immunogenicity monitoring services for HIV vaccine trials. The ex vivo interferon-gamma (IFN-gamma) ELISpot is used extensively as a primary immunogenicity assay to assess T cell-based vaccine candidates in trials for infectious diseases and cancer. Two independent, GCLP-accredited central laboratories of CTC-VIMC routinely use their own standard operating procedures (SOPs) for ELISpot within two major networks of HIV vaccine trials. Studies are imperatively needed to assess the comparability of ELISpot measurements across laboratories to benefit optimal advancement of vaccine candidates.
Methods: We describe an equivalence study of the two independently qualified IFN-g ELISpot SOPs. The study design, data collection and subsequent analysis were managed by independent statisticians to avoid subjectivity. The equivalence of both response rates and positivity calls to a given stimulus was assessed based on pre-specified acceptance criteria derived from a separate pilot study.
Findings: Detection of positive responses was found to be equivalent between both laboratories. The 95% C. I. on the difference in response rates, for CMV (-1.5%, 1.5%) and CEF (-0.4%, 7.8%) responses, were both contained in the pre-specified equivalence margin of interval [ -15%, 15%]. The lower bound of the 95% C. I. on the proportion of concordant positivity calls for CMV (97.2%) and CEF (89.5%) were both greater than the pre-specified margin of 70%. A third CTC-VIMC central laboratory already using one of the two SOPs also showed comparability when tested in a smaller sub-study.
Interpretation: The described study procedure provides a prototypical example for the comparison of bioanalytical methods in HIV vaccine and other disease fields. This study also provides valuable and unprecedented information for future vaccine candidate evaluations on the comparison and pooling of ELISpot results generated by the CTC-VIMC central core laboratories.
C1 [Gill, Dilbinder K.; Kopycinski, Jakub; Hayes, Peter; Tarragona-Fiol, Tony; Cooper, Andrew Raxworthy; Clark, Lorna] Univ London Imperial Coll Sci Technol & Med, Int AIDS Vaccine Initiat Human Immunol Lab, London, England.
[Huang, Yunda; Sato, Alicia; Self, Steven G.; Wood, Blake] Stat Ctr HIV AIDS Res & Prevent, Seattle, WA USA.
[Levine, Gail L.; Sambor, Anna] Fdn Natl Inst Hlth, Bethesda, MD USA.
[Carter, Donald K.; Hahn, Bridget; McElrath, M. Juliana; Hural, John] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Birungi, Josephine; Ssemaganda, Aloysius; Kaleebu, Pontiano] Uganda Virus Res Inst, Entebbe, Uganda.
[Wan, Hong; Randles, Mark; Cox, Josephine H.; Gilmour, Jill] Int AIDS Vaccine Initiat, New York, NY USA.
[Koup, Richard] Vaccine Res Ctr, Bethesda, MD USA.
RP Gill, DK (reprint author), Univ London Imperial Coll Sci Technol & Med, Int AIDS Vaccine Initiat Human Immunol Lab, London, England.
EM d.gill@imperial.ac.uk
FU Bill & Melinda Gates Foundation [38650]
FX This work was supported by the Collaboration for AIDS Vaccine Discovery
(CAVD) Grant 38650 from the Bill & Melinda Gates Foundation. The Bill &
Melinda Gates Foundation had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 24
TC 15
Z9 16
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 14
PY 2010
VL 5
IS 12
AR e14330
DI 10.1371/journal.pone.0014330
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 694JH
UT WOS:000285292500008
PM 21179404
ER
PT J
AU Xu, XM
Turanov, AA
Carlson, BA
Yoo, MH
Everley, RA
Nandakumar, R
Sorokina, I
Gygi, SP
Gladyshev, VN
Hatfield, DL
AF Xu, Xue-Ming
Turanov, Anton A.
Carlson, Bradley A.
Yoo, Min-Hyuk
Everley, Robert A.
Nandakumar, Renu
Sorokina, Irina
Gygi, Steven P.
Gladyshev, Vadim N.
Hatfield, Dolph L.
TI Targeted insertion of cysteine by decoding UGA codons with mammalian
selenocysteine machinery
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE de novo synthesis; new biosynthetic pathway; selenium deficiency
ID THIOREDOXIN REDUCTASE; SELENOPROTEIN SYNTHESIS; ESCHERICHIA-COLI;
GENETIC-CODE; SELENIUM; PURIFICATION; EUKARYOTES; KINASE; FORMS; MICE
AB Cysteine (Cys) is inserted into proteins in response to UGC and UGU codons. Herein, we show that supplementation of mammalian cells with thiophosphate led to targeted insertion of Cys at the UGA codon of thioredoxin reductase 1 (TR1). This Cys was synthesized by selenocysteine (Sec) synthase on tRNA(inverted right perpendicularSerinverted left perpendicularSec) and its insertion was dependent on the Sec insertion sequence element in the 3` UTR of TR1 mRNA. The substrate for this reaction, thiophosphate, was synthesized by selenophosphate synthetase 2 from ATP and sulfide and reacted with phosphoseryl-tRNA(inverted right perpendicularSerinverted left perpendicularSec) to generate Cys-tRNA(inverted right perpendicularSerinverted left perpendicularSec). Cys was inserted in vivo at UGA codons in natural mammalian TRs, and this process was regulated by dietary selenium and availability of thiophosphate. Cys occurred at 10% of the Sec levels in liver TR1 of mice maintained on a diet with normal amounts of selenium and at 50% in liver TR1 of mice maintained on a selenium deficient diet. These data reveal a novel Sec machinery-based mechanism for biosynthesis and insertion of Cys into protein at UGA codons and suggest new biological functions for thiophosphate and sulfide in mammals.
C1 [Turanov, Anton A.; Nandakumar, Renu; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA.
[Turanov, Anton A.; Nandakumar, Renu; Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68588 USA.
[Xu, Xue-Ming; Carlson, Bradley A.; Yoo, Min-Hyuk; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Turanov, Anton A.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA.
[Everley, Robert A.; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Sorokina, Irina] Midwest Bio Serv, Overland Pk, KS 66211 USA.
RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA.
EM vgladyshev@rics.bwh.harvard.edu; hatfield@mail.nih.gov
RI Gladyshev, Vadim/A-9894-2013
FU Intramural Research Program at the Center for Cancer Research; NCI; NIH;
NIH [GM061603, GM065204]
FX This work was supported by the Intramural Research Program at the Center
for Cancer Research, NCI, NIH (to D.L.H.) and by NIH Grants GM061603 and
GM065204 (to V.N.G.).
NR 28
TC 26
Z9 27
U1 1
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 14
PY 2010
VL 107
IS 50
BP 21430
EP 21434
DI 10.1073/pnas.1009947107
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697NY
UT WOS:000285521500040
PM 21115847
ER
PT J
AU Hummer, G
Szabo, A
AF Hummer, Gerhard
Szabo, Attila
TI Free energy profiles from single-molecule pulling experiments
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE atomic force microscope; force spectroscopy; free energy calculation;
nonequilibrium work relations; steered molecular dynamics
ID JARZYNSKIS EQUALITY; FORCE SPECTROSCOPY; RNA MOLECULES; EQUILIBRIUM;
SIMULATION; LANDSCAPE; FULL
AB Nonequilibrium pulling experiments provide detailed information about the thermodynamic and kinetic properties of molecules. We show that unperturbed free energy profiles as a function of molecular extension can be obtained rigorously from such experiments without using work-weighted position histograms. An inverse Weierstrass transform is used to relate the system free energy obtained from the Jarzynski equality directly to the underlying molecular free energy surface. An accurate approximation for the free energy surface is obtained by using the method of steepest descent to evaluate the inverse transform. The formalism is applied to simulated data obtained from a kinetic model of RNA folding, in which the dynamics consists of jumping between linker-dominated folded and unfolded free energy surfaces.
C1 [Hummer, Gerhard; Szabo, Attila] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Hummer, G (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA.
EM gerhard.hummer@nih.gov; attilas@nih.gov
RI Szabo, Attila/H-3867-2012; Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX We thank Prof. Olga Dudko and Drs. D. Minh and J. Chodera for
discussions. This work was supported by the Intramural Research Program
of the National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.
NR 26
TC 59
Z9 60
U1 3
U2 52
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 DEC 14
PY 2010
VL 107
IS 50
BP 21441
EP 21446
DI 10.1073/pnas.1015661107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697NY
UT WOS:000285521500042
PM 21098304
ER
PT J
AU Pfefferkorn, CM
McGlinchey, RP
Lee, JC
AF Pfefferkorn, Candace M.
McGlinchey, Ryan P.
Lee, Jennifer C.
TI Effects of pH on aggregation kinetics of the repeat domain of a
functional amyloid, Pmel17
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE fibril; fluorescence; melanosome; tryptophan; melanin
ID PINK-EYED DILUTION; MELANIN BIOSYNTHESIS; MURINE MELANOMA;
ALPHA-SYNUCLEIN; MELANOSOMES; FIBRILS; PROTEIN; GLYCOPROTEIN;
TRYPTOPHAN; MECHANISM
AB Pmel17 is a functional amyloidogenic protein whose fibrils act as scaffolds for pigment deposition in human skin and eyes. We have used the repeat domain (RPT, residues 315-444), an essential luminal polypeptide region of Pmel17, as a model system to study conformational changes from soluble unstructured monomers to beta-sheet-containing fibrils. Specifically, we report on the effects of solution pH (4 -> 7) mimicking pH conditions of melanosomes, acidic organelles where Pmel17 fibrils are formed. Local, secondary, and fibril structure were monitored via intrinsic Trp fluorescence, circular dichroism spectroscopy, and transmission electron microscopy, respectively. We find that W423 is a highly sensitive probe of amyloid assembly with spectral features reflecting local conformational and fibril morphological changes. A critical pH regime (5 +/- 0.5) was identified for fibril formation suggesting the involvement of at least three carboxylic acids in the structural rearrangement necessary for aggregation. Moreover, we demonstrate that RPT fibril morphology can be transformed directly by changing solution pH. Based on these results, we propose that intramelanosomal pH regulates Pmel17 amyloid formation and its subsequent dissolution in vivo.
C1 [Pfefferkorn, Candace M.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[McGlinchey, Ryan P.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Lee, JC (reprint author), NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
EM leej4@mail.nih.gov
RI Lee, Jennifer/E-9658-2015
OI Lee, Jennifer/0000-0003-0506-8349
FU Intramural Research Program at the National Institutes of Health (NIH);
NHLBI; National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK)
FX We thank J. Ferretti for insightful suggestions, M. Daniels and P.
Connelly [EM Core Facility, National Heart, Lung, and Blood Institute
(NHLBI)] for discussion, and G. Piszczek (Biophysics Facility, NHLBI)
for technical assistance. Supported by the Intramural Research Program
at the National Institutes of Health (NIH), NHLBI, and National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
NR 44
TC 35
Z9 35
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 DEC 14
PY 2010
VL 107
IS 50
BP 21447
EP 21452
DI 10.1073/pnas.1006424107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697NY
UT WOS:000285521500043
PM 21106765
ER
PT J
AU Kaila, VRI
Johansson, MP
Sundholm, D
Wikstrom, M
AF Kaila, Ville R. I.
Johansson, Mikael P.
Sundholm, Dage
Wikstroem, Marten
TI Interheme electron tunneling in cytochrome c oxidase
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE biological electron transfer; heme-copper oxidases; Moser-Dutton ruler;
reorganization energy
ID HEME-COPPER OXIDASES; PHOTOSYNTHETIC REACTION CENTERS; FREE-ENERGY
RELATIONSHIPS; ZETA VALENCE QUALITY; GAUSSIAN-BASIS SETS;
OXIDATION-REDUCTION; PROTON PUMP; POLAR-SOLVENTS; REORGANIZATION ENERGY;
BIOLOGICAL MOLECULES
AB Cytochrome c oxidase (CcO) is the terminal enzyme of the respiratory chain that catalyzes respiratory reduction of dioxygen (O(2)) to water in all eukaryotes and many aerobic bacteria. CcO, and its homologs among the heme-copper oxidases, has an active site composed of an oxygen-binding heme and a copper center in the vicinity, plus another heme group that donates electrons to this site. In most oxidoreduction enzymes, electron transfer (eT) takes place by quantum-mechanical electron tunneling. Here we show by independent molecular dynamics and quantum-chemical methods that the heme-heme eT in CcO differs from the majority of cases in having an exceptionally low reorganization energy. We show that the rate of interheme eT in CcO may nevertheless be predicted by the Moser-Dutton equation if reinterpreted as the average of the eT rates between all individual atoms of the donor and acceptor weighed by the respective packing densities between them. We argue that this modification may be necessary at short donor/acceptor distances comparable to the donor/acceptor radii.
C1 [Kaila, Ville R. I.; Wikstroem, Marten] Univ Helsinki, Inst Biotechnol, Struct Biol & Biophys Programme, Helsinki Bioenerget Grp, FI-00014 Helsinki, Finland.
[Kaila, Ville R. I.; Johansson, Mikael P.; Sundholm, Dage] Univ Helsinki, Dept Chem, FI-00014 Helsinki, Finland.
[Johansson, Mikael P.] Univ Girona, Inst Quim Computac, Girona 17071, Spain.
RP Kaila, VRI (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM ville.kaila@nih.gov; mikael.johansson@iki.fi;
marten.wikstrom@helsinki.fi
RI Johansson, Mikael/A-5889-2009;
OI Johansson, Mikael/0000-0002-9793-8235; Sundholm, Dage Matts
Borje/0000-0002-2367-9277
FU Academy of Finland via its Center of Excellence in Computational
Molecular Science; Academy of Finland; Ministerio de Ciencia e
Innovacion [MICINN CTQ2008-06532/BQU]; Departament d'Innovacio,
Universitats i Empresa (DIUE) of the Generalitat de Catalunya
[2009SGR528]; Juan de la Cierva fellowship; Helsingin yliopiston
nanotieteen koulutuksen ja tutkimuksen ohjausryhma (HENAKOTO);
Biocentrum Helsinki; Sigrid Juselius Foundation
FX We thank the CSC-The Finnish IT Center for Science for computational
resources. This work was supported by the Academy of Finland via its
Center of Excellence in Computational Molecular Science (D.S.), the
Academy of Finland (M.W., M.P.J.), Ministerio de Ciencia e Innovacion
(MICINN CTQ2008-06532/BQU, M.P.J.), the Departament d'Innovacio,
Universitats i Empresa (DIUE) of the Generalitat de Catalunya
(2009SGR528, M.P.J.), a Juan de la Cierva fellowship (M.P.J.), Helsingin
yliopiston nanotieteen koulutuksen ja tutkimuksen ohjausryhma
(HENAKOTO), Biocentrum Helsinki (M.W.), and the Sigrid Juselius
Foundation (V.R.I.K., M.W.).
NR 68
TC 14
Z9 14
U1 0
U2 15
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 14
PY 2010
VL 107
IS 50
BP 21470
EP 21475
DI 10.1073/pnas.1005889107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697NY
UT WOS:000285521500047
PM 21106766
ER
PT J
AU Qiu, XY
Parsegian, VA
Rau, DC
AF Qiu, Xiangyun
Parsegian, V. Adrian
Rau, Donald C.
TI Divalent counterion-induced condensation of triple-strand DNA
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE DNA condensation; small angle X-ray diffraction
ID HYDRATION FORCES; DOUBLE HELICES; RODLIKE POLYELECTROLYTES;
ELECTROSTATICS; AGGREGATION; ATTRACTION; ATAXIA
AB Understanding and manipulation of the forces assembling DNA/RNA helices have broad implications for biology, medicine, and physics. One subject of significance is the attractive force between dsDNA mediated by polycations of valence >= 3. Despite extensive studies, the physical origin of the "like-charge attraction" remains unsettled among competing theories. Here we show that triplestrand DNA (tsDNA), a more highly charged helix than dsDNA, is precipitated by alkaline-earth divalent cations that are unable to condense dsDNA. We further show that our observation is general by examining several cations (Mg(2+), Ba(2+), and Ca(2+)) and two distinct tsDNA constructs. Cation-condensed tsDNA forms ordered hexagonal arrays that redissolve upon adding monovalent salts. Forces between tsDNA helices, measured by osmotic stress, follow the form of hydration forces observed with condensed dsDNA. Probing a well-defined system of point-like cations and tsDNAs with more evenly spaced helical charges, the counterintuitive observation that the more highly charged tsDNA (vs. dsDNA) is condensed by cations of lower valence provides new insights into theories of polyelectrolytes and the biological and pathological roles of tsDNA. Cations and tsDNAs also hold promise as a model system for future studies of DNA-DNA interactions and electrostatic interactions in general.
C1 [Qiu, Xiangyun] George Washington Univ, Dept Phys, Washington, DC 20052 USA.
[Parsegian, V. Adrian] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
[Rau, Donald C.] NIH, Lab Phys & Struct Biol, Program Phys Biol, Bethesda, MD 20892 USA.
RP Qiu, XY (reprint author), George Washington Univ, Dept Phys, Washington, DC 20052 USA.
EM xqiu@gwu.edu
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development
FX We thank Drs. Igor Panyutin, Victor Zhurkin, Michaela Vorlickova,
Rengaswami Chandrasekaran, and Michael Seidman for helpful advice and
discussions. This research was supported by the Intramural Research
Program of the National Institutes of Health, Eunice Kennedy Shriver
National Institute of Child Health and Human Development.
NR 39
TC 28
Z9 28
U1 1
U2 16
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 14
PY 2010
VL 107
IS 50
BP 21482
EP 21486
DI 10.1073/pnas.1003374107
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697NY
UT WOS:000285521500049
PM 21098260
ER
PT J
AU Yang, JB
Huang, J
Dasgupta, M
Sears, N
Miyagi, M
Wang, BL
Chance, MR
Chen, X
Du, YP
Wang, YX
An, LZ
Wang, Q
Lu, T
Zhang, XD
Wang, ZH
Stark, GR
AF Yang, Jinbo
Huang, Jing
Dasgupta, Maupali
Sears, Nathan
Miyagi, Masaru
Wang, Benlian
Chance, Mark R.
Chen, Xing
Du, Yuping
Wang, Yuxin
An, Lizhe
Wang, Qin
Lu, Tao
Zhang, Xiaodong
Wang, Zhenghe
Stark, George R.
TI Reversible methylation of promoter-bound STAT3 by histone-modifying
enzymes
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE gene regulation; signal transduction; gene regulation; posttranslational
modifications
ID LYSINE DEMETHYLASE LSD1; NF-KAPPA-B; P53 ACTIVITY; TRANSCRIPTION;
ACETYLATION; CHROMATIN; DNA; PHOSPHORYLATION; INTERFERON; LANGUAGE
AB Following its tyrosine phosphorylation, STAT3 is methylated on K140 by the histone methyl transferase SET9 and demethylated by LSD1 when it is bound to a subset of the promoters that it activates. Methylation of K140 is a negative regulatory event, because its blockade greatly increases the steady-state amount of activated STAT3 and the expression of many (i.e., SOCS3) but not all (i.e., CD14) STAT3 target genes. Biological relevance is shown by the observation that overexpression of SOCS3 when K140 cannot be methylated blocks the ability of cells to activate STAT3 in response to IL-6. K140 methylation does not occur with mutants of STAT3 that do not enter nuclei or bind to DNA. Following treatment with IL-6, events at the SOCS3 promoter occur in an ordered sequence, as shown by chromatin immunoprecipitations. Y705-phosphoryl-STAT3 binds first and S727 is then phosphorylated, followed by the coincident binding of SET9 and dimethylation of K140, and lastly by the binding of LSD1. We conclude that the lysine methylation of promoter-bound STAT3 leads to biologically important down-regulation of the dependent responses and that SET9, which is known to help provide an activating methylation mark to H3K4, is recruited to the newly activated SOCS3 promoter by STAT3.
C1 [Yang, Jinbo; Chen, Xing; Du, Yuping; Wang, Yuxin; An, Lizhe; Wang, Qin] Lanzhou Univ, Sch Life Sci, Lanzhou 730000, Gansu, Peoples R China.
[Yang, Jinbo; Dasgupta, Maupali; Sears, Nathan; Lu, Tao; Stark, George R.] Cleveland Clin, Lerner Res Inst, Dept Mol Genet, Cleveland, OH 44195 USA.
[Huang, Jing] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Miyagi, Masaru; Wang, Benlian; Chance, Mark R.] Case Western Reserve Univ, Ctr Prote & Bioinformat, Cleveland, OH 44106 USA.
[Zhang, Xiaodong; Wang, Zhenghe; Stark, George R.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA.
[Zhang, Xiaodong; Wang, Zhenghe; Stark, George R.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
RP Yang, JB (reprint author), Lanzhou Univ, Sch Life Sci, Lanzhou 730000, Gansu, Peoples R China.
EM yangjb@lzu.edu.cn; starkg@ccf.org
RI Huang, Jing/A-2566-2009
OI Huang, Jing/0000-0002-7163-5156
FU Ministry of Education [P01 CA62220, R01 CA127590, NCET-08-0260];
Ministry of Science and Technology of the People's Republic of China
[2009DFA30990]; Gansu Provincial Ministry of Science and Technology
[0708WCGA149]; Case Comprehensive Cancer Center
FX We thank Dr. Judith Drazba of the Cleveland Clinic for expert help with
confocal microscopy. This work was supported by Grants P01 CA62220 (to
G.R.S.), R01 CA127590 (to Z.W.), NCET-08-0260 from the Ministry of
Education and 2009DFA30990 from the Ministry of Science and Technology
of the People's Republic of China, and 0708WCGA149 from the Gansu
Provincial Ministry of Science and Technology (to J.Y.). The mass
spectrometry experiments were supported in part by funds from the Case
Comprehensive Cancer Center.
NR 27
TC 101
Z9 105
U1 3
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 14
PY 2010
VL 107
IS 50
BP 21499
EP 21504
DI 10.1073/pnas.1016147107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697NY
UT WOS:000285521500052
PM 21098664
ER
PT J
AU Lu, J
Chiang, J
Iyer, RR
Thompson, E
Kaneski, CR
Xu, DS
Yang, CZ
Chen, M
Hodes, RJ
Lonser, RR
Brady, RO
Zhuang, ZP
AF Lu, Jie
Chiang, Jeffrey
Iyer, Rajiv R.
Thompson, Eli
Kaneski, Christine R.
Xu, David S.
Yang, Chunzhang
Chen, Masako
Hodes, Richard J.
Lonser, Russell R.
Brady, Roscoe O.
Zhuang, Zhengping
TI Decreased glucocerebrosidase activity in Gaucher disease parallels
quantitative enzyme loss due to abnormal interaction with TCP1 and c-Cbl
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID ACID-BETA-GLUCOSIDASE; GROUP-II CHAPERONIN; MUTATIONS; PHENOTYPE;
TYPE-1; DOMAIN; INHIBITION; DEFICIENCY; VARIANTS; PROTEINS
AB Gaucher disease (GD), the most common lysosomal storage disorder of humans, is caused by mutations in the gene coding for the enzyme glucocerebrosidase (GCase). Clinical manifestations vary among patients with the three types of GD, and phenotypic heterogeneity occurs even among patients with identical mutations. To gain insight into why phenotypic heterogeneity occurs in GD, we investigated mechanisms underlying the net loss of GCase catalytic activity in cultured skin fibroblasts derived from patients with the three types of GD. The findings indicate that the loss of catalytic activity of GCase correlates with its quantitative reduction, rather than a decrease in functional capacity of mutant enzyme. Use of a proteasome inhibitor, lactacystin, resulted in increased expression of GCase, suggesting a mechanism of protein degradation in GD. Furthermore, reduced binding of GCase to TCP1 ring complex (TRiC), a regulator of correct protein folding, may result in defective maturation of nascent GCase in GD cells. Additionally, increased interaction between GCase and c-Cbl, an E3 ubiquitin ligase, may be involved in the degradation and loss of GCase in GD. The findings suggest that specific molecular mediators involved in GCase maturation and degradation could be responsible for phenotypic variation among patients with the same genotypes and that these mediators could be therapeutically targeted to increase GCase activity in patients with GD.
C1 [Lu, Jie; Iyer, Rajiv R.; Thompson, Eli; Xu, David S.; Yang, Chunzhang; Chen, Masako; Lonser, Russell R.; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Chiang, Jeffrey; Hodes, Richard J.] NCI, NIH, Bethesda, MD 20892 USA.
[Kaneski, Christine R.] Baylor Res Inst, Inst Metab Dis, Dallas, TX 75204 USA.
[Brady, Roscoe O.] NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Brady, RO (reprint author), NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
EM bradyr@ninds.nih.gov; zhuangp@ninds.nih.gov
OI Kaneski, Christine/0000-0003-1453-2502; Xu, David/0000-0001-8987-4545
FU NINDS; National Cancer Institute at the National Institutes of Health
FX We thank Dr. Paul E. Gallant of the NINDS Light Microscopy Facility for
his assistance with confocal microscopy and Dr. Howard Jaffe of the
National Institute of Neurological Disorders and Stroke (NINDS)
Protein/Peptide Sequencing Facility for his assistance with protein
identification. This research was supported by the Intramural Research
Program of the NINDS and the National Cancer Institute at the National
Institutes of Health.
NR 32
TC 24
Z9 25
U1 0
U2 5
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 DEC 14
PY 2010
VL 107
IS 50
BP 21665
EP 21670
DI 10.1073/pnas.1014376107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697NY
UT WOS:000285521500080
PM 21098288
ER
PT J
AU Schwer, B
Schumacher, B
Lombard, DB
Xiao, CY
Kurtev, MV
Gao, J
Schneider, JI
Chai, H
Bronson, RT
Tsai, LH
Deng, CX
Alt, FW
AF Schwer, Bjoern
Schumacher, Bjoern
Lombard, David B.
Xiao, Cuiying
Kurtev, Martin V.
Gao, Jun
Schneider, Jennifer I.
Chai, Hua
Bronson, Roderick T.
Tsai, Li-Huei
Deng, Chu-Xia
Alt, Frederick W.
TI Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes
obesity
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID NERVOUS-SYSTEM; DEACETYLATION; MICE; DISRUPTION; CHROMATIN; MOUSE; GENE
AB In yeast, Sir2 family proteins (sirtuins) regulate gene silencing, recombination, DNA repair, and aging via histone deacetylation. Most of the seven mammalian sirtuins (Sirt1-Sirt7) have been implicated as NAD(+)-dependent protein deacetylases with targets ranging from transcriptional regulators to metabolic enzymes. We report that neural-specific deletion of sirtuin 6 (Sirt6) in mice leads to postnatal growth retardation due to somatotropic attenuation through low growth hormone (GH) and insulin-like growth factor 1 (IGF1) levels. However, unlike Sirt6 null mice, neural Sirt6-deleted mice do not die from hypoglycemia. Instead, over time, neural Sirt6-deleted mice reach normal size and ultimately become obese. Molecularly, Sirt6 deletion results in striking hyperacetylation of histone H3 lysine 9 (H3K9) and lysine 56 (H3K56), two chromatin marks implicated in the regulation of gene activity and chromatin structure, in various brain regions including those involved in neuroendocrine regulation. On the basis of these findings, we propose that Sirt6 functions as a central regulator of somatic growth and plays an important role in preventing obesity by modulating neural chromatin structure and gene activity.
C1 [Schwer, Bjoern; Lombard, David B.; Chai, Hua; Alt, Frederick W.] Harvard Univ, Childrens Hosp,Dept Genet, Sch Med,Immune Dis Inst, Howard Hughes Med Inst,Program Cellular & Mol Med, Boston, MA 02115 USA.
[Schumacher, Bjoern; Schneider, Jennifer I.] Univ Cologne, Inst Genet, D-50674 Cologne, Germany.
[Xiao, Cuiying; Deng, Chu-Xia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Kurtev, Martin V.] Harvard Univ, Sch Med, Dept Neurol & Neurobiol, Boston, MA 02115 USA.
[Gao, Jun; Tsai, Li-Huei] MIT, Howard Hughes Med Inst, Picower Inst Learning & Memory, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Bronson, Roderick T.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Tsai, Li-Huei] Harvard Univ, Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
RP Alt, FW (reprint author), Harvard Univ, Childrens Hosp,Dept Genet, Sch Med,Immune Dis Inst, Howard Hughes Med Inst,Program Cellular & Mol Med, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu
RI deng, chuxia/N-6713-2016; Schumacher, Bjorn/I-4829-2013
OI Schumacher, Bjorn/0000-0001-6097-5238
FU Ellison Medical Foundation/American Federation for Aging; Ellison
Foundation; National Institute on Aging/National Institutes of Health
(NIH) [AG022325]; Hartford Foundation; Deutsche Forschungsgemeinschaft;
Marie Curie European Reintegration Grant [PERG04-GA-2008-239330];
German-Israeli Foundation [YIG 2213]; NIH [PO1 AG027916]
FX We thank Hwei-Ling Cheng and members of the F.W.A. laboratory for
helpful discussions and Amanda Donahue and Melissa Cummings (Children's
Hospital Boston) for help with DXA. We thank Bruce Yankner (Harvard
Medical School) for comments on the manuscript. This work was supported
by an Ellison Medical Foundation/American Federation for Aging Research
Senior Postdoctoral Fellow Research Grant (to B. Schwer), an Ellison
Foundation Senior Scholar Award (to F.W.A), a National Institute on
Aging/National Institutes of Health (NIH) K08 Award (AG022325) and
Hartford Foundation Grant (to D.B.L), Deutsche Forschungsgemeinschaft
(Cologne Excellence Cluster for Cellular Stress Responses in
Aging-Associated Diseases and Sonderforschungsbereich 829), Marie Curie
European Reintegration Grant (PERG04-GA-2008-239330) and German-Israeli
Foundation (YIG 2213) grants (to B. Schumacher), and NIH Grant PO1
AG027916 (to L.-H.T.). F.W.A. and L.-H.T. are Investigators of the
Howard Hughes Medical Institute.
NR 30
TC 78
Z9 85
U1 1
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 14
PY 2010
VL 107
IS 50
BP 21790
EP 21794
DI 10.1073/pnas.1016306107
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697NY
UT WOS:000285521500101
PM 21098266
ER
PT J
AU Mousavi, K
Sartorelli, V
AF Mousavi, Kambiz
Sartorelli, Vittorio
TI Myc-Nick: The Force Behind c-Myc
SO SCIENCE SIGNALING
LA English
DT Article
ID MYOGENIC DIFFERENTIATION; ALPHA-TUBULIN; ACETYLATION; PRODUCT; MYOD
AB In the field of molecular oncology, the Myc basic helix-loop-helix family of transcription factors has been extensively studied. The Myc proto-oncogene c-Myc binds DNA, activates or represses gene transcription, and consequently affects cellular proliferation. However, emerging evidence presents the existence of c-Myc variants that lack transcriptional activity. A cytoplasmic variant of c-Myc called "Myc-nick," which arises from calpain-mediated cleavage of c-Myc, assists in stable microtubule assembly. Furthermore, Myc-nick promotes MyoD-mediated myogenic differentiation, thus antagonizing its precursor. These results provide exciting new opportunities in formulating molecular approaches for treatment of cancer and in our understanding of cell differentiation.
C1 [Mousavi, Kambiz; Sartorelli, Vittorio] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
RP Sartorelli, V (reprint author), NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM sartorev@mail.nih.gov
FU Intramural NIH HHS [ZIA AR041126-11]
NR 13
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD DEC 14
PY 2010
VL 3
IS 152
AR pe49
DI 10.1126/scisignal.3152pe49
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 694KB
UT WOS:000285295000002
PM 21156935
ER
PT J
AU Ginsburg, E
Alexander, S
Lieber, S
Tarplin, S
Jenkins, L
Pang, LD
Heger, CD
Goldsmith, P
Vonderhaar, BK
AF Ginsburg, Erika
Alexander, Stefanie
Lieber, Sarah
Tarplin, Sarah
Jenkins, Luwanda
Pang, Linda
Heger, Christopher D.
Goldsmith, Paul
Vonderhaar, Barbara K.
TI Characterization of ductal and lobular breast carcinomas using novel
prolactin receptor isoform specific antibodies
SO BMC CANCER
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; HUMAN PRL RECEPTORS; MAMMARY-CARCINOMA;
CANCER-CELLS; SHORT FORMS; EXPRESSION; LONG; VARIANTS; BINDING; RISK
AB Background: Prolactin is a polypeptide hormone responsible for proliferation and differentiation of the mammary gland. More recently, prolactin's role in mammary carcinogenesis has been studied with greater interest. Studies from our laboratory and from others have demonstrated that three specific isoforms of the prolactin receptor (PRLR) are expressed in both normal and cancerous breast cells and tissues. Until now, reliable isoform specific antibodies have been lacking. We have prepared and characterized polyclonal antibodies against each of the human PRLR isoforms that can effectively be used to characterize human breast cancers.
Methods: Rabbits were immunized with synthetic peptides of isoform unique regions and immune sera affinity purified prior to validation by Western blot and immunohistochemical analyses. Sections of ductal and lobular carcinomas were stained with each affinity purified isoform specific antibody to determine expression patterns in breast cancer subclasses.
Results: We show that the rabbit antibodies have high titer and could specifically recognize each isoform of PRLR. Differences in PRLR isoform expression levels were observed and quantified using histosections from xenografts of established human breast cancer cells lines, and ductal and lobular carcinoma human biopsy specimens. In addition, these results were verified by real-time PCR with isoform specific primers. While nearly all tumors contained LF and SF1b, the majority (76%) of ductal carcinoma biopsies expressed SF1a while the majority of lobular carcinomas lacked SF1a staining (72%) and 27% had only low levels of expression.
Conclusions: Differences in the receptor isoform expression profiles may be critical to understanding the role of PRL in mammary tumorigenesis. Since these antibodies are specifically directed against each PRLR isoform, they are valuable tools for the evaluation of breast cancer PRLR content and have potential clinical importance in treatment of this disease by providing new reagents to study the protein expression of the human PRLR.
C1 [Ginsburg, Erika; Alexander, Stefanie; Lieber, Sarah; Tarplin, Sarah; Jenkins, Luwanda; Pang, Linda; Vonderhaar, Barbara K.] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA.
[Heger, Christopher D.; Goldsmith, Paul] NCI, Antibody & Prot Purificat Unit, NIH, Bethesda, MD 20892 USA.
RP Ginsburg, E (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA.
EM eg20e@nih.gov
FU Center for Cancer Research; National Cancer Institute
FX This research was supported by the Center for Cancer Research, an
Intramural Research Program of the National Cancer Institute.
NR 35
TC 5
Z9 6
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD DEC 13
PY 2010
VL 10
AR 678
DI 10.1186/1471-2407-10-678
PG 11
WC Oncology
SC Oncology
GA 698EO
UT WOS:000285575500001
PM 21144038
ER
PT J
AU Gallardo, VE
Liang, J
Behra, M
Elkahloun, A
Villablanca, EJ
Russo, V
Allende, ML
Burgess, SM
AF Gallardo, Viviana E.
Liang, Jin
Behra, Martine
Elkahloun, Abdel
Villablanca, Eduardo J.
Russo, Vincenzo
Allende, Miguel L.
Burgess, Shawn M.
TI Molecular dissection of the migrating posterior lateral line primordium
during early development in zebrafish
SO BMC DEVELOPMENTAL BIOLOGY
LA English
DT Article
ID COLLECTIVE CELL-MIGRATION; TISSUE MIGRATION; NERVOUS-SYSTEM;
LASER-ABLATION; HAIR-CELLS; EXPRESSION; REGENERATION; GENE;
METALLOPROTEINASES; METASTASIS
AB Background: Development of the posterior lateral line (PLL) system in zebrafish involves cell migration, proliferation and differentiation of mechanosensory cells. The PLL forms when cranial placodal cells delaminate and become a coherent, migratory primordium that traverses the length of the fish to form this sensory system. As it migrates, the primordium deposits groups of cells called neuromasts, the specialized organs that contain the mechanosensory hair cells. Therefore the primordium provides both a model for studying collective directional cell migration and the differentiation of sensory cells from multipotent progenitor cells.
Results: Through the combined use of transgenic fish, Fluorescence Activated Cell Sorting and microarray analysis we identified a repertoire of key genes expressed in the migrating primordium and in differentiated neuromasts. We validated the specific expression in the primordium of a subset of the identified sequences by quantitative RTPCR, and by in situ hybridization. We also show that interfering with the function of two genes, f11r and cd9b, defects in primordium migration are induced. Finally, pathway construction revealed functional relationships among the genes enriched in the migrating cell population.
Conclusions: Our results demonstrate that this is a robust approach to globally analyze tissue-specific expression and we predict that many of the genes identified in this study will show critical functions in developmental events involving collective cell migration and possibly in pathological situations such as tumor metastasis.
C1 [Gallardo, Viviana E.; Liang, Jin; Behra, Martine; Elkahloun, Abdel; Burgess, Shawn M.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Gallardo, Viviana E.; Allende, Miguel L.] Univ Chile, Fac Ciencias, Ctr Genome Regulat, Santiago, Chile.
[Behra, Martine] Univ Puerto Rico, Sch Med, Dept Anat & Neurobiol, San Juan, PR 00936 USA.
[Villablanca, Eduardo J.; Russo, Vincenzo] Ist Sci San Raffaele, Canc Immunotherapy & Gene Therapy Program, Canc Gene Therapy Unit, I-20132 Milan, Italy.
RP Burgess, SM (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM burgess@mail.nih.gov
RI Allende, Miguel/C-5167-2008; Villablanca, Eduardo/E-1380-2016; Russo,
Vincenzo/K-5650-2016;
OI Allende, Miguel/0000-0002-2783-2152; Villablanca,
Eduardo/0000-0001-9522-9729; Russo, Vincenzo/0000-0003-1592-5041;
Burgess, Shawn/0000-0003-1147-0596
FU Fondecyt [1070867]; ICM [P06-039F]; FONDAP [15090007]; Conicyt;
Vicerrectoria de Asuntos Academicos; Departamento de Postgrado y
Postitulo; Universidad de Chile; MECESUP; National Human Genome Research
Institute, National Institutes of Health
FX We thank Martha Kirby for help with FACS analysis, Catalina Lafourcade
and A. Davis for expert fish care and Florencio Espinoza for technical
help. The CldnB:lynGFP strain was kindly provided by Darren Gilmour.
This work was supported by grants to M. A. from Fondecyt (1070867), ICM
(P06-039F) and FONDAP (15090007). V. G. was supported by a Conicyt
fellowship and travel fellowships from the Vicerrectoria de Asuntos
Academicos, Departamento de Postgrado y Postitulo, Universidad de Chile
and MECESUP. This research was supported by the Intramural Research
Program of the National Human Genome Research Institute, National
Institutes of Health (S. B.).
NR 51
TC 22
Z9 22
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-213X
J9 BMC DEV BIOL
JI BMC Dev. Biol.
PD DEC 13
PY 2010
VL 10
AR 120
DI 10.1186/1471-213X-10-120
PG 14
WC Developmental Biology
SC Developmental Biology
GA 702SQ
UT WOS:000285916200001
PM 21144052
ER
PT J
AU Webster, MT
McCaffery, JM
Cohen-Fix, O
AF Webster, Micah T.
McCaffery, J. Michael
Cohen-Fix, Orna
TI Vesicle trafficking maintains nuclear shape in Saccharomyces cerevisiae
during membrane proliferation
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID ARF-LIKE GTPASES; RIBOSOME SYNTHESIS; SECRETORY PATHWAY; ACID
RESISTANCE; PROTEIN SYS1P; YEAST-CELLS; GOLGI; TRANSPORT; SIZE; MUTATION
AB The parameters that control nuclear size and shape are poorly understood. In yeast, unregulated membrane proliferation, caused by deletion of the phospholipid biosynthesis inhibitor SPO7, leads to a single nuclear envelope "flare" that protrudes into the cytoplasm. This flare is always associated with the asymmetrically localized nucleolus, which suggests that the site of membrane expansion is spatially confined by an unknown mechanism. Here we show that in spo7. cells, mutations in vesicle-trafficking genes lead to multiple flares around the entire nucleus. These mutations also alter the distribution of small nucleolar RNA-associated nucleolar proteins independently of their effect on nuclear shape. Both single-and multi-flared nuclei have increased nuclear envelope surface area, yet they maintain the same nuclear/cell volume ratio as wild-type cells. These data suggest that, upon membrane expansion, the spatial confinement of the single nuclear flare is dependent on vesicle trafficking. Moreover, flares may facilitate maintenance of a constant nuclear/cell volume ratio in the face of altered membrane proliferation.
C1 [Webster, Micah T.; Cohen-Fix, Orna] NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA.
[Webster, Micah T.] Johns Hopkins Univ, Natl Inst Hlth Johns Hopkins Univ Grad Partnershi, Baltimore, MD 21218 USA.
[McCaffery, J. Michael] Johns Hopkins Univ, Dept Biol, Integrated Imaging Ctr, Baltimore, MD 21218 USA.
RP Cohen-Fix, O (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA.
EM ornacf@helix.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX M.T. Webster and O. Cohen-Fix were funded by an intramural National
Institute of Diabetes and Digestive and Kidney Diseases grant.
NR 39
TC 21
Z9 21
U1 0
U2 7
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD DEC 13
PY 2010
VL 191
IS 6
BP 1079
EP 1088
DI 10.1083/jcb.201006083
PG 10
WC Cell Biology
SC Cell Biology
GA 697GX
UT WOS:000285502400006
PM 21135138
ER
PT J
AU Otera, H
Wang, CX
Cleland, MM
Setoguchi, K
Yokota, S
Youle, RJ
Mihara, K
AF Otera, Hidenori
Wang, Chunxin
Cleland, Megan M.
Setoguchi, Kiyoko
Yokota, Sadaki
Youle, Richard J.
Mihara, Katsuyoshi
TI Mff is an essential factor for mitochondrial recruitment of Drp1 during
mitochondrial fission in mammalian cells
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID DYNAMIN-RELATED PROTEIN; DOMINANT OPTIC ATROPHY; OUTER-MEMBRANE;
PEROXISOMAL FISSION; CYTOCHROME-C; APOPTOSIS; DIVISION; MORPHOLOGY;
FIS1; FUSION
AB The cytoplasmic dynamin-related guanosine triphosphatase Drp1 is recruited to mitochondria and mediates mitochondrial fission. Although the mitochondrial outer membrane (MOM) protein Fis1 is thought to be a Drp1 receptor, this has not been confirmed. To analyze the mechanism of Drp1 recruitment, we manipulated the expression of mitochondrial fission and fusion proteins and demonstrated that (a) mitochondrial fission factor (Mff) knockdown released the Drp1 foci from the MOM accompanied by network extension, whereas Mff overexpression stimulated mitochondrial recruitment of Drp1 accompanied by mitochondrial fission; (b) Mff-dependent mitochondrial fission proceeded independent of Fis1; (c) a Mff mutant with the plasma membrane-targeted CAAX motif directed Drp1 to the target membrane; (d) Mff and Drp1 physically interacted in vitro and in vivo; (e) exogenous stimuli-induced mitochondrial fission and apoptosis were compromised by knockdown of Drp1 and Mff but not Fis1; and (f) conditional knockout of Fis1 in colon carcinoma cells revealed that it is dispensable for mitochondrial fission. Thus, Mff functions as an essential factor in mitochondrial recruitment of Drp1.
C1 [Otera, Hidenori; Setoguchi, Kiyoko; Mihara, Katsuyoshi] Kyushu Univ, Grad Sch Med Sci, Dept Mol Biol, Fukuoka 8128582, Japan.
[Wang, Chunxin; Cleland, Megan M.; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Yokota, Sadaki] Nagasaki Int Univ, Sasebo 8593298, Japan.
RP Mihara, K (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Mol Biol, Fukuoka 8128582, Japan.
EM mihara@cell.med.kyushu-u.ac.jp
RI Wang, Chunxin/B-9312-2016; U-ID, Kyushu/C-5291-2016;
OI Wang, Chunxin/0000-0001-6015-6806; Harwig, Megan/0000-0003-2140-5739
FU Ministry of Education, Science, and Culture of Japan; National Institute
of Neurological Disorders and Stroke, National Institutes of Health
FX This work was supported by grants from the Ministry of Education,
Science, and Culture of Japan and in part by the Intramural Research
Program of the National Institute of Neurological Disorders and Stroke,
National Institutes of Health.
NR 62
TC 308
Z9 318
U1 2
U2 18
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD DEC 13
PY 2010
VL 191
IS 6
BP 1141
EP 1158
DI 10.1083/jcb.201007152
PG 18
WC Cell Biology
SC Cell Biology
GA 697GX
UT WOS:000285502400011
PM 21149567
ER
PT J
AU Cadet, JL
Brannock, C
Krasnova, IN
Ladenheim, B
Mccoy, MT
Chou, J
Lehrmann, E
Wood, WH
Becker, KG
Wang, Y
AF Cadet, Jean Lud
Brannock, Christie
Krasnova, Irina N.
Ladenheim, Bruce
McCoy, Michael T.
Chou, Jenny
Lehrmann, Elin
Wood, William H.
Becker, Kevin G.
Wang, Yun
TI Methamphetamine-Induced Dopamine- Independent Alterations in Striatal
Gene Expression in the 6-Hydroxydopamine Hemiparkinsonian Rats
SO PLOS ONE
LA English
DT Article
ID MESSENGER-RNA EXPRESSION; CENTRAL-NERVOUS-SYSTEM; FENFLURAMINE-INDUCED
ACTIVATION; DA UPTAKE SITES; NEUROMEDIN-U; GROWTH-FACTOR;
STRIATOPALLIDAL NEURONS; PARKINSONS-DISEASE; GLUTAMATE RELEASE;
SUBSTANTIA-NIGRA
AB Unilateral injections of 6-hydroxydopamine into the medial forebrain bundle are used extensively as a model of Parkinson's disease. The present experiments sought to identify genes that were affected in the dopamine (DA)-denervated striatum after 6-hydroxydopamine-induced destruction of the nigrostriatal dopaminergic pathway in the rat. We also examined whether a single injection of methamphetamine (METH) (2.5 mg/kg) known to cause changes in gene expression in the normally DA-innervated striatum could still influence striatal gene expression in the absence of DA. Unilateral injections of 6-hydroxydopamine into the medial forebrain bundle resulted in METH-induced rotational behaviors ipsilateral to the lesioned side and total striatal DA depletion on the lesioned side. This injection also caused decrease in striatal serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels. DA depletion was associated with increases in 5-HIAA/5-HT ratios that were potentiated by the METH injection. Microarray analyses revealed changes (+/- 1.7-fold, p<0.025) in the expression of 67 genes on the lesioned side in comparison to the intact side of the saline-treated hemiparkinsonian animals. These include follistatin, neuromedin U, and tachykinin 2 which were up-regulated. METH administration caused increases in the expression of c-fos, Egr1, and Nor-1 on the intact side. On the DA-depleted side, METH administration also increased the expression of 61 genes including Pdgf-d and Cox-2. There were METH-induced changes in 16 genes that were common in the DA-innervated and DA-depleted sides. These include c-fos and Nor-1 which show greater changes on the normal DA side. Thus, the present study documents, for the first time, that METH mediated DA-independent changes in the levels of transcripts of several genes in the DA-denervated striatum. Our results also implicate 5-HT as a potential player in these METH-induced alterations in gene expression because the METH injection also caused significant increases in 5-HIAA/5-HT ratios on the DA-depleted side.
C1 [Cadet, Jean Lud; Brannock, Christie; Krasnova, Irina N.; Ladenheim, Bruce; McCoy, Michael T.; Chou, Jenny; Wang, Yun] NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA.
[Lehrmann, Elin; Wood, William H.; Becker, Kevin G.] NIDA, Gene Express & Genom Unit, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA.
RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA.
EM jcadet@intra.nida.nih.gov
OI Lehrmann, Elin/0000-0002-9869-9475; Becker, Kevin/0000-0002-6794-6656
FU National Institute on Drug Abuse and National Institute of Aging,
National Institutes of Health (NIH)/Department of Health and Human
Services (DHHS)
FX The study was supported by Intramural Research Programs of National
Institute on Drug Abuse and National Institute of Aging, National
Institutes of Health (NIH)/Department of Health and Human Services
(DHHS). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 99
TC 15
Z9 16
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 13
PY 2010
VL 5
IS 12
AR e15643
DI 10.1371/journal.pone.0015643
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 693SY
UT WOS:000285246900049
PM 21179447
ER
PT J
AU Lee, N
Iyer, SS
Mu, J
Weissman, JD
Ohali, A
Howcroft, TK
Lewis, BA
Singer, DS
AF Lee, Namhoon
Iyer, Shankar S.
Mu, Jie
Weissman, Jocelyn D.
Ohali, Anat
Howcroft, T. Kevin
Lewis, Brian A.
Singer, Dinah S.
TI Three Novel Downstream Promoter Elements Regulate MHC Class I Promoter
Activity in Mammalian Cells
SO PLOS ONE
LA English
DT Article
ID RNA-POLYMERASE-II; CORE PROMOTER; GENE-EXPRESSION; BASAL PROMOTER;
FUNCTIONAL-CHARACTERIZATION; REPRESSES TRANSCRIPTION; DNA-BINDING;
TATA-BOX; C-JUN; DROSOPHILA
AB Background: MHC class I transcription is regulated by two distinct types of regulatory pathways: 1) tissue-specific pathways that establish constitutive levels of expression within a given tissue and 2) dynamically modulated pathways that increase or decrease expression within that tissue in response to hormonal or cytokine mediated stimuli. These sets of pathways target distinct upstream regulatory elements, have distinct basal transcription factor requirements, and utilize discrete sets of transcription start sites within an extended core promoter.
Methodology/Principal Findings: We studied regulatory elements within the MHC class I promoter by cellular transfection and in vitro transcription assays in HeLa, HeLa/CIITA, and tsBN462 of various promoter constructs. We have identified three novel MHC class I regulatory elements (GLE, DPE-L1 and DPE-L2), located downstream of the major transcription start sites, that contribute to the regulation of both constitutive and activated MHC class I expression. These elements located at the 3' end of the core promoter preferentially regulate the multiple transcription start sites clustered at the 5' end of the core promoter.
Conclusions/Significance: Three novel downstream elements (GLE, DPE-L1, DPE-L2), located between +1 and +32 bp, regulate both constitutive and activated MHC class I gene expression by selectively increasing usage of transcription start sites clustered at the 5' end of the core promoter upstream of +1 bp. Results indicate that the downstream elements preferentially regulate TAF1-dependent, relative to TAF1-independent, transcription.
C1 [Lee, Namhoon; Iyer, Shankar S.; Mu, Jie; Weissman, Jocelyn D.; Ohali, Anat; Singer, Dinah S.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Namhoon] Johns Hopkins Univ, NIH, Bethesda, MD USA.
[Iyer, Shankar S.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA.
[Howcroft, T. Kevin] NCI, Div Canc Biol, Bethesda, MD 20892 USA.
[Lewis, Brian A.; Singer, Dinah S.] NCI, Metab Branch, Bethesda, MD 20892 USA.
RP Lee, N (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM Dinah.singer@nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 54
TC 5
Z9 5
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 13
PY 2010
VL 5
IS 12
AR e15278
DI 10.1371/journal.pone.0015278
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 693SY
UT WOS:000285246900041
PM 21179443
ER
PT J
AU Takikita, S
Schreiner, C
Baum, R
Xie, T
Ralston, E
Plotz, PH
Raben, N
AF Takikita, Shoichi
Schreiner, Cynthia
Baum, Rebecca
Xie, Tao
Ralston, Evelyn
Plotz, Paul H.
Raben, Nina
TI Fiber Type Conversion by PGC-1 alpha Activates Lysosomal and
Autophagosomal Biogenesis in Both Unaffected and Pompe Skeletal Muscle
SO PLOS ONE
LA English
DT Article
ID ACID ALPHA-GLUCOSIDASE; TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; ENZYME
REPLACEMENT THERAPY; ALGLUCOSIDASE ALPHA; GLYCOGEN AUTOPHAGY; PGC-1
COACTIVATORS; SIGNALING PATHWAYS; NATURAL COURSE; CELL-DEATH; DISEASE
AB PGC-1 alpha is a transcriptional co-activator that plays a central role in the regulation of energy metabolism. Our interest in this protein was driven by its ability to promote muscle remodeling. Conversion from fast glycolytic to slow oxidative fibers seemed a promising therapeutic approach in Pompe disease, a severe myopathy caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA) which is responsible for the degradation of glycogen. The recently approved enzyme replacement therapy (ERT) has only a partial effect in skeletal muscle. In our Pompe mouse model (KO), the poor muscle response is seen in fast but not in slow muscle and is associated with massive accumulation of autophagic debris and ineffective autophagy. In an attempt to turn the therapy-resistant fibers into fibers amenable to therapy, we made transgenic KO mice expressing PGC-1 alpha in muscle (tgKO). The successful switch from fast to slow fibers prevented the formation of autophagic buildup in the converted fibers, but PGC-1 alpha failed to improve the clearance of glycogen by ERT. This outcome is likely explained by an unexpected dramatic increase in muscle glycogen load to levels much closer to those observed in patients, in particular infants, with the disease. We have also found a remarkable rise in the number of lysosomes and autophagosomes in the tgKO compared to the KO. These data point to the role of PGC-1 alpha in muscle glucose metabolism and its possible role as a master regulator for organelle biogenesis - not only for mitochondria but also for lysosomes and autophagosomes. These findings may have implications for therapy of lysosomal diseases and other disorders with altered autophagy.
C1 [Takikita, Shoichi; Schreiner, Cynthia; Baum, Rebecca; Xie, Tao; Plotz, Paul H.; Raben, Nina] NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA.
[Ralston, Evelyn] NIAMSD, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA.
RP Takikita, S (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA.
EM rabenn@mail.nih.gov
FU National Institute of Arthritis and Musculoskeleta and Skin Diseases of
the National Institutes of Health; NIH; Genzyme Corporation
FX This research was supported by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health. Dr. Takikita was supported in part by
a Cooperative Research and Development Agreement (CRADA) between the NIH
and Genzyme Corporation. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 58
TC 26
Z9 26
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 13
PY 2010
VL 5
IS 12
AR e15239
DI 10.1371/journal.pone.0015239
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 693SY
UT WOS:000285246900035
PM 21179212
ER
PT J
AU Sambuughin, N
Yau, KS
Olive, M
Duff, RM
Bayarsaikhan, M
Lu, SJ
Gonzalez-Mera, L
Sivadorai, P
Nowak, KJ
Ravenscroft, G
Mastaglia, FL
North, KN
Ilkovski, B
Kremer, H
Lammens, M
van Engelen, BGM
Fabian, V
Lamont, P
Davis, MR
Laing, NG
Goldfarb, LG
AF Sambuughin, Nyamkhishig
Yau, Kyle S.
Olive, Montse
Duff, Rachael M.
Bayarsaikhan, Munkhuu
Lu, Shajia
Gonzalez-Mera, Laura
Sivadorai, Padma
Nowak, Kristen J.
Ravenscroft, Gianina
Mastaglia, Frank L.
North, Kathryn N.
Ilkovski, Biljana
Kremer, Hannie
Lammens, Martin
van Engelen, Baziel G. M.
Fabian, Vicki
Lamont, Phillipa
Davis, Mark R.
Laing, Nigel G.
Goldfarb, Lev G.
TI Dominant Mutations in KBTBD13, a Member of the BTB/Kelch Family, Cause
Nemaline Myopathy with Cores
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID ALPHA-TROPOMYOSIN; CONGENITAL MYOPATHY; RYANODINE RECEPTOR; UBIQUITIN
LIGASES; PROTEIN; CARDIOMYOPATHY; GIGAXONIN; DISEASE; RODS
AB We identified a member of the BTB/Kelch protein family that is mutated in nemaline myopathy type 6 (NEM6), an autosomal-dominant neuromuscular disorder characterized by the presence of nemaline rods and core lesions in the skeletal myofibers. Analysis of affected families allowed narrowing of the candidate region on chromosome 15q22.31, and mutation screening led to the identification of a previously uncharacterized gene, KBTBD13, coding for a hypothetical protein and containing missense mutations that perfectly cose-gregate with nemaline myopathy in the studied families. KBTBD13 contains a BTB/POZ domain and five Kelch repeats and is expressed primarily in skeletal and cardiac muscle. The identified disease-associated mutations, C.742C>A (p.Arg248Ser), c.1170G>C (p.Lys390Asn), and c.1222C>T (p.Arg408Cys), located in conserved domains of Kelch repeats, are predicted to disrupt the molecule's beta-propeller blades. Previously identified BTB/POZ/Kelch-domain-containing proteins have been implicated in a broad variety of biological processes, including cytoskeleton modulation, regulation of gene transcription, ubiquitination, and myofibril assembly. The functional role of KBTBD13 in skeletal muscle and the pathogenesis of NEM6 are subjects for further studies.
C1 [Sambuughin, Nyamkhishig; Bayarsaikhan, Munkhuu] Uniformed Serv Univ Hlth Sci, Dept Anesthesiol, Bethesda, MD 20814 USA.
[Yau, Kyle S.; Duff, Rachael M.; Nowak, Kristen J.; Ravenscroft, Gianina; Laing, Nigel G.] Univ Western Australia, Med Res Ctr, QEII Med Ctr, Western Australia Inst Med Res, Nedlands, WA 6009, Australia.
[Olive, Montse; Gonzalez-Mera, Laura] IDIBELL Hosp Bellvitge, Inst Neuropatol, Dept Pathol, Barcelona 08907, Spain.
[Olive, Montse; Gonzalez-Mera, Laura] IDIBELL Hosp Bellvitge, Dept Neurol, Neuromuscular Unit, Barcelona 08907, Spain.
[Olive, Montse; Gonzalez-Mera, Laura] CIBERNED, Barcelona 08907, Spain.
[Lu, Shajia] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Sivadorai, Padma; Fabian, Vicki; Davis, Mark R.] Royal Perth Hosp, Dept Anat Pathol, Perth, WA 6000, Australia.
[Mastaglia, Frank L.] Univ Western Australia, Ctr Neuromuscular & Neurol Disorders, Nedlands, WA 6009, Australia.
[North, Kathryn N.; Ilkovski, Biljana] Childrens Hosp Westmead, Inst Neurosci & Muscle Res, Westmead, NSW 2145, Australia.
[Kremer, Hannie; Lammens, Martin; van Engelen, Baziel G. M.] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, NL-6500 Nijmegen, Netherlands.
[Lamont, Phillipa] Royal Perth Hosp, Div Neurosci, Perth, WA 6000, Australia.
[Goldfarb, Lev G.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Sambuughin, N (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anesthesiol, Bethesda, MD 20814 USA.
EM nsambuughin@usuhs.mil
RI Kremer, Hannie/F-5126-2010; Engelen, B.G.M./H-8027-2014; Ravenscroft,
Gina/H-5695-2014; North, Kathryn/K-6476-2012;
OI Kremer, Hannie/0000-0002-0841-8693; North, Kathryn/0000-0003-0841-8009;
Olive, Montse/0000-0001-5727-0165; Gonzalez-Mera,
Laura/0000-0001-5691-0343
FU USU [R080CD]; Instituto Carlos III, Ministry of Education and Research,
Spain [PI08-574]; Australian National Health and Medical Research
Council (NHMRC) [403904, 403941]; National Institute of Neurological
Disorders and Stroke, NIH
FX The authors would like to thank the members of the affected families for
their participation in the study. We thank O. Mungunsukh, USU, for
technical advice and for providing RNA from mice tissues. We are
grateful to R. Horowits, NIH, for critical comments on the manuscript.
The authors thank the Biomedical Instrumentation Center of USU for oligo
synthesis, DNA sequencing, and assistance with confocal microscopy. This
research was supported by a USU R080CD grant to N.S. M.O. is supported
by FIS grant PI08-574 from the Instituto Carlos III, Ministry of
Education and Research, Spain. N.G.L. is supported by an Australian
National Health and Medical Research Council (NHMRC) fellowship grant,
403904. K.J.N., G.R., and B.I. are supported by NHMRC project grant
403941. This work was supported in part by the Intramural Research
Program of the National Institute of Neurological Disorders and Stroke,
NIH.
NR 29
TC 62
Z9 67
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD DEC 10
PY 2010
VL 87
IS 6
BP 842
EP 847
DI 10.1016/j.ajhg.2010.10.020
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 698AT
UT WOS:000285564600011
PM 21109227
ER
PT J
AU Carrasquillo, MM
Nicholson, AM
Finch, N
Gibbs, JR
Baker, M
Rutherford, NJ
Hunter, TA
DeJesus-Hernandez, M
Bisceglio, GD
Mackenzie, IR
Singleton, A
Cookson, MR
Crook, JE
Dillman, A
Hernandez, D
Petersen, RC
Graff-Radford, NR
Younkin, SG
Rademakers, R
AF Carrasquillo, Minerva M.
Nicholson, Alexandra M.
Finch, NiCole
Gibbs, J. Raphael
Baker, Matt
Rutherford, Nicola J.
Hunter, Talisha A.
DeJesus-Hernandez, Mariely
Bisceglio, Gina D.
Mackenzie, Ian R.
Singleton, Andrew
Cookson, Mark R.
Crook, Julia E.
Dillman, Allissa
Hernandez, Dena
Petersen, Ronald C.
Graff-Radford, Neill R.
Younkin, Steven G.
Rademakers, Rosa
TI Genome-wide Screen Identifies rs646776 near Sortilin as a Regulator of
Progranulin Levels in Human Plasma
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID FRONTOTEMPORAL LOBAR DEGENERATION; ALZHEIMERS-DISEASE;
GENETIC-VARIABILITY; DEMENTIA; ASSOCIATION; RECEPTOR; CHOLESTEROL;
MUTATIONS; PROTEIN; CONTRIBUTES
AB Recent studies suggest progranulin (GRN) is a neurotrophic factor. Loss-of-function mutations in the progranulin gene (GRN) cause frontotemporal lobar degeneration (FTLD), a progressive neurodegenerative disease affecting similar to 10% of early-onset dementia patients. Using an enzyme-linked immunosorbent assay, we previously showed that GRN is detectable in human plasma and can be used to predict URN mutation status. This study also showed a wide range in plasma GRN levels in non-GRN mutation carriers, including controls. We have now performed a genome-wide association study of 313,504 single-nucleotide polymorphisms (SNPs) in 533 control samples and identified on chromosome 1p13.3 two SNPs with genome-wide significant association with plasma GRN levels (top SNP rs646776; p = 1.7 x 10(-30)). The association of rs646776 with plasma GRN levels was replicated in two independent series of 508 controls (p = 1.9 x 10(-19)) and 197 FTLD patients (p = 6.4 x 10(-12)). Overall, each copy of the minor C allele decreased GRN levels by similar to 15%. SNP rs646776 is located near sortilin (SORT1), and the minor C allele of rs646776 was previously associated with increased SORT1 mRNA levels. Supporting these findings, overexpression of SORT1 in cultured HeLa cells dramatically reduced GRN levels in the conditioned media, whereas knockdown of SORT1 increased extracellular GRN levels. In summary, we identified significant association of a locus on chromosome 1p13.3 with plasma GRN levels through an unbiased genome-wide screening approach and implicated SORT1 as an important regulator of GRN levels. This finding opens avenues for future research into GRN biology and the pathophysiology of neurodegenerative diseases.
C1 [Carrasquillo, Minerva M.; Nicholson, Alexandra M.; Finch, NiCole; Baker, Matt; Rutherford, Nicola J.; Hunter, Talisha A.; DeJesus-Hernandez, Mariely; Bisceglio, Gina D.; Crook, Julia E.; Younkin, Steven G.; Rademakers, Rosa] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA.
[Gibbs, J. Raphael; Singleton, Andrew; Cookson, Mark R.; Dillman, Allissa; Hernandez, Dena] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Gibbs, J. Raphael; Hernandez, Dena] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Gibbs, J. Raphael; Hernandez, Dena] UCL, Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England.
[Mackenzie, Ian R.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 4H4, Canada.
[Petersen, Ronald C.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN 55905 USA.
[Graff-Radford, Neill R.] Mayo Clin, Coll Med, Dept Neurol, Jacksonville, FL 32224 USA.
RP Rademakers, R (reprint author), Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA.
EM rademakers.rosa@mayo.edu
RI Singleton, Andrew/C-3010-2009
FU National Institutes of Health, Mayo Alzheimer's Disease Research Center
[P50 AG16574]; National Institutes of Health, Mayo Alzheimer's Disease
Patient Registry [U01 AG06576]; National Institutes of Health [R01
NS065782, R01 AG18023]; Consortium for Frontotemporal Dementia Research;
Robert and Clarice Smith Postdoctoral Fellowship; Robert and Clarice
Smith and Abigail Van Buren Alzheimer's Disease Research Program;
Canadian Institutes of Health Research [74580]; Pacific Alzheimer's
Disease Research Foundation; National Institute on Aging, National
Institutes of Health, Department of Health and Human Services [ZIA
AG000932-03]
FX The authors wish to acknowledge and thank the families who contributed
samples that were critically important to this study. This work was
supported by the National Institutes of Health (grant numbers P50
AG16574 [Mayo Alzheimer's Disease Research Center, R.C.P. as PI; to
R.R., N.R.G.-R., and S.G.Y.], U01 AG06576 [Mayo Alzheimer's Disease
Patient Registry: R.C.P. as PI], R01 NS065782 [to R.R.], and R01 AG18023
[to N.R.G.-R. and S.G.Y.]). This project was also generously supported
by the Consortium for Frontotemporal Dementia Research (to R.R.), the
Robert and Clarice Smith Postdoctoral Fellowship (to M.M.C.), the Robert
and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research
Program (to R.C.P., N.R.G.-R., and S.G.Y.), and the Palumbo
Professorship in Alzheimer's Disease Research (to S.G.Y.). I.R.M. was
supported by the Canadian Institutes of Health Research Operating
(#74580) and the Pacific Alzheimer's Disease Research Foundation. This
work was supported in part by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health, Department
of Health and Human Services; project number ZIA AG000932-03.
NR 48
TC 54
Z9 54
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD DEC 10
PY 2010
VL 87
IS 6
BP 890
EP 897
DI 10.1016/j.ajhg.2010.11.002
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 698AT
UT WOS:000285564600017
PM 21087763
ER
PT J
AU Lee, HJ
Pagani, J
Young, WS
AF Lee, Heon-Jin
Pagani, Jerome
Young, W. Scott, III
TI Using transgenic mouse models to study oxytocin's role in the
facilitation of species propagation
SO BRAIN RESEARCH
LA English
DT Review
DE Oxytocin; Oxytocin receptor; Transgenic animal; Social behavior
ID ESTROGEN-RECEPTOR-ALPHA; KNOCKOUT MICE; SOCIAL RECOGNITION; SEXUAL
RECEPTIVITY; GENE-EXPRESSION; DEFICIENT MICE; VENTROMEDIAL HYPOTHALAMUS;
PLASMA OXYTOCIN; PENILE ERECTION; BINDING-SITES
AB Oxytocin and its receptor are important for a wide range of effects from social memory to uterine contractions It is an evolutionarily well conserved hormone that is particularly important in social and gregarious animals Research on small mammals has yielded a rich literature on oxytocin's many functions Recently a new tool has been created that has furthered our understanding of oxytocin s role in behavior transgenic mice that lack either the ability to synthesize oxytocin or the oxytocin receptor itself The study of these lines while still in its infancy is already bearing the fruit and offers the promise of insight into some human disorders characterized by aberrant social behavior Published by Elsevier B V
C1 [Lee, Heon-Jin] Kyungpook Natl Univ, Sch Dent, Dept Dent Microbiol, Taegu, South Korea.
[Pagani, Jerome; Young, W. Scott, III] NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA.
RP Young, WS (reprint author), 9000 Rockville Pike,Bldg 49,Room 5A60, Bethesda, MD 20892 USA.
RI Young, W Scott/A-9333-2009;
OI Young, W Scott/0000-0001-6614-5112; , Heon-Jin/0000-0002-1911-5014
FU NIMH [Z01 MH 002498 21]
FX This work was supported by the NIMH Intramural Research Program (Z01 MH
002498 21)
NR 112
TC 11
Z9 12
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD DEC 10
PY 2010
VL 1364
SI SI
BP 216
EP 224
DI 10.1016/j.brainres.2010.08.042
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 699ZH
UT WOS:000285701400021
PM 20732312
ER
PT J
AU Prinz, WA
AF Prinz, William A.
TI Lipid Trafficking sans Vesicles: Where, Why, How?
SO CELL
LA English
DT Article
ID OXYSTEROL-BINDING PROTEIN; PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM;
GLYCOSPHINGOLIPID SYNTHESIS; NONVESICULAR TRAFFICKING;
SACCHAROMYCES-CEREVISIAE; INTRACELLULAR-TRANSPORT; GOLGI-APPARATUS;
STEROL TRANSFER; CHOLESTEROL
AB Eukaryotic cells possess a remarkable diversity of lipids, which distribute among cellular membranes by well-characterized vesicle trafficking pathways. However, transport of lipids by alternate, or "nonvesicular," routes is also critical for lipid synthesis, metabolism, and proper membrane partitioning. In the past few years, considerable progress has been made in characterizing the mechanisms of nonvesicular lipid transport and how it may go awry in particular diseases, but many fundamental questions remain for this rising field.
C1 NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
RP Prinz, WA (reprint author), NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
EM williamp@intra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX I thank Ted Steck, Jim Hurley, and Tim Schulz for reading the
manuscript. This work was supported by the Intramural Research Program
of the National Institute of Diabetes and Digestive and Kidney Diseases.
NR 39
TC 52
Z9 52
U1 1
U2 18
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD DEC 10
PY 2010
VL 143
IS 6
BP 870
EP 874
DI 10.1016/j.cell.2010.11.031
PG 5
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 692VB
UT WOS:000285182600005
PM 21145454
ER
PT J
AU Hurley, JH
Boura, E
Carlson, LA
Rozycki, B
AF Hurley, James H.
Boura, Evzen
Carlson, Lars-Anders
Rozycki, Bartosz
TI Membrane Budding
SO CELL
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ESCRT-III PROTEIN; MULTIVESICULAR BODY
BIOGENESIS; CLATHRIN-MEDIATED ENDOCYTOSIS; VESICULAR-STOMATITIS-VIRUS;
COATED VESICLE FORMATION; PLASMA-MEMBRANE; MATRIX PROTEIN; STRUCTURAL
BASIS; INFLUENZA-VIRUS
AB Membrane budding is a key step in vesicular transport, multivesicular body biogenesis, and enveloped virus release. These events range from those that are primarily protein driven, such as the formation of coated vesicles, to those that are primarily lipid driven, such as microdomain-dependent biogenesis of multivesicular bodies. Other types of budding reside in the middle of this spectrum, including caveolae biogenesis, HIV-1 budding, and ESCRT-catalyzed multivesicular body formation. Some of these latter events involve budding away from cytosol, and this unusual topology involves unique mechanisms. This Review discusses progress toward understanding the structural and energetic bases of these different membrane-budding paradigms.
C1 [Hurley, James H.; Boura, Evzen; Carlson, Lars-Anders] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Rozycki, Bartosz] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM hurley@helix.nih.gov
RI Rozycki, Bartosz/B-7005-2009; Boura, Evzen/I-2626-2012; Boura,
Evzen/G-5275-2014
OI Rozycki, Bartosz/0000-0001-5938-7308;
FU National Institutes of Health; NIDDK; IATAP; European Community
FX We thank E. Freed, G. Raposo, W. Prinz, M. Marks, J. Gruenberg, and J.
Bonifacino for comments on drafts of the manuscript, J. Heuser for
providing the image used in Figure 1F, and many colleagues for
stimulating discussions. Research in the Hurley laboratory is supported
the Intramural program of the National Institutes of Health, NIDDK, and
IATAP. B.R. was supported by a Marie Curie International Outgoing
Fellowship within the 7th European Community Framework Programme.
NR 155
TC 118
Z9 118
U1 2
U2 54
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD DEC 10
PY 2010
VL 143
IS 6
BP 875
EP 887
DI 10.1016/j.cell.2010.11.030
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 692VB
UT WOS:000285182600006
PM 21145455
ER
PT J
AU Sloand, EM
Olnes, MJ
Shenoy, A
Weinstein, B
Boss, C
Loeliger, K
Wu, CO
More, K
Barrett, AJ
Scheinberg, P
Young, NS
AF Sloand, Elaine M.
Olnes, Matthew J.
Shenoy, Aarthie
Weinstein, Barbara
Boss, Carol
Loeliger, Kelsey
Wu, Colin O.
More, Kenneth
Barrett, A. John
Scheinberg, Phillip
Young, Neal S.
TI Alemtuzumab Treatment of Intermediate-1 Myelodysplasia Patients Is
Associated With Sustained Improvement in Blood Counts and Cytogenetic
Remissions
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID LOW-RISK MYELODYSPLASIA; SEVERE APLASTIC-ANEMIA; BONE-MARROW FAILURE;
ANTITHYMOCYTE GLOBULIN; IMMUNOSUPPRESSIVE THERAPY; RHEUMATOID-ARTHRITIS;
CYCLOSPORINE-A; MDS PATIENTS; PHASE-II; CAMPATH-1H
AB Purpose
Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and progression to leukemia. Clinical and experimental evidence suggests an immune-mediated pathophysiology in some patients, in whom immunosuppressive therapy (IST) with horse antithymocyte globulin (h-ATG) and cyclosporine (CsA) can be effective. Because of the toxicities associated with h-ATG/CsA, we investigated an alternative regimen with alemtuzumab in MDS.
Patients and Methods
We conducted a nonrandomized, off-label, pilot, phase I/II study of alemtuzumab monotherapy in patients with MDS who were judged likely to respond to IST based on the following criteria: HLA-DR15-negative patients whose age plus the number of months of RBC transfusion dependence (RCTD) was less than 58; and HLA-DR15-positive patients whose age plus RCTD was less than 72. In total, 121 patients with MDS were screened, of whom 32 met eligibility criteria to receive alemtuzumab 10 mg/d intravenously for 10 days. Primary end points were hematologic responses at 3, 6, and 12 months after alemtuzumab.
Results
Seventeen (77%) of 22 evaluable intermediate-1 patients and four (57%) of seven evaluable intermediate-2 patients responded to treatment with a median time to response of 3 months. Four of seven evaluable responders with cytogenetic abnormalities before treatment had normal cytogenetics by 1 year after treatment. Five (56%) of nine responding patients evaluable at 12 months had normal blood counts, and seven (78%) of nine patients were transfusion independent.
Conclusion
Alemtuzumab is safe and active in MDS and may be an attractive alternative to ATG in selected patients likely to respond to IST.
C1 [Sloand, Elaine M.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Sloand, EM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 4-5230, Bethesda, MD 20892 USA.
EM sloande@nhlbi.nih.gov
OI Scheinberg, Phillip/0000-0002-9047-4538
FU National Institutes of Health, National Heart, Lung, and Blood
Institute, Bethesda, MD
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Heart, Lung, and Blood Institute, Bethesda, MD.
NR 41
TC 59
Z9 60
U1 0
U2 3
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 10
PY 2010
VL 28
IS 35
BP 5166
EP 5173
DI 10.1200/JCO.2010.29.7010
PG 8
WC Oncology
SC Oncology
GA 691PH
UT WOS:000285092800018
PM 21041705
ER
PT J
AU Fox, E
Aplenc, R
Bagatell, R
Chuk, MK
Dombi, E
Goodspeed, W
Goodwin, A
Kromplewski, M
Jayaprakash, N
Marotti, M
Brown, KH
Wenrich, B
Adamson, PC
Widemann, BC
Balis, FM
AF Fox, Elizabeth
Aplenc, Richard
Bagatell, Rochelle
Chuk, Meredith K.
Dombi, Eva
Goodspeed, Wendy
Goodwin, Anne
Kromplewski, Marie
Jayaprakash, Nalini
Marotti, Marcelo
Brown, Kathryn H.
Wenrich, Barbara
Adamson, Peter C.
Widemann, Brigitte C.
Balis, Frank M.
TI A Phase 1 Trial and Pharmacokinetic Study of Cediranib, an Orally
Bioavailable Pan-Vascular Endothelial Growth Factor Receptor Inhibitor,
in Children and Adolescents With Refractory Solid Tumors
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID TYROSINE KINASE; AZD2171; PROGRAM; CANCER
AB Purpose
To determine the toxicity profile, dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of cediranib administered orally, once daily, continuously in children and adolescents with solid tumors.
Patients and Methods
Children and adolescents with refractory solid tumors, excluding primary brain tumors, were eligible. DLT at the starting dose of 12 mg/m(2)/d resulted in de-escalation to 8 mg/m(2)/d and subsequent re-escalation to 12 and 17 mg/m(2)/d. Pharmacokinetic and pharmacodynamic studies were performed during cycle 1. Response was evaluated using WHO criteria.
Results
Sixteen patients (median age, 15 years; range, 8 to 18 years) were evaluable for toxicity. DLTs (grade 3 nausea, vomiting, fatigue in one; hypertension and prolonged corrected QT interval in another) occurred in patients initially enrolled at 12 mg/m(2)/d. Subsequently, 8 mg/m(2)/d was well tolerated in three patients. An additional seven patients were enrolled at 12 mg/m(2)/d; one had DLT (grade 3 diarrhea). At 17 mg/m(2)/d, two of four patients had DLTs (grade 3 nausea; intolerable grade 2 fatigue). Non-dose-limiting toxicities included left ventricular dysfunction, elevated thyroid stimulating hormone, palmar-plantar erythrodysesthesia, weight loss, and headache. The MTD of cediranib was 12 mg/m(2)/d (adult fixed dose equivalent, 20 mg). At 12 mg/m2/d, the median area under the plasma concentration-time curve extrapolated to infinity (AUC(o-infinity)) was 900 ng center dot h/mL, which is similar to adults receiving 20 mg. Objective responses were observed in patients with Ewing sarcoma, synovial sarcoma, and osteosarcoma.
Conclusion
The recommended monotherapy dose of cediranib for children with extracranial solid tumors is 12 mg/m2/d administered orally, once daily, continuously. A phase II study is in development.
C1 [Fox, Elizabeth] Univ Penn, Div Oncol CTRB4016, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
AstraZeneca, Macclesfield, Cheshire, England.
AstraZeneca, Wilmington, DE USA.
RP Fox, E (reprint author), Univ Penn, Div Oncol CTRB4016, Childrens Hosp Philadelphia, Sch Med, 3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM foxe@e-mail.chop.edu
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research; AstraZeneca Pharmaceuticals, Wilmington, DE; Alex's
Lemonade Stand Foundation
FX Supported in part by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research, and AstraZeneca Pharmaceuticals, Wilmington, DE. The clinical
trial at The Children's Hospital of Philadelphia was funded, in part, by
the Alex's Lemonade Stand Foundation.
NR 16
TC 50
Z9 50
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD DEC 10
PY 2010
VL 28
IS 35
BP 5174
EP 5181
DI 10.1200/JCO.2010.30.9674
PG 8
WC Oncology
SC Oncology
GA 691PH
UT WOS:000285092800019
PM 21060028
ER
PT J
AU Korn, EL
Freidlin, B
Mooney, M
Abrams, JS
AF Korn, Edward L.
Freidlin, Boris
Mooney, Margaret
Abrams, Jeffrey S.
TI Accrual Experience of National Cancer Institute Cooperative Group Phase
III Trials Activated From 2000 to 2007
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID COSTS
AB Purpose
Recent reports have suggested that 40% or more of National Cancer Institute (NCI) -sponsored Cooperative Group phase III trials failed to achieve their accrual goals. We examine in detail the accrual experience of the Cooperative Group phase III trials.
Patients and Methods
All Cooperative Group phase III trials activated from 2000 to 2007 were examined for their accrual experience. For trials that stopped accrual with < 90% of their accrual goal, the reasons for having < 90% accrual were documented. We focus on trials that ended with < 90% accrual because of inadequate accrual rates rather than for other reasons, such as an interim monitoring analysis by an independent data monitoring committee that stops the trial early because one treatment is clearly superior.
Results
There were 191 trials activated from 2000 to 2007. We project that 22.0% of these trials will have < 90% accrual because of inadequate accrual rates. We project that there will be 176,627 patients eventually accrued on the 191 trials (current accrual, 154,579) and that 2,991 of these patients will be on trials that have < 90% accrual because of inadequate accrual rates (1.7%). For nonpediatric cancer trials, the corresponding percentages are 26.7% and 2.0%.
Conclusion
We find that insufficient accrual rates are not as high as previously reported and that only a small proportion of patients were enrolled on trials that ended with insufficient accrual because of an inadequate accrual rate. NCI has implemented new procedures to reduce the number of trials that fail to reach their accrual goals and to minimize the number of patients accrued on these trials.
C1 [Korn, Edward L.] NCI, Biometr Res Branch, Clin Invest Branch, Bethesda, MD 20892 USA.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Korn, EL (reprint author), NCI, Biometr Res Branch, Clin Invest Branch, EPN-8129, Bethesda, MD 20892 USA.
EM korne@ctep.nci.nih.gov
NR 15
TC 22
Z9 22
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD DEC 10
PY 2010
VL 28
IS 35
BP 5197
EP 5201
DI 10.1200/JCO.2010.31.5382
PG 5
WC Oncology
SC Oncology
GA 691PH
UT WOS:000285092800022
PM 21060029
ER
PT J
AU Miknis, ZJ
Magracheva, E
Li, W
Zdanov, A
Kotenko, SV
Wlodawer, A
AF Miknis, Zachary J.
Magracheva, Eugenia
Li, Wei
Zdanov, Alexander
Kotenko, Sergei V.
Wlodawer, Alexander
TI Crystal Structure of Human Interferon-lambda 1 in Complex with Its
High-Affinity Receptor Interferon-lambda R1
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE cytokine; crystallography; antiviral; immunity; signaling
ID HEPATITIS-C VIRUS; IFN-LAMBDA; INTERLEUKIN-10 REVEALS;
SIGNAL-TRANSDUCTION; ANTITUMOR-ACTIVITY; GENETIC-VARIATION; III
INTERFERONS; PROTEIN; CHAIN; GAMMA
AB Interferon (IFN)-lambda 1 [also known as interleukiun (IL)-29] belongs to the recently discovered group of type III IFNs. All type III IFNs initiate signaling processes through formation of specific heterodimeric receptor complexes consisting of IFN-lambda R1 and IL-10R2. We have determined the structure of human IFN-lambda 1 complexed with human IFN-lambda R1, a receptor unique to type III IFNs. The overall structure of IFN-lambda 1 is topologically similar to the structure of IL-10 and other members of the IL-10 family of cytokines. IFN-lambda R1 consists of two distinct domains having fibronectin type III topology. The ligand receptor interface includes helix A, loop AB, and helix F on the IFN site, as well as loops primarily from the N-terminal domain and inter-domain hinge region of IFN-lambda R1. Composition and architecture of the interface that includes only a few direct hydrogen bonds support an idea that long-range ionic interactions between ligand and receptor govern the process of initial recognition of the molecules while hydrophobic interactions finalize it. Published by Elsevier Ltd.
C1 [Miknis, Zachary J.; Magracheva, Eugenia; Zdanov, Alexander; Wlodawer, Alexander] NCI Frederick, Macromol Crystallog Lab, Frederick, MD 21702 USA.
[Magracheva, Eugenia] SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA.
[Li, Wei; Kotenko, Sergei V.] Univ Med & Dent New Jersey, New Jersey Med Sch, Univ Hosp Canc Ctr, Dept Biochem & Mol Biol, Newark, NJ 07103 USA.
RP Wlodawer, A (reprint author), NCI Frederick, Macromol Crystallog Lab, Frederick, MD 21702 USA.
EM wlodawer@nih.gov
RI Li, Wei/I-8060-2014
FU U.S. Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-21-109-Eng-38]; National Institutes of Health, National
Cancer Institute, Center for Cancer Research; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]; National Institute of
Allergy and Infectious Diseases [RO1 AI057468]
FX We would like to thank Dr. Mark Walter for providing us with the
coordinates of the models of ternary complexes of cytokines. Diffraction
data were collected at Southeast Regional Collaborative Access Team
22-ID (or 22-BM) beamline at the Advanced Photon Source, Argonne
National Laboratory. Use of the Advanced Photon Source was supported by
the U.S. Department of Energy, Office of Science, Office of Basic Energy
Sciences, under Contract No. W-21-109-Eng-38. This project was supported
in part by the Intramural Research Program of the National Institutes of
Health, National Cancer Institute, Center for Cancer Research, with
Federal funds from the National Cancer Institute, National Institutes of
Health, under Contract No. HHSN261200800001E, and by the U.S. Public
Health Services Grant RO1 AI057468 (S.V.K.) from the National Institute
of Allergy and Infectious Diseases. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services; neither does the mention of trade names,
commercial products, or organizations imply endorsement by the U.S.
Government.
NR 66
TC 34
Z9 43
U1 1
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD DEC 10
PY 2010
VL 404
IS 4
BP 650
EP 664
DI 10.1016/j.jmb.2010.09.068
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 703YN
UT WOS:000286018000009
PM 20934432
ER
PT J
AU Kumar, J
Mayer, ML
AF Kumar, Janesh
Mayer, Mark L.
TI Crystal Structures of the Glutamate Receptor Ion Channel GluK3 and GluK5
Amino-Terminal Domains
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE kainate receptor; glycosylation; structural biology; cell surface
receptor; synaptic plasticity
ID LIGAND-BINDING CORES; HIGH-AFFINITY; NMDA RECEPTORS; KAINATE; SUBUNIT;
PROTEIN; MECHANISM; RECOGNITION; EXPRESSION; CLONING
AB Ionotropic glutamate receptors (iGluRs) mediate the majority of fast excitatory synaptic neurotransmission in the central nervous system. The selective assembly of iGluRs into AMPA, kainate, and N-methyl-D-aspartic acid (NMDA) receptor subtypes is regulated by their extracellular amino-terminal domains (ATDs). Kainate receptors are further classified into low-affinity receptor families (GluK1-GluK3) and high-affinity receptor families (GluK4-GluK5) based on their affinity for the neurotoxin kainic acid. These two families share a 42% sequence identity for the intact receptor but only a 27% sequence identity at the level of ATD. We have determined for the first time the high-resolution crystal structures of GluK3 and GluK5 ATDs, both of which crystallize as dimers but with a strikingly different dimer assembly at the R1 interface. By contrast, for both GluK3 and GluK5, the R2 domain dimer assembly is similar to those reported previously for other non-NMDA iGluRs. This observation is consistent with the reports that GluK4-GluK5 cannot form functional homomeric ion channels and require obligate coassembly with GluK1-GluK3. Our analysis also reveals that the relative orientation of domains R1 and R2 in individual non-NMDA receptor ATDs varies by up to 10 degrees, in contrast to the 50 degrees difference reported for the NMDA receptor GluN2B subunit. This restricted domain movement in non-NMDA receptor ATDs seems to result both from extensive intramolecular contacts between domain R1 and domain R2 and from their assembly as dimers, which interact at both R1 and R2 domains. Our results provide the first insights into the structure and function of GluK4-GluK5, the least understood family of iGluRs. Published by Elsevier Ltd.
C1 [Kumar, Janesh; Mayer, Mark L.] NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Mayer, ML (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,Dept Hlth & Human Serv, Room 3B1002,Bldg 35, Bethesda, MD 20892 USA.
EM mayerm@mail.nih.gov
RI Mayer, Mark/H-5500-2013
FU National Cancer Institute [Y1-CO-1020]; National Institute of General
Medical Science [Y1-GM-1104]; US Department of Energy, Office of
Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; National
Institute of Child Health and Human Development, National Institutes of
Health, Department of Health and Human Services
FX We thank Dr. Jinjin Zhang for critical reading of the manuscript; Carla
Glasser for technical assistance; Drs. S. Hansen and Philip Reeves (MIT)
for the gift of GnTI- cells; and Dr. Howard Jaffe
(Protein/Peptide Sequencing Facility, National Institute of Neurological
Disorders and Stroke) for mass spectral analysis and N-terminal
sequencing. Nucleic acid sequencing was performed at the National
Institute of Neurological Disorders and Stroke DNA Sequencing Facility.
Synchrotron diffraction data were collected at the SER-CAT 22 ID and
GM/CA CAT 23 ID-B beamlines. GM/CA CAT was funded, in whole or in part,
with Federal funds from the National Cancer Institute (Y1-CO-1020) and
the National Institute of General Medical Science (Y1-GM-1104). Use of
the APS was supported by the US Department of Energy, Office of Science,
Office of Basic Energy Sciences, under contract no. DE-AC02-06CH11357.
This work was supported by the intramural research program of the
National Institute of Child Health and Human Development, National
Institutes of Health, Department of Health and Human Services (M.L.M.).
NR 58
TC 29
Z9 31
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD DEC 10
PY 2010
VL 404
IS 4
BP 680
EP 696
DI 10.1016/j.jmb.2010.10.006
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 703YN
UT WOS:000286018000011
PM 20951142
ER
PT J
AU Pereyra, FP
Jia, XM
McLaren, PJ
Telenti, A
de Bakker, PIW
Walker, BD
Ripke, S
Brumme, CJ
Pulit, SL
Carrington, M
Kadie, CM
Carlson, JM
Heckerman, D
Graham, RR
Plenge, RM
Deeks, SG
Gianniny, L
Crawford, G
Sullivan, J
Gonzalez, E
Davies, L
Camargo, A
Moore, JM
Beattie, N
Gupta, S
Crenshaw, A
Burtt, NP
Guiducci, C
Gupta, N
Carrington, M
Gao, XJ
Qi, Y
Yuki, Y
Piechocka-Trocha, A
Cutrell, E
Rosenberg, R
Moss, KL
Lemay, P
O'Leary, J
Schaefer, T
Verma, P
Toth, I
Block, B
Baker, B
Rothchild, A
Lian, J
Proudfoot, J
Alvino, DML
Vine, S
Addo, MM
Allen, TM
Altfeld, M
Henn, MR
Le Gall, S
Streeck, H
Haas, DW
Kuritzkes, DR
Robbins, GK
Shafer, RW
Gulick, RM
Shikuma, CM
Haubrich, R
Riddler, S
Sax, PE
Daar, ES
Ribaudo, HJ
Agan, B
Agarwal, S
Ahern, RL
Allen, BL
Altidor, S
Altschuler, EL
Ambardar, S
Anastos, K
Anderson, B
Anderson, V
Andrady, U
Antoniskis, D
Bangsberg, D
Barbaro, D
Barrie, W
Bartczak, J
Barton, S
Basden, P
Basgoz, N
Bazner, S
Bellos, NC
Benson, AM
Berger, J
Bernard, NF
Bernard, AM
Birch, C
Bodner, SJ
Bolan, RK
Boudreaux, ET
Bradley, M
Braun, JF
Brndjar, JE
Brown, SJ
Brown, K
Brown, ST
Burack, J
Bush, LM
Cafaro, V
Campbell, O
Campbell, J
Carlson, RH
Carmichael, JK
Casey, KK
Cavacuiti, C
Celestin, G
Chambers, ST
Chez, N
Chirch, LM
Cimoch, PJ
Cohen, D
Cohn, LE
Conway, B
Cooper, DA
Cornelson, B
Cox, DT
Cristofano, MV
Cuchural, G
Czartoski, JL
Dahman, JM
Daly, JS
Davis, BT
Davis, K
Davod, SM
Deeks, SG
DeJesus, E
Dietz, CA
Dunham, E
Dunn, ME
Ellerin, TB
Eron, JJ
Fangman, JJW
Farel, CE
Ferlazzo, H
Fidler, S
Fleenor-Ford, A
Frankel, R
Freedberg, KA
French, NK
Fuchs, JD
Fuller, JD
Gaberman, J
Gallant, JE
Gandhi, RT
Garcia, E
Garmon, D
Gathe, JC
Gaultier, CR
Gebre, W
Gilman, FD
Gilson, I
Goepfert, PA
Gottlieb, MS
Goulston, C
Groger, RK
Gurley, TD
Haber, S
Hardwicke, R
Hardy, WD
Harrigan, PR
Hawkins, TN
Heath, S
Hecht, FM
Henry, WK
Hladek, M
Hoffman, RP
Horton, JM
Hsu, RK
Huhn, GD
Hunt, P
Hupert, MJ
Illeman, ML
Jaeger, H
Jellinger, RM
John, M
Johnson, JA
Johnson, KL
Johnson, H
Johnson, K
Joly, J
Jordan, WC
Kauffman, CA
Khanlou, H
Killian, RK
Kim, AY
Kim, DD
Kinder, CA
Kirchner, JT
Kogelman, L
Kojic, EM
Korthuis, T
Kurisu, W
Kwon, DS
LaMar, M
Lampiris, H
Lanzafame, M
Lederman, MM
Lee, DM
Lee, JML
Lee, MJ
Lee, ETY
Lemoine, J
Levy, JA
Llibre, JM
Liguori, MA
Little, SJ
Liu, AY
Lopez, AJ
Loutfy, MR
Loy, D
Mohammed, DY
Man, A
Mansour, MK
Marconi, VC
Markowitz, M
Marques, R
Martin, JN
Martin, HL
Mayer, KH
McElrath, MJ
McGhee, TA
McGovern, BH
McGowan, K
McIntyre, D
Mcleod, GX
Menezes, P
Mesa, G
Metroka, CE
Meyer-Olson, D
Miller, AO
Montgomery, K
Mounzer, KC
Nagami, EH
Nagin, I
Nahass, RG
Nelson, MO
Nielsen, C
Norene, DL
O'Connor, DH
Ojikutu, BO
Okulicz, J
Oladehin, OO
Oldfield, EC
Olender, SA
Ostrowski, M
Owen, WF
Pae, E
Parsonnet, J
Pavlatos, AM
Perlmutter, AM
Pierce, MN
Pincus, JM
Pisani, L
Price, LJ
Proia, L
Prokesch, RC
Pujet, HC
Ramgopal, M
Rathod, A
Rausch, M
Ravishankar, J
Rhame, FS
Richards, CS
Richman, DD
Robbins, GK
Rodes, B
Rodriguez, M
Rose, RC
Rosenberg, ES
Rosenthal, D
Ross, PE
Rubin, DS
Rumbaugh, E
Saenz, L
Salvaggio, MR
Sanchez, WC
Sanjana, VM
Santiago, S
Schmidt, W
Schuitemaker, H
Sestak, PM
Shalit, P
Shay, W
Shirvani, VN
Silebi, VI
Sizemore, JM
Skolnik, PR
Sokol-Anderson, M
Sosman, JM
Stabile, P
Stapleton, JT
Starrett, S
Stein, F
Stellbrink, HJ
Sterman, FL
Stone, VE
Stone, DR
Tambussi, G
Taplitz, RA
Tedaldi, EM
Telenti, A
Theisen, W
Torres, R
Tosiello, L
Tremblay, C
Tribble, MA
Trinh, PD
Tsao, A
Ueda, P
Vaccaro, A
Valadas, E
Vanig, TJ
Vecino, I
Vega, VM
Veikley, W
Wade, BH
Walworth, C
Wanidworanun, C
Ward, DJ
Warner, DA
Weber, RD
Webster, D
Weis, S
Wheeler, DA
White, DJ
Wilkins, E
Winston, A
Wlodaver, CG
van't Wout, A
Wright, DP
Yang, OO
Yurdin, DL
Zabukovic, BW
Zachary, KC
Zeeman, B
Zhao, M
AF Pereyra, Florencia
Jia, Xiaoming
McLaren, Paul J.
Telenti, Amalio
de Bakker, Paul I. W.
Walker, Bruce D.
Ripke, Stephan
Brumme, Chanson J.
Pulit, Sara L.
Carrington, Mary
Kadie, Carl M.
Carlson, Jonathan M.
Heckerman, David
Graham, Robert R.
Plenge, Robert M.
Deeks, Steven G.
Gianniny, Lauren
Crawford, Gabriel
Sullivan, Jordan
Gonzalez, Elena
Davies, Leela
Camargo, Amy
Moore, Jamie M.
Beattie, Nicole
Gupta, Supriya
Crenshaw, Andrew
Burtt, Noel P.
Guiducci, Candace
Gupta, Namrata
Carrington, Mary
Gao, Xiaojiang
Qi, Ying
Yuki, Yuko
Piechocka-Trocha, Alicja
Cutrell, Emily
Rosenberg, Rachel
Moss, Kristin L.
Lemay, Paul
O'Leary, Jessica
Schaefer, Todd
Verma, Pranshu
Toth, Ildiko
Block, Brian
Baker, Brett
Rothchild, Alissa
Lian, Jeffrey
Proudfoot, Jacqueline
Alvino, Donna Marie L.
Vine, Seanna
Addo, Marylyn M.
Allen, Todd M.
Altfeld, Marcus
Henn, Matthew R.
Le Gall, Sylvie
Streeck, Hendrik
Haas, David W.
Kuritzkes, Daniel R.
Robbins, Gregory K.
Shafer, Robert W.
Gulick, Roy M.
Shikuma, Cecilia M.
Haubrich, Richard
Riddler, Sharon
Sax, Paul E.
Daar, Eric S.
Ribaudo, Heather J.
Agan, Brian
Agarwal, Shanu
Ahern, Richard L.
Allen, Brady L.
Altidor, Sherly
Altschuler, Eric L.
Ambardar, Sujata
Anastos, Kathryn
Anderson, Ben
Anderson, Val
Andrady, Ushan
Antoniskis, Diana
Bangsberg, David
Barbaro, Daniel
Barrie, William
Bartczak, J.
Barton, Simon
Basden, Patricia
Basgoz, Nesli
Bazner, Suzane
Bellos, Nicholaos C.
Benson, Anne M.
Berger, Judith
Bernard, Nicole F.
Bernard, Annette M.
Birch, Christopher
Bodner, Stanley J.
Bolan, Robert K.
Boudreaux, Emilie T.
Bradley, Meg
Braun, James F.
Brndjar, Jon E.
Brown, Stephen J.
Brown, Katherine
Brown, Sheldon T.
Burack, Jedidiah
Bush, Larry M.
Cafaro, Virginia
Campbell, Omobolaji
Campbell, John
Carlson, Robert H.
Carmichael, J. Kevin
Casey, Kathleen K.
Cavacuiti, Chris
Celestin, Gregory
Chambers, Steven T.
Chez, Nancy
Chirch, Lisa M.
Cimoch, Paul J.
Cohen, Daniel
Cohn, Lillian E.
Conway, Brian
Cooper, David A.
Cornelson, Brian
Cox, David T.
Cristofano, Michael V.
Cuchural, George, Jr.
Czartoski, Julie L.
Dahman, Joseph M.
Daly, Jennifer S.
Davis, Benjamin T.
Davis, Kristine
Davod, Sheila M.
Deeks, Steven G.
DeJesus, Edwin
Dietz, Craig A.
Dunham, Eleanor
Dunn, Michael E.
Ellerin, Todd B.
Eron, Joseph J.
Fangman, John J. W.
Farel, Claire E.
Ferlazzo, Helen
Fidler, Sarah
Fleenor-Ford, Anita
Frankel, Renee
Freedberg, Kenneth A.
French, Neel K.
Fuchs, Jonathan D.
Fuller, Jon D.
Gaberman, Jonna
Gallant, Joel E.
Gandhi, Rajesh T.
Garcia, Efrain
Garmon, Donald
Gathe, Joseph C., Jr.
Gaultier, Cyril R.
Gebre, Wondwoosen
Gilman, Frank D.
Gilson, Ian
Goepfert, Paul A.
Gottlieb, Michael S.
Goulston, Claudia
Groger, Richard K.
Gurley, T. Douglas
Haber, Stuart
Hardwicke, Robin
Hardy, W. David
Harrigan, P. Richard
Hawkins, Trevor N.
Heath, Sonya
Hecht, Frederick M.
Henry, W. Keith
Hladek, Melissa
Hoffman, Robert P.
Horton, James M.
Hsu, Ricky K.
Huhn, Gregory D.
Hunt, Peter
Hupert, Mark J.
Illeman, Mark L.
Jaeger, Hans
Jellinger, Robert M.
John, Mina
Johnson, Jennifer A.
Johnson, Kristin L.
Johnson, Heather
Johnson, Kay
Joly, Jennifer
Jordan, Wilbert C.
Kauffman, Carol A.
Khanlou, Homayoon
Killian, Robert K.
Kim, Arthur Y.
Kim, David D.
Kinder, Clifford A.
Kirchner, Jeffrey T.
Kogelman, Laura
Kojic, Erna Milunka
Korthuis, Todd
Kurisu, Wayne
Kwon, Douglas S.
LaMar, Melissa
Lampiris, Harry
Lanzafame, Massimiliano
Lederman, Michael M.
Lee, David M.
Lee, Jean M. L.
Lee, Marah J.
Lee, Edward T. Y.
Lemoine, Janice
Levy, Jay A.
Llibre, Josep M.
Liguori, Michael A.
Little, Susan J.
Liu, Anne Y.
Lopez, Alvaro J.
Loutfy, Mono R.
Loy, Dawn
Mohammed, Debbie Y.
Man, Alan
Mansour, Michael K.
Marconi, Vincent C.
Markowitz, Martin
Marques, Rui
Martin, Jeffrey N.
Martin, Harold L., Jr.
Mayer, Kenneth Hugh
McElrath, M. Juliana
McGhee, Theresa A.
McGovern, Barbara H.
McGowan, Katherine
McIntyre, Dawn
Mcleod, Gavin X.
Menezes, Prema
Mesa, Greg
Metroka, Craig E.
Meyer-Olson, Dirk
Miller, Andy O.
Montgomery, Kate
Mounzer, Karam C.
Nagami, Ellen H.
Nagin, Iris
Nahass, Ronald G.
Nelson, Margret O.
Nielsen, Craig
Norene, David L.
O'Connor, David H.
Ojikutu, Bisola O.
Okulicz, Jason
Oladehin, Olakunle O.
Oldfield, Edward C., III
Olender, Susan A.
Ostrowski, Mario
Owen, William F., Jr.
Pae, Eunice
Parsonnet, Jeffrey
Pavlatos, Andrew M.
Perlmutter, Aaron M.
Pierce, Michael N.
Pincus, Jonathan M.
Pisani, Leandro
Price, Lawrence Jay
Proia, Laurie
Prokesch, Richard C.
Pujet, Heather Calderon
Ramgopal, Moti
Rathod, Almas
Rausch, Michael
Ravishankar, J.
Rhame, Frank S.
Richards, Constance Shamuyarira
Richman, Douglas D.
Robbins, Gregory K.
Rodes, Berta
Rodriguez, Milagros
Rose, Richard C., III
Rosenberg, Eric S.
Rosenthal, Daniel
Ross, Polly E.
Rubin, David S.
Rumbaugh, Elease
Saenz, Luis
Salvaggio, Michelle R.
Sanchez, William C.
Sanjana, Veeraf M.
Santiago, Steven
Schmidt, Wolfgang
Schuitemaker, Hanneke
Sestak, Philip M.
Shalit, Peter
Shay, William
Shirvani, Vivian N.
Silebi, Vanessa I.
Sizemore, James M., Jr.
Skolnik, Paul R.
Sokol-Anderson, Marcia
Sosman, James M.
Stabile, Paul
Stapleton, Jack T.
Starrett, Sheree
Stein, Francine
Stellbrink, Hans-Jurgen
Sterman, F. Lisa
Stone, Valerie E.
Stone, David R.
Tambussi, Giuseppe
Taplitz, Randy A.
Tedaldi, Ellen M.
Telenti, Amalio
Theisen, William
Torres, Richard
Tosiello, Lorraine
Tremblay, Cecile
Tribble, Marc A.
Trinh, Phuong D.
Tsao, Alice
Ueda, Peggy
Vaccaro, Anthony
Valadas, Emilia
Vanig, Thanes J.
Vecino, Isabel
Vega, Vilma M.
Veikley, Wenoah
Wade, Barbara H.
Walworth, Charles
Wanidworanun, Chingchai
Ward, Douglas J.
Warner, Daniel A.
Weber, Robert D.
Webster, Duncan
Weis, Steve
Wheeler, David A.
White, David J.
Wilkins, Ed
Winston, Alan
Wlodaver, Clifford G.
van't Wout, Angelique
Wright, David P.
Yang, Otto O.
Yurdin, David L.
Zabukovic, Brandon W.
Zachary, Kimon C.
Zeeman, Beth
Zhao, Meng
CA Int HIV Controllers Study
TI The Major Genetic Determinants of HIV-1 Control Affect HLA Class I
Peptide Presentation
SO SCIENCE
LA English
DT Article
ID DISEASE PROGRESSION; SURFACE EXPRESSION; INFECTION; AIDS; ALLELES; MHC;
RESTRICTION; ASSOCIATION; THERAPY; ABSENCE
AB Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.
C1 [Pereyra, Florencia; Walker, Bruce D.; Brumme, Chanson J.; Carrington, Mary; Piechocka-Trocha, Alicja; Cutrell, Emily; Rosenberg, Rachel; Moss, Kristin L.; Lemay, Paul; O'Leary, Jessica; Schaefer, Todd; Verma, Pranshu; Toth, Ildiko; Block, Brian; Baker, Brett; Rothchild, Alissa; Lian, Jeffrey; Proudfoot, Jacqueline; Alvino, Donna Marie L.; Vine, Seanna; Addo, Marylyn M.; Allen, Todd M.; Altfeld, Marcus; Le Gall, Sylvie; Streeck, Hendrik; Bazner, Suzane; Birch, Christopher; Bradley, Meg; Kwon, Douglas S.; Nagami, Ellen H.; Pae, Eunice; Rathod, Almas; Tsao, Alice; Ueda, Peggy; Zeeman, Beth] Massachusetts Inst Technol & Harvard, Massachusetts Gen Hosp, Regon Inst, Boston, MA USA.
[Pereyra, Florencia; Kuritzkes, Daniel R.; Sax, Paul E.; Farel, Claire E.; Johnson, Jennifer A.; Liu, Anne Y.; McGowan, Katherine; Theisen, William] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Infect Dis, Boston, MA 02115 USA.
[Jia, Xiaoming] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA.
[McLaren, Paul J.; de Bakker, Paul I. W.; Ripke, Stephan; Pulit, Sara L.; Plenge, Robert M.; Gianniny, Lauren; Crawford, Gabriel; Sullivan, Jordan; Gonzalez, Elena; Davies, Leela; Camargo, Amy; Moore, Jamie M.; Beattie, Nicole; Gupta, Supriya; Crenshaw, Andrew; Burtt, Noel P.; Guiducci, Candace; Gupta, Namrata; Henn, Matthew R.] Harvard & MIT, Broad Inst, Cambridge, MA USA.
[McLaren, Paul J.; de Bakker, Paul I. W.; Pulit, Sara L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA.
[Telenti, Amalio] Univ Lausanne, Inst Microbiol, Lausanne, Switzerland.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Div Biomed Genet, Utrecht, Netherlands.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Ripke, Stephan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Dept Med, Boston, MA USA.
[Gao, Xiaojiang; Qi, Ying; Yuki, Yuko] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, Frederick, MD 21701 USA.
[Kadie, Carl M.] Microsoft Res, Redmond, WA USA.
[Carlson, Jonathan M.; Heckerman, David] Microsoft Res, Los Angeles, CA USA.
[Graham, Robert R.] Genentech Inc, San Francisco, CA 94080 USA.
[Plenge, Robert M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Deeks, Steven G.; Hecht, Frederick M.; Hunt, Peter; Lampiris, Harry; Levy, Jay A.; Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Haas, David W.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Shafer, Robert W.] Stanford Univ, Palo Alto, CA 94304 USA.
[Gulick, Roy M.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
[Shikuma, Cecilia M.] Univ Hawaii, John A Burns Sch Med, Hawaii Ctr AIDS, Honolulu, HI 96822 USA.
[Haubrich, Richard; Little, Susan J.; Richman, Douglas D.; Taplitz, Randy A.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Riddler, Sharon] Univ Pittsburgh, Pittsburgh, PA USA.
[Daar, Eric S.; Hardy, W. David; Yang, Otto O.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Ribaudo, Heather J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Agan, Brian] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA.
[Agarwal, Shanu] Summa Hlth Syst, Akron, OH USA.
[Allen, Brady L.; Lee, David M.] Uptown Phys Grp, Dallas, TX USA.
[Altidor, Sherly; Metroka, Craig E.] St Lukes Roosevelt Hosp, New York, NY 10025 USA.
[Altschuler, Eric L.; Mohammed, Debbie Y.] Univ Med & Dent New Jersey, New Jersey Med Sch, Univ Hosp, Newark, NJ 07103 USA.
[Anastos, Kathryn] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Anderson, Ben] St Leonards Med Ctr, St Leonards, NSW, Australia.
[Anderson, Val; Andrady, Ushan] Ysbyty Gwynedd Hosp, Bangor, Gwynedd, Wales.
[Antoniskis, Diana; Man, Alan; Rumbaugh, Elease] Kaiser Permanente, Portland, OR USA.
[Barbaro, Daniel; Hupert, Mark J.; Johnson, Heather] Tarrant Cty Infect Dis Associates, Ft Worth, TX USA.
[Bartczak, J.] Rowan Tree Med, Wilton Manors, FL USA.
[Barton, Simon] Chelsea & Westminster Hosp, St Stephens Ctr, London, England.
[Bellos, Nicholaos C.] SW Infect Dis Associates, Dallas, TX USA.
[Berger, Judith] St Barnabas Hosp, Bronx, NY USA.
[Bernard, Nicole F.] McGill Univ, Montreal Gen Hosp, Ctr Hlth, Res Inst, Montreal, PQ H3G 1A4, Canada.
[Bernard, Annette M.] Thacker Thompson & Bernard, Atlanta, GA USA.
[Bodner, Stanley J.] Vanderbilt Univ, Sch ofMedicine, Hermitage, TN USA.
[Bolan, Robert K.] LA Gay & Lesbian Ctr, Los Angeles, CA USA.
[Boudreaux, Emilie T.] Louisiana State Univ, Hlth Sci Ctr, Univ Med Ctr E Clin, Lafayatte, LA USA.
[Braun, James F.] Callen Lorde Community Hlth Ctr, Phys Res Network, New York, NY USA.
[Brndjar, Jon E.] Brndjar Med Associates, Allentown, PA USA.
[Brown, Stephen J.] AIDS Res Alliance, Los Angeles, CA USA.
[Brown, Katherine] David Powell Community Hlth Ctr, Austin, TX USA.
[Brown, Sheldon T.] James J Peters VA Med Ctr, Bronx, NY USA.
[Burack, Jedidiah] Sunrise Med Grp, Brooklyn, NY USA.
[Bush, Larry M.] Univ Miami, Miller Sch Med, Lake Worth, FL USA.
[Cafaro, Virginia] WellSpring Med Grp, San Francisco, CA USA.
[Campbell, John] Moses Cone Hlth Syst, Greensboro, NC USA.
[Carlson, Robert H.] HealthPartners Infect Dis, St Paul, MN USA.
[Carmichael, J. Kevin] El Rio Special Immunol Associates, Tucson, AZ USA.
[Casey, Kathleen K.; McIntyre, Dawn] Jersey Shore Univ, Med Ctr, Neptune, NJ USA.
[Cavacuiti, Chris; Cornelson, Brian] St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
[Celestin, Gregory] PATH Ctr, Brooklyn Hosp Ctr, Brooklyn, NY USA.
[Chambers, Steven T.] Univ Otago, Christchurch, New Zealand.
[Chez, Nancy] HELP Project Samaritan, Bronx, NY USA.
[Chirch, Lisa M.; Dunham, Eleanor; Joly, Jennifer] David E Rogers Ctr HIV AIDS Care, Southampton, NY USA.
[Cimoch, Paul J.; Walworth, Charles] Ctr Special Immunol, Fountain Valley, CA USA.
[Cohen, Daniel; Mayer, Kenneth Hugh] Fenway Community Hlth, Boston, MA USA.
[Cohn, Lillian E.] 9th St Internal Med Associates, Philadelphia, PA USA.
[Conway, Brian] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Cooper, David A.] Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia.
[Cox, David T.] Metro Infect Dis Consultants, Indianapolis, IN USA.
[Cristofano, Michael V.] John H Stroger Hosp Cook Cty, Chicago, IL USA.
[Cuchural, George, Jr.] New England Qual Care Alliance, Braintree, MA USA.
[Czartoski, Julie L.; Lee, Jean M. L.; McElrath, M. Juliana] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Dahman, Joseph M.] Desert AIDS Project, Palm Springs, CA USA.
[Daly, Jennifer S.] Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA.
[Davis, Kristine] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA.
[DeJesus, Edwin] Orlando Immunol Ctr, Orlando, FL USA.
[Dietz, Craig A.] Kansas City Free Hlth Clin, Kansas City, MO USA.
[Ellerin, Todd B.] S Shore Hosp, Weymouth, MA USA.
[Eron, Joseph J.; Menezes, Prema] Univ N Carolina, Chapel Hill, NC USA.
[Fangman, John J. W.] AIDS Resource Ctr Wisconsin, Milwaukee, WI USA.
[Ferlazzo, Helen; Stein, Francine] Visiting Nurse Assoc Cent New Jersey, Ctr Community Hlth, Asbury Pk, NJ USA.
[Fidler, Sarah; Winston, Alan] Univ London Imperial Coll Sci Technol & Med, London, England.
[Fleenor-Ford, Anita] Heartland Clin, Paducah, KY USA.
[Frankel, Renee] Morristown Mem Hosp, Morristown, NJ USA.
[Fuchs, Jonathan D.] San Francisco Dept Publ Hlth, San Francisco, CA USA.
[Fuller, Jon D.; Skolnik, Paul R.] Boston Univ, Med Ctr, Boston, MA USA.
[Gaberman, Jonna] Baystate Med Ctr, Springfield, MA USA.
[Gallant, Joel E.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Gaultier, Cyril R.] Tower Infect Dis, Los Angeles, CA USA.
[Gebre, Wondwoosen] Nassau Univ Med Ctr, E Meadow, NY USA.
[Gilman, Frank D.; Kurisu, Wayne] Sharp Rees Stealy Med Ctr, San Diego, CA USA.
[Gilson, Ian] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Goepfert, Paul A.; Heath, Sonya] Univ Alabama, Birmingham, AL USA.
[Gottlieb, Michael S.] Synergy Hematol & Oncol, Los Angeles, CA USA.
[Goulston, Claudia] Univ Utah, Salt Lake City, UT USA.
[Groger, Richard K.] S Dayton Acute Care Consultants, Dayton, OH USA.
[Haber, Stuart; Shay, William] St Vincents Hosp, New York, NY USA.
[Hardwicke, Robin] Univ Texas Hlth Sci Ctr, Houston, TX USA.
[Harrigan, P. Richard] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
[Hawkins, Trevor N.; Veikley, Wenoah] SW CARE Ctr, Santa Fe, NM USA.
[Henry, W. Keith] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[Hladek, Melissa] Catholic Univ Amer, Sch Nursing, Washington, DC 20064 USA.
[Hoffman, Robert P.] St Johns Mercy Med Ctr, Springfield, MA USA.
[Horton, James M.] CMC Myers Pk Med Ctr, Charlotte, NC USA.
[Hsu, Ricky K.; Liguori, Michael A.] NYU, Med Ctr, New York, NY 10016 USA.
[Huhn, Gregory D.] Ruth M Rothshon Care Ctr, Chicago, IL USA.
[Illeman, Mark L.] Feldman Med Grp, San Francisco, CA USA.
[Jaeger, Hans] HIV Res & Clin Care Ctr, Munich, Germany.
[Jellinger, Robert M.] Albany Med Coll, Albany, NY 12208 USA.
[John, Mina] Murdoch Univ, Murdoch, WA 6150, Australia.
[Johnson, Kay] Univ Cincinnati, Cincinnati, OH USA.
[Jordan, Wilbert C.] OASIS Clin, Los Angeles, CA USA.
[Kauffman, Carol A.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA.
[Khanlou, Homayoon] AIDS Healthcare Fdn, Los Angeles, CA USA.
[Killian, Robert K.] Capitol Hill Med, Seattle, WA USA.
[Kim, David D.] Astor Med Grp, New York, NY USA.
[Kinder, Clifford A.] Kinder Med Grp, Miami, FL USA.
[Kirchner, Jeffrey T.] Lancaster Gen Hosp, Lancaster, PA USA.
[Kogelman, Laura; McGovern, Barbara H.] Tufts Med Ctr, Boston, MA USA.
[Kojic, Erna Milunka] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Korthuis, Todd] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Lanzafame, Massimiliano] GB Rossi Hosp, Verona, Italy.
[Lederman, Michael M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Lee, Marah J.] LifeWay, Ft Lauderdale, FL USA.
[Lee, Edward T. Y.] St Claire Med Associate, Toronto, ON, Canada.
[Lemoine, Janice] Greater Lawrence Family Hlth Ctr, Lawrence, MA USA.
[Llibre, Josep M.] Hosp Badalona Germans Trias & Pujol, Barcelona, Spain.
[Lopez, Alvaro J.] Infect Dis Consultants, Tucker, GA USA.
[Loutfy, Mono R.; Ostrowski, Mario] Univ Toronto, Toronto, ON, Canada.
[Loy, Dawn; Prokesch, Richard C.; Vega, Vilma M.] Infect Dis Associates, Sarasota, FL USA.
[Marconi, Vincent C.] Emory Univ, Sch Med, Atlanta, GA USA.
[Markowitz, Martin] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA.
[Martin, Harold L., Jr.] Pk Nicollet Clin, St Louis, MN USA.
[McGhee, Theresa A.] Absolute Care, Atlanta, GA USA.
[Mcleod, Gavin X.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Mesa, Greg] Highland Med Associates, Hendersonville, NC USA.
[Meyer-Olson, Dirk] Hannover Med Sch, Abt Klin Immunol, D-30623 Hannover, Germany.
[Miller, Andy O.] Hosp Special Surg, New York, NY 10021 USA.
[Mounzer, Karam C.] Philadelphia FIGHT, Philadelphia, PA USA.
[Nagin, Iris] Lower E Side Serv Ctr, New York, NY USA.
[Nielsen, Craig] Univ Colorado, Aurora, CO USA.
[Norene, David L.] Sutter Med Grp, Sacramento, CA USA.
[O'Connor, David H.; Sosman, James M.] Univ Wisconsin, Madison, WI USA.
[Okulicz, Jason] Brooke Army Med Ctr, San Antonio, TX USA.
[Oldfield, Edward C., III] Eastern Virginia Med Sch, Norfolk, VA 23501 USA.
[Olender, Susan A.] Columbia Univ, Med Ctr, New York, NY USA.
[Owen, William F., Jr.] CA Pacific Med Ctr, San Francisco, CA USA.
[Parsonnet, Jeffrey] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
[Pavlatos, Andrew M.] St Joseph Hosp, Chicago, IL USA.
[Pincus, Jonathan M.] Codman Sq Hlth Ctr, Dorchester, MA USA.
[Pisani, Leandro; Rodriguez, Milagros; Saenz, Luis; Santiago, Steven] CARE Resource, Miami, FL USA.
[Price, Lawrence Jay] Castro Mission Hlth Ctr, San Francisco, CA USA.
[Proia, Laurie] Rush Med Coll, Chicago, IL 60612 USA.
[Pujet, Heather Calderon] Boulder Community Hosp, Boulder, CO USA.
[Ramgopal, Moti] Midway Immunol & Res Ctr, Ft Pierce, FL USA.
[Rausch, Michael] Aerztezentrum Nollendorfpl, Berlin, Germany.
[Ravishankar, J.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Rhame, Frank S.] Clin 42, Minneapolis, MN USA.
[Richards, Constance Shamuyarira] King Edward Mem Hosp, Paget, Bermuda.
[Rodes, Berta] Hosp Carlos III, Fdn Invest Biomed, Madrid, Spain.
[Rose, Richard C., III] Summit Med Grp, Knoxville, TN USA.
[Rosenthal, Daniel] Med Consultants S Florida, Coral Springs, FL USA.
[Ross, Polly E.] Western N Carolina Community Hlth Serv, Asheville, NC USA.
[Rubin, David S.] New York Hosp, Queens Med Ctr, Flushing, NY USA.
[Salvaggio, Michelle R.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Sanchez, William C.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
[Sanjana, Veeraf M.] Village Care Hlth Ctr, New York, NY USA.
[Schuitemaker, Hanneke; van't Wout, Angelique] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands.
[Sestak, Philip M.] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada.
[Shalit, Peter] Swedish Med Ctr, Seattle, WA USA.
[Shirvani, Vivian N.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Silebi, Vanessa I.] Mercy Hosp, Miami, FL USA.
[Sizemore, James M., Jr.] Univ Tennessee, Chattanooga, TN USA.
[Sokol-Anderson, Marcia] St Louis Univ, St Louis, MO 63103 USA.
[Stabile, Paul] William F Ryan Community Hlth Ctr, New York, NY USA.
[Stapleton, Jack T.] Univ Iowa, Iowa City, IA USA.
[Starrett, Sheree] Rivington House & Village Care, New York, NY USA.
[Stellbrink, Hans-Jurgen] Infekt Med Ctr Hamburg, Hamburg, Germany.
[Sterman, F. Lisa] Calif Pacific Med Ctr, San Francisco, CA USA.
[Stone, David R.] Lemuel Shattuck Hosp, Boston, MA USA.
[Tambussi, Giuseppe] Fdn San Raffaele Del Monte Tabor, Milan, Italy.
[Tedaldi, Ellen M.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA.
[Torres, Richard] Yale Univ, Sch Med, Bridgeport, CT USA.
[Tosiello, Lorraine] Jersey City Med Ctr, Jersey City, NJ USA.
[Tremblay, Cecile] Univ Montreal, Montreal, PQ, Canada.
[Tribble, Marc A.] Baylor Univ, Med Ctr, Dallas, TX USA.
[Trinh, Phuong D.] Montgomery Infect Dis Associates, Silver Spring, MD USA.
[Vaccaro, Anthony] Northwestern Univ, Chicago, IL 60611 USA.
[Valadas, Emilia] Hosp Santa Maria, Fac Med Lisboa, Lisbon, Portugal.
[Vanig, Thanes J.] Spectrum Med Grp, Phoenix, AZ USA.
[Vecino, Isabel; Weis, Steve] Univ N Texas, Hlth Sci Ctr, Ft Worth, TX USA.
[Wade, Barbara H.] Infect Dis Associates NW Florida, Pensacola, FL USA.
[Ward, Douglas J.] Dupont Circle Phys Grp, Washington, DC USA.
[Weber, Robert D.] Infect Dis Specialists, Colorado Springs, CO USA.
[Webster, Duncan] St Johns Hosp, St John, NB, Canada.
[Wheeler, David A.] Clin Alliance Res & Educ Infect Dis, Annandale, VA USA.
[White, David J.] Birmingham Heartlands Hosp, Birmingham B9 5ST, W Midlands, England.
[Wilkins, Ed] N Manchester Grp Hosp, Manchester, Lancs, England.
[Wright, David P.] Cent Texas Clin Res, Austin, TX USA.
[Yurdin, David L.] Primary Hlth Care, Des Moines, IA USA.
[Zabukovic, Brandon W.] Mem Neighborhood Hlth Ctr Cent Clin, South Bend, IN USA.
[Zhao, Meng] United Hlth Serv Hosp, Binghamton, NY USA.
[Pierce, Michael N.] All Med & Rehabil New York, Bronx, NY USA.
RP Walker, BD (reprint author), Massachusetts Inst Technol & Harvard, Massachusetts Gen Hosp, Regon Inst, Boston, MA USA.
EM pdebakker@rics.bwh.harvard.edu; bwalker@partners.org
RI Robbins, Gregory/F-7988-2011; de Bakker, Paul/B-8730-2009; SHCS,
all/G-4072-2011; SHCS, int. coll. A/G-4083-2011; Marconi,
Vincent/N-3210-2014;
OI de Bakker, Paul/0000-0001-7735-7858; Marconi,
Vincent/0000-0001-8409-4689; Valadas, Emilia/0000-0001-5213-1473;
Brumme, Chanson/0000-0003-2722-5288
FU Mark and Lisa Schwartz Foundation; Bill and Melinda Gates Foundation;
Harvard University Center for AIDS Research [P-30-AI060354]; University
of California San Francisco (UCSF) Center for AIDS Research [P-30
AI27763]; UCSF Clinical and Translational Science Institute [UL1
RR024131]; Center for AIDS Research Network of Integrated Clinical
Systems [R24 AI067039]; NIH [AI28568, AI030914, AI087145, K24AI069994,
AI069513, AI34835, AI069432, AI069423, AI069477, AI069501, AI069474,
AI069428, AI69467, AI069415, Al32782, AI27661, AI25859, AI30914,
AI069495, AI069471, AI069532, AI069452, AI069450, AI069556, AI069484,
AI069472, AI069465, AI069511]; Swiss National Science Foundation (SNF)
[33CSC0-108787, 310000-110012]; NIH/National Institute of Mental Health
[MH085520]; National Cancer Institute/NIH [HHSN261200800001E]; NIH,
National Cancer Institute, Center for Cancer Research
FX This work was made possible through a generous donation from the Mark
and Lisa Schwartz Foundation and a subsequent award from the
Collaboration for AIDS Vaccine Discovery of the Bill and Melinda Gates
Foundation. This work was also supported in part by the Harvard
University Center for AIDS Research (grant P-30-AI060354); University of
California San Francisco (UCSF) Center for AIDS Research (grant P-30
AI27763); UCSF Clinical and Translational Science Institute (grant UL1
RR024131); Center for AIDS Research Network of Integrated Clinical
Systems (grant R24 AI067039); and NIH grants AI28568 and AI030914 (B. D.
W.); AI087145 and K24AI069994 (S. G. D.); AI069513, AI34835, AI069432,
AI069423, AI069477, AI069501, AI069474, AI069428, AI69467, AI069415,
Al32782, AI27661, AI25859, AI28568, AI30914, AI069495, AI069471,
AI069532, AI069452, AI069450, AI069556, AI069484, AI069472, AI34853,
AI069465, AI069511, AI38844, AI069424, AI069434, AI46370, AI68634,
AI069502, AI069419, AI068636, and RR024975 (AIDS Clinical Trials Group);
and AI077505 and MH071205 (D. W. H.). The Swiss HIV Cohort Study is
supported by the Swiss National Science Foundation (SNF grants
33CSC0-108787 and 310000-110012). S. Ripke acknowledges support from
NIH/National Institute of Mental Health (grant MH085520). This project
has been funded in whole or in part with funds from National Cancer
Institute/NIH (grant HHSN261200800001E to M. Carrington). The content of
this publication does not necessarily reflect the views or policies of
the U. S. Department of Health and Human Services, nor does the mention
of trade names, commercial products, or organizations imply endorsement
by the U. S. government. This research was supported in part by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 31
TC 469
Z9 473
U1 5
U2 87
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD DEC 10
PY 2010
VL 330
IS 6010
BP 1551
EP 1557
DI 10.1126/science.1195271
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 692LE
UT WOS:000285153500069
ER
PT J
AU Qin, J
Zhang, BA
AF Qin, Jing
Zhang, Biao
TI Best combination of multiple diagnostic tests for screening purposes
SO STATISTICS IN MEDICINE
LA English
DT Article
DE bootstrap; density ratio model; empirical likelihood; Gaussian process;
likelihood ratio; logistic regression; ROC curve; semiparametric
likelihood; sensitivity; specificity; weak convergence
ID OPERATING CHARACTERISTIC CURVES; LOGISTIC-REGRESSION; PROSTATE-CANCER;
MODELS; MARKERS; BIAS
AB In a medical diagnostic testing problem multiple diagnostic tests are often available in distinguishing between diseased and nondiseased subjects Different diagnostic tests are usually sensitive to different aspects of the disease A desirable approach is to combine multiple diagnostic tests so as to obtain an optimal composite diagnostic test with higher sensitivity and specificity that detects the presence of the disease more accurately To accomplish this, it has been observed via signal detection theory developed in the 1950s and 1960s, that the optimal combination of different diagnostic variables (i e the diagnostic test results) is determined by the likelihood ratio function for the diseased and nondiseased groups The conventional approach is to fit parametric models for the diseased and nondiseased groups separately and then to use the fitted likelihood ratio function for the best combination of test results However, this approach is not so robust if the underlying distribution functions are misspecified Since the optimal combination depends only on the likelihood ratio function, it would be more appropriate to model this function directly A two sample semiparametric Inference technique is applied to the model for the likelihood ratio function We consider the best combination of multiple diagnostic tests, and study semiparametric likelihood estimation of the optimal receiver operating characteristic curve and the area under the curve We present a bootstrap procedure along with some results on simulation and on analysis of two real data sets Copyright (C) 2010 John Wiley & Sons, Ltd
C1 [Zhang, Biao] Univ Toledo, Dept Math, Toledo, OH 43606 USA.
[Qin, Jing] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Zhang, BA (reprint author), Univ Toledo, Dept Math, Toledo, OH 43606 USA.
FU National Science Foundation [DMS 0603873]
FX We are grateful to the Editor an Associate Editor and two referees for
their extremely careful reading and many valuable comments and
constructive suggestions on an earlier version of this paper which led
to a much improved presentation B Zhang wishes to thank the National
Science Foundation for support through grant DMS 0603873
NR 28
TC 5
Z9 5
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD DEC 10
PY 2010
VL 29
IS 28
BP 2905
EP 2919
DI 10.1002/sim.4068
PG 15
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 694GN
UT WOS:000285283100004
PM 20862668
ER
PT J
AU Mizurini, DM
Francischetti, IMB
Andersen, JF
Monteiro, RQ
AF Mizurini, Daniella M.
Francischetti, Ivo M. B.
Andersen, John F.
Monteiro, Robson Q.
TI Nitrophorin 2, a factor IX(a)-directed anticoagulant, inhibits arterial
thrombosis without impairing haemostasis
SO THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE Animal models; arterial thrombosis; coagulation inhibitors; haemostasis;
nitrophorin
ID HEPARIN-BINDING EXOSITE; X ACTIVATING COMPLEX; RHODNIUS-PROLIXUS;
FACTOR-IX; TISSUE FACTOR; INTRINSIC PATHWAY; NITRIC-OXIDE; COAGULATION
PATHWAY; BLOOD-COAGULATION; HEME PROTEIN
AB Nitrophorin 2 (NP2) is a 20 kDa lipocalin identified in the salivary gland of the blood sucking insect, Rhodnius prolixus. It functions as a potent inhibitor of the intrinsic pathway of coagulation upon binding to factor IX (FIX) or FIXa. Herein we have investigated the in vivo antithrombotic properties of NP2. Surface plasmon resonance assays demonstrated that NP2 binds to rat FIX and FIXa with high affinities (K(D) = 43 and 47 nM, respectively), and prolongs the aPTT without affecting the PT. In order to evaluate NP2 antithrombotic effects in vivo two distinct models of thrombosis in rats were carried out. In the rose Bengal/laser induced injury model of arterial thrombosis, NP2 increased the carotid artery occlusion time by approximate to 35 and approximate to 155%, at doses of 8 and 80 mu g/kg, respectively. NP2 also inhibited thrombus formation in an arterio-venous shunt model, showing approximate to 60% reduction at 400 mu g/kg (i.v. administration). The antithrombotic effect lasted for up to 48 hours after a single i.v. dose. Notably, effective doses of NP2 did not increase the blood loss as evaluated by tail-transection model. In conclusion, NP2 is a potent and long-lasting inhibitor of arterial thrombosis with minor effects on haemostasis. It might be regarded as a potential agent for the treatment of human cardiovascular diseases.
C1 [Monteiro, Robson Q.] Univ Fed Rio de Janeiro, Inst Bioquim Med, CCS, BR-21941590 Rio De Janeiro, Brazil.
[Francischetti, Ivo M. B.; Andersen, John F.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Monteiro, RQ (reprint author), Univ Fed Rio de Janeiro, Inst Bioquim Med, CCS, Ave Carlos Chagas Filho 373, BR-21941590 Rio De Janeiro, Brazil.
EM robsonqm@bioqmed.ufrj.br
RI Inbeb, Inct/K-2317-2013; Monteiro, Robson/B-8007-2014
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq);
Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro Carlos Chagas
Filho (FAPERJ); Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health, USA
FX We thank Dr. A.R. Rezaie (St. Louis University School of Medicine) for
careful revision of the manuscript and Leonardo M. Nascimento and
Natalia C. Rochael for technical assistance. This research was supported
by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq),
Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro Carlos Chagas
Filho (FAPERJ) and from the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, USA.
NR 48
TC 17
Z9 17
U1 1
U2 4
PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 0340-6245
J9 THROMB HAEMOSTASIS
JI Thromb. Haemost.
PD DEC 10
PY 2010
VL 104
IS 6
BP 1116
EP 1123
DI 10.1160/TH10.1160/TH10-03-0186
PG 8
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 695MJ
UT WOS:000285374300007
PM 20838739
ER
PT J
AU Lavine, J
Broutin, H
Harvill, ET
Bjornstad, ON
AF Lavine, Jennie
Broutin, Helene
Harvill, Eric T.
Bjornstad, Ottar N.
TI Imperfect vaccine-induced immunity and whooping cough transmission to
infants
SO VACCINE
LA English
DT Article
DE Bordetella; Immunity; Transmission
ID BORDETELLA-PARAPERTUSSIS INFECTION; ACELLULAR PERTUSSIS VACCINES;
WHOLE-CELL; MOUSE MODEL; ADULTS; ADOLESCENTS; EPIDEMIOLOGY; RESURGENCE;
EFFICACY; STRAINS
AB Whooping cough, caused by B. pertussis and B. parapertussis, has increased in incidence throughout much of the developed world since the 1980s despite high vaccine coverage, causing an increased risk of infection in infants who have substantial disease-induced mortality. Duration of immunity and epidemically significant routes of transmission across age groups remain unclear and deserve further investigation to inform vaccination strategies to better control pertussis burden. The authors analyze age- and species-specific whooping cough tests and vaccine histories in Massachusetts from 1990 to 2008. On average, the disease-free duration is 10.5 years. However, it has been decreasing over time, possibly due to a rising force of infection through increased circulation. Despite the importance of teenage cases during epidemics, wavelet analyses suggest that they are not the most important source of transmission to infants. In addition, the data indicate that the B. pertussis vaccine is not protective against disease induced by B. parapertussis. 2010 Elsevier Ltd. All rights reserved.
C1 [Lavine, Jennie; Bjornstad, Ottar N.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
[Broutin, Helene; Bjornstad, Ottar N.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Broutin, Helene] Univ Montpellier, Inst Rech Dev, UMR CNRS, MIVEGEC, F-34394 Montpellier, France.
[Bjornstad, Ottar N.] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
[Harvill, Eric T.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
RP Lavine, J (reprint author), Penn State Univ, Dept Biol, 501 ASI Bldg, University Pk, PA 16802 USA.
EM jsl236@psu.edu
RI Bjornstad, Ottar/I-4518-2012
FU Bill and Melinda Gates Foundation; RAPIDD program of the Science &
Technology Directorate; National Institute of Health [NIH/GM
R01-GM083983-01, NIH/NIAID R56-AI065507-01A2, NIH/GM R01-GM083113-01)];
NSF; intramural Research Group at Fogarty International Center, at the
NIH
FX This work was funded from the Bill and Melinda Gates Foundation (ONB),
the RAPIDD program of the Science & Technology Directorate (ONB), the
National Institute of Health (ONB; grant NIH/GM R01-GM083983-01, ONB and
ETH; grants NIH/NIAID R56-AI065507-01A2 and NIH/GM R01-GM083113-01), NSF
GREATT fellowship (JL and the intramural Research Group at Fogarty
International Center, at the NIH (HB).
NR 38
TC 25
Z9 26
U1 0
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD DEC 10
PY 2010
VL 29
IS 1
BP 11
EP 16
DI 10.1016/j.vaccine.2010.10.029
PG 6
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 708EP
UT WOS:000286345000003
PM 21034823
ER
PT J
AU DiNapoli, JM
Yang, LJ
Samal, SK
Murphy, BR
Collins, PL
Bukreyev, A
AF DiNapoli, Joshua M.
Yang, Lijuan
Samal, Siba K.
Murphy, Brian R.
Collins, Peter L.
Bukreyev, Alexander
TI Respiratory tract immunization of non-human primates with a Newcastle
disease virus-vectored vaccine candidate against Ebola virus elicits a
neutralizing antibody response
SO VACCINE
LA English
DT Article
DE Ebola virus; Newcastle disease virus; Vaccine; Monkey; Vector;
Immunization; Antibody; Respiratory tract
ID AVIAN INFLUENZA-VIRUS; SYNCYTIAL VIRUS; MEASLES-VIRUS; PROTEIN;
RECOMBINATION; GLYCOPROTEIN; MONKEYS; GENE; REPLICATION; CHALLENGE
AB We previously developed a respiratory tract vaccine candidate against Ebola virus (EBOV) based on human parainfluenza virus type 3 (HPIV3), a respiratory paramyxovirus, expressing the EBOV GP envelope protein (HPIV3/GP) from an added gene. Two doses of this vaccine candidate delivered by the intranasal and intratracheal route protected monkeys against intraperitoneal challenge with EBOV; however, concerns exist that the vaccine candidate may have reduced immunogenicity in the adult human population due to pre-existing immunity against HPIV3. Here we developed a new vaccine candidate (NDV/GP) based on Newcastle disease virus (NDV), an avian paramyxovirus that is antigenically distinct from human viral pathogens and is highly attenuated in monkeys. Following one intranasal and intratracheal inoculation of Rhesus monkeys with NDV/GP, titers of EBOV-specific antibodies in respiratory tract secretions and serum samples determined by ELISA, as well as serum EBOV-neutralizing antibodies, were undetectable or low compared to those induced by HPIV3/GP. A second immunization resulted in a substantial boost in serum IgG ELISA titers, yet the titers remained lower than those induced by a second dose of HPIV3/GP. In contrast, the ELISA IgA titers in respiratory tract secretions and, more importantly, the serum EBOV-neutralizing antibody titers were equal to those induced after the second dose of HPIV3/GP. These data suggest that NDV/GP can be effective for immunization against EBOV alone, or in combination with either HPIV3/GP or another vaccine platform in a heterologous prime-boost regimen. Published by Elsevier Ltd.
C1 [DiNapoli, Joshua M.; Yang, Lijuan; Murphy, Brian R.; Collins, Peter L.; Bukreyev, Alexander] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
RP Bukreyev, A (reprint author), Univ Texas Med Branch, Galveston Natl Lab, Dept Pathol, Galveston, TX 77555 USA.
EM alexander.bukreyev@utmb.edu
FU NIAID
FX We thank Fatemeh Davoodi and Ernest Williams (Laboratory of Infectious
Diseases, NIAID, NIH) for performing HAI assays, and Brad Finneyfrock
and Dr. Anthony Cook (Bioqual, Inc., Rockville, MD) for their assistance
with primate studies. We also thank Dr. Anthony Sanchez (Centers for
Disease Control and Prevention, Atlanta, GA) for providing the
inactivated EBOV antigen used in ELISA assays and Dr. Heinz Feldman
(National Institute of Allergy and Infectious Diseases) for providing
the VSV Delta G/EBOV GP virus used for neutralization assays. This
project was funded by the NIAID intramural program.
NR 44
TC 41
Z9 43
U1 0
U2 9
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD DEC 10
PY 2010
VL 29
IS 1
BP 17
EP 25
DI 10.1016/j.vaccine.2010.10.024
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 708EP
UT WOS:000286345000004
PM 21034822
ER
PT J
AU Wingard, JR
Carter, SL
Walsh, TJ
Kurtzberg, J
Small, TN
Baden, LR
Gersten, ID
Mendizabal, AM
Leather, HL
Confer, DL
Maziarz, RT
Stadtmauer, EA
Bolanos-Meade, J
Brown, J
DiPersio, JF
Boeckh, M
Marr, KA
AF Wingard, John R.
Carter, Shelly L.
Walsh, Thomas J.
Kurtzberg, Joanne
Small, Trudy N.
Baden, Lindsey R.
Gersten, Iris D.
Mendizabal, Adam M.
Leather, Helen L.
Confer, Dennis L.
Maziarz, Richard T.
Stadtmauer, Edward A.
Bolanos-Meade, Javier
Brown, Janice
DiPersio, John F.
Boeckh, Michael
Marr, Kieren A.
CA Blood & Marrow Transplant Clinical
TI Randomized, double-blind trial of fluconazole versus voriconazole for
prevention of invasive fungal infection after allogeneic hematopoietic
cell transplantation
SO BLOOD
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; STEM-CELL; ASPERGILLOSIS; PROPHYLAXIS;
RECIPIENTS; POSACONAZOLE; GALACTOMANNAN; SURVEILLANCE; ITRACONAZOLE;
MULTICENTER
AB Invasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice weekly for 60 days, then at least weekly until day 100. Positive galactomannan or suggestive signs triggered mandatory evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal-free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3% vs 11.2%; P = .12), Aspergillus infections (9 vs 17; P = .09), and less frequent empiric antifungal therapy (24.1% vs 30.2%, P = .11) with voriconazole, FFS rates (75% vs 78%; P = .49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and over-all survival and the incidence of severe adverse events were also similar. This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy, 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov as NCT00075803. (Blood. 2010;116(24):5111-5118)
C1 [Wingard, John R.] Univ Florida, Coll Med, Div Hematol Oncol, Gainesville, FL 32610 USA.
[Carter, Shelly L.; Gersten, Iris D.; Mendizabal, Adam M.] EMMES Corp, Rockville, MD USA.
[Walsh, Thomas J.] NCI, Bethesda, MD 20892 USA.
[Kurtzberg, Joanne] Duke Univ, Durham, NC USA.
[Small, Trudy N.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Baden, Lindsey R.] Dana Farber Partners Canc Inst, Boston, MA USA.
[Confer, Dennis L.] Natl Marrow Donor Program, Minneapolis, MN USA.
[Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Bolanos-Meade, Javier; Marr, Kieren A.] Johns Hopkins Univ, Baltimore, MD USA.
[Brown, Janice] Stanford Univ, Palo Alto, CA 94304 USA.
[DiPersio, John F.] Washington Univ, St Louis, MO USA.
[Boeckh, Michael; Marr, Kieren A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Wingard, JR (reprint author), Univ Florida, Coll Med, Div Hematol Oncol, 1600 SW Archer Rd,POB 100278, Gainesville, FL 32610 USA.
EM wingajr@medicine.ufl.edu
FU National Institutes of Health (NIH) [U01-8L069294]; NIH-NHLBI-NCI;
Pfizer; Astellas; Merck; Basilea; Novartis; Vestagen; Schering-Plough
FX We are also grateful to Pfizer for an unrestricted educational grant.
This work was supported by a National Institutes of Health (NIH) grant
(U01-8L069294).; Conflict-of-interest disclosure: J.R.W., J.K., L.R.B.,
J.B., E.A.S., J.B-M., M.B., S.L.C., and D.L.C. have received research
funding from NIH-NHLBI-NCI. J.R.W. has received consultancy fees,
honoraria, presentation fees, and travel reimbursement from Pfizer and
Astellas; consultancy fees, honoraria, and travel reimbursement from
Merck; and has served on data-monitoring boards for Basilea and Merck.
K.A.M. has received research funding from Merck, consultancy fees from
Basilea and Novartis, and has served on boards for Astellas, Merck, and
Pfizer. T.J.W. has received research funding from Vestagen. T.N.S. has
received honoraria from Pfizer, and a family member is employed by
Pfizer. H.L.L. has served on speakers' bureaus and received honoraria
from Pfizer, Merck, and Schering-Plough. R.T.M. has served on speakers'
bureaus for Schering-Plough. M.B. has received research funding and
honoraria from Pfizer and has a patent pending with Pfizer. I.D.G.,
A.M.M., and J.F.D declare no competing financial interests.
NR 32
TC 165
Z9 172
U1 1
U2 6
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 DEC 9
PY 2010
VL 116
IS 24
BP 5111
EP 5118
DI 10.1182/blood-2010-02-268151
PG 8
WC Hematology
SC Hematology
GA 692GL
UT WOS:000285141200008
PM 20826719
ER
PT J
AU Khandanpour, C
Sharif-Askari, E
Vassen, L
Gaudreau, MC
Zhu, JF
Paul, WE
Okayama, T
Kosan, C
Moroy, T
AF Khandanpour, Cyrus
Sharif-Askari, Ehssan
Vassen, Lothar
Gaudreau, Marie-Claude
Zhu, Jinfang
Paul, William E.
Okayama, Taro
Kosan, Christian
Moeroey, Tarik
TI Evidence that Growth factor independence 1b regulates dormancy and
peripheral blood mobilization of hematopoietic stem cells
SO BLOOD
LA English
DT Article
ID TRANSCRIPTION FACTOR GFI-1; SELF-RENEWAL; PROGENITOR CELLS; REAL-TIME;
DIFFERENTIATION; NICHE; GFI1B; PROTEIN; EXPRESSION; RECONSTITUTION
AB Donor-matched transplantation of hematopoietic stem cells (HSCs) is widely used to treat hematologic malignancies but is associated with high mortality. The expansion of HSC numbers and their mobilization into the bloodstream could significantly improve therapy. We report here that adult mice conditionally deficient for the transcription Growth factor independence 1b (Gfi1b) show a significant expansion of functional HSCs in the bone marrow and blood. Despite this expansion, Gfi1b(ko/ko) HSCs retain their ability to self-renew and to initiate multilineage differentiation but are no longer quiescent and contain elevated levels of reactive oxygen species. Treatment of Gfi1b(ko/ko) mice with N-acetyl-cystein significantly reduced HSC numbers indicating that increased reactive oxygen species levels are at least partially responsible for the expansion of Gfi1b-deficient HSCs. Moreover, Gfi1b(ko/ko) HSCs show decreased expression of CXCR4 and Vascular cell ad-hesion protein-1, which are required to retain dormant HSCs in the endosteal niche, suggesting that Gfi1b regulates HSC dormancy and pool size without affecting their function. Finally, the additional deletion of the related Gfi1 gene in Gfi1b(ko/ko) HSCs is incompatible with the maintenance of HSCs, suggesting that Gfi1b and Gfi1 have partially overlapping functions but that at least one Gfi gene is essential for the generation of HSCs. (Blood. 2010;116(24):5149-5161)
C1 [Moeroey, Tarik] Univ Montreal, Inst Rech Clin Montreal, IRCM, Montreal, PQ H2W 1R7, Canada.
[Khandanpour, Cyrus; Vassen, Lothar; Gaudreau, Marie-Claude; Moeroey, Tarik] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H2W 1R7, Canada.
[Zhu, Jinfang; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Moeroey, Tarik] Univ Duisburg Essen, ZMB, Essen, Germany.
RP Moroy, T (reprint author), Univ Montreal, Inst Rech Clin Montreal, IRCM, 110 Ave Pins Ouest, Montreal, PQ H2W 1R7, Canada.
EM Tarik.Moroy@ircm.qc.ca
RI Moroy, Tarik/D-9923-2011; Zhu, Jinfang/B-7574-2012; Kosan,
Christian/C-1213-2017;
OI Kosan, Christian/0000-0002-8387-3653; Gaudreau,
Marie-Claude/0000-0003-2833-7951
FU Roche Foundation for Anemia Research; Canadian Institutes of Health
Research [MOP-84 238, MOP-94 846]; Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by grants from the Roche Foundation for Anemia
Research and Canadian Institutes of Health Research (MOP-84 238, MOP-94
846; T.M.) and the Division of Intramural Research, National Institute
of Allergy and Infectious Diseases, National Institutes of Health (J.Z.,
W.E.P.). T.M. holds a Canada Research Chair (Tier 1), and C.K. is a Cole
Foundation fellow.
NR 50
TC 35
Z9 36
U1 0
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD DEC 9
PY 2010
VL 116
IS 24
BP 5149
EP 5161
DI 10.1182/blood-2010-04-280305
PG 13
WC Hematology
SC Hematology
GA 692GL
UT WOS:000285141200013
PM 20826720
ER
PT J
AU Ko, M
Huang, Y
Jankowska, AM
Pape, UJ
Tahiliani, M
Bandukwala, HS
An, J
Lamperti, ED
Koh, KP
Ganetzky, R
Liu, XS
Aravind, L
Agarwal, S
Maciejewski, JP
Rao, A
AF Ko, Myunggon
Huang, Yun
Jankowska, Anna M.
Pape, Utz J.
Tahiliani, Mamta
Bandukwala, Hozefa S.
An, Jungeun
Lamperti, Edward D.
Koh, Kian Peng
Ganetzky, Rebecca
Liu, X. Shirley
Aravind, L.
Agarwal, Suneet
Maciejewski, Jaroslaw P.
Rao, Anjana
TI Impaired hydroxylation of 5-methylcytosine in myeloid cancers with
mutant TET2
SO NATURE
LA English
DT Article
ID DNA METHYLATION; MUTATIONS; MALIGNANCIES; THERAPY; COMMON;
HYPOMETHYLATION; MYELOFIBROSIS; EPIGENETICS; CONVERSION; NEOPLASMS
AB TET2 is a close relative of TET1, an enzyme that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA(1,2). The gene encoding TET2 resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies(3). Somatic TET2 mutations are frequently observed in myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes including chronic myelomonocytic leukaemia (CMML), acute myeloid leukaemias (AML) and secondary AML (sAML)(4-12). We show here that TET2 mutations associated with myeloid malignancies compromise catalytic activity. Bone marrow samples from patients with TET2 mutations displayed uniformly low levels of 5hmC in genomic DNA compared to bone marrow samples from healthy controls. Moreover, small hairpin RNA (shRNA)-mediated depletion of Tet2 in mouse haematopoietic precursors skewed their differentiation towards monocyte/macrophage lineages in culture. There was no significant difference in DNA methylation between bone marrow samples from patients with high 5hmC versus healthy controls, but samples from patients with low 5hmC showed hypomethylation relative to controls at the majority of differentially methylated CpG sites. Our results demonstrate that Tet2 is important for normal myelopoiesis, and suggest that disruption of TET2 enzymatic activity favours myeloid tumorigenesis. Measurement of 5hmC levels in myeloid malignancies may prove valuable as a diagnostic and prognostic tool, to tailor therapies and assess responses to anticancer drugs.
C1 [Ko, Myunggon; Huang, Yun; Pape, Utz J.; Tahiliani, Mamta; Bandukwala, Hozefa S.; An, Jungeun; Lamperti, Edward D.; Koh, Kian Peng; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA.
[Ko, Myunggon; Huang, Yun; Pape, Utz J.; Tahiliani, Mamta; Bandukwala, Hozefa S.; An, Jungeun; Lamperti, Edward D.; Koh, Kian Peng; Rao, Anjana] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Jankowska, Anna M.; Ganetzky, Rebecca; Maciejewski, Jaroslaw P.] Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, Cleveland, OH 44195 USA.
[Jankowska, Anna M.; Ganetzky, Rebecca; Maciejewski, Jaroslaw P.] Cleveland Clin, Dept Hematol Oncol & Blood Disorders, Cleveland, OH 44195 USA.
[Pape, Utz J.; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Pape, Utz J.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Agarwal, Suneet] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Agarwal, Suneet] Harvard Stem Cell Inst, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Rao, A (reprint author), La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
EM maciejj@ccf.org; arao@idi.harvard.edu
OI Huang, Yun/0000-0001-5950-9168
FU NIH [R01 AI44432, RC1 DA028422, K24 HL077522, R01 HL098522, R01 HG4069];
Aplastic Anemia MDS Foundation; Bob Duggan Memorial Research Fund;
Harvard Catalyst; Harvard Clinical and Translational Science Center
(NIH) [1 UL1 RR 025758-02]; GlaxoSmithKline-Immune Disease Institute
(GSK-IDI) Alliance; Leukemia and Lymphoma Society of America
FX This work was supported by NIH grants R01 AI44432 and RC1 DA028422 (to
A.R.), NIH grants K24 HL077522 and R01 HL098522, an Established
Investigator award from the Aplastic Anemia & MDS Foundation, and an
award from the Bob Duggan Memorial Research Fund (to J.P.M), NIH grant
R01 HG4069 (to X.S.L.) and a pilot grant from Harvard Catalyst, The
Harvard Clinical and Translational Science Center (NIH Grant #1 UL1 RR
025758-02, to S.A.). Y.H. was supported by postdoctoral fellowships from
the GlaxoSmithKline-Immune Disease Institute (GSK-IDI) Alliance and the
Leukemia and Lymphoma Society of America. H.S.B. is supported by a
postdoctoral fellowship from the GSK-IDI Alliance.
NR 26
TC 583
Z9 604
U1 10
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD DEC 9
PY 2010
VL 468
IS 7325
BP 839
EP 843
DI 10.1038/nature09586
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700049
PM 21057493
ER
PT J
AU Bromberg-Martin, ES
Matsumoto, M
Hikosaka, O
AF Bromberg-Martin, Ethan S.
Matsumoto, Masayuki
Hikosaka, Okihide
TI Dopamine in Motivational Control: Rewarding, Aversive, and Alerting
SO NEURON
LA English
DT Review
ID VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS DOPAMINE; TONICALLY ACTIVE
NEURONS; ANTERIOR CINGULATE CORTEX; COCAINE-SEEKING BEHAVIOR; PRIMATE
CAUDATE-NUCLEUS; LATERAL HABENULA; MIDBRAIN DOPAMINE; SUBSTANTIA-NIGRA;
PREFRONTAL CORTEX
AB Midbrain dopamine neurons are well known for their strong responses to rewards and their critical role in positive motivation. It has become increasingly clear, however, that dopamine neurons also transmit signals related to salient but nonrewarding experiences such as aversive and alerting events. Here we review recent advances in understanding the reward and nonreward functions of dopamine. Based on this data, we propose that dopamine neurons come in multiple types that are connected with distinct brain networks and have distinct roles in motivational control. Some dopamine neurons encode motivational value, supporting brain networks for seeking, evaluation, and value learning. Others encode motivational salience, supporting brain networks for orienting, cognition, and general motivation. Both types of dopamine neurons are augmented by an alerting signal involved in rapid detection of potentially important sensory cues. We hypothesize that these dopanninergic pathways for value, salience, and alerting cooperate to support adaptive behavior.
C1 [Bromberg-Martin, Ethan S.; Matsumoto, Masayuki; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
[Matsumoto, Masayuki] Kyoto Univ, Primate Res Inst, Aichi 4848506, Japan.
RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
EM oh@lsr.nei.nih.gov
FU National Eye Institute
FX This work was supported by the Intramural Research Program at the
National Eye Institute. We also thank Amy Arnsten for valuable
discussions.
NR 266
TC 572
Z9 579
U1 22
U2 175
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD DEC 9
PY 2010
VL 68
IS 5
BP 815
EP 834
DI 10.1016/j.neuron.2010.11.022
PG 20
WC Neurosciences
SC Neurosciences & Neurology
GA 699LM
UT WOS:000285664900005
PM 21144997
ER
PT J
AU Johnson, JO
Mandrioli, J
Benatar, M
Abramzon, Y
Van Deerlin, VM
Trojanowski, JQ
Gibbs, JR
Brunetti, M
Gronka, S
Wuu, J
Ding, JH
McCluskey, L
Martinez-Lage, M
Falcone, D
Hernandez, DG
Arepalli, S
Chong, S
Schymick, JC
Rothstein, J
Landi, F
Wang, YD
Calvo, A
Mora, G
Sabatelli, M
Monsurro, MR
Battistini, S
Salvi, F
Spataro, R
Sola, P
Borghero, G
Galassi, G
Scholz, SW
Taylor, JP
Restagno, G
Chio, A
Traynor, BJ
AF Johnson, Jane O.
Mandrioli, Jessica
Benatar, Michael
Abramzon, Yevgeniya
Van Deerlin, Vivianna M.
Trojanowski, John Q.
Gibbs, J. Raphael
Brunetti, Maura
Gronka, Susan
Wuu, Joanne
Ding, Jinhui
McCluskey, Leo
Martinez-Lage, Maria
Falcone, Dana
Hernandez, Dena G.
Arepalli, Sampath
Chong, Sean
Schymick, Jennifer C.
Rothstein, Jeffrey
Landi, Francesco
Wang, Yong-Dong
Calvo, Andrea
Mora, Gabriele
Sabatelli, Mario
Monsurro, Maria Rosaria
Battistini, Stefania
Salvi, Fabrizio
Spataro, Rossella
Sola, Patrizia
Borghero, Giuseppe
Galassi, Giuliana
Scholz, Sonja W.
Taylor, J. Paul
Restagno, Gabriella
Chio, Adriano
Traynor, Bryan J.
CA ITALSGEN Consortium
TI Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS
SO NEURON
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; VALOSIN-CONTAINING PROTEIN;
FRONTOTEMPORAL LOBAR DEGENERATION; INCLUSION-BODY MYOPATHY;
PAGET-DISEASE; DEMENTIA; BONE; TDP-43; P97; VCP/P97
AB Using exome sequencing, we identified a p.R191Q amino acid change in the valosin-containing protein (VCP) gene in an Italian family with autosomal dominantly inherited amyotrophic lateral sclerosis (ALS). Mutations in VCP have previously been identified in families with Inclusion Body Myopathy, Paget disease, and Frontotemporal Dementia (IBMPFD). Screening of VCP in a cohort of 210 familial ALS cases and 78 autopsy-proven ALS cases identified four additional mutations including a p.R155H mutation in a pathologically proven case of ALS. VCP protein is essential for maturation of ubiquitin-containing autophagosomes, and mutant VCP toxicity is partially mediated through its effect on TDP-43 protein, a major constituent of ubiquitin inclusions that neuropathologically characterize ALS. Our data broaden the phenotype of IBMPFD to include motor neuron degeneration, suggest that VCP mutations may account for similar to 1%-2% of familial ALS, and provide evidence directly implicating defects in the ubiquitination/protein degradation pathway in motor neuron degeneration.
C1 [Johnson, Jane O.; Abramzon, Yevgeniya; Schymick, Jennifer C.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Hernandez, Dena G.; Arepalli, Sampath; Chong, Sean; Scholz, Sonja W.] NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Mandrioli, Jessica; Sola, Patrizia; Galassi, Giuliana] S Agostino Estense Hosp, Dept Neurosci, I-41126 Modena, Italy.
[Mandrioli, Jessica; Sola, Patrizia; Galassi, Giuliana] Univ Modena, I-41126 Modena, Italy.
[Benatar, Michael; Gronka, Susan; Wuu, Joanne] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
[Van Deerlin, Vivianna M.; Trojanowski, John Q.; Martinez-Lage, Maria; Falcone, Dana] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[McCluskey, Leo] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Gibbs, J. Raphael; Hernandez, Dena G.] UCL, Dept Mol Neurosci, London WC1 3BG, England.
[Gibbs, J. Raphael; Hernandez, Dena G.] UCL, Reta Lila Weston Labs, Inst Neurol, London WC1 3BG, England.
[Brunetti, Maura; Restagno, Gabriella] ASO OIRMS Anna, Mol Genet Unit, Dept Clin Pathol, I-10126 Turin, Italy.
[Rothstein, Jeffrey; Traynor, Bryan J.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA.
[Landi, Francesco] Univ Cattolica Sacro Cuore, Dept Gerontol Geriatr & Rehabil Med, I-00168 Rome, Italy.
[Wang, Yong-Dong; Taylor, J. Paul] St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
[Calvo, Andrea; Chio, Adriano] Univ Turin, Dept Neurosci, I-10126 Turin, Italy.
[Mora, Gabriele] Salvatore Maugeri Fdn, ALS Ctr, I-20100 Milan, Italy.
[Sabatelli, Mario] Catholic Univ, Neurol Inst, I-10100 Rome, Italy.
[Sabatelli, Mario] ICOMM Assoc ALS Res, I-10100 Rome, Italy.
[Monsurro, Maria Rosaria] Univ Naples 2, Dept Neurol Sci, I-80138 Naples, Italy.
[Battistini, Stefania] Univ Siena, Dept Neurosci, Neurol Sect, I-53100 Siena, Italy.
[Salvi, Fabrizio] Bellaria Hosp, Dept Neurol, Ctr Diag & Cure Rare Dis, I-40100 Bologna, Italy.
[Spataro, Rossella] Univ Palermo, Dept Clin Neurosci, I-90129 Palermo, Italy.
[Borghero, Giuseppe] Univ Cagliari, Azienda Hosp, Neurol Clin, I-09042 Monserrato, Italy.
[Scholz, Sonja W.] Georgetown Univ, Dept Neurosci, Washington, DC 20057 USA.
RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Porter Neurosci Bldg, Bethesda, MD 20892 USA.
EM traynorb@mail.nih.gov
RI Traynor, Bryan/G-5690-2010; Wang, Yong-Dong/K-3563-2013; Battistini,
Stefania/N-2596-2015; Calvo, Andrea/K-4141-2016; Spataro,
Rossella/B-3656-2016; MANDRIOLI, JESSICA/K-7235-2016;
OI Scholz, Sonja/0000-0002-6623-0429; Chio, Adriano/0000-0001-9579-5341;
Battistini, Stefania/0000-0003-2887-7624; Martinez-Lage,
Maria/0000-0002-5859-7562; Calvo, Andrea/0000-0002-5122-7243; Spataro,
Rossella/0000-0002-8910-3131; MANDRIOLI, JESSICA/0000-0002-9244-9782;
Sabatelli, Mario/0000-0001-6635-4985
FU NIH, National Institute on Aging [Z01-AG000949-02, AG17586]; NINDS;
Packard Center for ALS Research at Hopkins; Fondazione Vialli e Mauro
for ALS Research Onlus, Federazione Italians Giuoco Calcio (FIGC);
Ministero della Salute (Ricerca Sanitaria Finalizzata); Muscular
Dystrophy Association [4365]; Woodruff Health Sciences Center at Emory
University; Taub Institute, Columbia University [P50 AG08702];
University of Miami/National Parkinson Foundation Brain Endowment Bank
FX This work was supported in part by the Intramural Research Programs of
the NIH, National Institute on Aging (Z01-AG000949-02), and NINDS. The
work was also funded by the Packard Center for ALS Research at Hopkins,
the Fondazione Vialli e Mauro for ALS Research Onlus, Federazione
Italians Giuoco Calcio (FIGC), the Ministero della Salute (Ricerca
Sanitaria Finalizzata 2007), the Muscular Dystrophy Association (Grant
4365), and the Woodruff Health Sciences Center at Emory University. DNA
samples for this study were obtained in part from the NINDS repository
at the Coriell Cell Repositories (http://www.coriell.org/). We
gratefully acknowledge the assistance of the New York Brain Bank: The
Taub Institute, Columbia University (Federal grant No. P50 AG08702) and
the University of Miami/National Parkinson Foundation Brain Endowment
Bank. This work was supported by funding from the NIH (AG17586). J.Q.T.
is the William Maul Measey-Truman G. Schnabel, Jr. Professor of
Geriatric Medicine and Gerontology. J.R. is Director of the Packard
Center for ALS Research at Hopkins. None of the other authors have any
conflicts of interest. We thank the patients and research subjects who
contributed samples for this study.
NR 43
TC 487
Z9 505
U1 8
U2 63
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD DEC 9
PY 2010
VL 68
IS 5
BP 857
EP 864
DI 10.1016/j.neuron.2010.11.036
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 699LM
UT WOS:000285664900008
PM 21145000
ER
PT J
AU Chertow, GM
Levin, NW
Beck, GJ
Depner, TA
Eggers, PW
Gassman, JJ
Gorodetskaya, I
Greene, T
James, S
Larive, B
Lindsay, RM
Mehta, RL
Miller, B
Ornt, DB
Rajagopalan, S
Rastogi, A
Rocco, MV
Schiller, B
Sergeyeva, O
Schulman, G
Ting, GO
Unruh, ML
Star, RA
Kliger, AS
AF Chertow, Glenn M.
Levin, Nathan W.
Beck, Gerald J.
Depner, Thomas A.
Eggers, Paul W.
Gassman, Jennifer J.
Gorodetskaya, Irina
Greene, Tom
James, Sam
Larive, Brett
Lindsay, Robert M.
Mehta, Ravindra L.
Miller, Brent
Ornt, Daniel B.
Rajagopalan, Sanjay
Rastogi, Anjay
Rocco, Michael V.
Schiller, Brigitte
Sergeyeva, Olga
Schulman, Gerald
Ting, George O.
Unruh, Mark L.
Star, Robert A.
Kliger, Alan S.
CA FHN Trial Grp
TI In-Center Hemodialysis Six Times per Week versus Three Times per Week
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID LEFT-VENTRICULAR HYPERTROPHY; QUALITY-OF-LIFE; STAGE RENAL-DISEASE;
CONVENTIONAL HEMODIALYSIS; NOCTURNAL HEMODIALYSIS; BLOOD-PRESSURE; ESRD
PATIENTS; LONG-TERM; FOLLOW-UP; DIALYSIS
AB BACKGROUND
In this randomized clinical trial, we aimed to determine whether increasing the frequency of in-center hemodialysis would result in beneficial changes in left ventricular mass, self-reported physical health, and other intermediate outcomes among patients undergoing maintenance hemodialysis.
METHODS
Patients were randomly assigned to undergo hemodialysis six times per week (frequent hemodialysis, 125 patients) or three times per week (conventional hemodialysis, 120 patients) for 12 months. The two coprimary composite outcomes were death or change (from baseline to 12 months) in left ventricular mass, as assessed by cardiac magnetic resonance imaging, and death or change in the physical-health composite score of the RAND 36-item health survey. Secondary outcomes included cognitive performance; self-reported depression; laboratory markers of nutrition, mineral metabolism, and anemia; blood pressure; and rates of hospitalization and of interventions related to vascular access.
RESULTS
Patients in the frequent-hemodialysis group averaged 5.2 sessions per week; the weekly standard Kt/V(urea) (the product of the urea clearance and the duration of the dialysis session normalized to the volume of distribution of urea) was significantly higher in the frequent-hemodialysis group than in the conventional-hemodialysis group (3.54 +/- 0.56 vs. 2.49 +/- 0.27). Frequent hemodialysis was associated with significant benefits with respect to both coprimary composite outcomes (hazard ratio for death or increase in left ventricular mass, 0.61; 95% confidence interval [CI], 0.46 to 0.82; hazard ratio for death or a decrease in the physical-health composite score, 0.70; 95% CI, 0.53 to 0.92). Patients randomly assigned to frequent hemodialysis were more likely to undergo interventions related to vascular access than were patients assigned to conventional hemodialysis (hazard ratio, 1.71; 95% CI, 1.08 to 2.73). Frequent hemodialysis was associated with improved control of hypertension and hyperphosphatemia. There were no significant effects of frequent hemodialysis on cognitive performance, self-reported depression, serum albumin concentration, or use of erythropoiesis-stimulating agents.
CONCLUSIONS
Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access.
C1 [Chertow, Glenn M.; Gorodetskaya, Irina; Schiller, Brigitte; Ting, George O.] Stanford Univ, Palo Alto, CA 94304 USA.
[Chertow, Glenn M.; Gorodetskaya, Irina; James, Sam] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Levin, Nathan W.; Sergeyeva, Olga] Renal Res Inst, New York, NY USA.
[Beck, Gerald J.; Gassman, Jennifer J.; Greene, Tom; Larive, Brett] Cleveland Clin Fdn, Cleveland, OH USA.
[Depner, Thomas A.] Univ Calif Davis, Davis, CA 95616 USA.
[Eggers, Paul W.; Star, Robert A.] NIDDK, Bethesda, MD USA.
[Greene, Tom] Univ Utah, Salt Lake City, UT USA.
[Lindsay, Robert M.] Univ Western Ontario, London, ON, Canada.
[Mehta, Ravindra L.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Miller, Brent] Washington Univ, St Louis, MO 63130 USA.
[Ornt, Daniel B.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Rajagopalan, Sanjay] Ohio State Univ, Columbus, OH 43210 USA.
[Rastogi, Anjay] Univ Calif Los Angeles, Los Angeles, CA USA.
[Rocco, Michael V.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Schiller, Brigitte] Satellite Healthcare, San Jose, CA USA.
[Schulman, Gerald] Vanderbilt Univ, Nashville, TN USA.
[Ting, George O.] El Camino Hosp, Mountain View, CA USA.
[Unruh, Mark L.] Univ Pittsburgh, Pittsburgh, PA USA.
[Kliger, Alan S.] Hosp St Raphael, New Haven, CT 06511 USA.
[Kliger, Alan S.] Yale Univ, New Haven, CT USA.
RP Chertow, GM (reprint author), Stanford Univ, Palo Alto, CA 94304 USA.
FU National Institutes of Health (NIH), National Institutes of Diabetes and
Digestive and Kidney Diseases; Center for Medicare and Medical Services;
NIH Research Foundation; Amgen; Baxter; Dialysis Clinics
FX Supported by the National Institutes of Health (NIH), National
Institutes of Diabetes and Digestive and Kidney Diseases, the Center for
Medicare and Medical Services, and the NIH Research Foundation.
Contributors to the NIH Foundation in support of the FHN trials included
Amgen, Baxter, and Dialysis Clinics. Additional support was provided by
DaVita, Dialysis Clinics, Fresenius Medical Care, Renal Advantage, Renal
Research Institute, and Satellite Healthcare.
NR 39
TC 403
Z9 408
U1 4
U2 15
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD DEC 9
PY 2010
VL 363
IS 24
BP 2287
EP 2300
DI 10.1056/NEJMoa1001593
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA 691PA
UT WOS:000285092100004
ER
PT J
AU Chaudhry, SI
Mattera, JA
Curtis, JP
Spertus, JA
Herrin, J
Lin, ZQ
Phillips, CO
Hodshon, BV
Cooper, LS
Krumholz, HM
AF Chaudhry, Sarwat I.
Mattera, Jennifer A.
Curtis, Jeptha P.
Spertus, John A.
Herrin, Jeph
Lin, Zhenqiu
Phillips, Christopher O.
Hodshon, Beth V.
Cooper, Lawton S.
Krumholz, Harlan M.
TI Telemonitoring in Patients with Heart Failure
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID DISEASE-MANAGEMENT; RANDOMIZED-TRIAL; READMISSION; OUTCOMES
AB BACKGROUND
Small studies suggest that telemonitoring may improve heart-failure outcomes, but its effect in a large trial has not been established.
METHODS
We randomly assigned 1653 patients who had recently been hospitalized for heart failure to undergo either telemonitoring (826 patients) or usual care (827 patients). Telemonitoring was accomplished by means of a telephone-based interactive voice-response system that collected daily information about symptoms and weight that was reviewed by the patients' clinicians. The primary end point was readmission for any reason or death from any cause within 180 days after enrollment. Secondary end points included hospitalization for heart failure, number of days in the hospital, and number of hospitalizations.
RESULTS
The median age of the patients was 61 years; 42.0% were female, and 39.0% were black. The telemonitoring group and the usual-care group did not differ significantly with respect to the primary end point, which occurred in 52.3% and 51.5% of patients, respectively (difference, 0.8 percentage points; 95% confidence interval [CI], -4.0 to 5.6; P = 0.75 by the chi-square test). Readmission for any reason occurred in 49.3% of patients in the telemonitoring group and 47.4% of patients in the usual-care group (difference, 1.9 percentage points; 95% CI, -3.0 to 6.7; P = 0.45 by the chi-square test). Death occurred in 11.1% of the telemonitoring group and 11.4% of the usual care group (difference, -0.2 percentage points; 95% CI, -3.3 to 2.8; P = 0.88 by the chi-square test). There were no significant differences between the two groups with respect to the secondary end points or the time to the primary end point or its components. No adverse events were reported.
CONCLUSIONS
Among patients recently hospitalized for heart failure, telemonitoring did not improve outcomes. The results indicate the importance of a thorough, independent evaluation of disease-management strategies before their adoption.
C1 [Curtis, Jeptha P.; Herrin, Jeph; Hodshon, Beth V.; Krumholz, Harlan M.] Yale Univ, Sch Med, Sch Publ Hlth, Sect Cardiovasc Med, New Haven, CT 06510 USA.
[Chaudhry, Sarwat I.] Yale Univ, Sch Med, Sch Publ Hlth, Sect Gen Med, New Haven, CT 06510 USA.
[Krumholz, Harlan M.] Yale Univ, Sch Med, Sch Publ Hlth, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA.
[Mattera, Jennifer A.; Krumholz, Harlan M.] Yale Univ, Sch Med, Sch Publ Hlth, Dept Med, New Haven, CT 06510 USA.
[Mattera, Jennifer A.; Krumholz, Harlan M.] Yale Univ, Sch Med, Sch Publ Hlth, Sect Hlth Policy & Adm, New Haven, CT 06510 USA.
[Mattera, Jennifer A.; Curtis, Jeptha P.; Lin, Zhenqiu; Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA.
[Spertus, John A.] Univ Missouri, Sch Med, Kansas City, MO 64108 USA.
[Spertus, John A.] St Lukes Hlth Syst, Mid Amer Heart & Vasc Inst, Kansas City, MO USA.
[Phillips, Christopher O.] Morehouse Sch Med, Dept Med, Atlanta, GA 30310 USA.
[Cooper, Lawton S.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Sch Publ Hlth, Sect Cardiovasc Med, 1 Church St,Suite 200, New Haven, CT 06510 USA.
EM harlan.krumholz@yale.edu
FU National Heart, Lung, and Blood Institute [5 R01 HL080228]
FX Supported by a grant (5 R01 HL080228) from the National Heart, Lung, and
Blood Institute.
NR 16
TC 373
Z9 382
U1 4
U2 22
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD DEC 9
PY 2010
VL 363
IS 24
BP 2301
EP 2309
DI 10.1056/NEJMoa1010029
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 691PA
UT WOS:000285092100005
PM 21080835
ER
PT J
AU Chattopadhyay, M
Goswami, S
Rodes, DB
Kodela, R
Velazquez, CA
Boring, D
Crowell, JA
Kashfi, K
AF Chattopadhyay, Mitali
Goswami, Satindra
Rodes, Deborah B.
Kodela, Ravinder
Velazquez, Carlos A.
Boring, Daniel
Crowell, James A.
Kashfi, Khosrow
TI NO-releasing NSAIDs suppress NF-kappa B signaling in vitro and in vivo
through S-nitrosylation
SO CANCER LETTERS
LA English
DT Article
DE NF-kappa B; Caspase 3; NO-NSAIDs; S-nitrosylation; Chemoprevention
ID OXIDE-DONATING ASPIRIN; BIOTIN-SWITCH TECHNIQUE; COLON-CANCER CELLS;
NITRIC-OXIDE; BIOLOGICAL EVALUATION; OXIDATIVE STRESS; HYBRID DRUGS;
INHIBITION; KINASE; GROWTH
AB NO-NSAIDs are promising anticancer drugs comprising an NSAID an NO-releasing moiety and a spacer linking them Although the effect of NO-NSAIDs on a wide variety of signaling and other cellular mechanisms has been deciphered a key question remains unanswered that being the role of NO to the overall biological effect of these agents It has been shown that NO can directly modify sulfhydryl residues of proteins through S-nitrosylation and induce apoptosis We studied 3 NO-NSAIDs having a different NSAID spacer and NO-releasing moiety In vitro aspirin NO-ASA naproxen and NO-naproxen inhibited HT-29 human colon cancer cell growth the IC(50)s being >5000 192 +/- 6 2800 +/- 210 and 95 5 mu M at 24 h respectively NO-Aspirin and NO-naproxen reduced NF-kappa B protein levels and activated caspase-3 enzyme in a dose- and time-dependent manner Based on the biotin switch assay NO-ASA and NO-naproxen S-nitrosylated NF-kappa B p65 in a time-dependent manner Pretreatment of the cells with carboxy-PTIO abrogated the S-nitrosylation of NF-kappa B p65 In vivo rats treated with NO-ASA NONO-ASA and NO-naproxen showed S-nitrosylation of NF-kappa B p65 in the stomach tissue increases in plasma TNE-alpha and reductions in mucosal PGE(2) levels These data provide a mechanistic role for NO and a rational for the chemopreventive effects of NO-NSAIDs (C) 2010 Elsevier Ireland Ltd All rights reserved
C1 [Chattopadhyay, Mitali; Goswami, Satindra; Rodes, Deborah B.; Kodela, Ravinder; Kashfi, Khosrow] CUNY, Sch Med, Dept Physiol & Pharmacol, New York, NY 10031 USA.
[Velazquez, Carlos A.] Univ Alberta, Dept Pharm & Pharmaceut Sci, Edmonton, AB, Canada.
[Boring, Daniel; Crowell, James A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Kashfi, K (reprint author), CUNY, Sch Med, Dept Physiol & Pharmacol, 138th St & Convent Ave, New York, NY 10031 USA.
FU National Cancer Institute [FBS-43312-26]
FX Supported in part by the National Cancer Institute through a subcontract
from Thermaisher contract # FBS-43312-26
NR 32
TC 21
Z9 23
U1 1
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD DEC 8
PY 2010
VL 298
IS 2
BP 204
EP 211
DI 10.1016/j.canlet.2010.07.006
PG 8
WC Oncology
SC Oncology
GA 681GS
UT WOS:000284300000008
PM 20674154
ER
PT J
AU Sabir, N
Riazuddin, SA
Butt, T
Iqbal, F
Nasir, IA
Zafar, AU
Qazi, ZA
Butt, NH
Khan, SN
Husnain, T
Hejtmancik, JF
Riazuddin, S
AF Sabir, Namerah
Riazuddin, S. Amer
Butt, Tariq
Iqbal, Farheena
Nasir, Idrees A.
Zafar, Ahmad U.
Qazi, Zaheeruddin A.
Butt, Nadeem H.
Khan, Shaheen N.
Husnain, Tayyab
Hejtmancik, J. Fielding
Riazuddin, Sheikh
TI Mapping of a new locus associated with autosomal recessive congenital
cataract to chromosome 3q
SO MOLECULAR VISION
LA English
DT Article
ID PAKISTANI FAMILY; NONSENSE MUTATION; GENE; BLINDNESS; MAPS
AB Purpose: To localize the disease interval for autosomal recessive congenital cataracts in a consanguineous Pakistani family.
Methods: All affected individuals underwent detailed ophthalmologic examination. Blood samples were collected and genomic DNA was extracted. A genome-wide scan was performed with fluorescently-labeled microsatellite markers on genomic DNA from affected and unaffected family members and logarithm of odds (LOD) scores were calculated.
Results: Clinical records and ophthalmological examinations suggested that affected individuals have bilateral congenital cataracts. Genome-wide linkage analysis localized the critical interval to chromosome 3q with a maximum LOD score of 3.87 at theta=0; with marker D3S3609. Haplotype analyses refined the critical interval to a 23.39 cM (18.01 Mb) interval on chromosome 3q, flanked by D3S1614 proximally and D3S1262, distally.
Conclusions: Here, we report a new locus for autosomal recessive congenital cataract localized to chromosome 3q in a consanguineous Pakistani family.
C1 [Sabir, Namerah; Riazuddin, S. Amer; Butt, Tariq; Iqbal, Farheena; Nasir, Idrees A.; Zafar, Ahmad U.; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan.
[Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Qazi, Zaheeruddin A.] Layton Rahmatulla Benevolent Trust Hosp Lahore, Lahore, Pakistan.
[Butt, Nadeem H.; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan.
[Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd, Lahore 53700, Pakistan.
EM riaz@aimrc.org
RI Nasim Khan, Shaheen/F-2135-2015; Husnain, Tayyab/G-3805-2015
FU Higher Education Commission and Ministry of Science and Technology
Islamabad, Pakistan; National Academy of Sciences; U.S. Department of
State, Washington DC USA
FX The authors are thankful to all the family members for their
participation in this study. This study was supported, in part by Higher
Education Commission and Ministry of Science and Technology Islamabad,
Pakistan, and the National Academy of Sciences, and the U.S. Department
of State, Washington DC USA (Note: All findings and conclusions are
those of the authors and do not necessarily reflect the views of the
National Academy of Sciences and the U.S. Department of State).
NR 20
TC 5
Z9 5
U1 0
U2 0
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 DEC 8
PY 2010
VL 16
IS 280-84
BP 2634
EP 2637
PG 4
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 697IH
UT WOS:000285506300003
PM 21179239
ER
PT J
AU Becker, RE
Greig, NH
AF Becker, Robert E.
Greig, Nigel H.
TI Lost in Translation: Neuropsychiatric Drug Development
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIALS; ALZHEIMERS-DISEASE; CLINICAL-TRIALS;
ANIMAL-MODELS; CHRONIC-SCHIZOPHRENIA; PLACEBO-RESPONSE; CATIE; EFFICACY;
OUTCOMES; DEPRESSION
AB Recent studies have identified troubling method and practice lapses in neuropsychiatric drug developments. These problems have resulted in errors that are of sufficient magnitude to invalidate clinical trial data and interpretations. We identify two potential sources for these difficulties: investigators selectively choosing scientific practices for demonstrations of efficacy in human-testing phases of drug development and investigators failing to anticipate the needs of practitioners who must optimize treatment for the individual patient. When clinical investigators neglect to use clinical trials as opportunities to test hypotheses of disease mechanisms in humans, the neuropsychiatric knowledge base loses both credibility and scope. When clinical investigators do not anticipate the need to translate discoveries into applications, the practitioner cannot provide optimal care for the patient. We conclude from this evidence that clinical trials, and other aspects of neuropsychiatric drug development, must adopt more practices from basic science and show greater responsiveness to conditions of clinical practice. We feel that these changes are necessary to overcome current threats to the validity and utility of studies of neurological and psychiatric drugs.
C1 [Becker, Robert E.] Aristea Translational Med Corp, Freeport, ME 04078 USA.
[Becker, Robert E.; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Becker, RE (reprint author), Aristea Translational Med Corp, Freeport, ME 04078 USA.
EM rebecker2008@comcast.net
FU National Institute on Aging, NIH
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging, NIH.
NR 65
TC 17
Z9 17
U1 0
U2 4
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD DEC 8
PY 2010
VL 2
IS 61
AR 61rv6
DI 10.1126/scitranslmed.3000446
PG 7
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 735UC
UT WOS:000288443500004
PM 21148128
ER
PT J
AU Wolf, R
Mascia, F
Dharamsi, A
Howard, OMZ
Cataisson, C
Bliskovski, V
Winston, J
Feigenbaum, L
Lichti, U
Ruzicka, T
Chavakis, T
Yuspa, SH
AF Wolf, Ronald
Mascia, Francesca
Dharamsi, Alif
Howard, O. M. Zack
Cataisson, Christophe
Bliskovski, Val
Winston, Jason
Feigenbaum, Lionel
Lichti, Ulrike
Ruzicka, Thomas
Chavakis, Triantafyllos
Yuspa, Stuart H.
TI Gene from a Psoriasis Susceptibility Locus Primes the Skin for
Inflammation
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID CELL RECRUITMENT; MOLECULAR-CLONING; S100 PROTEINS; KERATINOCYTES;
EXPRESSION; ALPHA; PATHOGENESIS; CYTOKINE; RECEPTOR; DISEASE
AB Psoriasis is a common complex genetic disease characterized by hyperplasia and inflammation in the skin; however, the relative contributions of epidermal cells and the immune system to disease pathogenesis remain unclear. Linkage studies have defined a psoriasis susceptibility locus (PSORS4) on 1q21, the epidermal differentiation complex, which includes genes for small S100 calcium-binding proteins. These proteins are involved in extracellular and intracellular signaling during epithelial host defense, linking innate and adaptive immunity. Inflammation-prone psoriatic skin constitutively expresses elevated concentrations of S100A7 (psoriasin) and S100A15 (koebnerisin) in the epidermis. Here, we report that genetically modified mice expressing elevated amounts of doxycycline-regulated mS100a7a15 in skin keratinocytes demonstrated an exaggerated inflammatory response when challenged by exogenous stimuli such as abrasion (Koebner phenomenon). This immune response was characterized by immune cell infiltration and elevated concentrations of T helper 1 (T(H)1) and T(H)17 proinflammatory cytokines, which have been linked to the pathogenesis of psoriasis and were further amplified upon challenge. Both inflammation priming and amplification required mS100a7a15 binding to the receptor of advanced glycation end products (RAGE). mS100a7a15 potentiated inflammation by acting directly as a chemoattractant for leukocytes, further increasing the number of inflammatory cells infiltrating the skin. This study provides a pathogenetic psoriasis model using a psoriasis candidate gene to link the epidermis and innate immune system in inflammation priming, highlighting the S100A7A15-RAGE axis as a potential therapeutic target.
C1 [Wolf, Ronald; Mascia, Francesca; Dharamsi, Alif; Cataisson, Christophe; Bliskovski, Val; Winston, Jason; Lichti, Ulrike; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Wolf, Ronald; Ruzicka, Thomas] Univ Munich, Dept Dermatol & Allergol, D-80337 Munich, Germany.
[Howard, O. M. Zack] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Feigenbaum, Lionel] Sci Applicat Int Corp, Lab Anim Sci Program, Frederick, MD 21702 USA.
[Chavakis, Triantafyllos] NCI, Expt Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Chavakis, Triantafyllos] Tech Univ Dresden, Dept Med, Div Vasc Inflammat Diabet & Kidney, D-01307 Dresden, Germany.
[Chavakis, Triantafyllos] Tech Univ Dresden, Inst Physiol, D-01307 Dresden, Germany.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
EM yuspas@mail.nih.gov
RI Howard, O M Zack/B-6117-2012
OI Howard, O M Zack/0000-0002-0505-7052
FU NIH, National Cancer Institute, Center for Cancer Research; German
Research Foundation [Wo843/3-1]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. R.W.
is funded by the German Research Foundation (Wo843/3-1).
NR 60
TC 26
Z9 26
U1 0
U2 4
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD DEC 8
PY 2010
VL 2
IS 61
AR 61ra90
DI 10.1126/scitranslmed.3001108
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 735UC
UT WOS:000288443500002
PM 21148126
ER
PT J
AU Mulenga, C
Mwakazanga, D
Vereecken, K
Khondowe, S
Kapata, N
Shamputa, IC
Meulemans, H
Rigouts, L
AF Mulenga, Chanda
Mwakazanga, David
Vereecken, Kim
Khondowe, Shepherd
Kapata, Nathan
Shamputa, Isdore Chola
Meulemans, Herman
Rigouts, Leen
TI Management of pulmonary tuberculosis patients in an urban setting in
Zambia: a patient's perspective
SO BMC PUBLIC HEALTH
LA English
DT Article
ID TREATMENT ADHERENCE; MEDICATION; KNOWLEDGE; AFRICA; DELAY; DOTS; CARE
AB Background: Zambia continues to grapple with a high tuberculosis (TB) burden despite a long running Directly Observed Treatment Short course programme. Understanding issues that affect patient adherence to treatment programme is an important component in implementation of a successful TB control programme. We set out to investigate pulmonary TB patient's attitudes to seek health care, assess the care received from government health care centres based on TB patients' reports, and to seek associations with patient adherence to TB treatment programme.
Methods: This was a cross-sectional study of 105 respondents who had been registered as pulmonary TB patients (new and retreatment cases) in Ndola District between January 2006 and July 2007. We administered a structured questionnaire, bearing questions to obtain individual data on socio-demographics, health seeking behaviour, knowledge on TB, reported adherence to TB treatment, and health centre care received during treatment to consenting respondents.
Results: We identified that respondents delayed to seek treatment (68%) even when knowledge of TB symptoms was high (78%) or when they suspected that they had TB (73%). Respondent adherence to taking medication was high (77%) but low adherence to submitting follow-up sputum (47%) was observed in this group. Similarly, caregivers educate their patients more often on the treatment of the disease (98%) and drug taking (100%), than on submitting sputum during treatment (53%) and its importance (54%). Respondent adherence to treatment was significantly associated with respondent's knowledge about the disease and its treatment (p < 0.0001), and with caregiver's adherence to treatment guidelines (p = 0.0027).
Conclusions: There is a need to emphasise the importance of submitting follow-up sputum during patient education and counselling in order to enhance patient adherence and ultimately treatment outcome.
C1 [Mulenga, Chanda; Mwakazanga, David; Khondowe, Shepherd; Shamputa, Isdore Chola] Trop Dis Res Ctr, Dept Biomed Sci, Ndola, Zambia.
[Mulenga, Chanda; Rigouts, Leen] Inst Trop Med, Dept Microbiol, Mycobacteriol Unit, B-2000 Antwerp, Belgium.
[Vereecken, Kim] Inst Trop Med, Dept Parasitol, Helminthol Unit, B-2000 Antwerp, Belgium.
[Kapata, Nathan] Minist Hlth, Natl TB & Leprosy Program, Lusaka, Zambia.
[Shamputa, Isdore Chola] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Meulemans, Herman] Univ Antwerp, Dept Sociol, B-2000 Antwerp, Belgium.
[Meulemans, Herman] Res Ctr Longitudinal & Life Course Studies CELLO, B-2000 Antwerp, Belgium.
[Rigouts, Leen] Univ Antwerp, Fac Biomed Pharmaceut & Vet Sci, Dept Biomed Sci, B-2000 Antwerp, Belgium.
RP Mulenga, C (reprint author), Trop Dis Res Ctr, Dept Biomed Sci, POB 71769, Ndola, Zambia.
EM chandamulenga@yahoo.com
FU Belgian Directorate-General for Development Cooperation (DGDC); Damien
Action, Brussels, Belgium
FX This study was supported by funds from a grant of the Belgian
Directorate-General for Development Cooperation (DGDC) from which Chanda
Mulenga is a scholarship recipient, and the Damien Action, Brussels,
Belgium. We would like to thank, the two research assistants from TDRC,
Joyce W Mulenga and Victoria Luo for their hard work in questionnaire
administration, the NDHMT, and the TB Focal Persons in the participating
health centres for the assistance in implementation of the study. We
also acknowledge Webster Kasongo for his useful contributions to the
manuscript.
NR 24
TC 7
Z9 7
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD DEC 7
PY 2010
VL 10
AR 756
DI 10.1186/1471-2458-10-756
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 696ZZ
UT WOS:000285481200001
PM 21138565
ER
PT J
AU Rotunno, M
Zhao, Y
Bergen, AW
Koshiol, J
Burdette, L
Rubagotti, M
Linnoila, RI
Marincola, FM
Bertazzi, PA
Pesatori, AC
Caporaso, NE
McShane, LM
Wang, E
Landi, MT
AF Rotunno, M.
Zhao, Y.
Bergen, A. W.
Koshiol, J.
Burdette, L.
Rubagotti, M.
Linnoila, R. I.
Marincola, F. M.
Bertazzi, P. A.
Pesatori, A. C.
Caporaso, N. E.
McShane, L. M.
Wang, E.
Landi, M. T.
TI Inherited polymorphisms in the RNA-mediated interference machinery
affect microRNA expression and lung cancer survival
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE microRNA biogenesis; polymorphism; lung cancer; survival
ID PREDICTS SURVIVAL; GENES; PROGNOSIS; OVEREXPRESSION; PROFILES; INVASION;
TARGETS; LESIONS; DICER
AB BACKGROUND: MicroRNAs (miRs) have an important role in lung carcinogenesis and progression. Single-nucleotide polymorphisms (SNPs) in genes involved in miR biogenesis may affect miR expression in lung tissue and be associated with lung carcinogenesis and progression.
METHODS: We analysed 12 SNPs in POLR2A, RNASEN and DICER1 genes in 1984 cases and 2073 controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We investigated miR expression profiles in 165 lung adenocarcinoma (AD) and 125 squamous cell carcinoma tissue samples from the same population. We used logistic and Cox regression models to examine the association of individual genotypes and haplotypes with lung cancer risk and with lung cancer-specific survival, respectively. SNPs-miR expression associations in cases were assessed using two-sample t-tests and global permutation tests.
RESULTS: A haplotype in RNASEN (Drosha) was significantly associated with shorter lung cancer survival (hazard ratio = 1.86, 95% CI = 1.19-2.92, P = 0.007). In AD cases, a SNP within the same haplotype was associated with reduced RNASEN mRNA expression (P = 0.013) and with miR expression changes (global P = 0.007) of miRs known to be associated with cancer (e. g., let-7 family, miR-21, miR-25, miR-126 and miR15a).
CONCLUSION: Inherited variation in the miR-processing machinery can affect miR expression levels and lung cancer-specific survival. British Journal of Cancer (2010) 103, 1870-1874. doi:10.1038/sj.bjc.6605976 www.bjcancer.com Published online 23 November 2010 (C) 2010 Cancer Research UK
C1 [Rotunno, M.; Koshiol, J.; Burdette, L.; Caporaso, N. E.; Landi, M. T.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Zhao, Y.; McShane, L. M.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Bergen, A. W.] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA.
[Rubagotti, M.; Bertazzi, P. A.; Pesatori, A. C.] Univ Milan, EPOCA, Epidemiol Res Ctr, I-20122 Milan, Italy.
[Rubagotti, M.; Bertazzi, P. A.; Pesatori, A. C.] Osped Maggiore Policlin Mangiagalli & Regina Elen, Fdn Ist Ricovero & Cura Carattere Sci, I-20122 Milan, Italy.
[Linnoila, R. I.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Marincola, F. M.; Wang, E.] NCI, Dept Transfus Med, Clin Ctr & Ctr Human Immunol, NIH, Bethesda, MD 20892 USA.
RP Landi, MT (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM landim@mail.nih.gov
RI bertazzi, pietro alberto/D-5039-2017;
OI bertazzi, pietro alberto/0000-0003-3475-2449; Bergen,
Andrew/0000-0002-1237-7644; pesatori, angela/0000-0002-0261-3252
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
NIH, DHHS, Bethesda, MD; NCI
FX This research was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
NIH, DHHS, Bethesda, MD and by a 2006 NCI Director's Innovation Award to
MTL. We thank the EAGLE participants and study collaborators listed on
the EAGLE website (http://eagle.cancer.gov/).
NR 24
TC 19
Z9 21
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD DEC 7
PY 2010
VL 103
IS 12
BP 1870
EP 1874
DI 10.1038/sj.bjc.6605976
PG 5
WC Oncology
SC Oncology
GA 691MD
UT WOS:000285083400016
PM 21102586
ER
PT J
AU de Gonzalez, AB
Kim, KP
Smith-Bindman, R
McAreavey, D
AF de Gonzalez, Amy Berrington
Kim, Kwang-Pyo
Smith-Bindman, Rebecca
McAreavey, Dorothea
TI Myocardial Perfusion Scans Projected Population Cancer Risks From
Current Levels of Use in the United States
SO CIRCULATION
LA English
DT Article
DE cancer risks; computed tomography; nuclear medicine; perfusion;
radioisotopes
ID EMISSION COMPUTED-TOMOGRAPHY; CORONARY-ARTERY-DISEASE; ATOMIC-BOMB
SURVIVORS; IONIZING-RADIATION; NUCLEAR CARDIOLOGY; POOLED ANALYSIS;
EXPOSURE; RADIOLOGY; MORTALITY; MEDICINE
AB Background-Myocardial perfusion scans contribute up to 20% of the estimated annual collective radiation dose to the US population. We estimated potential future cancer risk from these scans by age at exposure and current frequency of use in the United States.
Methods and Results-Usage patterns were determined from national survey data, and radionuclide dosage was based on current guidelines. Cancer risk projection models were generated on the basis of the National Research Council Biological Effects of Ionizing Radiation VII report, under the assumption that risk has a linear relationship with radiation exposure even at low doses. The mean projected number of radiation-related incident cancers and 95% uncertainty intervals were estimated with the use of Monte Carlo simulations. Estimated risks for a scan performed at age 50 years ranged from 2 cancers per 10 000 scans (95% uncertainty interval, 1 to 5) for a positron emission tomography ammonia-13 test to 25 cancers per 10 000 scans (95% uncertainty interval, 9 to 58) for a dual-isotope (thallium-201 plus technetium-99m) scan. Risks were 50% lower at age 70 years but were similar for men and women. The combination of cancer risk estimates and data on frequency of use suggests that the 9.1 million myocardial perfusion scans performed annually in the United States could result in 7400 (95% uncertainty interval, 3300 to 13 700) additional future cancers.
Conclusions-The lifetime cancer risk from a single myocardial perfusion scan is small and should be balanced against likely benefit and appropriateness of the test. The estimates depend on a number of assumptions, including life expectancy. They apply directly to asymptomatic individuals with life expectancies similar to those of the general population. For individuals with a symptomatic clinical profile, on whom such scans are typically performed, the risks will be lower because of shorter life expectancy. (Circulation. 2010;122:2403-2410.)
C1 [de Gonzalez, Amy Berrington] NCI, Radiat Epidemiol Branch, DCEG, Bethesda, MD 20892 USA.
[Kim, Kwang-Pyo] Kyung Hee Univ, Dept Nucl Engn, Gyeonggi Do, South Korea.
[Smith-Bindman, Rebecca] Univ San Francisco, Dept Radiol, San Francisco, CA 94117 USA.
[McAreavey, Dorothea] NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA.
[McAreavey, Dorothea] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
RP de Gonzalez, AB (reprint author), NCI, Radiat Epidemiol Branch, DCEG, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM berringtona@mail.nih.gov
FU National Institutes of Health; National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health and the National Cancer Institute.
NR 47
TC 48
Z9 49
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD DEC 7
PY 2010
VL 122
IS 23
BP 2403
EP 2410
DI 10.1161/CIRCULATIONAHA.110.941625
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 690JZ
UT WOS:000285002100014
ER
PT J
AU Butterfield, LH
Disis, ML
Khleif, SN
Balwit, JM
Marincola, FM
AF Butterfield, Lisa H.
Disis, Mary L.
Khleif, Samir N.
Balwit, James M.
Marincola, Francesco M.
TI Immuno-Oncology biomarkers 2010 and beyond: Perspectives from the
iSBTc/SITC biomarker task force
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID OVARIAN-CANCER; T-CELLS; SURVIVAL; LYMPHOCYTES
AB The International Society for Biological Therapy of Cancer (iSBTc, recently renamed the Society for Immunotherapy of Cancer, SITC) hosted a one-day symposium at the National Institutes of Health on September 30, 2010 to address development and application of biomarkers in cancer immunotherapy. The symposium, titled Immuno-Oncology Biomarkers 2010 and Beyond: Perspectives from the iSBTc/SITC Biomarker Task Force, gathered approximately 230 investigators equally from academia, industry and governmental/regulatory agencies from around the globe for panel discussions and presentations on the following topics: 1) immunologic monitoring: standardization and validation of assays; 2) correlation of immunity to biologic activity, clinical response and potency assays; 3) novel methodologies for assessing the immune landscape: clinical utility of novel technologies; and 4) recommendations on incorporation of biomarkers into the clinical arena. The presentations are summarized in this report; additional program information and slides are available online at the iSBTc/SITC website.
C1 [Marincola, Francesco M.] NIH, IDIS, Dept Translat Med, Ctr Clin, Bethesda, MD 20892 USA.
[Marincola, Francesco M.] NIH, CHI, Bethesda, MD 20892 USA.
[Butterfield, Lisa H.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Butterfield, Lisa H.] Univ Pittsburgh, Dept Surg & Immunol, Pittsburgh, PA USA.
[Disis, Mary L.] Univ Washington, Tumor Vaccine Grp, Div Oncol, Seattle, WA 98195 USA.
[Khleif, Samir N.] NCI, Canc Vaccine Sect, NIH, Bethesda, MD 20892 USA.
[Balwit, James M.] Soc Immunotherapy Canc & Execut Director Inc, Milwaukee, WI USA.
RP Marincola, FM (reprint author), NIH, IDIS, Dept Translat Med, Ctr Clin, Bethesda, MD 20892 USA.
EM Fmarincola@mail.cc.nih.gov
NR 15
TC 19
Z9 19
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD DEC 7
PY 2010
VL 8
AR 130
DI 10.1186/1479-5876-8-130
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 702HH
UT WOS:000285884700001
PM 21138581
ER
PT J
AU Bogoslovsky, T
Chaudhry, A
Latour, L
Maric, D
Luby, M
Spatz, M
Frank, J
Warach, S
AF Bogoslovsky, T.
Chaudhry, A.
Latour, L.
Maric, D.
Luby, M.
Spatz, M.
Frank, J.
Warach, S.
TI Endothelial progenitor cells correlate with lesion volume and growth in
acute stroke
SO NEUROLOGY
LA English
DT Article
ID INFARCTION; MRI
AB Objectives: Circulating endothelial progenitor cells (EPC) are markers of vascular injury and their numbers decrease in acute stroke. However, the relation of EPC levels to stroke severity has not been quantified. MRI measurements of lesion volume provide an objective method for stroke severity assessment and outcome prediction. This cross-sectional study aims to determine whether EPC are correlated with lesion volume at baseline, lesion growth, and final lesion volume.
Methods: Seventeen patients (median age 63 years, NIH Stroke Scale score 7) were selected from 175 patients with imaging-confirmed acute ischemic stroke. EPC were quantified by flow cytometry using CD34, CD133, and VEGFR2 surface markers. Brain MRI was performed at baseline and at days 1 and 5 after the stroke onset. Stroke lesion volumes were quantified.
Results: Larger lesion volumes measured on diffusion-weighted images (DWI) at baseline were associated with low EPC levels, while smaller lesion volumes and less lesion growth were linked with high levels of EPC subsets (CD34+CD133+, CD133+VEGFR2+, and CD34+ CD133+VEGFR2+). Similar results were observed with DWI lesion volumes and EPC (CD34+CD133+) on day 1. Lesion growth volume, represented as a difference between final lesion volume and baseline DWI, was larger in patients with lower day 1 EPC (CD133+VEGFR2+). After adjustments for age and admission glucose (model 1), mean arterial pressure and white blood cells (model 2), INR and hematocrit (model 3), the CD34+CD133+ subset remained predictive of baseline and day 1 lesion volumes, while CD133+VEGFR2+ predicted baseline lesion volume and growth of lesion volume.
Conclusions: Higher EPC levels were indicative of smaller volumes of acute lesion, final lesion, and lesion growth, and may serve as markers of acute phase stroke severity. However, a larger prospective study is needed to confirm our findings. Neurology (R) 2010;75:2059-2062
C1 [Bogoslovsky, T.; Latour, L.; Luby, M.; Warach, S.] NIH, Stroke Diagnost & Therapeut Sect, Lab Diagnost Radiol, Bethesda, MD 20892 USA.
[Spatz, M.] NIH, Stroke Branch, Lab Diagnost Radiol, Bethesda, MD 20892 USA.
[Maric, D.] NIH, NINDS Flow Cytometry Core Facil, Lab Diagnost Radiol, Bethesda, MD 20892 USA.
[Chaudhry, A.; Frank, J.] Natl Inst Biomed Imaging & Bioengn, Natl Inst Neurol Disorders & Stroke, Lab Diagnost Radiol, NIH, Bethesda, MD USA.
RP Bogoslovsky, T (reprint author), Uniformed Serv Univ Hlth Sci, CNRM, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA.
EM Tanya.Bogoslovsky.CTR@usuhs.mil
FU Division of Intramural Research of the NIH/NINDS; Finnish Cultural
Foundation; Paivikki and Sakari Sohlberg Foundation; Paavo Nurmi
Foundation
FX Supported by the Division of Intramural Research of the NIH/NINDS and by
the Finnish Cultural Foundation, the Paivikki and Sakari Sohlberg
Foundation, and the Paavo Nurmi Foundation.
NR 10
TC 26
Z9 32
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD DEC 7
PY 2010
VL 75
IS 23
BP 2059
EP 2062
DI 10.1212/WNL.0b013e318200d741
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 690XV
UT WOS:000285044300007
PM 21135380
ER
PT J
AU Popescu, BFG
Parisi, JE
Cabrera-Gomez, JA
Newell, K
Mandler, RN
Pittock, SJ
Lennon, VA
Weinshenker, BG
Lucchinetti, CF
AF Popescu, B. F. Gh.
Parisi, J. E.
Cabrera-Gomez, J. A.
Newell, K.
Mandler, R. N.
Pittock, S. J.
Lennon, V. A.
Weinshenker, B. G.
Lucchinetti, C. F.
TI Absence of cortical demyelination in neuromyelitis optica
SO NEUROLOGY
LA English
DT Article
ID BLOOD-BRAIN-BARRIER; MULTIPLE-SCLEROSIS; WHITE-MATTER; GRAY-MATTER;
LESIONS; INJURY; CORTEX; MARKER
AB Objective: To asses the presence of cortical demyelination in brains of patients with neuromyelitis optica (NMO). NMO is an autoimmune inflammatory demyelinating disease that specifically targets aquaporin-4-rich regions of the CNS. Since aquaporin-4 is highly expressed in normal cortex, we anticipated that cortical demyelination may occur in NMO.
Methods: This is a cross-sectional neuropathologic study performed on archival forebrain and cerebellar tissue sections from 19 autopsied patients with a clinically and/or pathologically confirmed NMO spectrum disorder.
Results: Detailed immunohistochemical analyses of 19 archival NMO cases revealed preservation of aquaporin-4 in a normal distribution within cerebral and cerebellar cortices, and no evidence of cortical demyelination.
Conclusions: This study provides a plausible explanation for the absence of a secondary progressive clinical course in NMO and shows that cognitive and cortical neuroimaging abnormalities previously reported in NMO cannot be attributed to cortical demyelination. Lack of cortical demyelination is another characteristic that further distinguishes NMO from MS. Neurology (R) 2010;75:2103-2109
C1 [Lucchinetti, C. F.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN 55905 USA.
[Parisi, J. E.; Pittock, S. J.; Lennon, V. A.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Lennon, V. A.] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA.
[Cabrera-Gomez, J. A.] Internac Neurol Ctr, Cuban Multiple Sclerosis Soc, Havana, Cuba.
[Cabrera-Gomez, J. A.] Internac Neurol Ctr, Multiple Sclerosis Clin, Havana, Cuba.
Int Ctr Neurol Restorat CIREN, Havana, Cuba.
[Newell, K.] Univ Kansas, Med Ctr, Dept Pathol, Kansas City, KS USA.
[Mandler, R. N.] NIH, NIDA, Bethesda, MD 20892 USA.
RP Lucchinetti, CF (reprint author), Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55905 USA.
EM lucchinetti.claudia@mayo.edu
FU NIH [NS32352-13, U01 AG031106, R21 AG027419, R01 DK71209-05,
NS49577-R01]; Alexion Pharmaceuticals, Inc.; Guthy Jackson Charitable
Foundation; Jackson Charitable Foundation; Genzyme Corporation;
Guthy-Jackson Charitable Foundation; National MS Society [RG 3185-B-3]
FX Dr. Popescu reports no disclosures. Dr. Parisi serves on scientific
advisory boards for the US Government Defense Health Board and the
Subcommittee for Laboratory Services and Pathology; serves as a Section
Editor for Neurology; receives royalties from the publication of
Principles & Practice of Neuropathology, 2nd ed. (Oxford University
Press, 2003); and receives research support from the NIH (NS32352-13
[coinvestigator]). Dr. Cabrera-Gomez reports no disclosures. Dr. Newell
receives/has received research support from the NIH (U01 AG031106
[coinvestigator] and R21 AG027419 [coinvestigator]). Dr. Mandler reports
no disclosures. Dr. Pittock may accrue revenue for patents re:
Aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica
and aquaporin-4 autoantibody as a cancer marker; and has received
research support from Alexion Pharmaceuticals, Inc. and the Guthy
Jackson Charitable Foundation. Dr. Lennon is a named investor on a
patent application filed by the Mayo Foundation for Medical Education
and Research that relates to the NMO antigen and its application to the
diagnosis of NMO; may accrue revenue for a patent re: Aquaporin-4
associated antibodies for diagnosis of neuromyelitis optica; receives
research support from the NIH (R01 DK71209-05 [PI]) and the Guthy
Jackson Charitable Foundation. Dr. Weinshenker serves on data safety
monitoring boards for Novartis and Biogen Idec; serves on the editorial
boards of the Canadian Journal of Neurological Sciences and the Turkish
Journal of Neurology; has received research support from Genzyme
Corporation and the Guthy-Jackson Charitable Foundation; and receives
license royalties from RSR Ltd. for a patent re: Aquaporin-4 associated
antibodies for diagnosis of neuromyelitis optica. Dr. Lucchinetti may
accrue revenue for a patent re: Aquaporin-4 associated antibodies for
diagnosis of neuromyelitis optica; receives royalties from the
publication of Blue Books of Neurology: Multiple Sclerosis 3 (Saunders
Elsevier, 2010); and receives research support from the NIH (NS49577-R01
[PI]), the Guthy Jackson Charitable Foundation (PI), and the National MS
Society (RG 3185-B-3 [PI]).
NR 26
TC 51
Z9 54
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD DEC 7
PY 2010
VL 75
IS 23
BP 2103
EP 2109
DI 10.1212/WNL.0b013e318200d80c
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 690XV
UT WOS:000285044300013
PM 21135384
ER
PT J
AU Volkow, ND
Fowler, JS
Wang, GJ
Shumay, E
Telang, F
Thanos, PK
Alexoff, D
AF Volkow, Nora D.
Fowler, Joanna S.
Wang, Gene-Jack
Shumay, Elena
Telang, Frank
Thanos, Peter K.
Alexoff, David
TI Distribution and Pharmacokinetics of Methamphetamine in the Human Body:
Clinical Implications
SO PLOS ONE
LA English
DT Article
ID AMPHETAMINE; PET; DOPAMINE; SMOKING; COCAINE; BINDING; MICE
AB Background: Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body.
Methods: Positron Emission Tomography (PET) was used in conjunction with [(11)C]d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans).
Results: Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight similar to 1246 g), liver (23%; weight similar to 1677 g) and intermediate in brain (10%; weight similar to 1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7-16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22-50 minutes). Lung accumulation of [(11)C]d-methamphetamine was 30% higher for African Americans than Caucasians (p<0.05) but did not differ in other organs.
Conclusions: The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans.
C1 [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA.
[Volkow, Nora D.; Telang, Frank; Thanos, Peter K.] Natl Inst Alcohol Abuse & Alcoholism, Bethesda, MD USA.
[Fowler, Joanna S.; Wang, Gene-Jack; Shumay, Elena; Alexoff, David] Brookhaven Natl Lab, Upton, NY 11973 USA.
RP Volkow, ND (reprint author), Natl Inst Drug Abuse, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
FU National Institutes of Health (NIH), National Institute on Alcohol Abuse
and Alcoholism, the National Institute on Drug Abuse [K05DA020001];
Department of Energy; [MO1RR10710]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Institute on Alcohol Abuse
and Alcoholism, the National Institute on Drug Abuse (K05DA020001) and
infrastructure support from the Department of Energy and GCRC grant
MO1RR10710. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 36
TC 37
Z9 39
U1 1
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 7
PY 2010
VL 5
IS 12
AR e15269
DI 10.1371/journal.pone.0015269
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 690XB
UT WOS:000285041800013
PM 21151866
ER
PT J
AU McElhinny, SAN
Kissling, GE
Kunkel, TA
AF McElhinny, Stephanie A. Nick
Kissling, Grace E.
Kunkel, Thomas A.
TI Differential correction of lagging-strand replication errors made by DNA
polymerases alpha and delta
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE replication fork; DNA repair; infidelity; mutagenesis; base
substitutions
ID MISMATCH-REPAIR SYSTEM; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI;
YEAST; EXONUCLEASE; MECHANISM; EPSILON; COMPLEX; CANCER; FORK
AB Mismatch repair (MMR) of replication errors requires DNA ends that can direct repair to the newly synthesized strand containing the error. For all but those organisms that use adenine methylation to generate nicks, the source of these ends in vivo is unknown. One possibility is that MMR may have a "special relation to the replication complex" [Wagner R, Jr., Meselson M (1976) Proc Natl Acad Sci USA 73: 4135-4139], perhaps one that allows 5' or 3' DNA ends associated with replication to act as strand discrimination signals. Here we examine this hypothesis, based on the logic that errors made by yeast DNA polymerase alpha (Pol alpha), which initiates Okazaki fragments during lagging-strand replication, will always be closer to a 5' end than will bemore internal errors generated by DNA polymerase delta (Pol delta), which takes over for Pol alpha to complete lagging-strand replication. When we compared MMR efficiency for errors made by variant forms of these two polymerases, Msh2-dependent repair efficiencies for mismatches made by Pol alpha were consistently higher than for those same mismatches when made by Pol delta. Thus, one special relationship between MMR and replication is that MMR is more efficient for the least accurate of the major replicative polymerases, exonuclease-deficient Pol alpha. This observation is consistent with the close proximity and possible use of 5' ends of Okazaki fragments for strand discrimination, which could increase the probability of Msh2-dependent MMR by 5' excision, by aMsh2-dependent strand displacement mechanism, or both.
C1 [McElhinny, Stephanie A. Nick; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[McElhinny, Stephanie A. Nick; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Kissling, Grace E.] NIEHS, Biostat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, 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
ES065089]
FX We thank Jana Stone and Zachary Pursell for contributing to the mutation
spectra in the wild-type yeast strains, the National Institute of
Environmental Health Sciences DNA Sequencing Core and Molecular Genetics
Core for technical support, Dmitry Gordenin for advice, and Mercedes
Arana and Scott Lujan for helpful comments on the manuscript. This work
was supported by Project Z01 ES065089 (to T. A. K.) in the Division of
Intramural Research of the National Institute of Environmental Health
Sciences, National Institutes of Health.
NR 45
TC 30
Z9 30
U1 0
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 7
PY 2010
VL 107
IS 49
BP 21070
EP 21075
DI 10.1073/pnas.1013048107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 690ZY
UT WOS:000285050800042
ER
PT J
AU Kong, KC
Butcher, AJ
McWilliams, P
Jones, D
Wess, J
Hamdan, FF
Werry, T
Rosethorne, EM
Charlton, SJ
Munson, SE
Cragg, HA
Smart, AD
Tobin, AB
AF Kong, Kok Choi
Butcher, Adrian J.
McWilliams, Phillip
Jones, David
Wess, Juergen
Hamdan, Fadi F.
Werry, Tim
Rosethorne, Elizabeth M.
Charlton, Steven J.
Munson, Sarah E.
Cragg, Hannah A.
Smart, Alison D.
Tobin, Andrew B.
TI M-3-muscarinic receptor promotes insulin release via receptor
phosphorylation/arrestin-dependent activation of protein kinase D1
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE G-protein coupled receptor; ligand bias
ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; BETA-CELL FUNCTION; COUPLED-RECEPTOR;
7-TRANSMEMBRANE RECEPTORS; GLUCOSE-HOMEOSTASIS; DISTINCT MECHANISMS;
ARRESTINS; SECRETION; ROLES; MICE
AB The activity of G protein-coupled receptors is regulated via hyper-phosphorylation following agonist stimulation. Despite the universal nature of this regulatory process, the physiological impact of receptor phosphorylation remains poorly studied. To address this question, we have generated a knock-in mouse strain that expresses a phosphorylation-deficient mutant of the M-3-muscarinic receptor, a prototypical Gq/11-coupled receptor. This mutant mouse strain was used here to investigate the role of M-3-muscarinic receptor phosphorylation in the regulation of insulin secretion from pancreatic islets. Importantly, the phosphorylation deficient receptor coupled to G(q/11)-signaling pathways but was uncoupled from phosphorylation-dependent processes, such as receptor internalization and beta-arrestin recruitment. The knock-in mice showed impaired glucose tolerance and insulin secretion, indicating that M-3-muscarinic receptors expressed on pancreatic islets regulate glucose homeostasis via receptor phosphorylation-/arrestin-dependent signaling. The mechanism centers on the activation of protein kinase D1, which operates downstream of the recruitment of beta-arrestin to the phosphorylated M-3-muscarinic receptor. In conclusion, our findings support the unique concept that M-3-muscarinic receptor-mediated augmentation of sustained insulin release is largely independent of G protein-coupling but involves phosphorylation-/ arrestin-dependent coupling of the receptor to protein kinase D1.
C1 [Kong, Kok Choi; Butcher, Adrian J.; McWilliams, Phillip; Tobin, Andrew B.] Univ Leicester, Dept Cell Physiol & Pharmacol, Leicester LE1 9HN, Leics, England.
[Munson, Sarah E.] Univ Leicester, Geneta Ctr Core Biotechnol Serv, Leicester LE1 9HN, Leics, England.
[Cragg, Hannah A.; Smart, Alison D.] Univ Leicester, Biomed Serv Div, Leicester LE1 9HN, Leics, England.
[Wess, Juergen] NIDDKD, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA.
[Hamdan, Fadi F.] Univ Montreal, Ctr Excellence Neur, St Justine Hosp, Res Ctr, Montreal, PQ H3T 1C5, Canada.
[Werry, Tim] GlaxoSmithKline Inc, Neurosci Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England.
[Rosethorne, Elizabeth M.; Charlton, Steven J.] Novartis Inst Biomed Res, Horsham W RH125AB, Sussex, England.
RP Tobin, AB (reprint author), Univ Leicester, Dept Cell Physiol & Pharmacol, Leicester LE1 9HN, Leics, England.
EM tba@leicester.ac.uk
OI Rosethorne, Elizabeth/0000-0001-6877-2320
FU Wellcome Trust [047600]; National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health, US Department of
Health and Human Services
FX This work was supported by the Wellcome Trust (Grant 047600) and the
Intramural Research Program, National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health, US
Department of Health and Human Services.
NR 29
TC 38
Z9 38
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD DEC 7
PY 2010
VL 107
IS 49
BP 21181
EP 21186
DI 10.1073/pnas.1011651107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 690ZY
UT WOS:000285050800061
PM 21078968
ER
PT J
AU Maximova, OA
Murphy, BR
Pletnev, AG
AF Maximova, Olga A.
Murphy, Brian R.
Pletnev, Alexander G.
TI High-throughput automated image analysis of neuroinflammation and
neurodegeneration enables quantitative assessment of virus
neurovirulence
SO VACCINE
LA English
DT Article
DE Virus neurovirulence; Nonhuman primates; Neuroinflammation;
Neurodegeneration; Digital pathology; Automated image analysis (AIA)
ID GROUP-B ARBOVIRUSES; LIVE FLAVIVIRAL VACCINES; NONHUMAN-PRIMATES; MONKEY
NEUROVIRULENCE; RHESUS-MONKEYS; NEURONAL MARKER; SAFETY TEST;
ENCEPHALITIS; NEUN; NEUROPATHOGENESIS
AB Historically, the safety of live attenuated vaccine candidates against neurotropic viruses was assessed by semi-quantitative analysis of virus-induced histopathology in the central nervous system of monkeys. We have developed a high-throughput automated image analysis (AIA) for the quantitative assessment of virus-induced neuroinflammation and neurodegeneration. Evaluation of the results generated by AIA showed that quantitative estimates of lymphocytic infiltration, microglial activation, and neurodegeneration strongly and significantly correlated with results of traditional histopathological scoring. In addition, we show that AIA is a targeted, objective, accurate, and time-efficient approach that provides reliable differentiation of virus neurovirulence. As such, it may become a useful tool in establishing consistent analytical standards across research and development laboratories and regulatory agencies, and may improve the safety evaluation of live virus vaccines. The implementation of this high-throughput ALA will markedly advance many fields of research including virology, neuroinflammation, neuroscience, and vaccinology. Published by Elsevier Ltd.
C1 [Maximova, Olga A.; Murphy, Brian R.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Maximova, OA (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM maximovao@niaid.nih.gov; bmurphy@niaid.nih.gov; apletnev@niaid.nih.gov
FU NIAID
FX We acknowledge the staff of Bioqual, Inc. (Rockville, MD) and Pathology
Associates Division of Charles River Laboratories (Frederick, MD), and
Dr. J. Ward, Dr. R. Montali, Lawrence Faucette, Marina Rahman, and
Katherine Shea (Comparative Medicine Branch, NIAID, NIH) for their help
in conducting the studies. We also thank Drs. J. Taubenberger and S.
Whitehead, NIAID, NIH for helpful discussions and critical reading of
the manuscript. This work was supported by funds provided by the NIAID
Intramural Research Program.
NR 33
TC 5
Z9 6
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD DEC 6
PY 2010
VL 28
IS 52
BP 8315
EP 8326
DI 10.1016/j.vaccine.2010.07.070
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 708MQ
UT WOS:000286366300010
PM 20688036
ER
PT J
AU Zhang, Y
Yu, L
Tang, ZR
Huang, SB
Zheng, YJ
Meng, ZH
Sun, K
Wang, LM
Chen, RY
Zhang, FJ
AF Zhang Yao
Yu Lan
Tang Zhi-rong
Huang Shao-biao
Zheng Yuan-jia
Meng Zhi-hao
Sun Kai
Wang Li-ming
Chen, Ray Y.
Zhang Fu-jie
TI Diagnosis of pulmonary tuberculosis among asymptomatic HIV+ patients in
Guangxi, China
SO CHINESE MEDICAL JOURNAL
LA English
DT Article
DE tuberculosis human immunodeficiency virus; diagnosis
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESOURCE-LIMITED SETTINGS; INFECTED
PATIENTS; OPPORTUNISTIC INFECTIONS; ANTIRETROVIRAL THERAPY; ADULTS;
MORTALITY; PREVENTION; SURVIVAL; AMERICA
AB Background Pulmonary tuberculosis (PTB) among asymptomatic Chinese patients with HIV infection has not been investigated despite high tuberculosis burden in China This study was aimed to evaluate the prevalence, risk factors and clinical outcomes of PTB among asymptomatic patients with HIV/AIDS in Guangxi to facilitate the development of diagnostic and treatment strategies
Methods All asymptomatic adult HIV-infected patients with CD4 <350 cells/mu l who attended four HIV clinics in Guangxi between August 2006 and March 2008 were evaluated for active PTB with physical examination, chest X-ray (CXR), sputum smear and/or sputum liquid culture Data were described using median (interquartile range, IQR) and frequencies Univariate and multivariate Logistic regression analyses were performed to identify risk factors associated with PTB
Results Among 340 asymptomatic subjects, 15 (4%) were diagnosed with PTB, with 4 (27%) sputum smear positive and 8 (53%) sputum culture positive CXR has higher diagnostic sensitivity (87%) than sputum smear (25%) and sputum culture (67%), but lower specificity (56%) compared with sputum smear (99%) and culture (100%) In univariate analysis, injection drug user body mass index (BMI) <18 kg/m(2) CD4 <50 cells/mu l and presence of peripheral lymphadenopathy were associated with an increased risk of asymptomatic PTB, while in multivariate analysis only peripheral lymphadenopathy maintained statistical significance (OR=7 6, 95% CI 1 4-40) Patients with negative smear and minor or no abnormalities on CXR had longer interval between screening and TB treatment
Conclusions PTB was relatively common in this group of HIV+ asymptomatic Chinese patients Diagnosis is challenging especially where sputum culture is unavailable These findings suggest that an enhanced evaluation for PTB needs to be integrated with HIV care in China and transmission prevention in China to control at both households and health care facilities, especially for patients with factors associated with a higher risk of PTB
C1 [Zhang Yao; Yu Lan; Zhang Fu-jie] Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent, Div Treatment & Care, Beijing 100050, Peoples R China.
[Zhang Fu-jie] Beijing Ditan Hosp, Beijing 100015, Peoples R China.
[Tang Zhi-rong] Prov Ctr Dis Control & Prevent, Nanning 53000, Guangxi, Peoples R China.
[Huang Shao-biao] Nanning 4th Peoples Hosp, Nanning 530000, Guangxi, Peoples R China.
[Zheng Yuan-jia] Ctr Dis Control & Prevent Liuzhou City, Liuzhou 545000, Guangxi, Peoples R China.
[Meng Zhi-hao] Liuzhou Longtan Hosp, Liuzhou 545000, Guangxi, Peoples R China.
[Sun Kai] Univ N Carolina, Chapel Hill, NC USA.
[Sun Kai] Washington Univ, Sch Med, St Louis, MO USA.
[Wang Li-ming] US Ctr Dis Control & Prevent, Global AIDS Program, Beijing 100600, Peoples R China.
[Chen, Ray Y.] US Natl Inst Hlth, NIAID, Off Global Res, Beijing 100600, Peoples R China.
RP Zhang, FJ (reprint author), Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent, Div Treatment & Care, Beijing 100050, Peoples R China.
OI Chen, Ray/0000-0001-6344-1442
FU Chinese National Basic Research Program (973) [2006CB504201]
FX This study was supported by a grant from the Chinese National Basic
Research Program (973) (No 2006CB504201)
NR 33
TC 2
Z9 3
U1 0
U2 4
PU CHINESE MEDICAL ASSOC
PI BEIJING
PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA
SN 0366-6999
J9 CHINESE MED J-PEKING
JI Chin. Med. J.
PD DEC 5
PY 2010
VL 123
IS 23
BP 3400
EP 3405
DI 10.3760/cma.j.issn.0366-6999.2010.23.005
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 695VQ
UT WOS:000285401100005
PM 22166521
ER
PT J
AU Tigabu, B
Juelich, T
Holbrook, MR
AF Tigabu, Bersabeh
Juelich, Terry
Holbrook, Michael R.
TI Comparative analysis of immune responses to Russian spring-summer
encephalitis and Omsk hemorrhagic fever viruses in mouse models
SO VIROLOGY
LA English
DT Article
DE OHFV; RSSEV; TBE; Omsk hemorrhagic fever; Russian spring-summer
encephalitis; Pathogenesis; Host response
ID TICK-BORNE ENCEPHALITIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;
JAPANESE ENCEPHALITIS; CEREBROSPINAL-FLUID; INFECTION; SERUM;
IMMUNOPATHOLOGY; MENINGITIS; EXPRESSION; CYTOKINES
AB Omsk hemorrhagic fever virus (OHFV) and Russian spring-summer encephalitis virus (RSSEV) are tick-borne flaviviruses that have close homology but different pathology and disease outcomes. Previously, we reported that C57BL/6 and BALB/c mice were excellent models to study the pathology and clinical signs of human RSSEV and OHFV infection. In the study described here, we found that RSSEV infection induced robust release of proinflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6 and TNF-alpha) and chemokines (MCP-1, MIP-1 beta, RANTES and KC) in the brain at 9 and 11dpi, together with moderate to low Th1 and Th2 cytokines. In contrast, OHFV infection stimulated an early and prominent induction of IL-1 alpha, TNF-alpha, IL-12p70, MCP-1, MIP-1 alpha and MIP-1 beta in the spleen of infected mice. Collectively our data suggest that a differential host response to infection may lead to the alternate disease outcomes seen following OHFV or RSSEV infection. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Tigabu, Bersabeh; Juelich, Terry; Holbrook, Michael R.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77550 USA.
[Holbrook, Michael R.] NIAID, Integrated Res Facil, Frederick, MD 21702 USA.
RP Holbrook, MR (reprint author), NIAID, Integrated Res Facil, 8200 Res Plaza, Ft Detrick Frederick, MD 21702 USA.
EM michael.holbrook@nih.gov
FU Western Regional Center of Excellence [U54 AI057156]
FX We thank N. Seth Linde, Allison Poussard, Colette Pietzsch and Melissa
Worthy for their excellent technical assistance. This project was
supported in part by a Western Regional Center of Excellence Career
Development award (U54 AI057156) to MRH.
NR 34
TC 10
Z9 10
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 0042-6822
J9 VIROLOGY
JI Virology
PD DEC 5
PY 2010
VL 408
IS 1
BP 57
EP 63
DI 10.1016/j.virol.2010.08.021
PG 7
WC Virology
SC Virology
GA 677DY
UT WOS:000283970500006
PM 20875909
ER
PT J
AU Borges, AR
Wieczorek, L
Johnson, B
Benesi, AJ
Brown, BK
Kensinger, RD
Krebs, FC
Wigdahl, B
Blumenthal, R
Puri, A
McCutchan, FE
Birx, DL
Polonis, VR
Schengrund, CL
AF Borges, Andrew Rosa
Wieczorek, Lindsay
Johnson, Benitra
Benesi, Alan J.
Brown, Bruce K.
Kensinger, Richard D.
Krebs, Fred C.
Wigdahl, Brian
Blumenthal, Robert
Puri, Anu
McCutchan, Francine E.
Birx, Deborah L.
Polonis, Victoria R.
Schengrund, Cara-Lynne
TI Multivalent dendrimeric compounds containing carbohydrates expressed on
immune cells inhibit infection by primary isolates of HIV-1
SO VIROLOGY
LA English
DT Article
DE Human immunodeficiency virus-1; Multivalent carbohydrates; 3
'-sialyllactose; Globotriose; Peripheral blood mononuclear cells; T cell
lines
ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; GANGLIOSIDE GM3;
ENVELOPE GLYCOPROTEIN; V3 LOOP; SURFACE GLYCOSPHINGOLIPIDS; MEMBRANE
MICRODOMAINS; MONOCLONAL-ANTIBODIES; GALACTOSYL CERAMIDE; TYPE-1
INFECTION
AB Specific glycosphingolipids (GSL), found on the surface of target immune cells, are recognized as alternate cell surface receptors by the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein. In this study, the globotriose and 3'-sialyllactose carbohydrate head groups found on two GSL were covalently attached to a dendrimer core to produce two types of unique multivalent carbohydrates (MVC). These MVC inhibited HIV-1 infection of T cell lines and primary peripheral blood mononuclear cells (PBMC) by T cell line-adapted viruses or primary isolates, with IC(50)s ranging from 0.1 to 7.4 mu g/ml. Inhibition of Env-mediated membrane fusion by MVC was also observed using a dye-transfer assay. These carbohydrate compounds warrant further investigation as a potential new class of HIV-1 entry inhibitors. The data presented also shed light on the role of carbohydrate moieties in HIV-1 virus-host cell interactions. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Borges, Andrew Rosa; Wieczorek, Lindsay; Brown, Bruce K.; McCutchan, Francine E.] Henry M Jackson Fdn, Mil HIV Res Program, Rockville, MD 20850 USA.
[Johnson, Benitra; Blumenthal, Robert; Puri, Anu] NCI, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
[Benesi, Alan J.] Penn State Univ, Dept Chem, State Coll, PA USA.
[Kensinger, Richard D.; Schengrund, Cara-Lynne] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA USA.
[Krebs, Fred C.; Wigdahl, Brian] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA.
[Birx, Deborah L.; Polonis, Victoria R.] Walter Reed Army Inst Res, Mil HIV Res Program, Div Retrovirol, Rockville, MD USA.
RP Schengrund, CL (reprint author), Penn State Coll Med, Dept Biochem & Mol Biol, 500 Univ Dr, Hershey, PA 17033 USA.
EM cxs8@psu.edu
FU National Institute of Allergy and Infectious Diseases [RO1 NS40231];
NIH, National Cancer Institute, Center for Cancer Research; U.S. Army
Medical Research and Material Command [DAMD W81XWH-04-2-0005]; Henry M.
Jackson Foundation for the Advancement of Military Medicine [DAMD
W81XWH-04-2-0005]
FX This work was supported in part by grant RO1 NS40231 from the National
Institute of Allergy and Infectious Diseases (CLS), the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research (AP and RB), and by Cooperative Agreement no. DAMD
W81XWH-04-2-0005 between the U.S. Army Medical Research and Material
Command and the Henry M. Jackson Foundation for the Advancement of
Military Medicine, working with the Division of AIDS, National Institute
for Allergy and Infectious Diseases, National Institutes of Health.
NR 80
TC 18
Z9 18
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD DEC 5
PY 2010
VL 408
IS 1
BP 80
EP 88
DI 10.1016/j.virol.2010.09.004
PG 9
WC Virology
SC Virology
GA 677DY
UT WOS:000283970500009
ER
PT J
AU Min, JY
Chen, GL
Santos, C
Lamirande, EW
Matsuoka, Y
Subbarao, K
AF Min, Ji-Young
Chen, Grace L.
Santos, Celia
Lamirande, Elaine W.
Matsuoka, Yumiko
Subbarao, Kanta
TI Classical swine H1N1 influenza viruses confer cross protection from
swine-origin 2009 pandemic H1N1 influenza virus infection in mice and
ferrets
SO VIROLOGY
LA English
DT Article
DE 2009 pandemic influenza; Classical swine H1N1 influenza;
Cross-protection
ID JANUARY-FEBRUARY 1976; NEW-JERSEY; FORT-DIX; TRANSMISSION; HUMANS;
VACCINE; PATHOGENESIS; EVOLUTION; OUTBREAK
AB The hemagglutinin of the 2009 pandemic H1N1 influenza virus is a derivative of and is antigenically related to classical swine but not to seasonal human H1N1 viruses. We compared the A/California/7/2009 (CA/7/09) virus recommended by the WHO as the reference virus for vaccine development, with two classical swine influenza viruses A/swine/Iowa/31 (sw/IA/31) and A/New Jersey/8/1976 (NJ/76) to establish the extent of immunologic cross-reactivity and cross-protection in animal models. Primary infection with 2009 pandemic or NJ/76 viruses elicited antibodies against the CA/7/09 virus and provided complete protection from challenge with this virus in ferrets: the response in mice was variable and conferred partial protection. Although ferrets infected with sw/IA/31 virus developed low titers of cross-neutralizing antibody, they were protected from pulmonary replication of the CA/7/09 virus. The data suggest that prior exposure to antigenically related H1N1 viruses of swine-origin provide some protective immunity against the 2009 pandemic H1N1 virus. Published by Elsevier Inc.
C1 [Min, Ji-Young; Chen, Grace L.; Santos, Celia; Lamirande, Elaine W.; Matsuoka, Yumiko; Subbarao, Kanta] NIAID, LID, NIH, Bethesda, MD 20892 USA.
RP Subbarao, K (reprint author), NIAID, LID, NIH, 33 North Dr,MSC 3203,Room 3E-13C-1, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
FU NIH, NIAID
FX We thank Jadon Jackson and the staff of the Comparative Medicine Branch,
NIAID for technical support for animal studies performed at the NIH. We
thank Dr. Catherine Luke for invaluable discussion throughout this work.
This research was supported in part by the Intramural Research Program
of the NIH, NIAID.
NR 32
TC 18
Z9 18
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD DEC 5
PY 2010
VL 408
IS 1
BP 128
EP 133
DI 10.1016/j.virol.2010.09.009
PG 6
WC Virology
SC Virology
GA 677DY
UT WOS:000283970500014
PM 20926110
ER
PT J
AU Morens, DM
North, M
Taubenberger, JK
AF Morens, David M.
North, Michael
Taubenberger, Jeffery K.
TI The art of medicine Eyewitness accounts of the 1510 influenza pandemic
in Europe
SO LANCET
LA English
DT Editorial Material
C1 [Morens, David M.; Taubenberger, Jeffery K.] NIAID, NIH, Bethesda, MD 20892 USA.
[North, Michael] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, NIH, Bethesda, MD 20892 USA.
EM dmorens@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI000995-04]
NR 0
TC 3
Z9 3
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD DEC 4
PY 2010
VL 376
IS 9756
BP 1894
EP 1895
DI 10.1016/S0140-6736(10)62204-0
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 696KH
UT WOS:000285439800015
PM 21155080
ER
PT J
AU Spence, SJ
Thurm, A
AF Spence, S. J.
Thurm, A.
TI Testing autism interventions: trials and tribulations (vol 375, pg 2124,
2010)
SO LANCET
LA English
DT Correction
C1 [Spence, S. J.; Thurm, A.] NIMH, Pediat & Dev Neurosci Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Spence, SJ (reprint author), NIMH, Pediat & Dev Neurosci Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD DEC 4
PY 2010
VL 376
IS 9756
BP 1902
EP 1902
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 696KH
UT WOS:000285439800030
ER
PT J
AU Tozan, Y
Klein, EY
Darley, S
Panicker, R
Laxminarayan, R
Breman, JG
AF Tozan, Yesim
Klein, Eili Y.
Darley, Sarah
Panicker, Rajashree
Laxminarayan, Ramanan
Breman, Joel G.
TI Prereferral rectal artesunate for treatment of severe childhood malaria:
a cost-effectiveness analysis
SO LANCET
LA English
DT Article
ID FALCIPARUM-MALARIA; CHILDREN; PRIORITIES; TANZANIA; HEALTH
AB Background Severely ill patients with malaria with vomiting, prostration, and altered consciousness cannot be treated orally and need injections. In rural areas, access to health facilities that provide parenteral antimalarial treatment is poor. Safe and effective treatment of most severe malaria cases is delayed or not achieved. Rectal artesunate interrupts disease progression by rapidly reducing parasite density, but should be followed by further antimalarial treatment. We estimated the cost-effectiveness of community-based prereferral artesunate treatment of children suspected to have severe malaria in areas with poor access to formal health care.
Methods We assessed the cost-effectiveness (in international dollars) of the intervention from the provider perspective. We studied a cohort of 1000 newborn babies until 5 years of age. The analysis assessed how the cost-effectiveness results changed with low (25%), moderate (50%), high (75%), and full (100%) referral compliance and intervention uptake.
Findings At low intervention uptake and referral compliance (25%), the intervention was estimated to avert 19 disability-adjusted life-years (DALYs; 95% CI 16-21) and to cost I$1173 (95% CI 1050-1297) per DALY averted. Under the full uptake and compliance scenario (100%), the intervention could avert 967 DALYs (884-1050) at a cost of I$77 (73-81) per DALY averted.
Interpretation Prereferral artesunate treatment is a cost-effective, life-saving intervention, which can substantially improve the management of severe childhood malaria in rural African settings in which programmes for community health workers are in place.
C1 [Tozan, Yesim] Boston Univ, Sch Publ Hlth, Dept Int Hlth, Boston, MA 02118 USA.
[Klein, Eili Y.; Darley, Sarah; Panicker, Rajashree; Laxminarayan, Ramanan] Ctr Dis Dynam Econ & Policy, Washington, DC USA.
[Klein, Eili Y.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Laxminarayan, Ramanan] Princeton Univ, Princeton Environm Inst, Princeton, NJ 08544 USA.
[Tozan, Yesim; Breman, Joel G.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Tozan, Y (reprint author), Boston Univ, Sch Publ Hlth, Dept Int Hlth, 801 Massachusetts Ave, Boston, MA 02118 USA.
EM tozan@bu.edu
RI Klein, Eili/C-3745-2012;
OI Klein, Eili/0000-0002-1304-5289
FU Disease Control Priorities Project; Fogarty International Center; US
National Institutes of Health; Boston University
FX Funding The Disease Control Priorities Project; Fogarty International
Center; US National Institutes of Health; and the Peter Paul Career
Development Professorship, Boston University.
NR 30
TC 13
Z9 14
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD DEC 4
PY 2010
VL 376
IS 9756
BP 1910
EP 1915
DI 10.1016/S0140-6736(10)61460-2
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 696KH
UT WOS:000285439800032
PM 21122910
ER
PT J
AU Watanabe, K
Salomon, DS
AF Watanabe, Kazuhide
Salomon, David S.
TI Intercellular transfer regulation of the paracrine activity of
GPI-anchored Cripto-1 as a Nodal co-receptor
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Cripto-1; GPI-anchored protein; Intercellular transfer; Nodal
ID GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHOR; TUMOR-CELLS; ENHANCEMENT; ROLES;
GENE
AB Cripto-1 (CR-1) is a glycosylphosphatidylinositol-anchored glycoprotein which acts as an obligate co-receptor of a TGF beta family ligand, Nodal. Previous studies have demonstrated that CR-1 functions in a paracrine fashion by a cellular mechanism which has not been fully described. This paracrine activity was observed only when CR-1 was expressed as a membrane-bound form and was abolished when CR-1 was expressed in a soluble form. In the current study, we found that there were few biochemical differences in post-translational modifications between membrane-anchored and soluble forms of CR-1. Flow cytometric analysis revealed an intercellular transfer of the membrane-bound form of CR-1 between cells. CR-1-expressing cells formed unique membrane extensions, generated more membrane fragments than control cells, and exhibited enhanced cellular adhesion. Thus, expression of CR-1 may alter the physiochemical properties of the plasma membrane resulting in an enhancement of intercellular transfer of cellular signaling components which may account for the paracrine activity of CR-1. Published by Elsevier Inc.
C1 [Watanabe, Kazuhide; Salomon, David S.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Watanabe, Kazuhide] Univ Calif Irvine, Dept Biol Chem, Sch Med, Irvine, CA 92697 USA.
RP Salomon, DS (reprint author), Bldg37,Rm1118B,37 Convent Dr, Bethesda, MD 20892 USA.
EM salomond@mail.nih.gov
FU Intramural NIH HHS [Z01 BC009003-25]
NR 19
TC 2
Z9 2
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD DEC 3
PY 2010
VL 403
IS 1
BP 108
EP 113
DI 10.1016/j.bbrc.2010.10.128
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 693LV
UT WOS:000285226500019
PM 21055389
ER
PT J
AU Matsuno, K
Nakayama, E
Noyori, O
Marzi, A
Ebihara, H
Irimura, T
Feldmann, H
Takada, A
AF Matsuno, Keita
Nakayama, Eri
Noyori, Osamu
Marzi, Andrea
Ebihara, Hideki
Irimura, Tatsuro
Feldmann, Heinz
Takada, Ayato
TI C-type lectins do not act as functional receptors for filovirus entry
into cells
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Filovirus; Virus entry; C-type lectin
ID EBOLA-VIRUS GLYCOPROTEIN; DC-SIGN; MARBURG VIRUS; ENDOTHELIAL-CELLS;
BINDING; INFECTION; RESIDUES; IDENTIFICATION; CORONAVIRUS; MACROPHAGES
AB Cellular C-type lectins have been reported to facilitate filovirus infection by binding to glycans on filovirus glycoprotein (GP). However, it is not clearly known whether interaction between C-type lectins and GP mediates all the steps of virus entry (i.e., attachment, internalization, and membrane fusion). In this study, we generated vesicular stomatitis viruses pseudotyped with mutant GPs that have impaired structures of the putative receptor binding regions and thus reduced ability to infect the monkey kidney cells that are routinely used for virus propagation. We found that infectivities of viruses with the mutant GPs dropped in C-type lectin-expressing cells, parallel with those in the monkey kidney cells, whereas binding activities of these GPs to the C-type lectins were not correlated with the reduced infectivities. These results suggest that C-type lectin-mediated entry of filoviruses requires other cellular molecule(s) that may be involved in virion internalization or membrane fusion. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Matsuno, Keita; Nakayama, Eri; Noyori, Osamu; Takada, Ayato] Hokkaido Univ, Res Ctr Zoonosis Control, Dept Global Epidemiol, Sapporo, Hokkaido, Japan.
[Marzi, Andrea; Ebihara, Hideki; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Irimura, Tatsuro] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan.
RP Takada, A (reprint author), Hokkaido Univ, Res Ctr Zoonosis Control, Dept Global Epidemiol, Sapporo, Hokkaido, Japan.
EM atakada@czc.hokudai.ac.jp
RI Takada, Ayato/A-6679-2012
FU Japan Society for the Promotion of Science; Takeda Science Foundation
[19041001]; Ministry of Education, Culture, Sports, Science and
Technology (MEXT), Japan [05021011, F-001]
FX We thank Hiroko Miyamoto, Ayaka Yokoyama, Teiji Murakami, and Aiko
Ohnuma for technical assistance and Kim Barrymore for editing the
manuscript. This work was supported by Research Fellowships for Young
Scientists from the Japan Society for the Promotion of Science, the
Takeda Science Foundation, a Grant-in-Aid for Scientific Research on
Priority Areas (19041001), and in part, by the Program of Founding
Research Centers for Emerging and Reemerging Infectious Diseases
(05021011) and Global COE Program "Establishment of International
Collaboration Centers for Zoonosis Control" (F-001) from the Ministry of
Education, Culture, Sports, Science and Technology (MEXT), Japan
(http://www.mext.go.jp/english/index.htm).
NR 29
TC 15
Z9 16
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD DEC 3
PY 2010
VL 403
IS 1
BP 144
EP 148
DI 10.1016/j.bbrc.2010.10.136
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 693LV
UT WOS:000285226500025
PM 21056544
ER
PT J
AU Lee, KP
Yuan, JP
So, I
Worley, PF
Muallem, S
AF Lee, Kyu Pil
Yuan, Joseph P.
So, Insuk
Worley, Paul F.
Muallem, Shmuel
TI STIM1-dependent and STIM1-independent Function of Transient Receptor
Potential Canonical (TRPC) Channels Tunes Their Store-operated Mode
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FAST CA2+-DEPENDENT INACTIVATION; STROMAL INTERACTION MOLECULE-1;
PLASMA-MEMBRANE; CRAC CHANNELS; CA2+ ENTRY; ORAI CHANNELS; STIM1;
DOMAIN; DEPLETION; OLIGOMERIZATION
AB Ca(2+)influx by store-operated Ca2+ channels is a key component of the receptor-evoked Ca2+ signal. In all cells examined, transient receptor potential canonical (TRPC) channels mediate a significant portion of the receptor-stimulated Ca2+ influx. Recent studies have revealed how STIM1 activates TRPC1 in response to store depletion; however, the role of STIM1 in TRPC channel activation by receptor stimulation is not fully understood. Here, we established mutants of TRPC channels that could not be activated by STIM1 but were activated by the "charge-swap" mutant STIM1(K684E,K685E). Significantly, WT but not mutant TRPC channels were inhibited by scavenging STIM1 with Orai1(R91W), indicating the STIM1 dependence and independence of WT and mutant TRPC channels, respectively. Importantly, mutant TRPC channels were robustly activated by receptor stimulation. Moreover, STIM1 and STIM1(K684E, K685E) reciprocally affected receptor-activated WT and mutant TRPC channels. Together, these findings indicate that TRPC channels can function as STIM1-dependent and STIM1-independent channels, which increases the versatility of TRPC channel function and their role in receptor-stimulated Ca2+ influx.
C1 [Lee, Kyu Pil; Yuan, Joseph P.; Muallem, Shmuel] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
[Lee, Kyu Pil; Muallem, Shmuel] NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[So, Insuk] Seoul Natl Univ, Coll Med, Dept Physiol & Biophys, Seoul 110799, South Korea.
[Worley, Paul F.] Johns Hopkins Univ, Sch Med, Dept Neurosci & Neurol, Baltimore, MD 21205 USA.
RP Muallem, S (reprint author), Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
EM shmuel.muallem@nih.gov
RI So, Insuk/J-2762-2012
FU National Institutes of Health [DE12302, DK38938]; NIDCR/DIR
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DE12302 and DK38938 and by NIDCR/DIR.
NR 26
TC 33
Z9 33
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD DEC 3
PY 2010
VL 285
IS 49
BP 38666
EP 38673
DI 10.1074/jbc.M110.155036
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 685JS
UT WOS:000284625600071
PM 20926378
ER
PT J
AU Sekine, O
Love, DC
Rubenstein, DS
Hanover, JA
AF Sekine, Osamu
Love, Dona C.
Rubenstein, David S.
Hanover, John A.
TI Blocking O-Linked GlcNAc Cycling in Drosophila Insulin-producing Cells
Perturbs Glucose-Insulin Homeostasis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID N-ACETYLGLUCOSAMINE; TETRATRICOPEPTIDE REPEATS; SIGNAL-TRANSDUCTION;
SKELETAL-MUSCLE; X-CHROMOSOME; BETA-CELLS; RESISTANCE; GLYCOSYLATION;
TRANSFERASE; PROTEIN
AB A dynamic cycle of O-linked GlcNAc (O-GlcNAc) addition and removal is catalyzed by O-GlcNAc transferase and O-GlcNAcase, respectively, in a process that serves as the final step in a nutrient-driven "hexosamine-signaling pathway." Evidence points to a role for O-GlcNAc cycling in diabetes and insulin resistance. We have used Drosophila melanogaster to determine whether O-GlcNAc metabolism plays a role in modulating Drosophila insulin-like peptide (dilp) production and insulin signaling. We employed transgenesis to either overexpress or knock down Drosophila Ogt(sxc) and Oga in insulin-producing cells (IPCs) or fat bodies using the GAL4-UAS system. Knockdown of Ogt decreased Dilp2, Dilp3, and Dilp5 production, with reduced body size and decreased phosphorylation of Akt in vivo. In contrast, knockdown of Oga increased Dilp2, Dilp3, and Dilp5 production, increased body size, and enhanced phosphorylation of Akt in vivo. However, knockdown of either Ogt(sxc) or Oga in the IPCs increased the hemolymph carbohydrate concentration. Furthermore, phosphorylation of Akt stimulated by extraneous insulin in an ex vivo cultured fat body of third instar larvae was diminished in strains subjected to IPC knockdown of Ogt or Oga. Knockdown of O-GlcNAc cycling enzymes in the fat body dramatically reduced neutral lipid stores. These results demonstrate that altered O-GlcNAc cycling in Drosophila IPCs modulates insulin production and influences the insulin responsiveness of peripheral tissues. The observed phenotypes in O-GlcNAc cycling mimic pancreatic beta-cell dysfunction and glucose toxicity related to sustained hyperglycemia in mammals.
C1 [Sekine, Osamu] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
[Rubenstein, David S.] Univ N Carolina, Dept Dermatol, Chapel Hill, NC 27599 USA.
RP Hanover, JA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
EM jah@helix.nih.gov
FU National Institutes of Health NIDDK; Cell Science Research Foundation in
Japan; Manpei Suzuki Diabetes Foundation in Japan
FX This work was supported, in whole or in part, by the National Institutes
of Health NIDDK Intramural Research Program. This work was also
supported by a scholarship from the Cell Science Research Foundation in
Japan and the Manpei Suzuki Diabetes Foundation in Japan.
NR 47
TC 25
Z9 25
U1 1
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD DEC 3
PY 2010
VL 285
IS 49
BP 38684
EP 38691
DI 10.1074/jbc.M110.155192
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 685JS
UT WOS:000284625600073
PM 20926386
ER
PT J
AU Pendse, PY
Brooks, BR
Klauda, JB
AF Pendse, Pushkar Y.
Brooks, Bernard R.
Klauda, Jeffery B.
TI Probing the Periplasmic-Open State of Lactose Permease in Response to
Sugar Binding and Proton Trans location
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE major facilitator superfamily; secondary active transporters; protein
folding; enhanced conformational sampling; membrane protein
ID MOLECULAR-DYNAMICS SIMULATIONS; GUIDED LANGEVIN DYNAMICS; SITE-DIRECTED
ALKYLATION; ESCHERICHIA-COLI; FORCE-FIELD; CONFORMATIONAL-CHANGES;
PROTEIN STRUCTURES; MEMBRANE-PROTEINS; SUBSTRATE-BINDING; LACY
AB Based on the crystal structure of lactose permease (LacY) open to the cytoplasm, a hybrid molecular simulation approach with self-guided Langevin dynamics is used to describe conformational changes that lead to a periplasmic-open state. This hybrid approach consists of implicit (IM) and explicit (EX) membrane simulations and requires self-guided Langevin dynamics to enhance protein motions during the IM simulations. The pore radius of the lumen increases by 3.5 A on the periplasmic side and decreases by 2.5 A on the cytoplasmic side (relative to the crystal structure), suggesting a lumen that is fully open to the periplasm to allow for extracellular sugar transport and closed to the cytoplasm. Based on our simulations, the mechanism that triggers this conformational change to the periplasmic-open state is the protonation of G1u269 and binding of the disaccharide. Then, helix packing is destabilized by breaking of several side chains involved in hydrogen bonding (Asn245, Ser41, G1u374, Lys42, and Gln242). For the periplasmic-open conformations obtained from our simulations, helix-helix distances agree well with experimental measurements using double electron-electron resonance, fluorescence resonance energy transfer, and varying sized cross-linkers. The periplasmic-open conformations are also in compliance with various substrate accessibility/reactivity measurements that indicate an opening of the protein lumen on the periplasmic side on sugar binding. The comparison with these measurements suggests a possible incomplete closure of the cytoplasmic half in our simulations. However, the closure is sufficient to prevent the disaccharide from transporting to the cytoplasm, which is in accordance with the well-established alternating access model. Ser53, G1n60, and Phe354 are determined to be important in sugar transport during the periplasmic-open stage of the sugar transport cycle and the sugar is found to undergo an orientational change in order to escape the protein lumen. (c) 2010 Elsevier Ltd. All rights reserved.
C1 [Pendse, Pushkar Y.; Klauda, Jeffery B.] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA.
[Brooks, Bernard R.; Klauda, Jeffery B.] NIH, Lab Computat Biol, Bethesda, MD 20892 USA.
RP Klauda, JB (reprint author), Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA.
EM jbklauda@umd.edu
FU University of Maryland; National Institutes of Health; National Heart,
Lung and Blood Institute
FX This research was supported in part by University of Maryland startup
funds (J.B.K and P.Y.P.) and the Intramural Research Program of the
National Institutes of Health, National Heart, Lung and Blood Institute
(B.R.B.). Simulations were run on the High-Performance Computational
Cluster at the University of Maryland. We also thank Ron Kaback and
Vladimir Kasho at the University of California, Los Angeles for
supplying us with the raw experimental DEER data to compare with our
simulations.
NR 67
TC 19
Z9 19
U1 0
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD DEC 3
PY 2010
VL 404
IS 3
BP 506
EP 521
DI 10.1016/j.jmb.2010.09.045
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 695LX
UT WOS:000285372700012
PM 20875429
ER
PT J
AU Arima, H
Baler, R
Aguilera, G
AF Arima, Hiroshi
Baler, Ruben
Aguilera, Greti
TI Fos proteins are not prerequisite for osmotic induction of vasopressin
transcription in supraoptic nucleus of rats
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Vasopressin; Fos
ID IMMEDIATE-EARLY GENES; C-FOS; PARAVENTRICULAR NUCLEI; DNA-BINDING;
HETERONUCLEAR RNA; JUN EXPRESSION; MESSENGER-RNA; CROSS-TALK; NEURONS;
PROMOTER
AB While it is well known that osmotic stimulation induces the expression of Fos family members in the supraoptic nucleus (SON), it is unclear whether the induced protein products are involved in the regulation of the gene transcription of arginine vasopressin (AVP). In the present study, we examined the in vivo correlation between changes in AVP gene transcription and expression of the various Fos family members in the SON after acute osmotic stimuli. The data demonstrated that the peak of AVP transcription (measured by intronic in situ hybridization) observed 15 min after an injection of hypertonic saline preceded the expression of Fos proteins, which became detectable at 30 min and peaked at 120 min. Electrophoretic mobility shift assay showed that the expressed Fos proteins bound to the composite AP-1/CRE-like site in the AVP promoter. These data suggest that Fos proteins in the SON induced by acute osmotic stimuli could affect AVP gene transcription by binding to the AVP promoter, but they are not prerequisite for the induction of AVP gene transcription. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Arima, Hiroshi; Aguilera, Greti] Natl Inst Child Hlth & Dis, Sect Endocrine Physiol, Dev Endocrinol Branch, Bethesda, MD 20892 USA.
[Baler, Ruben] NIMH, Unit Temporal Gene Express, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA.
RP Arima, H (reprint author), Nagoya Univ, Grad Sch Med, Dept Endocrinol & Diabet, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan.
EM arima105@med.nagoya-u.ac.jp
RI Arima, Hiroshi/I-7383-2014
OI Arima, Hiroshi/0000-0003-3746-1997
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH
FX This work was supported by the Intramural Research Program of Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH.
NR 36
TC 3
Z9 3
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD DEC 3
PY 2010
VL 486
IS 1
BP 5
EP 9
DI 10.1016/j.neulet.2010.09.030
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 681EC
UT WOS:000284293200002
PM 20850504
ER
PT J
AU Luo, Y
Wang, Y
Kuang, SY
Chiang, YH
Hoffer, B
AF Luo, Yu
Wang, Yun
Kuang, Serena Y.
Chiang, Yung-Hsiao
Hoffer, Barry
TI Decreased Level of Nurr1 in Heterozygous Young Adult Mice Leads to
Exacerbated Acute and Long-Term Toxicity after Repeated Methamphetamine
Exposure
SO PLOS ONE
LA English
DT Article
ID PARKINSONS-DISEASE; DOPAMINE SYNTHESIS; NEURONS; EXPRESSION; BRAIN;
GENE; CELLS; RATS
AB The abuse of psychostimulants, such as methamphetamine (METH), is prevalent in young adults and could lead to long-term adaptations in the midbrain dopamine system in abstinent human METH abusers. Nurr1 is a gene that is critical for the survival and maintenance of dopaminergic neurons and has been implicated in dopaminergic neuron related disorders. In this study, we examined the synergistic effects of repeated early exposure to methamphetamine in adolescence and reduction in Nurr1 gene levels. METH binge exposure in adolescence led to greater damage in the nigrostrial dopaminergic system when mice were exposed to METH binge later in life, suggesting a long-term adverse effect on the dopaminergic system. Compared to naive mice that received METH binge treatment for the first time, mice pretreated with METH in adolescence showed a greater loss of tyrosine hydroxylase (TH) immunoreactivity in striatum, loss of THir fibers in the substantia nigra reticulata (SNr) as well as decreased dopamine transporter (DAT) level and compromised DA clearance in striatum. These effects were further exacerbated in Nurr1 heterozygous mice. Our data suggest that a prolonged adverse effect exists following adolescent METH binge exposure which may lead to greater damage to the dopaminergic system when exposed to repeated METH later in life. Furthermore, our data support that Nurr1 mutations or deficiency could be a potential genetic predisposition which may lead to higher vulnerability in some individuals.
C1 [Luo, Yu; Wang, Yun; Kuang, Serena Y.; Hoffer, Barry] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
[Chiang, Yung-Hsiao] Taipei Med Univ Hosp, Dept Surg, Div Neurosurg, Taipei, Taiwan Authorit, Taiwan.
[Chiang, Yung-Hsiao] Taipei Med Univ, Dept Surg, Coll Med, Taipei, Taiwan Authorit, Taiwan.
RP Luo, Y (reprint author), NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
EM luoy@mail.nih.gov
FU National Institute on Drug Abuse, National Institutes of Health; Taiwan
Authority NSC [98-2314-B-038-011-MY3]
FX Funding for this study was provided by the Intramural Research Program,
National Institute on Drug Abuse, National Institutes of Health, and by
Taiwan Authority NSC grant 98-2314-B-038-011-MY3. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 25
TC 13
Z9 13
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 3
PY 2010
VL 5
IS 12
AR e15193
DI 10.1371/journal.pone.0015193
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 689PF
UT WOS:000284939600031
PM 21151937
ER
PT J
AU Collins, FS
Glass, RI
Whitescarver, J
Wakefield, M
Goosby, EP
AF Collins, Francis S.
Glass, Roger I.
Whitescarver, Jack
Wakefield, Mary
Goosby, Eric P.
TI Developing Health Workforce Capacity in Africa
SO SCIENCE
LA English
DT Editorial Material
C1 [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Whitescarver, Jack] NIH, Off AIDS Res, Bethesda, MD 20892 USA.
[Wakefield, Mary] US Hlth Resources & Serv Adm, Rockville, MD 20857 USA.
[Goosby, Eric P.] Off Global AIDS Coordinator, Washington, DC 20522 USA.
RP Glass, RI (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM glassr@mail.nih.gov
NR 8
TC 34
Z9 34
U1 0
U2 5
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD DEC 3
PY 2010
VL 330
IS 6009
BP 1324
EP 1325
DI 10.1126/science.1199930
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 689BK
UT WOS:000284902100023
PM 21127233
ER
PT J
AU Denoeud, F
Henriet, S
Mungpakdee, S
Aury, JM
Da Silva, C
Brinkmann, H
Mikhaleva, J
Olsen, LC
Jubin, C
Canestro, C
Bouquet, JM
Danks, G
Poulain, J
Campsteijn, C
Adamski, M
Cross, I
Yadetie, F
Muffato, M
Louis, A
Butcher, S
Tsagkogeorga, G
Konrad, A
Singh, S
Jensen, MF
Cong, EH
Eikeseth-Otteraa, H
Noel, B
Anthouard, V
Porcel, BM
Kachouri-Lafond, R
Nishino, A
Ugolini, M
Chourrout, P
Nishida, H
Aasland, R
Huzurbazar, S
Westhof, E
Delsuc, F
Lehrach, H
Reinhardt, R
Weissenbach, J
Roy, SW
Artiguenave, F
Postlethwait, JH
Manak, JR
Thompson, EM
Jaillon, O
Du Pasquier, L
Boudinot, P
Liberles, DA
Volff, JN
Philippe, H
Lenhard, B
Crollius, HR
Wincker, P
Chourrout, D
AF Denoeud, France
Henriet, Simon
Mungpakdee, Sutada
Aury, Jean-Marc
Da Silva, Corinne
Brinkmann, Henner
Mikhaleva, Jana
Olsen, Lisbeth Charlotte
Jubin, Claire
Canestro, Cristian
Bouquet, Jean-Marie
Danks, Gemma
Poulain, Julie
Campsteijn, Coen
Adamski, Marcin
Cross, Ismael
Yadetie, Fekadu
Muffato, Matthieu
Louis, Alexandra
Butcher, Stephen
Tsagkogeorga, Georgia
Konrad, Anke
Singh, Sarabdeep
Jensen, Marit Flo
Cong, Evelyne Huynh
Eikeseth-Otteraa, Helen
Noel, Benjamin
Anthouard, Veronique
Porcel, Betina M.
Kachouri-Lafond, Rym
Nishino, Atsuo
Ugolini, Matteo
Chourrout, Pascal
Nishida, Hiroki
Aasland, Rein
Huzurbazar, Snehalata
Westhof, Eric
Delsuc, Frederic
Lehrach, Hans
Reinhardt, Richard
Weissenbach, Jean
Roy, Scott W.
Artiguenave, Francois
Postlethwait, John H.
Manak, J. Robert
Thompson, Eric M.
Jaillon, Olivier
Du Pasquier, Louis
Boudinot, Pierre
Liberles, David A.
Volff, Jean-Nicolas
Philippe, Herve
Lenhard, Boris
Crollius, Hugues Roest
Wincker, Patrick
Chourrout, Daniel
TI Plasticity of Animal Genome Architecture Unmasked by Rapid Evolution of
a Pelagic Tunicate
SO SCIENCE
LA English
DT Article
ID OIKOPLEURA-DIOICA; CAENORHABDITIS-ELEGANS; COMPLEXITY; ORIGINS; INTRON;
GENES
AB Genomes of animals as different as sponges and humans show conservation of global architecture. Here we show that multiple genomic features including transposon diversity, developmental gene repertoire, physical gene order, and intron-exon organization are shattered in the tunicate Oikopleura, belonging to the sister group of vertebrates and retaining chordate morphology. Ancestral architecture of animal genomes can be deeply modified and may therefore be largely nonadaptive. This rapidly evolving animal lineage thus offers unique perspectives on the level of genome plasticity. It also illuminates issues as fundamental as the mechanisms of intron gain.
C1 [Denoeud, France; Aury, Jean-Marc; Da Silva, Corinne; Jubin, Claire; Poulain, Julie; Noel, Benjamin; Anthouard, Veronique; Porcel, Betina M.; Weissenbach, Jean; Artiguenave, Francois; Jaillon, Olivier; Wincker, Patrick] CEA, Inst Genom, Evry, France.
[Denoeud, France; Aury, Jean-Marc; Da Silva, Corinne; Jubin, Claire; Poulain, Julie; Noel, Benjamin; Anthouard, Veronique; Porcel, Betina M.; Weissenbach, Jean; Artiguenave, Francois; Jaillon, Olivier; Wincker, Patrick] CNRS, UMR 8030, Evry, France.
[Denoeud, France; Aury, Jean-Marc; Da Silva, Corinne; Jubin, Claire; Poulain, Julie; Noel, Benjamin; Anthouard, Veronique; Porcel, Betina M.; Weissenbach, Jean; Artiguenave, Francois; Jaillon, Olivier; Wincker, Patrick] Univ Evry, Evry, France.
[Henriet, Simon; Mungpakdee, Sutada; Mikhaleva, Jana; Olsen, Lisbeth Charlotte; Bouquet, Jean-Marie; Danks, Gemma; Campsteijn, Coen; Adamski, Marcin; Yadetie, Fekadu; Jensen, Marit Flo; Cong, Evelyne Huynh; Eikeseth-Otteraa, Helen; Ugolini, Matteo; Thompson, Eric M.; Lenhard, Boris; Chourrout, Daniel] Univ Bergen, Sars Int Ctr Marine Mol Biol, Bergen, Norway.
[Brinkmann, Henner; Philippe, Herve] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada.
[Canestro, Cristian; Postlethwait, John H.] Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA.
[Danks, Gemma; Lenhard, Boris] Univ Bergen, Bergen Ctr Computat Sci, Bergen, Norway.
[Cross, Ismael] Univ Cadiz, Genet Lab, Cadiz, Spain.
[Muffato, Matthieu; Louis, Alexandra; Crollius, Hugues Roest] Ecole Normale Super, CNRS, IBENS, Dyogen Lab,UMR8197, Paris, France.
[Butcher, Stephen; Manak, J. Robert] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA.
[Tsagkogeorga, Georgia; Delsuc, Frederic] Univ Montpellier 2, CNRS, Inst Sci Evolut, Lab Paleontol Phylogenie & Paleobiol,UMR 5554, Montpellier, France.
[Singh, Sarabdeep; Huzurbazar, Snehalata] Univ Wyoming, Dept Stat, Laramie, WY 82071 USA.
[Kachouri-Lafond, Rym; Westhof, Eric] Univ Strasbourg, CNRS, Inst Biol Cellulaire & Mol, Strasbourg, France.
[Nishino, Atsuo; Nishida, Hiroki] Osaka Univ, Dept Biol Sci, Osaka, Japan.
[Chourrout, Pascal] Ctr Hosp Albi, Albi, France.
[Aasland, Rein] Univ Bergen, Dept Mol Biol, Bergen, Norway.
[Lehrach, Hans; Reinhardt, Richard] Max Planck Inst Mol Genet, Berlin, Germany.
[Roy, Scott W.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Thompson, Eric M.; Lenhard, Boris] Univ Bergen, Dept Biol, Bergen, Norway.
[Du Pasquier, Louis] Univ Basel, Inst Zool & Evolutionary Biol, Basel, Switzerland.
[Boudinot, Pierre] INRA Virol & Immunol Mol, Jouy En Josas, France.
[Konrad, Anke; Liberles, David A.] Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA.
[Volff, Jean-Nicolas] Univ Lyon 1, Ecole Normale Super Lyon, Ecole Normale Super, Inst Genom Fonct Lyon,UMR 5242,CNRS,INRA, F-69365 Lyon, France.
[Canestro, Cristian] Univ Barcelona, Dept Genet, E-08007 Barcelona, Spain.
RP Wincker, P (reprint author), CEA, Inst Genom, Evry, France.
EM pwincker@genoscope.cns.fr; Daniel.Chourrout@sars.uib.no
RI Nishida, Hiroki/B-1851-2008; Nishino, Atsuo/F-5393-2013; Cross,
Ismael/K-1674-2014; Canestro, Cristian/L-9661-2014; Delsuc,
Frederic/B-4381-2009; boudinot, pierre/L-4246-2016; Singh,
Sarabdeep/D-7881-2017;
OI Lenhard, Boris/0000-0002-1114-1509; Muffato,
Matthieu/0000-0002-7860-3560; Nishida, Hiroki/0000-0002-7249-1668;
Cross, Ismael/0000-0002-2291-5629; Yadetie, Fekadu/0000-0002-2484-9047;
AURY, Jean-Marc/0000-0003-1718-3010; Canestro,
Cristian/0000-0003-4623-8105; Delsuc, Frederic/0000-0002-6501-6287;
ROEST CROLLIUS, Hugues/0000-0002-8209-173X
FU Sars Centre; Norwegian Research Council; Genoscope; NSF [IOS-0719577,
DBI-0743374]
FX The Sars Centre budget, the Functional Genomics (FUGE) Programme of the
Norwegian Research Council, Genoscope, and NSF grants IOS-0719577 and
DBI-0743374 supported the research. This is publication ISEM-2010-123 of
the Institut des Sciences de l'Evolution de Montpellier.
GENBANK/European Molecular Biology Laboratory sequence accession numbers
are CABV01000001-CABV01005917, CABW01000001-CABW01006678,
FN653015-FN654274, FN654275-FN658470, FP700189-FP710243,
FP710258-FP791398, and FP791400-FP884219. The sequence data for
Capitella teleta, Daphnia pulex, Helobdella robusta and Lottia gigantea
were produced by the U.S. Department of Energy Joint Genome Institute
(www.jgi.doe.gov/) in collaboration with the community of users. We
thank I. Ahel, B. Haubold, and one anonymous reviewer for generous
advice. This article is dedicated to Hans Prydz and Kare Rommetveit for
their pioneer roles in the Sars Centre establishment.
NR 25
TC 113
Z9 115
U1 2
U2 25
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD DEC 3
PY 2010
VL 330
IS 6009
BP 1381
EP 1385
DI 10.1126/science.1194167
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 689BK
UT WOS:000284902100043
PM 21097902
ER
PT J
AU Kreuzer, KN
Brister, JR
AF Kreuzer, Kenneth N.
Brister, J. Rodney
TI Initiation of bacteriophage T4 DNA replication and replication fork
dynamics: a review in the Virology Journal series on bacteriophage T4
and its relatives
SO VIROLOGY JOURNAL
LA English
DT Review
ID DOUBLE-STRAND BREAKS; ORIGIN-DEPENDENT REPLICATION; ESCHERICHIA-COLI
CHROMOSOME; ROLLING-CIRCLE REPLICATION; HELICASE-LOADING PROTEIN;
DEFECTIVE PHAGE SYSTEM; GENETIC-RECOMBINATION; MITOCHONDRIAL-DNA;
DEOXYRIBONUCLEIC ACID; ENDONUCLEASE-VII
AB Bacteriophage T4 initiates DNA replication from specialized structures that form in its genome. Immediately after infection, RNA-DNA hybrids (R-loops) occur on (at least some) replication origins, with the annealed RNA serving as a primer for leading-strand synthesis in one direction. As the infection progresses, replication initiation becomes dependent on recombination proteins in a process called recombination-dependent replication (RDR). RDR occurs when the replication machinery is assembled onto D-loop recombination intermediates, and in this case, the invading 3' DNA end is used as a primer for leading strand synthesis. Over the last 15 years, these two modes of T4 DNA replication initiation have been studied in vivo using a variety of approaches, including replication of plasmids with segments of the T4 genome, analysis of replication intermediates by two-dimensional gel electrophoresis, and genomic approaches that measure DNA copy number as the infection progresses. In addition, biochemical approaches have reconstituted replication from origin R-loop structures and have clarified some detailed roles of both replication and recombination proteins in the process of RDR and related pathways. We will also discuss the parallels between T4 DNA replication modes and similar events in cellular and eukaryotic organelle DNA replication, and close with some current questions of interest concerning the mechanisms of replication, recombination and repair in phage T4.
C1 [Kreuzer, Kenneth N.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
[Brister, J. Rodney] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Kreuzer, KN (reprint author), Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
EM kenneth.kreuzer@duke.edu
NR 135
TC 30
Z9 30
U1 0
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-422X
J9 VIROL J
JI Virol. J.
PD DEC 3
PY 2010
VL 7
AR 358
DI 10.1186/1743-422X-7-358
PG 16
WC Virology
SC Virology
GA 703LH
UT WOS:000285978900002
PM 21129203
ER
PT J
AU Burbelo, PD
Browne, SK
Sampaio, EP
Giaccone, G
Zaman, R
Kristosturyan, E
Rajan, A
Ding, L
Ching, KH
Berman, A
Oliveira, JB
Hsu, AP
Klimavicz, CM
Iadarola, MJ
Holland, SM
AF Burbelo, Peter D.
Browne, Sarah K.
Sampaio, Elizabeth P.
Giaccone, Giuseppe
Zaman, Rifat
Kristosturyan, Ervand
Rajan, Arun
Ding, Li
Ching, Kathryn H.
Berman, Arlene
Oliveira, Joao B.
Hsu, Amy P.
Klimavicz, Caitlin M.
Iadarola, Michael J.
Holland, Steven M.
TI Anti-cytokine autoantibodies are associated with opportunistic infection
in patients with thymic neoplasia
SO BLOOD
LA English
DT Article
ID RED-CELL APLASIA; LUCIFERASE IMMUNOPRECIPITATION SYSTEMS; CHRONIC
MUCOCUTANEOUS CANDIDIASIS; PULMONARY ALVEOLAR PROTEINOSIS; HYPER-IGE
SYNDROME; SYNDROME TYPE-I; IFN-GAMMA; T-CELLS; LUPUS-ERYTHEMATOSUS;
AUTOIMMUNE-DISEASE
AB Patients with thymic malignancy have high rates of autoimmunity leading to a variety of autoimmune diseases, most commonly myasthenia gravis caused by anti-acetylcholine receptor autoantibodies. High rates of autoantibodies to cytokines have also been described, although prevalence, spectrum, and functionality of these anti-cytokine autoantibodies are poorly defined. To better understand the presence and function of anti-cytokine autoantibodies, we created a luciferase immunoprecipitation system panel to search for autoantibodies against 39 different cytokines and examined plasma from controls (n = 30) and patients with thymic neoplasia (n = 17). In this screen, our patients showed statistically elevated, but highly heterogeneous immunoreactivity against 16 of the 39 cytokines. Some patients showed autoantibodies to multiple cytokines. Functional testing proved that autoantibodies directed against interferon-alpha, interferon-beta, interleukin-1 alpha (IL-1 alpha), IL-12p35, IL-12p40, and IL-17A had biologic blocking activity in vitro. All patients with opportunistic infection showed multiple anti-cytokine autoantibodies (range 3-11), suggesting that anti-cytokine autoantibodies may be important in the pathogenesis of opportunistic infections in patients with thymic malignancy. This study was registered at http://clinicaltrials.gov as NCT00001355. (Blood. 2010;116(23):4848-4858)
C1 [Burbelo, Peter D.; Ching, Kathryn H.; Hsu, Amy P.; Klimavicz, Caitlin M.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Lab Sensory Biol, NIH, Bethesda, MD USA.
[Browne, Sarah K.; Sampaio, Elizabeth P.; Zaman, Rifat; Kristosturyan, Ervand; Ding, Li; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Sampaio, Elizabeth P.] Fiocruz MS, Inst Oswaldo Cruz, Leprosy Lab, BR-21045900 Rio De Janeiro, Brazil.
[Giaccone, Giuseppe; Rajan, Arun; Berman, Arlene] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Oliveira, Joao B.] NIH, Immunol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Browne, SK (reprint author), CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA.
EM brownesa@niaid.nih.gov
RI Giaccone, Giuseppe/E-8297-2017;
OI Giaccone, Giuseppe/0000-0002-5023-7562; Oliveira,
Joao/0000-0001-9388-8173
FU Division of Intramural Research; National Institute of Allergy and
Infectious Diseases; National Cancer Institute; National Institute of
Dental and Craniofacial Research; National Institutes of Health
FX Financial support of this work was supported in part by the Division of
Intramural Research, the National Institute of Allergy and Infectious
Diseases, the National Cancer Institute, and the National Institute of
Dental and Craniofacial Research, all at the National Institutes of
Health.
NR 47
TC 49
Z9 53
U1 1
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD DEC 2
PY 2010
VL 116
IS 23
BP 4848
EP 4858
DI 10.1182/blood-2010-05-286161
PG 11
WC Hematology
SC Hematology
GA 688UU
UT WOS:000284880200022
PM 20716769
ER
PT J
AU Harvey, RC
Mullighan, CG
Wang, XF
Dobbin, KK
Davidson, GS
Bedrick, EJ
Chen, IM
Atlas, SR
Kang, HN
Ar, K
Wilson, CS
Wharton, W
Murphy, M
Devidas, M
Carroll, AJ
Borowitz, MJ
Bowman, WP
Downing, JR
Relling, M
Yang, J
Bhojwani, D
Carroll, WL
Camitta, B
Reaman, GH
Smith, M
Hunger, SP
Willman, CL
AF Harvey, Richard C.
Mullighan, Charles G.
Wang, Xuefei
Dobbin, Kevin K.
Davidson, George S.
Bedrick, Edward J.
Chen, I-Ming
Atlas, Susan R.
Kang, Huining
Ar, Kerem
Wilson, Carla S.
Wharton, Walker
Murphy, Maurice
Devidas, Meenakshi
Carroll, Andrew J.
Borowitz, Michael J.
Bowman, W. Paul
Downing, James R.
Relling, Mary
Yang, Jun
Bhojwani, Deepa
Carroll, William L.
Camitta, Bruce
Reaman, Gregory H.
Smith, Malcolm
Hunger, Stephen P.
Willman, Cheryl L.
TI Identification of novel cluster groups in pediatric high-risk
B-precursor acute lymphoblastic leukemia with gene expression profiling:
correlation with genome-wide DNA copy number alterations, clinical
characteristics, and outcome
SO BLOOD
LA English
DT Article
ID CHILDRENS ONCOLOGY GROUP; MINIMAL RESIDUAL DISEASE; SURVIVAL;
CLASSIFICATION; CRLF2; PROGENITOR; REARRANGEMENT; PREDICTION; ETHNICITY;
PATTERNS
AB To resolve the genetic heterogeneity within pediatric high-risk B-precursor acute lymphoblastic leukemia (ALL), a clinically defined poor-risk group with few known recurring cytogenetic abnormalities, we performed gene expression profiling in a cohort of 207 uniformly treated children with high-risk ALL. Expression profiles were correlated with genome-wide DNA copy number abnormalities and clinical and outcome features. Unsupervised clustering of gene expression profiling data revealed 8 unique cluster groups within these high-risk ALL patients, 2 of which were associated with known chromosomal translocations (t(1;19)(TCF3-PBX1) or MLL), and 6 of which lacked any previously known cytogenetic lesion. One unique cluster was characterized by high expression of distinct outlier genes AGAP1, CCNJ, CHST2/7, CLEC12A/B, and PTPRM; ERG DNA deletions; and 4-year relapse-free survival of 94.7% +/- 5.1%, compared with 63.5% +/- 3.7% for the cohort (P = .01). A second cluster, characterized by high expression of BMPR1B, CRLF2, GPR110, and MUC4; frequent deletion of EBF1, IKZF1, RAG1-2, and IL3RA-CSF2RA; JAK mutations and CRLF2 rearrangements (P < .0001); and Hispanic ethnicity (P < .001) had a very poor 4-year relapse-free survival (21.0% +/- 9.5%; P < .001). These studies reveal striking clinical and genetic heterogeneity in high-risk ALL and point to novel genes that may serve as new targets for diagnosis, risk classification, and therapy. (Blood. 2010;116(23):4874-4884)
C1 [Harvey, Richard C.; Wang, Xuefei; Bedrick, Edward J.; Chen, I-Ming; Atlas, Susan R.; Kang, Huining; Ar, Kerem; Wilson, Carla S.; Wharton, Walker; Murphy, Maurice; Willman, Cheryl L.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA.
[Harvey, Richard C.; Wang, Xuefei; Bedrick, Edward J.; Chen, I-Ming; Atlas, Susan R.; Kang, Huining; Ar, Kerem; Wilson, Carla S.; Wharton, Walker; Murphy, Maurice; Willman, Cheryl L.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA.
[Harvey, Richard C.; Wang, Xuefei; Bedrick, Edward J.; Chen, I-Ming; Atlas, Susan R.; Kang, Huining; Ar, Kerem; Wilson, Carla S.; Wharton, Walker; Murphy, Maurice; Willman, Cheryl L.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA.
[Harvey, Richard C.; Wang, Xuefei; Bedrick, Edward J.; Chen, I-Ming; Atlas, Susan R.; Kang, Huining; Ar, Kerem; Wilson, Carla S.; Wharton, Walker; Murphy, Maurice; Willman, Cheryl L.] Univ New Mexico, Dept Math & Stat, Albuquerque, NM 87131 USA.
[Harvey, Richard C.; Wang, Xuefei; Bedrick, Edward J.; Chen, I-Ming; Atlas, Susan R.; Kang, Huining; Ar, Kerem; Wilson, Carla S.; Wharton, Walker; Murphy, Maurice; Willman, Cheryl L.] Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA.
[Harvey, Richard C.; Chen, I-Ming; Devidas, Meenakshi; Borowitz, Michael J.; Bowman, W. Paul; Carroll, William L.; Camitta, Bruce; Reaman, Gregory H.; Hunger, Stephen P.; Willman, Cheryl L.] Childrens Oncol Grp, Arcadia, CA USA.
[Mullighan, Charles G.; Downing, James R.; Relling, Mary; Yang, Jun; Bhojwani, Deepa] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Mullighan, Charles G.; Downing, James R.; Relling, Mary; Yang, Jun; Bhojwani, Deepa] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
[Dobbin, Kevin K.] Univ Georgia, Coll Publ Hlth, Athens, GA 30602 USA.
[Davidson, George S.] Sandia Natl Labs, Albuquerque, NM 87185 USA.
[Devidas, Meenakshi; Carroll, Andrew J.] Univ Florida, Coll Med, Childrens Oncol Grp, Stat & Data Ctr, Gainesville, FL USA.
[Devidas, Meenakshi; Carroll, Andrew J.] Univ Florida, Coll Med, Dept Epidemiol & Hlth Policy Res, Gainesville, FL USA.
[Carroll, Andrew J.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA.
[Borowitz, Michael J.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Bowman, W. Paul] Cook Childrens Med Ctr, Ft Worth, TX USA.
[Carroll, William L.] NYU, Med Ctr, Dept Pediat, New York, NY 10016 USA.
[Carroll, William L.] NYU, Med Ctr, Dept Hematol & Oncol, New York, NY 10016 USA.
[Carroll, William L.] NYU, Med Ctr, Ctr Canc, New York, NY 10016 USA.
[Camitta, Bruce] Med Coll Wisconsin, Dept Pediat Hematol Oncol & Transplantat, Milwaukee, WI 53226 USA.
[Reaman, Gregory H.] Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA.
[Smith, Malcolm] NCI, Canc Therapy Evaluat Program, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Hunger, Stephen P.] Univ Colorado Denver, Sch Med, Univ Colorado Canc Ctr, Aurora, CO USA.
[Hunger, Stephen P.] Childrens Hosp, Dept Pediat, Aurora, CO USA.
RP Willman, CL (reprint author), Univ New Mexico, Ctr Canc, MSC08 4630 1, Albuquerque, NM 87131 USA.
EM cwillman@salud.unm.edu
RI Yang, Jun/B-6976-2008;
OI Yang, Jun/0000-0002-0770-9659; Harvey, Richard/0000-0002-4904-9767;
Bhojwani, Deepa/0000-0002-7559-7927; Mullighan,
Charles/0000-0002-1871-1850
FU National Institutes of Health Department of Health and Human Services,
National Cancer Institute [NCI U01 CA11476, NCI U10CA98543]; American
Lebanese Syrian Associated Charities; National Childhood Cancer
Foundation, COG [U24 CA114766]; Leukemia & Lymphoma Society Specialized
Center of Research [7388-06]; U.S. Department of Energy's National
Nuclear Security Administration [DE-AC04-94AL85000]; National Cancer
Institute [NCI P30 CA118100]
FX This work was supported by the National Institutes of Health Department
of Health and Human Services, National Cancer Institute Strategic
Partnerships to Evaluate Cancer Gene Signatures Program (grant NCI U01
CA11476, principal investigator C.L.W.; and grant NCI U10CA98543
Supporting the Children's Oncology Group and Statistical Center,
principal investigator G.H.R.), the American Lebanese Syrian Associated
Charities (J.Y.), the National Childhood Cancer Foundation, COG (cell
banking grant U24 CA114766) (G.H.R.), and a Leukemia & Lymphoma Society
Specialized Center of Research (program grant 7388-06) (principal
investigator C.L.W.). Sandia is a multiprogram laboratory operated by
Sandia Corporation, a Lockheed Martin Company, for the U.S. Department
of Energy's National Nuclear Security Administration (contract
DE-AC04-94AL85000). University of New Mexico Cancer Center Shared
Facilities (KUGR Genomics, Biostatistics, and Bioinformatics &
Computational Biology) are supported in part by the National Cancer
Institute (grant NCI P30 CA118100) and were critical for this work. S.
P. H. holds the Ergen Family Chair in Pediatric Cancer.
NR 36
TC 148
Z9 151
U1 1
U2 9
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 DEC 2
PY 2010
VL 116
IS 23
BP 4874
EP 4884
DI 10.1182/blood-2009-08-239681
PG 11
WC Hematology
SC Hematology
GA 688UU
UT WOS:000284880200025
PM 20699438
ER
PT J
AU Liu, WL
Lee, HW
Liu, YQ
Wang, RH
Rodgers, GP
AF Liu, Wenli
Lee, Hyun Woo
Liu, Yueqin
Wang, Ruihong
Rodgers, Griffin P.
TI Olfactomedin 4 is a novel target gene of retinoic acids and 5-aza-2
'-deoxycytidine involved in human myeloid leukemia cell growth,
differentiation, and apoptosis
SO BLOOD
LA English
DT Article
ID ACUTE PROMYELOCYTIC LEUKEMIA; TRANSCRIPTION FACTOR; POSSIBLE MECHANISMS;
PROTEIN; EXPRESSION; COLON; HGC-1; OVEREXPRESSION; TRANSLATION;
INITIATION
AB Clinical application of retinoic acids (RAs) and demethylation agents has proven to be effective in treating certain myeloid leukemia patients. However, the target genes that mediate these antileukemia activities are still poorly understood. In this study, we identified olfactomedin 4 (OLFM4), a myeloid-lineage-specific gene from the olfactomedin family, as a novel target gene for RAs and the demethylation agent, 5-aza-2'-deoxycytidine. We demonstrated that the retinoic acid receptor alpha/retinoic X receptor alpha heterodimer binds to a retinoic acid response-element (DR5) site in the OLFM4 promoter and mediates all-trans-retinoic acid (ATRA)induced transactivation of the OLFM4 gene. OLFM4 overexpression in HL-60 cells led to growth inhibition, differentiation, and apoptosis, and potentiated ATRA induction of these effects. Conversely, down-regulation of endogenous OLFM4 in acute myeloid leukemia-193 cells compromised ATRA-induced growth inhibition, differentiation, and apoptosis. Overexpression of OLFM4 in HL-60 cells inhibited constitutive and ATRA-induced phosphorylation of the eukaryote initiation factor 4E-binding protein 1 (4E-BP1), whereas down-regulation of OLFM4 protein in acute myeloid leukemia-193 cells increased 4E-BP1 phosphorylation, suggesting that OLFM4 is a potent upstream inhibitor of 4E-BP1 phosphorylation/deactivation. Thus, our study demonstrates that OLFM4 plays an important role in myeloid leukemia cellular functions and induction of OLFM4-mediated effects may contribute to the therapeutic value of ATRA. (Blood. 2010;116(23):4938-4947)
C1 [Liu, Wenli; Lee, Hyun Woo; Rodgers, Griffin P.] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Yueqin] NIDDKD, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Wang, Ruihong] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Rodgers, GP (reprint author), NHLBI, Mol & Clin Hematol Branch, NIH, Bldg 10,Rm 9N111,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gr5n@nih.gov
FU National Heart, Lung, and Blood Institute, National Institutes of Health
FX This work is supported by the intramural research fund of the National
Heart, Lung, and Blood Institute, National Institutes of Health.
NR 35
TC 22
Z9 23
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD DEC 2
PY 2010
VL 116
IS 23
BP 4938
EP 4947
DI 10.1182/blood-2009-10-246439
PG 10
WC Hematology
SC Hematology
GA 688UU
UT WOS:000284880200032
PM 20724538
ER
PT J
AU Gunay-Aygun, M
Zivony-Elboum, Y
Gumruk, F
Geiger, D
Cetin, M
Khayat, M
Kleta, R
Kfir, N
Anikster, Y
Chezar, J
Arcos-Burgos, M
Shalata, A
Stanescu, H
Manaster, J
Arat, M
Edwards, H
Freiberg, AS
Hart, PS
Riney, LC
Patzel, K
Tanpaiboon, P
Markello, T
Huizing, M
Maric, I
Horne, M
Kehrel, BE
Jurk, K
Hansen, NF
Cherukuri, PF
Jones, M
Cruz, P
Mullikin, JC
Nurden, A
White, JG
Gahl, WA
Falik-Zaccai, T
AF Gunay-Aygun, Meral
Zivony-Elboum, Yifat
Gumruk, Fatma
Geiger, Dan
Cetin, Mualla
Khayat, Morad
Kleta, Robert
Kfir, Nehama
Anikster, Yair
Chezar, Judith
Arcos-Burgos, Mauricio
Shalata, Adel
Stanescu, Horia
Manaster, Joseph
Arat, Mutlu
Edwards, Hailey
Freiberg, Andrew S.
Hart, P. Suzanne
Riney, Lauren C.
Patzel, Katherine
Tanpaiboon, Pranoot
Markello, Tom
Huizing, Marjan
Maric, Irina
Horne, McDonald
Kehrel, Beate E.
Jurk, Kerstin
Hansen, Nancy F.
Cherukuri, Praveen F.
Jones, Marypat
Cruz, Pedro
Mullikin, Jim C.
Nurden, Alan
White, James G.
Gahl, William A.
Falik-Zaccai, Tzippora
TI Gray platelet syndrome: natural history of a large patient cohort and
locus assignment to chromosome 3p
SO BLOOD
LA English
DT Article
ID STORAGE POOL DEFICIENCY; ALPHA-GRANULE DEFICIENCY; MULTIPOINT LINKAGE
ANALYSIS; GATA1 ARG216GLN MUTATION; DISORDERS; THROMBOCYTOPENIA; BLOOD;
PROTEINS; THROMBIN; FAMILIES
AB Gray platelet syndrome (GPS) is an inherited bleeding disorder characterized by macrothrombocytopenia and absence of platelet alpha-granules resulting in typical gray platelets on peripheral smears. GPS is associated with a bleeding tendency, myelofibrosis, and splenomegaly. Reports on GPS are limited to case presentations. The causative gene and underlying pathophysiology are largely unknown. We present the results of molecular genetic analysis of 116 individuals including 25 GPS patients from 14 independent families as well as novel clinical data on the natural history of the disease. The mode of inheritance was autosomal recessive (AR) in 11 and indeterminate in 3 families. Using genome-wide linkage analysis, we mapped the AR-GPS gene to a 9.4-Mb interval on 3p21.1-3p22.1, containing 197 protein-coding genes. Sequencing of 1423 (69%) of the 2075 exons in the interval did not identify the GPS gene. Long-term follow-up data demonstrated the progressive nature of the thrombocytopenia and myelofibrosis of GPS resulting in fatal hemorrhages in some patients. We identified high serum vitamin B(12) as a consistent, novel finding in GPS. Chromosome 3p21.1-3p22.1 has not been previously linked to a platelet disorder; identification of the GPS gene will likely lead to the discovery of novel components of platelet organelle biogenesis. This study is registered at www.clinicaltrials.gov as NCT00069680 and NCT00369421. (Blood. 2010;116(23):4990-5001)
C1 [Gunay-Aygun, Meral; Kleta, Robert; Anikster, Yair; Arcos-Burgos, Mauricio; Stanescu, Horia; Edwards, Hailey; Hart, P. Suzanne; Riney, Lauren C.; Patzel, Katherine; Tanpaiboon, Pranoot; Markello, Tom; Huizing, Marjan; Gahl, William A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Gunay-Aygun, Meral] NIH, Off Director, Off Rare Dis Res, Bethesda, MD 20892 USA.
[Zivony-Elboum, Yifat; Khayat, Morad; Kfir, Nehama; Shalata, Adel; Falik-Zaccai, Tzippora] Western Galilee Hosp, Inst Human Genet, Nahariyya, Israel.
[Gumruk, Fatma; Cetin, Mualla] Hacettepe Univ, Childrens Hosp, Pediat Hematol Unit, Ankara, Turkey.
[Geiger, Dan] Technion Israel Inst Technol, Dept Comp Sci, IL-32000 Haifa, Israel.
[Chezar, Judith; Manaster, Joseph] Western Galilee Hosp, Dept Hematol, Nahariyya, Israel.
[Arat, Mutlu] Ankara Univ, Dept Hematol, Fac Med, TR-06100 Ankara, Turkey.
[Freiberg, Andrew S.] Penn State Hershey Childrens Hosp, Div Pediat Hematol Oncol, Hershey, PA USA.
[Maric, Irina; Horne, McDonald] NIH Clin Ctr, Dept Lab Med, Bethesda, MD USA.
[Kehrel, Beate E.; Jurk, Kerstin] Univ Hosp Munster, Dept Anaesthesiol & Intens Care, Munster, Germany.
[Hansen, Nancy F.; Cherukuri, Praveen F.; Jones, Marypat; Cruz, Pedro; Mullikin, Jim C.] NIH, NIH Intramural Sequencing Ctr, Bethesda, MD 20892 USA.
[Cherukuri, Praveen F.] NIH, Genome Technol Branch, Bethesda, MD 20892 USA.
[Nurden, Alan] Hop Xavier Arnozan, Ctr Reference Pathol Plaquettaires Plateforme Tec, Pessac, France.
[White, James G.] Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA.
[Falik-Zaccai, Tzippora] Technion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, Haifa, Israel.
RP Gunay-Aygun, M (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, 10 Ctr Dr Bldg 10,Rm 10C103, Bethesda, MD 20892 USA.
EM mgaygun@mail.nih.gov
OI Arat, Mutlu/0000-0003-2039-8557
FU National Human Genome Research Institute; Khanh Nghiem; NIH Clinical
Center; Marcy Krumwiede
FX We thank all GPS patients and families for numerous interviews, physical
examinations, laboratory and imaging testing and for providing samples.
We thank Isa Bernardini, and Roxanne Fischer, funded by National Human
Genome Research Institute and Khanh Nghiem, funded by NIH Clinical
Center and Marcy Krumwiede for handling and processing specimens.; This
study was supported by the Intramural Research Programs of the National
Human Genome Research Institute, and the NIH Clinical Center, and by the
Israeli Ministry of Justice; Izvonot Fund, grants 84/2004, 85/2004, and
9090-25/2007 to T.F.-Z.
NR 51
TC 50
Z9 51
U1 2
U2 9
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 DEC 2
PY 2010
VL 116
IS 23
BP 4990
EP 5001
DI 10.1182/blood-2010-05-286534
PG 12
WC Hematology
SC Hematology
GA 688UU
UT WOS:000284880200037
PM 20709904
ER
PT J
AU Jima, DD
Zhang, J
Jacobs, C
Richards, KL
Dunphy, CH
Choi, WWL
Au, WY
Srivastava, G
Czader, MB
Rizzieri, DA
Lagoo, AS
Lugar, PL
Mann, KP
Flowers, CR
Bernal-Mizrachi, L
Naresh, KN
Evens, AM
Gordon, LI
Luftig, M
Friedman, DR
Weinberg, JB
Thompson, MA
Gill, JI
Liu, QA
How, T
Grubor, V
Gao, YA
Patel, A
Wu, H
Zhu, J
Blobe, GC
Lipsky, PE
Chadburn, A
Dave, SS
AF Jima, Dereje D.
Zhang, Jenny
Jacobs, Cassandra
Richards, Kristy L.
Dunphy, Cherie H.
Choi, William W. L.
Au, Wing Yan
Srivastava, Gopesh
Czader, Magdalena B.
Rizzieri, David A.
Lagoo, Anand S.
Lugar, Patricia L.
Mann, Karen P.
Flowers, Christopher R.
Bernal-Mizrachi, Leon
Naresh, Kikkeri N.
Evens, Andrew M.
Gordon, Leo I.
Luftig, Micah
Friedman, Daphne R.
Weinberg, J. Brice
Thompson, Michael A.
Gill, Javed I.
Liu, Qingquan
How, Tam
Grubor, Vladimir
Gao, Yuan
Patel, Amee
Wu, Han
Zhu, Jun
Blobe, Gerard C.
Lipsky, Peter E.
Chadburn, Amy
Dave, Sandeep S.
CA HMRC
TI Deep sequencing of the small RNA transcriptome of normal and malignant
human B cells identifies hundreds of novel microRNAs
SO BLOOD
LA English
DT Article
ID EXPRESSION PROFILES; ENRICHMENT ANALYSIS; GENE ONTOLOGY; LYMPHOMA;
DIFFERENTIATION; DROSOPHILA; LYMPHOCYTES; ANNOTATION; LEUKEMIA; MIRBASE
AB A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNAs, which is more than twice the number previously recognized in any tissue type. We further identified the expression of 286 candidate novel miRNAs in normal and malignant B cells. These miRNAs were validated at a high rate (92%) using quantitative polymerase chain reaction, and we demonstrated their application in the distinction of clinically relevant subgroups of lymphoma. We further demonstrated that a novel miRNA cluster, previously annotated as a hypothetical gene LOC100130622, contains 6 novel miRNAs that regulate the transforming growth factor-beta pathway. Thus, our work suggests that more than a third of the miRNAs present in most cellular types are currently unknown and that these miRNAs may regulate important cellular functions. (Blood. 2010;116(23):e118-e127)
C1 [Jima, Dereje D.; Zhang, Jenny; Jacobs, Cassandra; Liu, Qingquan; Grubor, Vladimir; Patel, Amee; Wu, Han; Zhu, Jun; Dave, Sandeep S.] Duke Univ, Duke Inst Genome Sci & Policy, Durham, NC 27710 USA.
[Richards, Kristy L.; Dunphy, Cherie H.] Univ N Carolina, Chapel Hill, NC USA.
[Choi, William W. L.; Au, Wing Yan; Srivastava, Gopesh] Univ Hong Kong, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China.
[Czader, Magdalena B.] Indiana Univ, Indianapolis, IN 46204 USA.
[Rizzieri, David A.; Lagoo, Anand S.; Lugar, Patricia L.; Luftig, Micah; Friedman, Daphne R.; Weinberg, J. Brice; How, Tam; Blobe, Gerard C.; Dave, Sandeep S.] Duke Univ, Med Ctr, Durham, NC 27710 USA.
[Mann, Karen P.; Flowers, Christopher R.; Bernal-Mizrachi, Leon] Emory Univ, Atlanta, GA 30322 USA.
[Naresh, Kikkeri N.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Evens, Andrew M.; Gordon, Leo I.; Chadburn, Amy] Northwestern Univ, Chicago, IL 60611 USA.
[Weinberg, J. Brice] Vet Adm Med Ctr, Durham, NC USA.
[Thompson, Michael A.] ProHlth Care Reg Canc Ctr, Waukesha, WI USA.
[Gill, Javed I.] Baylor Univ, Med Ctr, Dallas, TX USA.
[Gao, Yuan] Virginia Commonwealth Univ, Ctr Study Biol Complex, Richmond, VA USA.
[Lipsky, Peter E.] NIAMSD, Autoimmun Branch, Bethesda, MD 20892 USA.
RP Dave, SS (reprint author), Duke Univ, Duke Inst Genome Sci & Policy, 101 Sci Dr,Box 3382, Durham, NC 27710 USA.
EM sandeep.dave@duke.edu
RI Gao, Yuan/E-1706-2011; Wu, Han/E-3455-2013; Flowers,
Christopher/F-1953-2010;
OI Wu, Han/0000-0002-3972-698X; Flowers, Christopher/0000-0002-9524-3990;
Gordon, Leo/0000-0003-1666-7064
FU Doris Duke Charitable Foundation; National Institutes of Health
FX S.S.D. was supported by the Doris Duke Charitable Foundation and the
National Institutes of Health.
NR 42
TC 101
Z9 273
U1 1
U2 8
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 DEC 2
PY 2010
VL 116
IS 23
BP E118
EP E127
DI 10.1182/blood-2010-05-285403
PG 10
WC Hematology
SC Hematology
GA 688UU
UT WOS:000284880200001
PM 20733160
ER
PT J
AU Freedman, DM
Kimlin, MG
Hoffbeck, RW
Alexander, BH
Linet, MS
AF Freedman, D. Michal
Kimlin, Michael G.
Hoffbeck, Richard W.
Alexander, Bruce H.
Linet, Martha S.
TI Multiple indicators of ambient and personal ultraviolet radiation
exposure and risk of non-Hodgkin lymphoma (United States)
SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
LA English
DT Article
DE Non Hodgkin lymphoma; Ultraviolet radiation; Epidemiology; Vitamin D
ID SUN EXPOSURE; VITAMIN-D; PIGMENTARY CHARACTERISTICS; MALIGNANT-LYMPHOMA;
SUNLIGHT; CANCER; WOMEN
AB Recent epidemiologic studies have suggested that ultraviolet radiation (UV) may protect against non-Hodgkin lymphoma (NHL) but few if any have assessed multiple indicators of ambient and personal UV exposure Using the US Radiologic Technologists study we examined the association between NHL and self-reported time outdoors in summer as well as average year-round and seasonal ambient exposures based on satellite estimates for different age periods and sun susceptibility in participants who had responded to two questionnaires (1994-1998 2003-2005) and who were cancer-free as of the earlier questionnaire Using unconditional logistic regression we estimated the odds ratio (OR) and 95% confidence Intervals for 64 103 participants with 137 NHL cases self-reported time outdoors in summer was unrelated to risk Lower risk was somewhat related to higher average year-round and winter ambient exposure for the period closest in time and prior to diagnosis (ages 20-39) Relative to 1 0 for the lowest quartile of average year-round ambient UV the estimated OR for successively higher quartiles was 068 (0 42-1 10) 082 (0 52-1 29) and 0 64 (0 40-1 03) is-trend = 0 06) for this age period The lower NHL risk associated with higher year-round average and winter ambient UV provides modest additional support for a protective relationship between UV and NHL Published by Elsevier B V
C1 [Freedman, D. Michal; Linet, Martha S.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Kimlin, Michael G.] Queensland Univ Technol, AusSun Res Lab, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia.
[Hoffbeck, Richard W.; Alexander, Bruce H.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA.
RP Freedman, DM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
OI Kimlin, Michael/0000-0002-9536-8646
FU National Institutes of Health National Cancer Institute; US Public
Health Service of the Department of Health and Human Services; Cancer
Council Queensland
FX This research was supported by the Intramural Research Program of the
National Institutes of Health National Cancer Institute and the US
Public Health Service of the Department of Health and Human Services We
thank Li Cheung of Information Management Services Inc for biomedical
computer assistance Dr Michael Kimlin is supported through a Cancer
Council Queensland Senior Research Fellowship
NR 23
TC 13
Z9 13
U1 0
U2 4
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 1011-1344
J9 J PHOTOCH PHOTOBIO B
JI J. Photochem. Photobiol. B-Biol.
PD DEC 2
PY 2010
VL 101
IS 3
BP 321
EP 325
DI 10.1016/j.jphotobiol.2010.08.001
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 687YP
UT WOS:000284814700018
PM 20826094
ER
PT J
AU Larkin, JD
Fossey, JS
James, TD
Brooks, BR
Bock, CW
AF Larkin, Joseph D.
Fossey, John S.
James, Tony D.
Brooks, Bernard R.
Bock, Charles W.
TI A Computational Investigation of the Nitrogen-Boron Interaction in
o-(N,N-Dialkylaminomethyl)arylboronate Systems
SO JOURNAL OF PHYSICAL CHEMISTRY A
LA English
DT Article
ID POLARIZABLE CONTINUUM MODEL; GENERALIZED GRADIENT APPROXIMATION;
CORRELATED MOLECULAR CALCULATIONS; FLUORESCENT SACCHARIDE SENSORS;
DENSITY-FUNCTIONAL THEORY; METHYL TRANSFER-REACTIONS; GAUSSIAN-BASIS
SETS; B-N BOND; WAVE-FUNCTIONS; ANISOTROPIC DIELECTRICS
AB o-(N N-Dialkylaminomethyl)arylboronate systems are an important class of compounds in diol-sensor development We report results from a computational investigation of fourteen o-(N N-dialkylaminomethyl)-arylboronates using second-order Moller-Plesset (MP2) perturbation theory Geometry optimizations were performed at the MP2/cc-pVDZ level and followed by single-point calculations at the MP2/aug cc-pVD7(cc pVTZ) levels These results are compared to those from density functional theory (DFT) at the PBE1PBE(PBE1PBE-D)/6-311++G(d p)(aug-cc-pVDZ) levels as well as to experiment Results from continuum PCM and CPCM solvation models were employed to assess the effects of a bulk aqueous environment Although the behavior of o-(N N-dialkylaminomethyl) free acid and ester proved to be complicated we were able to extract some important trends from our calculations (1) for the free acids the intramolecular hydrogen-bonded B-O-H N seven-membered ring conformers 12 and 16 are found to be slightly lower in energy than the dative-bonded N -> B five-membered ring conformers 10 and 14 while conformers 13 and 17 with no direct boron nitrogen interaction are significantly higher in energy than 12 and 16 (2) for the esters where no intramolecular B-O-H N bonded form is possible the N -> B conformers 18 and 21 are significantly lower in energy than the no-interaction forms 20 and 23 (3) H2O insertion reactions into the N -> B structures 10 14 18, and 21 leading to the seven-membered intermolecular hydrogen-bonded B OH2 N ring structures 11 15 19 and 22 are all energetically favorable
C1 [Larkin, Joseph D.; Brooks, Bernard R.] NHLBI, NIH, Bethesda, MD 20851 USA.
[Fossey, John S.] Univ Birmingham, Sch Chem, Birmingham B15 2TT, W Midlands, England.
[James, Tony D.] Univ Bath, Dept Chem, Bath BA2 7AY, Avon, England.
[Bock, Charles W.] Philadelphia Univ, Dept Chem & Biochem, Sch Sci & Hlth, Philadelphia, PA 19144 USA.
[Bock, Charles W.] Fox Chase Canc Ctr, Inst Canc Res, Philadelphia, PA 19111 USA.
RP Larkin, JD (reprint author), NHLBI, NIH, Bldg 50, Bethesda, MD 20851 USA.
RI James, Tony/B-5125-2009; Fossey, John/C-3172-2009
OI James, Tony/0000-0002-4095-2191; Fossey, John/0000-0002-2626-5117
FU NIH NHLBI; University of Bath; University of Birmingham; ERDF AWMII
FX This research was supported in part (J D L and B R B) by the Intramural
Research Program of the NIH NHLBI The PQS Cluster Facility at
Philadelphia University (C W B) was extensively used for the
calculations described in this manuscript This study also utilized the
high performance computational capabilities of the Biowulf Linux cluster
at the National Institutes of Health Bethesda MD (http // biowulf nih
gov) T D J thanks the University of Bath for support and J S F thanks
the University of Birmingham and ERDF AWMII for support J D L also
thanks Dr Yihan Shao of QChem for his helpful discussions with respect
to the Incorporation of PBE1PBE-D functional
NR 74
TC 35
Z9 35
U1 6
U2 31
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1089-5639
J9 J PHYS CHEM A
JI J. Phys. Chem. A
PD DEC 2
PY 2010
VL 114
IS 47
BP 12531
EP 12539
DI 10.1021/jp1087674
PG 9
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 683EP
UT WOS:000284454800021
PM 21050022
ER
PT J
AU Horkay, F
Falus, P
Hecht, AM
Geissler, E
AF Horkay, Ferenc
Falus, Peter
Hecht, Anne-Marie
Geissler, Erik
TI Length Scale Dependence of the Dynamic Properties of Hyaluronic Acid
Solutions in the Presence of Salt
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID LIGHT-SCATTERING; FLEXIBLE POLYELECTROLYTES; DIFFUSION
AB In solutions of the charged semirigid biopolymer hyaluronic acid in salt-free conditions, the diffusion coefficient D-NSE measured at high transfer momentum q by neutron spin echo is more than an order of magnitude smaller than that determined by dynamic light scattering, D-DLS. This behavior contrasts with neutral polymer solutions. With increasing salt content, D-DLS approaches D-NSE, which is independent of ionic strength. Contrary to theoretical expectation, the ion-polymer coupling, which dominates the low q dynamics of polyelectrolyte solutions, already breaks down at distance scales greater than the Debye-Huckel length.
C1 [Hecht, Anne-Marie; Geissler, Erik] Univ Grenoble 1, CNRS, Spectrometrie Phys Lab, UMR 5588, F-38402 St Martin Dheres, France.
[Horkay, Ferenc] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA.
[Falus, Peter] Inst Max Von Laue Paul Langevin, F-38042 Grenoble 9, France.
RP Geissler, E (reprint author), Univ Grenoble 1, CNRS, Spectrometrie Phys Lab, UMR 5588, BP 87, F-38402 St Martin Dheres, France.
EM horkay@helix.nih.gov; erik.geissler@ujf-grenoble.fr
FU NICHD, NIH
FX We are grateful to the ILL, Grenoble, for access to the INI5, and to
APS, Argonne, USA, for SAXS measurements. This research was supported by
the Intramural Research Program of the NICHD, NIH.
NR 19
TC 4
Z9 4
U1 1
U2 18
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD DEC 2
PY 2010
VL 114
IS 47
BP 15445
EP 15450
DI 10.1021/jp106578f
PG 6
WC Chemistry, Physical
SC Chemistry
GA 683EM
UT WOS:000284454500003
PM 21049966
ER
PT J
AU de Gonzalez, AB
Hartge, P
Cerhan, JR
Flint, AJ
Hannan, L
MacInnis, RJ
Moore, SC
Tobias, GS
Anton-Culver, H
Freeman, LB
Beeson, WL
Clipp, SL
English, DR
Folsom, AR
Freedman, DM
Giles, G
Hakansson, N
Henderson, KD
Hoffman-Bolton, J
Hoppin, JA
Koenig, KL
Lee, IM
Linet, MS
Park, Y
Pocobelli, G
Schatzkin, A
Sesso, HD
Weiderpass, E
Willcox, BJ
Wolk, A
Zeleniuch-Jacquotte, A
Willett, WC
Thun, MJ
AF de Gonzalez, Amy Berrington
Hartge, Patricia
Cerhan, James R.
Flint, Alan J.
Hannan, Lindsay
MacInnis, Robert J.
Moore, Steven C.
Tobias, Geoffrey S.
Anton-Culver, Hoda
Freeman, Laura Beane
Beeson, W. Lawrence
Clipp, Sandra L.
English, Dallas R.
Folsom, Aaron R.
Freedman, D. Michal
Giles, Graham
Hakansson, Niclas
Henderson, Katherine D.
Hoffman-Bolton, Judith
Hoppin, Jane A.
Koenig, Karen L.
Lee, I-Min
Linet, Martha S.
Park, Yikyung
Pocobelli, Gaia
Schatzkin, Arthur
Sesso, Howard D.
Weiderpass, Elisabete
Willcox, Bradley J.
Wolk, Alicja
Zeleniuch-Jacquotte, Anne
Willett, Walter C.
Thun, Michael J.
TI Body-Mass Index and Mortality among 1.46 Million White Adults.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; CANCER SCREENING TRIAL; LOW-DOSE ASPIRIN;
CARDIOVASCULAR-DISEASE; BREAST-CANCER; PRIMARY PREVENTION;
UNITED-STATES; PREDICTING MORTALITY; PHYSICAL-ACTIVITY; WOMENS HEALTH
AB Background: A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain.
Methods: We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58).
Results: The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up.
Conclusions: In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.
N Engl J Med 2010;363:2211-9.
C1 [de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Cerhan, James R.] Mayo Clin, Coll Med, Div Epidemiol, Rochester, MN USA.
[Flint, Alan J.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Sesso, Howard D.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Sesso, Howard D.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Lee, I-Min] Harvard Univ, Sch Med, Boston, MA USA.
[Hannan, Lindsay; Thun, Michael J.] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA.
[MacInnis, Robert J.; English, Dallas R.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Giles, Graham] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[MacInnis, Robert J.] Univ Cambridge, Canc Res UK Genet Epidemiol Unit, Cambridge, England.
[Anton-Culver, Hoda] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA.
[Beeson, W. Lawrence] Loma Linda Univ, Sch Publ Hlth, Loma Linda, CA 92350 USA.
[Henderson, Katherine D.] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA 91010 USA.
[Clipp, Sandra L.; Hoffman-Bolton, Judith] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Hakansson, Niclas; Wolk, Alicja] Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
[Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Hoppin, Jane A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
[Koenig, Karen L.; Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Environm Med, New York, NY USA.
[Pocobelli, Gaia] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Pocobelli, Gaia] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA.
[Weiderpass, Elisabete] Canc Registry Norway, Oslo, Norway.
[Weiderpass, Elisabete] Dept Community Med, Tromso, Norway.
[Weiderpass, Elisabete] Samfundet Folkhalsan, Helsinki, Finland.
[Willcox, Bradley J.] Pacific Hlth Res Inst, Honolulu, HI USA.
[Willcox, Bradley J.] Queens Med Ctr, Honolulu, HI USA.
RP de Gonzalez, AB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Rm 7034,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM berringtona@mail.nih.gov
RI Hakansson, Niclas/L-7913-2013; Tobias, Geoffrey/M-4135-2016; Weiderpass,
Elisabete/M-4029-2016; Beane Freeman, Laura/C-4468-2015; Moore,
Steven/D-8760-2016;
OI Hakansson, Niclas/0000-0001-7673-5554; Tobias,
Geoffrey/0000-0002-2878-8253; Weiderpass, Elisabete/0000-0003-2237-0128;
Beane Freeman, Laura/0000-0003-1294-4124; Moore,
Steven/0000-0002-8169-1661; Giles, Graham/0000-0003-4946-9099; English,
Dallas/0000-0001-7828-8188; Park, Yikyung/0000-0002-6281-489X
FU National Institutes of Health (NIH); Division of Cancer Control and
Population Sciences, National Cancer Institute (NCI), NIH; Iovate Health
Sciences USA
FX Supported by the Intramural Research Program of the National Institutes
of Health (NIH) and the Division of Cancer Control and Population
Sciences, National Cancer Institute (NCI), NIH. Details regarding
funding for the individual studies are listed in the Supplementary
Appendix.; Dr. Sesso reports receiving consulting fees from Iovate
Health Sciences USA. No other potential conflict of interest relevant to
this article was reported.
NR 45
TC 418
Z9 429
U1 5
U2 60
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD DEC 2
PY 2010
VL 363
IS 23
BP 2211
EP 2219
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 688EP
UT WOS:000284832900008
ER
PT J
AU Musunuru, K
Pirruccello, JP
Do, R
Peloso, GM
Guiducci, C
Sougnez, C
Garimella, KV
Fisher, S
Abreu, J
Barry, AJ
Fennell, T
Banks, E
Ambrogio, L
Cibulskis, K
Kernytsky, A
Gonzalez, E
Rudzicz, N
Engert, JC
DePristo, MA
Daly, MJ
Cohen, JC
Hobbs, HH
Altshuler, D
Schonfeld, G
Gabriel, SB
Yue, P
Kathiresan, S
AF Musunuru, Kiran
Pirruccello, James P.
Do, Ron
Peloso, Gina M.
Guiducci, Candace
Sougnez, Carrie
Garimella, Kiran V.
Fisher, Sheila
Abreu, Justin
Barry, Andrew J.
Fennell, Tim
Banks, Eric
Ambrogio, Lauren
Cibulskis, Kristian
Kernytsky, Andrew
Gonzalez, Elena
Rudzicz, Nicholas
Engert, James C.
DePristo, Mark A.
Daly, Mark J.
Cohen, Jonathan C.
Hobbs, Helen H.
Altshuler, David
Schonfeld, Gustav
Gabriel, Stacey B.
Yue, Pin
Kathiresan, Sekar
TI Exome Sequencing, ANGPTL3 Mutations, and Familial Combined Hypolipidemia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID LOW-DENSITY-LIPOPROTEIN; APO-B GENE; APOLIPOPROTEIN-B; FATTY LIVER;
CAUCASIAN FAMILIES; HYPOBETALIPOPROTEINEMIA; METABOLISM; LIPASE;
INHIBITION; CAPTURE
AB We sequenced all protein-coding regions of the genome (the "exome") in two family members with combined hypolipidemia, marked by extremely low plasma levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. These two participants were compound heterozygotes for two distinct nonsense mutations in ANGPTL3 (encoding the angiopoietin-like 3 protein). ANGPTL3 has been reported to inhibit lipoprotein lipase and endothelial lipase, thereby increasing plasma triglyceride and HDL cholesterol levels in rodents. Our finding of ANGPTL3 mutations highlights a role for the gene in LDL cholesterol metabolism in humans and shows the usefulness of exome sequencing for identification of novel genetic causes of inherited disorders.
C1 [Musunuru, Kiran; Pirruccello, James P.; Do, Ron; Daly, Mark J.; Altshuler, David; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Musunuru, Kiran; Pirruccello, James P.; Do, Ron; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Musunuru, Kiran; Daly, Mark J.; Altshuler, David; Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
[Peloso, Gina M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Musunuru, Kiran; Pirruccello, James P.; Do, Ron; Guiducci, Candace; Sougnez, Carrie; Garimella, Kiran V.; Fisher, Sheila; Abreu, Justin; Barry, Andrew J.; Fennell, Tim; Banks, Eric; Ambrogio, Lauren; Cibulskis, Kristian; Kernytsky, Andrew; Gonzalez, Elena; DePristo, Mark A.; Daly, Mark J.; Altshuler, David; Gabriel, Stacey B.; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Musunuru, Kiran; Pirruccello, James P.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Do, Ron; Rudzicz, Nicholas; Engert, James C.] McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
[Peloso, Gina M.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Cohen, Jonathan C.; Hobbs, Helen H.] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA.
[Cohen, Jonathan C.; Hobbs, Helen H.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Schonfeld, Gustav; Yue, Pin] Washington Univ, Sch Med, St Louis, MO USA.
RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-252, Boston, MA 02114 USA.
EM skathiresan@partners.org
RI Altshuler, David/A-4476-2009
OI Altshuler, David/0000-0002-7250-4107
FU National Human Genome Research Institute of the National Institutes of
Health (NIH) [U54 HG003067]; National Heart, Lung, and Blood Institute
(NHLBI) of the NIH [RC1 HL099793, RC1 HL099634, RC2 HL101864, K99
HL098364, R01 HL082896]; Donovan Family Foundation; Sarnoff
Cardiovascular Research Foundation; Canadian Institutes of Health
Research; National Human Genome Research Institute
FX Supported by grants from the National Human Genome Research Institute of
the National Institutes of Health (NIH) (Medical Sequencing Program
grant U54 HG003067, to the Broad Institute for exome sequencing), the
National Heart, Lung, and Blood Institute (NHLBI) of the NIH (RC1
HL099793, RC1 HL099634, and RC2 HL101864, to Dr. Kathiresan; K99
HL098364, to Dr. Musunuru; and R01 HL082896, to Drs. Cohen and Hobbs for
analysis of ANGPTL3 in the Dallas Heart Study), the Donovan Family
Foundation (to Dr. Kathiresan), the Sarnoff Cardiovascular Research
Foundation (a research fellowship, to Mr. Pirruccello), and the Canadian
Institutes of Health Research (a Canada Graduate Doctoral Scholarship,
to Mr. Do).; Funded by the National Human Genome Research Institute and
others
NR 22
TC 215
Z9 234
U1 0
U2 10
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD DEC 2
PY 2010
VL 363
IS 23
BP 2220
EP 2227
DI 10.1056/NEJMoa1002926
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 688EP
UT WOS:000284832900009
PM 20942659
ER
PT J
AU Thanos, PK
Kim, R
Cho, J
Michaelides, M
Anderson, BJ
Primeaux, SD
Bray, GA
Wang, GJ
Robinson, JK
Volkow, ND
AF Thanos, Panayotis K.
Kim, Ronald
Cho, Jacob
Michaelides, Michael
Anderson, Brenda J.
Primeaux, Stefany D.
Bray, George A.
Wang, Gene-Jack
Robinson, John K.
Volkow, Nora D.
TI Obesity-resistant S5B rats showed greater cocaine conditioned place
preference than the obesity-prone OM rats
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE Addiction; Psychostimulant; Bromocriptine; Conditioned place preference
ID HIGH-FAT DIET; D2 DOPAMINE ANTAGONISTS; DRUG-ADDICTION; BROMOCRIPTINE
TREATMENT; ALCOHOL-DRINKING; FOOD RESTRICTION; ZUCKER RATS; RECEPTOR;
TRANSPORTER; REWARD
AB Background Dopamine (DA) and the DA D2 receptor (D2R) are involved in the rewarding and conditioned responses to food and drug rewards Osborne-Mendel (OM) rats are genetically prone and S5B/P rats are genetically resistant to obesity when fed a high-fat diet We hypothesized that the differential sensitivity of these two rat strains to natural rewards may also be reflected in sensitivity to drugs of abuse Therefore we tested whether OM and S5B/P rats showed a differential preference to cocaine using conditioned place preference (CPP) To also evaluate whether there is specific involvement of the D2R in this differential conditioning sensitivity we then tested whether the D2R agonist bromocriptine (BC) would differentially affect the effects of cocaine in the two strains
Methods OM and S5B/P rats were conditioned with cocaine (5 or 10 mg/kg) in one chamber and saline in another for 8 days Rats were then tested for cocaine preference The effects of BC (0 5 1 5 10 20 mg/kg) on cocaine preference were then assessed in subsequent test sessions
Results OM rats did not show a significant preference for the cocaine paired chamber on test day Only the S5B/P rats showed cocaine CPP Later treatment with only the highest dose of BC resulted in reduced cocaine CPP in S5B/P rats when treated with 5 mg/kg cocaine and in OM rats treated with 10 mg/kg cocaine
Conclusion Our results indicated that obesity-resistant S5B rats showed greater cocaine CPP than the obesity-prone OM rats These findings do not support a theory of common vulnerability for reinforcer preferences (food and cocaine) However they show that BC reduced cocaine conditioning effects supporting at least a partial regulatory role of D2R in conditioned responses to drugs Published by Elsevier Inc
C1 [Thanos, Panayotis K.; Kim, Ronald; Cho, Jacob; Michaelides, Michael; Wang, Gene-Jack] Brookhaven Natl Lab, Behav Pharmacol & Neuroimaging Lab, Dept Med, Upton, NY 11973 USA.
[Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, Lab Neuroimaging, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Thanos, Panayotis K.; Kim, Ronald; Michaelides, Michael; Anderson, Brenda J.; Robinson, John K.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY USA.
[Primeaux, Stefany D.; Bray, George A.] Pennington Biomed Res Ctr, Dietary Obes Lab, Baton Rouge, LA USA.
RP Thanos, PK (reprint author), Brookhaven Natl Lab, Behav Pharmacol & Neuroimaging Lab, Dept Med, Upton, NY 11973 USA.
RI Michaelides, Michael/K-4736-2013
OI Michaelides, Michael/0000-0003-0398-4917
FU NIAAA (LNI)
FX Support contributed by the NIAAA (Intramural Research Program, LNI) is
duly acknowledged
NR 40
TC 13
Z9 13
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD DEC 2
PY 2010
VL 101
IS 5
BP 713
EP 718
DI 10.1016/j.physbeh.2010.08.011
PG 6
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA 692BK
UT WOS:000285126300025
PM 20801137
ER
PT J
AU Bartee, E
Eyster, CA
Viswanathan, K
Mansouri, M
Donaldson, JG
Fruh, K
AF Bartee, Eric
Eyster, Craig A.
Viswanathan, Kasinath
Mansouri, Mandana
Donaldson, Julie G.
Frueh, Klaus
TI Membrane-Associated RING-CH Proteins Associate with Bap31 and Target
CD81 and CD44 to Lysosomes
SO PLOS ONE
LA English
DT Article
ID MHC CLASS-II; COMPLEX CLASS-I; E3 UBIQUITIN LIGASE;
ENDOPLASMIC-RETICULUM; DOWN-REGULATION; DENDRITIC CELLS; AMINO-ACIDS;
MASS-SPECTROMETRY; MARCH-II; MOLECULES
AB Membrane-associated RING-CH (MARCH) proteins represent a family of transmembrane ubiquitin ligases modulating intracellular trafficking and turnover of transmembrane protein targets. While homologous proteins encoded by gamma-2 herpesviruses and leporipoxviruses have been studied extensively, limited information is available regarding the physiological targets of cellular MARCH proteins. To identify host cell proteins targeted by the human MARCH-VIII ubiquitin ligase we used stable isotope labeling of amino-acids in cell culture (SILAC) to monitor MARCH-dependent changes in the membrane proteomes of human fibroblasts. Unexpectedly, we observed that MARCH-VIII reduced the surface expression of Bap31, a chaperone that predominantly resides in the endoplasmic reticulum (ER). We demonstrate that Bap31 associates with the transmembrane domains of several MARCH proteins and controls intracellular transport of MARCH proteins. In addition, we observed that MARCH-VIII reduced the surface expression of the hyaluronic acid-receptor CD44 and both MARCH-VIII and MARCH-IV sequestered the tetraspanin CD81 in endo-lysosomal vesicles. Moreover, gene knockdown of MARCH-IV increased surface levels of endogenous CD81 suggesting a constitutive involvement of this family of ubiquitin ligases in the turnover of tetraspanins. Our data thus suggest a role of MARCH-VIII and MARCH-IV in the regulated turnover of CD81 and CD44, two ubiquitously expressed, multifunctional proteins.
C1 [Bartee, Eric] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
[Viswanathan, Kasinath; Mansouri, Mandana; Frueh, Klaus] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.
[Eyster, Craig A.; Donaldson, Julie G.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Bartee, E (reprint author), Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
EM Fruehk@ohsu.edu
FU National Institutes of Health [RO1 CA/AI 094011, R21 CA 109674];
National Center for Research Resources [RR00163]; Ruth L. Kirschstein
National Research Service Awards [T32 AI007472]; Oregon Health and
Science University Tartar Trust
FX This work is funded by National Institutes of Health (RO1 CA/AI 094011,
R21 CA 109674) and the National Center for Research Resources (RR00163)
to K.F. and by the Ruth L. Kirschstein National Research Service Awards
T32 AI007472 and the Oregon Health and Science University Tartar Trust
to E.B. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 58
TC 18
Z9 19
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 2
PY 2010
VL 5
IS 12
AR e15132
DI 10.1371/journal.pone.0015132
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688QY
UT WOS:000284868000025
PM 21151997
ER
PT J
AU Sokolov, MV
Neumann, RD
AF Sokolov, Mykyta V.
Neumann, Ronald D.
TI Radiation-Induced Bystander Effects in Cultured Human Stem Cells
SO PLOS ONE
LA English
DT Article
ID NORMAL HUMAN FIBROBLASTS; MEDIATED INTERCELLULAR COMMUNICATION;
DOUBLE-STRAND BREAKS; IONIZING-RADIATION; ALPHA-PARTICLE; DNA-DAMAGE;
MICROBEAM IRRADIATION; CELLULAR-RESPONSE; LET RADIATION; GLIOMA-CELLS
AB Background: The radiation-induced "bystander effect" (RIBE) was shown to occur in a number of experimental systems both in vitro and in vivo as a result of exposure to ionizing radiation (IR). RIBE manifests itself by intercellular communication from irradiated cells to non-irradiated cells which may cause DNA damage and eventual death in these bystander cells. It is known that human stem cells (hSC) are ultimately involved in numerous crucial biological processes such as embryologic development; maintenance of normal homeostasis; aging; and aging-related pathologies such as cancerogenesis and other diseases. However, very little is known about radiation-induced bystander effect in hSC. To mechanistically interrogate RIBE responses and to gain novel insights into RIBE specifically in hSC compartment, both medium transfer and cell co-culture bystander protocols were employed.
Methodology/Principal Findings: Human bone-marrow mesenchymal stem cells (hMSC) and embryonic stem cells (hESC) were irradiated with doses 0.2 Gy, 2 Gy and 10 Gy of X-rays, allowed to recover either for 1 hr or 24 hr. Then conditioned medium was collected and transferred to non-irradiated hSC for time course studies. In addition, irradiated hMSC were labeled with a vital CMRA dye and co-cultured with non-irradiated bystander hMSC. The medium transfer data showed no evidence for RIBE either in hMSC and hESC by the criteria of induction of DNA damage and for apoptotic cell death compared to non-irradiated cells (p>0.05). A lack of robust RIBE was also demonstrated in hMSC co-cultured with irradiated cells (p>0.05).
Conclusions/Significance: These data indicate that hSC might not be susceptible to damaging effects of RIBE signaling compared to differentiated adult human somatic cells as shown previously. This finding could have profound implications in a field of radiation biology/oncology, in evaluating radiation risk of IR exposures, and for the safety and efficacy of hSC regenerative-based therapies.
C1 [Sokolov, Mykyta V.; Neumann, Ronald D.] NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Sokolov, MV (reprint author), NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM sokolovm@mail.nih.gov
FU National Institutes of Health, Clinical Center
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, Clinical Center. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 54
TC 20
Z9 20
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD DEC 2
PY 2010
VL 5
IS 12
AR e14195
DI 10.1371/journal.pone.0014195
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688QY
UT WOS:000284868000011
PM 21152027
ER
PT J
AU Tuleuova, N
Revzin, A
AF Tuleuova, Nazgul
Revzin, Alexander
TI Micropatterning of Aptamer Beacons to Create Cytokine-Sensing Surfaces
SO CELLULAR AND MOLECULAR BIOENGINEERING
LA English
DT Article
DE High-throughput screening; Biosensors; Cell arrays; Aptamers; Surface
micropatterning
ID GENE-EXPRESSION; CELL ARRAYS; PHOTOLITHOGRAPHY; LYMPHOCYTES;
MICROARRAYS; ASSAYS; GAMMA
AB Aptamer beacons are DNA or RNA probes that bind proteins or small molecules of interest and emit signal directly upon interaction with the target analyte. This paper describes micropatterning of aptamer beacons for detection of IFN-gamma-an important inflammatory cytokine. The beacon consisted of a fluorophore-labeled aptamer strand hybridized with a shorter, quencher-carrying complementary strand. Cytokine molecules were expected to displace quenching strands of the beacon, disrupting FRET effect and resulting in fluorescence signal. The glass substrate was first micropatterned with poly(ethylene glycol) (PEG) hydrogel microwells (35 mu m diameter individual wells) so as to define sites for attachment of beacon molecules. PEG microwell arrays were then incubated with avidin followed by biotin-aptamer-fluorophore constructs. Subsequent incubation with quencher-carrying complementary strands resulted in formation of DNA duplex and caused quenching of fluorescence due to FRET effect. When exposed to IFN-gamma, microwells changed fluorescence from low (quencher hybridized with fluorophore-carrying strand) to high (quenching strand displaced by cytokine molecules). The fluorescence signal was confined to microwells, was changing in real-time and was dependent on the concentration of IFN-gamma. In the future, we plan to co-localize aptamer beacons and cells on micropatterned surfaces in order to monitor in real-time cytokine secretion from immune cells in microwells.
C1 [Tuleuova, Nazgul; Revzin, Alexander] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA.
[Tuleuova, Nazgul] Natl Biotechnol Ctr, Astana, Kazakhstan.
RP Revzin, A (reprint author), Univ Calif Davis, Dept Biomed Engn, 451 Hlth Sci Dr,2519, Davis, CA 95616 USA.
EM arevzin@ucdavis.edu
FU NSF EFRI [0937997]
FX The authors would like to acknowledge Prof. Yohei Yokobayashi at UC
Davis for helpful advice regarding aptamer beacon construction. The use
of fluorescence microscopy equipment in the laboratory of Prof. Laura
Marcu at UC Davis is greatly appreciated. We thank Dr. Michael Howland
and Ms. Jun Yan for help with manuscript preparation. This work was
supported by an NSF EFRI (#0937997) grant awarded to AR.
NR 33
TC 21
Z9 21
U1 4
U2 42
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1865-5025
J9 CELL MOL BIOENG
JI Cell. Mol. Bioeng.
PD DEC
PY 2010
VL 3
IS 4
BP 337
EP 344
DI 10.1007/s12195-010-0148-5
PG 8
WC Cell & Tissue Engineering; Biophysics; Cell Biology
SC Cell Biology; Biophysics
GA 693GB
UT WOS:000285211500003
ER
PT J
AU Gibbons, DL
Raine, T
Abeler-Dorner, L
Jandke, A
Hwang, IY
Irving, PM
Kehrl, JH
Hayday, AC
AF Gibbons, D. L.
Raine, T.
Abeler-Dorner, L.
Jandke, A.
Hwang, I. -Y.
Irving, P. M.
Kehrl, J. H.
Hayday, A. C.
TI RGS1 is a key regulator of human T cell migration and a potential target
for therapy in Inflammatory Bowel Disease (IBD)
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Congress of the British-Society-for-Immunology
CY DEC 06-10, 2010
CL Liverpool, ENGLAND
SP British Soc Immunol
C1 [Gibbons, D. L.; Abeler-Dorner, L.; Irving, P. M.; Hayday, A. C.] Kings Coll London, London WC2R 2LS, England.
[Gibbons, D. L.; Abeler-Dorner, L.; Jandke, A.; Hayday, A. C.] Canc Res UK, London, England.
[Gibbons, D. L.; Abeler-Dorner, L.; Irving, P. M.; Hayday, A. C.] Guys & St Thomas Fdn Trust, Biomed Res Ctr, London, England.
[Raine, T.] Univ Cambridge, Cambridge, England.
[Hwang, I. -Y.; Kehrl, J. H.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD DEC
PY 2010
VL 131
SU 1
BP 75
EP 75
PG 1
WC Immunology
SC Immunology
GA 689XL
UT WOS:000284964100216
ER
PT J
AU Royle, C
Doumazos, S
Aquino, VN
Biasin, M
Piacentini, L
Fuchs, D
Lo Caputo, S
Shearer, GM
Clerici, M
Graham, DR
Boasso, A
AF Royle, C.
Doumazos, S.
Aquino, V. N.
Biasin, M.
Piacentini, L.
Fuchs, D.
Lo Caputo, S.
Shearer, G. M.
Clerici, M.
Graham, D. R.
Boasso, A.
TI Permeabilization of HIV via envelope cholesterol depletion enhances HIV
recall antigen responses by weakening its immunopathogenic potential
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Congress of the British-Society-for-Immunology
CY DEC 06-10, 2010
CL Liverpool, ENGLAND
SP British Soc Immunol
C1 [Royle, C.; Doumazos, S.; Boasso, A.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Med, Immunol Sect,Chelsea & Westminster Hosp,Div Infec, London, England.
[Aquino, V. N.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Retrovirus Lab, Baltimore, MD USA.
[Biasin, M.; Piacentini, L.] Univ Milan, Cattedra Immunol, Milan, Italy.
[Fuchs, D.] Innsbruck Med Univ, Div Biol Chem, Bioctr, Innsbruck, Austria.
[Lo Caputo, S.] Osped SM Annunziata, Div Malattie Infett, Florence, Italy.
[Shearer, G. M.] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Graham, D. R.] Fdn Don Gnocchi IRCCS, Milan, Italy.
[Graham, D. R.] Johns Hopkins Sch Med, Dept Med, Johns Hopkins Bayview Prote Ctr, Baltimore, MD USA.
RI biasin, mara/G-7426-2012
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD DEC
PY 2010
VL 131
SU 1
BP 87
EP 88
PG 2
WC Immunology
SC Immunology
GA 689XL
UT WOS:000284964100263
ER
PT J
AU al Basatena, NKS
Macnamara, A
Vine, AM
Thio, CL
Astemborski, J
Usuku, K
Osame, M
Kirk, GD
Donfield, SM
Goedert, JJ
Bangham, CRM
Carrington, M
Khakoo, SI
Asquith, B
AF al Basatena, N-K Seich
Macnamara, A.
Vine, A. M.
Thio, C. L.
Astemborski, J.
Usuku, K.
Osame, M.
Kirk, G. D.
Donfield, S. M.
Goedert, J. J.
Bangham, C. R. M.
Carrington, M.
Khakoo, S. I.
Asquith, B.
TI KIR2DL2 enhances protective and detrimental HLA class I-mediated
immunity in chronic viral infection
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Congress of the British-Society-for-Immunology
CY DEC 06-10, 2010
CL Liverpool, ENGLAND
SP British Soc Immunol
C1 [Thio, C. L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[al Basatena, N-K Seich; Macnamara, A.; Vine, A. M.; Bangham, C. R. M.; Khakoo, S. I.; Asquith, B.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Astemborski, J.; Kirk, G. D.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Usuku, K.] Kumamoto Univ, Kumamoto, Japan.
[Donfield, S. M.] Rho Inc, Chapel Hill, NC USA.
[Osame, M.] Kagoshima Univ, Kagoshima 890, Japan.
[Goedert, J. J.] NCI, Rockville, MD USA.
[Carrington, M.] NCI, Frederick, MD 21701 USA.
[Carrington, M.] MIT & Havard, Ragon Inst MGH, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD DEC
PY 2010
VL 131
SU 1
BP 148
EP 148
PG 1
WC Immunology
SC Immunology
GA 689XL
UT WOS:000284964100488
ER
PT J
AU Lin, TH
Hsieh, TY
Horowitz, AM
Chen, KK
Lin, SS
Lai, YJ
Hsiao, FY
Chang, CS
AF Lin, Tzu-Hsien
Hsieh, Tien-Yu
Horowitz, Alice M.
Chen, Ker-Kong
Lin, Shiu-Shiung
Lai, Yi-Jen
Hsiao, Feng-Ying
Chang, Chin-Shun
TI Knowledge and practices of caries prevention among Taiwanese dentists
attending a national conference
SO JOURNAL OF DENTAL SCIENCES
LA English
DT Article
DE knowledge of dental caries prevention; Taiwanese dentists; sealant
fluoride
ID DENTAL HYGIENISTS KNOWLEDGE; OPINIONS; ETIOLOGY
AB Background/purpose: This study was carried out to evaluate Taiwanese dentists' knowledge and practice towards preventive dental care.
Materials and methods: A questionnaire survey was conducted at the nationwide annual dental congress in 2008 in Taipei, Taiwan. Dentists' knowledge about preventive dentistry was assessed based on their responses to 19 statements. Dentists' attitudes towards preventive dentistry were assessed based on responses to the effectiveness of 16 preventive procedures. The dentists were also asked about their experience with the use of sealants and fluoride.
Results: More than 80% could not distinguish between new and old theories of the mechanism of action of fluoride. The correct answer was "remineralization of incipient decay", not "incorporation of fluoride into developing teeth". Also 68% incorrectly answered that "lacto-bacilli play a more-significant role in the initiation of smooth surface carious lesions than do mutans streptococci", an older theory. Over 80% perceived the effectiveness of "pit and fissure sealants", "professional prophylaxis", and "flossing" for preventing caries in children, and the last 2 procedures for adults. "Community water fluoridation" and sealants were selected as the most effective procedures for caries prevention in children, and "professional prophylaxis" and "flossing" for adults. Although sealants were perceived as being effective, 44% of dentists reported that they only applied sealants to <= 10% of their [children/pediatric?] patients. The reasons were that patients had difficulty understanding the value (67%) and were unwilling to pay (63%). Nearly 55% of dentists provided topical fluoride treatments to children more than 2 times per year. However, the frequency decreased to less than once per year for teenagers and adults. Most of the dentists finished a fluoride application in 1 min for in-office treatments.
Conclusions: A portion of Taiwanese dentists seemed to have limited up-to-date information about certain topics related to caries prevention. The frequency of treatments for caries prevention, such as topical fluoride and sealants, did not match the perceived effectiveness of these treatments by participants. Copyright (C) 2010, Association for Dental Sciences of the Republic of China. Published by Elsevier Taiwan LLC. All rights reserved.
C1 [Chang, Chin-Shun] Kaohsiung Med Univ, Global Ctr Excellence Oral Hlth Res & Dev, Kaohsiung 80708, Taiwan.
[Lin, Tzu-Hsien; Lai, Yi-Jen; Hsiao, Feng-Ying] China Med Univ, Dept Dent Hyg, Taichung, Taiwan.
[Hsieh, Tien-Yu; Chen, Ker-Kong; Lin, Shiu-Shiung] Kaohsiung Med Univ, Coll Dent Med, Kaohsiung 80708, Taiwan.
[Horowitz, Alice M.] Natl Inst Dent & Craniofacial Res, Off Sci Policy & Anal, NIH, Bethesda, MD USA.
RP Chang, CS (reprint author), Kaohsiung Med Univ, Global Ctr Excellence Oral Hlth Res & Dev, 100 Shih Chuan 1st Rd, Kaohsiung 80708, Taiwan.
EM csc1201@seed.net.tw
FU Association for Dental Sciences of the Republic of China
FX This study was supported, in part, by a grant from the Association for
Dental Sciences of the Republic of China. Special thanks go to Y.H.
Hsieh and H.F. Wang for conducting the questionnaire survey and coding
the data.
NR 18
TC 2
Z9 2
U1 1
U2 2
PU ELSEVIER TAIWAN
PI TAIPEI
PA RM N-412, 4F, CHIA HSIN BUILDING 11, NO 96, ZHONG SHAN N ROAD SEC 2,
TAIPEI, 10449, TAIWAN
SN 1991-7902
J9 J DENT SCI
JI J. Dental Sci.
PD DEC
PY 2010
VL 5
IS 4
BP 229
EP 236
DI 10.1016/j.jds.2010.11.007
PG 8
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 703YR
UT WOS:000286018400008
ER
PT J
AU Carbone, M
Baris, YI
Bertino, P
Brass, B
Dogan, U
Emri, S
Gaudino, G
Gultekin, M
Jube, S
Kanodia, S
Lockey, J
Partridge, CR
Rinaudo, C
Rivera, Z
Ryan, PH
Sens, MA
Steele, I
Tuncer, M
Way, S
Yang, H
Miller, A
AF Carbone, M.
Baris, Y. I.
Bertino, P.
Brass, B.
Dogan, U.
Emri, S.
Gaudino, G.
Gultekin, M.
Jube, S.
Kanodia, S.
Lockey, J.
Partridge, C. R.
Rinaudo, C.
Rivera, Z.
Ryan, P. H.
Sens, M. A.
Steele, I.
Tuncer, M.
Way, S.
Yang, H.
Miller, A.
TI Erionite Exposure in North Dakota is Comparable to That Found in Turkish
Villages Which Experience a High Incidence of Mesothelioma
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Carbone, M.; Bertino, P.; Gaudino, G.; Jube, S.; Kanodia, S.; Rivera, Z.; Yang, H.] Univ Hawaii, Univ Hawaii Canc Ctr, Honolulu, HI 96822 USA.
[Baris, Y. I.; Emri, S.; Tuncer, M.] Hacettepe Univ, Ankara, Turkey.
[Brass, B.; Partridge, C. R.; Way, S.] US EPA, Denver, CO USA.
[Dogan, U.] Univ Iowa, Iowa City, IA USA.
[Gultekin, M.; Tuncer, M.] Turkish Minist Hlth, Ankara, Turkey.
[Lockey, J.; Ryan, P. H.] Univ Cincinnati, Cincinnati, OH USA.
[Rinaudo, C.] Univ Piemonte Orientale, Alessandria, Italy.
[Rivera, Z.] Univ Hawaii, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA.
[Sens, M. A.] Univ N Dakota, Grand Forks, ND 58201 USA.
[Steele, I.] Univ Chicago, Chicago, IL 60637 USA.
[Yang, H.] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.
[Miller, A.] NIEHS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD DEC
PY 2010
VL 5
IS 12
SU 7
BP S561
EP S561
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 690HQ
UT WOS:000284994100154
ER
PT J
AU Masumoto, H
Ohzeki, J
Nakano, M
Bergmann, J
Noskov, V
Kouprina, N
Earnshaw, W
Larionov, V
AF Masumoto, Hiroshi
Ohzeki, Jun-ichirou
Nakano, Megumi
Bergmann, Jan
Noskov, Vladimir
Kouprina, Natalay
Earnshaw, William
Larionov, Vladimir
TI A Human Artificial Chromosome (HAC) with a conditional centromere
SO GENES & GENETIC SYSTEMS
LA English
DT Meeting Abstract
C1 [Masumoto, Hiroshi; Ohzeki, Jun-ichirou; Nakano, Megumi] Kazusa DNA Res Inst, Dept Human Genome Res, Kisarazu, Chiba, Japan.
[Bergmann, Jan; Earnshaw, William] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH8 9YL, Midlothian, Scotland.
[Noskov, Vladimir; Kouprina, Natalay; Larionov, Vladimir] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU GENETICS SOC JAPAN
PI SHIZUOKA-KEN
PA NATIONAL INST GENETICS YATA 1111, MISHIMA, SHIZUOKA-KEN, 411-8540, JAPAN
SN 1341-7568
EI 1880-5779
J9 GENES GENET SYST
JI Genes Genet. Syst.
PD DEC
PY 2010
VL 85
IS 6
BP 458
EP 458
PG 1
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 759KX
UT WOS:000290243200242
ER
PT J
AU Hangartner, TN
Short, DF
Zemel, BS
Gilsanz, V
Kalkwarf, HJ
Lappe, JM
Mahboubi, S
Oberfield, SE
Shepherd, JA
Winer, KK
AF Hangartner, T. N.
Short, D. F.
Zemel, B. S.
Gilsanz, V.
Kalkwarf, H. J.
Lappe, J. M.
Mahboubi, S.
Oberfield, S. E.
Shepherd, J. A.
Winer, K. K.
TI MODELING OF PEDIATRIC SPINE BMD WITH CONSIDERATION OF ANTHROPOMETRIC
PARAMETERS
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Meeting Abstract
CT 1st Asia-Pacific Osteoporosis Meeting
CY DEC 10-13, 2010
CL Singapore, SINGAPORE
C1 [Hangartner, T. N.; Short, D. F.] Wright State Univ, BioMed Imaging Lab, Dayton, OH 45435 USA.
[Zemel, B. S.; Mahboubi, S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Gilsanz, V.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Kalkwarf, H. J.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Lappe, J. M.] Creighton Univ, Omaha, NE 68178 USA.
[Oberfield, S. E.] Columbia Univ, New York, NY USA.
[Shepherd, J. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Winer, K. K.] NICHHD, Bethesda, MD 20892 USA.
RI Zemel, Babette/D-1117-2009
NR 1
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD DEC
PY 2010
VL 21
SU 5
BP S682
EP S683
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 754XA
UT WOS:000289889900044
ER
PT J
AU Isle, LB
Plescia, M
La Porta, M
Shepherd, W
AF Isle, Lori Belle
Plescia, Marcus
La Porta, Madeline
Shepherd, Walter
TI In conclusion: looking to the future of comprehensive cancer control
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Comprehensive cancer control; Global health; Non-communicable diseases
ID UNITED-STATES
AB The articles in this monograph illustrate the progress and successes of comprehensive cancer control (CCC) since our 2005 publication. The strides made in CCC demonstrate the energy and commitment of this nationwide movement to reduce the burden of cancer for all people. The purpose of this conclusion paper is to discuss the future of CCC, which promises a new emphasis on policy, primary prevention, public health, evidence-based interventions, and global health supported by advanced communication tools.
C1 [Isle, Lori Belle] Amer Canc Soc, Hlth Promot Dept, Natl Home Off, Atlanta, GA 30303 USA.
[Plescia, Marcus] Ctr Dis Control & Prevent, Atlanta, GA USA.
[La Porta, Madeline] NCI, Off Commun & Educ Partnerships & Disseminat Initi, Bethesda, MD 20892 USA.
[Shepherd, Walter] Comprehens Canc Consulting Serv, Chapel Hill, NC USA.
RP Isle, LB (reprint author), Amer Canc Soc, Hlth Promot Dept, Natl Home Off, 250 Williams St, Atlanta, GA 30303 USA.
EM lbellei1@cancer.org
NR 17
TC 7
Z9 8
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD DEC
PY 2010
VL 21
IS 12
SI SI
BP 2049
EP 2057
DI 10.1007/s10552-010-9666-7
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 737ZR
UT WOS:000288609600011
ER
PT J
AU von Leupoldt, A
AF von Leupoldt, Andreas
TI Emotions, brain and breathlessness
SO BIOLOGICAL PSYCHOLOGY
LA English
DT Meeting Abstract
CT 16th Annual Meeting/28th Symposium on Respiratory Psychophysiology
CY OCT 25-27, 2009
CL Berlin, GERMANY
SP Int Soc Adv Resp Psychophysiol (ISARP)
C1 [von Leupoldt, Andreas] Univ Florida, Dept Physiol Sci, Gainesville, FL 32610 USA.
[von Leupoldt, Andreas] Univ Hamburg, Dept Psychol, Hamburg, Germany.
[von Leupoldt, Andreas] Univ Med Ctr Hamburg Eppendorf, Dept Syst Neurosci, Hamburg, Germany.
[von Leupoldt, Andreas] Univ Florida, NIMH Ctr Study Emot & Attent, Gainesville, FL USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-0511
J9 BIOL PSYCHOL
JI Biol. Psychol.
PD DEC
PY 2010
VL 85
IS 3
BP 510
EP 510
PG 1
WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology,
Experimental
SC Psychology; Behavioral Sciences
GA 728TG
UT WOS:000287896800025
ER
PT J
AU Aschard, H
Hancock, DB
London, SJ
Kraft, P
AF Aschard, Hugues
Hancock, Dana B.
London, Stephanie J.
Kraft, Peter
TI Genome Wide Meta-Analysis of Joint Tests for Genetic and
Gene-Environment Interaction Effects
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Aschard, Hugues; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA.
[Hancock, Dana B.; London, Stephanie J.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
RI Hancock, Dana/D-8577-2012
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 7
BP 918
EP 919
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100020
ER
PT J
AU Krishnan, M
Wilson, AF
AF Krishnan, Mera
Wilson, Alexander F.
CA NIH Working Grp Stat Genetics
TI A Characterization of the Training Needs in Genetic Epidemiology
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Krishnan, Mera; Wilson, Alexander F.; NIH Working Grp Stat Genetics] NHGRI, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 4
BP 918
EP 918
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100017
ER
PT J
AU Jacobs, KB
Yeager, M
Cullen, MG
Zhang, XJ
Boland, J
Bacior, J
Lonsberry, V
Matthews, C
Roberson, D
Chen, QA
Burdett, L
Menashe, I
Yang, XR
Goldin, LR
McMaster, ML
Caporaso, NE
Taylor, PR
Landi, MT
Sampson, J
Chatterjee, N
Nickerson, ML
Mcgee, K
Dean, MC
Khan, J
Tucker, MA
Chanock, SJ
Goldstein, AM
AF Jacobs, Kevin B.
Yeager, Meredith
Cullen, Michael G.
Zhang, Xijun
Boland, Joseph
Bacior, Jennifer
Lonsberry, Victor
Matthews, Casey
Roberson, David
Chen, Quan
Burdett, Laurie
Menashe, Idan
Yang, Xiaohong R.
Goldin, Lynn R.
McMaster, Mary L.
Caporaso, Neil E.
Taylor, Philip R.
Landi, Maria Teresa
Sampson, Joshua
Chatterjee, Nilanjan
Nickerson, Michael L.
Mcgee, Kate
Dean, Michael C.
Khan, Javed
Tucker, Margaret A.
Chanock, Stephen J.
Goldstein, Alisa M.
TI Realities and Limitations of Coverage in Current "Whole''-Exome
Sequencing Capture Approaches
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Jacobs, Kevin B.; Yeager, Meredith; Cullen, Michael G.; Zhang, Xijun; Boland, Joseph; Bacior, Jennifer; Lonsberry, Victor; Matthews, Casey; Roberson, David; Chen, Quan; Burdett, Laurie] NCI Frederick, Core Genotyping Facil, Frederick, MD USA.
[Jacobs, Kevin B.; Yeager, Meredith; Cullen, Michael G.; Zhang, Xijun; Boland, Joseph; Bacior, Jennifer; Lonsberry, Victor; Matthews, Casey; Roberson, David; Chen, Quan; Burdett, Laurie; Menashe, Idan; Yang, Xiaohong R.; Goldin, Lynn R.; McMaster, Mary L.; Caporaso, Neil E.; Taylor, Philip R.; Landi, Maria Teresa; Sampson, Joshua; Chatterjee, Nilanjan; Tucker, Margaret A.; Chanock, Stephen J.; Goldstein, Alisa M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Nickerson, Michael L.; Mcgee, Kate; Dean, Michael C.] NCI, Expt Immunol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Khan, Javed] NCI, Oncogenom Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RI Tucker, Margaret/B-4297-2015
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 11
BP 919
EP 920
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100024
ER
PT J
AU Cornelis, MC
Tchetgen, EJ
Liming, L
Qi, L
Chatterjee, N
Hu, FB
Kraft, P
AF Cornelis, Marilyn C.
Tchetgen, Eric J.
Liming, Liang
Qi, Lu
Chatterjee, Nilanjan
Hu, Frank B.
Kraft, Peter
TI Gene-Environment Interactions in Genome-Wide Association Studies: A
Comparative Study of Tests Applied to Empirical Studies of Type 2
Diabetes
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Cornelis, Marilyn C.; Tchetgen, Eric J.; Liming, Liang; Qi, Lu; Hu, Frank B.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Chatterjee, Nilanjan] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 16
BP 921
EP 921
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100029
ER
PT J
AU Pendergrass, SA
Brown-Gentry, KD
Dudek, S
Ambite, JL
Avery, CL
Buyske, S
Cai, CX
Heiss, G
Hindorff, L
Kooperberg, C
Lin, Y
Manolio, TA
Matise, T
Wilkens, L
Fesinmeyer, MD
Hsu, CN
Crawford, DC
Ritchie, MD
AF Pendergrass, Sarah A.
Brown-Gentry, Kristin D.
Dudek, Scott
Ambite, Jose L.
Avery, Christy L.
Buyske, Steve
Cai, Congxing
Heiss, Gerardo
Hindorff, Lucia
Kooperberg, Charles
Lin, Yi
Manolio, Teri A.
Matise, Tara
Wilkens, Lynne
Fesinmeyer, Megan D.
Hsu, Chun-Nan
Crawford, Dana C.
Ritchie, Marylyn D.
TI Phenotype-Wide Association Study (PheWAS) for Exploration of Novel SNP
and Phenotype Relationships within PAGE
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Pendergrass, Sarah A.; Brown-Gentry, Kristin D.; Dudek, Scott; Crawford, Dana C.; Ritchie, Marylyn D.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN USA.
[Ambite, Jose L.; Cai, Congxing; Hsu, Chun-Nan] Univ So Calif, Inst Informat Sci, Marina Del Rey, CA 90292 USA.
[Avery, Christy L.; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Buyske, Steve; Matise, Tara] Rutgers State Univ, Dept Genet, Piscataway, NJ USA.
[Buyske, Steve] Rutgers State Univ, Dept Stat, Piscataway, NJ USA.
[Hindorff, Lucia; Manolio, Teri A.] NHGRI, Bethesda, MD 20892 USA.
[Kooperberg, Charles; Lin, Yi; Fesinmeyer, Megan D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Wilkens, Lynne] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 19
BP 922
EP 922
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100032
ER
PT J
AU Goldin, LR
Yang, XHR
McMaster, ML
Jacobs, KB
Yeager, M
Cullen, MG
Zhang, XJ
Boland, J
Chen, QA
Burdett, L
Taylor, PR
Landi, MT
Caporaso, NE
Goldstein, AM
Chanock, SJ
Tucker, MA
AF Goldin, Lynn R.
Yang, Xiaohong R.
McMaster, Mary L.
Jacobs, Kevin B.
Yeager, Meredith
Cullen, Michael G.
Zhang, Xijun
Boland, Joseph
Chen, Quan
Burdett, Laurie
Taylor, Phillip R.
Landi, Maria T.
Caporaso, Neil E.
Goldstein, Alisa M.
Chanock, Stephen J.
Tucker, Margaret A.
TI The Use of Whole Exome Sequencing to Identify Rare Susceptibility
Variants in Cancer Prone Families
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Goldin, Lynn R.; Yang, Xiaohong R.; McMaster, Mary L.; Jacobs, Kevin B.; Yeager, Meredith; Cullen, Michael G.; Zhang, Xijun; Boland, Joseph; Chen, Quan; Burdett, Laurie; Taylor, Phillip R.; Landi, Maria T.; Caporaso, Neil E.; Goldstein, Alisa M.; Chanock, Stephen J.; Tucker, Margaret A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RI Tucker, Margaret/B-4297-2015
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 27
BP 924
EP 924
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100040
ER
PT J
AU Jung, J
Kim, I
Kwon, D
AF Jung, Jeesun
Kim, Inyoung
Kwon, Deukwoo
TI Statistical Models for Detecting Rare Variants Associated with a Disease
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Kim, Inyoung] Virginia Tech, Dept Stat, Blacksburg, VA 24061 USA.
[Kwon, Deukwoo] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Jung, Jeesun] Indiana Univ, Sch Med, Bloomington, IN 47405 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 28
BP 924
EP 925
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100041
ER
PT J
AU Li, Y
Barmada, MM
Sabol, S
Chatterjee, B
Pazour, G
Leigh, MW
Ferkol, TW
Lamb, J
Knowles, M
Zariwala, M
Lo, C
AF Li, You
Barmada, Michael M.
Sabol, Steve
Chatterjee, Bishwanath
Pazour, Gregory
Leigh, Margaret W.
Ferkol, Thomas W.
Lamb, Janette
Knowles, Michael
Zariwala, Maimoona
Lo, Cecilia
TI Systematic Interrogation for Mutations in Nearly 1000 Cilia Related
Genes in Patients with Primary Cilia Dyskinesia Using Targeted
Sequence-Capture and Massively Parallel Sequencing
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Li, You; Lo, Cecilia] Univ Pittsburgh, Sch Med, Dept Dev Biol, Pittsburgh, PA USA.
[Barmada, Michael M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Sabol, Steve; Chatterjee, Bishwanath] NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
[Pazour, Gregory] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA USA.
[Leigh, Margaret W.] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA.
[Ferkol, Thomas W.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Lamb, Janette] Univ Pittsburgh, Genom & Prote Core Lab, Pittsburgh, PA USA.
[Knowles, Michael; Zariwala, Maimoona] Univ N Carolina, Pulm & Cyst Fibrosis Ctr, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 33
BP 926
EP 926
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100046
ER
PT J
AU Sung, H
Pemov, A
Kim, Y
Cai, J
Sorant, AJ
Sloan, JL
Coombes, SL
Mullikin, J
Cruz, P
Stewart, DR
Wilson, AF
AF Sung, Heejong
Pemov, Alexander
Kim, Yoonhee
Cai, Juanliang
Sorant, Alexa J.
Sloan, Jennifer L.
Coombes, Sarah L.
Mullikin, Jim
Cruz, Pedro
Stewart, Douglas R.
Wilson, Alexander F.
TI Tiled Regression Applied to Cafe-Au-Lait Macule Burden in
Neurofibromatosis Type 1 Sequence Data
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Sung, Heejong; Kim, Yoonhee; Cai, Juanliang; Sorant, Alexa J.; Wilson, Alexander F.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
[Pemov, Alexander; Coombes, Sarah L.; Stewart, Douglas R.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Sloan, Jennifer L.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Mullikin, Jim; Cruz, Pedro] NHGRI, NIH Intramural Sequencing Ctr NISC, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 36
BP 927
EP 927
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100049
ER
PT J
AU Hein, R
Chatterjee, N
Montserrat, GC
Jenny, CC
AF Hein, Rebecca
Chatterjee, Nilanjan
Montserrat, Garcia-Closas
Jenny, Chang-Claude
TI Adaption of an Empirical Bayes Approach to Investigate Gene-environment
Interactions in Large Consortia
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Hein, Rebecca; Jenny, Chang-Claude] German Canc Res Ctr, Heidelberg, Germany.
[Chatterjee, Nilanjan] NCI, NIH, Bethesda, MD 20892 USA.
[Montserrat, Garcia-Closas] Univ Cambridge, Cambridge CB2 1TN, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 67
BP 935
EP 935
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100078
ER
PT J
AU Menashe, I
Maeder, D
Chanock, S
Rosenberg, PS
Chatterjee, N
AF Menashe, Idan
Maeder, Dennis
Chanock, Stephen
Rosenberg, Philip S.
Chatterjee, Nilanjan
TI Sharpening Pathway-Based Analyses using Hierarchical Clustering: Results
of a Prostate Cancer Genome-Wide Association Study
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Menashe, Idan; Maeder, Dennis; Chanock, Stephen; Rosenberg, Philip S.; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 84
BP 939
EP 939
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100095
ER
PT J
AU Moslehi, R
Kumar, A
Signore, C
Mills, JL
Dzutsev, A
AF Moslehi, Roxana
Kumar, A.
Signore, C.
Mills, J. L.
Dzutsev, A.
TI Adverse Effects of Nucleotide Excision Repair and Transcription Gene
Abnormalities on Human Fetal and Placental Development
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Moslehi, Roxana; Kumar, A.] SUNY Albany, Sch Publ Hlth, Rensselaer, NY USA.
[Signore, C.; Mills, J. L.] NICHD, NIH, Bethesda, MD USA.
[Dzutsev, A.] NCI, NIH, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 91
BP 941
EP 941
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100102
ER
PT J
AU Shriner, D
AF Shriner, Daniel
TI Factor Analysis of Population Structure and Admixture
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Shriner, Daniel] NHGRI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 109
BP 946
EP 946
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100119
ER
PT J
AU Zhang, FY
AF Zhang, Fengyu
TI Alternative Approach to Control for Population Structure in Analysis of
Genome-wide Association Data
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Zhang, Fengyu] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 110
BP 946
EP 947
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100120
ER
PT J
AU Graff, M
Gordon-Larsen, P
White, CC
Ngwa, J
Amin, N
Esko, T
Scheet, P
Schurmann, C
Teumer, A
Fox, CS
Qi, L
van Dam, RM
Strachen, D
Metspalu, A
van Duijn, CM
Schlessinger, D
Voelzke, H
North, KE
Berndt, S
Cupples, LA
AF Graff, Mariaelisa
Gordon-Larsen, Penny
White, Charles C.
Ngwa, Julius
Amin, Najaf
Esko, Tonu
Scheet, Paul
Schurmann, Claudia
Teumer, Alexander
Fox, Caroline S.
Qi, Lu
van Dam, Rob M.
Strachen, David
Metspalu, Andres
van Duijn, Cornelia M.
Schlessinger, David
Voelzke, Henry
North, Kari E.
Berndt, Sonja
Cupples, L. A.
TI Genetic Loci for BMI and BMI Change in the Transition from Adolescence
to Young Adulthood
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Graff, Mariaelisa; Gordon-Larsen, Penny] Univ N Carolina, Carolina Populat Ctr, Dept Nutr, Chapel Hill, NC 02215 USA.
[White, Charles C.; Ngwa, Julius] Boston Univ, Sch Publ Hlth, Dept Biostat, EE-50090 Boston, MA USA.
[Amin, Najaf; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, Inst Mol & Cell Biol, Tartu, Estonia.
[Esko, Tonu; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, 77030, Netherlands.
[Scheet, Paul] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, D-17487 Houston, TX USA.
[Schurmann, Claudia; Teumer, Alexander; Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
[Fox, Caroline S.; Cupples, L. A.] Framingham Heart Dis Epidemiol Study, Framingham, MA 02115 USA.
[Qi, Lu; van Dam, Rob M.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA USA.
[van Dam, Rob M.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore, Singapore.
[Strachen, David] St Georges Univ London, Div Community Hlth Sci, London, 21224, England.
[Schlessinger, David] NIA, Gerontol Res Ctr, Baltimore, MD USA.
[North, Kari E.] Univ N Carolina, Dept Epidemiol, Carolina Ctr Genome Sci, Chapel Hill, NC 20892 USA.
[Berndt, Sonja] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA.
[Cupples, L. A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Framingham, MA USA.
[Amin, Najaf; Metspalu, Andres] Estonian Bioctr, Tartu, 02115, Estonia.
[Qi, Lu] Brigham & Womens Hosp, Channing Lab, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 130
BP 952
EP 952
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100140
ER
PT J
AU Konig, IR
Erdmann, J
Thompson, JR
Preuss, M
Absher, D
Assimes, TL
Blankenberg, S
Boerwinkle, E
Chen, L
Cupples, A
Hall, AS
Halperin, E
Hengstenberg, C
Holm, H
Laaksonen, R
Li, MY
Marz, W
McPherson, R
Musunuru, K
Nelson, CP
Burnett, MS
Epstein, SE
O'Donnell, CJ
Quertermous, T
Rader, DJ
Roberts, R
Schillert, A
Stewart, AF
Thorleifsson, G
Thorsteinsdottir, U
Voight, BF
Wells, GA
Ziegler, A
Kathiresan, S
Reilly, MP
Samani, NJ
Schunkert, H
AF Konig, Inke R.
Erdmann, Jeanette
Thompson, John R.
Preuss, Michael
Absher, Devin
Assimes, Themistocles L.
Blankenberg, Stefan
Boerwinkle, Eric
Chen, Li
Cupples, Adrienne
Hall, Alistair S.
Halperin, Eran
Hengstenberg, Christian
Holm, Hilma
Laaksonen, Reijo
Li, Mingyao
Marz, Winfried
McPherson, Ruth
Musunuru, Kiran
Nelson, Christopher P.
Burnett, Mary S.
Epstein, Stephen E.
O'Donnell, Christopher J.
Quertermous, Thomas
Rader, Daniel J.
Roberts, Robert
Schillert, Arne
Stewart, Alexandre F.
Thorleifsson, Gudmar
Thorsteinsdottir, Unnur
Voight, Benjamin F.
Wells, George A.
Ziegler, Andreas
Kathiresan, Sekar
Reilly, Muredach P.
Samani, Nilesh J.
Schunkert, Heribert
TI Genetics of Coronary Artery Disease: Results from the CARDIOGRAM
Meta-analysis
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Konig, Inke R.; Preuss, Michael; Schillert, Arne; Ziegler, Andreas] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany.
[Erdmann, Jeanette; Schunkert, Heribert] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
[Thompson, John R.; Nelson, Christopher P.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[Absher, Devin] Hudson Alpha Inst, Huntsville, AL USA.
[Assimes, Themistocles L.; Quertermous, Thomas] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Blankenberg, Stefan] Johannes Gutenberg Univ Mainz, Med Klin & Poliklin, Univ Med, Mainz, Germany.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA.
[Chen, Li; McPherson, Ruth; Roberts, Robert; Stewart, Alexandre F.; Wells, George A.] Univ Ottawa, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada.
[Cupples, Adrienne] Boston Univ, Dept Biostat & Epidemiol, Boston, MA 02215 USA.
[Hall, Alistair S.] Univ Leeds, LIGHT Res Inst, Fac Med & Hlth, Leeds, W Yorkshire, England.
[Halperin, Eran] Tel Aviv Univ, Blavatnik Sch Comp Sci, Tel Aviv, Israel.
[Halperin, Eran] Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, Tel Aviv, Israel.
[Hengstenberg, Christian] Univ Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany.
[Holm, Hilma; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur] deCODE Genet, IS-101 Reykjavik, Iceland.
[Laaksonen, Reijo] Tampere Univ Hosp, Ctr Sci, Tampere, Finland.
[Marz, Winfried] Synlab Ctr Lab Diagnost Heidelberg, Heidelberg, Germany.
[Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Burnett, Mary S.; Epstein, Stephen E.] Washington Hosp Ctr, Cardiovasc Res Inst, MedStar Res Inst, Washington, DC 20010 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[O'Donnell, Christopher J.] Massachusetts Gen, Div Cardiol, Boston, MA USA.
[Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.
RI Laaksonen, Reijo/D-6323-2014
NR 0
TC 0
Z9 0
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 132
BP 953
EP 953
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100142
ER
PT J
AU Ritchie, M
Armstong, L
Bradford, Y
Carlson, C
Crawford, D
Crenshaw, A
de Andrade, M
Doheny, K
Haines, J
Hayes, G
Jarvik, G
Jiang, L
Ling, H
Kullo, I
Li, RL
Manolio, T
Matsumoto, M
McCarty, C
McDavid, A
Mirel, D
Olson, L
Paschall, J
Pugh, E
Rasmussen, L
Wilke, R
Zuvich, R
Turner, S
AF Ritchie, Marylyn
Armstong, Loren
Bradford, Yuki
Carlson, Chris
Crawford, Dana
Crenshaw, Andrew
de Andrade, Mariza
Doheny, Kim
Haines, Jonathan
Hayes, Geoff
Jarvik, Gail
Jiang, Lan
Ling, Hua
Kullo, Iftikhar
Li, Rongling
Manolio, Teri
Matsumoto, Martha
McCarty, Cathy
McDavid, Andrew
Mirel, Daniel
Olson, Lana
Paschall, Justin
Pugh, Elizabeth
Rasmussen, Luke
Wilke, Russ
Zuvich, Rebecca
Turner, Stephen
TI Quality Control Pipeline for Genome-Wide Association Studies in the
eMERGE Network: Comparing Single Site QC to a Merged QC Approach
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Ritchie, Marylyn; Bradford, Yuki; Crawford, Dana; Haines, Jonathan; Jiang, Lan; Olson, Lana; Wilke, Russ; Zuvich, Rebecca; Turner, Stephen] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN USA.
[Armstong, Loren; Hayes, Geoff] Northwestern Univ, Chicago, IL 60611 USA.
[Carlson, Chris; Jarvik, Gail; McDavid, Andrew] Univ Washington, Grp Hlth Cooperat, Seattle, WA 98195 USA.
[Crenshaw, Andrew; Mirel, Daniel] Broad Inst MIT & Harvard, Cambridge, MA USA.
[de Andrade, Mariza; Kullo, Iftikhar; Matsumoto, Martha] Mayo Clin, Rochester, MN USA.
[Doheny, Kim; Pugh, Elizabeth] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD USA.
[Li, Rongling; Manolio, Teri] NHGRI, Bethesda, MD 20892 USA.
[McCarty, Cathy; Rasmussen, Luke] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA.
RI Jarvik, Gail/N-6476-2014
OI Jarvik, Gail/0000-0002-6710-8708
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 146
BP 957
EP 957
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100156
ER
PT J
AU Cropp, CD
Simpson, CL
Wahlfors, T
George, A
Nati, H
Tammela, T
Schleutker, J
Bailey-Wilson, JE
AF Cropp, Cheryl D.
Simpson, Claire L.
Wahlfors, Tiina
George, Asha
Nati, Ha
Tammela, Teuvo
Schleutker, Johanna
Bailey-Wilson, Joan E.
TI Exploratory Association Analysis in a Subset of Finnish Prostate Cancer
Families Linked to 8q24
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Cropp, Cheryl D.; Simpson, Claire L.; George, Asha; Bailey-Wilson, Joan E.] NHGRI, NIH, Baltimore, MD USA.
[Wahlfors, Tiina; Nati, Ha; Schleutker, Johanna] Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland.
[George, Asha] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Tammela, Teuvo] Univ Tampere, Tampere Univ Hosp, Dept Urol, FIN-33101 Tampere, Finland.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 157
BP 960
EP 960
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100166
ER
PT J
AU Fang, SY
Pinney, SM
Bailey-Wilson, JE
de Andrade, MA
Li, YF
You, M
Schwartz, AG
Yang, P
Anderson, MW
Amos, CI
AF Fang, Shenying
Pinney, Susan M.
Bailey-Wilson, Joan E.
de Andrade, Mariza A.
Li, Yafang
You, Ming
Schwartz, Ann G.
Yang, Ping
Anderson, Marshall W.
Amos, Christopher I.
TI Ordered Subset Analysis Identifies Loci Influencing Lung Cancer Risk on
Chromosomes 6q and 12q
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Fang, Shenying; Li, Yafang; Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
[Pinney, Susan M.; Anderson, Marshall W.] Univ Cincinnati, Cincinnati, OH 45221 USA.
[Bailey-Wilson, Joan E.] NHGRI, Bethesda, MD USA.
[de Andrade, Mariza A.; Yang, Ping] Mayo Clin, Coll Med, Rochester, MN 55905 USA.
[You, Ming] Washington Univ, St Louis, MO 63130 USA.
[Schwartz, Ann G.] Karmanos Canc Inst, Detroit, MI USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 161
BP 961
EP 962
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100170
ER
PT J
AU Kim, Y
Justice, C
Sung, H
Cai, JL
Sorant, AJM
Behneman, D
Krishnan, M
Miller, NH
Wilson, AF
AF Kim, Yoonhee
Justice, Cristina
Sung, Heejong
Cai, Juanliang
Sorant, Alexa J. M.
Behneman, Dana
Krishnan, Mera
Miller, Nancy H.
Wilson, Alexander F.
TI Tests of Association for Family Data: Tiled Regression with Generalized
Estimation Equations
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Kim, Yoonhee; Justice, Cristina; Sung, Heejong; Cai, Juanliang; Sorant, Alexa J. M.; Behneman, Dana; Krishnan, Mera; Wilson, Alexander F.] NHGRI, Genometr Sect, IDRB, NIH, Bethesda, MD 20892 USA.
[Miller, Nancy H.] Univ Colorado, Childrens Hosp, Boulder, CO 80309 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 163
BP 962
EP 962
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100172
ER
PT J
AU Ledet, EM
Bailey-Wilson, JE
Mandal, DM
AF Ledet, Elisa M.
Bailey-Wilson, Joan E.
Mandal, Diptasri M.
TI Linkage Study of Prostate Cancer in High-risk African American Families
from Louisiana
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Ledet, Elisa M.; Mandal, Diptasri M.] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA USA.
[Bailey-Wilson, Joan E.] NHGRI, NIH, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 166
BP 963
EP 963
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100175
ER
PT J
AU Li, Q
Fallin, MD
Bailey-Wilson, JE
AF Li, Qing
Fallin, M. Daniele
Bailey-Wilson, Joan E.
TI Efficient Haplotype Reconstruction for Pedigree Data with Zero
Individual Genotype Mismatches
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Li, Qing; Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, NIH, Bethesda, MD USA.
[Fallin, M. Daniele] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 167
BP 963
EP 963
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100176
ER
PT J
AU Simpson, CL
Cropp, CD
Wahlfors, T
George, A
Ha, N
Tammela, TLJ
Schleutker, J
Bailey-Wilson, JE
AF Simpson, Claire L.
Cropp, Cheryl D.
Wahlfors, Tiina
George, Asha
Ha, Nati
Tammela, Teuvo L. J.
Schleutker, Johanna
Bailey-Wilson, Joan E.
TI Genetic Heterogeneity of Prostate Cancer Susceptibility in Finland:
Evidence for Several Novel Loci and Replication of HPCX1 and HPC10 Loci
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Simpson, Claire L.; Cropp, Cheryl D.; George, Asha; Bailey-Wilson, Joan E.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Wahlfors, Tiina; Ha, Nati; Schleutker, Johanna] Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland.
[George, Asha] Fox Chase Canc Ctr, Philadelphia, PA USA.
[Tammela, Teuvo L. J.] Tampere Univ Hosp, Dept Urol, Tampere, Finland.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 174
BP 965
EP 965
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100182
ER
PT J
AU Paterson, AD
Hosseini, M
Waggott, D
Boright, AP
Shen, EQ
Sylvestre, MP
Cleary, PA
Lachin, JM
Below, JE
Nicolae, D
Cox, NJ
Sandholm, N
Forsblom, C
Groop, PH
Canty, AJ
Sun, L
Bull, SB
AF Paterson, Andrew D.
Hosseini, Mohsen
Waggott, Daryl
Boright, Andrew P.
Shen, Enqing
Sylvestre, Marie-Pierre
Cleary, Patricia A.
Lachin, John M.
Below, Jennifer E.
Nicolae, Dan
Cox, Nancy J.
Sandholm, Niina
Forsblom, Carol
Groop, Per-Henrik
Canty, Angelo J.
Sun, Lei
Bull, Shelley B.
CA DCCT EDIC Res Grp
TI Genetic Variation at Adenylate Cyclase 5 (ADCY5) is Associated with
Glycemic Control in type 1 Diabetes
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Paterson, Andrew D.; Hosseini, Mohsen] Hosp Sick Children, Toronto, ON, Canada.
[Boright, Andrew P.] UHN, Toronto, ON, Canada.
[Cleary, Patricia A.; Lachin, John M.] George Washington Univ, Washington, DC 20052 USA.
[Below, Jennifer E.; Nicolae, Dan; Cox, Nancy J.] U Chicago, Chicago, IL USA.
[Sandholm, Niina; Forsblom, Carol; Groop, Per-Henrik] Univ Helsinki, FIN-00014 Helsinki, Finland.
[Canty, Angelo J.] McMaster Univ, Hamilton, ON L8S 4L8, Canada.
[Sun, Lei] Univ Toronto, Toronto, ON M5S 1A1, Canada.
[DCCT EDIC Res Grp] NIDDK, Bethesda, MD 20892 USA.
RI Bull, Shelley/A-1920-2013; Paterson, Andrew/A-4088-2011
OI Paterson, Andrew/0000-0002-9169-118X
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 192
BP 970
EP 970
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100199
ER
PT J
AU Tranah, GJ
Manini, TM
Lohman, KK
Nalls, MA
Kritchevsky, S
Newman, AB
Harris, TB
Biffi, A
Cummings, SR
Liu, YM
AF Tranah, Gregory J.
Manini, Todd M.
Lohman, Kurt K.
Nalls, Michael A.
Kritchevsky, Stephen
Newman, Anne B.
Harris, Tamara B.
Biffi, Alessandro
Cummings, Steven R.
Liu, Yongmei
TI Mitochondrial DNA Variation in Human Metabolic Rate, Energy Expenditure
and Mortality: The Health, Aging and Body Composition Study
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Manini, Todd M.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL 32611 USA.
[Lohman, Kurt K.] Wake Forest Univ, Dept Biostat Sci, Sch Med, Winston Salem, NC 27109 USA.
[Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA.
[Kritchevsky, Stephen; Liu, Yongmei] Wake Forest Univ, Sticht Ctr Aging, Sch Med, Winston Salem, NC 27109 USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Biffi, Alessandro] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 199
BP 972
EP 973
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100206
ER
PT J
AU Ye, C
Canty, AJ
Waggott, D
Sylvestre, MP
Shen, EQ
Hosseini, M
Boright, AP
Sun, L
Bull, SB
Paterson, AD
AF Ye, Chang
Canty, Angelo J.
Waggott, Daryl
Sylvestre, Marie-Pierre
Shen, Enqing
Hosseini, Mohsen
Boright, Andrew P.
Sun, Lei
Bull, Shelley B.
Paterson, Andrew D.
CA DCCT EDIC Res Grp
TI A Repeated Measures Genome Wide Association Study of Blood Pressure in
Type 1 Diabetes
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Ye, Chang; Canty, Angelo J.] McMaster Univ, Hamilton, ON L8S 4L8, Canada.
[Hosseini, Mohsen; Paterson, Andrew D.] Hosp Sick Children, Toronto, ON, Canada.
[Boright, Andrew P.] Univ Hlth Network, Toronto, ON, Canada.
[Sun, Lei] Univ Toronto, Toronto, ON M5S 1A1, Canada.
[DCCT EDIC Res Grp] NIDDK, Bethesda, MD 20892 USA.
RI Bull, Shelley/A-1920-2013; Paterson, Andrew/A-4088-2011
OI Paterson, Andrew/0000-0002-9169-118X
NR 0
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 203
BP 973
EP 973
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100209
ER
PT J
AU Sandstrom, D
Mozer, B
AF Sandstrom, David
Mozer, Brian
TI Drosophila neuroligin2 regulates the size and strength of the larval
neuromuscular synapse
SO JOURNAL OF NEUROGENETICS
LA English
DT Meeting Abstract
C1 [Sandstrom, David] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA.
[Mozer, Brian] NHLBI, Lab Biochem Genet, Bethesda, MD 20892 USA.
EM sandstrd@mail.nih.gov
NR 0
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 0167-7063
J9 J NEUROGENET
JI J. Neurogenet.
PD DEC
PY 2010
VL 24
SU 1
BP 8
EP 8
PG 1
WC Genetics & Heredity; Neurosciences
SC Genetics & Heredity; Neurosciences & Neurology
GA 684GD
UT WOS:000284537500020
ER
PT J
AU Brody, T
Kundu, M
Ross, J
Kuzin, A
Odenwald, WF
AF Brody, Thomas
Kundu, Mukta
Ross, Jermaine
Kuzin, Alexander
Odenwald, Ward F.
TI Use of a Genome-Wide Conserved Sequence Cluster Database to Identify
Functionally Related cis-Regulatory Enhancers
SO JOURNAL OF NEUROGENETICS
LA English
DT Meeting Abstract
C1 [Brody, Thomas; Kundu, Mukta; Ross, Jermaine; Kuzin, Alexander; Odenwald, Ward F.] NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD USA.
EM brodyt@ninds.nih.gov
NR 0
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 0167-7063
J9 J NEUROGENET
JI J. Neurogenet.
PD DEC
PY 2010
VL 24
SU 1
BP 86
EP 87
PG 2
WC Genetics & Heredity; Neurosciences
SC Genetics & Heredity; Neurosciences & Neurology
GA 684GD
UT WOS:000284537500229
ER
PT J
AU Hicks, C
Sweeney, D
Danner, R
Eichacker, P
Suffredini, A
Feng, J
Sun, JF
Behrend, E
Solomon, S
Natanson, C
AF Hicks, Caitlin
Sweeney, Daniel
Danner, Robert
Eichacker, Peter
Suffredini, Anthony
Feng, Jing
Sun, Junfeng
Behrend, Ellen
Solomon, Steven
Natanson, Charles
TI MINERALOCORTICOID THERAPY IMPROVES SHOCK, LUNG DYSFUNCTION, AND SURVIVAL
IN A CANINE MODEL OF BACTERIAL PNEUMONIA
SO CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT 40th Critical Care Congress
CY JAN 15-19, 2011
CL San Diego, CA
SP Soc Crit Care Med
C1 [Hicks, Caitlin; Sweeney, Daniel; Danner, Robert; Eichacker, Peter; Suffredini, Anthony; Feng, Jing; Sun, Junfeng; Solomon, Steven; Natanson, Charles] NIH, Bethesda, MD 20892 USA.
[Behrend, Ellen] Auburn Univ, Auburn, AL 36849 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD DEC
PY 2010
VL 38
IS 12
SU S
MA 173
BP U49
EP U49
PG 1
WC Critical Care Medicine
SC General & Internal Medicine
GA 684BA
UT WOS:000284520800161
ER
PT J
AU Mourlat, B
Gathion, S
Nowak, F
Labouret, NH
AF Mourlat, Benoit
Gathion, Stephanie
Nowak, Frederique
Labouret, Natalie Hoog
TI The situation of cancer chemotherapy in 2010
SO ONCOLOGIE
LA French
DT Article
C1 [Mourlat, Benoit; Labouret, Natalie Hoog] Natl Canc Inst, Dept Medicaments, Direct Soins & Vie Malad, Bethesda, MD 20892 USA.
[Gathion, Stephanie] Natl Canc Inst, Dept Parcours Soins & Vie Malad, Direct Soins & Vie Malad, Bethesda, MD USA.
RP Mourlat, B (reprint author), Natl Canc Inst, Dept Medicaments, Direct Soins & Vie Malad, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER FRANCE
PI PARIS
PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE
SN 1292-3818
J9 ONCOLOGIE
JI Oncologie
PD DEC
PY 2010
VL 12
IS 11-12
BP 687
EP 708
DI 10.1007/s10269-010-1961-4
PG 22
WC Oncology
SC Oncology
GA 703IU
UT WOS:000285972400009
ER
PT J
AU Long, GH
Sinha, D
Read, AF
Pritt, S
Kline, B
Harvill, ET
Hudson, PJ
Bjornstad, ON
AF Long, Grainne H.
Sinha, Divya
Read, Andrew F.
Pritt, Stacy
Kline, Barry
Harvill, Eric T.
Hudson, Peter J.
Bjornstad, Ottar N.
TI Identifying the Age Cohort Responsible for Transmission in a Natural
Outbreak of Bordetella bronchiseptica
SO PLOS PATHOGENS
LA English
DT Article
ID HOST-NEMATODE SYSTEM; PASTEURELLA-MULTOCIDA; PATHOGEN TRANSMISSION;
POPULATION-DYNAMICS; MYCOBACTERIUM-BOVIS; INFECTIOUS AGENTS; DISEASE;
EPIDEMIOLOGY; MODELS; PREVALENCE
AB Identifying the major routes of disease transmission and reservoirs of infection are needed to increase our understanding of disease dynamics and improve disease control. Despite this, transmission events are rarely observed directly. Here we had the unique opportunity to study natural transmission of Bordetella bronchiseptica - a directly transmitted respiratory pathogen with a wide mammalian host range, including sporadic infection of humans - within a commercial rabbitry to evaluate the relative effects of sex and age on the transmission dynamics therein. We did this by developing an a priori set of hypotheses outlining how natural B. bronchiseptica infections may be transmitted between rabbits. We discriminated between these hypotheses by using force-of-infection estimates coupled with random effects binomial regression analysis of B. bronchiseptica age-prevalence data from within our rabbit population. Force-of-infection analysis allowed us to quantify the apparent prevalence of B. bronchiseptica while correcting for age structure. To determine whether transmission is largely within social groups (in this case litter), or from an external group, we used random-effect binomial regression to evaluate the importance of social mixing in disease spread. Between these two approaches our results support young weanlings - as opposed to, for example, breeder or maternal cohorts - as the age cohort primarily responsible for B. bronchiseptica transmission. Thus age-prevalence data, which is relatively easy to gather in clinical or agricultural settings, can be used to evaluate contact patterns and infer the likely age-cohort responsible for transmission of directly transmitted infections. These insights shed light on the dynamics of disease spread and allow an assessment to be made of the best methods for effective long-term disease control.
C1 [Long, Grainne H.; Read, Andrew F.; Harvill, Eric T.; Hudson, Peter J.; Bjornstad, Ottar N.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Read, Andrew F.; Bjornstad, Ottar N.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Pritt, Stacy; Kline, Barry] Covance Res Prod Inc, Denver, PA USA.
RP Long, GH (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM grainne.long@lshtm.ac.uk
RI Bjornstad, Ottar/I-4518-2012; Long, Grainne/B-3635-2012
OI Long, Grainne/0000-0001-5080-9885
FU Center for Infectious Disease, NSF [EF-0520468]; NIH [GM083113]
FX This research was supported by a Center for Infectious Disease Dynamics
Postdoctoral Fellowship (GHL), NSF grant EF-0520468 as part of the joint
NSF-NIH Ecology of Infectious Disease program (PJH) and NIH grant
GM083113 (ETH) and benefited from the RAPIDD working group on zoonoses
and emerging disease threats. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 46
TC 3
Z9 3
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD DEC
PY 2010
VL 6
IS 12
AR e1001224
DI 10.1371/journal.ppat.1001224
PG 10
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 698IM
UT WOS:000285587500012
PM 21187891
ER
PT J
AU Keselman, A
Rosemblat, G
Kilicoglu, H
Fiszman, M
Jin, HL
Shin, D
Rindflesch, TC
AF Keselman, Alla
Rosemblat, Graciela
Kilicoglu, Halil
Fiszman, Marcelo
Jin, Honglan
Shin, Dongwook
Rindflesch, Thomas C.
TI Adapting Semantic Natural Language Processing Technology to Address
Information Overload in Influenza Epidemic Management
SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE AND TECHNOLOGY
LA English
DT Article
ID TEXT
AB The explosion of disaster health information results in information overload among response professionals. The objective of this project was to determine the feasibility of applying semantic natural language processing (NLP) technology to addressing this overload. The project characterizes concepts and relationships commonly used in disaster health-related documents on influenza pandemics, as the basis for adapting an existing semantic summarizer to the domain. Methods include human review and semantic NLP analysis of a set of relevant documents. This is followed by a pilot test in which two information specialists use the adapted application for a realistic information-seeking task. According to the results, the ontology of influenza epidemics management can be described via a manageable number of semantic relationships that involve concepts from a limited number of semantic types. Test users demonstrate several ways to engage with the application to obtain useful information. This suggests that existing semantic NLP algorithms can be adapted to support information summarization and visualization in influenza epidemics and other disaster health areas. However, additional research is needed in the areas of terminology development (as many relevant relationships and terms are not part of existing standardized vocabularies), NLP, and user interface design.
C1 [Keselman, Alla; Rosemblat, Graciela; Fiszman, Marcelo; Jin, Honglan; Shin, Dongwook; Rindflesch, Thomas C.] Natl Lib Med, Bethesda, MD 20894 USA.
[Kilicoglu, Halil] Concordia Univ, Montreal, PQ, Canada.
RP Keselman, A (reprint author), Natl Lib Med, Bethesda, MD 20894 USA.
EM keselmana@mail.nih.gov; grosemblat@mail.nih.gov; kilicoglu@mail.nih.gov;
fiszmanm@mail.nih.gov; shindongwoo@mail.nih.gov;
trindflesch@mail.nih.gov
FU National Institutes of Health, National Library of Medicine
FX This study was supported in part by the Intramural Research Program of
the National Institutes of Health, National Library of Medicine.
NR 28
TC 4
Z9 4
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1532-2882
J9 J AM SOC INF SCI TEC
JI J. Am. Soc. Inf. Sci. Technol.
PD DEC
PY 2010
VL 61
IS 12
BP 2531
EP 2543
DI 10.1002/asi.21414
PG 13
WC Computer Science, Information Systems; Information Science & Library
Science
SC Computer Science; Information Science & Library Science
GA 680KP
UT WOS:000284231100012
ER
PT J
AU Jacobs, MA
Stearns, V
Wolff, AC
Macura, K
Argani, P
Khouri, N
Tsangaris, T
Barker, PB
Davidson, NE
Bhujwalla, ZM
Bluemke, DA
Ouwerkerk, R
AF Jacobs, Michael A.
Stearns, Vered
Wolff, Antonio C.
Macura, Katarzyna
Argani, Pedram
Khouri, Nagi
Tsangaris, Theodore
Barker, Peter B.
Davidson, Nancy E.
Bhujwalla, Zaver M.
Bluemke, David A.
Ouwerkerk, Ronald
TI Multiparametric Magnetic Resonance Imaging, Spectroscopy and
Multinuclear (Na-23) Imaging Monitoring of Preoperative Chemotherapy for
Locally Advanced Breast Cancer
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Breast; magnetic resonance imaging; sodium MR; Na-23; spectroscopy;
proton; advanced cancer
ID H-1 MR SPECTROSCOPY; APPARENT DIFFUSION-COEFFICIENT; TISSUE SODIUM
CONCENTRATION; SURGICAL ADJUVANT BREAST; QUANTUM-FILTERED NA-23;
CONTRAST-ENHANCED MRI; NEOADJUVANT CHEMOTHERAPY; IN-VIVO; SYSTEMIC
THERAPY; HUMAN BRAIN
AB Rationale and Objectives: The aim of this prospective study was to investigate using multiparametric and multinuclear magnetic resonance imaging during preoperative systemic therapy for locally advanced breast cancer.
Materials and Methods: Women with operable stage 2 or 3 breast cancer who received preoperative systemic therapy were studied using dynamic contrast-enhanced magnetic resonance imaging, magnetic resonance spectroscopy, and Na-23 magnetic resonance. Quantitative metrics of choline peak signal-to-noise ratio, total tissue sodium concentration, tumor volumes, and Response Evaluation Criteria in Solid Tumors were determined and compared to final pathologic results using receiver-operating characteristic analysis. Hormonal markers were investigated. Statistical significance was set at P < .05.
Results: Eighteen eligible women were studied. Fifteen responded to therapy, four (22%) with pathologic complete response and 11(61%) with pathologic partial response. Three patients (17%) had no response. Among estrogen receptor-positive, HER2-positive, and triple-negative phenotypes, observed frequencies of pathologic complete response, pathologic partial response, and no response were 2, 5, and 0; 1, 4, and 0; and 1, 1, and 3, respectively. Responders (pathologic complete response and pathologic partial response) had the largest reductions in choline signal-to-noise ratio (35%, from 7.2 +/- 2.3 to 4.6 +/- 2; P < .01) compared to nonresponders (11%, from 8.4 +/- 2.7 to 7.5 +/- 3.6; P = .13) after the first cycle. Total tissue sodium concentration significantly decreased in responders (27%, from 66 +/- 18 to 48.4 +/- 8 mmol/L; P = .01), while there was little change in nonresponders (51.7 +/- 7.6 to 56.5 +/- 1.6 mmol/L; P = .50). Lesion volume decreased in responders (40%, from 78 +/- 78 to 46 +/- 51 mm(3); P = .01) and nonresponders (21%, from 100 +/- 104 to 79.2 +/- 87 mm(3); P = .23) after the first cycle. The largest reduction in Response Evaluation Criteria in Solid Tumors occurred after the first treatment in responders (18%, from 24.5 +/- 20 to 20.2 +/- 18 mm; P = .01), with a slight decrease in tumor diameter noted in nonresponders (17%, from 23 +/- 19 to 19.2 +/- 19.1 mm; P = .80).
Conclusions: Multiparametric and multinuclear imaging parameters were significantly reduced after the first cycle of preoperative systemic therapy in responders, specifically, choline signal-to-noise ratio and sodium. These new surrogate radiologic biomarkers maybe able to predict and provide a platform for potential adaptive therapy in patients.
C1 [Jacobs, Michael A.; Macura, Katarzyna; Khouri, Nagi; Barker, Peter B.; Bhujwalla, Zaver M.; Bluemke, David A.; Ouwerkerk, Ronald] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA.
[Jacobs, Michael A.; Stearns, Vered; Wolff, Antonio C.; Argani, Pedram; Tsangaris, Theodore; Davidson, Nancy E.; Bhujwalla, Zaver M.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
[Argani, Pedram] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Bluemke, David A.] Ctr Clin, Bethesda, MD 20892 USA.
[Ouwerkerk, Ronald] Natl Inst Diabet & Digest & Kidney Dis NIDKK, Natior Inst Diabet & Digest & Kidney Dis, Bethesda, MD 20892 USA.
RP Jacobs, MA (reprint author), Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Traylor Bldg,Room 217,712 Rutland Ave, Baltimore, MD 21205 USA.
EM mikej@mri.jhu.edu
RI Jacobs, Michael/G-2901-2010;
OI Wolff, Antonio/0000-0003-3734-1063; Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health (Bethesda, MD) [R01CA100184, R01CA125258,
P50CA103175, 5P30CA06973, Breast SPORE CA88843, Avon:01-2009-031,
U01CA070095]
FX This work was supported in part by grants R01CA100184, R01CA125258,
P50CA103175, 5P30CA06973, Breast SPORE CA88843, Avon:01-2009-031, and
U01CA070095 from the National Institutes of Health (Bethesda, MD).
NR 51
TC 21
Z9 23
U1 2
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
J9 ACAD RADIOL
JI Acad. Radiol.
PD DEC
PY 2010
VL 17
IS 12
BP 1477
EP 1485
DI 10.1016/j.acra.2010.07.009
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 684ML
UT WOS:000284553900004
PM 20863721
ER
PT J
AU Hou, X
Kim, HO
Alexander, V
Kim, K
Choi, S
Park, SG
Lee, JH
Yoo, LS
Gao, ZG
Jacobson, KA
Jeong, LS
AF Hou, Xiyan
Kim, Hea Ok
Alexander, Varughese
Kim, Kyunglim
Choi, Sun
Park, Seul-gi
Lee, Jin Hee
Yoo, Lena S.
Gao, Zhan-Guo
Jacobson, Kenneth A.
Jeong, Lak Shin
TI Discovery of A New Human A(2A) Adenosine Receptor Agonist, Truncated
2-Hexynyl-4 '-thioadenosine
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE A(2A) adenosine receptor agonists; truncated 2-hexynyl-4
'-thioadenosine; palladium-catalyzed cross-coupling reactions; binding
mode
ID ADENINE-DERIVATIVES; SELECTIVE AGONISTS; HIGHLY POTENT; A(3);
ANTAGONISTS; D-4'-THIOADENOSINE; AFFINITY; LIGANDS; BRAIN
AB The truncated C2- and C8-substituted 4'-thioadenosine derivatives 4a-d were synthesized from D-mannose, using palladium-Catalyzed cross-coupling reactions as key steps. In this study, an A(3) adenosine receptor. (AR) antagonist, truncated 4'-thioadenosine derivative 3, was successfully converted into a potent A(2A) AR agonist 4a (K-i = 7.19 +/- 0.6 nM) by appending a 2-hexynyl group at the C2-position of a derivative of 3 that was N-6-substituted. However, C8-substitution greatly reduced binding affinity at the human A(2A) AR. All synthesized compounds 4a-d maintained their affinity at the human A(3) AR, but 4a was found to be a competitive A(3) AR antagonist/A(2A) AR agonist in cyclic AMP assays. This study indicates that the truncated C2-substituted 4'-thioadenosine derivatives 4a and 4b can serve as novel templates for the development of new A(2A) AR ligands.
C1 [Hou, Xiyan; Kim, Hea Ok; Alexander, Varughese; Kim, Kyunglim; Choi, Sun; Park, Seul-gi; Lee, Jin Hee; Jeong, Lak Shin] Ewha Womans Univ, Med Chem Lab, Coll Pharm, Seoul 120750, South Korea.
[Yoo, Lena S.; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Jeong, Lak Shin] Ewha Womans Univ, Dept Bioinspired Sci, Seoul 120750, South Korea.
RP Jeong, LS (reprint author), Ewha Womans Univ, Med Chem Lab, Coll Pharm, Seoul 120750, South Korea.
EM lakjeong@ewha.ac.kr
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU National Research Foundation (NRF) (Korea) [NRF-2008-314-E00304,
R15-2006-020, R31-2008-000-10010-0]; NIDDK, NIH (Bethesda, MD)
FX This work was supported by the Basic Science Research grant
(NRF-2008-314-E00304), the National Core Research Center grant
(R15-2006-020), the World Class University grant (R31-2008-000-10010-0)
from National Research Foundation (NRF) (Korea), and the Intramural
Research Program of NIDDK, NIH (Bethesda, MD).
NR 28
TC 12
Z9 12
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-5875
J9 ACS MED CHEM LETT
JI ACS Med. Chem. Lett.
PD DEC
PY 2010
VL 1
IS 9
BP 516
EP 520
DI 10.1021/ml1001823
PG 5
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 693PW
UT WOS:000285237000012
ER
PT J
AU Huang, J
Bu, LH
Xie, J
Chen, K
Cheng, Z
Li, XG
Chen, XY
AF Huang, Jing
Bu, Lihong
Xie, Jin
Chen, Kai
Cheng, Zhen
Li, Xingguo
Chen, Xiaoyuan
TI Effects of Nanoparticle Size on Cellular Uptake and Liver MRI with
Polyvinylpyrrolidone-Coated Iron Oxide Nanoparticles
SO ACS NANO
LA English
DT Article
DE magnetic nanoparticles; Iron oxide; magnetic resonance imaging; size
dependent
ID MAGNETIC NANOPARTICLES; CONTRAST AGENTS; IN-VIVO; BIOMEDICAL
APPLICATIONS; NANOCRYSTALS; CELLS; RELAXIVITY; DIAGNOSIS; PARTICLES;
DESIGN
AB The effect of nanoparticle size (30-120 nm) on magnetic resonance imaging (MRI) of hepatic lesions in vivo has been systematically examined using polyvinylpyrrolidone (PVP)-coated iron oxide nanopartides (PVP-10s). Such biocompatible PVP-10s with different sizes were synthesized by a simple one-pot pyrolysis method. These PVP-10s exhibited good crystallinity and high T(2) relaxivities, and the relaxivity increased with the size of the magnetic nanopartides. It was found that cellular uptake changed with both size and surface physiochemical properties, and that PVP-10-37 with a core size of 37 nm and hydrodynamic particle size of 100 nm exhibited higher cellular uptake rate and greater distribution than other PVP-10s and Feridex. We systematically investigated the effect of nanoparticle size on MRI of normal liver and hepatic lesions in vivo. The physical and chemical properties of the nanoparticles influenced their pharmacokinetic behavior, which ultimately determined their ability to accumulate in the liver. The contrast enhancement of PVP-10s within the liver was highly dependent on the overall size of the nanopartides, and the 100 nm PVP-10-37 nanopartides exhibited the greatest enhancement. These results will have implications in designing engineered nanoparticles that are optimized as MR contrast agents or for use in therapeutics.
C1 [Huang, Jing; Li, Xingguo] Peking Univ, BNLMS, State Key Lab Rare Earth Mat Chem & Applicat, Coll Chem & Mol Engn, Beijing 100871, Peoples R China.
[Huang, Jing; Bu, Lihong; Chen, Kai; Cheng, Zhen; Chen, Xiaoyuan] Stanford Univ, Dept Radiol & Bio X Program, Stanford, CA 94305 USA.
[Xie, Jin; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[Bu, Lihong] Harbin Med Coll, Hosp 4, Dept Radiol, Harbin 150001, Heilongjiang, Peoples R China.
RP Li, XG (reprint author), Peking Univ, BNLMS, State Key Lab Rare Earth Mat Chem & Applicat, Coll Chem & Mol Engn, Beijing 100871, Peoples R China.
EM xgli@pku.edu.cn; shawn.chen@nih.gov
RI Xie, Jin/E-8193-2010; Cheng, Zhen/K-2843-2012
FU NIH, National Institute of Biomedical Imaging and Bioengineering;
National Science Foundation of China (NSFC) [20971009, 20821091];
Ministry of Science and Technology (MOST) of China [2009CB939902,
2010CB631301]
FX This research was supported in part by the Intramural Research Program
of the NIH, including the National Institute of Biomedical Imaging and
Bioengineering, by the National Science Foundation of China (NSFC) (No.
20971009 and 20821091), and by the Ministry of Science and Technology
(MOST) of China (No. 2009CB939902 and 2010CB631301). We thank Dr. Henry
S. Eden for proof-reading the manuscript.
NR 53
TC 179
Z9 185
U1 12
U2 156
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
J9 ACS NANO
JI ACS Nano
PD DEC
PY 2010
VL 4
IS 12
BP 7151
EP 7160
DI 10.1021/nn101643u
PG 10
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA 696NW
UT WOS:000285449100015
PM 21043459
ER
PT J
AU Czerwinski, A
Valenzuela, F
Afonine, P
Dauter, M
Dauter, Z
AF Czerwinski, Andrzej
Valenzuela, Francisco
Afonine, Pavel
Dauter, Miroslawa
Dauter, Zbigniew
TI N-{N-[2-(3,5-Difluorophenyl)acetyl]-(S)-alanyl}-(S)-phenylglycine
tert-butyl ester (DAPT): an inhibitor of gamma-secretase, revealing fine
electronic and hydrogen-bonding features
SO ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS
LA English
DT Article
ID ALZHEIMERS-DISEASE; IN-VIVO; BETA-SECRETASE; NOTCH; DENSITY; REFINEMENT;
TARGET; BRAIN; CELLS; FLUID
AB The title compound, C23H26F2N2O4, is a dipeptidic inhibitor of gamma-secretase, one of the enzymes involved in Alzheimer's disease. The molecule adopts a compact conformation, without intramolecular hydrogen bonds. In the crystal structure, one of the amide N atoms forms the only intermolecular N-H center dot center dot center dot O hydrogen bond; the second amide N atom does not form hydrogen bonds. High-resolution synchrotron diffraction data permitted the unequivocal location and refinement without restraints of all H atoms, and the identification of the characteristic shift of the amide H atom engaged in the hydrogen bond from its ideal position, resulting in a more linear hydrogen bond. Significant residual densities for bonding electrons were revealed after the usual SHELXL refinement, and modeling of these features as additional interatomic scatterers (IAS) using the program PHENIX led to a significant decrease in the R factor from 0.0411 to 0.0325 and diminished the r.m.s. deviation level of noise in the final difference Fourier map from 0.063 to 0.037 e angstrom (3).
C1 [Dauter, Miroslawa] NCI, Basic Res Program, SAIC Frederick Inc,Biosci Div, Synchrotron Radiat Res Sect,MCL,Argonne Natl Lab, Argonne, IL 60439 USA.
[Czerwinski, Andrzej; Valenzuela, Francisco] Peptides Int Inc, Louisville, KY 40299 USA.
[Afonine, Pavel] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
[Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab,Biosci Div, Argonne, IL 60439 USA.
RP Dauter, M (reprint author), NCI, Basic Res Program, SAIC Frederick Inc,Biosci Div, Synchrotron Radiat Res Sect,MCL,Argonne Natl Lab, Bldg 202, Argonne, IL 60439 USA.
EM dauter@anl.gov
FU National Cancer Institute [NO1-CO-12400]; US Department of Energy
[W-31-109-Eng-38]
FX Richard Gildea and Luc Bourhis are thanked for their help with using
smtbx tools. This work was funded in part with federal funds from the
National Cancer Institute under contract No. NO1-CO-12400. The X-ray
data were collected at the SERCAT 22ID beamline of the Advanced Photon
Source, Argonne National Laboratory; use of the APS was supported by the
US Department of Energy under contract No. W-31-109-Eng-38.
NR 33
TC 2
Z9 2
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0108-2701
J9 ACTA CRYSTALLOGR C
JI Acta Crystallogr. Sect. C-Cryst. Struct. Commun.
PD DEC
PY 2010
VL 66
BP O585
EP O588
DI 10.1107/S0108270110044136
PN 12
PG 4
WC Chemistry, Multidisciplinary; Crystallography
SC Chemistry; Crystallography
GA 692FD
UT WOS:000285137500013
PM 21123889
ER
PT J
AU North, KE
Franceschini, N
Avery, CL
Baird, L
Graff, M
Leppert, M
Chung, JH
Zhang, JH
Hanis, C
Boerwinkle, E
Volcik, KA
Grove, ML
Mosley, TH
Gu, C
Heiss, G
Pankow, JS
Couper, DJ
Ballantyne, CM
Kao, WHL
Weder, AB
Cooper, RS
Ehret, GB
O'Connor, AA
Chakravarti, A
Hunt, SC
AF North, Kari E.
Franceschini, Nora
Avery, Christy L.
Baird, Lisa
Graff, Mariaelisa
Leppert, Mark
Chung, Jay H.
Zhang, Jinghui
Hanis, Craig
Boerwinkle, Eric
Volcik, Kelly A.
Grove, Megan L.
Mosley, Thomas H.
Gu, Charles
Heiss, Gerardo
Pankow, James S.
Couper, David J.
Ballantyne, Christie M.
Kao, W. H. Linda
Weder, Alan B.
Cooper, Richard S.
Ehret, Georg B.
O'Connor, Ashley A.
Chakravarti, Aravinda
Hunt, Steven C.
TI Variation in the checkpoint kinase 2 gene is associated with type 2
diabetes in multiple populations
SO ACTA DIABETOLOGICA
LA English
DT Article
DE CHEK2 gene; CHEK2 SNPs; Type 2 diabetes; Family Blood Pressure Program;
Atherosclerosis Risk in Communities Study
ID ENDOPLASMIC-RETICULUM STRESS; BLOOD-PRESSURE PROGRAM; DNA-DAMAGE
CHECKPOINTS; ATHEROSCLEROSIS RISK; INSULIN-RESISTANCE; COMMUNITIES;
MELLITUS; INSIGHTS; EPIDEMIOLOGY; HYPERTENSION
AB Identification and characterization of the genetic variants underlying type 2 diabetes susceptibility can provide important understanding of the etiology and pathogenesis of type 2 diabetes. We previously identified strong evidence of linkage for type 2 diabetes on chromosome 22 among 3,383 Hypertension Genetic Epidemiology Network (HyperGEN) participants from 1,124 families. The checkpoint 2 (CHEK2) gene, an important mediator of cellular responses to DNA damage, is located 0.22 Mb from this linkage peak. In this study, we tested the hypothesis that the CHEK2 gene contains one or more polymorphic variants that are associated with type 2 diabetes in HyperGEN individuals. In addition, we replicated our findings in two other Family Blood Pressure Program (FBPP) populations and in the population-based Atherosclerosis Risk in Communities (ARIC) study. We genotyped 1,584 African-American and 1,531 white HyperGEN participants, 1,843 African-American and 1,569 white GENOA participants, 871 African-American and 1,009 white GenNet participants, and 4,266 African-American and 11,478 white ARIC participants for four single nucleotide polymorphisms (SNPs) in CHEK2. Using additive models, we evaluated the association of CHEK2 SNPs with type 2 diabetes in participants within each study population stratified by race, and in a meta-analysis, adjusting for age, age 2, sex, sex-by-age interaction, study center, and relatedness. One CHEK2 variant, rs4035540, was associated with an increased risk of type 2 diabetes in HyperGEN participants, two replication samples, and in the meta-analysis. These results may suggest a new pathway in the pathogenesis of type 2 diabetes that involves pancreatic beta-cell damage and apoptosis.
C1 [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27516 USA.
[North, Kari E.; Franceschini, Nora; Avery, Christy L.; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA.
[Baird, Lisa; Leppert, Mark] Univ Utah, Dept Human Genet, Salt Lake City, UT USA.
[Graff, Mariaelisa] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27516 USA.
[Graff, Mariaelisa] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27516 USA.
[Chung, Jay H.] NHLBI, Lab Biochem Genet, Bethesda, MD 20892 USA.
[Zhang, Jinghui] Ctr Biomed Informat & Informat Technol, Rockville, MD USA.
[Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Sect Atherosclerosis & Vasc Med, Houston, TX 77030 USA.
[Couper, David J.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27516 USA.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Gu, Charles] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Gu, Charles] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Geriatr Med, Jackson, MS 39216 USA.
[Hanis, Craig; Boerwinkle, Eric; Volcik, Kelly A.; Grove, Megan L.] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Weder, Alan B.] Univ Michigan, Sch Med, Div Hypertens, Ann Arbor, MI USA.
[Cooper, Richard S.] Loyola Univ, Sch Med, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA.
[Ehret, Georg B.; O'Connor, Ashley A.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Hunt, Steven C.] Univ Utah, Sch Med, Div Cardiovasc Genet, Salt Lake City, UT USA.
RP North, KE (reprint author), Univ N Carolina, Carolina Ctr Genome Sci, 137 E Franklin St,Suite 306, Chapel Hill, NC 27516 USA.
EM kari_north@unc.edu; mgraff@unc.edu
RI EHRET, Georg/A-9532-2009; Gu, Charles/A-7934-2010;
OI EHRET, Georg/0000-0002-5730-0675; Gu, Charles/0000-0002-8527-8145;
Pankow, James/0000-0001-7076-483X
FU National Heart, Lung and Blood Institute (NHLBI), Bethesda, MD [HL54471,
HL54472, HL54473, HL54495, HL54496, HL54509, HL54515]; NHLBI
[N01-HC-55015, N01-HC-55016, N01-HC55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021, N01-HC-55022]
FX The following investigators are associated with the Family Blood
Pressure Program: GenNet Network: Alan B. Weder (Network Director),
Lillian Gleiberman (Network Coordinator), Anne E. Kwitek, Aravinda
Chakravarti, Richard S. Cooper, Carolina Delgado, Howard J. Jacob, and
Nicholas J. Schork. GENOA Network: Eric Boerwinkle (Network Director),
Tom Mosley, Alanna Morrison, Kathy Klos, Craig Hanis, Sharon Kardia, and
Stephen Turner. HyperGEN Network: Steven C. Hunt (Network Director),
Janet Hood, Donna Arnett, John H. Eckfeldt, R. Curtis Ellison, Chi Gu,
Gerardo Heiss, Paul Hopkins, Aldi T. Kraja, Jean-Marc Lalouel, Mark
Leppert, Albert Oberman, Michael A. Province, D. C. Rao, Treva Rice, and
Robert Weiss. SAPPHIRe Network: David Curb (Network Director), David
Cox, Timothy Donlon, Victor Dzau, John Grove, Kamal Masaki, Richard
Myers, Richard Olshen, Richard Pratt, Tom Quertermous, Neil Risch and
Beatriz Rodriguez. National Heart, Lung, and Blood Institute: Dina
Paltoo and Cashell E. Jaquish. Web Site:
http://www.biostat.wustl.edu/fbpp/FBPP.shtml. The Family Blood Pressure
Program Project is supported by cooperative agreement grants HL54471,
HL54472, HL54473, HL54495, HL54496, HL54509, HL54515 from the National
Heart, Lung and Blood Institute (NHLBI), Bethesda, MD. The
Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by NHLBI contracts N01-HC-55015,
N01-HC-55016, N01-HC55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and
N01-HC-55022. The authors thank the staff and participants of the FBPP
and ARIC study for their important contributions.
NR 28
TC 2
Z9 2
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0940-5429
J9 ACTA DIABETOL
JI Acta Diabetol.
PD DEC
PY 2010
VL 47
SU 1
BP S199
EP S207
DI 10.1007/s00592-009-0162-z
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 752GR
UT WOS:000289680000028
PM 19855918
ER
PT J
AU Asad, N
Karmaliani, R
Sullaiman, N
Bann, CM
McClure, EM
Pasha, O
Wright, LL
Goldenberg, RL
AF Asad, Nargis
Karmaliani, Rozina
Sullaiman, Nasreen
Bann, Carla M.
McClure, Elizabeth M.
Pasha, Omrana
Wright, Linda L.
Goldenberg, Robert L.
TI Prevalence of suicidal thoughts and attempts among pregnant Pakistani
women
SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA
LA English
DT Article
DE Suicidal thoughts; suicide attempts; pregnancy; abuse;
anxiety/depression
ID RISK-FACTORS; MATERNAL MORTALITY; PREVENTION; DEPRESSION; BANGLADESH;
MORBIDITY; IDEATION; VIOLENCE; ANXIETY
AB Objective. To determine the prevalence of suicidal thoughts and attempts and to identify demographic variables and mental health correlates such as anxiety/depression and domestic violence among pregnant women in an urban community in Pakistan. Design. Cross-sectional data from a prospective cohort study are presented. Setting. Women enrolled in an antenatal care clinic and followed to delivery in an urban area of Pakistan. Population. Cohort of pregnant women in Pakistan. Methods. A total of 1,369 pregnant women were enrolled and interviewed regarding various maternal characteristics and pregnancy outcomes, and were asked specific questions about suicidal thoughts and attempts and administered the Aga Khan University Anxiety Depression Scale at 20-26 weeks of gestation. Main outcome measures. Suicidal thoughts and attempts, verbal, sexual or physical abuse. Results. Overall, 148 of the 1,369 (11%) women studied had considered suicide. Of these, 148 women, 67 (45%) had attempted suicide. In all, 18% of the women were classified as having depression/anxiety, almost half (48%) reported experiencing verbal abuse and 20% reported physical/sexual abuse. Women who had anxiety/depression or had experienced verbal or physical/sexual abuse were significantly more likely to have had suicidal thoughts and attempts. Conclusions. Women at the greatest risk for having suicidal thoughts or a suicide attempt were those who were depressed/anxious and had experienced some form of domestic abuse. With the high prevalence of these conditions, attention should be given to the establishment of effective mental health treatment programs for pregnant women.
C1 [Asad, Nargis] Aga Khan Univ, Dept Psychiat, Karachi 74800, Pakistan.
[Bann, Carla M.; McClure, Elizabeth M.] Res Triangle Inst, Durham, NC USA.
[Goldenberg, Robert L.] Drexel Univ, Philadelphia, PA 19104 USA.
[Wright, Linda L.] NICHHD, Bethesda, MD 20892 USA.
RP Asad, N (reprint author), Aga Khan Univ, Dept Psychiat, Karachi 74800, Pakistan.
EM nargis.asad@aku.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; Aga Khan University [U01 HD040607, U01 HD040636]; Bill and
Melinda Gates Foundation
FX This study was funded through grants from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development and the Aga
Khan University (grants U01 HD040607, U01 HD040636) and the Bill and
Melinda Gates Foundation.
NR 26
TC 17
Z9 17
U1 2
U2 3
PU TAYLOR & FRANCIS AS
PI OSLO
PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY
SN 0001-6349
J9 ACTA OBSTET GYN SCAN
JI Acta Obstet. Gynecol. Scand.
PD DEC
PY 2010
VL 89
IS 12
BP 1545
EP 1551
DI 10.3109/00016349.2010.526185
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 681ME
UT WOS:000284318900008
PM 21050149
ER
PT J
AU Morgan, IG
Rose, KA
Ellwein, LB
AF Morgan, Ian G.
Rose, Kathryn A.
Ellwein, Leon B.
CA Refractive Error Study Children Su
TI Is emmetropia the natural endpoint for human refractive development? An
analysis of population-based data from the refractive error study in
children (RESC)
SO ACTA OPHTHALMOLOGICA
LA English
DT Article
DE children; development; emmetropia; emmetropization; hyperopia; myopia;
refractive error
ID BEAVER DAM EYE; VISUAL IMPAIRMENT; AUSTRALIAN CHILDREN; OCULAR
REFRACTION; OUTDOOR ACTIVITY; MINUS-LENS; MYOPIA; AGE; GROWTH;
PREVALENCE
AB Purpose:
To determine the natural end-point for refractive development during childhood.
Methods:
Cycloplegic (1% cyclopentolate) autorefraction was performed on 38 811 children aged 5 and 15 in population-based samples at eight sites in the Refractive Error Study in Children (RESC). Refractions (right eye) were categorized as myopic (<-0.5 D), emmetropic (>-0.5 to <+0.5 D), mildly hyperopic (>+0.5 to <+2.0 D and hyperopic (>+2.0 D).
Results:
At five sites (Jhapa - rural Nepal, New Delhi - urban India, Mahabubnagar - rural India, Durban - semi-urban South Africa and La Florida - urban Chile), there was < 20% myopia by age 15. Mild hyperopia was the most prevalent category at all ages, except for Mahabubnagar where emmetropia became the marginally most prevalent category at ages 14 and 15. At the other sites (Gombak - semi-urban Malaysia, Shunyi - semi-rural China and Guangzhou - urban China), there was substantial (> 35%) myopia by age 15. At these sites, mild hyperopia was the most prevalent category during early childhood, and myopia became the predominant category later. In Gombak district and Guangzhou, emmetropia was a minor category at all ages, with myopia increasing as mild hyperopia decreased. In Shunyi district, emmetropia was the most prevalent category over the ages 11-14.
Conclusion:
Emmetropia was not the predominant outcome for refractive development in children. Instead, populations were predominantly mildly hyperopic or substantial amounts of myopia appeared in them. This suggests that mild hyperopia is the natural state of refractive development in children and that emmetropia during childhood carries the risk of subsequent progression to myopia.
C1 [Morgan, Ian G.] Australian Natl Univ, ARC Ctr Excellence Vis Sci, Coll Med Biol & Environm, Canberra, ACT 2601, Australia.
[Morgan, Ian G.] Australian Natl Univ, Res Sch Biol, Coll Med Biol & Environm, Canberra, ACT 2601, Australia.
[Rose, Kathryn A.] Univ Sydney, Fac Hlth Sci, Discipline Orthopt, Lidcombe, NSW, Australia.
[Ellwein, Leon B.] NEI, NIH, Bethesda, MD 20892 USA.
RP Morgan, IG (reprint author), Australian Natl Univ, ARC Ctr Excellence Vis Sci, Coll Med Biol & Environm, GPO Box 475, Canberra, ACT 2601, Australia.
EM ian.morgan@anu.edu.au
RI Rose, Kathryn/B-4981-2009
FU World Health Organization under National Institutes of Health
[N01-EY-2103]; International Centre for Eyecare Education;
Christoffel-Blindenmission; Sight Savers International; Helen Keller
International; Ministry of Health, Government of India; Ministry of
Health, Government of Malaysia; Australian Research Council (ARC Centre
of Excellence in Vision Science) [COE561903]
FX This study was supported by the World Health Organization under National
Institutes of Health contract N01-EY-2103; International Centre for
Eyecare Education; Christoffel-Blindenmission; Sight Savers
International; Helen Keller International; Ministry of Health,
Government of India; Ministry of Health, Government of Malaysia; and the
Australian Research Council (ARC Centre of Excellence in Vision Science,
COE561903). The sponsors or funding organizations had no role in the
design or conduct of this research. No conflicting relationship exists
for any author.
NR 47
TC 18
Z9 19
U1 2
U2 12
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-375X
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD DEC
PY 2010
VL 88
IS 8
BP 877
EP 884
DI 10.1111/j.1755-3768.2009.01800.x
PG 8
WC Ophthalmology
SC Ophthalmology
GA 686LZ
UT WOS:000284699100025
PM 19958289
ER
PT J
AU Okuyemi, KS
Lawrence, D
Hammons, G
Alexander, LA
AF Okuyemi, Kolawole S.
Lawrence, Deirdre
Hammons, George
Alexander, Linda A.
TI Use of mentholated cigarettes: what can we learn from national data
sets?
SO ADDICTION
LA English
DT Editorial Material
DE Mentholated cigarettes; national data sets; secondary analysis
ID AFRICAN-AMERICAN; SMOKERS; SMOKING; EXPERIENCES; CESSATION
C1 [Okuyemi, Kolawole S.] Univ Minnesota, Sch Med, Dept Family Med & Community Hlth, Minneapolis, MN 55455 USA.
[Okuyemi, Kolawole S.] Univ Minnesota, Sch Med, Program Hlth Dispar Res, Minneapolis, MN 55455 USA.
[Lawrence, Deirdre] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Lawrence, Deirdre] Pinney Associates Inc, Bethesda Metro Ctr 3, Bethesda, MD USA.
[Hammons, George] Philander Smith Coll, Dept Chem, Little Rock, AR USA.
[Alexander, Linda A.] Univ Kentucky, Dept Hlth Behav, Coll Publ Hlth, Lexington, KY USA.
RP Okuyemi, KS (reprint author), Univ Minnesota, Sch Med, Dept Family Med & Community Hlth, Minneapolis, MN 55455 USA.
EM kokuyemi@umn.edu
NR 7
TC 5
Z9 6
U1 1
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD DEC
PY 2010
VL 105
SU 1
BP 1
EP 4
DI 10.1111/j.1360-0443.2010.03239.x
PG 4
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 682AF
UT WOS:000284366800001
PM 21059130
ER
PT J
AU Lawrence, D
Rose, A
Fagan, P
Moolchan, ET
Gibson, JT
Backinger, CL
AF Lawrence, Deirdre
Rose, Allison
Fagan, Pebbles
Moolchan, Eric T.
Gibson, James Todd
Backinger, Cathy L.
TI National patterns and correlates of mentholated cigarette use in the
United States
SO ADDICTION
LA English
DT Article
DE Menthol; tobacco; gender; race; epidemiology; ethnic groups; adult;
smoking; survey; prevalence
ID LUNG-CANCER RISK; AFRICAN-AMERICAN SMOKERS; SMOKING-CESSATION; NICOTINE
DEPENDENCE; HEALTH DISPARITIES; YOUNG-ADULTS; WHITE; MORTALITY;
EXPOSURE; BEHAVIOR
AB Aim To examine the patterns and correlates of mentholated cigarette smoking among adult smokers in the United States. Design Cross-sectional data on adult current smokers (n = 63 193) were pooled from the 2003 and 2006/07 Tobacco Use Supplements to the Current Population Survey. Measurements The associations between socio-demographic and smoking variables were examined with gender-and race/ethnicity-stratified multivariate logistic regression models predicting current use of mentholated cigarettes. Findings Multivariate logistic regression analyses demonstrated that black smokers were 10-11 times more likely to smoke mentholated cigarettes than white smokers men: odds ratio (OR): 11.59, 99% confidence interval (CI): 9.79-13.72; women: OR: 10.12, 99% CI: 8.45-12.11). With the exception of American Indian/Aleut/Eskimo smokers, non-white smokers were significantly more likely to smoke mentholated cigarettes than were white smokers. Additional significant factors associated with mentholated cigarette smoking included being unmarried (never married: OR: 1.21, 99% CI: 1.09-1.34; divorced/separated: OR: 1.13, 99% CI: 1.03-1.23), being born in a US territory (OR: 2.01, 99% CI: 1.35-3.01), living in a non-metropolitan area (OR: 0.87, 99% CI: 0.80-0.96), being unemployed (OR: 1.24, 99% CI: 1.06-1.44) and lower levels of education. Race/ethnicity-stratified analyses showed that women were more likely than men to smoke mentholated cigarettes. Among black smokers, young adults (aged 18-24 years) were four times more likely to smoke mentholated cigarettes compared with individuals aged 65+. Conclusions Race/ethnicity, gender and age are significant correlates of mentholated cigarette smoking among current smokers. Given the importance of menthol in the cigarette market and the potential untoward health effects of this additive, continued surveillance of the prevalence and correlates of mentholated cigarette use among diverse socio-demographic groups is warranted to inform appropriate interventions.
C1 [Lawrence, Deirdre; Fagan, Pebbles; Backinger, Cathy L.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Rose, Allison] NCI, Clin Res Directorate CMRP, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Moolchan, Eric T.] Alkermes Inc, Cambridge, MA USA.
[Gibson, James Todd] Informat Management Syst, Silver Spring, MD USA.
RP Lawrence, D (reprint author), Pinney Associates Inc, 3 Bethesda Metro Ctr Suite 1400, Bethesda, MD 20814 USA.
EM dlawrence@pinneyassociates.com
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX Drs Lawrence, Fagan and Backinger, Mr Gibson and Ms Rose are funded by
the National Cancer Institute. This project has been funded in whole or
in part with federal funds from the National Cancer Institute, National
Institutes of Health, under Contract no. HHSN261200800001E. 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. The authors thank Lori Alexander, MTPW, ELS, for her
assistance in editing this manuscript and Dr William Klein for his
review of the manuscript.
NR 74
TC 35
Z9 36
U1 4
U2 9
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD DEC
PY 2010
VL 105
SU 1
BP 13
EP 31
DI 10.1111/j.1360-0443.2010.03203.x
PG 19
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 682AF
UT WOS:000284366800005
PM 21059133
ER
PT J
AU Fagan, P
Moolchan, ET
Hart, A
Rose, A
Lawrence, D
Shavers, VL
Gibson, JT
AF Fagan, Pebbles
Moolchan, Eric T.
Hart, Alton, Jr.
Rose, Allison
Lawrence, Deirdre
Shavers, Vickie L.
Gibson, James Todd
TI Nicotine dependence and quitting behaviors among menthol and non-menthol
smokers with similar consumptive patterns
SO ADDICTION
LA English
DT Article
DE Menthol; nicotine dependence; light smoker; quitting; tobacco; smoking;
quit attempts; time to first cigarette
ID LUNG-CANCER RISK; ENVIRONMENTAL TOBACCO-SMOKE; AFRICAN-AMERICAN SMOKERS;
CIGARETTE-SMOKING; FAGERSTROM TEST; UNITED-STATES; LIGHT SMOKERS;
COTININE LEVELS; 1ST CIGARETTE; WHITE SMOKERS
AB Aims This study examines the associations between usual cigarette brand (i.e. menthol, non-menthol) and markers for nicotine dependence and quitting behaviors. Design The 2003 and 2006/07 Tobacco Use Supplements to the Current Population Surveys were pooled to conduct secondary data analysis. Setting National data were collected using in-person and telephone computer-assisted interviews by the United States Census Bureau among civilian, non-institutionalized people aged 15 years and older. Participants Data were analyzed among daily current smokers aged 18+ (n = 46 273). Measurements The associations between usual cigarette brand and time to first cigarette within 5 and 30 minutes after waking, quit attempts in the past 12 months and length of smoking abstinence in the past 12 months were examined. Bivariate and multivariate logistic regression models were stratified by smoking intensity: <= 5, 6-10, 11-19 and 20+ cigarettes per day. Findings Menthol smokers reported a mean of 13.05 compared with 15.01 cigarettes per day among non-menthol smokers (P < 0.001). Multivariate results showed that among smokers consuming 6-10 cigarettes per day, menthol smokers were significantly more likely than non-menthol smokers to consume their first cigarette within 5 minutes after waking (odds ratio = 1.22, 95% confidence interval = 1.05,1.43). The multivariate models did not show significant associations between usual cigarette brand and quit attempts in past 12 months or duration of smoking abstinence >2 weeks in the past 12 months. Conclusions Findings from this national survey of daily smokers demonstrate that menthol smokers in the United States who report consuming 6-10 cigarettes per day show greater signs of nicotine dependence than comparable non-menthol smokers.
C1 [Fagan, Pebbles; Lawrence, Deirdre] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Moolchan, Eric T.] Alkermes Inc, Cambridge, MA USA.
[Hart, Alton, Jr.] Virginia Commonwealth Univ, Div Qual Hlth Care, Dept Internal Med, Ctr Hlth Dispar, Richmond, VA USA.
[Rose, Allison] NCI, Clin Res Directorate, Clin Monitoring Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Shavers, Vickie L.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Gibson, James Todd] Informat Management Syst, Silver Spring, MD USA.
RP Fagan, P (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4034, Bethesda, MD 20892 USA.
EM faganp@mail.nih.gov
FU National Cancer Institute [HHSN261200800001E]; Virginia Commonwealth
University; Massey Cancer Center
FX We thank Drs Cathy Backinger and William Klein for reviewing this
manuscript. We also thank Anne Hartman and Dennis Buckman for their
advice on using the Tobacco Use Supplement to the Current Population
Survey and conducting the analyses. Support for these analyses was
provided by the National Cancer Institute. Drs Fagan, Lawrence and
Shavers and Mr Gibson were funded by the National Cancer Institute at
the time of the analyses. Allison Rose was funded by the National Cancer
Institute under contract no. HHSN261200800001E to SAIC Frederick. Dr
Hart was funded by Virginia Commonwealth University and the Massey
Cancer Center. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does the mention of trade names, commercial products or
organizations imply endorsement by the US Government.
NR 95
TC 30
Z9 32
U1 5
U2 6
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD DEC
PY 2010
VL 105
SU 1
BP 55
EP 74
DI 10.1111/j.1360-0443.2010.03190.x
PG 20
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 682AF
UT WOS:000284366800009
PM 21059137
ER
PT J
AU Gray, TR
Choo, RE
Concheiro, M
Williams, E
Elko, A
Jansson, LM
Jones, HE
Huestis, MA
AF Gray, Teresa R.
Choo, Robin E.
Concheiro, Marta
Williams, Erica
Elko, Andrea
Jansson, Lauren M.
Jones, Hendree E.
Huestis, Marilyn A.
TI Prenatal methadone exposure, meconium biomarker concentrations and
neonatal abstinence syndrome
SO ADDICTION
LA English
DT Article
DE Cocaine; meconium; methadone; neonatal abstinence syndrome; opioid;
pregnancy
ID TANDEM MASS-SPECTROMETRY; PREGNANT-WOMEN; WITHDRAWAL SYNDROME; DEPENDENT
MOTHERS; PERINATAL-PERIOD; INFANTS BORN; OPIATE USE; MAINTENANCE; DRUGS;
BUPRENORPHINE
AB Aims
Methadone is standard pharmacotherapy for opioid-dependent pregnant women, yet the relationship between maternal methadone dose and neonatal abstinence syndrome (NAS) severity is still unclear. This research evaluated whether quantification of fetal methadone and drug exposure via meconium would reflect maternal dose and predict neonatal outcomes.
Design
Prospective clinical study.
Setting
An urban drug treatment facility treating pregnant and post-partum women and their children.
Participants
Forty-nine opioid-dependent pregnant women received 30-110 mg methadone daily.
Measurements
Maternal methadone dose, infant birth parameters and NAS assessments were extracted from medical records. Thrice-weekly urine specimens were screened for opioids and cocaine. Newborn meconium specimens were quantified for methadone, opioid, cocaine and tobacco biomarkers.
Findings
There was no relationship between meconium methadone concentrations, presence of opioids, cocaine and/or tobacco in meconium, maternal methadone dose or NAS severity. Opioid and cocaine were also found in 36.7 and 38.8 of meconium specimens, respectively, and were associated with positive urine specimens in the third trimester. The presence of opioids other than methadone in meconium correlated with increased rates of preterm birth, longer infant hospital stays and decreased maternal time in drug treatment.
Conclusions
Methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) concentrations in meconium did not predict infant birth parameters or NAS severity. Prospective urine testing defined meconium drug detection windows for opiates and cocaine as 3 months, rather than the currently accepted 6 months. The presence of opioids in meconium could be used as a biomarker for infants at elevated risk in the newborn period.
C1 [Gray, Teresa R.; Concheiro, Marta; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Choo, Robin E.] Univ Pittsburgh, Titusville, PA USA.
[Williams, Erica; Elko, Andrea; Jansson, Lauren M.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Jones, Hendree E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Jones, Hendree E.] Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU NIDA, National Institutes of Health [DA12403, DA019934]
FX This study was supported by the Extramural (Grants DA12403 and DA019934)
and Intramural Research Program of the NIDA, National Institutes of
Health. We would like to acknowledge the participants, research and
clinical staff at the CAP and the JHBMC newborn nursery for their
assistance.
NR 50
TC 12
Z9 12
U1 1
U2 5
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD DEC
PY 2010
VL 105
IS 12
BP 2151
EP 2159
DI 10.1111/j.1360-0443.2010.03097.x
PG 9
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 676VK
UT WOS:000283946600021
PM 20854338
ER
PT J
AU Leventhal, AM
Waters, AJ
Moolchan, ET
Heishman, SJ
Pickworth, WB
AF Leventhal, Adam M.
Waters, Andrew J.
Moolchan, Eric T.
Heishman, Stephen J.
Pickworth, Wallace B.
TI A quantitative analysis of subjective, cognitive, and physiological
manifestations of the acute tobacco abstinence syndrome
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Tobacco abstinence; Smoking deprivation; Nicotine withdrawal; Smoking;
Tobacco dependence
ID SMOKING ABSTINENCE; NICOTINE WITHDRAWAL; ATTENTIONAL BIAS;
NEGATIVE-AFFECT; SMOKERS; PERFORMANCE; DEPENDENCE; ADDICTION; MOOD; EEG
AB Rationale: Previous studies have documented the existence of signs and symptoms of the acute tobacco abstinence syndrome; however, less attention has been paid to quantifying the magnitude of these effects. Objective: The present study quantified the relative magnitude of subjective, cognitive, and physiological manifestations of acute tobacco abstinence.
Method: Smokers (N = 203, >= 15 cig/day) attended two counterbalanced laboratory sessions, one following 12-h of abstinence and the other following ad-lib smoking. At both sessions, they completed an extensive battery of self-report measures (withdrawal, affect, hunger, craving, subjective attentional bias towards smoking cues), physiological assessments (heart rate, blood pressure, brain EEG), and cognitive performance tasks (psychomotor processing, sustained attention, objective attentional bias).
Results: Abstinence effects were largest for craving, subjective attentional bias, negative affect, overall withdrawal severity, concentration difficulty, hunger, and heart rate. Effects were moderate for positive affect and EEG power. Effects were small, but reliable, for psychomotor speed, sustained attention, and somatic symptoms. Effects on performance-based indices of attentional bias towards smoking-related cues were small and reliable for some indices but not others. Effects were small and inconsistent for blood pressure and EEG frequency. Variation in internal consistency accounted for 33% of the variation in abstinence effect sizes across measures.
Conclusions: There was a wide range of effect sizes both across and within domains, indicating that the acute tobacco abstinence syndrome is not a monotonic phenomenon. These findings may be indicative of the relative magnitudes of signs and symptoms that the average smoker may exhibit during acute abstinence. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Leventhal, Adam M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Waters, Andrew J.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Moolchan, Eric T.; Heishman, Stephen J.; Pickworth, Wallace B.] Natl Inst Drug Abuse, Intramural Res Program, Clin Pharmacol & Therapeut Branch, Baltimore, MD USA.
RP Leventhal, AM (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, 2250 Alcazar St,CSC 240, Los Angeles, CA 90033 USA.
EM adam.leventhal@usc.edu
FU National Cancer Institute and National Institute on Drug Abuse
[P5084718]; NIH, National Institute on Drug Abuse; NIH [DA025041]
FX This research was supported by a Transdisciplinary Tobacco Use Research
Center Grant from the National Cancer Institute and National Institute
on Drug Abuse (P5084718), and by the Intramural Research Program of the
NIH, National Institute on Drug Abuse. Dr. Leventhal's effort was
supported by NIH grant (DA025041).
NR 49
TC 39
Z9 40
U1 4
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
J9 ADDICT BEHAV
JI Addict. Behav.
PD DEC
PY 2010
VL 35
IS 12
BP 1120
EP 1130
DI 10.1016/j.addbeh.2010.08.007
PG 11
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 670ER
UT WOS:000283404500012
PM 20807673
ER
PT J
AU Williams, LR
Fox, NA
Lejuez, CW
Reynolds, EK
Henderson, HA
Perez-Edgar, KE
Steinberg, L
Pine, DS
AF Williams, Lela Rankin
Fox, Nathan A.
Lejuez, C. W.
Reynolds, Elizabeth K.
Henderson, Heather A.
Perez-Edgar, Koraly E.
Steinberg, Laurence
Pine, Daniel S.
TI Early temperament, propensity for risk-taking and adolescent
substance-related problems: A prospective multi-method investigation
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Behavioral inhibition; Substance-use; Risk-taking; Longitudinal;
Adolescence
ID INNER-CITY ADOLESCENTS; BEHAVIORAL-INHIBITION; TASK BART; ANXIETY
DISORDERS; DISCONTINUITY; VALIDITY
AB One hundred thirty seven adolescents (M=15.3 yrs, SD=1.0 yr, n=72 girls) were recruited into temperament groups when they were 4 months of age based on reactivity to novel auditory/visual stimuli (Fox, Henderson, Rubin, Calkins, & Schmidt, 2001). Behavioral inhibition was observed across infancy (14 and 24 months). Additionally, self-reported substance-related problems and behavioral risk-taking was assessed during adolescence. High behavioral inhibition increased risk for substance-related problems among boys, whereas high behavioral inhibition protected against substance-related problems among girls. B=-1.18. SE=.48,95% CI = -2.13 to -.24; p<.05. Additionally, high behavioral inhibition protected lower risk-taking children from adolescent substance-related problems whereas high behavioral inhibition increased risk for substance-related problems among higher risk-taking children, B=.04, SE=.02, 95% CI=.00 to .08. Findings from this prospective, multi-informant, longitudinal study suggest that risk-taking and gender may interact with temperamental traits to place adolescents at differential risk for substance-related related behavior problems. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Williams, Lela Rankin] Arizona State Univ, Sch Social Work, Phoenix, AZ 85004 USA.
[Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
[Lejuez, C. W.; Reynolds, Elizabeth K.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA.
[Lejuez, C. W.; Reynolds, Elizabeth K.] Univ Maryland, Ctr Addict Personal & Emot Res, College Pk, MD 20742 USA.
[Henderson, Heather A.] Univ Miami, Dept Psychol, Miami, FL USA.
[Perez-Edgar, Koraly E.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[Steinberg, Laurence] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA.
[Pine, Daniel S.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
RP Williams, LR (reprint author), Arizona State Univ, Sch Social Work, 411 N Cent Ave,Suite 800, Phoenix, AZ 85004 USA.
EM lrw@asu.edu
OI Perez-Edgar, Koraly/0000-0003-4051-9563
FU National Institute of Mental Health [R01MH074454]; NICHD [R37HD17899]
FX This work was supported, in part, by National Institute of Mental Health
grant R01MH074454 and NICHD R37HD17899 (awarded to Nathan A. Fox).
NR 28
TC 14
Z9 14
U1 0
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
J9 ADDICT BEHAV
JI Addict. Behav.
PD DEC
PY 2010
VL 35
IS 12
BP 1148
EP 1151
DI 10.1016/j.addbeh.2010.07.005
PG 4
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 670ER
UT WOS:000283404500016
PM 20813463
ER
PT J
AU Sutin, AR
Costa, PT
Uda, M
Ferrucci, L
Schlessinger, D
Terracciano, A
AF Sutin, Angelina R.
Costa, Paul T., Jr.
Uda, Manuela
Ferrucci, Luigi
Schlessinger, David
Terracciano, Antonio
TI Personality and metabolic syndrome
SO AGE
LA English
DT Article
DE Metabolic syndrome; Physical health; Personality; Impulsivity; Hostility
ID 5-FACTOR MODEL; TRAITS; HEALTH; POPULATION; OVERWEIGHT; CHILDHOOD;
SUPPORT; WEIGHT; SAMPLE; ADULTS
AB The prevalence of metabolic syndrome has paralleled the sharp increase in obesity. Given its tremendous physical, emotional, and financial burden, it is of critical importance to identify who is most at risk and the potential points of intervention. Psychological traits, in addition to physiological and social risk factors, may contribute to metabolic syndrome. The objective of the present research is to test whether personality traits are associated with metabolic syndrome in a large community sample. Participants (N = 5,662) from Sardinia, Italy, completed a comprehensive personality questionnaire, the NEO-PI-R, and were assessed on all components of metabolic syndrome (waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose). Logistic regressions were used to predict metabolic syndrome from personality traits, controlling for age, sex, education, and current smoking status. Among adults over age 45 (n = 2,419), Neuroticism and low Agreeableness were associated with metabolic syndrome, whereas high Conscientiousness was protective. Individuals who scored in the top 10% on Conscientiousness were approximately 40% less likely to have metabolic syndrome (OR = 0.61, 95% CI = 0.41-0.92), whereas those who scored in the lowest 10% on Agreeableness were 50% more likely to have it (OR = 1.53, 95% CI = 1.09-2.16). At the facet level, traits related to impulsivity and hostility were the most strongly associated with metabolic syndrome. The present research indicates that those with fewer psychological resources are more vulnerable to metabolic syndrome and suggests a psychological component to other established risk factors.
C1 [Sutin, Angelina R.; Costa, Paul T., Jr.; Terracciano, Antonio] NIA, Lab Personal & Cognit, NIH, DHHS, Baltimore, MD 21224 USA.
[Ferrucci, Luigi] NIA, Clin Res Branch, NIH, DHHS, Baltimore, MD 21224 USA.
[Schlessinger, David] NIA, Genet Lab, NIH, DHHS, Baltimore, MD 21224 USA.
[Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy.
RP Sutin, AR (reprint author), NIA, Lab Personal & Cognit, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sutina@mail.nih.gov
RI terracciano, antonio/B-1884-2008;
OI Costa, Paul/0000-0003-4375-1712
FU National Institutes of Health, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging. Paul
Costa receives royalties from the Revised NEO Personality Inventory.
NR 35
TC 44
Z9 45
U1 1
U2 12
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
J9 AGE
JI Age
PD DEC
PY 2010
VL 32
IS 4
BP 513
EP 519
DI 10.1007/s11357-010-9153-9
PG 7
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 679IB
UT WOS:000284154000008
PM 20567927
ER
PT J
AU Soerensen, M
Dato, S
Christensen, K
McGue, M
Stevnsner, T
Bohr, VA
Christiansen, L
AF Soerensen, Mette
Dato, Serena
Christensen, Kaare
McGue, Matt
Stevnsner, Tinna
Bohr, Vilhelm A.
Christiansen, Lene
TI Replication of an association of variation in the FOXO3A gene with human
longevity using both case-control and longitudinal data
SO AGING CELL
LA English
DT Article
DE human longevity; Forkhead box O3A (FOXO3A); association study;
case-control and longitudinal data
ID COHORT
AB Genetic variation in FOXO3A has previously been associated with human longevity. Studies published so far have been case-control studies and hence vulnerable to bias introduced by cohort effects. In this study we extended the previous findings in the cohorts of oldest old Danes (the Danish 1905 cohort, N = 1089) and middle-aged Danes (N = 736), applying a longitudinal study design as well as the case-control study design. Fifteen SNPs were chosen in order to cover the known common variation in FOXO3A. Comparing SNP frequencies in the oldest old with middle-aged individuals, we found association (after correction for multiple testing) of eight SNPs; 4 (rs13217795, rs2764264, rs479744, and rs9400239) previously reported to be associated with longevity and four novel SNPs (rs12206094, rs13220810, rs7762395, and rs9486902 (corrected P-values 0.001-0.044). Moreover, we found association of the haplotypes TAC and CAC of rs9486902, rs10499051, and rs12206094 (corrected P-values: 0.01-0.03) with longevity. Finally, we here present data applying a longitudinal study design; when using follow-up survival data on the oldest old in a longitudinal analysis, we found no SNPs to remain significant after the correction for multiple testing (Bonferroni correction). Hence, our results support and extent the proposed role of FOXO3A as a candidate longevity gene for survival from younger ages to old age, yet not during old age.
C1 [Soerensen, Mette; Dato, Serena; Christensen, Kaare; McGue, Matt; Christiansen, Lene] Univ So Denmark, Danish Aging Res Ctr, Inst Publ Hlth, DK-5000 Odense C, Denmark.
[Soerensen, Mette; Dato, Serena; Christiansen, Lene] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark.
[Dato, Serena] Univ Calabria, Dept Cell Biol, I-87036 Arcavacata Di Rende, Cs, Italy.
[McGue, Matt] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
[Stevnsner, Tinna; Bohr, Vilhelm A.] Univ Aarhus, Danish Aging Res Ctr, Dept Mol Biol, DK-8000 Aarhus C, Denmark.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Soerensen, M (reprint author), Univ So Denmark, Danish Aging Res Ctr, Inst Publ Hlth, JB Winsloews Vej 9B, DK-5000 Odense C, Denmark.
EM msoerensen@health.sdu.dk
RI Christensen, Kaare/C-2360-2009; Soerensen, Mette/O-1817-2015;
OI Christensen, Kaare/0000-0002-5429-5292; Soerensen,
Mette/0000-0001-5268-3366; dato, serena/0000-0003-2589-7929
FU Max-Planck Institute for Demographic Research, (Rostock, Germany);
National Institute on Aging [P01 AG08761]; European Regional Development
Fund; Novo Nordisk Foundation; Aase and Ejnar Danielsen Foundation;
Augustinus Foundation; Brodrene Hartmann Foundation; King Christian the
10th foundation; Einer Willumsens Mindelegat Foundation; VELUX
Foundation
FX This study was financially supported by the Max-Planck Institute for
Demographic Research, (Rostock, Germany), the National Institute on
Aging (P01 AG08761), the INTERREG 4 A programme
Syddanmark-Schleswig-K.E.R.N (by EU funds from the European Regional
Development Fund), the Novo Nordisk Foundation, the Aase and Ejnar
Danielsen Foundation, the Augustinus Foundation, the Brodrene Hartmann
Foundation, the King Christian the 10th foundation, and the Einer
Willumsens Mindelegat Foundation. The Danish Aging Research Center is
supported by a grant from the VELUX Foundation. Susanne Knudsen, Steen
Gregersen, Ulla Munk and Shuxia Li are thanked for excellent technical
work.
NR 14
TC 81
Z9 84
U1 0
U2 5
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD DEC
PY 2010
VL 9
IS 6
BP 1010
EP 1017
DI 10.1111/j.1474-9726.2010.00627.x
PG 8
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 678KB
UT WOS:000284071400009
PM 20849522
ER
PT J
AU Tassiopoulos, K
Read, JS
Brogly, S
Rich, K
Lester, B
Spector, SA
Yogev, R
Seage, GR
AF Tassiopoulos, Katherine
Read, Jennifer S.
Brogly, Susan
Rich, Kenneth
Lester, Barry
Spector, Stephen A.
Yogev, Ram
Seage, George R., III
TI Substance Use in HIV-Infected Women During Pregnancy: Self-Report Versus
Meconium Analysis
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Substance use; Prenatal exposure; Meconium; HIV
ID PRENATAL MARIJUANA EXPOSURE; LOW-BIRTH-WEIGHT; ALCOHOL SPECTRUM
DISORDERS; COCAINE EXPOSURE; DRUG-USE; MITOCHONDRIAL DYSFUNCTION;
MATERNAL SMOKING; LARGE-SCALE; AGE 3; TOBACCO
AB We evaluated prenatal substance use in a cohort of 480 HIV-infected women and their uninfected children Substance use was reported by 29%, the most common substances reported were tobacco (18%), alcohol (10%), and marijuana (7 2%) Fewer than 4% of women reported cocaine or opiate use Substance use was more common in the first trimester (25%) than the second (17%) and third (15%) (trend p-value <0 01), and was associated with race/ethnicity, education, birthplace, age and marital status For 264 mother/infant pairs with meconium results, sensitivity of self-report was 86% for tobacco, 80% for marijuana and 67% for cocaine Higher discordance between self-report and urine/blood toxicology was observed for cocaine, marijuana and opiates in a non-random subset of mothers/infants with these tests Findings suggest reasonably complete self-reporting of substance use as confirmed by meconium analysis Illicit substance use was low and substantially less than that reported in earlier studies of HIV-infected women but alcohol and tobacco exposure was prevalent
C1 [Tassiopoulos, Katherine; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Brogly, Susan] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Rich, Kenneth] Univ Illinois, Dept Pediat, Chicago, IL USA.
[Lester, Barry] Brown Univ, Warren Alpert Med Sch, Ctr Study Children Risk, Providence, RI 02912 USA.
[Lester, Barry] Women & Infants Hosp Rhode Isl, Providence, RI USA.
[Spector, Stephen A.] Univ Calif San Diego, Dept Pediat, Div Infect Dis, La Jolla, CA 92093 USA.
[Yogev, Ram] Childrens Mem Hosp, Sect Pediat Adolescent & Maternal HIV Infect, Chicago, IL 60614 USA.
RP Tassiopoulos, K (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge 816, Boston, MA 02115 USA.
FU NICHD NIH HHS [U01 HD052102-04, U01 HD052102, U01 HD052104, U01
HD052104-01]; NINDS NIH HHS [R01 NS077874]
NR 57
TC 18
Z9 18
U1 1
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS behav.
PD DEC
PY 2010
VL 14
IS 6
BP 1269
EP 1278
DI 10.1007/s10461-010-9705-0
PG 10
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 679CX
UT WOS:000284138100006
PM 20532607
ER
PT J
AU Rego, FFD
Mota-Miranda, A
Santos, ED
Galvao-Castro, B
Alcantara, LC
AF de Almeida Rego, Filipe Ferreira
Mota-Miranda, Aline
Santos, Edson de Souza
Galvao-Castro, Bernardo
Alcantara, Luiz Carlos
TI Seroprevalence and Molecular Epidemiology of HTLV-1 Isolates from HIV-1
Co-Infected Women in Feira de Santana, Bahia, Brazil
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID VIRUS TYPE-I; CELL LYMPHOTROPIC VIRUS; POST-COLUMBIAN INTRODUCTION;
INTRAVENOUS-DRUG-USERS; LONG TERMINAL REPEAT; LEUKEMIA-VIRUS;
PHYLOGENETIC SUBTYPES; AFRICAN ORIGIN; TYPE-1; STRAINS
AB HTLV-1/HIV-1 co-infection is associated with severe clinical manifestations, marked immunodeficiency, and opportunistic pathogenic infections, as well as risk behavior. Salvador, the capital of the State of Bahia, Brazil, has the highest HTLV-1 prevalence (1.74%) found in Brazil. Few studies exist which describe this co-infection found in Salvador and its surrounding areas, much less investigate how these viruses circulate or assess the relationship between them. To describe the epidemiological and molecular features of HTLV in HIV co-infected women. To investigate the prevalence of HTLV/HIV co-infection in surrounding areas, as well as the molecular epidemiology of HTLV, a cross sectional study was carried out involving 107 women infected with HIV-1 from the STD/HIV/AIDS Reference Center located in the neighboring City of Feira de Santana. Patient samples were submitted to ELISA, and HTLV infection was confirmed using Western Blot and Polymerase Chain Reaction (PCR). Phylogenetic analysis using Neighbor-Joining (NJ) and Maximum Likelihood (ML) was performed on HTLV LTR sequences in order to gain further insights about molecular epidemiology and the origins of this virus in Bahia. Four out of five reactive samples were confirmed to be infected with HTLV-1, and one with HTLV-2. The seroprevalence of HTLV among HIV-1 co-infected women was 4.7%. Phylogenetic analysis of the LTR region from four HTLV-1 sequences showed that all isolates were clustered into the main Latin American group within the Transcontinental subgroup of the Cosmopolitan subtype. The HTLV-2 sequence was classified as the HTLV-2c subtype. It was also observed that four HTLV/HIV-1 co-infected women exhibited risk behavior with two having parenteral exposure, while another two were sex workers. This article describes the characteristics of co-infected patients. This co-infection is known to be severe and further studies should be conducted to confirm the suggestion that HTLV-1 is spreading from Salvador to surrounding areas.
C1 [Alcantara, Luiz Carlos] NCI, NIH, Vaccine Branch, Bethesda, MD 20892 USA.
[de Almeida Rego, Filipe Ferreira; Mota-Miranda, Aline; Santos, Edson de Souza; Galvao-Castro, Bernardo; Alcantara, Luiz Carlos] Bahia Fdn Sci Dev, Bahia Sch Med & Publ Hlth, HTLV Ctr, Salvador, BA, Brazil.
[de Almeida Rego, Filipe Ferreira; Mota-Miranda, Aline; Galvao-Castro, Bernardo; Alcantara, Luiz Carlos] Fundacao Oswaldo Cruz, Goncalo Moniz Res Ctr, Adv Publ Hlth Lab, Salvador, BA, Brazil.
RP Alcantara, LC (reprint author), NCI, NIH, Vaccine Branch, Bldg 41,Room C303,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA.
EM alcantaralc@mail.nih.gov
FU FAPESB [303/03]; Brazilian Ministry of Health [306/04, 307/04]
FX Bioinformatics analysis was performed at the LASP/CPqGM/FIOCRUZ
Bioinformatics Unit, supported by FAPESB (Grants 303/03) and the
Brazilian Ministry of Health (306/04 and 307/04). The authors are
grateful to Noilson Lazaro de Souza Goncalves and Elisabeth Deliege for
their technical assistance.
NR 41
TC 3
Z9 5
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD DEC
PY 2010
VL 26
IS 12
BP 1333
EP 1339
DI 10.1089/aid.2009.0298
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 692YP
UT WOS:000285192100014
ER
PT J
AU Falk, D
Wang, XQ
Liu, L
Fertig, J
Mattson, M
Ryan, M
Johnson, B
Stout, R
Litten, RZ
AF Falk, Daniel
Wang, Xin Qun
Liu, Lei
Fertig, Joanne
Mattson, Margaret
Ryan, Megan
Johnson, Bankole
Stout, Robert
Litten, Raye Z.
TI Percentage of Subjects With No Heavy Drinking Days: Evaluation as an
Efficacy Endpoint for Alcohol Clinical Trials
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol; Treatment End Point; Outcome Measure; Heavy Drinking Days;
Topiramate; Naltrexone; Grace Period; COMBINE
ID RANDOMIZED CONTROLLED-TRIAL; COMBINED PHARMACOTHERAPIES; BEHAVIORAL
INTERVENTIONS; DEPENDENCE; COMBINE; UTILITY
AB Background: Percent subjects with no heavy drinking days (PSNHDDs), an efficacy end point recommended by the Food and Drug Administration, considers abstinent individuals or those engaging in low-risk drinking behavior as successful responders to treatment. As PSNHDD has been used infrequently in previous alcohol clinical trials, we evaluated the utility and validity of the PSNHDD outcome measure in 2 large alcohol clinical trials.
Methods: Data sets from 2 alcohol trials, COMBINE and a multisite topiramate trial, were used to analyze PSNHDDs and other traditional end points for the topiramate, naltrexone, acamprosate, and placebo groups. Effect sizes of PSNHDDs were determined for each month of active treatment and by varying grace periods-early periods in the trial where outcome is not considered in the analysis-and were compared with that of other traditional outcome measures. Longterm outcomes were compared for groups that had no heavy drinking days versus those that had heavy drinking days during active treatment.
Results: PSNHDD effect sizes were significant for both topiramate (0.34 and 0.25 at months 2 and 3, respectively) and naltrexone (0.24 and 0.26 at months 3 and 4, respectively). Given a 2-month grace period for naltrexone, the effect size of PSNHDDs was comparable to the effect sizes using traditional outcome measures. With a 1-month grace period for topiramate, it was greater than the majority of traditional outcome measures. Little is gained by allowing up to 1, 2, or 3 heavy drinking days as an end point. Subjects with no HDDs during treatment fared better than those with some HDDs on drinking outcomes and alcohol-related consequences during a 1-year follow-up.
Conclusions: PSNHDD appears to be a clinically informative end point measure, especially when used with a grace period, and is as sensitive as most traditional outcome measures in detecting differences between the medication and placebo groups. Nonetheless, these findings should be replicated in other clinical data sets, particularly with medications that work via different mechanisms.
C1 [Falk, Daniel; Fertig, Joanne; Mattson, Margaret; Ryan, Megan; Litten, Raye Z.] NIAAA, Div Treatment & Recovery Res, Bethesda, MD 20892 USA.
[Wang, Xin Qun; Liu, Lei] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
[Johnson, Bankole] Univ Virginia, Dept Psychiat Med, Charlottesville, VA USA.
[Stout, Robert] Decis Sci Inst PIRE, Pawtucket, RI USA.
RP Falk, D (reprint author), NIAAA, Div Treatment & Recovery Res, 5635 Fishers Lane,Room 2040, Bethesda, MD 20892 USA.
EM falkde@mail.nih.gov
RI Liu, Lei/B-4968-2009
OI Liu, Lei/0000-0003-1844-338X
NR 20
TC 59
Z9 59
U1 1
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD DEC
PY 2010
VL 34
IS 12
BP 2022
EP 2034
DI 10.1111/j.1530-0277.2010.01290.x
PG 13
WC Substance Abuse
SC Substance Abuse
GA 682AB
UT WOS:000284366100007
PM 20659066
ER
PT J
AU Hunninghake, GM
Soto-Quiros, ME
Avila, L
Kim, HP
Lasky-Su, J
Rafaels, N
Ruczinski, I
Beaty, TH
Mathias, RA
Barnes, KC
Wilk, JB
O'Connor, GT
Gauderman, WJ
Vora, H
Baurley, JW
Gilliland, F
Liang, C
Sylvia, JS
Klanderman, BJ
Sharma, SS
Himes, BE
Bossley, CJ
Israel, E
Raby, BA
Bush, A
Choi, AM
Weiss, ST
Celedon, JC
AF Hunninghake, G. M.
Soto-Quiros, M. E.
Avila, L.
Kim, H. P.
Lasky-Su, J.
Rafaels, N.
Ruczinski, I.
Beaty, T. H.
Mathias, R. A.
Barnes, K. C.
Wilk, J. B.
O'Connor, G. T.
Gauderman, W. James
Vora, H.
Baurley, J. W.
Gilliland, F.
Liang, C.
Sylvia, J. S.
Klanderman, B. J.
Sharma, S. S.
Himes, B. E.
Bossley, C. J.
Israel, E.
Raby, B. A.
Bush, A.
Choi, A. M.
Weiss, S. T.
Celedon, J. C.
TI TSLP polymorphisms are associated with asthma in a sex-specific fashion
SO ALLERGY
LA English
DT Article
DE asthma; genetic association; sex-specific; thymic stromal lymphopoietin;
TSLP
ID THYMIC STROMAL LYMPHOPOIETIN; CHILDHOOD ASTHMA; CELLS; INFLAMMATION;
EXPRESSION; RESPONSES; SEVERITY; DISEASE; GROWTH; MICE
AB Background: Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion.
Methods: We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of children with asthma in Costa Rica. Significant findings were replicated in whites and African-American participants in the Childhood Asthma Management Program, in African-Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children's Health Study, and in whites in the Framingham Heart Study (FHS).
Main Results: Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (P values of 2 x 10(-5) and 1 x 10(-5), respectively). In a sex-stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (P = 3 x 10(-6)). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (P = 2 x 10(-4)). Findings for rs2289276 were consistent in all cohorts except the FHS.
Conclusions: TSLP variants are associated with asthma in a sex-specific fashion.
C1 [Hunninghake, G. M.; Lasky-Su, J.; Liang, C.; Sylvia, J. S.; Klanderman, B. J.; Sharma, S. S.; Himes, B. E.; Raby, B. A.; Weiss, S. T.; Celedon, J. C.] Channing Labs, Boston, MA 02115 USA.
[Hunninghake, G. M.; Kim, H. P.; Sharma, S. S.; Israel, E.; Raby, B. A.; Choi, A. M.; Celedon, J. C.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Hunninghake, G. M.; Kim, H. P.; Lasky-Su, J.; Klanderman, B. J.; Sharma, S. S.; Israel, E.; Raby, B. A.; Choi, A. M.; Weiss, S. T.; Celedon, J. C.] Harvard Univ, Sch Med, Boston, MA USA.
[Soto-Quiros, M. E.; Avila, L.] Hosp Nacl Ninos Dr Carlos Saenz Herrera, Div Pediat Pulmonol, San Jose, Costa Rica.
[Rafaels, N.; Barnes, K. C.] Johns Hopkins Univ, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD USA.
[Ruczinski, I.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Beaty, T. H.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Mathias, R. A.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
[Wilk, J. B.; O'Connor, G. T.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Wilk, J. B.; O'Connor, G. T.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Gauderman, W. James; Vora, H.; Baurley, J. W.; Gilliland, F.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Himes, B. E.; Raby, B. A.; Weiss, S. T.; Celedon, J. C.] Brigham & Womens Hosp, Dept Med, Ctr Genom Med, Boston, MA 02115 USA.
[Himes, B. E.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Bossley, C. J.; Bush, A.] Royal Brompton Hosp, Imperial Sch Med, Natl Heart & Lung Inst, London SW3 6LY, England.
RP Celedon, JC (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA.
EM juan.celedon@channing.harvard.edu
RI Beaty, Terri/A-6032-2008
FU National Heart, Lung and Blood Institute, National Institutes of Health
[U01 HL075419, U01 HL65899, P01 HL083069, R01 HL 086601, T32 HL07427];
U.S. National Institutes of Health [HL04370, HL66289]; NIH [HL04370,
HL66289, HL 087699]; National Institutes of Health [K08HL092222];
National Heart, Lung, and Blood Institute; Mary Beryl Patch Turnbull
Scholar Program; National Heart, Lung and Blood Institute (NHLBI),
National Institutes of Health [U01 HL075419, U01 HL65899, P01 HL083069,
R01 HL086601]; National Institute of Environmental Health Sciences
(NIEHS) [P01 ES011627, P30 ES007048]; NHLBI [T32 HL07427, K08HL092222,
R01 HL087680, R01 HL087699]; NIH/NHLBI [NO1-HC25195]; National Library
of Medicine [2T15LM007092-16]
FX We thank all families for their invaluable participation in the Genetics
of Asthma in Costa Rica and the CAMP studies. We also acknowledge the
CAMP investigators and research team for their help in data collection.
We acknowledge the CAMP investigators and research team, supported by
NHLBI, for collection of CAMP Genetic Ancillary Study data. All work on
data collected from the Genetics of Asthma in Costa Rica and the CAMP
Genetic Ancillary Study was conducted at the Channing Laboratory of the
Brigham and Women's Hospital under appropriate CAMP policies and human
subject's protections. The CAMP Genetics Ancillary Study is supported by
U01 HL075419, U01 HL65899, P01 HL083069, R01 HL 086601 and T32 HL07427
from the National Heart, Lung and Blood Institute, National Institutes
of Health. The Genetics of Asthma in Costa Rica study is supported by
Grants HL04370 and HL66289 from the U.S. National Institutes of Health.
The GRAAD study is supported by NIH grant HL 087699. G.M.H. is supported
by K08HL092222 from the National Institutes of Health and the National
Heart, Lung, and Blood Institute. KCB was supported in part by the Mary
Beryl Patch Turnbull Scholar Program. We also thank Dr. Charles Alpers
for his prompt and personal responses and for his unique insight. Dr.
Celedon had full access to all of the data in the study and took
responsibility for the integrity of the data and the accuracy of the
data analysis.; The Genetics of Asthma in Costa Rica Study is supported
by NIH grants HL66289 and HL04370. The CAMP Genetics Ancillary Study is
supported by U01 HL075419, U01 HL65899, P01 HL083069 and R01 HL086601
from the National Heart, Lung and Blood Institute (NHLBI), National
Institutes of Health. The Children's Health Study is supported by P01
ES011627, and P30 ES007048 from the National Institute of Environmental
Health Sciences (NIEHS), and R01 HL087680 from the NHLBI. The Genomic
Research on the African-American Diaspora study is supported by R01
HL087699 from the NHLBI. The Framingham Heart Study is supported from
NIH/NHLBI Contract NO1-HC25195. G.M.H. is supported by K08HL092222, and
S.S.S. is supported by T32 HL07427 from the NHLBI. KCB was supported in
part by the Mary Beryl Patch Turnbull Scholar Program. B.E.H. is
supported by 2T15LM007092-16 from the National Library of Medicine.
NR 30
TC 52
Z9 53
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0105-4538
J9 ALLERGY
JI Allergy
PD DEC
PY 2010
VL 65
IS 12
BP 1566
EP 1575
DI 10.1111/j.1398-9995.2010.02415.x
PG 10
WC Allergy; Immunology
SC Allergy; Immunology
GA 673UG
UT WOS:000283688400009
PM 20560908
ER
PT J
AU Cohen, MS
Zak, V
Atz, AM
Printz, BF
Pinto, N
Lambert, L
Pemberton, V
Li, JS
Margossian, R
Dunbar-Masterson, C
McCrindle, BW
AF Cohen, Meryl S.
Zak, Victor
Atz, Andrew M.
Printz, Beth F.
Pinto, Nelangi
Lambert, Linda
Pemberton, Victoria
Li, Jennifer S.
Margossian, Renee
Dunbar-Masterson, Carolyn
McCrindle, Brian W.
TI Anthropometric measures after Fontan procedure: Implications for
suboptimal functional outcome
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID QUALITY-OF-LIFE; HEART-DISEASE; SINGLE VENTRICLE; SOMATIC GROWTH;
RISK-FACTORS; OPERATION; CHILDREN; OBESITY; IMPACT
AB Background Abnormal height and adiposity are observed after the Fontan operation. These abnormalities may be associated with worse functional outcome.
Methods We analyzed data from the National Heart, Lung, and Blood Institute Pediatric Heart Network cross-sectional study of Fontan patients. Groups were defined by height (z-score <-1.5 or >=-1.5) and body mass index (body mass index [BMI] z-score <-1.5 or -1.5 to 1.5 or >= 1.5). Associations of anthropometric measures with measurements from clinical testing (exercise, echocardiography, magnetic resonance imaging) were determined adjusting for demographics, anatomy, and pre-Fontan status. Relationships between anthropometric measures and functional health status (FHS) were assessed using the Child Health Questionnaire.
Results Mean age of the cohort (n = 544) was 11.9 +/- 3.4 years. Lower height-z patients (n = 124, 23%) were more likely to have pre-Fontan atrioventricular valve regurgitation (P = .029), as well as orthopedic and developmental problems (both P < .001). Lower height-z patients also had lower physical and psychosocial FHS summary scores (both P < .01). Higher BMI-z patients (n = 45, 8%) and lower BMI-z patients (n = 53, 10%) did not have worse FHS compared to midrange BMI-z patients (n = 446, 82%). However, higher BMI-z patients had higher ventricular mass-to-volume ratio (P = .03) and lower % predicted maximum work (P = .004) compared to midrange and lower BMI-z patients.
Conclusions Abnormal anthropometry is common in Fontan patients. Shorter stature is associated with poorer FHS and non-cardiac problems. Increased adiposity is associated with more ventricular hypertrophy and poorer exercise performance, which may have significant long-term implications in this at-risk population. (Am Heart J 2010;160:1092-1098.e1.)
C1 [Cohen, Meryl S.] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA.
[Zak, Victor] New England Res Inst, Watertown, MA 02172 USA.
[Atz, Andrew M.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Printz, Beth F.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Pinto, Nelangi; Lambert, Linda] Univ Utah, Salt Lake City, UT USA.
[Pemberton, Victoria] NHLBI, Bethesda, MD 20892 USA.
[Li, Jennifer S.] Duke Univ, Sch Med, Durham, NC USA.
[Margossian, Renee; Dunbar-Masterson, Carolyn] Boston Childrens Hosp, Boston, MA USA.
[McCrindle, Brian W.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
RP Cohen, MS (reprint author), Childrens Hosp Philadelphia, Div Cardiol, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM cohenm@email.chop.edu
FU NHLBI NIH HHS [HL068270, U10 HL068270, U01 HL068288, U01 HL068285, U01
HL068270, HL068288, U01 HL068279, HL068285, HL068279, U01 HL068292,
HL068292, HL068269, HL068281, HL068290, U01 HL068269, U01 HL068279-01,
U01 HL068281, U01 HL068290]
NR 26
TC 22
Z9 22
U1 1
U2 2
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 2010
VL 160
IS 6
BP 1092
EP U130
DI 10.1016/j.ahj.2010.07.039
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 692WW
UT WOS:000285187600020
PM 21146663
ER
PT J
AU Ali, AH
Yanoff, LB
Stern, EA
Akomeah, A
Courville, A
Kozlosky, M
Brady, SM
Calis, KA
Reynolds, JC
Crocker, MK
Barak, N
Yanovski, JA
AF Ali, Asem H.
Yanoff, Lisa B.
Stern, Elizabeth A.
Akomeah, Abena
Courville, Amber
Kozlosky, Merel
Brady, Sheila M.
Calis, Karim A.
Reynolds, James C.
Crocker, Melissa K.
Barak, Nir
Yanovski, Jack A.
TI Acute effects of betahistine hydrochloride on food intake and appetite
in obese women a randomized, placebo-controlled trial
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID HISTAMINE H-1 RECEPTOR; INDUCED WEIGHT-GAIN; NEURONAL HISTAMINE;
FEEDING-BEHAVIOR; RATS; HYPOTHALAMUS; INFUSION; HUNGER; ADULTS; BRAIN
AB Background Central nervous system histaminergic tone is thought to play a role in appetite regulation In animal models histamine receptor 1 (HRH1) agonists and histamine receptor 3 (HRH3) an tagonists decrease food intake
Objective The objective of this study was to examine the acute effects of betahistine hydrochloride (an HRH1 agonist and HRH3 antagonist) on food intakes and appetites
Design The study was a proof of concept rindomized double blinded placebo controlled dose ranging study performed to exam me the effects of betahistine in women with class I or II obesity [body mass Index (BMI in kg/m(2)) of 30-39 991 After a 24 h placebo run in period subjects received a placebo (n = 19) or 48 (n = 19) 96 (n = 17) or 144 (n = 21) mg betahistine/d for 24 h Treatment was followed by a buffet test meal to assess energy intake Hunger satiety and desire to eat were measured after consuming the meal by using visual analog scales Data were analyzed by using regression models with the assumption that there would be an in creasing effect of betahistine doses Analyses were adjusted for age log fat and lean mass food preferences and intake during a buffet test meal obtained during the placebo run in period
Results Of the 79 obese women (mean +/- SD age 42 +/- 11 y BMI 35 +/- 3) enrolled in the study 76 women completed the study The betahistine dose did not significantly change intakes from those observed during the run in period of the buffet test meal (P = 0 78) Hunger fullness and desire to eat (all P > 0 62) similarly showed no differences according to the betahistine close
Conclusions Betahistine did not produce an effect on food intakes or appetites More potent histaminergic modulators may he required to elucidate the possible role of histaminergic pathways in human obesity This trial was registered at clinicaltrials gov as NCT00459992 Am J Clin Nutr 2010 92 1290-7
C1 [Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, NIH, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Ali, Asem H.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA.
[Courville, Amber; Kozlosky, Merel] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA.
[Reynolds, James C.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Barak, Nir] Sackler Univ, Sch Med, Tel Aviv, Israel.
[Barak, Nir] Obecure Ltd, Ramat Gan, Israel.
RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, NIH, Hatfield Clin Res Ctr, 9000 Rockville Pike,Room 1E 3330,MSC 1103, Bethesda, MD 20892 USA.
OI barak, nir/0000-0002-0827-6509
FU National Institutes of Health (NIH) [Z01 HD 00641]; NIH Office of
Research on Women s Health; Obecure Ltd; NICHD
FX Supported by the National Institutes of Health (NIH) Intramural Re
search Program grant Z01 HD 00641 from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD) with
supplemental funding from the NIH Office of Research on Women s Health
(to JAY) and by a cooperative research agreement with Obecure Ltd to the
NICHD (to JAY) Obecure Ltd provided some research support for the study
and the betahistine and matching placebo capsules under a material
transfer agreement with the NICHD The study was designed implemented and
data were analyzed and Interpreted independent of Obecure Ltd however
the manuscript was reviewed and approved by NB who is an employee of
Obecure Ltd
NR 34
TC 9
Z9 10
U1 0
U2 0
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD DEC
PY 2010
VL 92
IS 6
BP 1290
EP 1297
DI 10.3945/ajcn.110.001586
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 690HM
UT WOS:000284993600004
PM 20881066
ER
PT J
AU Cercamondi, CI
Egli, IM
Ahouandjinou, E
Dossa, R
Zeder, C
Salami, L
Tjalsma, H
Wiegerinck, E
Tanno, T
Hurrell, RF
Hounhoutgan, J
Zimmermann, MB
AF Cercamondi, Colin I.
Egli, Ines M.
Ahouandjinou, Ella
Dossa, Romain
Zeder, Christophe
Salami, Lamidhi
Tjalsma, Harold
Wiegerinck, Erwin
Tanno, Toshihiko
Hurrell, Richard F.
Hounhoutgan, Joseph
Zimmermann, Michael B.
TI Afebrile Plasmodium falciparum parasitemia decreases absorption of
fortification iron but does not affect systemic iron utilization a
double stable-isotope study in young Beninese women
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID INTERMITTENT PREVENTIVE TREATMENT; RANDOMIZED CONTROLLED-TRIAL;
MALARIA-ENDEMIC AREA; SERUM HEPCIDIN; CHILDREN; ANEMIA; INFECTION;
BLOOD; INTERLEUKIN-6; PREVALENCE
AB Background Iron deficiency anemia (IDA) affects many young women in sub Saharan Africa Its etiology is multifactorial but the major cause is low dietary iron bioavailability exacerbated by parasitic infections such as malaria
Objective We investigated whether asymptomatic Plasmodium falciparum parasitemia in Beninese women would impair absorption of dietary iron or utilization of circulating iron
Design Iron absorption and utilization from an iron fortified sorghum based meal were estimated by using oral and intravenous isotope labels in 23 afebrile women with a positive malaria smear (asexual P falciparum parasitemia >500 parasites/mu L blood) The women were studied while Infected treated and then restudied 10 d after treatment Iron status hepcidin and inflammation indexes were measured before and after treatment
Results Treatment reduced low grade inflammation as reflected by decreases in serum ferritin C reactive protein interleukin 6 inter leukin 8 and interleukin 10 (P < 0 05) this was accompanied by a reduction in median serum hepcidin of approximate to 50% from 2 7 to 1 4 nmol/L (P < 0 005) Treatment decreased serum erythropoietin and growth differentiation factor 15 (P < 0 05) Clearance of parasitemia increased geometric mean dietary iron absorption (from 10 2% to 176% P = 0 008) but did not affect systemic iron utilization (85 0% compared with 83 1% NS)
Conclusions Dietary iron absorption is reduced by approximate to 40% in asymptomatic P falciparum parasitemia likely because of low grade inflammation and Its modulation of circulating hepcidin Be cause asymptomatic parasitemia has a protracted course and is very common in malarial areas this effect may contribute to IDA and blunt the efficacy of Iron supplementation and fortification programs This trial was registered at clinicaltrials gov as NCT01108939 Am J Clin Nutr 2010 92 1385-92
C1 [Cercamondi, Colin I.] Swiss Fed Inst Technol, Human Nutr Lab, Inst Food Nutr & Hlth, CH-8092 Zurich, Switzerland.
[Ahouandjinou, Ella; Dossa, Romain; Hounhoutgan, Joseph] Univ Abomey Calavi, Lab Physiol Nutr, Cotonou, Benin.
[Salami, Lamidhi] Zone Sanit Atacora Donga, Natitingou, Benin.
[Tjalsma, Harold; Wiegerinck, Erwin] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, NL-6525 ED Nijmegen, Netherlands.
[Tanno, Toshihiko] NIH, Mol Med Branch, Bethesda, MD 20892 USA.
[Zimmermann, Michael B.] Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
RP Cercamondi, CI (reprint author), Swiss Fed Inst Technol, Human Nutr Lab, Inst Food Nutr & Hlth, Zentrum Schmelzbergstr 7,LFV D11 2, CH-8092 Zurich, Switzerland.
RI Tjalsma, Harold/I-7146-2012; Zimmermann, Michael/C-3062-2016;
OI Zeder, Christophe/0000-0001-6675-3708
FU European Community [FP7/2007 2013, 211484]; Molecular Medicine Branch
National Institutes of Health Bethesda MD
FX Supported by The INSTAPA project, which receives funding from the
European Community s Seventh Framework Programme (FP7/2007 2013) under
grant agreement no 211484 and the Intramural Research Program of the
Molecular Medicine Branch National Institutes of Health Bethesda MD
NR 71
TC 52
Z9 52
U1 1
U2 6
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD DEC
PY 2010
VL 92
IS 6
BP 1385
EP 1392
DI 10.3945/ajcn.2010.30051
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 690HM
UT WOS:000284993600015
PM 20926522
ER
PT J
AU Gaskins, AJ
Rovner, AJ
Mumford, SL
Yeung, E
Browne, RW
Trevisan, M
Perkins, NJ
Wactawski-Wende, J
Schisterman, ES
AF Gaskins, Audrey J.
Rovner, Alisha J.
Mumford, Sunni L.
Yeung, Edwina
Browne, Richard W.
Trevisan, Maurizio
Perkins, Neil J.
Wactawski-Wende, Jean
Schisterman, Enrique S.
CA BioCycle Study Grp
TI Adherence to a Mediterranean diet and plasma concentrations of lipid
peroxidation in premenopausal women
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; LOW-DENSITY-LIPOPROTEIN;
VITAMIN-E-DEFICIENCY; OXIDATIVE STRESS; BIOLOGICAL VARIATION;
ALPHA-TOCOPHEROL; MENSTRUAL-CYCLE; F-2-ISOPROSTANES; ANTIOXIDANTS;
FLAVONOIDS
AB Background A Mediterranean diet has been associated with a reduced risk of cardiovascular disease and mortality A possible mechanism is through a decrease in lipid peroxidation (LPO) how ever evidence linking the Mediterranean diet with lower LPO in premenopausal women is sparse
Objective We investigated whether adherence to a Mediterranean diet was associated with lower LPO concentrations in premeno pausal women
Design Two hundred fifty nine healthy women aged 18-44 y were followed for <= 2 menstrual cycles Plasma concentrations of F(2) isoprostane (8 iso PGF2 alpha) 9 hydroxyoctadecadieneoic acid (9 HODE) and thiobarbituric acid reactive substances (TBARS) were measured <= 8 times per cycle at visits scheduled by using fertility monitors Diet was assessed <= 4 times per cycle by using 24 h dietary recalls The alternate Mediterranean Diet Score (aMED) (range 0-9) was calculated on the basis of Intake of vegetables legumes fruit nuts whole grains red and processed merit fish and alcohol and the ratio of monounsaturated to saturated fat
Results A 1 unit increase in aMED was associated with a 4 50% decrease in 8 iso PGF2 alpha concentrations (95% CI -6 32% -2 65%) and a 14 01% decrease in 9 HODE concentrations (95% CI -17 88% -9 96%) after adjustment for energy intake age race body mass index plasma ascorbic acid and serum cholesterol No significant association was observed between aMED and TBARS A 1 unit Increase in aMED was associated with a 1 39% Increase (95% CI 0 07% 2 72%) in plasma ascorbic acid concentrations
Conclusions Adherence to a Mediterranean diet is associated with lower LPO and higher ascorbic ricid concentrations These results confirm that decreased LPO is a plausible mechanism linking a Mediterranean diet to reduced cardiovascular disease risk Am J Clin Nutr 2010 92 1461-7
C1 [Gaskins, Audrey J.; Rovner, Alisha J.; Mumford, Sunni L.; Yeung, Edwina; Perkins, Neil J.; Schisterman, Enrique S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Browne, Richard W.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14260 USA.
[Trevisan, Maurizio] Hlth Sci Syst Nevada Syst Higher Educ, Las Vegas, NV USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Schisterman, ES (reprint author), 6100 Execut Blvd,7B03M, Rockville, MD 20852 USA.
RI Yeung, Edwina/F-5992-2015;
OI Yeung, Edwina/0000-0002-3851-2613; Perkins, Neil/0000-0002-6802-4733;
Schisterman, Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development National Institutes of Health
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
National Institutes of Health
NR 48
TC 30
Z9 30
U1 1
U2 3
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD DEC
PY 2010
VL 92
IS 6
BP 1461
EP 1467
DI 10.3945/ajcn.110.000026
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 690HM
UT WOS:000284993600025
PM 20943796
ER
PT J
AU Kabat, GC
Cross, AJ
Park, Y
Schatzkin, A
Hollenbeck, AR
Rohan, TE
Sinha, R
AF Kabat, Geoffrey C.
Cross, Amanda J.
Park, Yikyung
Schatzkin, Arthur
Hollenbeck, Albert R.
Rohan, Thomas E.
Sinha, Rashmi
TI Intakes of dietary iron and heme-iron and risk of postmenopausal breast
cancer in the National Institutes of Health-AARP Diet and Health Study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID FREE-RADICALS; NONHEME IRON; COHORT; MEAT; CARCINOGENESIS;
MICRONUTRIENTS; ASSOCIATION; STORES; RAW; FAT
AB Background Intakes of dietary Iron and in particular heme iron may increase breast cancer risk because of the prooxidant properties of iron However few studies have examined the association of iron and heme iron intakes with breast cancer risk
Objective We assessed the association of intakes of dietary iron and heme iron with risk of postmenopausal breast cancer
Design We used data from the National Institutes of Health-AARP Diet and Health Study to assess intakes of total dietary iron iron from meat iron from red meat and heme iron in relation to breast cancer risk in 116 674 postmenopausal women who completed a de tailed questionnaire regarding meat preparation methods and degrees of doneness During 6 5 y of follow up 3396 cases of invasive breast cancer were identified Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% CIs
Results After adjustment for covariates HRs for the highest corn pared with the lowest quintiles of Intakes of total iron Iron from meat iron from red meat and heme iron were all close to unity and there were no increasing trends with increasing intakes The multi variable adjusted HR for the highest compared with the lowest quintile of heme iron intake was 1 01 (95% CI 0 89 114 P for trend = 0 97) In addition no associations were seen when iron variables were stratified by possible effect modifiers or hormone receptor status
Conclusion The results of this large cohort study do not support an association between iron or heme iron intakes and postmenopausal breast cancer Am J Clin Nutr 2010 92 1478-83
C1 [Kabat, Geoffrey C.; Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
[Cross, Amanda J.; Park, Yikyung; Schatzkin, Arthur; Sinha, Rashmi] NCI, Nutr Epidemiol Branch, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Kabat, GC (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
RI Sinha, Rashmi/G-7446-2015;
OI Sinha, Rashmi/0000-0002-2466-7462; Park, Yikyung/0000-0002-6281-489X
FU Albert Einstein College of Medicine
FX Supported by institutional funds (Albert Einstein College of Medicine)
NR 41
TC 19
Z9 20
U1 0
U2 5
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 2010
VL 92
IS 6
BP 1478
EP 1483
DI 10.3945/ajcn.2010.29753
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 690HM
UT WOS:000284993600027
PM 20962158
ER
PT J
AU Sridhar, SS
Hotte, SJ
Chin, JL
Hudes, GR
Gregg, R
Trachtenberg, J
Wang, LS
Tran-Thanh, D
Pham, NA
Tsao, MS
Hedley, D
Dancey, JE
Moore, MJ
AF Sridhar, Srikala S.
Hotte, Sebastien J.
Chin, Joseph L.
Hudes, Gary R.
Gregg, Richard
Trachtenberg, John
Wang, Lisa
Tran-Thanh, Danh
Pham, Nhu-An
Tsao, Ming-Sound
Hedley, David
Dancey, Janet E.
Moore, Malcolm J.
TI A Multicenter Phase II Clinical Trial of Lapatinib (GW572016) in
Hormonally Untreated Advanced Prostate Cancer
SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS
LA English
DT Article
DE hormonally untreated prostate cancer; lapatinib; EGFR/HER2 tyrosine
kinase inhibitor; Phase II
ID ANDROGEN-INDEPENDENCE; KINASE INHIBITOR; RECEPTOR FAMILY; BREAST-CANCER;
OPEN-LABEL; EXPRESSION; GEFITINIB; PROGRESSION; MUTATIONS; PROTEIN
AB Objectives: Lapatinib (GW572016) is a selective and potent dual tyrosine kinase inhibitor of the epidermal growth factor 1 (EGFR) and 2 (HER2), approved in the treatment of HER2 positive breast cancer. Since EGFR and HER2 overexpression has also been seen in prostate cancer and appears to correlate with a worse clinical outcome, Lapatinib may represent a novel therapeutic strategy in prostate cancer. This Phase II multicenter clinical trial is the first to evaluate Lapatinib in early stage, hormonally untreated recurrent or metastatic prostate cancer.
Methods: Eligible patients received lapatinib 1500 mg PO daily until progression. The primary end point was prostate specific antigen (PSA) response. Archival tumor tissue was collected for EGFR and HER2 analysis.
Results: A total of 23 patients, median age 67, ECOG PS 0-2, mean baseline PSA 7.5, were evaluable for response. In total, 125 cycles were administered. The most frequent adverse events were lymphopenia, fatigue, rash, dyspepsia, and diarrhea. Grade 3+ increased alanine aminotransferase (ALT) was reported in 2 patients, and grade 4 blurry vision in 1 patient. No PSA responses were seen. Median time to progression (TTP) was 4.6 months and 6 months progression-free estimate was 44.5%.
Conclusions: Lapatinib was well tolerated but like other EGFR-and HER2-targeted agents in advanced HRPC failed to show significant antitumor activity even in this very early stage hormonally untreated population.
C1 [Sridhar, Srikala S.] Univ Toronto, Princess Margaret Hosp, Phase Consortium 2, Toronto, ON, Canada.
[Hotte, Sebastien J.] Juravinski Canc Ctr, Div Med Oncol, Dept Oncol, Hamilton, ON, Canada.
[Chin, Joseph L.] London Reg Canc Ctr, Div Surg Oncol, London, ON N6A 4L6, Canada.
[Hudes, Gary R.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA.
[Gregg, Richard] Kingston Reg Canc Ctr, Dept Oncol, Div Med Oncol, Kingston, ON, Canada.
[Dancey, Janet E.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Sridhar, SS (reprint author), Univ Toronto, Princess Margaret Hosp, Phase Consortium 2, 610 Univ Ave,Suite 5-222, Toronto, ON, Canada.
EM srikala.sridhar@uhn.on.ca
FU NIH; NCI [N01CM17107, N01CM62203]
FX Supported by NIH grant to the Princess Margaret Hospital Consortium. NCI
Contracts N01CM17107, N01CM62203.
NR 26
TC 28
Z9 28
U1 0
U2 4
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 2010
VL 33
IS 6
BP 609
EP 613
DI 10.1097/COC.0b013e3181beac33
PG 5
WC Oncology
SC Oncology
GA 688BR
UT WOS:000284825000015
PM 20042973
ER
PT J
AU Johnson, CC
Hayes, RB
Schoen, RE
Gunter, MJ
Huang, WY
AF Johnson, Christine Cole
Hayes, Richard B.
Schoen, Robert E.
Gunter, Marc J.
Huang, Wen-Yi
CA PLCO Trial Team
TI Non-Steroidal Anti-Inflammatory Drug Use and Colorectal Polyps in the
Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID HORMONE-REPLACEMENT-THERAPY; SERVICES-TASK-FORCE; LOW-DOSE ASPIRIN;
LONG-TERM USE; CYCLOOXYGENASE-2 INHIBITORS; PRIMARY PREVENTION;
RANDOMIZED-TRIAL; UNITED-STATES; COLON-CANCER; POOLED ANALYSIS
AB OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs) have been documented in animal and human studies to reduce risk for colorectal cancer and adenomatous polyps, but risk modification for subgroups of the population and effects on hyperplastic polyps have been less studied.
METHODS: Data on recent use of two frequently ingested NSAIDs, aspirin and ibuprofen, were collected at baseline from participants aged 55-74 years in the 10 centers of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Participants randomized to the intervention arm of the trial received a flexible sigmoidoscopy during a baseline examination. Follow-up of detected polyps was accomplished outside the Trial setting and relevant records were sought and abstracted. Cases (n = 4,017) included subjects with a biopsy-proven polyp in the left side of the colon (descending colon, sigmoid, and rectum) detected as a consequence of PLCO screening; controls (n = 38,396) were subjects with no left-sided colon polyp.
RESULTS: Regular use of aspirin (>= 4 times/month) in the past year was inversely associated with hyperplastic polyps (odds ratios (OR) = 0.8, 95% confidence interval (CI) = 0.7-0.9), adenomatous polyps (OR = 0.8, 95% CI = 0.8-0.9), and advanced adenomas (OR = 0.8, 95% CI = 0.7-0.9). As frequency of aspirin use increased, the prevalence of polyps decreased significantly for each histological classification (P for trend <= 0.0004). Similar patterns were found for adenomas and ibuprofen. Overall protection was consistent in both the descending colon or sigmoid and the rectum, but more evident in males. In males, the OR for heavy use of combined aspirin and ibuprofen (>= 2 times/day) was 0.6 (95% CI = 0.5-0.8), as opposed to 0.9 (95% CI = 0.8-1.1) in females. The protective effects of NSAIDs for females were apparent only among those with body mass index (BMI) <25 (OR = 0.8, 95% CI = 0.7-1.0 for regular use of NSAIDs; P interaction = 0.04). We also found a slightly stronger protection of NSAIDs in the 70-74 years age group compared with those aged 55-69 years.
CONCLUSIONS: This study of a large general risk population supports previous work that recent use of aspirin and ibuprofen is associated with a decreased risk of colorectal adenomas and demonstrates that this protective effect may be stronger in certain population subgroups and is also evident for aspirin and hyperplastic polyps.
C1 [Johnson, Christine Cole] Henry Ford Hosp, Dept Biostat & Res Epidemiol, Josephine Ford Canc Ctr, Detroit, MI 48202 USA.
[Hayes, Richard B.; Gunter, Marc J.; Huang, Wen-Yi] NCI, Div Canc Epidemiol & Genet, DHHS, NIH, Bethesda, MD 20892 USA.
[Schoen, Robert E.] Univ Pittsburgh, Dept Med & Epidemiol, Pittsburgh, PA USA.
RP Johnson, CC (reprint author), Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Josephine Ford Canc Ctr, 1 Ford Pl,5C, Detroit, MI 48202 USA.
EM cjohnso1@hfhs.org
OI Johnson, Christine Cole/0000-0002-6864-6604; Hayes,
Richard/0000-0002-0918-661X
FU NIH, National Cancer Institute, Division of Cancer Epidemiology and
Genetics; National Cancer Institute
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Division of Cancer Epidemiology and
Genetics. We thank Drs Christine Berg and Philip Prorok, Division of
Cancer Prevention, National Cancer Institute; the Screening Center
investigators and staff of the Prostate, Lung, Colorectal and Ovarian
Cancer Screening Trial; Mr Thomas Riley and staff, Information
Management Services; and Ms Barbara O'Brien and staff, Westat.; This
work was supported by individual contracts from the National Cancer
Institute to each of the 10 screening centers and to the coordinating
center and by the NCI intramural program. C.C.J and R. E. S. were
supported through the NCI PLCO Trial funding to the clinical sites. R.
B. H., M.J.G., and W.-Y.H. were supported through their employment at
NCI.
NR 68
TC 23
Z9 23
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD DEC
PY 2010
VL 105
IS 12
BP 2646
EP 2655
DI 10.1038/ajg.2010.349
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 689PQ
UT WOS:000284940900020
PM 20808298
ER
PT J
AU Boztug, K
Ding, XQ
Hartmann, H
Ziesenitz, L
Schaffer, AA
Diestelhorst, J
Pfeifer, D
Appaswamy, G
Kehbel, S
Simon, T
Al Jefri, A
Lanfermann, H
Klein, C
AF Boztug, Kaan
Ding, Xiao-Qi
Hartmann, Hans
Ziesenitz, Lena
Schaeffer, Alejandro A.
Diestelhorst, Jana
Pfeifer, Dietmar
Appaswamy, Giridharan
Kehbel, Sonja
Simon, Thorsten
Al Jefri, Abdullah
Lanfermann, Heinrich
Klein, Christoph
TI HAX1 Mutations Causing Severe Congenital Neuropenia and Neurological
Disease Lead to Cerebral Microstructural Abnormalities Documented by
Quantitative MRI
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE severe congenital neutropenia; HAX1; apoptosis; neurodegeneration;
quantitative MRI; immunodeficiency
ID UNFOLDED PROTEIN RESPONSE; NEUTROPHIL ELASTASE; LINKAGE ANALYSIS; GENE;
DEFICIENCY; APOPTOSIS; KOSTMANN; FAMILY; TISSUE
AB Biallelic mutations in the gene encoding HCLS-associated protein X-1 (HAX1) cause autosomal recessive severe congenital neutropenia (SCN). Some of these patients have neurological abnormalities including developmental delay, cognitive impairment, and/or epilepsy. Recent genotype-phenotype studies have shown that mutations in HAX1 affecting transcripts A (NM_006118.3) and B (NM_001018837.1) cause the phenotype of SCN with neurological impairment, while mutations affecting isoform A but not B lead to SCN without neurological aberrations. In this study, we identified a consanguineous family with two patients suffering from SCN and neurological disease caused by a novel, homozygous genomic deletion including exons 4-7 of the HAX1 gene. Quantitative MRI analyses showed generalized alterations in cerebral proton density in both of the patients, as well as in an additional unrelated patient with another HAX1 mutation (Arg86X) known to be associated with neurological manifestations. This study provides first in vivo evidence of aberrant neuroimaging findings associated with HAX1 deficiency in SCN patients. (C) 2010 Wiley-Liss, Inc.
C1 [Boztug, Kaan; Ziesenitz, Lena; Diestelhorst, Jana; Appaswamy, Giridharan; Klein, Christoph] Hannover Med Sch, Dept Pediat Hematol Oncol, D-30625 Hannover, Germany.
[Ding, Xiao-Qi; Kehbel, Sonja; Lanfermann, Heinrich] Hannover Med Sch, Dept Neuroradiol, D-30625 Hannover, Germany.
[Hartmann, Hans] Hannover Med Sch, Dept Pediat Nephrol Hepatol & Metab Dis, D-30625 Hannover, Germany.
[Schaeffer, Alejandro A.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, US Dept HHS, Bethesda, MD 20892 USA.
[Pfeifer, Dietmar] Univ Freiburg, Med Ctr, Core Facil Genom 2, Dept Hematol Oncol, D-7800 Freiburg, Germany.
[Simon, Thorsten] Univ Cologne, Childrens Hosp, Dept Pediat Oncol & Hematol, Cologne, Germany.
[Al Jefri, Abdullah] King Faisal Specialist Hosp & Res Ctr, Dept Pediat Hematol Oncol, Riyadh 11211, Saudi Arabia.
RP Klein, C (reprint author), Hannover Med Sch, Dept Pediat Hematol Oncol, Carl Neuberg Str 1, D-30625 Hannover, Germany.
EM klein.christoph@mh-hannover.de
RI Schaffer, Alejandro/F-2902-2012
FU Severe Chronic Neutropenia International Registry (SCNIR) at Hannover
Medical School; Clotten Stiftung; Fritz-Thyssen Foundation; NIH, NLM;
Else-Kroner-Fresenius-Stiftung
FX We thank the families and patients for support of our studies and all
clinical and nursing staff as well as the Severe Chronic Neutropenia
International Registry (SCNIR) at Hannover Medical School for great
support. This research was supported by grants from the Clotten Stiftung
(C. K.), and the Fritz-Thyssen Foundation (K. B. and C. K.). This
research was also supported by the Intramural Research Program of the
NIH, NLM (A. A. S.). K. B. is supported by a fellowship from the
Else-Kroner-Fresenius-Stiftung.
NR 35
TC 8
Z9 8
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD DEC
PY 2010
VL 152A
IS 12
BP 3157
EP 3163
DI 10.1002/ajmg.a.33748
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 693UV
UT WOS:000285251800036
PM 21108402
ER
PT J
AU Koren, G
Clark, S
Hankins, GDV
Caritis, SN
Miodovnik, M
Umans, JG
Mattison, DR
AF Koren, Gideon
Clark, Shannon
Hankins, Gary D. V.
Caritis, Steve N.
Miodovnik, Menachem
Umans, Jason G.
Mattison, Donald R.
TI Effectiveness of delayed-release doxylamine and pyridoxine for nausea
and vomiting of pregnancy: a randomized placebo controlled trial
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE doxylamine; effectivenss; nausea and vomiting of pregnancy; pyridoxine;
safety
ID BENDECTIN; DICLECTIN; THERAPY; BURDEN; IMPACT; WOMEN
AB OBJECTIVE: To evaluate the effectiveness of Diclectin (doxylamine succinate 10 mg-pyridoxine hydrochloride 10 mg, delayed-release preparation) as compared with placebo for nausea and vomiting of pregnancy.
STUDY DESIGN: A randomized, double-blind, multicenter placebo controlled trial studying pregnant women suffering from nausea and vomiting of pregnancy, analyzed by intention to treat. Women received Diclectin (n = 131) or placebo (n = 125) for 14 days. Nausea and vomiting of pregnancy symptoms were evaluated daily using the pregnancy unique quantification of emesis scale.
RESULTS: Diclectin use resulted in a significantly larger improvement in symptoms of nausea and vomiting of pregnancy compared with placebo based on both the pregnancy unique quantification of emesis score (-4.8 +/- 2.7 vs -3.9 +/- 2.6; P = .006) and quality of life. After the trial, 64 (48.9%) women receiving Diclectin asked to continue compassionate use of their medication, as compared with 41 (32.8%) of placebo-treated women (P = .009).
CONCLUSION: Diclectin delayed release formulation of doxylamine succinate and pyridoxine hydrochloride is effective and well tolerated in treating nausea and vomiting of pregnancy.
C1 [Koren, Gideon] Hosp Sick Children, Div Clin Pharmacol Toxicol, Motherisk Program, Toronto, ON M5G 1X8, Canada.
[Koren, Gideon] Univ Toronto, Toronto, ON, Canada.
[Clark, Shannon; Hankins, Gary D. V.; Caritis, Steve N.; Miodovnik, Menachem; Umans, Jason G.; Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child & Human De, Obstet Pharmacol Res Unit Network, Bethesda, MD USA.
[Clark, Shannon; Hankins, Gary D. V.] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX USA.
[Caritis, Steve N.] Univ Pittsburgh, Med Ctr, Dept Obstet & Gynecol, Pittsburgh, PA USA.
[Miodovnik, Menachem; Umans, Jason G.] Georgetown Univ, Dept Obstet & Gynecol, Washington, DC 20007 USA.
[Miodovnik, Menachem; Umans, Jason G.] Washington Hosp Ctr, Dept Obstet & Gynecol, Washington, DC 20010 USA.
RP Koren, G (reprint author), Hosp Sick Children, Div Clin Pharmacol Toxicol, Motherisk Program, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
EM gkoren@sickkids.ca
RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013
OI caritis, steve/0000-0002-2169-0712; Mattison, Donald/0000-0001-5623-0874
FU Duchesnay Inc., Blainville, QC, Canada
FX The study was supported by Duchesnay Inc., Blainville, QC, Canada, and
executed by Premier Research Group, Philadelphia, PA. Clinical Trial
Registration no. NCT00614445.
NR 28
TC 11
Z9 11
U1 1
U2 11
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 2010
VL 203
IS 6
AR 571.e1
DI 10.1016/j.ajog.2010.07.030
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 685CJ
UT WOS:000284602400034
PM 20843504
ER
PT J
AU Muniyappa, R
Irving, BA
Unni, US
Briggs, WM
Nair, KS
Quon, MJ
Kurpad, AV
AF Muniyappa, Ranganath
Irving, Brian A.
Unni, Uma S.
Briggs, William M.
Nair, K. Sreekumaran
Quon, Michael J.
Kurpad, Anura V.
TI Limited predictive ability of surrogate indices of insulin
sensitivity/resistance in Asian-Indian men
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE quantitative insulin-sensitivity check index
ID HOMEOSTASIS MODEL ASSESSMENT; SKELETAL-MUSCLE; CHECK INDEX; RESISTANCE;
ASSOCIATION; PREVALENCE; OBESITY; WEIGHT; ACCURACY; CHENNAI
AB Muniyappa R, Irving BA, Unni US, Briggs WM, Nair KS, Quon MJ, Kurpad AV. Limited predictive ability of surrogate indices of insulin sensitivity/resistance in Asian-Indian men. Am J Physiol Endocrinol Metab 299: E1106-E1112, 2010. First published October 13, 2010; doi:10.1152/ajpendo.00454.2010.-Insulin resistance is highly prevalent in Asian Indians and contributes to worldwide public health problems, including diabetes and related disorders. Surrogate measurements of insulin sensitivity/resistance are used frequently to study Asian Indians, but these are not formally validated in this population. In this study, we compared the ability of simple surrogate indices to accurately predict insulin sensitivity as determined by the reference glucose clamp method. In this cross-sectional study of Asian-Indian men (n = 70), we used a calibration model to assess the ability of simple surrogate indices for insulin sensitivity [quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment (HOMA2-IR), fasting insulin-to-glucose ratio (FIGR), and fasting insulin (FI)] to predict an insulin sensitivity index derived from the reference glucose clamp method (SI(Clamp)). Predictive accuracy was assessed by both root mean squared error (RMSE) of prediction as well as leave-one-out cross-validation-type RMSE of prediction (CVPE). QUICKI, FIGR, and FI, but not HOMA2-IR, had modest linear correlations with SIClamp (QUICKI: r = 0.36; FIGR: r = -0.36; FI: r = -0.27; P < 0.05). No significant differences were noted among CVPE or RMSE from any of the surrogate indices when compared with QUICKI. Surrogate measurements of insulin sensitivity/resistance such as QUICKI, FIGR, and FI are easily obtainable in large clinical studies, but these may only be useful as secondary outcome measurements in assessing insulin sensitivity/resistance in clinical studies of Asian Indians.
C1 [Muniyappa, Ranganath; Quon, Michael J.] NIH, Diabet Unit, NCCAM, Bethesda, MD 20892 USA.
[Irving, Brian A.; Nair, K. Sreekumaran] Mayo Clin, Div Endocrinol, Endocrinol Res Unit, Coll Med, Rochester, MN USA.
[Unni, Uma S.; Kurpad, Anura V.] St Johns Med Coll & Res Inst, Dept Physiol, Bangalore, Karnataka, India.
[Briggs, William M.] New York Methodist Hosp, Dept Emergency Med, Brooklyn, NY USA.
RP Muniyappa, R (reprint author), NIH, Diabet Unit, NCCAM, 10 Ctr Dr,Bldg 10,Rm 4-1730,MSC 1302, Bethesda, MD 20892 USA.
EM muniyapr@mail.nih.gov
RI Irving, Brian/B-9683-2016;
OI Irving, Brian/0000-0002-4131-9523; Quon, Michael/0000-0002-9601-9915;
Quon , Michael /0000-0002-5289-3707
FU National Center for Complementary and Alternative Medicine, Bethesda,
MD; Ajinomoto Amino Acid Research Program; American Association of
Physicians of Indian Origin; [T32-DK-07352-28]; [KL2-RR-084151];
[UL1-RR-24150]; [R01-DK-41973]
FX This work was supported, in part, by the Intramural Research Program of
the National Center for Complementary and Alternative Medicine,
Bethesda, MD; the Ajinomoto Amino Acid Research Program (to A.V.
Kurpad); Public Service Grants T32-DK-07352-28 and KL2-RR-084151 (to
B.A. Irving); and Public Service Grants UL1-RR-24150 (Mayo Clinic Center
for Clinical and Translational Research) and R01-DK-41973 and Centers
for Disease Control and Prevention Grant 10 awarded through the American
Association of Physicians of Indian Origin (to K.S. Nair).
NR 30
TC 4
Z9 4
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD DEC
PY 2010
VL 299
IS 6
BP E1106
EP E1112
DI 10.1152/ajpendo.00454.2010
PG 7
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 700CN
UT WOS:000285710400028
PM 20943755
ER
PT J
AU Gorman, MW
Rooke, GA
Savage, MV
Jayasekara, MPS
Jacobson, KA
Feigl, EO
AF Gorman, Mark W.
Rooke, G. Alec
Savage, Margaret V.
Jayasekara, M. P. Suresh
Jacobson, Kenneth A.
Feigl, Eric O.
TI Adenine nucleotide control of coronary blood flow during exercise
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE ATP; ADP; AMP; purinergic receptors; feedback control; dog
ID VASCULAR-TONE; ATP RELEASE; TREADMILL EXERCISE; HUMAN ERYTHROCYTES;
EXTRACELLULAR ATP; SMOOTH-MUSCLE; NITRIC-OXIDE; ADENOSINE; FEEDFORWARD;
METABOLISM
AB Gorman MW, Rooke GA, Savage MV, Jayasekara MP, Jacobson KA, Feigl EO. Adenine nucleotide control of coronary blood flow during exercise. Am J Physiol Heart Circ Physiol 299: H1981-H1989, 2010. First published September 17, 2010; doi:10.1152/ajpheart.00611.2010.The adenine nucleotide hypothesis postulates that the ATP released from red blood cells is broken down to ADP and AMP in coronary capillaries and that ATP, ADP, and AMP act on purinergic receptors on the surface of capillary endothelial cells. Purinergic receptor activation initiates a retrograde conducted vasodilator signal to the upstream arteriole that controls coronary blood flow in a negative feedback manner. A previous study (M. Farias 3rd, M. W. Gorman, M. V. Savage, and E. O. Feigl, Am J Physiol Heart Circ Physiol 288: H1586-H1590, 2005) demonstrated that coronary venous plasma ATP concentration increased during exercise and correlated with coronary blood flow. The present experiments test the adenine nucleotide hypothesis by examining the balance between oxygen delivery (via coronary blood flow) and myocardial oxygen consumption during exercise before and after purinergic receptor blockade. Dogs (n = 7) were chronically instrumented with catheters in the aorta and coronary sinus and a flow transducer around the circumflex coronary artery. During control treadmill exercise, myocardial oxygen consumption increased and the balance between oxygen delivery and myocardial oxygen consumption fell as indicated by a declining coronary venous oxygen tension. Blockade of P1 and P2Y(1) purinergic receptors combined with inhibition of nitric oxide synthesis significantly decreased the balance between oxygen delivery and myocardial oxygen consumption compared with control. The results support the hypothesis that ATP and its breakdown products ADP and AMP are part of a negative feedback control mechanism that matches coronary blood flow to myocardial oxygen consumption at rest and during exercise.
C1 [Gorman, Mark W.; Savage, Margaret V.; Feigl, Eric O.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA.
[Rooke, G. Alec] Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA.
[Jayasekara, M. P. Suresh; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA.
RP Feigl, EO (reprint author), Univ Washington, Dept Physiol & Biophys, G424 Hlth Sci Bldg, Seattle, WA 98195 USA.
EM efeigl@u.washington.edu
RI Jacobson, Kenneth/A-1530-2009; Rooke, Alec/F-8909-2013
OI Jacobson, Kenneth/0000-0001-8104-1493;
FU NIH [RO1 HL 82781]; NIDDK, NIH
FX This work was supported by NIH grant RO1 HL 82781 (E. O. Feigl) and NIH
Intramural Research Program NIDDK (K. A. Jacobson).
NR 48
TC 17
Z9 17
U1 1
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD DEC
PY 2010
VL 299
IS 6
BP H1981
EP H1989
DI 10.1152/ajpheart.00611.2010
PG 9
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 689OC
UT WOS:000284936600028
PM 20852039
ER
PT J
AU Mungunsukh, O
Lee, YH
Marquez, AP
Cecchi, F
Bottaro, DP
Day, RM
AF Mungunsukh, Ognoon
Lee, Young H.
Marquez, Ana P.
Cecchi, Fabiola
Bottaro, Donald P.
Day, Regina M.
TI A tandem repeat of a fragment of Listeria monocytogenes internalin B
protein induces cell survival and proliferation
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE apoptosis; angiotensin II; Akt; ERK1/2
ID HEPATOCYTE GROWTH-FACTOR; MET PROTOONCOGENE PRODUCT; RECEPTOR TYROSINE
KINASE; VIVO GENE TRANSFECTION; C-MET; IN-VIVO; PHOSPHOINOSITIDE
3-KINASE; BACTERIAL INVASION; PULMONARY-FIBROSIS; ENDOTHELIAL-CELLS
AB Mungunsukh O, Lee YH, Marquez AP, Cecchi F, Bottaro DP, Day RM. A tandem repeat of a fragment of Listeria monocytogenes internalin B protein induces cell survival and proliferation. Am J Physiol Lung Cell Mol Physiol 299: L905-L914, 2010. First published October 1, 2010; doi:10.1152/ajplung.00094.2010.-Hepatocyte growth factor (HGF) is critical for tissue homeostasis and repair in many organs including the lung, heart, kidney, liver, nervous system, and skin. HGF is a heterodimeric protein containing 20 disulfide bonds distributed among an amino-terminal hairpin, four kringle domains, and a serine protease-like domain. Due to its complex structure, recombinant production of HGF in prokaryotes requires denaturation and refolding, processes that are impractical for large-scale manufacture. Thus, pharmaceutical quantities of HGF are not available despite its potential applications. A fragment of the Listeria monocytogenes internalin B protein from amino acids 36-321 (InlB(36-321)) was demonstrated to bind to and partially activate the HGF receptor Met. InlB(36-321) has a stable beta-sheet structure and is easily produced in its native conformation by Escherichia coli. We cloned InlB(36-321) (1xInlB(36-321)) and engineered a head-to-tail repeat of InlB(36-321) with a linker peptide (2xInlB(36-321)); 1xInlB(36-321) and 2xInlB(36-321) were purified from E. coli. Both 1xand 2xInlB(36-321) activated the Met tyrosine kinase. We subsequently compared signal transduction of the two proteins in primary lung endothelial cells. 2xInlB(36-321) activated ERK1/2, STAT3, and phosphatidylinositol 3-kinase/Akt pathways, whereas 1xInlB(36-321) activated only STAT3 and ERK1/2. The 2xInlB(36-321) promoted improved motility compared with 1xInlB(36-321) and additionally stimulated proliferation equivalent to full-length HGF. Both the 1xand 2xInlB(36-321) prevented apoptosis by the profibrotic peptide angiotensin II in cell culture and ex vivo lung slice cultures. The ease of large-scale production and capacity of 2 x InlB(36-321) to mimic HGF make it a potential candidate as a pharmaceutical agent for tissue repair.
C1 [Mungunsukh, Ognoon; Lee, Young H.; Marquez, Ana P.; Day, Regina M.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA.
[Cecchi, Fabiola; Bottaro, Donald P.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Day, RM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bldg C,Rm 2023,4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM rday@usuhs.mil
RI Bottaro, Donald/F-8550-2010;
OI Bottaro, Donald/0000-0002-5057-5334; Cecchi, Franco/0000-0002-2035-5621
FU National Institutes of Health [HL-073929]; USUHS; USUHS-Henry Jackson
Foundation; American Heart Association; NIH, National Cancer Institute,
Center for Cancer Research
FX This work was supported by National Institutes of Health Grant
HL-073929, a USUHS research grant, a joint USUHS-Henry Jackson
Foundation Technology Development Award to R. M. Day, and by an American
Heart Association predoctoral fellowship to Y. H. Lee. This research was
also supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 68
TC 1
Z9 1
U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD DEC
PY 2010
VL 299
IS 6
BP L905
EP L914
DI 10.1152/ajplung.00094.2010
PG 10
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 689PW
UT WOS:000284941600020
PM 20889677
ER
PT J
AU Hennessy, E
Kraak, VI
Hyatt, RR
Bloom, J
Fenton, M
Wagoner, C
Economos, CD
AF Hennessy, Erin
Kraak, Vivica I.
Hyatt, Raymond R.
Bloom, Julia
Fenton, Mark
Wagoner, Colby
Economos, Christina D.
TI Active Living for Rural Children Community Perspectives Using PhotoVOICE
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID PHYSICAL-ACTIVITY; PARTICIPATORY RESEARCH; OBJECTIVE MEASURES;
ENVIRONMENTS; OBESITY; ADULTS; YOUTH; BEHAVIORS; PARENTS; WALKING
AB Background: Active living integrates physical activity into one's daily routine. Current understanding of active living among children and their families living in rural communities is limited. A community perspective is critical to understand the contextual factors that influence children's physical activity in rural areas.
Purpose: The purpose of this study was to identify the perceived environmental factors that support or hinder physical activity among rural children to develop testable hypotheses to inform future interventions for reducing unhealthy weight gain and preventing chronic diseases associated with physical inactivity.
Methods: PhotoVOICE was used to explore active living opportunities and barriers for children living in four low-income, rural U.S. communities. In 2007, parents (n=99) and elementary school staff (n=17) received disposable cameras to document their perspective. Using their photographs and narratives, participants developed emergent themes during a facilitated group discussion. In 2008, study authors used the Analysis Grid for Environments Linked to Obesity (ANGELO) framework to categorize the themes.
Results: Microenvironment themes include physical (e.g., natural features, topography); sociocultural (e.g., isolation); policy (e.g., time for school recess); and economic (e.g., funding for physical activity programs). Macroenvironmental themes related to the built and natural environments and transportation infrastructure.
Conclusions: This study identified rural environment elements that community members perceived as influencing children's physical activity patterns. Certain aspects were unique to rural areas, whereas other urban and suburban factors may be generalizable to rural settings. PhotoVOICE was a useful participatory research method to gain insight into perceived factors affecting rural children's physical activity behaviors. (Am J Prev Med 2010; 39(6): 537-545) (C) 2010 American Journal of Preventive Medicine
C1 [Hennessy, Erin] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA.
[Bloom, Julia; Economos, Christina D.] Tufts Univ, John Hancock Res Ctr Phys Act Nutr & Obes Prevent, Gerald J & Dorothy R Friedman Sch Nutr Sci Policy, Boston, MA 02111 USA.
[Hyatt, Raymond R.] Tufts Univ, Sch Med, Dept Family Med & Publ Hlth, Boston, MA 02111 USA.
[Kraak, Vivica I.] Deakin Univ, Deakin Populat Hlth Strateg Res Ctr, Melbourne, Vic, Australia.
[Wagoner, Colby] Kentucky Dept Educ, Coordinated Sch Hlth, Frankfort, KY USA.
RP Hennessy, E (reprint author), NCI, Canc Prevent Fellowship Program, NIH, Execut Plaza S,Suite 150E,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM erin.hennessy@nih.gov
OI Kraak, Vivica/0000-0002-9303-5530
FU Robert Wood Johnson Foundation [59458]; Save the Children's U.S.
Programs; New Balance Foundation
FX This study was funded by the Robert Wood Johnson Foundation's Active
Living Research Program (Grant No. 59458). Additional support was
provided by Save the Children's U.S. Programs and the New Balance
Foundation. The authors would like to thank the families and school
staff who participated in this study and Save the Children's field staff
who facilitated the participant recruitment and assisted with data
collection.
NR 53
TC 16
Z9 16
U1 1
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD DEC
PY 2010
VL 39
IS 6
BP 537
EP 545
DI 10.1016/j.amepre.2010.09.013
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 680LT
UT WOS:000284234100010
PM 21084074
ER
PT J
AU Phelan, S
Wing, RR
Loria, CM
Kim, Y
Lewis, CE
AF Phelan, Suzanne
Wing, Rena R.
Loria, Catherine M.
Kim, Yongin
Lewis, Cora E.
TI Prevalence and Predictors of Weight-Loss Maintenance in a Biracial
Cohort Results from the Coronary Artery Risk Development in Young Adults
Study
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID SUGAR-SWEETENED BEVERAGES; BODY-MASS INDEX; SOCIAL SUPPORT; LIFE-STYLE;
FOLLOW-UP; OBESITY; OVERWEIGHT; CARDIA; METAANALYSIS; HEALTH
AB Background: Few population-based studies have examined the behavioral and psychosocial predictors of long-term weight-loss maintenance.
Purpose: The goal of this study was to determine the prevalence and predictors of weight-loss maintenance in a biracial cohort of younger adults.
Methods: This study examined a population-based sample of overweight/obese African-American and white men and women who had >= 5% weight loss between 1995 and 2000. Subsequent changes in weight, physical activity, and behavioral and psychosocial factors were examined between 2000 and 2005. Analyses were conducted in 2008-2009.
Results: Among the 1869 overweight/obese individuals without major disease in 1995, a total of 536 (29%) lost >= 5% between 1995 and 2000. Among those who lost weight, 34% (n=180) maintained at least 75% of their weight loss between 2000 and 2005, whereas 66% subsequently regained. Higher odds of successful weight-loss maintenance were related to African-American race (OR=1.7, p=0.03); smoking (OR=3.4, p=0.0001); history of diabetes (OR=2.2, p=0.04); increases in moderate physical activity between 2000 and 2005 (OR=1.4, p=0.005); increases in emotional support over the same period (OR=1.6, p=0.01); and less sugar-sweetened soft drink consumption in 2005 (OR=0.8, p=0.006).
Conclusions: One third of overweight men and women who lost weight were able to maintain 75% or more of their weight loss over 5 years. Interventions to promote weight-loss maintenance may benefit from targeting increased physical activity and emotional support and decreased sugar-sweetened soft drink consumption. (Am J Prev Med 2010;39(6):546-554) (C) 2010 American Journal of Preventive Medicine
C1 [Phelan, Suzanne] Calif Polytech State Univ San Luis Obispo, Dept Kinesiol, San Luis Obispo, CA 93407 USA.
[Wing, Rena R.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Wing, Rena R.] Miriam Hosp, Providence, RI 02906 USA.
[Loria, Catherine M.] NHLBI, Bethesda, MD 20892 USA.
[Kim, Yongin; Lewis, Cora E.] Univ Alabama, Div Prevent Med, Birmingham, AL USA.
RP Phelan, S (reprint author), 1 Grand Ave, San Luis Obispo, CA 93407 USA.
EM sphelan@calpoly.edu
FU University of Alabama at Birmingham, Coordinating Center [N01-HC-95095];
University of Alabama at Birmingham, Field Center [N01-HC-48047];
University of Minnesota, Field Center and Diet Reading Center
[N01-HC-48048]; Northwestern University, Field Center [N01-HC-48049];
Kaiser Foundation Research Institute [N01-HC-48050]; National Heart,
Lung, and Blood Institute
FX Work on this manuscript was supported (or partially supported) by the
following contracts: University of Alabama at Birmingham, Coordinating
Center, N01-HC-95095; University of Alabama at Birmingham, Field Center,
N01-HC-48047; University of Minnesota, Field Center and Diet Reading
Center (Year 20 Exam), N01-HC-48048; Northwestern University, Field
Center, N01-HC-48049; and Kaiser Foundation Research Institute,
N01-HC-48050, from the National Heart, Lung, and Blood Institute. NHLBI
had input into the overall design and conduct of the CARDIA study. The
NHLBI co-author, Dr. Loria, was involved in all stages of the current
study, including study concept and design, analysis, interpretation, and
write-up.
NR 64
TC 30
Z9 30
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD DEC
PY 2010
VL 39
IS 6
BP 546
EP 554
DI 10.1016/j.amepre.2010.08.008
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 680LT
UT WOS:000284234100011
PM 21084075
ER
PT J
AU Hesse, BW
AF Hesse, Bradford W.
TI Time to Reboot Resetting Health Care to Support Tobacco Dependency
Treatment Services
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Editorial Material
ID INFORMATION-TECHNOLOGY; SMOKING-CESSATION; CANCER CARE; INTERVENTION;
QUALITY; REFORM; RECORD
C1 NCI, Hlth Commun & Informat Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Hesse, BW (reprint author), NCI, Hlth Commun & Informat Res Branch, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7365, Bethesda, MD 20892 USA.
EM hesseb@mail.nih.gov
OI Hesse, Bradford/0000-0003-1142-1161
FU Intramural NIH HHS [Z99 CA999999]
NR 29
TC 10
Z9 10
U1 1
U2 1
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 2010
VL 39
IS 6
SU 1
BP S85
EP S87
DI 10.1016/j.amepre.2010.08.017
PG 3
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 679GK
UT WOS:000284149600014
PM 21074683
ER
PT J
AU Cuthbert, B
AF Cuthbert, Bruce
TI Early Prevention in Childhood Anxiety Disorders
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Editorial Material
ID BEHAVIORAL-INHIBITION; SOCIAL ANXIETY; CHILDREN; ADOLESCENTS;
PERSONALITY; FRAMEWORK; RISK
C1 NIMH, Bethesda, MD 20892 USA.
RP Cuthbert, B (reprint author), NIMH, 6001 Executive Blvd MSC 9632, Bethesda, MD 20892 USA.
EM bcuthber@mail.nih.gov
NR 12
TC 1
Z9 2
U1 0
U2 1
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD DEC
PY 2010
VL 167
IS 12
BP 1428
EP 1430
DI 10.1176/appi.ajp.2010.10091316
PG 3
WC Psychiatry
SC Psychiatry
GA 689ON
UT WOS:000284937700004
PM 21131407
ER
PT J
AU Perlis, RH
Huang, J
Purcell, S
Fava, M
Rush, AJ
Sullivan, PF
Hamilton, SP
McMahon, FJ
Schulze, T
Potash, JB
Zandi, PP
Willour, VL
Penninx, BW
Boomsma, DI
Vogelzangs, N
Middeldorp, CM
Rietschel, M
Nothen, M
Cichon, S
Gurling, H
Bass, N
McQuillin, A
Hamshere, M
Craddock, N
Sklar, P
Smoller, JW
AF Perlis, Roy H.
Huang, Jie
Purcell, Shaun
Fava, Maurizio
Rush, A. John
Sullivan, Patrick F.
Hamilton, Steven P.
McMahon, Francis J.
Schulze, Thomas
Potash, James B.
Zandi, Peter P.
Willour, Virginia L.
Penninx, Brenda W.
Boomsma, Dorret I.
Vogelzangs, Nicole
Middeldorp, Christel M.
Rietschel, Marcella
Noethen, Markus
Cichon, Sven
Gurling, Hugh
Bass, Nick
McQuillin, Andrew
Hamshere, Marian
Craddock, Nick
Sklar, Pamela
Smoller, Jordan W.
CA Wellcome Trust Case Control Consor
TI Genome-Wide Association Study of Suicide Attempts in Mood Disorder
Patients
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID TREATMENT ENHANCEMENT PROGRAM; BIPOLAR DISORDER; PSYCHIATRIC-DISORDERS;
DIAGNOSTIC INTERVIEW; DEPRESSIVE DISORDER; MAJOR DEPRESSION;
BINDING-PROTEIN; STEP-BD; GENE; BEHAVIOR
AB Objective: Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts.
Method: The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/ Netherlands Twin Register depression cohort.
Results: Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. Conclusions: The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.
C1 Massachusetts Gen Hosp, Dept Psychiat, Depress & Bipolar Clin, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA.
Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore.
Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
NIMH, Genet Basis Mood & Anxiety Disorders Div, Bethesda, MD 20892 USA.
Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA.
Vrije Univ Amsterdam, Univ Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
Vrije Univ Amsterdam, Univ Med Ctr, Dept Biol Psychol, Amsterdam, Netherlands.
Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany.
Univ Heidelberg, Heidelberg, Germany.
Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany.
Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany.
Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany.
Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany.
UCL, Dept Mol Psychiat, Sch Med, London WC1E 6BT, England.
Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales.
Massachusetts Gen Hosp, Res Programs, Boston, MA 02114 USA.
RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Bipolar Clin, 50 Staniford St,Suite 580, Boston, MA 02114 USA.
EM rperlis@partners.org
RI Gurling, Hugh/A-5029-2010; Cichon, Sven/H-8803-2013; Cichon,
Sven/B-9618-2014; McQuillin, Andrew/C-1623-2008;
OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X;
McQuillin, Andrew/0000-0003-1567-2240; Hamilton,
Steven/0000-0001-8106-6260; Rush, Augustus/0000-0003-2004-2382; McMahon,
Francis/0000-0002-9469-305X; Nothen, Markus/0000-0002-8770-2464;
Middeldorp, Christel/0000-0002-6218-0428
FU Eli Lilly; Elan/Eisai; AstraZeneca; Bristol-Myers Squibb; Pfizer;
GlaxoSmithKline; Abbott Laboratories; Alkermes; Aspect Medical Systems;
Cephalon; Forest Pharmaceuticals; J and J Pharmaceuticals; Lichtwer
Pharma GmbH; Lorex Pharmaceuticals; Novartis; Organon; Pamlab;
Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals;
Wyeth-Ayerst Laboratories; Bayer AG; Biovail Pharmaceuticals;
BrainCells; Compellis; Cypress Pharmaceuticals; Dov Pharmaceuticals;
EPIX Pharmaceuticals; Fabre-Kramer Pharmaceuticals; Grunenthal GmbH;
Janssen Pharmaceutica; Jazz Pharmaceuticals; Knoll Pharmaceutical;
Lundbeck; MedAvante; Neuronetics; Nutrition 21; PharmaStar; Sepracor;
Somaxon; Somerset Pharmaceuticals; Boehringer-Ingelheim; Guilford
Publications and Healthcare Technology Systems; National Institute of
Mental Health [R01MH-086026]; NIMH
FX Dr. Perlis has received research support from Eli Lilly and Elan/Eisai;
he has received advisory/consulting fees from AstraZeneca, Bristol-Myers
Squibb, Eli Lilly, and Pfizer; he has received speaking fees or
honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly,
GlaxoSmithKline, and Pfizer; and he has equity holdings and patents with
Concordant Rater Systems. Dr. Fava has received research support from
Abbott Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca,
Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Pharmaceuticals,
GlaxoSmithKline, J and J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex
Pharmaceuticals, Novartis, Organon, Pamlab, Pfizer, Pharmavite, Roche,
Sanofi/Synthelabo, Solvay Pharmaceuticals, and Wyeth-Ayerst
Laboratories; he has received advisory/consulting fees from Aspect
Medical Systems, AstraZeneca, Bayer AG, Biovail Pharmaceuticals,
BrainCells, Bristol-Myers Squibb, Cephalon, Compellis, Cypress
Pharmaceuticals, Dov Pharmaceuticals, Eli Lilly, EPIX Pharmaceuticals,
Fabre-Kramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline,
Grunenthal GmbH, Janssen Pharmaceutica, Jazz Pharmaceuticals, J and J
Pharmaceuticals, Knoll Pharmaceutical, Lundbeck, MedAvante, Neuronetics,
Novartis, Nutrition 21, Organon, Pamlab, Pfizer, PharmaStar, Pharmavite,
Roche, Sanofi/Synthelabo, Sepracor, Solvay Pharmaceuticals, Somaxon,
Somerset Pharmaceuticals, and Wyeth-Ayerst Laboratories; he has received
speaking fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers
Squibb, Cephalon, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline,
Novartis, Organon, Pfizer, PharmaStar, and Wyeth-Ayerst Laboratories;
and he is a share holder with Compellis and MedAvante. Dr. Rush has
served as a consultant for AstraZeneca, Bristol-Myers Squibb/Otsuka,
Merck, and Otsuka Pharmaceuticals; he has also received royalties from
Guilford Publications and Healthcare Technology Systems. Dr. Smoller has
served as a consultant to Eli Lilly; he has received honoraria from
Hoffman-La Roche, Enterprise Analysis, and MPM Capital; and he has
served on an advisory board for Roche Diagnostics Corporation. Dr
Sullivan receives unrestricted research funding from Eli Lilly for
genetic research in schizophrenia. All other authors report no financial
relationships with commercial interests.; Supported by National
Institute of Mental Health grant R01MH-086026 (Dr. Perlis). Drs. McMahon
and Schulze are supported by the NIMH Intramural Research Program.
NR 66
TC 51
Z9 51
U1 2
U2 7
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD DEC
PY 2010
VL 167
IS 12
BP 1499
EP 1507
DI 10.1176/appi.ajp.2010.10040541
PG 9
WC Psychiatry
SC Psychiatry
GA 689ON
UT WOS:000284937700014
PM 21041247
ER
PT J
AU Feyder, M
Karlsson, RM
Mathur, P
Lyman, M
Bock, R
Momenan, R
Munasinghe, J
Scattoni, ML
Ihne, J
Camp, M
Graybeal, C
Strathdee, D
Begg, A
Alvarez, VA
Kirsch, P
Rietschel, M
Cichon, S
Walter, H
Meyer-Lindenberg, A
Grant, SGN
Holmes, A
AF Feyder, Michael
Karlsson, Rose-Marie
Mathur, Poonam
Lyman, Matthew
Bock, Roland
Momenan, Reza
Munasinghe, Jeeva
Scattoni, Maria Luisa
Ihne, Jessica
Camp, Marguerite
Graybeal, Carolyn
Strathdee, Douglas
Begg, Alison
Alvarez, Veronica A.
Kirsch, Peter
Rietschel, Marcella
Cichon, Sven
Walter, Henrik
Meyer-Lindenberg, Andreas
Grant, Seth G. N.
Holmes, Andrew
TI Association of Mouse Dlg4 (PSD-95) Gene Deletion and Human DLG4 Gene
Variation With Phenotypes Relevant to Autism Spectrum Disorders and
Williams' Syndrome
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID SUPRAVALVULAR AORTIC STENOSIS; DENDRITIC SPINES; BEHAVIORAL PHENOTYPES;
SYNAPTIC-TRANSMISSION; MENTAL-RETARDATION; NEURAL MECHANISMS; FRAGILE-X;
MICE; PROTEIN; MODEL
AB Objective: Research is increasingly linking autism spectrum disorders and other neurodevelopmental disorders to synaptic abnormalities ("synaptopathies"). PSD-95 (postsynaptic density-95, DLG4) orchestrates protein-protein interactions at excitatory synapses and is a major functional bridge interconnecting a neurexin-neuroligin-SHANK pathway implicated in autism spectrum disorders.
Method: The authors characterized behavioral, dendritic, and molecular phenotypic abnormalities relevant to autism spectrum disorders in mice with PSD-95 deletion (Dlg4(-/-)). The data from mice led to the identification of single-nucleotide polymorphisms (SNPs) in human DLG4 and the examination of associations between these variants and neural signatures of Williams' syndrome in a normal population, using functional and structural neuroimaging.
Results: Dlg4(-/-) showed increased repetitive behaviors, abnormal communication and social behaviors, impaired motor coordination, and increased stress reactivity and anxiety-related responses. Dlg4(-/-) had subtle dysmorphology of amygdala dendritic spines and altered forebrain expression of various synaptic genes, including Cyln2, which regulates cytoskeletal dynamics and is a candidate gene for Williams' syndrome. A significant association was observed between variations in two human DLG4 SNPs and reduced intraparietal sulcus volume and abnormal cortico-amygdala coupling, both of which characterize Williams' syndrome.
Conclusions: These findings demonstrate that Dlg4 gene disruption in mice produces a complex range of behavioral and molecular abnormalities relevant to autism spectrum disorders and Williams' syndrome. The study provides an initial link between human DLG4 gene variation and key neural endophenotypes of Williams' syndrome and perhaps cortico-amygdala regulation of emotional and social processes more generally.
C1 [Feyder, Michael] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, Rockville, MD 20852 USA.
NIAAA, Sect Synapt Pharmacol, Rockville, MD 20852 USA.
NIAAA, Sect Neuronal Struct, Lab Integrat Neurosci, Rockville, MD 20852 USA.
NIAAA, Sect Brain Electrophysiol & Imaging, Lab Clin & Translat Studies, Rockville, MD 20852 USA.
Ist Super Sanita, Sect Neurotoxicol & Neuroendocrinol, Dept Cell Biol & Neurosci, I-00161 Rome, Italy.
Wellcome Trust Sanger Inst, Hinxton, England.
Univ Edinburgh, Ctr Neurosci, Edinburgh, Midlothian, Scotland.
Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-6800 Mannheim, Germany.
Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany.
Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany.
Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany.
Univ Bonn, Div Med Psychol, Dept Psychiat & Psychotherapy, D-5300 Bonn, Germany.
RP Feyder, M (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, 5625 Fishers Lane,Rm 2N09, Rockville, MD 20852 USA.
EM michael.feyder@ki.se
RI Walter, Henrik/O-2612-2013; Cichon, Sven/H-8803-2013; Alvarez, Veronica
/E-9745-2015; Bock, Roland/G-2982-2016; Meyer-Lindenberg,
Andreas/H-1076-2011;
OI Cichon, Sven/0000-0002-9475-086X; Alvarez, Veronica
/0000-0003-2611-8675; Bock, Roland/0000-0002-8654-1080;
Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Kirsch,
Peter/0000-0002-0817-1248; Reed, Jessica/0000-0003-0550-7284
FU AstraZeneca; Hoffmann LaRoche; Janssen-Cilag; Pfizer; Landes-Offensive
zur Entwicklung Wissenschaftlich-okonomischer Exzellenz; NIAAA;
Bundesministerium fur Bildung und Forschung (Nationales
Genomforschungsnetz plus MooDs); Deutsche Forschungsgemeinschaft [SFB
636-B7]; Wellcome Trust
FX Dr. Meyer-Lindenberg has received funding from AstraZeneca, Hoffmann
LaRoche, Janssen-Cilag, Pfizer, and Landes-Offensive zur Entwicklung
Wissenschaftlich-okonomischer Exzellenz and receives compensation from
Thieme for serving as an editor of Pharmacopsychiatry. All other authors
report no competing interests.; Supported by the NIAAA Intramural
Research Program (Dr. Holmes), Bundesministerium fur Bildung und
Forschung (Nationales Genomforschungsnetz plus MooDs) (Dr.
Meyer-Lindenberg), Deutsche Forschungsgemeinschaft (SFB 636-B7) (Dr.
Meyer-Lindenberg), and the Wellcome Trust Genes to Cognition program
(Dr. Grant).
NR 45
TC 75
Z9 77
U1 1
U2 17
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD DEC
PY 2010
VL 167
IS 12
BP 1508
EP 1517
DI 10.1176/appi.ajp.2010.10040484
PG 10
WC Psychiatry
SC Psychiatry
GA 689ON
UT WOS:000284937700015
PM 20952458
ER
PT J
AU Blair, KS
Geraci, M
Hollon, N
Otero, M
DeVido, J
Majestic, C
Jacobs, M
Blair, RJR
Pine, DS
AF Blair, Karina S.
Geraci, Marilla
Hollon, Nick
Otero, Marcela
DeVido, Jeffrey
Majestic, Catherine
Jacobs, Madeline
Blair, R. J. R.
Pine, Daniel S.
TI Social Norm Processing in Adult Social Phobia: Atypically Increased
Ventromedial Frontal Cortex Responsiveness to Unintentional
(Embarrassing) Transgressions
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID ANXIETY-DISORDER; PREFRONTAL CORTEX; NEURAL RESPONSE; SELF-CRITICISM;
FMRI; BRAIN; METAANALYSIS; COMORBIDITY; ACTIVATION; JUDGMENTS
AB Objective: Little is known about the neural underpinnings of generalized social phobia, which is defined by a persistent heightened fear of social disapproval. Using event-related functional MRI (fMRI), the authors examined whether the intent of an event, which mediates the neural response to social disapproval in healthy individuals, differentially affects response in generalized social phobia.
Method: Sixteen patients with generalized social phobia and 16 healthy comparison subjects group-matched on age, gender, and IQ underwent fMRI scans while reading stories that involved neutral social events, unintentional social transgressions (e.g., choking on food at a party and coughing it up), or intentional social transgressions (e.g., disliking food at a party and spitting it out).
Results: Significant group-by-transgression interactions were observed in ventral regions of the medial prefrontal cortex. Healthy individuals tended to show increased blood-oxygen-level-dependent responses to intentional relative to unintentional transgressions. Patients with generalized social phobia, however, showed significantly increased responses to the unintentional transgressions. They also rated the unintentional transgressions as significantly more embarrassing than did the comparison subjects. Results also revealed significant group main effects in the amygdala and insula bilaterally, reflecting elevated generalized social phobia responses in these regions to all event types.
Conclusions: These results further implicate the medial prefrontal cortex in the pathophysiology of generalized social phobia, specifically through its involvement in distorted self-referential processing. These results also further underscore the extended role of the amygdala and insula in the processing of social stimuli more generally in generalized social phobia.
C1 [Blair, Karina S.; Geraci, Marilla; Hollon, Nick; Otero, Marcela; DeVido, Jeffrey; Majestic, Catherine; Jacobs, Madeline; Blair, R. J. R.; Pine, Daniel S.] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA.
RP Blair, KS (reprint author), NIMH, Mood & Anxiety Program, 15K N Dr,MSC 2670, Bethesda, MD 20892 USA.
EM peschark@mail.nih.gov
FU NIMH
FX Supported by the NIMH Intramural Research Program.
NR 34
TC 23
Z9 23
U1 7
U2 18
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD DEC
PY 2010
VL 167
IS 12
BP 1526
EP 1532
DI 10.1176/appi.ajp.2010.09121797
PG 7
WC Psychiatry
SC Psychiatry
GA 689ON
UT WOS:000284937700017
PM 20889651
ER
PT J
AU Parry, M
AF Parry, Manon
TI From a Patient's Perspective: Clifford Whittingham Beers' Work to Reform
Mental Health Services
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 Natl Lib Med, Exhibit Program, Bethesda, MD 20894 USA.
RP Parry, M (reprint author), Natl Lib Med, Exhibit Program, 8600 Rockville Pike,Bldg 38,Room 1E-21, Bethesda, MD 20894 USA.
NR 6
TC 0
Z9 0
U1 0
U2 1
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD DEC
PY 2010
VL 100
IS 12
BP 2356
EP 2357
DI 10.2105/AJPH.2010.191411
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 684QB
UT WOS:000284563300010
PM 21068416
ER
PT J
AU Cai, XO
Pacheco-Rodriguez, G
Fan, QY
Haughey, M
Samsel, L
El-Chemaly, S
Wu, HP
McCoy, JP
Steagall, WK
Lin, JP
Darling, TN
Moss, J
AF Cai, Xiong
Pacheco-Rodriguez, Gustavo
Fan, Qing-Yuan
Haughey, Mary
Samsel, Leigh
El-Chemaly, Souheil
Wu, Hai-Ping
McCoy, J. Philip
Steagall, Wendy K.
Lin, Jing-Ping
Darling, Thomas N.
Moss, Joel
TI Phenotypic Characterization of Disseminated Cells with TSC2 Loss of
Heterozygosity in Patients with Lymphangioleiomyomatosis
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE lymphangioleiomyomatosis; metastasis; loss of heterozygosity; CD9;
CD44v6
ID TUBEROUS SCLEROSIS COMPLEX; PULMONARY LYMPHANGIOLEIOMYOMATOSIS;
TETRASPANIN PROTEINS; TUMOR-CELLS; CANCER; METASTASIS; GENE; MUTATIONS;
16P13; CD44
AB Rationale: Lymphangioleiomyomatosis (LAM), occurring sporadically (S-LAM) or in patients with tuberous sclerosis complex (TSC), results from abnormal proliferation of LAM cells exhibiting mutations or loss of heterozygosity (LOH) of the TSC genes, TSC1 or TSC2.
Objectives: To identify molecular markers useful for isolating LAM cells from body fluids and determine the frequency of TSC1 or TSC2 LOH.
Methods: Candidate cell surface markers were identified using gene microarray analysis of human TSC2(-/-) cells. Cells from bronchoalveolar lavage fluid (BALF), urine, chylous effusions, and blood were sorted based on reactivity with antibodies against these proteins (e.g., CD9, CD44v6) and analyzed for LOH using TSC1- and TSC2-related microsatellite markers and single nucleotide polymorphisms in the TSC2 gene.
Measurements and Main Results: CD44v6(+)CD9(+) cells from BALF, urine, and chyle showed TSC2 LOH in 80%, 69%, and 50% of patient samples, respectively. LAM cells with TSC2 LOH were detected in more than 90% of blood samples. LAM cells from different body fluids of the same patients showed, in most cases, identical LOH patterns, that is, loss of alleles at the same microsatellite loci. In a few patients with S-LAM, LAM cells from different body fluids differed in LOH patterns. No patients with S-LAM with TSC1 LOH were identified, suggesting that TSC2 abnormalities are responsible for the vast majority of S-LAM cases and that TSC1-disease may be subclinical.
Conclusions: Our data support a common genetic origin of LAM cells in most patients with S-LAM, consistent with a metastatic model. In some cases, however, there was evidence for genetic heterogeneity between LAM cells in different sites or within a site.
C1 [Cai, Xiong; Pacheco-Rodriguez, Gustavo; Fan, Qing-Yuan; Haughey, Mary; El-Chemaly, Souheil; Wu, Hai-Ping; Steagall, Wendy K.; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Samsel, Leigh; McCoy, J. Philip] NHLBI, Flow Cytometry Core Facil, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Lin, Jing-Ping] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD USA.
RP Moss, J (reprint author), NHLBI, Translat Med Branch, Natl Inst Hlth, Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA.
EM mossj@nhlbi.nih.gov
OI Darling, Thomas/0000-0002-5161-1974
FU National Institutes of Health [R01, R21]; National Heart, Lung, and
Blood Institute; Department of Defense; [RO1 CA100907]
FX Supported in part by the Intramural Research Program of the National
Institutes of Health, National Heart, Lung, and Blood Institute (J.M.);
and by RO1 CA100907 (T.N.D.).; Disclosure: X.C. is employed by the
National Institutes of Health (NIH) as a postdoctoral visiting fellow.
G.P-R. does not have a financial relationship with a commercial entity
that has an interest in the subject of this manuscript. Q-Y.F. does not
have a financial relationship with a commercial entity that has an
interest in the subject of this manuscript. M.H. is an employee of the
NIH. L.S. is a full-time employee of the NIH. S.E-C. does not have a
financial relationship with a commercial entity that has an interest in
the subject of this manuscript. H-P.W. is an employee of the NIH. J.P.M.
and J.P.M.'s spouse/life partner are employees of the NIH and owned
$5,001-$10,000 in stock ownership or options in Altria within the last
12 months or at present. W.K.S. is an employee of the NIH. J-P.L. does
not have a financial relationship with a commercial entity that has an
interest in the subject of this manuscript. T.N.D. received more than
$100,001 from the NIH in sponsored grants (R01, R21) and more than
$100,001 from the Department of Defense in sponsored grants (CDMRP,
DMRDP grants). J.M. has received $1,001-$5000 in patent royalties from
the NIH for an invention licensed by Emiliem. J.M. is employed by the
NIH.
NR 48
TC 30
Z9 30
U1 0
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD DEC 1
PY 2010
VL 182
IS 11
BP 1410
EP 1418
DI 10.1164/rccm.201003-0489OC
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 690OA
UT WOS:000285012900012
PM 20639436
ER
PT J
AU Zheng, CL
Wang, LY
Li, R
Ma, B
Tu, L
Xu, XZ
Dackor, RT
Zeldin, DC
Wang, DW
AF Zheng, Changlong
Wang, Luyun
Li, Rui
Ma, Ben
Tu, Ling
Xu, Xizhen
Dackor, Ryan T.
Zeldin, Darryl C.
Wang, Dao Wen
TI Gene Delivery of Cytochrome P450 Epoxygenase Ameliorates
Monocrotaline-Induced Pulmonary Artery Hypertension in Rats
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE arachidonic acids; cytochrome P450 epoxygenase; gene therapy;
monocrotaline
ID NITRIC-OXIDE SYNTHASE; GROWTH-FACTOR-BETA; SOLUBLE EPOXIDE HYDROLASE;
ACTIVATED PROTEIN-KINASE; ENDOTHELIAL-CELL GROWTH; EPOXYEICOSATRIENOIC
ACIDS; SMOOTH-MUSCLE; SIGNALING PATHWAYS; 5,6-EPOXYEICOSATRIENOIC ACID;
GERMLINE MUTATIONS
AB Pulmonary arterial hypertension (PAH) is a life-threatening disease that leads to progressive pulmonary hypertension, right heart failure, and death. Endothelial dysfunction and inflammation were implicated in the pathogenesis of PAH. Epoxyeicosatrienoic acids (EETs), products of the cytochrome P450 epoxygenase metabolism of arachidonic acid, are potent vasodilators that possess anti-inflammatory and other protective properties in endothelial cells. We investigated whether gene delivery with the human cytochrome P450 epoxygenase 2J2 (CYP2J2) ameliorates monocrotaline (MCT)-induced pulmonary hypertension in rats. Significant pulmonary hypertension developed 3 weeks after the administration of MCT, but gene therapy with CYP2J2 significantly attenuated the development of pulmonary hypertension and pulmonary vascular remodeling, without causing changes in systemic arterial pressure or heart rate. These effects were associated with increased pulmonary endothelial NO synthase (eNOS) expression and its activity, inhibition of inflammation in the lungs, and transforming growth factor (TGF)-beta/type II bonemorphogenetic protein receptor (BMPRII)-drosophila mothers against decapentaplegic proteins (Smads) signaling. Collectively, these data suggest that gene therapy with CYP2J2 may have potential as a novel therapeutic approach to this progressive and oftentimes lethal disorder.
C1 [Zheng, Changlong; Wang, Luyun; Li, Rui; Ma, Ben; Tu, Ling; Xu, Xizhen; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Internal Med, Wuhan 430030, Peoples R China.
[Zheng, Changlong; Wang, Luyun; Li, Rui; Ma, Ben; Tu, Ling; Xu, Xizhen; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Gene Therapy Ctr, Wuhan 430030, Peoples R China.
[Dackor, Ryan T.; Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, Res Triangle Pk, NC USA.
RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Internal Med, Wuhan 430030, Peoples R China.
EM dwwang@tjh.tjmu.edu.cn
FU 973 Program [2007CB512004, 2006CB503801]; National Nature Science
Foundation Committee of China [30430320, 30971247]; National Institute
of Environmental Health Sciences at the National Institutes of Health
[Z01 ES025034]
FX This work was supported by grants 2007CB512004 and 2006CB503801 from the
973 Program, and by grants 30430320 and 30971247 from National Nature
Science Foundation Committee of China. This work was also supported, in
part, by grant Z01 ES025034 from the Intramural Research Program of the
National Institute of Environmental Health Sciences at the National
Institutes of Health.
NR 55
TC 16
Z9 18
U1 1
U2 5
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1044-1549
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD DEC
PY 2010
VL 43
IS 6
BP 740
EP 749
DI 10.1165/rcmb.2009-0161OC
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 690OD
UT WOS:000285013200013
PM 20118222
ER
PT J
AU Guerrero, MA
Suh, I
Vriens, MR
Shen, WT
Gosnell, J
Kebebew, E
Clark, OH
Duh, QY
AF Guerrero, Marlon A.
Suh, Insoo
Vriens, Menno R.
Shen, Wen T.
Gosnell, Jessica
Kebebew, Electron
Clark, Orlo H.
Duh, Quan-Yang
TI The number of needle passes affects the accuracy of parathyroid hormone
assay with intraoperative parathyroid aspiration
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Article
DE Intraoperative; Parathyroid hormone assay; Parathyroid aspiration;
Aspiration technique; Needle passes; Primary hyperparathyroidism
ID FROZEN-SECTION; TISSUE
AB INTRODUCTION: Intraoperative aspiration of a nodule and parathyroid hormone (PTH) assay has been shown to accurately confirm parathyroid tissue. However, the reported aspiration technique varies in the literature. We sought to determine if the number of passes affected the accuracy of PTH analysis.
METHODS: A prospective analysis was performed on 25 consecutive patients who underwent a parathyroidectomy for primary hyperparathyroidism. The excised parathyroid gland was aspirated using 1, 3, and 5 passes. The data were analyzed using the Wilcoxon rank, chi-square, and Fisher exact tests to calculate the 2-tailed P value.
RESULTS: Of the 26 glands aspirated, the mean PTH value varied with the number of passes, 2,073 pg/mL for I pass, 2,347 for 3 passes, and 2,695 for 5 passes (P = .02). Accuracy was dependent on the number of passes,,with 5 passes (P = .018) having less PTH variation than 1 or 3 passes.
CONCLUSIONS: Aspiration of nodules to determine the PTH level helps confirm the presence of parathyroid tissue. The number of needle passes affects the accuracy of the PTH level, with 5 passes being the optimal number of passes to attain no false-negative results. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Guerrero, Marlon A.] Univ Arizona, Dept Surg, Tucson, AZ 85724 USA.
[Suh, Insoo; Vriens, Menno R.; Shen, Wen T.; Gosnell, Jessica; Clark, Orlo H.; Duh, Quan-Yang] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA.
[Kebebew, Electron] NCI, Surg Branch, Bethesda, MD 20892 USA.
RP Guerrero, MA (reprint author), Univ Arizona, Dept Surg, 1515 N Campbell Ave, Tucson, AZ 85724 USA.
EM mguerrero@surgery.arizona.edu
NR 11
TC 4
Z9 5
U1 0
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
J9 AM J SURG
JI Am. J. Surg.
PD DEC
PY 2010
VL 200
IS 6
BP 701
EP 705
DI 10.1016/j.amjsurg.2010.06.012
PG 5
WC Surgery
SC Surgery
GA 708EO
UT WOS:000286344900008
PM 21146006
ER
PT J
AU Crump, JA
Sugarman, J
AF Crump, John A.
Sugarman, Jeremy
CA Working Grp Ethics
TI Ethics and Best Practice Guidelines for Training Experiences in Global
Health
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID MEDICAL-STUDENTS; INTERNATIONAL HEALTH; DEVELOPING-COUNTRIES; ELECTIVES;
OPPORTUNITIES; SCHOOL; US
AB Academic global health programs are growing rapidly in scale and number. Students of many disciplines increasingly desire global health content in their curricula. Global health curricula often include field experiences that involve crossing international and socio-cultural borders. Although global health training experiences offer potential benefits to trainees and to sending institutions, these experiences are sometimes problematic and raise ethical challenges. The Working Group on Ethics Guidelines for Global Health Training (WEIGHT) developed a set of guidelines for institutions, trainees, and sponsors of field-based global health training on ethics and best practices in this setting. Because only limited data have been collected within the context of existing global health training, the guidelines were informed by the published literature and the experience of WEIGHT members. The Working Group on Ethics Guidelines for Global Health Training encourages efforts to develop and implement a means of assessing the potential benefits and harms of global health training programs.
C1 [Crump, John A.] Duke Univ, Div Infect Dis & Int Hlth, Med Ctr, Durham, NC 27710 USA.
[Sugarman, Jeremy] Johns Hopkins Univ, Berman Inst Bioeth, Baltimore, MD 21205 USA.
[Sugarman, Jeremy] Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA.
Kilimanjaro Christian Med Ctr, Moshi, Tanzania.
Duke Univ, Duke Global Hlth Inst, Durham, NC USA.
Tumaini Univ, Kilimanjaro Christian Med Coll, Moshi, Tanzania.
Stanford Univ, Off Global Hlth, Stanford, CA 94305 USA.
Bioeth & Global Hlth, Pune, Maharashtra, India.
NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
SUNY Stony Brook, Dept Med, Sch Med, Stony Brook, NY 11794 USA.
SUNY Stony Brook, Sch Med, Dept Publ Hlth, Stony Brook, NY 11794 USA.
Emory Univ, Emory Global Hlth Inst, Atlanta, GA 30322 USA.
Naval Med Res Ctr Detachment, Lima, Peru.
Doris Duke Charitable Fdn, New York, NY USA.
BMJ, London, England.
London Sch Hyg & Trop Med, Clin Res Unit, London WC1, England.
Chulalongkorn Univ, Fac Med, Chula MRC, Bangkok 10330, Thailand.
Thai Red Cross AIDS Res Ctr, HIVNAT, Bangkok, Thailand.
Makerere Univ, Coll Hlth Sci, Kampala, Uganda.
RP Crump, JA (reprint author), Duke Univ, Div Infect Dis & Int Hlth, Med Ctr, Box 102359, Durham, NC 27710 USA.
EM crump017@mc.duke.edu; jsugarm1@jhmi.edu
RI yan, liu/A-1822-2015;
OI yan, liu/0000-0001-8517-1084; Sewankambo, Nelson/0000-0001-9362-053X
FU Wellcome Trust [WT089272MF]
FX The development of these guidelines was supported by grant no.
WT089272MF from the Wellcome Trust (http://www.wellcome.ac.uk/).
NR 30
TC 120
Z9 121
U1 4
U2 18
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD DEC
PY 2010
VL 83
IS 6
BP 1178
EP 1182
DI 10.4269/ajtmh.2010.10-0527
PG 5
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 697RX
UT WOS:000285534900003
PM 21118918
ER
PT J
AU Aravindhan, V
Mohan, V
Surendar, J
Rao, MM
Ranjani, H
Kumaraswami, V
Nutman, TB
Babu, S
AF Aravindhan, Vivekanandhan
Mohan, Vishwanathan
Surendar, Jayagopi
Rao, Maradana Muralidhara
Ranjani, Harish
Kumaraswami, V.
Nutman, Thomas B.
Babu, Subash
TI Decreased Prevalence of Lymphatic Filariasis Among Subjects with Type-1
Diabetes
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID HYGIENE HYPOTHESIS; SOUTH-INDIA; INFECTION; DISEASES; MICE; INHIBITION;
PREVENTION; INDUCTION; HELMINTHS; MELLITUS
AB Several animal studies have shown a protective effect of helminth infections against type-1 diabetes mellitus (T1DM). However, epidemiologic studies demonstrating this protective relationship with T1DM are largely lacking, although an inverse correlation between the prevalence of lymphatic filariasis (LF) and prevalence of allergies and autoimmunity has been shown. A cross-sectional study was undertaken in southern India to assess the baseline prevalence of seropositivity of LF among persons with T1DM (n = 200) and normal glucose tolerant (NGT) persons (n = 562). The prevalence of LF was 0% among persons with T1DM and 2.6% among NGT persons (P = 0.026). The percentage of persons who were positive for filarial antigen-specific IgG4 (but not antigen-specific IgG) was also significantly lower in persons with T1DM (2%) compared with NGT persons (28%) (P < 0.001). Thus, there appears to be a striking inverse relationship between the prevalence of LF and T1DM in southern India.
C1 [Aravindhan, Vivekanandhan] Anna Univ, KB Chandrashekar Res Ctr, Lab Mol Immunol, Chennai 600025, Tamil Nadu, India.
[Mohan, Vishwanathan; Surendar, Jayagopi; Rao, Maradana Muralidhara] Madras Diabet Res Fdn, Chennai, Tamil Nadu, India.
[Kumaraswami, V.; Babu, Subash] Indian Council Med Res, TB Res Ctr, Chennai, Tamil Nadu, India.
[Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Babu, Subash] Int Ctr Excellence Res, Natl Inst Hlth, Chennai, Tamil Nadu, India.
[Babu, Subash] Sci Applicat Int Corp Frederick Inc, Natl Canc Inst Frederick, Frederick, MD USA.
[Aravindhan, Vivekanandhan] Anna Univ, KB Chandrashekar Res Ctr Life Sci, Chennai 600025, Tamil Nadu, India.
RP Aravindhan, V (reprint author), Anna Univ, KB Chandrashekar Res Ctr, Lab Mol Immunol, Chennai 600025, Tamil Nadu, India.
EM cvaravindhan@gmail.com; drmohans@vsnl.net; surendarj85@gmail.com;
raoinfoster@gmail.com; ranjani_h@gmail.com; kumaraswamiv@trcchennai.in;
tnutman@niaid.nih.gov; sbabu@mail.nih.gov
OI Aravindhan, Vivekanandhan/0000-0002-5639-4948
FU Division of Intramural Research, National Institutes of Allergy and
Infectious Diseases, National Institutes of Health
FX This study was supported by the Intramural Research Program of the
Division of Intramural Research, National Institutes of Allergy and
Infectious Diseases, National Institutes of Health.
NR 33
TC 17
Z9 17
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD DEC
PY 2010
VL 83
IS 6
BP 1336
EP 1339
DI 10.4269/ajtmh.2010.10-0410
PG 4
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 697RX
UT WOS:000285534900030
PM 21118945
ER
PT J
AU Prause, AS
Guionaud, CT
Stoffel, MH
Portier, CJ
Mevissen, M
AF Prause, Andrea S.
Guionaud, Christophe T.
Stoffel, Michael H.
Portier, Christopher J.
Mevissen, Meike
TI Expression and function of 5-hydroxytryptamine 4 receptors in smooth
muscle preparations from the duodenum, ileum, and pelvic flexure of
horses without gastrointestinal tract disease
SO AMERICAN JOURNAL OF VETERINARY RESEARCH
LA English
DT Article
ID CIRCUIT CURRENT RESPONSE; GUINEA-PIG COLON; 5-HT4 RECEPTOR; IN-VITRO;
INTERSTITIAL-CELLS; PHARMACOLOGICAL CHARACTERIZATION; BICARBONATE
SECRETION; PULMONARY-ARTERY; PARTIAL AGONIST; SMALL-INTESTINE
AB Objective-To evaluate the expression of the 5-hydroxytryptamine 4 (5-HT(4)) receptor subtype and investigate the modulating function of those receptors on contractility in intestinal tissues obtained from horses without gastrointestinal tract disease
Sample Population-Smooth muscle preparations from the duodenum ileum and pelvic flexure collected immediately after slaughter of 24 horses with no history or signs of gastrointestinal tract disease
Procedures-In isometric organ baths the contractile activities of smooth muscle preparations in response to 5-hydroxytryptamine and electric field stimulation were assessed the effect of tegaserod alone or in combination with 5-hydroxytryptamine on contractility of intestinal specimens was also investigated Presence and distribution of 5-HT(4) receptors in intestinal tissues and localization on interstitial cells of Cajal were examined by use of an immunofluorescence technique
Results-Widespread 5-HT(4) receptor immunoreactivity was observed in all intestinal smooth muscle layers 5 HT(4) receptors were absent from the myenteric plexus and interstitial cells of Cajal In electrical field stimulated tissue preparations of duodenum and pelvic flexure tegaserod increased the amplitude of smooth muscle contractions in a concentration dependent manner Preincubation with tegaserod significantly decreased the basal tone of the 5-HT evoked contractility in small intestine specimens compared with the effect of 5-HT alone thereby confirming that tegaserod was acting as a partial agonist
Conclusions and Clinical Relevance-In horses 5 HT(4) receptors on smooth muscle cells appear to be involved in the contractile response of the intestinal tract to 5-hydroxytryptamine Results suggest that tegaserod may be useful for treatment of reduced gastrointestinal tract motility in horses (Am J Vet Res 2010 71 1432-1442)
C1 [Prause, Andrea S.; Guionaud, Christophe T.; Mevissen, Meike] Univ Bern, Div Vet Pharmacol & Toxicol, CH-3012 Bern, Switzerland.
[Stoffel, Michael H.] Univ Bern, Div Vet Anat, Vetsuisse Fac, CH-3012 Bern, Switzerland.
[Portier, Christopher J.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Mevissen, M (reprint author), Univ Bern, Div Vet Pharmacol & Toxicol, CH-3012 Bern, Switzerland.
RI Portier, Christopher/A-3160-2010; Stoffel, Michael/I-6939-2015
OI Portier, Christopher/0000-0002-0954-0279; Stoffel,
Michael/0000-0002-4699-5125
FU Vetsuisse
FX Supported by a grant of Vetsuisse
NR 52
TC 2
Z9 3
U1 0
U2 6
PU AMER VETERINARY MEDICAL ASSOC
PI SCHAUMBURG
PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA
SN 0002-9645
J9 AM J VET RES
JI Am. J. Vet. Res.
PD DEC
PY 2010
VL 71
IS 12
BP 1432
EP 1442
DI 10.2460/ajvr.71.12.1432
PG 11
WC Veterinary Sciences
SC Veterinary Sciences
GA 690BD
UT WOS:000284974200005
PM 21117994
ER
PT J
AU Cleveland, D
Long, SE
Sander, LC
Davis, WC
Murphy, KE
Case, RJ
Rimmer, CA
Francini, L
Patri, AK
AF Cleveland, Danielle
Long, Stephen E.
Sander, Lane C.
Davis, W. Clay
Murphy, Karen E.
Case, Ryan J.
Rimmer, Catherine A.
Francini, Lorena
Patri, Anil K.
TI Chromatographic methods for the quantification of free and chelated
gadolinium species in MRI contrast agent formulations
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Gadolinium speciation; MRI contrast agent formulations; Species-specific
isotope dilution analysis; ICP-MS; Fluorescence detection; High-pressure
size-exclusion chromatography; Reversed-phase chromatography;
Nanoemulsion; DTPA-DMPE; Liposome
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ICP-MS; NANOEMULSION FORMULATIONS;
ACID COMPLEX; TUMOR-CELLS; CYTOTOXICITY; RELAXIVITY; SPECIATION; WATER;
GD3+
AB Speciation measurements of gadolinium in liposomal MRI contrast agents (CAs) are complicated by the presence of emulsifiers, surfactants, and therapeutic agents in the formulations. The present paper describes two robust, hyphenated chromatography methods for the separation and quantification of gadolinium in nanoemulsion-based CA formulations. Three potential species of gadolinium, free gadolinium ion, gadolinium chelated by diethylenetriamine pentaacetic acid, and gadolinium chelated by 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-diethylenetriaminepentaacetic acid, were present in the CA formulations. The species were separated by reversed-phase chromatography (reversed phase high-performance liquid chromatography, RP-HPLC) or by high-pressure size-exclusion chromatography (HPSEC). For RP-HPLC, fluorescence detection and post-column online isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS) were used to measure the amount of gadolinium in each species. Online ID-ICP-MS and species-specific isotope dilution (SID)-ICP-MS were used in combination with the HPSEC column. The results indicated that some inter-species conversions and degradation had occurred within the samples and that SID-ICP-MS should be used to provide the most reliable measurements of total and speciated gadolinium. However, fluorescence and online ID-ICP-MS might usefully be applied as qualitative, rapid screening procedures for the presence of free gadolinium ions.
C1 [Cleveland, Danielle; Long, Stephen E.; Sander, Lane C.; Murphy, Karen E.; Case, Ryan J.; Rimmer, Catherine A.; Francini, Lorena] Natl Inst Stand & Technol, Div Analyt Chem, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA.
[Davis, W. Clay] Natl Inst Stand & Technol, Hollings Marine Lab, Div Analyt Chem, Charleston, SC 29412 USA.
[Patri, Anil K.] NCI, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA.
RP Long, SE (reprint author), Natl Inst Stand & Technol, Div Analyt Chem, Chem Sci & Technol Lab, 100 Bur Dr, Gaithersburg, MD 20899 USA.
EM stephen.long@nist.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012;
OI Cleveland, Danielle/0000-0003-3880-4584
NR 23
TC 12
Z9 12
U1 0
U2 28
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD DEC
PY 2010
VL 398
IS 7-8
BP 2987
EP 2995
DI 10.1007/s00216-010-4226-2
PG 9
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 684HZ
UT WOS:000284542300025
PM 20890749
ER
PT J
AU Heo, JI
Oh, SJ
Kho, YJ
Kim, JH
Kang, HJ
Park, SH
Kim, HS
Shin, JY
Lee, SY
Kim, MJ
Min, BH
Kim, SC
Park, JB
Kim, J
Lee, JY
AF Heo, Jee-In
Oh, Soo-Jin
Kho, Yoon-Jung
Kim, Jeong-hyeon
Kang, Hong-Joon
Park, Seong-Hoon
Kim, Hyun-Seok
Shin, Jong-Yeon
Lee, Sung-Young
Kim, Min-Ju
Min, Bon-Hong
Kim, Sung Chan
Park, Jae-Bong
Kim, Jaebong
Lee, Jae-Yong
TI Butyrate-induced differentiation of PC12 cells to chromaffin cells
involves cell adhesion and induction of extracellular proteins and cell
adhesion proteins
SO ANIMAL CELLS AND SYSTEMS
LA English
DT Article
DE butyrate; PC12; differentiation; chromaffin cells; cell adhesion
proteins
ID SODIUM-BUTYRATE; PHEOCHROMOCYTOMA CELLS; HISTONE ACETYLATION;
NUCLEOSOMAL DNA; EXPRESSION; LINE; STIMULATION; MOLECULES; CANCER
AB PC12 cells were differentiated into the cells of chromaffin phenotype by butyrate treatment. Cells were aggregated and formed tight cell adhesion. To investigate the molecular change in this differentiation, we examined expression levels of cell adhesion proteins and extracellular proteins during butyrate induced-differentiation of PC12 cells. Integrin 1, integrin 7, E cadherin, VCAM, collagen-I, fibronectin, desmoglein and connexin were increased during differentiation. The levels of clusterin and secreted clusterin were also increased. These increased levels of cell adhesion proteins and extracellular proteins appear to induce cell aggregation and tight cell adhesion. The levels of p21, p27 and p16 were increased probably because of differentiation-related growth arrest during differentiation. Prolonged incubation of butyrate up to 1 day was required for differentiation. Signal transduction pathways for this differentiatiom could not be identified since various inhibitors had no effect. The results showed that butyrate-induced differentiation of PC12 cells to chromaffin cells involves tight cell adhesion and induction of extracellular proteins and cell adhesion proteins.
C1 [Heo, Jee-In; Oh, Soo-Jin; Kim, Jeong-hyeon; Kang, Hong-Joon; Lee, Sung-Young; Kim, Sung Chan; Park, Jae-Bong; Kim, Jaebong; Lee, Jae-Yong] Hallym Univ, Coll Med, Dept Biochem, Chunchon 200702, Gangwon Do, South Korea.
[Heo, Jee-In; Kho, Yoon-Jung; Lee, Jae-Yong] Hallym Univ, Coll Med, Inst Nat Med, Chunchon 200702, Gangwon Do, South Korea.
[Park, Seong-Hoon; Kim, Hyun-Seok] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Shin, Jong-Yeon] Seoul Natl Univ, Med Res Ctr, Genom Med Inst, Seoul, South Korea.
[Lee, Sung-Young] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA.
[Kim, Min-Ju] Hallym Univ, Coll Med, Dept Anat & Neurobiol, Chunchon 200702, Gangwon Do, South Korea.
[Min, Bon-Hong] Korea Univ, Coll Med, Dept Pharmacol, Seoul 136705, South Korea.
RP Lee, JY (reprint author), Hallym Univ, Coll Med, Dept Biochem, Chunchon 200702, Gangwon Do, South Korea.
EM jyolee@hallym.ac.kr
FU Ministry of Education, Science and Technology [2009-0094074]
FX This work was supported by the Priority Research Centers Program through
the National Research Foundation of Korea (NRF) funded by the Ministry
of Education, Science and Technology (2009-0094074).
NR 18
TC 3
Z9 3
U1 0
U2 1
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1976-8354
J9 ANIM CELLS SYST
JI Anim. Cells Syst.
PD DEC
PY 2010
VL 14
IS 4
BP 261
EP 266
AR PII 930982096
DI 10.1080/19768354.2010.528204
PG 6
WC Cell Biology; Zoology
SC Cell Biology; Zoology
GA 693AA
UT WOS:000285195800004
ER
PT J
AU Pfeiffer, RM
Wheeler, WA
Mbisa, G
Whitby, D
Goedert, JJ
De The, G
Mbulaiteye, SM
AF Pfeiffer, Ruth M.
Wheeler, William A.
Mbisa, Georgina
Whitby, Denise
Goedert, James J.
De The, Guy
Mbulaiteye, Sam M.
TI Geographic Heterogeneity of Prevalence of the Human Herpesvirus 8 in
Sub-Saharan Africa: Clues About Etiology
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Kaposi Sarcoma-Associated Herpesvirus; KSHV Infection; Transmission
ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; INFECTION;
TRANSMISSION; CHILDREN; SEROPREVALENCE; EPIDEMIOLOGY; POPULATION;
ANTIBODIES; UGANDA
AB PURPOSE: Human herpesvirus 8 (HHV-8, or Kaposi sarcoma [KS]-associated herpesvirus, KSHV) is a necessary but insufficient cause of KS, as KS develops in few HHV-8-infected persons. In sub-Saharan Africa, marked differences in the geographic distribution of HHV-8 and KS suggest that environmental cofactors influence HHV-8 transmission, control, and progression to KS. However, a direct comparison of HHV-8 prevalence estimates is complicated because studies used different serologic assays and analytic methods. We assessed HHV-8 seropositivity in several African countries with heterogeneous environments and varying KS incidence using a unified approach.
METHODS: HHV-8 antibodies were measured among 3196 adults (aged 20+ years) and 2404 children (aged < 20 years) from five studies in four sub-Saharan countries in Africa. Serum samples were tested by the same laboratory using K8.1 and orf73 enzyme immunoassays.
RESULTS: Children's HHV-8-seropositivity ranged from 18.1% in Kampala, Uganda, to 33.8% in North Mara, Tanzania, increasing steeply with age in all populations. Among adults, HHV-8-seropositivity ranged from 23.5% in Nigeria to 70.6% in rural West Nile, Uganda. It was higher in males and rural areas.
CONCLUSIONS: Our data indicate that geographical exposures, gender, age, and factors correlated with rural residence impact HHV-8 seropositivity in sub-Saharan Africa. Ann Epidemiol 2010;20:958-963. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Pfeiffer, Ruth M.] NCI, Div Canc Epidemiol & Genet, NIH, HHS, Bethesda, MD 20892 USA.
[Wheeler, William A.] Informat Management Serv Inc, Rockville, MD USA.
[Mbisa, Georgina; Whitby, Denise] SAIC Frederick Inc, NCI Frederick, AIDS & Canc Virus Program, Frederick, MD USA.
[De The, Guy] Inst Pasteur, Paris, France.
RP Pfeiffer, RM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, HHS, 6120 Execut Blvd,EPS RM 8030, Bethesda, MD 20892 USA.
EM pfeiffer@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011
FU National Cancer Institute, DHHS [N02-CP-91027, N01-CO-12400,
HHSN261200800001E]
FX We thank Robert Biggar for helpful comments and BJ Stone (both formerly
at the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, Bethesda, Maryland, USA) for help with editing. This project
was funded, in part, through contracts N02-CP-91027, N01-CO-12400 and
HHSN261200800001E from the National Cancer Institute, DHHS.
NR 26
TC 15
Z9 15
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD DEC
PY 2010
VL 20
IS 12
BP 958
EP 963
DI 10.1016/j.annepidem.2010.07.098
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 686AK
UT WOS:000284669000012
PM 21074111
ER
PT J
AU Hallett, M
Deuschl, G
AF Hallett, Mark
Deuschl, Guenther
TI Are We Making Progress in the Understanding of Tremor in Parkinson's
Disease?
SO ANNALS OF NEUROLOGY
LA English
DT Editorial Material
ID CEREBELLOTHALAMOCORTICAL PATHWAY; STIMULATION; SUPPRESSION
C1 [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Deuschl, Guenther] Univ Kiel, Neurol Klin, D-2300 Kiel, Germany.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RI Deuschl, Gunther/A-7986-2010
FU Intramural NIH HHS [ZIA NS003031-03]
NR 15
TC 10
Z9 10
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD DEC
PY 2010
VL 68
IS 6
BP 780
EP 781
DI 10.1002/ana.22253
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 703DE
UT WOS:000285953500004
PM 21194149
ER
PT J
AU Kaufmann, P
Annis, C
Griggs, RC
AF Kaufmann, Petra
Annis, Christine
Griggs, Robert C.
CA Muscle Study Grp Executive Comm
TI The Authorship Lottery: An Impediment to Research Collaboration?
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID GENOMEWIDE ASSOCIATION; MEDICAL JOURNALS; DISCLOSURE; STROKE
AB Authorship of scientific publications holds great importance for basic and clinical researchers. Academic appointments and promotions, grant funding, and salary support depend to some extent on published recognition through authorship. Peer-recognition and personal satisfaction are additional incentives for authorship. Some current "rules" and conventions for assigning authorship are based on largely unwritten but widely-accepted arbitrary decisions. We hypothesize that the inherent uncertainties about assigning "credit where credit is due" serve as a disincentive for clinicians considering an academic career and may discourage or at least impede the collaborations essential to address most translational and clinical research issues. Surveys of the New England Journal of Medicine and the Annals of Neurology suggest that neurologists have been slow to adopt ways of sharing "credit" appropriately. We recommend that authorship of reports of the primary results of multicenter or multidisciplinary studies should be in the name of the group of investigators collaborating on the work. Given the availability of digital methods that could apportion credit quantitatively, academic leaders, including funding agencies and promotions committees, should consider challenging outmoded authorship conventions. Authorship is too important to be left to chance. ANN NEUROL 2010;68:782-786
C1 [Annis, Christine; Griggs, Robert C.] Univ Rochester, Dept Neurol, Sch Med & Dent, Rochester, NY 14620 USA.
[Kaufmann, Petra] NINDS, NIH, Bethesda, MD 20892 USA.
RP Griggs, RC (reprint author), Univ Rochester, Dept Neurol, Sch Med & Dent, 1351 Mt Hope Ave,Suite 203, Rochester, NY 14620 USA.
NR 13
TC 5
Z9 5
U1 1
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD DEC
PY 2010
VL 68
IS 6
BP 782
EP 786
DI 10.1002/ana.22232
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 703DE
UT WOS:000285953500005
PM 21194150
ER
PT J
AU Boumpas, DT
Bertsias, GK
Balow, JE
AF Boumpas, Dimitrios T.
Bertsias, George K.
Balow, James E.
TI A decade of mycophenolate mofetil for lupus nephritis: is the glass
half-empty or half-full?
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; INTRAVENOUS CYCLOPHOSPHAMIDE; MAINTENANCE
THERAPY; PULSE CYCLOPHOSPHAMIDE; INDUCTION THERAPY; MANAGEMENT;
ERYTHEMATOSUS; AZATHIOPRINE
C1 [Boumpas, Dimitrios T.; Bertsias, George K.] Univ Crete, Sch Med, Inst Mol Biol & Biotechnol, Iraklion 71500, Greece.
[Balow, James E.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Boumpas, DT (reprint author), Univ Crete, Sch Med, Inst Mol Biol & Biotechnol, 1 Voutes St, Iraklion 71500, Greece.
EM boumpasd@med.uoc.gr
FU Intramural NIH HHS [Z99 DK999999]
NR 21
TC 6
Z9 6
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD DEC
PY 2010
VL 69
IS 12
BP 2059
EP 2061
DI 10.1136/ard.2010.139683
PG 3
WC Rheumatology
SC Rheumatology
GA 682MI
UT WOS:000284407300001
PM 21097656
ER
PT J
AU Bertsias, GK
Ioannidis, JPA
Aringer, M
Bollen, E
Bombardieri, S
Bruce, IN
Cervera, R
Dalakas, M
Doria, A
Hanly, JG
Huizinga, TWJ
Isenberg, D
Kallenberg, C
Piette, JC
Schneider, M
Scolding, N
Smolen, J
Stara, A
Tassiulas, I
Tektonidou, M
Tincani, A
van Buchem, MA
van Vollenhoven, R
Ward, M
Gordon, C
Boumpas, DT
AF Bertsias, G. K.
Ioannidis, J. P. A.
Aringer, M.
Bollen, E.
Bombardieri, S.
Bruce, I. N.
Cervera, R.
Dalakas, M.
Doria, A.
Hanly, J. G.
Huizinga, T. W. J.
Isenberg, D.
Kallenberg, C.
Piette, J. C.
Schneider, M.
Scolding, N.
Smolen, J.
Stara, A.
Tassiulas, I.
Tektonidou, M.
Tincani, A.
van Buchem, M. A.
van Vollenhoven, R.
Ward, M.
Gordon, C.
Boumpas, D. T.
TI EULAR recommendations for the management of systemic lupus erythematosus
with neuropsychiatric manifestations: report of a task force of the
EULAR standing committee for clinical affairs
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Review
ID CENTRAL-NERVOUS-SYSTEM; EMISSION COMPUTED-TOMOGRAPHY;
ANTIPHOSPHOLIPID-ANTIBODY-SYNDROME; MAGNETIC-RESONANCE SPECTROSCOPY;
PRIMARY THROMBOSIS PREVENTION; OF-THE-LITERATURE; RECURRENT THROMBOSIS;
RISK-FACTORS; INTRAVENOUS IMMUNOGLOBULIN; COGNITIVE DYSFUNCTION
AB Objectives To develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations.
Methods The authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design.
Results Systemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence >5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1-5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD.
Conclusions Neuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.
C1 [Boumpas, D. T.] Univ Crete, Sch Med, Dept Internal Med, Iraklion 71003, Greece.
[Ioannidis, J. P. A.] Univ Ioannina, Sch Med, Clin Trials & Evidence Based Med Unit, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Aringer, M.] Tech Univ Dresden, Univ Med Ctr Carl Gustav Carus, Div Rheumatol, Dept Med 3, Dresden, Germany.
[Bollen, E.] Leiden Univ, Med Ctr, Div Neurol, Leiden, Netherlands.
[Bombardieri, S.] Univ Pisa, Cattedra Reumatol, Pisa, Italy.
[Bruce, I. N.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Arc Epidemiol Unit, Manchester, Lancs, England.
[Cervera, R.] Hosp Clin Barcelona, Dept Autoimmune Dis, Barcelona, Catalonia, Spain.
[Dalakas, M.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Doria, A.] Univ Padua, Div Rheumatol Clin & Expt Med, Padua, Italy.
[Hanly, J. G.] Capital Hlth, Dept Med, Div Rheumatol, Halifax, NS, Canada.
[Hanly, J. G.] Capital Hlth, Dept Pathol, Halifax, NS, Canada.
[Huizinga, T. W. J.] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands.
[Isenberg, D.] Univ Coll London Hosp, Ctr Rheumatol, London, England.
[Kallenberg, C.] Univ Groningen, Univ Med Ctr Groningen, Dept Rheumatol & Clin Immunol, NL-9713 AV Groningen, Netherlands.
[Piette, J. C.] Univ Paris 06, CHU Pitie Salpetriere, Serv Med Interne, Paris, France.
[Schneider, M.] Univ Dusseldorf, Dusseldorf, Germany.
[Scolding, N.] Frenchay Hosp, Inst Clin Neurosci, Bristol BS16 1LE, Avon, England.
[Smolen, J.] Med Univ Vienna, Dept Rheumatol, Vienna, Austria.
[Tassiulas, I.] Hosp Special Surg, New York, NY 10021 USA.
[Tektonidou, M.] Univ Athens, Div Rheumatol, Athens, Greece.
[Tincani, A.] Univ Brescia, Brescia, Italy.
[van Buchem, M. A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
[van Vollenhoven, R.] Karolinska Univ, Dept Med, Rheumatol Unit, Stockholm, Sweden.
[Ward, M.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Gordon, C.] Univ Birmingham, Sch Immun & Infect, Ctr Immune Regulat, Birmingham, W Midlands, England.
[Tincani, A.] Spedali Civil Brescia, I-25125 Brescia, Italy.
[Hanly, J. G.] Dalhousie Univ, Halifax, NS, Canada.
RP Boumpas, DT (reprint author), Univ Crete, Sch Med, Dept Internal Med, 1 Voutes St, Iraklion 71003, Greece.
EM boumpasd@med.uoc.gr
RI Tincani, Angela/E-7608-2010; Ioannidis, John/G-9836-2011;
OI Aringer, Martin/0000-0003-4471-8375; Isenberg,
David/0000-0001-9514-2455; Bruce, Ian/0000-0003-3047-500X
FU European League Against Rheumatism; EULAR Executive Committee
FX The committee wishes to acknowledge the support of the EULAR Executive
Committee and Alan Tyndall, the chairman of the Standing Committee for
Clinical Affairs. The committee expresses its sincere appreciation and
gratitude to the EULAR secretariat and especially to Anja Schonbachler,
executive assistant, for their warm hospitality and outstanding
organisation.This study was funded by the European League Against
Rheumatism.
NR 85
TC 161
Z9 179
U1 2
U2 24
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD DEC
PY 2010
VL 69
IS 12
BP 2074
EP 2082
DI 10.1136/ard.2010.130476
PG 9
WC Rheumatology
SC Rheumatology
GA 682MI
UT WOS:000284407300004
PM 20724309
ER
PT J
AU Karahalil, B
Bohr, VA
De Souza-Pinto, NC
AF Karahalil, Bensu
Bohr, Vilhelm A.
de Souza-Pinto, Nadia C.
TI Base Excision Repair Activities Differ in Human Lung Cancer Cells and
Corresponding Normal Controls
SO ANTICANCER RESEARCH
LA English
DT Article
DE OGG1; NTH1; UDG; APE1; DNA repair; mtDNA; nDNA; lung cancer cells.
ID HOGG1 SER326CYS POLYMORPHISM; MITOCHONDRIAL-DNA MUTATIONS; NONMELANOMA
SKIN-CANCER; AP ENDONUCLEASE-1; BREAST-CANCER; DAMAGE; ASSOCIATION;
RISK; OGG1; SUSCEPTIBILITY
AB Oxidative damage to DNA is thought to play a role in carcinogenesis by causing Mutations, and indeed accumulation of oxidized DNA bases has been observed in samples obtained from tumors but not from surrounding tissue within the same patient. Base excision repair (BER) is the main pathway for the repair of oxidized modifications both in nuclear and mitochondrial, DNA. In order to ascertain whether diminished BER capacity might account for increased levels of oxidative DNA damage in cancer cells, the activities of BER enzymes in three different lung cancer cell lines and their non-cancerous counterparts were measured using oligonucleotide substrates with single DNA lesions to assess specific BER enzymes. The activities of four BER enzymes, OGG1, NTH1, UDG and APE1, were compared in mitochondrial and nuclear extracts. For each specific lesion, the repair activities were similar among the three cell lines used. However, the specific activities and cancer versus control comparison differed significantly between the nuclear and mitochondrial compartments. OGG1 activity, as measured by 8-oxodA incision, was upregulated in cancer cell mitochondria but down-regulated in the nucleus when compared to control cells. Similarly, NTH1 activity was also up-regulated in mitochondrial extracts from cancer cells but did not change significantly in the nucleus. Together, these results support the idea that alterations in BER capacity are associated with carcinogenesis.
C1 [de Souza-Pinto, Nadia C.] Univ Sao Paulo, Dept Biochem, IQ, BR-05508000 Sao Paulo, Brazil.
[Karahalil, Bensu; Bohr, Vilhelm A.; de Souza-Pinto, Nadia C.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Karahalil, Bensu] Gazi Univ, Fac Pharm, Dept Toxicol, TR-06330 Ankara, Turkey.
RP De Souza-Pinto, NC (reprint author), Univ Sao Paulo, Depto Bioquim, IQ, BR-05508000 Sao Paulo, Brazil.
EM nadja@iq.usp.br
RI Souza-Pinto, Nadja/C-3462-2013
OI Souza-Pinto, Nadja/0000-0003-4206-964X
FU National Institute on Aging, NIH; FAPESP; CNPq - INCT Processos Redox em
Biomedicina
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, NIH. NCS-P is supported by grants from
FAPESP and CNPq - INCT Processos Redox em Biomedicina.
NR 35
TC 9
Z9 9
U1 0
U2 3
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 2010
VL 30
IS 12
BP 4963
EP 4971
PG 9
WC Oncology
SC Oncology
GA 717BV
UT WOS:000287018100024
PM 21187477
ER
PT J
AU Holland, R
Fishbein, JC
AF Holland, Ryan
Fishbein, James C.
TI Chemistry of the Cysteine Sensors in Kelch-Like ECH-Associated Protein 1
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID ANTIOXIDANT RESPONSE ELEMENT; OXIDATIVE STRESS; IN-VITRO;
CHEMOPREVENTIVE AGENT; NUCLEAR ACCUMULATION; S-GLUTATHIOLATION; PHASE-2
RESPONSE; NRF2 ACTIVATION; GENE-EXPRESSION; UP-REGULATION
AB The protein Kelch-like ECH-associated protein 1 (Keap1) is a cysteine-rich regulatory and scaffold protein. Human Keap1 contains 27 cysteines. Some of these cysteines are believed to mediate derepression of the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which subsequently upregulates phase 2 enzymes, in response to electrophilic/oxidative assault. Some current models depict a highly select group of two and possibly a few more cysteine residues as key sensors. The assumptions and approaches undergirding these models are commented upon. The chemical reactivity of the cysteines of Keap1 toward an array of electrophiles and one oxidant is reviewed. A number of reports in the recent literature of molecules that putatively modify cysteines of Keap1 are also included. Insights into the current molecular basis of electrophile/oxidant activation of the Nrf2 pathway via reaction at cysteines of Keap1 are discussed. Finally, important knowns and unknowns are summarized. Antioxid. Redox Signal. 13, 1749-1761.
C1 [Fishbein, James C.] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA.
[Holland, Ryan] NCI, Comparat Carcinogenesis Lab, NIH, Frederick, MD USA.
RP Fishbein, JC (reprint author), Univ Maryland Baltimore Cty, Dept Chem & Biochem, 1000 Hilltop Circle, Baltimore, MD 21250 USA.
EM jfishbei@umbc.edu
NR 65
TC 45
Z9 46
U1 0
U2 8
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 2010
VL 13
IS 11
BP 1749
EP 1761
DI 10.1089/ars.2010.3273
PG 13
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 665RL
UT WOS:000283053100009
PM 20486763
ER
PT J
AU Calabrese, V
Cornelius, C
Dinkova-Kostova, AT
Calabrese, EJ
Mattson, MP
AF Calabrese, Vittorio
Cornelius, Carolin
Dinkova-Kostova, Albena T.
Calabrese, Edward J.
Mattson, Mark P.
TI Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel
Targets for Therapeutic Intervention in Neurodegenerative Disorders
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID NF-KAPPA-B; TRANSCRIPTION FACTOR NRF2; SHAPED DOSE-RESPONSES;
AMYLOID-BETA-PEPTIDE; HEAT-SHOCK PROTEINS; MANGANESE
SUPEROXIDE-DISMUTASE; AMYOTROPHIC-LATERAL-SCLEROSIS; CHOLINERGIC
DRUG-COMBINATIONS; ENDOPLASMIC-RETICULUM STRESS; CANCER-PROTECTIVE
ENZYMES
AB Despite the capacity of chaperones and other homeostatic components to restore folding equilibrium, cells appear poorly adapted for chronic oxidative stress that increases in cancer and in metabolic and neurodegenerative diseases. Modulation of endogenous cellular defense mechanisms represents an innovative approach to therapeutic intervention in diseases causing chronic tissue damage, such as in neurodegeneration. This article introduces the concept of hormesis and its applications to the field of neuroprotection. It is argued that the hormetic dose response provides the central underpinning of neuroprotective responses, providing a framework for explaining the common quantitative features of their dose-response relationships, their mechanistic foundations, and their relationship to the concept of biological plasticity, as well as providing a key insight for improving the accuracy of the therapeutic dose of pharmaceutical agents within the highly heterogeneous human population. This article describes in mechanistic detail how hormetic dose responses are mediated for endogenous cellular defense pathways, including sirtuin and Nrf2 and related pathways that integrate adaptive stress responses in the prevention of neurodegenerative diseases. Particular attention is given to the emerging role of nitric oxide, carbon monoxide, and hydrogen sulfide gases in hormetic-based neuroprotection and their relationship to membrane radical dynamics and mitochondrial redox signaling. Antioxid. Redox Signal. 13, 1763-1811.
C1 [Calabrese, Vittorio; Cornelius, Carolin] Univ Catania, Dept Chem, I-95100 Catania, Italy.
[Dinkova-Kostova, Albena T.] Univ Dundee, Biomed Res Inst, Dundee DD1 4HN, Scotland.
[Dinkova-Kostova, Albena T.] Johns Hopkins Univ, Sch Med, Dept Med & Pharmacol, Div Clin Pharmacol, Baltimore, MD USA.
[Dinkova-Kostova, Albena T.] Johns Hopkins Univ, Sch Med, Dept Mol Sci, Div Clin Pharmacol, Baltimore, MD 21205 USA.
[Calabrese, Edward J.] Univ Massachusetts, Sch Publ Hlth, Environm Hlth Sci Div, Amherst, MA 01003 USA.
[Mattson, Mark P.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
RP Calabrese, V (reprint author), Univ Catania, Dept Chem, Via Andrea Doria, I-95100 Catania, Italy.
EM calabres@unict.it
RI Mattson, Mark/F-6038-2012
FU MIUR; FIRB [RBRN07BMCT]; I.N.B.B; RCUK; American Cancer Society
[RSG-07-157-01-CNE]; Cancer Research UK [C20953/A10270]; Tenovus; Royal
Society; Anonymous Trust; Fondi Ateneo; National Institute on Aging
Intramural Research
FX Work from the authors' laboratories was supported by grants from MIUR,
FIRB RBRN07BMCT, I.N.B.B., RCUK, the American Cancer Society
(RSG-07-157-01-CNE), Cancer Research UK (C20953/A10270), Tenovus, the
Royal Society, the Anonymous Trust, and by "Fondi Ateneo" 2007 and 2008,
and the National Institute on Aging Intramural Research Program
(M.P.M.). The authors acknowledge helpful discussions for the HSF
posttranslational regulation with M.G. Santoro (Department of Biology,
University of Rome Tor Vergata, Rome).
NR 487
TC 161
Z9 163
U1 6
U2 28
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 2010
VL 13
IS 11
BP 1763
EP 1811
DI 10.1089/ars.2009.3074
PG 49
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 665RL
UT WOS:000283053100010
PM 20446769
ER
PT J
AU Vereecken, C
Rovner, A
Maes, L
AF Vereecken, Carine
Rovner, Alisha
Maes, Lea
TI Associations of parenting styles, parental feeding practices and child
characteristics with young children's fruit and vegetable consumption
SO APPETITE
LA English
DT Article
DE Preschool children; Fruit; Vegetables; Parental feeding practices;
Parenting styles; Child temperament; Modelling
ID FOOD FREQUENCY QUESTIONNAIRE; DIETARY-INTAKE; NUTRITIONAL KNOWLEDGE;
11-YEAR-OLD CHILDREN; PRESCHOOL-CHILDREN; RESTRICTING ACCESS;
BITTER-TASTE; MOTHERS; GIRLS; PREFERENCES
AB The purpose of this study was to investigate the role of parent and child characteristics in explaining children's fruit and vegetable intakes. In 2008, parents of preschoolers (mean age 3.5 years) from 56 schools in Belgium-Flanders completed questionnaires including a parent and child fruit and vegetable food frequency questionnaire, general parenting styles (laxness, overreactivity and positive interactions), specific food parenting practices (child-centered and parent-centered feeding practices) and children's characteristics (children's shyness, emotionality, stubbornness, activity, sociability, and negative reactions to food). Multiple linear regression analyses (n = 755) indicated a significant positive association between children's fruit and vegetable intake and parent's intake and a negative association with children's negative reactions to food. No general parenting style dimension or child personality characteristic explained differences in children's fruit and vegetable intakes. Child-centered feeding practices were positively related to children's fruit and vegetable intakes, while parent-centered feeding practices were negatively related to children's vegetable intakes. In order to try to increase children's fruit and vegetable consumption, parents should be guided to improve their own diet and to use child-centered parenting practices and strategies known to decrease negative reactions to food. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Vereecken, Carine; Maes, Lea] Univ Ghent, Fac Med & Hlth Sci, Dept Publ Hlth, B-9000 Ghent, Belgium.
[Rovner, Alisha] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, NIH, Rockville, MD 20852 USA.
EM carine.vereecken@ugent.be
FU Research Foundation-Flanders (FWO-Vlaanderen); Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health, Department of Health and Human Services
FX Carine Vereecken is postdoctoral researcher supported by the Research
Foundation-Flanders (FWO-Vlaanderen). Alisha Rovner is supported by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Department of Health and Human Services. There are no conflicts
of interest. CV coordinated the study, analysed the data and wrote the
manuscript. AR assisted in writing the paper. LM revised the paper.
NR 71
TC 45
Z9 45
U1 12
U2 51
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 2010
VL 55
IS 3
BP 589
EP 596
DI 10.1016/j.appet.2010.09.009
PG 8
WC Behavioral Sciences; Nutrition & Dietetics
SC Behavioral Sciences; Nutrition & Dietetics
GA 703OU
UT WOS:000285988900031
PM 20849895
ER
PT J
AU Ferris, FL
AF Ferris, Frederick L.
TI Arnall Patz, MD The Spirit of Collaboration
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Editorial Material
C1 NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
RP Ferris, FL (reprint author), NEI, Div Epidemiol & Clin Res, NIH, Bldg 10,CRC 3-2531,10 Ctr Dr, Bethesda, MD 20892 USA.
EM flf@nei.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD DEC
PY 2010
VL 128
IS 12
BP 1602
EP 1603
DI 10.1001/archophthalmol.2010.294
PG 2
WC Ophthalmology
SC Ophthalmology
GA 693GL
UT WOS:000285212500017
PM 21149787
ER
PT J
AU Yeh, S
Forooghian, F
Wong, WT
Sen, HN
Chew, EY
Nussenblatt, RB
AF Yeh, Steven
Forooghian, Farzin
Wong, Wai T.
Sen, H. Nida
Chew, Emily Y.
Nussenblatt, Robert B.
TI Foveal Hypoautofluorescence: Does It Correlate to Visual Acuity in White
Dot Syndromes? In reply
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Letter
ID PUNCTATE INNER CHOROIDOPATHY; FUNDUS AUTOFLUORESCENCE; MULTIFOCAL
CHOROIDITIS; MACULAR EDEMA; PANUVEITIS
C1 [Yeh, Steven; Forooghian, Farzin; Wong, Wai T.; Sen, H. Nida; Chew, Emily Y.; Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA.
[Yeh, Steven] Emory Univ, Sch Med, Emory Eye Ctr, Atlanta, GA USA.
RP Nussenblatt, RB (reprint author), NEI, NIH, Bldg 10,Suite Room 10N-112, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
NR 9
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD DEC
PY 2010
VL 128
IS 12
BP 1629
EP 1630
DI 10.1001/archophthalmol.2010.279
PG 2
WC Ophthalmology
SC Ophthalmology
GA 693GL
UT WOS:000285212500027
ER
PT J
AU Ambrosius, WT
Danis, RP
Riddle, MC
Goff, DC
Gerstein, HC
Greven, CM
Chew, EY
AF Ambrosius, Walter T.
Danis, Ronald P.
Riddle, Matthew C.
Goff, David C., Jr.
Gerstein, Hertzel C.
Greven, Craig M.
Chew, Emily Y.
TI Macular Edema and Thiazolidinediones In reply
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Letter
C1 [Ambrosius, Walter T.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC 27157 USA.
[Danis, Ronald P.] Univ Wisconsin, Dept Ophthalmol, Madison, WI USA.
[Riddle, Matthew C.] Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97201 USA.
[Goff, David C., Jr.] Wake Forest Univ, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA.
[Gerstein, Hertzel C.] McMaster Univ, Dept Med, Hamilton, ON, Canada.
[Gerstein, Hertzel C.] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
[Greven, Craig M.] Wake Forest Univ, Dept Ophthalmol, Winston Salem, NC 27109 USA.
[Chew, Emily Y.] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
RP Ambrosius, WT (reprint author), Wake Forest Univ Hlth Sci, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM wambrosi@wfubmc.edu
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD DEC
PY 2010
VL 128
IS 12
BP 1631
EP 1632
DI 10.1001/archophthalmol.2010.288
PG 2
WC Ophthalmology
SC Ophthalmology
GA 693GL
UT WOS:000285212500029
ER
PT J
AU Ang, JY
Lua, JL
Asmar, BI
Shankaran, S
Heyne, RJ
Schelonka, RL
Das, A
Li, L
Jackson, DM
Higgins, RD
D'Angio, CT
AF Ang, Jocelyn Y.
Lua, Jorge L.
Asmar, Basim I.
Shankaran, Seetha
Heyne, Roy J.
Schelonka, Robert L.
Das, Abhik
Li, Lei
Jackson, Delois M.
Higgins, Rosemary D.
D'Angio, Carl T.
CA Eunice Kennedy Shriver Natl Inst C
TI Nasopharyngeal Carriage of Streptococcus Pneumoniae in Very
Low-Birth-Weight Infants After Administration of Heptavalent
Pneumococcal Conjugate Vaccine
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Letter
ID IMMUNOGENICITY
C1 [Ang, Jocelyn Y.; Asmar, Basim I.] Wayne State Univ, Div Infect Dis, Dept Pediat, Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Lua, Jorge L.; Shankaran, Seetha] Wayne State Univ, Div Neonatal Perinatal Med, Dept Pediat, Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Heyne, Roy J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Div Neonatal Perinatal Med, Dallas, TX 75390 USA.
[Schelonka, Robert L.] Univ Alabama, Dept Pediat, Div Neonatol, Birmingham, AL USA.
[Das, Abhik] Res Triangle Inst Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Li, Lei] Res Triangle Inst Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Jackson, Delois M.] Ctr Dis Control & Prevent, Streptococcus Lab, Resp Dis Branch, Atlanta, GA USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[D'Angio, Carl T.] Univ Rochester, Sch Med & Dent, Dept Pediat, Div Neonatal Perinatal Med,Strong Childrens Res C, Rochester, NY 14642 USA.
RP Ang, JY (reprint author), Wayne State Univ, Carman & Ann Adams Dept Pediat, Div Infect Dis, Childrens Hosp Michigan,Sch Med, 3901 Beaubien Blvd, Detroit, MI 48201 USA.
EM jang@med.wayne.edu
FU NCRR NIH HHS [M01 RR000044, M01 RR000633-35, M01 RR000044-45, M01
RR000032-45]; NICHD NIH HHS [U01 HD36790, U10 HD040521, U10 HD021385,
U10 HD040689, U10 HD036790, U10 HD40689, U10 HD040689-12, U10
HD034216-15, U10 HD040521-05, U01 HD036790, U10 HD21385, U10
HD036790-15, U10 HD40521, U10 HD34216, U10 HD034216, U10 HD021385-27]
NR 6
TC 1
Z9 1
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 1072-4710
J9 ARCH PEDIAT ADOL MED
JI Arch. Pediatr. Adolesc. Med.
PD DEC
PY 2010
VL 164
IS 12
BP 1173
EP 1175
DI 10.1001/archpediatrics.2010.233
PG 3
WC Pediatrics
SC Pediatrics
GA 690MW
UT WOS:000285009900023
PM 21135351
ER
PT J
AU Hoffman, JM
Ciol, MA
Huynh, M
Chan, L
AF Hoffman, Jeanne M.
Ciol, Marcia A.
Huynh, Minh
Chan, Leighton
TI Estimating Transition Probabilities in Mobility and Total Costs for
Medicare Beneficiaries
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Delivery of health care; Disabled persons; Health care reform;
Rehabilitation
ID OLDER PERSONS; FUNCTIONAL TRANSITIONS; SAMPLE SELECTION; 2-PART MODELS;
DISABILITY; POPULATION; HEALTH; LIMITATIONS; PREDICTORS; SERVICES
AB Hoffman JM, Clot MA, Huynh M, Chan L. Estimating transition probabilities in mobility and total costs for Medicare beneficiaries. Arch Phys Med Rehabil 2010;91: 1849-55.
Objective: To examine how persons move back and forth along levels of mobility disability.
Design: Self-reported mobility limitations were used to create categories of annual transition states. The total cost to Medicare associated with each year was calculated for each participant. In addition, we examined cost relative to transition state, adjusting for demographic and other health status variables,
Setting: National survey.
Participants: Participants in the longitudinal Medicare Current Beneficiary Survey from 1992 to 2005.
Interventions: Not applicable.
Main Outcome Measures: Annual self-reported mobility limitations and total Medi costs.
Results: Most participants remained without mobility limitations or improved over time. Reported average costs were 10 times higher for those who transitioned to severe limitations, unable to walk, or death compared with persons who reported no mobility limitation. Estimated costs were highest for those transitioning to increased states of disability and to death.
Conclusions: Mobility limitations in older adults are dynamic, and improvement (as measured by annual transitions) occurred for a large number of Medicare beneficiaries. High total annual costs were observed in groups that transitioned to worsening mobility states, suggesting a link between mobility limitation transitions and cost. Prevention and treatment of mobility limitation may be an important factor to consider in health care reform.
C1 [Hoffman, Jeanne M.; Ciol, Marcia A.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Huynh, Minh; Chan, Leighton] NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20892 USA.
RP Hoffman, JM (reprint author), Univ Washington, Dep Rehabil Med, Box 356490, Seattle, WA 98195 USA.
EM jeanneh@u.washington.edu
FU National Institutes of Health
FX Supported by the National Institutes of Health Intramural Research
Program.
NR 23
TC 3
Z9 3
U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
EI 1532-821X
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD DEC
PY 2010
VL 91
IS 12
BP 1849
EP 1855
DI 10.1016/j.apmr.2010.08.010
PG 7
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 700KY
UT WOS:000285738900005
PM 21112425
ER
PT J
AU Kuhn, JH
Becker, S
Ebihara, H
Geisbert, TW
Johnson, KM
Kawaoka, Y
Lipkin, WI
Negredo, AI
Netesov, SV
Nichol, ST
Palacios, G
Peters, CJ
Tenorio, A
Volchkov, VE
Jahrling, PB
AF Kuhn, Jens H.
Becker, Stephan
Ebihara, Hideki
Geisbert, Thomas W.
Johnson, Karl M.
Kawaoka, Yoshihiro
Lipkin, W. Ian
Negredo, Ana I.
Netesov, Sergey V.
Nichol, Stuart T.
Palacios, Gustavo
Peters, Clarence J.
Tenorio, Antonio
Volchkov, Viktor E.
Jahrling, Peter B.
TI Proposal for a revised taxonomy of the family Filoviridae:
classification, names of taxa and viruses, and virus abbreviations
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID EBOLA-VIRUS; MARBURG-VIRUS; HEMORRHAGIC-FEVER; ORDER MONONEGAVIRALES;
NUCLEOTIDE-SEQUENCE; MESSENGER-RNA; SPECIES NAMES; L-GENE;
IDENTIFICATION; GLYCOPROTEIN
AB The taxonomy of the family Filoviridae (marburgviruses and ebolaviruses) has changed several times since the discovery of its members, resulting in a plethora of species and virus names and abbreviations. The current taxonomy has only been partially accepted by most laboratory virologists. Confusion likely arose for several reasons: species names that consist of several words or which (should) contain diacritical marks, the current orthographic identity of species and virus names, and the similar pronunciation of several virus abbreviations in the absence of guidance for the correct use of vernacular names. To rectify this problem, we suggest (1) to retain the current species names Reston ebolavirus, Sudan ebolavirus, and Zaire ebolavirus, but to replace the name Cote d'Ivoire ebolavirus [sic] with Ta < Forest ebolavirus and Lake Victoria marburgvirus with Marburg marburgvirus; (2) to revert the virus names of the type marburgviruses and ebolaviruses to those used for decades in the field (Marburg virus instead of Lake Victoria marburgvirus and Ebola virus instead of Zaire ebolavirus); (3) to introduce names for the remaining viruses reminiscent of jargon used by laboratory virologists but nevertheless different from species names (Reston virus, Sudan virus, Ta < Forest virus), and (4) to introduce distinct abbreviations for the individual viruses (RESTV for Reston virus, SUDV for Sudan virus, and TAFV for Ta < Forest virus), while retaining that for Marburg virus (MARV) and reintroducing that used over decades for Ebola virus (EBOV). Paying tribute to developments in the field, we propose (a) to create a new ebolavirus species (Bundibugyo ebolavirus) for one member virus (Bundibugyo virus, BDBV); (b) to assign a second virus to the species Marburg marburgvirus (Ravn virus, RAVV) for better reflection of now available high-resolution phylogeny; and (c) to create a new tentative genus (Cuevavirus) with one tentative species (Lloviu cuevavirus) for the recently discovered Lloviu virus (LLOV). Furthermore, we explain the etymological derivation of individual names, their pronunciation, and their correct use, and we elaborate on demarcation criteria for each taxon and virus.
C1 [Kuhn, Jens H.; Jahrling, Peter B.] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, Div Clin Res DCR, NIH,NIBC, Frederick, MD 21702 USA.
[Kuhn, Jens H.] Tunnell Consulting Inc, King Of Prussia, PA USA.
[Becker, Stephan] Univ Marburg, Inst Virol, D-3550 Marburg, Germany.
[Ebihara, Hideki] NIAID, Rocky Mt Labs, Integrated Res Facil, NIH, Hamilton, MT 59840 USA.
[Geisbert, Thomas W.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX USA.
[Johnson, Karl M.] Univ New Mexico, Albuquerque, NM 87131 USA.
[Kawaoka, Yoshihiro] Univ Wisconsin, Sch Vet Med, Madison, WI 53706 USA.
[Lipkin, W. Ian; Palacios, Gustavo] Columbia Univ, Med Ctr, Ctr Infect & Immun, New York, NY USA.
[Negredo, Ana I.; Tenorio, Antonio] Inst Salud Carlos III, Ctr Nacl Microbiol, Madrid, Spain.
[Netesov, Sergey V.] Novosibirsk State Univ, Novosibirsk 630090, Russia.
[Nichol, Stuart T.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Peters, Clarence J.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX USA.
[Volchkov, Viktor E.] Univ Lyon, UCB Lyon 1, Ecole Normale Super, Lab Filovirus Inserm U758, Lyon, France.
RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, Div Clin Res DCR, NIH,NIBC, B-8200 Res Plaza, Frederick, MD 21702 USA.
EM kuhnjens@mail.nih.gov
RI Becker, Stephan/A-1065-2010; Palacios, Gustavo/I-7773-2015; Kuhn, Jens
H./B-7615-2011; Netesov, Sergey/A-3751-2013; Volchkov,
Viktor/M-7846-2014
OI Becker, Stephan/0000-0002-2794-5659; Palacios,
Gustavo/0000-0001-5062-1938; Kuhn, Jens H./0000-0002-7800-6045; Netesov,
Sergey/0000-0002-7786-2464; Volchkov, Viktor/0000-0001-7896-8706
FU Intramural NIH HHS [Z99 AI999999, ZIA AI001025-03]
NR 74
TC 175
Z9 190
U1 8
U2 42
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0304-8608
J9 ARCH VIROL
JI Arch. Virol.
PD DEC
PY 2010
VL 155
IS 12
BP 2083
EP 2103
DI 10.1007/s00705-010-0814-x
PG 21
WC Virology
SC Virology
GA 681QD
UT WOS:000284331000023
PM 21046175
ER
PT J
AU Louie, GH
Wang, Z
Ward, MM
AF Louie, Grant H.
Wang, Zhong
Ward, Michael M.
TI Trends in hospitalizations for Pneumocystis jiroveci pneumonia among
patients with rheumatoid arthritis in the US: 1996-2007
SO ARTHRITIS AND RHEUMATISM
LA English
DT Editorial Material
ID POSTMARKETING SURVEILLANCE; CARINII-PNEUMONIA; SAFETY
C1 [Louie, Grant H.; Wang, Zhong; Ward, Michael M.] NIH, Bethesda, MD 20892 USA.
RP Louie, GH (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [NIH0012168550, Z01 AR041153-04]
NR 9
TC 7
Z9 7
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD DEC
PY 2010
VL 62
IS 12
BP 3826
EP 3827
DI 10.1002/art.27735
PG 2
WC Rheumatology
SC Rheumatology
GA 693FO
UT WOS:000285210200037
PM 20824796
ER
PT J
AU Huang, XP
Mangano, T
Hufeisen, S
Setola, V
Roth, BL
AF Huang, Xi-Ping
Mangano, Thomas
Hufeisen, Sandy
Setola, Vincent
Roth, Bryan L.
TI Identification of Human Ether-a-go-go Related Gene Modulators by Three
Screening Platforms in an Academic Drug-Discovery Setting
SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
LA English
DT Article
ID LONG QT SYNDROME; HERG POTASSIUM CHANNEL; K+ CHANNEL;
CARDIAC-ARRHYTHMIA; EXTRACELLULAR K+; ION CHANNELS; ASSAY; TRAFFICKING;
CELLS; INHIBITION
AB The human Ether-a-go-go related gene (hERG) potassium channel is responsible for the rapid delayed rectifier potassium current that plays a critical role in the repolarization of cardiomyocytes during the cardiac action potential. In humans, inhibition of hERG by drugs can prolong the electrocardiographic QT interval, which, in rare instance, leads to ventricular arrhythmia and sudden cardiac death. As such, several medications that block hERG channels in vitro have been withdrawn from the market due to QT prolongation and arrhythmias. The current FDA guidelines recommend that drug candidates destined for human use be evaluated for potential hERG activity (www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm074963.pdf). Here, we employed automated planar patch clamp (APPC), high-throughput fluorescent Tl+ flux, and moderate-throughput [H-3]dofetilide competition binding assays to characterize a panel of 49 drugs for their activities at the hERG channel. Notably, we used the same HEK293-hERG cell line for all assays, facilitating comparisons of hERG potencies across screening platforms. In general, hERG inhibitors were most potent in APPC assays, intermediate potent in [H-3] dofetilide binding assays, and least potent in Tl+ flux assays. Binding affinity constants (pK(i) values) and Tl+ flux potencies (pEC(50) values) correlated well with APPC pEC(50) values. Further, the inhibitory potencies of many known hERG inhibitors in APPC matched literature values from manual and/or automated patch clamp systems. We also developed a novel fluorescent Tl+ flux assays to measure the effects of drugs that modulate hERG trafficking and surface expression.
C1 [Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
Univ N Carolina, Natl Inst Mental Hlth, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
Univ N Carolina, Div Med Chem, Sch Med, Chapel Hill, NC 27599 USA.
Univ N Carolina, Div Med Chem, Sch Pharm, Chapel Hill, NC 27599 USA.
RP Roth, BL (reprint author), Univ N Carolina, Dept Pharmacol, 4072 Genet Med Bldg,CB 7365, Chapel Hill, NC 27599 USA.
EM bryan_roth@med.unc.edu
RI Roth, Bryan/F-3928-2010
FU National Institute of Mental Health Psychoactive Drug Screening
FX The authors would like to thank Sarah Rogan and Wes Kroeze for careful
reading of the article and making suggestions. Authors would also like
to thank Drs. Richard Kondo, Robert Rosenberg, and Thomas Kash for
technical support in setting up and optimization of the PatchXpress
system. Supported by the National Institute of Mental Health
Psychoactive Drug Screening Program and the Michael Hooker Distinguished
Professorship in Protein Therapeutics and Translational Proteomics.
NR 56
TC 29
Z9 29
U1 0
U2 5
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-658X
J9 ASSAY DRUG DEV TECHN
JI ASSAY DRUG DEV. TECHNOL.
PD DEC
PY 2010
VL 8
IS 6
BP 727
EP 742
DI 10.1089/adt.2010.0331
PG 16
WC Biochemical Research Methods; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 695AX
UT WOS:000285344100008
PM 21158687
ER
PT J
AU Grether, JK
Croen, LA
Anderson, MC
Nelson, KB
Yolken, RH
AF Grether, Judith K.
Croen, Lisa A.
Anderson, Meredith C.
Nelson, Karin B.
Yolken, Robert H.
TI Neonatally Measured Immunoglobulins and Risk of Autism
SO AUTISM RESEARCH
LA English
DT Article
DE autism; ASD; maternal immune function; immunoglobulins and pregnancy
ID CONGENITAL CYTOMEGALOVIRUS-INFECTION; MATERNAL INFLUENZA INFECTION;
SPECTRUM DISORDERS; AUTOIMMUNE-DISEASES; CHILDREN; BRAIN; ASSOCIATION;
PREVALENCE; PREGNANCY; PSYCHOSIS
AB Previous studies indicate that prenatal exposure to infections is a possible pathway through which autism spectrum disorders (ASD) could be initiated. We investigated whether immunoglobulin levels in archived specimens obtained from newborns subsequently diagnosed with ASD are different from levels in newborn specimens from controls. Children with ASD born in six California counties in 1994 were ascertained through records of the California Department of Developmental Services (DDS) and Kaiser Permanente; controls were randomly selected using birth certificates. Archived newborn blood specimens were obtained from the California Genetic Disease Screening Program (GDSP) for N=213 cases and N=265 controls and assayed to determine levels of total IgG, antigen-specific IgG to selected common pathogens, total IgM, total IgA, and C-reactive protein (CRP). We did not find measurable levels of total IgM or IgA in any neonate and measurable CRP was present in only a few. No antigen-specific IgG antibodies were elevated in cases compared to controls and total IgG levels were lower. In adjusted models, a 10-unit increase in total IgG yielded an OR = 0.72 (950/0 Cl 0.56, 0.91); a significantly decreasing trend in risk of ASD was observed across increasing exposure quartiles of total IgG (P=0.01). The finding of lower IgG in cases may indicate maternal immune dysfunction during gestation and/or impaired transplacental transfer of immunoglobulins. Further investigation of IgG levels in newborns and the mechanisms by which they might be associated with ASD are warranted.
C1 [Grether, Judith K.; Anderson, Meredith C.] Calif Dept Publ Hlth, Richmond, CA 94804 USA.
[Croen, Lisa A.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Nelson, Karin B.] NINDS, Bethesda, MD 20892 USA.
[Yolken, Robert H.] Johns Hopkins Sch Med, Stanley Neurovirol Lab, Dept Pediat, Baltimore, MD USA.
RP Grether, JK (reprint author), Calif Dept Publ Hlth, 850 Marina Bay Pkwy, Richmond, CA 94804 USA.
EM judith.grether@cdph.ca.gov
FU Stanley Medical Research Institute, The Centers for Disease Control and
Prevention [CDC U10/CCU920392]; California Department of Public Health
FX Grant sponsor: Stanley Medical Research Institute, The Centers for
Disease Control and Prevention; Grant number: CDC U10/CCU920392; Grant
sponsor: California Department of Public Health.
NR 45
TC 19
Z9 20
U1 3
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1939-3792
J9 AUTISM RES
JI Autism Res.
PD DEC
PY 2010
VL 3
IS 6
BP 323
EP 332
DI 10.1002/aur.160
PG 10
WC Behavioral Sciences; Psychology, Developmental
SC Behavioral Sciences; Psychology
GA 707QJ
UT WOS:000286300800004
PM 21182209
ER
PT J
AU Rowen, L
Milner, JA
Ross, S
AF Rowen, Lisa
Milner, John A.
Ross, Sharon
TI Obesity, Cancer and Epigenetics
SO BARIATRIC NURSING AND SURGICAL PATIENT CARE
LA English
DT Editorial Material
ID BREAST-CANCER; MODULATION; MECHANISMS; CHILDHOOD; ORIGINS; HEALTH;
COHORT; ADULTS; WOMEN; MICE
C1 [Rowen, Lisa] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA.
[Milner, John A.; Ross, Sharon] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Rowen, L (reprint author), Univ Maryland, Med Ctr, Baltimore, MD 21201 USA.
NR 32
TC 2
Z9 3
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1557-1459
J9 BARIAT NURS SURG PAT
JI Bariatr. Nurs. Surg. Patient Care
PD DEC
PY 2010
VL 5
IS 4
BP 275
EP 283
DI 10.1089/bar.2010.9987
PG 9
WC Nursing
SC Nursing
GA 688UO
UT WOS:000284879600003
ER
PT J
AU Malkova, L
Mishkin, M
Suomi, SJ
Bachevalier, J
AF Malkova, Ludise
Mishkin, Mortimer
Suomi, Stephen J.
Bachevalier, Jocelyne
TI Long-Term Effects of Neonatal Medial Temporal Ablations on
Socioemotional Behavior in Monkeys (Macaca mulatta)
SO BEHAVIORAL NEUROSCIENCE
LA English
DT Article
DE amygdala; hippocampus; area TE; infants; social interactions
ID KLUVER-BUCY-SYNDROME; VISUAL RECOGNITION MEMORY; RHESUS-MONKEYS;
AMYGDALA LESIONS; SOCIAL-BEHAVIOR; INFANT MONKEYS; LOBE LESIONS;
BILATERAL LESIONS; PERIRHINAL CORTEX; MACAQUE MONKEYS
AB Socioemotional abnormalities, including decreased social interactions and increased self-directed activity, were reported when rhesus monkeys with neonatal ablations of either the medial temporal lobe (AH) or the inferior temporal cortex (TE) were paired with unoperated peers at two and six months of age, though these abnormalities were more severe in Group AH (Bachevalier et al., 2001). As adults (Experiment 1), the monkeys were re-evaluated in the same dyads and their reactivity to novel toys, social status, and reactions to separation were also assessed. Group TE now showed only few if any of the abnormal behaviors observed in infancy. In contrast, Group AH continued to display decreased social interactions and increased self-directed activity and showed also increased submission and reduced responses to separation, but normal reactivity to novel toys. To determine whether this degree of socioemotional impairment was less severe than that produced by the same damage in adulthood, we assessed dyadic social interactions of monkeys raised until adulthood in laboratory conditions similar to those in Experiment 1 and then given the All ablations (Experiment 2). Two months postoperatively these monkeys showed a small reduction in social interactions that became more pronounced six months postoperatively, yet remained less severe than that seen in the infant-lesioned monkeys. No other socioemotional effects, except for an increase in food/water consumption, were observed. The finding that neonatal AH lesions produce more severe socioemotional disturbances than the same lesion in adulthood is the reverse of the effect commonly reported for other cognitive functions after cerebral damage.
C1 [Malkova, Ludise; Mishkin, Mortimer; Bachevalier, Jocelyne] NIMH, Bethesda, MD 20892 USA.
[Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Malkova, L (reprint author), Georgetown Univ, Sch Med, Dept Pharmacol, 3900 Reservoir Rd NW, Washington, DC 20007 USA.
EM malkoval@georgetown.edu
FU National Institute of Mental Health; Division of Intramural Research,
Eunice Kennedy Shriver National Institute of Child Health and Human
Development; [KO2HD42269]; [R01MH084069]; [R01MH58846]; [P01HD35471]
FX This work was supported by Intramural Research Program of the National
Institute of Mental Health and Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, the work on the manuscript was supported in part by
KO2HD42269 and R01MH084069 to Ludise Malkova and R01MH58846 and
P01HD35471 to Jocelyne Bachevalier. We thank Bryan Kirkpatrick for
behavioral analyses of the videotapes as the second observer. We also
thank Norma Minters for postoperative care of the animals, John Sewell
III for histological processing of the brains, and Richard C. Saunders
for MRI scans of the animals.
NR 65
TC 13
Z9 13
U1 1
U2 6
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0735-7044
J9 BEHAV NEUROSCI
JI Behav. Neurosci.
PD DEC
PY 2010
VL 124
IS 6
BP 742
EP 760
DI 10.1037/a0021622
PG 19
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 697PK
UT WOS:000285527100002
PM 21133531
ER
PT J
AU Almeida, MQ
Stratakis, CA
AF Almeida, Madson Q.
Stratakis, Constantine A.
TI Carney complex and other conditions associated with micronodular adrenal
hyperplasias
SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
DE Carney complex; PPNAD; PRKAR1A; phosphodiesterase
ID NODULAR ADRENOCORTICAL DISEASE; SPOTTY SKIN PIGMENTATION; DEPENDENT
PROTEIN-KINASE; FAMILIAL CARDIAC MYXOMAS; ENDOCRINE OVERACTIVITY;
REGULATORY SUBUNIT; PRKAR1A MUTATION; PHOSPHODIESTERASE 11A; SIGNALING
PATHWAYS; GENE
AB Carney complex (CNC) is a multiple neoplasia syndrome that is inherited in an autosomal dominant manner and is characterized by skin tumors and pigmented lesions, myxomas, schwannomas, and various endocrine tumors. Inactivating mutations of the PRKAR1A gene coding for the regulatory type I-alpha (RI alpha) subunit of protein kinase A (PKA) are responsible for the disease in most CNC patients. The overall penetrance of CNC among PRKAR1A mutation carriers is near 98%. Most PRKAR1A mutations result in premature stop codon generation and lead to nonsense-mediated mRNA decay. CNC is genetically and clinically heterogeneous, with specific mutations providing some genotype-phenotype correlation. Phosphodiesterase-11A (the PDE11A gene) and -8B (the PDE8B gene) mutations were found in patients with isolated adrenal hyperplasia and Cushing syndrome, as well in patients with PPNAD. Recent evidences demonstrated that dysregulation of cAMP/PKA pathway can modulate other signaling pathways and contributes to adrenocortical tumorigenesis. Published by Elsevier Ltd.
C1 [Almeida, Madson Q.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), NICHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH,CRC, Bldg 10,Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU Intramural NIH HHS [ZIA HD000642-12]
NR 51
TC 22
Z9 23
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1521-690X
J9 BEST PRACT RES CL EN
JI Best Pract. Res. Clin. Endoc. Metab.
PD DEC
PY 2010
VL 24
IS 6
BP 907
EP 914
DI 10.1016/j.beem.2010.10.006
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 705IA
UT WOS:000286120900007
PM 21115159
ER
PT J
AU Nath, N
Chattopadhyay, M
Pospishi, L
Cieciura, LZ
Goswami, S
Kodela, R
Saavedra, JE
Keefer, LK
Kashfi, K
AF Nath, Niharika
Chattopadhyay, Mitali
Pospishi, Liliya
Cieciura, Lucyna Z.
Goswami, Satindra
Kodela, Ravinder
Saavedra, Joseph E.
Keefer, Larry K.
Kashfi, Khosrow
TI JS-K; a nitric oxide-releasing prodrug, modulates beta-catenin/TCF
signaling in leukemic Jurkat cells: Evidence of an S-nitrosylated
mechanism
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Leukemia; JS-K; S-nitrosylation; beta-Catenin; Chemoprevention
ID CYCLIN D1; IN-VITRO; BREAST-CANCER; EXPRESSION; APOPTOSIS; GROWTH;
PATHWAYS; DRUGS; VIVO
AB beta-Catenin is a central player of the Wnt signaling pathway that regulates cell-cell adhesion and may promote leukemia cell proliferation We examined whether JS-K, an NO-donating prodrug, modulates the Wnt/beta-catenin/TCF-4 signaling pathway in Jurkat T-Acute Lymphoblastic Leukemia cells JS-K inhibited Jurkat T cell growth in a concentration and time-dependent manner. The IC(50)s for cell growth inhibition were 14 +/- 0.7 and 9 +/- 1.2 mu M at 24 and 48 h, respectively. Treatment of the cells with JS-K for 24 h, caused a dose-dependent increase in apoptosis from 16 +/- 3.3% at 10 mu M to 74.8 +/- 2% at 100 mu M and a decrease in proliferation. This growth inhibition was also due, in part, to alterations in the different phases of the cell cycle JS-K exhibited a dose-dependent cytotoxicity as measured by LDH release at 24 h. However, between 2 and 811, LDH release was less than 20% for any indicated JS-K concentration. The beta-catenin/TCF-4 transcriptional inhibitory activity was reduced by 32 +/- 8, 63 +/- 5, and 93 +/- 2% at 2, 10, and 25 mu M JS-K. respectively, based on luciferase reporter assays. JS-K reduced nuclear beta-catenin and cyclin D1 protein levels, but cytosolic beta-catenin expression did not change. Based on a time-course assay of S-nitrosylation of proteins by a biotin switch assay. S-nitrsolyation of nuclear beta-catenin was determined to precede its degradation A comparison of the S-nitrosylated nuclear beta-catenin to the total nuclear beta-catenin showed that beta-catenin protein levels were degraded at 24 h. while S-nitrosylation of beta-catenin occurred earlier at 0-6 h. The NO scavenger PTIO abrogated the JS-K mediated degradation of beta-catenin demonstrating the need for NO (C) 2010 Elsevier Inc. All rights reserved
C1 [Nath, Niharika; Chattopadhyay, Mitali; Pospishi, Liliya; Cieciura, Lucyna Z.; Goswami, Satindra; Kodela, Ravinder; Kashfi, Khosrow] CUNY, Sch Med, Dept Physiol & Pharmacol, New York, NY 10031 USA.
[Nath, Niharika] New York Inst Technol, Dept Life Sci, New York, NY USA.
[Saavedra, Joseph E.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA.
RP Kashfi, K (reprint author), CUNY, Sch Med, Dept Physiol & Pharmacol, 138th St & Convent Ave, New York, NY 10031 USA.
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU NIH, National Cancer Institute, Center for Cancer Research; NCI
[HHSN261200800001E]
FX This work was supported in part by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research, and by
NCI contract HHSN261200800001E
NR 44
TC 11
Z9 13
U1 0
U2 1
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 2010
VL 80
IS 11
BP 1641
EP 1649
DI 10.1016/j.bcp.2010.08.011
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 673CS
UT WOS:000283636900003
PM 20797387
ER
PT J
AU Ray, DM
Rogers, BA
Sunman, JA
Akiyama, SK
Olden, K
Roberts, JD
AF Ray, Denise M.
Rogers, Brian A.
Sunman, Jeffrey A.
Akiyama, Steven K.
Olden, Kenneth
Roberts, John D.
TI Lysine 63-linked ubiquitination is important for arachidonic
acid-induced cellular adhesion and migration
SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE
LA English
DT Article
DE adhesion; ubiquitin; metastasis; signal transduction; arachidonic acid
ID BREAST-CARCINOMA CELLS; SIGNALING PATHWAY; ACTIVATING ENZYME; CANCER
CELLS; IV COLLAGEN; FATTY-ACIDS; DIETARY-FAT; P38 MAPK; PROTEIN; KINASE
AB L'acide arachidonique, un acide gras cis-polyinsature de la diete, stimule d'adhesion et la migration des cellules cancereuses d'origine humaine sur la matrice extracellulaire en activant des voies de signalisation intracellulaire. Les chaines de poly-ubiquitine liees via differents residus lysine transmettent des informations structurales et fonctionnelles distinctes importantes pour la transduction de signaux. Nous avons examine si l'induction par l'acide arachidonique de l'adhesion et de la migration des cellules MDA-MB-435 au collagene de type IV necessitait l'ubiquitination. Un inhibiteur de l'enzyme d'activation de l'ubiquitine E1, le PYR-431, a completement aboli l'adhesion stimulee par l'acide arachidonique. De plus, l'expression d'une ubiquitine mutante depourvue de residus lysine empechait l'activation de l'adhesion cellulaire. Les cellules exprimant une ubiquitine dans laquelle la lysine 63 (K63) etait mutee en arginine (K63R) ne pouvaient adherer au collagene a la suite d'une exposition a l'acide arachidonique. Lorsque la K63 etait la seule lysine presente, les cellules conservaient leur capacite d'adhesion, indiquant que seule l'ubiquitine liee par la K63 est necessaire et suffisante. De plus, l'ubiquitine liee par la K63 etait requise a l'induction de la migration cellulaire par l'acide arachidonique. L'ubiquitine mutee et le PYR-431 n'empechaient pas la phosphorylation induite par l'acide arachidonique des kinases TAK1 (TGF-beta activated kinase 1) et p38 MAPK, suggerant que l'ubiquitination via la K63 se produit en aval de MAPK. Ces resultats originaux sont les premiers a demontrer le role de l'ubiquitination via la K63 dans la promotion de l'adhesion et de la migration cellulaires.
C1 [Ray, Denise M.; Rogers, Brian A.; Sunman, Jeffrey A.; Akiyama, Steven K.; Olden, Kenneth; Roberts, John D.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Rogers, Brian A.] N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA.
RP Roberts, JD (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM roberts1@niehs.nih.gov
FU NIEHS; NIH
FX We thank Drs. Harriet Kinyamu and Thomas Eling for a careful review of
the manuscript. This work has been supported in part or in whole by the
Intramural Research Program of the NIEHS and the NIH.
NR 38
TC 4
Z9 4
U1 1
U2 3
PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS
PI OTTAWA
PA 1200 MONTREAL ROAD, BUILDING M-55, OTTAWA, ON K1A 0R6, CANADA
SN 0829-8211
J9 BIOCHEM CELL BIOL
JI Biochem. Cell Biol.
PD DEC
PY 2010
VL 88
IS 6
BP 947
EP 956
DI 10.1139/O10-148
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 697YE
UT WOS:000285554900008
PM 21102657
ER
PT J
AU Fedorova, OV
Shapiro, JI
Bagrov, AY
AF Fedorova, Olga V.
Shapiro, Joseph I.
Bagrov, Alexei Y.
TI Endogenous cardiotonic steroids and salt-sensitive hypertension
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Review
DE Hypertension; Salt, dietary; Salt-sensitivity; Dahl salt-sensitive rats;
Na/K-ATPase; Marinobufagenin; Ouabain; Chronic kidney disease; Uremic
cardiomyopathy; Collagen; Fibrosis
ID BLOOD-PRESSURE REGULATION; PLASMALEMMAL NA/K-ATPASE; DAHL-S RATS;
EXPERIMENTAL UREMIC CARDIOMYOPATHY; SIGNAL-TRANSDUCING FUNCTION;
ACTIVATED PROTEIN-KINASES; DIGITALIS-LIKE SUBSTANCE; SODIUM-PUMP
INHIBITION; GLYCOSIDE BINDING-SITE; CARDIAC NA+/K+-ATPASE
AB Endogenous cardiotonic steroids (CTS), also called digitalis like factors, have been postulated to play important roles in pathogenesis of hypertension for nearly half of a century. For the past 50 years biomedical scientists have been in quest of an unidentified factor or hormone that both increases blood pressure and renal sodium excretion; this "natriuretic hormone" was, in fact, postulated to interact With the Na/K-ATPase. Recent discoveries have led to the identification of steroid molecules which are present in humans, rodents and amphibians, and which, in a complex manner, interact with each other and with the other systems that regulate renal salt handling and contribute to the salt-sensitivity of blood pressure.
Recent findings include the specific identification of endogenous cardenolide (endogenous ouabain) and bufadienolide (marinobufagenin) CTS in humans along with the delineation of mechanisms by which CI'S can signal through the Na/K-ATPase. Although CTS were first considered important in the regulation of renal sodium transport and arterial pressure, more recent work implicates these hormones in the central regulation of blood pressure and regulation of cell growth, and development of cardiovascular and renal fibrosis in particular. Published by Elsevier B.V.
C1 [Fedorova, Olga V.; Bagrov, Alexei Y.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Shapiro, Joseph I.] Univ Toledo, Dept Med, Toledo, OH 43606 USA.
RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM bagrova@mail.nih.gov
FU National Institute on Aging, National Institutes of Health; NIH
[HL071556]
FX This work was supported by the Intramural Research Program, National
Institute on Aging, National Institutes of Health (OVF and AYB), and by
NIH grant HL071556 (JIS).
NR 101
TC 30
Z9 34
U1 1
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-4439
J9 BBA-MOL BASIS DIS
JI Biochim. Biophys. Acta-Mol. Basis Dis.
PD DEC
PY 2010
VL 1802
IS 12
SI SI
BP 1230
EP 1236
DI 10.1016/j.bbadis.2010.03.011
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 682HW
UT WOS:000284393000013
PM 20347967
ER
PT J
AU Villaraza, AJL
Milenic, DE
Brechbiel, MW
AF Villaraza, Aaron Joseph L.
Milenic, Diane E.
Brechbiel, Martin W.
TI Improved Speciation Characteristics of PEGylated Indocyanine
Green-Labeled Panitumumab: Revisiting the Solution and Spectroscopic
Properties of a Near-Infrared Emitting anti-HER1 Antibody for Optical
Imaging of Cancer
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID IN-VIVO; SUCCINIMIDYL ESTERS; MONOCLONAL-ANTIBODIES; MONITORED
AMINOLYSIS; CYANINE DYES; FLUORESCENCE; REAGENTS; PROTEIN; AGENT; HEAD
AB A water-soluble amine-reactive PEGylated analogue of near-infrared emitting dye indocyanine green (5) was synthesized and used to label the anti-HER I antibody panitumumab (Vectibix) at various equivalents. These conjugates were compared with non-PEGylated analogue conjugate products and the solution speciation analyzed with UV-vis spectrophotometry, size exclusion HPLC, and SDS-PAGE. PEGylation of the bioconjugates was successful in preventing aggregation in solution, a phenomenon observed with the non-PEGylated bioconjugates presumably clue to the hydrophobicity of indocyanine green. Competitive radioimmunoassay demonstrated that the targeting moiety of the PEGylated bioconjugates was conserved. Fluorescence microscopy also demonstrated membrane binding of the bioconjugate to HER1-expressing A431 cells. Hence, these bioconjugates are suitable candidates for the in vivo optical imaging of HER1-expressing tumors.
C1 [Villaraza, Aaron Joseph L.; Milenic, Diane E.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room B3B69, Bethesda, MD 20892 USA.
EM martinwb@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. We would
like to acknowledge the assistance of Dr. Kwamena Baidoo for supplying
the 125I-labeled panitumumab for the radioimmunoassay and Dr.
Hisataka Kobayashi for the use of the confocal fluorescence microscope.
NR 48
TC 16
Z9 16
U1 1
U2 15
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD DEC
PY 2010
VL 21
IS 12
BP 2305
EP 2312
DI 10.1021/bc100336b
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 693PP
UT WOS:000285236300022
PM 21073171
ER
PT J
AU Hakamata, Y
Lissek, S
Bar-Haim, Y
Britton, JC
Fox, NA
Leibenluft, E
Ernst, M
Pine, DS
AF Hakamata, Yuko
Lissek, Shmuel
Bar-Haim, Yair
Britton, Jennifer C.
Fox, Nathan A.
Leibenluft, Ellen
Ernst, Monique
Pine, Daniel S.
TI Attention Bias Modification Treatment: A Meta-Analysis Toward the
Establishment of Novel Treatment for Anxiety
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Anxiety disorders; attention bias modification treatment; cognitive
bias; meta-analysis; novel treatment; psychotherapy
ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; SOCIAL
ANXIETY; EXPERIMENTAL MANIPULATION; MODIFICATION PROGRAM; INDIVIDUALS;
THREAT; RATES; VULNERABILITY; INFORMATION
AB Background: Attention Bias Modification Treatment (ABMT) is a newly emerging, promising treatment for anxiety disorders. Although recent randomized control trials (RCTs) suggest that ABMT reduces anxiety, therapeutic effects have not been summarized quantitatively.
Methods: Standard meta-analytic procedures were used to summarize the effect of ABMT on anxiety. With MEDLINE, January 1995 to February 2010, we identified RCTs comparing the effects on anxiety of ABMT and quantified effect sizes with Hedge's d.
Results: Twelve studies met inclusion criteria, including 467 participants from 10 publications. Attention Bias Modification Treatment produced significantly greater reductions in anxiety than control training, with a medium effect (d = .61, p < .001). Age and gender did not moderate the effect of ABMT on anxiety, whereas several characteristics of the ABMT training did.
Conclusions: Attention Bias Modification Treatment shows promise as a novel treatment for anxiety. Additional RCTs are needed to fully evaluate the degree to which these findings replicate and apply to patients. Future work should consider the precise role for ABMT in the broader anxiety-disorder therapeutic armamentarium.
C1 [Hakamata, Yuko] Univ Tokyo, Dept Clin Psychol, Tokyo, Japan.
[Lissek, Shmuel; Britton, Jennifer C.; Leibenluft, Ellen; Ernst, Monique; Pine, Daniel S.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
[Fox, Nathan A.] Univ Maryland, College Pk, MD 20742 USA.
[Bar-Haim, Yair] Tel Aviv Univ, IL-69978 Tel Aviv, Israel.
[Hakamata, Yuko] NIMH, Div Adult Mental Hlth, Bethesda, MD 20892 USA.
RP Hakamata, Y (reprint author), Univ Tokyo, Dept Clin Psychol, Tokyo, Japan.
EM yumhakamata@gmail.com
RI Britton, Jennifer/J-4501-2013
FU Japan Society for the Promotion of Science
FX Yuko Hakamata was a visiting fellow in the National Institute of Mental
Health from 2009 to 2010. The stipend was supported by the Japan Society
for the Promotion of Science. Sincere appreciation is extended to Dr.
Yoshiharu Kim, Dr. Tetsuya Suhara, Dr. Haruhiko Shimoyama, Dr. Toshiya
Inada, Dr. Yutaka Matsuoka, Dr. Masatoshi Inagaki, Dr. Kiyoto Kasai, Dr.
Robert B. Innis, and Dr. Danny Pine for their help and support in this
matter.
NR 45
TC 343
Z9 351
U1 8
U2 112
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD DEC 1
PY 2010
VL 68
IS 11
BP 982
EP 990
DI 10.1016/j.biopsych.2010.07.021
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 688FG
UT WOS:000284834600005
PM 20887977
ER
PT J
AU Gill, J
Luckenbaugh, D
Charney, D
Vythilingam, M
AF Gill, Jessica
Luckenbaugh, David
Charney, Dennis
Vythilingam, Meena
TI Sustained Elevation of Serum Interleukin-6 and Relative Insensitivity to
Hydrocortisone Differentiates Posttraumatic Stress Disorder with and
Without Depression
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Depression; glucocorticoid sensitivity; hydrocortisone; PTSD; serial
sampling; serum IL-6
ID ENHANCED CORTISOL SUPPRESSION; CORONARY-ARTERY-DISEASE; PEPTIDASE-IV
ACTIVITY; MAJOR DEPRESSION; DEXAMETHASONE-SUPPRESSION; ACTH RESPONSE;
PSYCHOMETRIC PROPERTIES; MYOCARDIAL-INFARCTION; CYTOKINE PRODUCTION;
METABOLIC SYNDROME
AB Background: Elevated levels of proinflammatory cytokines, especially interleukin-6 (IL-6), can mediate the greater risk for cardiovascular disease in individuals with posttraumatic stress disorder (PTSD), particularly in those with comorbid major depressive disorder (MDD). However, IL-6 levels are not consistently elevated in either PTSD or MDD. Although PTSD is associated with supersensitivity to glucocorticoids; prior studies have not evaluated the effect of comorbid MDD.
Methods: Serum IL-6 levels were measured hourly between 7: 00 PM and 7: 00 AM in individuals with PTSD with comorbid MDD (PTSD + MDD) (n = 9) and compared with those with PTSD without MDD (PTSD - MDD) (n = 9) and nontraumatized healthy control subjects (n = 14). Group differences in serum IL-6, plasma adrenocorticotropic hormone (ACTH), and plasma cortisol response to 30 mg of intravenous hydrocortisone were evaluated using linear mixed models.
Results: Only subjects with PTSD + MDD exhibited higher, overnight serum IL-6 levels compared with individuals with PTSD - MDD (p < .01) and healthy control subjects (p < .001). Peak overnight IL-6 levels positively correlated with severity of PTSD (r = .56, p < .01) and depressive symptoms (r = .54, p < .01). Hydrocortisone administration significantly reduced IL-6 levels in both PTSD groups; however, IL-6 levels in PTSD + MDD were higher than both PTSD - MDD (p < .05) and healthy control subjects (p < .01). Following hydrocortisone administration, there was a greater reduction in levels of ACTH in PTSD - MDD compared with control subjects (p < .01).
Conclusions: Sustained elevations of overnight IL-6 levels and relatively decreased sensitivity to hydrocortisone distinguish PTSD + MDD from PTSD - MDD. Novel strategies that decrease IL-6 levels offer a new direction in the prevention and treatment of PTSD and associated comorbid medical illnesses.
C1 [Vythilingam, Meena] Off Assistant Secretary Def Hlth Affairs, Psychol Hlth Strateg Operat, Force Hlth Protect & Readiness, Falls Church, VA 22041 USA.
[Gill, Jessica] NIMH, NINR, Bethesda, MD 20892 USA.
[Luckenbaugh, David; Vythilingam, Meena] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Charney, Dennis] Mt Sinai Sch Med, New York, NY USA.
RP Vythilingam, M (reprint author), Off Assistant Secretary Def Hlth Affairs, Psychol Hlth Strateg Operat, Force Hlth Protect & Readiness, Skyline 4,Suite 800A,5113 Leesburg Pike, Falls Church, VA 22041 USA.
EM meena.vythilingam@ha.osd.mil
FU National Institute of Mental Health Intramural Research Program
FX The research reported in this manuscript was undertaken at the National
Institutes of Health and funded by the National Institute of Mental
Health Intramural Research Program.
NR 77
TC 33
Z9 33
U1 3
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD DEC 1
PY 2010
VL 68
IS 11
BP 999
EP 1006
DI 10.1016/j.biopsych.2010.07.033
PG 8
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 688FG
UT WOS:000284834600007
PM 20951370
ER
PT J
AU von Leupoldt, A
Vovk, A
Bradley, MM
Keil, A
Lang, PJ
Davenport, PW
AF von Leupoldt, Andreas
Vovk, Andrea
Bradley, Margaret M.
Keil, Andreas
Lang, Peter J.
Davenport, Paul W.
TI The impact of emotion on respiratory-related evoked potentials in
healthy volunteers
SO BIOLOGICAL PSYCHOLOGY
LA English
DT Meeting Abstract
CT 16th Annual Meeting/28th Symposium on Respiratory Psychophysiology
CY OCT 25-27, 2009
CL Berlin, GERMANY
SP Int Soc Adv Resp Psychophysiol (ISARP)
C1 [von Leupoldt, Andreas; Vovk, Andrea; Davenport, Paul W.] Univ Florida, Dept Physiol Sci, Gainesville, FL 32610 USA.
[von Leupoldt, Andreas] Univ Hamburg, Dept Psychol, Hamburg, Germany.
[von Leupoldt, Andreas] Univ Med Ctr Hamburg Eppendorf, Dept Syst Neurosci, Hamburg, Germany.
[von Leupoldt, Andreas; Bradley, Margaret M.; Keil, Andreas; Lang, Peter J.] Univ Florida, NIMH Ctr Study Emot & Attent, Gainesville, FL USA.
RI Keil, Andreas/F-9427-2011
OI Keil, Andreas/0000-0002-4064-1924
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-0511
J9 BIOL PSYCHOL
JI Biol. Psychol.
PD DEC
PY 2010
VL 85
IS 3
BP 521
EP 521
PG 1
WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology,
Experimental
SC Psychology; Behavioral Sciences
GA 728TG
UT WOS:000287896800061
ER
PT J
AU Wolff, D
Gerbitz, A
Ayuk, F
Kiani, A
Hildebrandt, GC
Vogelsang, GB
Elad, S
Lawitschka, A
Socie, G
Pavletic, SZ
Holler, E
Greinix, H
AF Wolff, Daniel
Gerbitz, Armin
Ayuk, Francis
Kiani, Alexander
Hildebrandt, Gerhard C.
Vogelsang, Georgia B.
Elad, Sharon
Lawitschka, Anita
Socie, Gerard
Pavletic, Steven Z.
Holler, Ernst
Greinix, Hildegard
TI Consensus Conference on Clinical Practice in Chronic Graft-versus-Host
Disease (GVHD): First-Line and Topical Treatment of Chronic GVHD
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Allogeneic hematopoietic stem cell transplantation; Graft-versus-host
disease; Immunosuppressive therapy
ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; WORKING
GROUP-REPORT; ORAL BECLOMETHASONE DIPROPIONATE; OBSTRUCTIVE AIRWAY
DISEASE; ALTERNATE-DAY PREDNISONE; DEVELOPMENT PROJECT; EXTRACORPOREAL
PHOTOCHEMOTHERAPY; LICHEN-PLANUS; PUVA THERAPY
AB Chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation is still associated with significant morbidity and mortality First-line treatment of cGVHD is based on steroids of I mg/kg/day of prednisone The role of calcineurin inhibitors remains controversial especially in patients with low risk for mortality (normal platelets counts) whereas patients with low platelets at diagnosis and/or high risk for steroid toxicity may be treated upfront with the combination of prednisone and a calcineurin inhibitor Additional systemic immuno uppressive agents like thalidomide mycophenolic acid and azathio prine failed to improve treatment results in the primary treatment of cGVHD and are in part associated with higher morbidity and in the case of azathioprine with higher mortality Despite advances in diagnosis of cGVHD as well as supportive care half of the patients fail to achieve a long lasting response to first line treatment and infectious morbidity continues to be significant Therefore immunomodulatory interventions with low infectious morbidity and mortality such as photopheresis need urgent evaluation in clinical trials Beside systemic immunosuppression the use of topical immunosuppressive interventions may improve local response rates and may be used as the only treatment in mild localized organ manifestations of cGVHD Biol Blood Marrow Transplant 16 1611-1028 (2010) (C) 2010 American Society for Blood and Marrow Transplantation
C1 [Wolff, Daniel; Hildebrandt, Gerhard C.; Holler, Ernst] Univ Regensburg, Dept Hematol & Clin Oncol, D-93053 Regensburg, Germany.
[Gerbitz, Armin] Charite, Dept Immunol, Berlin, Germany.
[Ayuk, Francis] UCCH, Interdisciplinary Clin Stem Cell Transplantat, Hamburg, Germany.
[Kiani, Alexander] Univ Dresden, Dept Internal Med 1, Dresden, Germany.
[Vogelsang, Georgia B.] Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA.
[Elad, Sharon] Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Dept Oral Med, Jerusalem, Israel.
[Lawitschka, Anita] St Anna Childrens Hosp, A-1090 Vienna, Austria.
[Socie, Gerard] Hosp St Louis, Serv Hematol Greffe, Paris, France.
[Socie, Gerard] Hosp St Louis, INSERM, Paris, France.
[Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Greinix, Hildegard] Med Univ Vienna, Dept Internal Med 1, Vienna, Austria.
RP Wolff, D (reprint author), Univ Regensburg, Dept Hematol & Oncol, FJ Strauss Allee 11, D-93053 Regensburg, Germany.
FU Jose Carreras Foundation
FX The authors thank all participating centers of conferences and surveys,
which included participants from the transplant centers in Augsburg,
Basel, Berlin, Cologne, Dresden, Duesseldorf, Erlangen, Essen, Freiburg,
Greifswald, Hamburg, Hannover, Heidelberg, Jena, Kiel, Leipzig, Linz,
Mainz, Munster, Munich, Nantes, Nuernberg, Oldenburg, Paris, Regensburg,
Rostock, Tuebingen, Ulm, Vienna, Wiesbaden, and Wuerzburg The authors
thank Anna Hackl for evaluating the survey on treatment of cGVHD The
conference was supported by the Jose Carreras Foundation project
"Competence Center GVHD Regensburg"
NR 112
TC 90
Z9 96
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD DEC
PY 2010
VL 16
IS 12
BP 1611
EP 1628
DI 10.1016/j.bbmt.2010.06.015
PG 18
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 684RL
UT WOS:000284566900001
PM 20601036
ER
PT J
AU Sloand, EM
Pfannes, L
Ling, C
Feng, XM
Jasek, M
Calado, R
Tucker, ZCG
Hematti, P
Maciejewski, J
Dunbar, C
Barrett, J
Young, N
AF Sloand, Elaine M.
Pfannes, Loretta
Ling, Casey
Feng, Xingmin
Jasek, Monika
Calado, Rodrigo
Tucker, Zachary C. G.
Hematti, Peiman
Maciejewski, Jaroslaw
Dunbar, Cynthia
Barrett, John
Young, Neal
TI Graft-versus-Host Disease: Role of Inflammation in the Development of
Chromosomal Abnormalities of Keratinocytes
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Squamous cell carcinoma; Inflammation; Keratinocytes; Genomic
instability; Aneuploidy; Tetraploidy
ID SQUAMOUS-CELL CARCINOMA; OXYRADICAL OVERLOAD DISEASE; IN-SITU
HYBRIDIZATION; SKIN-CANCER; MARROW TRANSPLANTATION; TELOMERE LENGTH;
SOLID CANCERS; NITRIC-OXIDE; DNA-DAMAGE; STEM-CELLS
AB Graft-versus-host disease (GVHD) is a major risk factor for secondary malignancy after hematopoietic stem cell transplantation Squamous cell carcinoma (SCC) of the skin and mucous membranes are especially frequent in this setting where aneuploidy and tetraploidy are associated with aggressive disease The current study is directed at the mechanism of neoplasia in this setting Unmanipulated keratinocytes from areas of oral GVHD in 9 patients showed tetraploidy in 10% to 46% of cells when examined by florescein in situ hybridization (FISH) Keratinocytes isolated from biopsy sites of GVHD but not from normal tissue showed even greater numbers of tetraploid cells (mean = 78% range 15% 85% N = 9) after culture To mimic the inflammatory process in GVHD allogeneic HLA mismatched lymphocytes were mixed with normal keratinocytes After 2 weeks substantial numbers of aneuploid and tetraploid cells were evident in cultures with lymphocytes and with purified CD8 but not CD4 cells Telomere length was substantially decreased in the lymphocyte treated sample No mutations were present in the p53 gene although haploinsufficiency for p53 due to the loss of chromosome 17 was common in cells exposed to lymphocytes These findings suggest that in GVHD inflammation and repeated cell division correlate with the development of karyotypic abnormalities Biol Blood Marrow Transplant 16 1665-1673 (2010) (C) 2010 American Society for Blood and Marrow Transplantation
C1 [Sloand, Elaine M.; Pfannes, Loretta; Ling, Casey; Feng, Xingmin; Jasek, Monika; Calado, Rodrigo; Tucker, Zachary C. G.; Hematti, Peiman; Maciejewski, Jaroslaw; Dunbar, Cynthia; Barrett, John; Young, Neal] NHLBI, Bethesda, MD 20892 USA.
RP Sloand, EM (reprint author), NHLBI, Bldg 10,CRC 4-5230, Bethesda, MD 20892 USA.
RI Calado, Rodrigo/G-2619-2011
FU National Heart Lung and Blood Institute
FX Financial disclosure This research is supported by the National Heart
Lung and Blood Institute
NR 52
TC 8
Z9 8
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD DEC
PY 2010
VL 16
IS 12
BP 1665
EP 1673
DI 10.1016/j.bbmt.2010.07.014
PG 9
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 684RL
UT WOS:000284566900005
PM 20659573
ER
PT J
AU Kawut, SM
Barr, RG
Johnson, WC
Chahal, H
Tandri, H
Jain, A
Bristow, MR
Kizer, JR
Bagiella, E
Lima, JAC
Bluemke, DA
AF Kawut, Steven M.
Barr, R. Graham
Johnson, W. Craig
Chahal, Harjit
Tandri, Harikrishna
Jain, Aditya
Bristow, Michael R.
Kizer, Jorge R.
Bagiella, Emilia
Lima, Joao A. C.
Bluemke, David A.
TI Matrix metalloproteinase-9 and plasminogen activator inhibitor-1 are
associated with right ventricular structure and function: The MESA-RV
Study
SO BIOMARKERS
LA English
DT Article
DE Inflammation; thrombosis; hypertension; pulmonary
ID PRIMARY PULMONARY-HYPERTENSION; CARDIOVASCULAR RISK-FACTORS;
ARTERIAL-HYPERTENSION; HEART-FAILURE; MATRIX METALLOPROTEINASES;
ATHEROSCLEROSIS; EXPRESSION; MONOCYTES; GEOMETRY; LUNG
AB Elevated resistance and reduced compliance of the pulmonary vasculature increase right ventricular (RV) afterload. Local and systemic inflammation and haemostatic abnormalities are prominent in pulmonary vascular diseases. We hypothesized that plasma biomarker levels indicating greater inflammation and coagulability associated with pulmonary vascular disease would be associated with RV structure and function measured by cardiac magnetic resonance imaging (MRI). The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI among participants aged 45-84 years without clinical cardiovascular disease. We assessed the associations of RV mass, RV end-diastolic volume (RVEDV), RV stroke volume (RVSV) and RV ejection fraction (RVEF) with plasma measures of inflammation (matrix metalloproteinase (MMP)-3 and -9, intercellular adhesion molecule (ICAM)-1, tumour necrosis factor receptor (TNF-R1), and E-selectin) and thrombosis (plasminogen activator inhibitor (PAI)-1, tissue factor, tissue factor pathway inhibitor and CD40 ligand).The study sample included 731 subjects. Higher MMP-9 levels were associated with lower RV mass before and after adjustment for left ventricular (LV) mass (p = 0.008 and p = 0.044, respectively). Higher levels of MMP-9 and PAI-1 were also associated with smaller RVEDV (p < 0.05). Higher PAI-1 levels were associated with lower RVEF even after adjustment for LV ejection fraction (p = 0.017). In conclusion, MMP-9 and PAI-1 are associated with changes in RV structure and function which could be potentially related to a subclinical increase in pulmonary vascular resistance.Competing risks arise naturally in time-to-event studies. In this article, we propose time-dependent accuracy measures for a marker when we have censored survival times and competing risks. Time-dependent versions of sensitivity or true positive (TP) fraction naturally correspond to consideration of either cumulative (or prevalent) cases that accrue over a fixed time period, or alternatively to incident cases that are observed among event-free subjects at any select time. Time-dependent (dynamic) specificity (1-false positive (FP)) can be based on the marker distribution among event-free subjects. We extend these definitions to incorporate cause of failure for competing risks outcomes. The proposed estimation for cause-specific cumulative TP/dynamic FP is based on the nearest neighbor estimation of bivariate distribution function of the marker and the event time. On the other hand, incident TP/dynamic FP can be estimated using a possibly nonproportional hazards Cox model for the cause-specific hazards and riskset reweighting of the marker distribution. The proposed methods extend the time-dependent predictive accuracy measures of Heagerty, Lumley, and Pepe (2000, Biometrics 56, 337-344) and Heagerty and Zheng (2005, Biometrics 61, 92-105).
C1 [Saha, P.; Heagerty, P. J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
RP Saha, P (reprint author), NIEHS, Biostat Branch, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA.
EM psaha@u.washington.edu; heagerty@u.washington.edu
RI Saha Chaudhuri, Paramita/F-3835-2010;
OI Saha Chaudhuri, Paramita/0000-0003-1987-320X
FU NIH, National Institute of Environmental Health Sciences; [UL1
RR025014]; [R01 HL072966]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences (PS),
and Grants UL1 RR025014 and R01 HL072966 (PJH). The authors thank Dr
Gregg Dinse and Dr Tracy Xu for helpful comments.
NR 23
TC 31
Z9 32
U1 2
U2 18
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD DEC
PY 2010
VL 66
IS 4
BP 999
EP 1011
DI 10.1111/j.1541-0420.2009.01375.x
PG 13
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 693DN
UT WOS:000285204900001
PM 20070296
ER
PT J
AU Shih, JH
Albert, PS
AF Shih, Joanna H.
Albert, Paul S.
TI Modeling Familial Association of Ages at Onset of Disease in the
Presence of Competing Risk
SO BIOMETRICS
LA English
DT Article
DE Cause-specific cross-ratio; Competing risk; Familial association;
Odds-ratio
ID FAILURE TIME ASSOCIATIONS; BIVARIATE SURVIVAL-DATA;
NONPARAMETRIC-ESTIMATION; RATIO
AB P>In genetic family studies, ages at onset of diseases are routinely collected. Often one is interested in assessing the familial association of ages at the onset of a certain disease type. However, when a competing risk is present and is related to the disease of interest, the usual measure of association by treating the competing event as an independent censoring event is biased. We propose a bivariate model that incorporates two types of association: one is between the first event time of paired members, and the other is between the failure types given the first event time. We consider flexible measures for both types of association, and estimate the corresponding association parameters by adopting the two-stage estimation of Shih and Louis (1995, Biometrics 51, 1384-1399) and Nan et al. (2006, Journal of the American Statistical Association 101, 65-77). The proposed method is illustrated using the kinship data from the Washington Ashkenazi Study.
C1 [Shih, Joanna H.] NCI, Biometr Res Branch, Rockville, MD 20852 USA.
[Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
RP Shih, JH (reprint author), NCI, Biometr Res Branch, 6130 Execut Blvd,Rm 8132, Rockville, MD 20852 USA.
EM jshih@mail.nih.gov; albertp@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 19
TC 8
Z9 8
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD DEC
PY 2010
VL 66
IS 4
BP 1012
EP 1023
DI 10.1111/j.1541-0420.2009.01372.x
PG 12
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 693DN
UT WOS:000285204900002
PM 20002400
ER
PT J
AU Westfall, PH
Troendle, JF
Pennello, G
AF Westfall, Peter H.
Troendle, James F.
Pennello, Gene
TI Multiple McNemar Tests
SO BIOMETRICS
LA English
DT Article
DE Bonferroni-Holm; Bootstrap; Discreteness; Exact tests; Multiple
comparisons; Postmarket surveillance; Predictive model
ID BOOTSTRAP
AB P>Methods for performing multiple tests of paired proportions are described. A broadly applicable method using McNemar's exact test and the exact distributions of all test statistics is developed; the method controls the familywise error rate in the strong sense under minimal assumptions. A closed form (not simulation-based) algorithm for carrying out the method is provided. A bootstrap alternative is developed to account for correlation structures. Operating characteristics of these and other methods are evaluated via a simulation study. Applications to multiple comparisons of predictive models for disease classification and to postmarket surveillance of adverse events are given.
C1 [Westfall, Peter H.] Texas Tech Univ, Area ISQS, Lubbock, TX 79409 USA.
[Troendle, James F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Bethesda, MD 20892 USA.
[Pennello, Gene] US FDA, Epidemiol Branch, Ctr Devices & Radiol Hlth, HFZ 541, Rockville, MD 20850 USA.
RP Westfall, PH (reprint author), Texas Tech Univ, Area ISQS, Lubbock, TX 79409 USA.
EM peter.westfall@ttu.edu
FU NIH, NICHD
FX This research was supported in part by the Intramural Research Program
of the NIH, NICHD.
NR 20
TC 7
Z9 7
U1 2
U2 6
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD DEC
PY 2010
VL 66
IS 4
BP 1185
EP 1191
DI 10.1111/j.1541-0420.2010.01408.x
PG 7
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 693DN
UT WOS:000285204900020
PM 20345498
ER
PT J
AU Sarkar, P
Luchowski, R
Raut, S
Sabnis, N
Remaley, A
Lacko, AG
Thamake, S
Gryczynski, Z
Gryczynski, I
AF Sarkar, Pabak
Luchowski, Rafal
Raut, Sangram
Sabnis, Nirupama
Remaley, Alan
Lacko, Andras G.
Thamake, Sanjay
Gryczynski, Zygmunt
Gryczynski, Ignacy
TI Studies on solvatochromic properties of aminophenylstyryl-quinolinum
dye, LDS 798, and its application in studying submicron lipid based
structure
SO BIOPHYSICAL CHEMISTRY
LA English
DT Article
DE Aminostyryl quinolinum dye; Fluorescence correlation Spectroscopy;
Solvatochromism
ID FLUORESCENCE CORRELATION SPECTROSCOPY; HIGH-DENSITY-LIPOPROTEINS;
APOLIPOPROTEIN-A-I; PROBES
AB The stytyl group of dyes has been used in cellular studies for over 20 years because of their solvatochromic and/or electrochromic properties. Here we report characterization of solubility and solvatochromic properties of a near infra-red styryl dye, styryl 11 or LDS 798. We have extended our studies to small unilamellar vesicles and lipid based nanoparticles and found that solvatochromic properties of this dye used in tandem with fluorescence correlation spectroscopy can be used to efficiently determine the diffusion coefficient and hence the size of the submicron lipid based particles. This technique has the potential to provide essential information about liposomal and vesicular structures and their movement in vitro and in situ. Published by Elsevier B.V.
C1 [Sarkar, Pabak] Univ N Texas Hlth Sci Ctr, Dept Mol Microbiol & Immunol, Ctr Commercializat Fluorescence Technol, Ft Worth, TX 76107 USA.
[Raut, Sangram; Thamake, Sanjay] Univ N Texas Hlth Sci Ctr, Dept Biomed Sci, Ft Worth, TX 76107 USA.
[Gryczynski, Ignacy] Univ N Texas Hlth Sci Ctr, Dept Cell Biol & Anat, Ft Worth, TX 76107 USA.
[Remaley, Alan] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
RP Sarkar, P (reprint author), Univ N Texas Hlth Sci Ctr, Dept Mol Microbiol & Immunol, Ctr Commercializat Fluorescence Technol, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA.
EM psarkar@live.unthsc.edu; ignacy.gryczynski@unthsc.edu
RI Raut, Sangram/P-6921-2014
FU Texas Emerging Technology; DOD [BC093521]
FX This work was supported by the Texas Emerging Technology Funding grant
(given to the Center for Commercialization of Fluorescence Technology).
ST was funded by a predoctoral fellowship (BC093521) DOD Breast Cancer
Research Program (SIT). We would also like to thank Dr. Jamboor K.
Viswanatha for allowing us to use the NanoTrack dynamic light scattering
instrument and sonication system; Dr. Thomas Just Sorenson, for helping
with solvent relaxation studies; and Dr. Badri Prasad Maliwal and Dr.
Valeriya Trusova for the SUV preparation.
NR 20
TC 3
Z9 3
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-4622
J9 BIOPHYS CHEM
JI Biophys. Chem.
PD DEC
PY 2010
VL 153
IS 1
BP 61
EP 69
DI 10.1016/j.bpc.2010.10.005
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical
SC Biochemistry & Molecular Biology; Biophysics; Chemistry
GA 702MI
UT WOS:000285898400008
PM 21041016
ER
PT J
AU Jo, J
Guo, JE
Liu, T
Mullen, S
Hall, KD
Cushman, SW
Periwal, V
AF Jo, Junghyo
Guo, Juen
Liu, Teresa
Mullen, Shawn
Hall, Kevin D.
Cushman, Samuel W.
Periwal, Vipul
TI Hypertrophy-Driven Adopocyte Death Overwhelms Recruitment under
Prolonged Weight Gain
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID ADIPOSE-TISSUE; OBESE MICE; IN-VITRO; CELLS; DYNAMICS; TRANSPLANTATION;
APOPTOSIS; GROWTH; SIZE
AB Fat pads dynamically regulate energy storage capacity under energy excess and deficit This remodeling process is not completely understood with controversies regarding differences between fat depots and plasticity of adipose cell number We examined changes of mouse adipose cell size distributions in epididymal inguinal retroperitoneal and mesenteric fat under both weight gain and loss With mathematical modeling we specifically analyzed the recruitment growth/shrinkage and loss of adipose cells including the size dependence of these processes We found a qualitatively universal adipose tissue remodeling process in all four fat depots 1) There is continuous recruitment of new cells under weight gain 2) the growth and shrinkage of larger cells (diameter >50 mu m) is proportional to cell surface area and 3) cell loss occurs under prolonged weight gain with larger cells more susceptible The mathematical model gives a predictive integrative picture of adipose tissue remodeling in obesity
C1 [Jo, Junghyo; Guo, Juen; Hall, Kevin D.; Periwal, Vipul] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Liu, Teresa; Mullen, Shawn; Cushman, Samuel W.] NIDDK, Diabet Branch, NIH, Bethesda, MD USA.
RP Periwal, V (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RI Jo, Junghyo/D-4889-2011; Periwal, Vipul/I-1728-2012
FU National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases
FX This work was supported by funding from the intramural research program
of the National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases
NR 35
TC 17
Z9 17
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD DEC 1
PY 2010
VL 99
IS 11
BP 3535
EP 3544
DI 10.1016/j.bpj.010.10.009
PG 10
WC Biophysics
SC Biophysics
GA 690UL
UT WOS:000285033800005
PM 21112277
ER
PT J
AU Pezza, RJ
Camerini-Otero, RD
Bianco, PR
AF Pezza, Roberto J.
Camerini-Otero, R. Daniel
Bianco, Piero R.
TI Hop2-Mnd1 Condenses DNA to Stimulate the Synapsis Phase of DNA Strand
Exchange
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID HOMOLOGOUS RECOMBINATION; MEIOTIC RECOMBINATION; RECA PROTEIN; RAD51;
DMC1; MEIOSIS; COMPLEX; YEAST; HOP2; MND1
AB Hop2 Mnd1 is a meiotic recombination mediator that stimulates DNA strand invasion by both Dmc1 and Rad51 To understand the biochemical mechanism of this stimulation we directly visualized the heterodimer acting on single molecules of duplex DNA using optical tweezers and video fluorescence microscopy The results show that the Hop2 Mnd1 heterodimer efficiently condenses double stranded DNA via formation of a bright spot or DNA condensate The condensation of DNA is Hop2 Mnd1 concentration dependent reversible and specific to the heterodimer as neither Hop2 nor Mnd1 acting alone can facilitate this reaction The results also show that the rate limiting nucleation step of DNA condensation is overcome in the presence of divalent metal ions with the following order of preference Mn(2+)>Mg(2+)>Ca(2+) Hop2 Mnd1/Dmc1/single stranded DNA nucleoprotein filaments also condense double stranded DNA in a heterodimer concentration dependent manner Of importance the concentration dependence parallels that seen in DNA strand exchange We propose that rapid DNA condensation is a key factor in stimulating synapsis whereas decondensation may facilitate the invasion step and/or the ensuing branch migration process
C1 [Bianco, Piero R.] SUNY Buffalo, Dept Microbiol & Immunol, Ctr Single Mol Biophys, Buffalo, NY 14260 USA.
[Pezza, Roberto J.; Camerini-Otero, R. Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD USA.
RP Bianco, PR (reprint author), SUNY Buffalo, Dept Microbiol & Immunol, Ctr Single Mol Biophys, Buffalo, NY 14260 USA.
FU Susan G Komen Breast Cancer Foundation [BCTR0601350]
FX Work on this project was supported by a Susan G Komen Breast Cancer
Foundation Grant No BCTR0601350 to P R B
NR 42
TC 11
Z9 11
U1 1
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD DEC 1
PY 2010
VL 99
IS 11
BP 3763
EP 3772
DI 10.1016/j.bpj.2010.10.028
PG 10
WC Biophysics
SC Biophysics
GA 690UL
UT WOS:000285033800029
PM 21112301
ER
PT J
AU Hafer, N
Maidment, BW
Hatchett, RJ
AF Hafer, Nathaniel
Maidment, Bert W.
Hatchett, Richard J.
TI THE NIAID RADIATION COUNTERMEASURES PROGRAM BUSINESS MODEL
SO BIOSECURITY AND BIOTERRORISM-BIODEFENSE STRATEGY PRACTICE AND SCIENCE
LA English
DT Editorial Material
ID MEDICAL COUNTERMEASURES
AB The National Institute of Allergy and Infectious Diseases (NIAID) Radiation/Nuclear Medical Countermeasures Development Program has developed an integrated approach to providing the resources and expertise required for the research, discovery, and development of radiation/nuclear medical countermeasures (MCMs). These resources and services lower the opportunity costs and reduce the barriers to entry for companies interested in working in this area and accelerate translational progress by providing goal-oriented stewardship of promising projects. In many ways, the radiation countermeasures program functions as a "virtual pharmaceutical firm,'' coordinating the early and mid-stage development of a wide array of radiation/nuclear MCMs. This commentary describes the radiation countermeasures program and discusses a novel business model that has facilitated product development partnerships between the federal government and academic investigators and biopharmaceutical companies.
C1 [Maidment, Bert W.; Hatchett, Richard J.] NIAID, NIH, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA.
[Hafer, Nathaniel] NIAID, Radiat Nucl Med Countermeasures Dev Program, Washington, DC USA.
[Hafer, Nathaniel] Amer Assoc Advancement Sci, Sci Program, Washington, DC USA.
[Hafer, Nathaniel] Amer Assoc Advancement Sci, Policy Program, Washington, DC USA.
RP Hatchett, RJ (reprint author), NIAID, NIH, Div Allergy Immunol & Transplantat, 6610 Rockledge Dr, Bethesda, MD 20892 USA.
EM hatchettr@niaid.nih.gov
OI Hafer, Nathaniel/0000-0002-0164-5092
NR 8
TC 2
Z9 2
U1 0
U2 5
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1538-7135
J9 BIOSECUR BIOTERROR
JI Biosecur. Bioterror.
PD DEC
PY 2010
VL 8
IS 4
BP 357
EP 363
DI 10.1089/bsp.2010.0041
PG 7
WC Public, Environmental & Occupational Health; International Relations
SC Public, Environmental & Occupational Health; International Relations
GA 692WO
UT WOS:000285186800007
PM 21142762
ER
PT J
AU Phue, JN
Lee, SJ
Kaufman, JB
Negrete, A
Shiloach, J
AF Phue, Je-Nie
Lee, Sang Jun
Kaufman, Jeanne B.
Negrete, Alejandro
Shiloach, Joseph
TI Acetate accumulation through alternative metabolic pathways in ackA(-)
pta(-) poxB(-) triple mutant in E. coli B (BL21)
SO BIOTECHNOLOGY LETTERS
LA English
DT Article
DE E. coli B (BL21) mutant; Acetate excretion; High glucose
ID ESCHERICHIA-COLI; AEROBIC GROWTH
AB Individual deletions of acs and aceA genes in E. coli B (BL21) showed little difference in the metabolite accumulation patterns but deletion of the ackA gene alone or together with pta showed acetic acid gradually accumulated to 3.1 and 1.7 g/l, respectively, with a minimal extended lag in bacterial growth and a higher pyruvate formation. Single poxB deletion in E. coli B (BL21) or additional poxB deletion in the ackA-pta mutants did not change the acetate accumulation pattern. When the acetate production genes (ackA-pta-poxB) were deleted in E. coli B (BL21) acetate still accumulated. This may be an indication that perhaps acetate is not only a by-product of carbon metabolism; it is possible that acetate plays also a role in other cellular metabolite pathways. It is likely that there are alternative acetate production pathways.
C1 [Phue, Je-Nie; Kaufman, Jeanne B.; Negrete, Alejandro; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
[Lee, Sang Jun] KRIBB, Ind Biotechnol & Bioenergy Res Ctr, Taejon 305806, South Korea.
RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, Bldg 14A,Room 173, Bethesda, MD 20892 USA.
EM yossi@nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX Funding was provided by the Intramural program at the National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of
Health. The authors would like to thank D. Livnat for proof reading of
the manuscript.
NR 13
TC 18
Z9 18
U1 1
U2 18
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-5492
J9 BIOTECHNOL LETT
JI Biotechnol. Lett.
PD DEC
PY 2010
VL 32
IS 12
BP 1897
EP 1903
DI 10.1007/s10529-010-0369-7
PG 7
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 702RQ
UT WOS:000285912900019
PM 20703804
ER
PT J
AU Napoli, N
Pedone, C
Pozzilli, P
Lauretani, F
Ferrucci, L
Incalzi, RA
AF Napoli, Nicola
Pedone, Claudio
Pozzilli, Paolo
Lauretani, Fulvio
Ferrucci, Luigi
Incalzi, Raffaele Antonelli
TI Adiponectin and bone mass density The InCHIANTI study
SO BONE
LA English
DT Article
DE Adiponectin; Bone mass; pQCT
ID SYMPATHETIC-NERVOUS-SYSTEM; MINERAL DENSITY; POSTMENOPAUSAL WOMEN;
INSULIN-RESISTANCE; FAT MASS; PERIMENOPAUSAL WOMEN; COMPUTED-TOMOGRAPHY;
PLASMA ADIPONECTIN; SERUM ADIPONECTIN; BODY-COMPOSITION
AB Introduction Adiponectin serum concentration has been reported to be inversely correlated with bone mineral density (BMD) in humans The data on this Issue however are biased by small study sample size and lack of controlling for body composition
Methods We used data from the third follow-up of the InCHIANTI study which included measurements of BMD using quantitative CT of the tibia and of body composition using bioimpedenziometry Serum adiponectin was measured using radioimmunoassay We excluded participants with diabetes hyperthyroidism using hormone replacement or corticosteroid therapy We evaluated the correlation of adiponectin with total trabecular and cortical BMD using Pearson s coefficient and linear regression models to estimate the association between adiponectin and BMD controlling for potential confounders (age body mass index alcohol intake fat mass smoking)
Results Our sample was made up of 320 men (mean age 67 years SD 158 range 29-97 years) and 271 postmenopausal women (mean age 76 years SD 82 range 42-97 years) In men serum adiponectin was not independently associated with BMD In women after correction for potential confounders adiponectin was associated with total (beta= -0626 P<0 001) trabecular (beta= -0696 P<0 001) and cortical (beta= -1076 P=0001) BMD
Conclusion Our results show that adiponectin is Inversely associated with bone mass in women Further studies are needed to confirm these findings prospectively and then to clarify the explanatory mechanisms (C) 2010 Elsevier Inc All rights reserved
C1 [Pedone, Claudio; Incalzi, Raffaele Antonelli] Univ Campus Biomed, Area Geriatria, Ctr Salute Anziano, I-00128 Rome, Italy.
[Napoli, Nicola; Pozzilli, Paolo] Univ Campus Biomed, Div Endocrinol & Diabet, I-00128 Rome, Italy.
[Napoli, Nicola] Washington Univ, Div Bone & Mineral Dis, St Louis, MO USA.
[Lauretani, Fulvio] Tuscany Reg Hlth Agcy, Florence, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Incalzi, Raffaele Antonelli] Fdn San Raffaele Cittadella Canta, Taranto, Italy.
RP Pedone, C (reprint author), Univ Campus Biomed, Area Geriatria, Ctr Salute Anziano, Via Alvaro Portillo 21, I-00128 Rome, Italy.
RI Antonelli Incalzi, Raffaele/G-3978-2012; Lauretani, Fulvio/K-5115-2016;
OI Napoli, Nicola/0000-0002-3091-8205; Pedone, Claudio/0000-0003-1847-9032;
Antonelli Incalzi, Raffaele/0000-0003-2100-2075; Lauretani,
Fulvio/0000-0002-5287-9972; Pozzilli, Paolo/0000-0001-5090-636X
FU Intramural NIH HHS [ZIA AG001050-07]
NR 48
TC 27
Z9 29
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD DEC
PY 2010
VL 47
IS 6
BP 1001
EP 1005
DI 10.1016/j.bone.2010.08.010
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 694EP
UT WOS:000285278100001
PM 20804877
ER
PT J
AU Singleton, AB
Gibbs, JR
AF Singleton, Andrew B.
Gibbs, J. Raphael
TI Another locus, a new method
SO BRAIN
LA English
DT Editorial Material
ID MUTATIONS
C1 [Singleton, Andrew B.; Gibbs, J. Raphael] NIH, Molecuar Genet Sect, Bethesda, MD 20892 USA.
RP Singleton, AB (reprint author), NIH, Molecuar Genet Sect, Bldg 35,Rm 1A1000,35 Lincoln Dr, Bethesda, MD 20892 USA.
EM singleta@mail.nih.gov
RI Singleton, Andrew/C-3010-2009
FU Intramural NIH HHS
NR 8
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD DEC
PY 2010
VL 133
BP 3492
EP 3493
DI 10.1093/brain/awq331
PN 12
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 689TH
UT WOS:000284951600009
PM 21126992
ER
PT J
AU Wallace, GL
Dankner, N
Kenworthy, L
Giedd, JN
Martin, A
AF Wallace, Gregory L.
Dankner, Nathan
Kenworthy, Lauren
Giedd, Jay N.
Martin, Alex
TI Age-related temporal and parietal cortical thinning in autism spectrum
disorders
SO BRAIN
LA English
DT Article
DE autism; brain; MRI; cortical thickness; age-related changes
ID HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; HEAD CIRCUMFERENCE;
DIAGNOSTIC INTERVIEW; BRAIN MORPHOMETRY; THICKNESS; MRI; CHILDREN;
CHILDHOOD; ADOLESCENCE
AB Studies of head size and brain volume in autism spectrum disorders have suggested that early cortical overgrowth may be followed by prematurely arrested growth. However, the few investigations quantifying cortical thickness have yielded inconsistent results, probably due to variable ages and/or small sample sizes. We assessed differences in cortical thickness between high-functioning adolescent and young adult males with autism spectrum disorders (n = 41) and matched typically developing males (n = 40). We hypothesized thinner cortex, particularly in frontal, parietal and temporal regions, for individuals with autism spectrum disorders in comparison with typically developing controls. Furthermore, we expected to find an age x diagnosis interaction: with increasing age, more pronounced cortical thinning would be observed in autism spectrum disorders than typically developing participants. T(1)-weighted magnetization prepared rapid gradient echo 3 T magnetic resonance imaging scans were acquired from high-functioning males with autism spectrum disorders and from typically developing males matched group-wise on age (range 12-24 years), intelligence quotient (>= 85) and handedness. Both gyral-level and vertex-based analyses revealed significantly thinner cortex in the autism spectrum disorders group that was located predominantly in left temporal and parietal regions (i.e. the superior temporal sulcus, inferior temporal, postcentral/superior parietal and supramarginal gyri). These findings remained largely unchanged after controlling for intelligence quotient and after accounting for psychotropic medication usage and comorbid psychopathology. Furthermore, a significant age x diagnosis interaction was found in the left fusiform/inferior temporal cortex: participants with autism spectrum disorders had thinner cortex in this region with increasing age to a greater degree than did typically developing participants. Follow-up within group comparisons revealed significant age-related thinning in the autism spectrum disorders group but not in the typically developing group. Both thinner temporal and parietal cortices during adolescence and young adulthood and discrepantly accelerated age-related cortical thinning in autism spectrum disorders suggest that a second period of abnormal cortical growth (i.e. greater thinning) may be characteristic of these disorders.
C1 [Wallace, Gregory L.; Dankner, Nathan; Kenworthy, Lauren; Martin, Alex] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Wallace, GL (reprint author), NIMH, Lab Brain & Cognit, 10 Ctr Dr,Room 4C104,MSC 1366, Bethesda, MD 20892 USA.
EM gregwallace@mail.nih.gov
RI Giedd, Jay/A-3080-2008; martin, alex/B-6176-2009; Giedd,
Jay/B-7302-2012; Giedd, Jay/J-9644-2015;
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Wallace,
Gregory/0000-0003-0329-5054
FU National Institutes of Health, National Institute of Mental Health
FX Funding for this article was provided by Intramural Research Program of
the National Institutes of Health, National Institute of Mental Health.
NR 49
TC 103
Z9 104
U1 4
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD DEC
PY 2010
VL 133
BP 3745
EP 3754
DI 10.1093/brain/awq279
PN 12
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 689TH
UT WOS:000284951600029
PM 20926367
ER
PT J
AU Cox, B
Ballard-Barbash, R
Broeders, M
Dowling, E
Malila, N
Shumak, R
Taplin, S
Buist, D
Miglioretti, D
AF Cox, Brian
Ballard-Barbash, Rachel
Broeders, Mireille
Dowling, Emily
Malila, Nea
Shumak, Rene
Taplin, Stephen
Buist, Diana
Miglioretti, Diana
TI Recording of hormone therapy and breast density in breast screening
programs: summary and recommendations of the International Cancer
Screening Network
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast screening; Breast density; Hormone therapy; Program monitoring
ID MAMMOGRAPHIC PARENCHYMAL PATTERNS; ESTROGEN REPLACEMENT THERAPY;
POSTMENOPAUSAL WOMEN; QUALITY ASSURANCE; 22 COUNTRIES; COLLABORATIVE
REANALYSIS; PLUS PROGESTIN; UNITED-STATES; RISK; AGE
AB Breast density and the use of hormone therapy (HT) for menopausal symptoms alter the risk of breast cancer and both factors influence screening mammography performance. The International Cancer Screening Network (ICSN) surveyed its 29 member countries and found that few programs record breast density or the use of HT among screening participants. This may affect the ability of programs to assess their effectiveness in reducing breast cancer mortality. Seven countries recorded the use of HT at screening, and some were able to link screening records to individual prescribing records of HT. Eight countries reported recording breast density at screening mammography for some or all women screened. The recommendations of the ICSN for recording information about breast density and HT are presented.
C1 [Cox, Brian] Univ Otago, Hugh Adam Canc Epidemiol Unit, Dept Prevent & Social Med, Dunedin Sch Med, Dunedin 9054, New Zealand.
[Ballard-Barbash, Rachel; Dowling, Emily; Taplin, Stephen] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Broeders, Mireille] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & Hlth Technol Assessment, NL-6500 HB Nijmegen, Netherlands.
[Malila, Nea] Finnish Canc Registry, Mass Screening Registry, Helsinki 00130, Finland.
[Malila, Nea] Univ Tampere, Tampere Sch Publ Hlth, FIN-33101 Tampere, Finland.
[Shumak, Rene] Canc Care Ontario, Ontario Breast Screening Program, Toronto, ON MN 6G9, Canada.
[Buist, Diana; Miglioretti, Diana] Grp Hlth Res Inst, Seattle, WA 98101 USA.
RP Cox, B (reprint author), Univ Otago, Hugh Adam Canc Epidemiol Unit, Dept Prevent & Social Med, Dunedin Sch Med, Dunedin 9054, New Zealand.
EM brian.cox@otago.ac.nz
RI Broeders, Mireille/C-8820-2015
FU Director's Cancer Research Trust; National Cancer Institute, National
Institutes of Health, United States; National Cancer Institute Breast
Cancer Surveillance Consortium (BCSC) [U01CA63740, U01CA86076,
U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040]
FX We gratefully acknowledge the following members of the International
Cancer Screening Network who provided information about their screening
programs: Julianne Quaine (Australia), Ronaldo Silva Correa (Brazil),
Jay Onysko (Canada), Adam Svoboknik (Czech Republic), Elsebeth Lynge
(Denmark), Dominik Deitz (Germany), Gad Rennert (Israel), Noriaki
Hiroshi (Japan), Won Chul Lee (Korea), Jacques Fracheboud (Netherlands),
Solveig Hofvind (Norway), Jean-Luc Bulliard (Switzerland), Sue Moss
(United Kingdom), Rod Walker (United States), and Gonzalo Pou (Uruguay).
We also thank Gretchen Keel at Information Management Systems, Inc. for
her programing support for the development and synopsis of the web
survey, and Kathy Sedgwick at NOVA Research Company for her logistical
support for the working group. Brian Cox was supported by the Director's
Cancer Research Trust. We also acknowledge funding support for this
project from the National Cancer Institute, National Institutes of
Health, United States. This study was partially supported by the
National Cancer Institute Breast Cancer Surveillance Consortium (BCSC)
(U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976,
U01CA63731, U01CA70040).
NR 55
TC 3
Z9 3
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD DEC
PY 2010
VL 124
IS 3
BP 793
EP 800
DI 10.1007/s10549-010-0893-0
PG 8
WC Oncology
SC Oncology
GA 683WJ
UT WOS:000284508300022
PM 20414718
ER
PT J
AU McMahon, L
Tamary, H
Askin, M
Adams-Graves, P
Eberhardt, RT
Sutton, M
Wright, EC
Castaneda, SA
Faller, DV
Perrine, SP
AF McMahon, Lillian
Tamary, Hannah
Askin, Melissa
Adams-Graves, Patricia
Eberhardt, Robert T.
Sutton, Millicent
Wright, Elizabeth C.
Castaneda, Serguei A.
Faller, Douglas V.
Perrine, Susan P.
TI A randomized phase II trial of Arginine Butyrate with standard local
therapy in refractory sickle cell leg ulcers
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE randomized controlled trial; arginine butyrate; wound healing; leg
ulcer; sickle cell anaemia
ID DISTAL ULCERATIVE-COLITIS; CHAIN FATTY-ACIDS; NF-KAPPA-B;
GENE-EXPRESSION; IMMUNE FUNCTION; HUMAN-BEINGS; WOUND FLUID; DISEASE;
ANEMIA; MATRIX
AB P>Sickle cell leg ulcers are often debilitating, refractory to healing, and prone to recurrence. Healing of leg ulcers was incidentally observed during dose-ranging trials of Arginine Butyrate in beta haemoglobinopathies. Here, a controlled Phase II trial was performed in sickle cell patients who had lower extremity ulcers refractory to standard care for at least 6 months. Patients were randomized to receive standard local care alone (Control Arm) or standard care with Arginine Butyrate administered 5 d/week (Treatment Arm), for 12 weeks. Ulcers were photographed weekly, traced, and ulcer areas were calculated by computerized planimetry and compared between the two study arms. Twenty-seven study courses were evaluated. Control Arm subjects had 25 ulcers with a mean area of 25 center dot 7 cm2 initially and 23 center dot 2 cm2 after 12 weeks; 2/25 (8%) healed completely. Treatment Arm subjects had 37 ulcers with a mean area of 50 center dot 6 cm2 initially and 28 center dot 3 cm2 at 12 weeks; 11/37 of these (30%) healed completely. After 3 months, proportions of ulcers which healed were 6/25 (24%) and 29/37 (78%), in the Control and Treatment Arms respectively (P < 0 center dot 001). These findings strongly suggest that Arginine Butyrate merits further evaluation for the treatment of refractory sickle cell leg ulcers in larger trials.
C1 [McMahon, Lillian; Askin, Melissa; Eberhardt, Robert T.; Castaneda, Serguei A.; Faller, Douglas V.; Perrine, Susan P.] Boston Univ, Sch Med, Ctr Canc, Boston, MA 02118 USA.
[McMahon, Lillian; Askin, Melissa; Eberhardt, Robert T.; Castaneda, Serguei A.; Faller, Douglas V.; Perrine, Susan P.] Boston Univ, Sch Med, Hemoglobinopathy Thalassemia Res Unit, Boston, MA 02118 USA.
[Tamary, Hannah] Schneider Childrens Med Ctr Israel, Petah Tiqwa, Israel.
[Adams-Graves, Patricia] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA.
[Sutton, Millicent] New York Blood Ctr, Valhalla, NY USA.
[Wright, Elizabeth C.] NIH, Bethesda, MD 20892 USA.
RP Perrine, SP (reprint author), Boston Univ, Sch Med, Ctr Canc, 72 E Concord St,L-909, Boston, MA 02118 USA.
EM sperrine@bu.edu
OI Eberhardt, Robert/0000-0002-5076-7416; Perrine-Faller,
Susan/0000-0003-2179-8376
FU Food and Drug Administration, Office of Orphan Product Development
[FD-R-000176]; General Clinical Research Center at Boston University
[M01 RR00533]
FX This work was supported by grant FD-R-000176 from the Food and Drug
Administration, Office of Orphan Product Development and grant M01
RR00533 from the General Clinical Research Center at Boston University
(S.P. Perrine). We thank Drs Mabel Koshy and Ronald Rucknagel for caring
for many patients on this trial and Rana Mokhtar for assistance with
data review and analysis. Drs Douglas Faller and Susan Perrine are
inventors on a patent related to this study. The other authors declare
that they do not have any conflict of interest.
NR 62
TC 25
Z9 25
U1 0
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD DEC
PY 2010
VL 151
IS 5
BP 516
EP 524
DI 10.1111/j.1365-2141.2010.08395.x
PG 9
WC Hematology
SC Hematology
GA 679OC
UT WOS:000284169700014
PM 20955402
ER
PT J
AU Ramsden, CE
Hibbeln, JR
Majchrzak, SF
Davis, JM
AF Ramsden, Christopher E.
Hibbeln, Joseph R.
Majchrzak, Sharon F.
Davis, John M.
TI n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions
have different effects on CHD risk: a meta-analysis of randomised
controlled trials
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Review
DE Linoleic acid; n-6 Fatty acids; PUFA; Randomised controlled trials
ID CORONARY-HEART-DISEASE; CHOLESTEROL-LOWERING DIET; CONTROLLED CLINICAL
TRIAL; HYDROGENATED FISH-OIL; UNSATURATED-FAT; MYOCARDIAL-INFARCTION;
ARTERY DISEASE; LINOLEIC-ACID; PSYCHIATRIC-INPATIENTS; MEDITERRANEAN
DIET
AB Randomised controlled trials (RCT) of mixed n-6 and n-3 PUFA diets, and meta-analyses of their CHD outcomes, have been considered decisive evidence in specifically advising consumption of 'at least 5-10% of energy as n-6 PUFA'. Here we (1) performed an extensive literature search and extracted detailed dietary and outcome data enabling a critical examination of all RCT that increased PUFA and reported relevant CHD outcomes; (2) determined if dietary interventions increased n-6 PUFA with specificity, or increased both n-3 and n-6 PUFA (i.e. mixed n-3/n-6 PUFA diets); (3) compared mixed n-3/n-6 PUFA to n-6 specific PUFA diets on relevant CHD outcomes in meta-analyses; (4) evaluated the potential confounding role of trans-fatty acids (TFA). n-3 PUFA intakes were increased substantially in four of eight datasets, and the n-6 PUFA linoleic acid was raised with specificity in four datasets. n-3 and n-6 PUFA replaced a combination of TFA and SFA in all eight datasets. For non-fatal myocardial infarction (MI) + CHD death, the pooled risk reduction for mixed n-3/n-6 PUFA diets was 22% (risk ratio (RR) 0.78; 95% CI 0.65, 0.93) compared to an increased risk of 13% for n-6 specific PUFA diets (RR 1.13; 95% CI 0.84, 1.53). Risk of non-fatal MI + CHD death was significantly higher in n-6 specific PUFA diets compared to mixed n-3/n-6 PUFA diets (P=0.02). RCT that substituted n-6 PUFA for TFA and SFA without simultaneously increasing n-3 PUFA produced an increase in risk of death that approached statistical significance (RR 1.16; 95% CI 0.95, 1.42). Advice to specifically increase n-6 PUFA intake, based on mixed n-3/n-6 RCT data, is unlikely to provide the intended benefits, and may actually increase the risks of CHD and death.
C1 [Ramsden, Christopher E.; Hibbeln, Joseph R.; Majchrzak, Sharon F.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
[Davis, John M.] Univ Illinois, Sch Med, Dept Psychiat, Chicago, IL USA.
RP Ramsden, CE (reprint author), NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
EM chris.ramsden@nih.gov
FU National Institute on Alcohol Abuse and Alcoholism
FX This project was supported by the intramural research programme of the
National Institute on Alcohol Abuse and Alcoholism. Its contents are
solely the responsibility of the authors and do not necessarily
represent the official views of the National Institute on Alcohol Abuse
and Alcoholism or National Institutes of Health. We would like to
acknowledge the efforts of everyone who helped us find missing data,
especially Marcia Zorn (National Library of Medicine), Bradley Kuennen
and Matthew Schuler (Iowa State University Library), Rachael Davis (E.G.
Miner Medical Library), Vanessa Perez (American Heart Association
National Center Library), Gillian Swan (UK Food Standards Agency), and
the interlibrary loan departments of the Northwestern Galter Health
Sciences Library, the University of North Carolina-Chapel Hill Health
Sciences Library and the National Institutes of Health. We thank RCT
investigators that provided useful information including Boonseng
Leelarthaepin, Michael Burr and Lael Gatewood. We are grateful to Arthur
Spector, Bill Lands, Klaus Gawrisch, Artemis Simopoulos and Keturah
Faurot for contributing valuable comments on the manuscript before
submission. C. E. R. designed the study, performed the review of the
literature and public records, located missing data and was the main
writer of the manuscript. J. R. H. directed the study and critically
revised the manuscript. S. F. M. performed the literature review,
located missing data and assisted in writing and revising the
manuscript. J. M. D. conducted the statistical analyses and revised the
manuscript. The authors declare that they have no conflicts of interest.
NR 94
TC 129
Z9 133
U1 2
U2 38
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
J9 BRIT J NUTR
JI Br. J. Nutr.
PD DEC
PY 2010
VL 104
IS 11
BP 1586
EP 1600
DI 10.1017/S0007114510004010
PG 15
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 696TI
UT WOS:000285463900003
PM 21118617
ER
PT J
AU Duan, XG
Qin, J
Wang, QH
AF Duan, Xiaogang
Qin, Jing
Wang, Qihua
TI Optimal estimation in surrogate outcome regression problems
SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE
LA English
DT Article
DE Estimating equations; minimization of the trace or covariance matrix;
missing data; propensity score; surrogate outcome
ID CLINICAL-TRIALS; END-POINTS; VALIDATION; ENDPOINTS; CANCER; AIDS
AB The authors consider a double robust estimation of the regression parameter defined by an estimating equation in a surrogate outcome set up Under a correct specification of the propensity score the proposed estimator has smallest trace of asymptotic covariance matrix whether the working outcome regression model involved is specified correct or not and it is particularly meaningful when it is incorrectly specified Simulations are conducted to examine the finite sample performance of the proposed procedure Data on obesity and high blood pressure are analyzed for illustration The Canadian Journal of Static tics 38 633-646, 2010 (C) 2010 Statistical Society of Canada
C1 [Wang, Qihua] Yunnan Univ, Dept Math & Stat, Kunming 650091, Peoples R China.
[Qin, Jing] NIAID, NIH, Bethesda, MD 20892 USA.
[Duan, Xiaogang; Wang, Qihua] Chinese Acad Sci, Acad Math & Syst, Beijing 100190, Peoples R China.
RP Wang, QH (reprint author), Yunnan Univ, Dept Math & Stat, Kunming 650091, Peoples R China.
FU National Science Fund for Distinguished Young Scholars in China
[10725106]; National Natural Science Foundation of China [10671198];
National Science Fund for Creative Research Groups in China; Key Lab of
Complex Structure and Data Science
FX The authors acknowledge the valuable comments of the editor, the
associate editor, and two anonymous referees which substantially
improved the presentation of the paper Qihua Wang s research was
supported by the National Science Fund for Distinguished Young Scholars
in China (10725106), the National Natural Science Foundation of China
(10671198), the National Science Fund for Creative Research Groups in
China and a Grant from the Key Lab of Complex Structure and Data Science
NR 17
TC 0
Z9 0
U1 2
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0319-5724
J9 CAN J STAT
JI Can. J. Stat.-Rev. Can. Stat.
PD DEC
PY 2010
VL 38
IS 4
BP 633
EP 646
DI 10.1002/cjs.10086
PG 14
WC Statistics & Probability
SC Mathematics
GA 686CR
UT WOS:000284674900007
ER
PT J
AU Shiels, MS
Goedert, JJ
Engels, EA
AF Shiels, Meredith S.
Goedert, James J.
Engels, Eric A.
TI Recent Trends and Future Directions in Human Immunodeficiency
Virus-Associated Cancer
SO CANCER
LA English
DT Editorial Material
ID HIV-INFECTED PATIENTS; ANTIRETROVIRAL THERAPY; LUNG-CANCER;
UNITED-STATES; ANAL CANCER; HAART ERA; RISK; AIDS; PEOPLE
C1 [Shiels, Meredith S.; Goedert, James J.; Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Shiels, MS (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7059, Rockville, MD 20892 USA.
EM shielsms@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 20
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD DEC 1
PY 2010
VL 116
IS 23
BP 5344
EP 5347
DI 10.1002/cncr.25705
PG 4
WC Oncology
SC Oncology
GA 685ZB
UT WOS:000284665500005
PM 20960526
ER
PT J
AU Troutman, SM
Price, DK
Figg, WD
AF Troutman, Sarah M.
Price, Douglas K.
Figg, William D.
TI Prostate cancer genomic signature offers prognostic value
SO CANCER BIOLOGY & THERAPY
LA English
DT Editorial Material
DE prostate cancer; pharmaco-genetics; prognosis; copy number alterations;
androgen receptor; TMPRSS-ERG; PI3K pathways; NCOA2
C1 [Troutman, Sarah M.; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA.
[Figg, William D.] NCI, Clin Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
NR 8
TC 1
Z9 1
U1 0
U2 1
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 1
PY 2010
VL 10
IS 11
BP 1079
EP 1080
DI 10.4161/cbt.10.11.14086
PG 2
WC Oncology
SC Oncology
GA 688UI
UT WOS:000284879000002
PM 21088497
ER
PT J
AU Given, LS
Hohman, K
La Porta, M
Belle-Isle, L
Rochester, P
AF Given, Leslie S.
Hohman, Karin
La Porta, Madeline
Belle-Isle, Lori
Rochester, Phyllis
TI Comprehensive cancer control in the United States: progress and
opportunity
SO CANCER CAUSES & CONTROL
LA English
DT Editorial Material
C1 [Given, Leslie S.] Strateg Hlth Concepts, Atlanta, GA USA.
[Hohman, Karin] Strateg Hlth Concepts, Arvada, CO USA.
[La Porta, Madeline] NCI, Bethesda, MD 20892 USA.
[Belle-Isle, Lori] Amer Canc Soc, Atlanta, GA 30329 USA.
[Rochester, Phyllis] Ctr Dis Control & Prevent, Atlanta, GA 30341 USA.
RP Given, LS (reprint author), Strateg Hlth Concepts, Atlanta, GA USA.
EM leslie@shconcepts.com
NR 0
TC 4
Z9 4
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD DEC
PY 2010
VL 21
IS 12
SI SI
BP 1965
EP 1965
DI 10.1007/s10552-010-9670-y
PG 1
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 737ZR
UT WOS:000288609600001
PM 21058026
ER
PT J
AU Rochester, PW
Townsend, JS
Given, L
Krebill, H
Balderrama, S
Vinson, C
AF Rochester, Phyllis W.
Townsend, Julie S.
Given, Leslie
Krebill, Hope
Balderrama, Sandra
Vinson, Cynthia
TI Comprehensive cancer control: progress and accomplishments
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Cancer control; Comprehensive cancer control
ID MORTALITY; TRENDS
AB The potential for Comprehensive Cancer Control (CCC) across the nation has been realized in the last decade with 69 Coalitions developing and implementing CCC plans. Many partners at all levels-national, state, jurisdictional, tribal and communities-have contributed to this success. This article details the contribution of these partners across these various levels, with a selection of the many activities contributing to this success. Consequently the cancer burden, although still of major importance, continues to be addressed in significant ways. Although there are future challenges, CCC coalitions continue to play an important role in addressing the cancer burden.
C1 [Rochester, Phyllis W.; Townsend, Julie S.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA.
[Given, Leslie] Strateg Hlth Concepts, Atlanta, GA USA.
[Krebill, Hope] Univ Kansas, Ctr Canc, Kansas City, KS USA.
[Balderrama, Sandra] Canc Prevent & Res Inst Texas, Houston, TX USA.
[Vinson, Cynthia] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Rochester, PW (reprint author), POB 191, Pfafftown, NC 27040 USA.
EM Phyllis@phyllisrochester.com
NR 13
TC 7
Z9 8
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD DEC
PY 2010
VL 21
IS 12
SI SI
BP 1967
EP 1977
DI 10.1007/s10552-010-9657-8
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 737ZR
UT WOS:000288609600002
PM 21069448
ER
PT J
AU Vinson, C
La Porta, M
Todd, W
Palafox, NA
Wilson, KM
Fairley, T
AF Vinson, Cynthia
La Porta, Madeline
Todd, William
Palafox, Neal A.
Wilson, Katherine M.
Fairley, Temeika
TI Research and comprehensive cancer control coalitions
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Dissemination; Implementation; Research; Knowledge transfer;
Comprehensive cancer control
ID INTERVENTIONS; TRANSLATION
AB The goal of cancer control research is "to generate basic knowledge about how to monitor and change individual and collective behavior and to ensure that knowledge is translated into practice and policy rapidly, effectively, and efficiently" (Division of Cancer Control and Population Sciences in Cancer control framework and synthese rationale, 2010). Research activities span the cancer control continuum from prevention to early detection and diagnosis through treatment and survivorship (Division of Cancer Control and Population Sciences in Cancer control framework and synthese rationale, 2010). While significant advancements have been made in understanding, preventing and treating cancer in the past few decades, these benefits have yielded disproportionate results in cancer morbidity and mortality across various socioeconomic and racial/ethnic subgroups (Ozols et al in J Clin Oncol, 25(1): 146-1622, 2007). It has been a high priority since the beginning of the Comprehensive Cancer Control (CCC) movement to utilize research in the development and implementation of cancer plans in the states, tribes and tribal organizations, territories and US Pacific Island Jurisdictions. Nevertheless, dissemination and implementation of research in coalition activities has been challenging for many programs. Lessons learned from programs and coalitions in the implementation and evaluation of CCC activities, as well as resources provided by national partners, can assist coalitions with the translation of research into practice.
C1 [Vinson, Cynthia] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[La Porta, Madeline] NCI, Off Commun & Educ, Bethesda, MD 20892 USA.
[Todd, William] Georgia Canc Coalit, Atlanta, GA USA.
[Palafox, Neal A.] Univ Hawaii, John A Burns Sch Med, Mililani, HI USA.
[Wilson, Katherine M.; Fairley, Temeika] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA.
RP Vinson, C (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd 6140, Bethesda, MD 20892 USA.
EM cvinson@mail.nih.gov
NR 19
TC 4
Z9 5
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD DEC
PY 2010
VL 21
IS 12
SI SI
BP 2033
EP 2040
DI 10.1007/s10552-010-9667-6
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 737ZR
UT WOS:000288609600009
PM 21046447
ER
PT J
AU Hirvonen, T
Kontto, J
Jestoi, M
Valsta, L
Peltonen, K
Pietinen, P
Virtanen, SM
Sinkko, H
Kronberg-Kippila, C
Albanes, D
Virtamo, J
AF Hirvonen, T.
Kontto, J.
Jestoi, M.
Valsta, L.
Peltonen, K.
Pietinen, P.
Virtanen, S. M.
Sinkko, H.
Kronberg-Kippila, C.
Albanes, D.
Virtamo, J.
TI Dietary acrylamide intake and the risk of cancer among Finnish male
smokers
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Acrylamide intake; Food; Cancer; Cohort studies
ID BREAST-CANCER; PROSPECTIVE COHORT; PROSTATE-CANCER; SWEDISH WOMEN;
RENAL-CELL; EXPOSURE; SWEDEN; FOOD; CARCINOGENICITY; QUESTIONNAIRE
AB Objective To assess the association between dietary acrylamide intake and the risk of cancer among male smokers.
Methods The study consisted of 27,111 male smokers, aged 50-69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire and a questionnaire on general background characteristics (including smoking habits) at baseline. Incident cases of cancer were identified through the national Finnish Cancer Registry.
Results During an average 10.2 year follow-up, 1,703 lung cancers, 799 prostate cancers, 365 urothelial cancers, 316 colorectal cancers, 224 stomach cancers, 192 pancreatic cancers, 184 renal cell cancers, and 175 lymphomas were diagnosed. Dietary acrylamide intake was positively associated with the risk of lung cancer; relative risk (RR) in the highest versus the lowest quintile in the multivariable-adjusted model was 1.18 (95% confidence interval (CI) 1.01-1.38, p for trend 0.11). Other cancers were not associated with acrylamide intake.
Conclusions High acrylamide intake is associated with increased risk of lung cancer but not with other cancers in male smokers.
C1 [Hirvonen, T.] Finnish Food Safety Author, Risk Assessment Unit, FI-00790 Helsinki, Finland.
[Kontto, J.; Pietinen, P.; Virtamo, J.] Natl Inst Hlth & Welf THL, Dept Chron Dis Prevent, FI-00271 Helsinki, Finland.
[Jestoi, M.; Peltonen, K.] Finnish Food Safety Author, Unit Chem & Toxicol, Res Dept, FI-00790 Helsinki, Finland.
[Valsta, L.; Virtanen, S. M.; Sinkko, H.; Kronberg-Kippila, C.] Natl Inst Hlth & Welf THL, Dept Lifestyle & Participat, FI-00271 Helsinki, Finland.
[Albanes, D.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA.
RP Hirvonen, T (reprint author), Finnish Food Safety Author, Risk Assessment Unit, Mustialankatu 3, FI-00790 Helsinki, Finland.
EM terohirvonen69@gmail.com
RI Albanes, Demetrius/B-9749-2015;
OI Kontto, Jukka/0000-0003-3899-9852
FU Intramural NIH HHS [ZIA CP010195-05]
NR 37
TC 10
Z9 10
U1 0
U2 10
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD DEC
PY 2010
VL 21
IS 12
SI SI
BP 2223
EP 2229
DI 10.1007/s10552-010-9642-2
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 737ZR
UT WOS:000288609600030
PM 20859673
ER
PT J
AU O'Doherty, MG
Abnet, CC
Murray, LJ
Woodside, JV
Anderson, LA
Brockman, JD
Cantwell, MM
AF O'Doherty, Mark G.
Abnet, Christian C.
Murray, Liam J.
Woodside, Jayne V.
Anderson, Lesley A.
Brockman, John D.
Cantwell, Marie M.
TI Iron intake and markers of iron status and risk of Barrett's esophagus
and esophageal adenocarcinoma
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Adenocarcinoma; Barrett's esophagus; Epidemiology; Ferritin; Iron
ID IOWA WOMENS HEALTH; CANCER-RISK; HEME IRON; DIETARY IRON; HEREDITARY
HEMOCHROMATOSIS; HELICOBACTER-PYLORI; PROSPECTIVE COHORT;
COLORECTAL-CANCER; OXIDATIVE DAMAGE; GASTRIC CARDIA
AB Objective To investigate the association between iron intake and iron status with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC).
Methods A total of 220 BE patients, 224 EAC patients, and 256 frequency-matched controls completed a lifestyle and food frequency questionnaire and provided serum and toenail samples between 2002 and 2005. Using multiple logistic regression, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated within quartiles of intake/status.
Results Comparing the fourth to the first quartile, ferritin (OR 0.47; 95% CI: 0.23, 0.97) and transferrin saturation (OR 0.41; 95% CI: 0.20, 0.82) were negatively associated with BE; while total iron binding capacity was positively associated per 50 mu g/dl increment (OR 1.47; 95% CI: 1.12, 1.92). Comparing the fourth to the first quartile, iron intake (OR 0.50; 95% CI: 0.25, 0.98), non-heme iron intake per 10 mg/day increment (OR 0.29; 95% CI: 0.08, 0.99), and toenail iron (OR 0.40; 95% CI: 0.17, 0.93) were negatively associated with EAC; while heme iron intake was positively associated (OR 3.11 95% CI: 1.46, 6.61).
Principal conclusion In contrast to the hypothesis that increased iron intakes and higher iron stores are a risk factor for BE and EAC, this study suggests that higher iron intakes and stores may have a protective association with BE and EAC, with the exception of what was found for heme iron intake.
C1 [O'Doherty, Mark G.; Murray, Liam J.; Anderson, Lesley A.; Cantwell, Marie M.] Queens Univ Belfast, Ctr Publ Hlth, Canc Epidemiol Hlth Serv Res Grp, Belfast BT12 6BJ, Antrim, North Ireland.
[Abnet, Christian C.] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Woodside, Jayne V.] Queens Univ Belfast, Inst Clin Sci B, Ctr Publ Hlth, Nutr & Metab Grp, Belfast BT12 6BJ, Antrim, North Ireland.
[Brockman, John D.] Univ Missouri, Res Reactor Ctr, Columbia, MO 65211 USA.
RP O'Doherty, MG (reprint author), Queens Univ Belfast, Ctr Publ Hlth, Canc Epidemiol Hlth Serv Res Grp, Mulhouse Bldg,Grosvenor Rd, Belfast BT12 6BJ, Antrim, North Ireland.
EM m.odoherty@qub.ac.uk
RI Abnet, Christian/C-4111-2015;
OI Abnet, Christian/0000-0002-3008-7843; Brockman,
John/0000-0001-7419-5558; Anderson, Lesley/0000-0002-1000-3649
FU Health and Social Care Research & Development Office; National Cancer
Institute; Health and Social Care Research & Development Office
(Belfast, Northern Ireland); National Cancer Institute (Bethesda, MD,
USA)
FX The authors thank the study participants and their families for their
contributions; the clinicians who were contacted throughout the study
period and their secretaries for administrative support; Siobhan
Reynolds, Majella Gallagher, Carol Anderson, Martin McAnaespie, and Dr.
Damian McManus for their contributions; and the Health and Social Care
Research & Development Office and the National Cancer Institute for
their support and involvement in the research. Special thanks to Dr.
Caroline Mercer for all of her assistance and guidance with the
serological measures of iron status.; Joint Research Project in Cancer
sponsored by the Health and Social Care Research & Development Office
(Belfast, Northern Ireland) and the National Cancer Institute (Bethesda,
MD, USA).
NR 67
TC 9
Z9 9
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD DEC
PY 2010
VL 21
IS 12
SI SI
BP 2269
EP 2279
DI 10.1007/s10552-010-9652-0
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 737ZR
UT WOS:000288609600035
PM 20936528
ER
PT J
AU Gonzalez, P
Hildesheim, A
Rodriguez, AC
Schiffman, M
Porras, C
Wacholder, S
Pineres, AG
Pinto, LA
Burk, RD
Herrero, R
AF Gonzalez, Paula
Hildesheim, Allan
Cecilia Rodriguez, Ana
Schiffman, Mark
Porras, Carolina
Wacholder, Sholom
Garcia Pineres, Alfonso
Pinto, Ligia A.
Burk, Robert D.
Herrero, Rolando
TI Behavioral/Lifestyle and Immunologic Factors Associated with HPV
Infection among Women Older Than 45 Years
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS INFECTION; VAGINAL HUMAN-PAPILLOMAVIRUS;
COSTA-RICA; CERVICAL NEOPLASIA; NATURAL-HISTORY; COLOMBIAN WOMEN;
RISK-FACTORS; YOUNG-WOMEN; PREVALENCE; DETERMINANTS
AB Background: Cervical human papilloma virus (HPV) detection increases after menopause, but its determinants need clarification.
Methods: In a case-control study nested within a 10,049 women cohort, we evaluated women 45 to 75 years old who acquired HPV infection and were HPV positive 5 to 6 years after enrollment (N = 252), and HPV-negative women as matched controls (N = 265). Detailed sexual behavior and cellular immune response were investigated. Odds ratios (OR) and attributable fractions were estimated.
Results: Women with 2+ lifetime partners had 1.7-fold (95% CI = 1.1-2.7) higher risk than monogamous women, with similar findings if their partners had other partners. Women with 2+ partners after last HPV-negative result had the highest risk (OR = 3.9; 95% CI = 1.2-12.4 compared with 0-1 partners). Weaker immune response to HPV-16 virus-like particles increased risk (OR = 1.7; 95% CI = 1.1-2.7 comparing lowest to highest tertile). Among women with no sexual activity in the period before HPV appearance, reduced immune response to phytohemagglutinin was the only determinant (OR = 2.9; 95% CI = 0.94-8.8). Twenty-one percent of infections were explained by recent sexual behavior, 21% by past sexual behavior, and 12% by reduced immune response.
Conclusions: New infections among older women may result from sexual activity of women and/or their partners or reappearance of past (latent) infections possibly related to weakened immune response.
Impact: HPV infections among older women are associated with current and past sexual exposures and possibly with immune senescence. The risk of cancer from these infections is likely to be low but could not be fully evaluated in the context of this study. Cancer Epidemiol Biomarkers Prev; 19(12); 3044-54. (C) 2010 AACR.
C1 [Gonzalez, Paula; Cecilia Rodriguez, Ana; Porras, Carolina; Herrero, Rolando] Proyecto Epidemiol Guanacaste, Fdn INCIENSA, Liberia, Costa Rica.
[Hildesheim, Allan; Schiffman, Mark; Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Garcia Pineres, Alfonso] Univ Costa Rica, Escuela Quim, San Jose, Costa Rica.
[Pinto, Ligia A.] NCI, HPV Immunol Lab, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA.
[Burk, Robert D.] Albert Einstein Coll Med, New York, NY USA.
RP Gonzalez, P (reprint author), Proyecto Epidemiol Guanacaste, Fdn INCIENSA, 300 Oeste ICE,Piso 7, San Jose, Costa Rica.
EM pgonzalez@proyectoguanacaste.org
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU National Cancer Institute, National Institutes of Health [N01-CP21081,
N01-CP33061, N01-CP40542, N01-CP50535, N01-CP81023, N02-CP-31003,
U01-CA78527, CA78527, N01-CO-12400]; National Institutes of Health
Office of Research on Women's Health
FX The Guanacaste cohort (design and conduct of the study, sample
collection, management, analysis, and interpretation of the data) for
the enrollment, follow-up, and additional visit was funded by the
National Cancer Institute, National Institutes of Health, under multiple
contracts (N01-CP21081, N01-CP33061, N01-CP40542, N01-CP50535,
N01-CP81023, intramural program N02-CP-31003, U01-CA78527, and CA78527
to R. B and N01-CO-12400 to immunology laboratory). Support for this
effort was also provided by the National Institutes of Health Office of
Research on Women's Health.
NR 28
TC 34
Z9 35
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD DEC
PY 2010
VL 19
IS 12
BP 3044
EP 3054
DI 10.1158/1055-9965.EPI-10-0645
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 694HP
UT WOS:000285285900008
PM 20952561
ER
PT J
AU Kocarnik, JD
Hutter, CM
Slattery, ML
Berndt, SI
Hsu, L
Duggan, DJ
Muehling, J
Caan, BJ
Beresford, SAA
Rajkovic, A
Sarto, GE
Marshall, JR
Hammad, N
Wallace, RB
Makar, KW
Prentice, RL
Potter, JD
Hayes, RB
Peters, U
AF Kocarnik, Jonathan D.
Hutter, Carolyn M.
Slattery, Martha L.
Berndt, Sonja I.
Hsu, Li
Duggan, David J.
Muehling, Jill
Caan, Bette J.
Beresford, Shirley A. A.
Rajkovic, Aleksandar
Sarto, Gloria E.
Marshall, James R.
Hammad, Nazik
Wallace, Robert B.
Makar, Karen W.
Prentice, Ross L.
Potter, John D.
Hayes, Richard B.
Peters, Ulrike
TI Characterization of 9p24 Risk Locus and Colorectal Adenoma and Cancer:
Gene-Environment Interaction and Meta-Analysis
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CHROMOSOME 8Q24; COLON-CANCER; SUSCEPTIBILITY
AB Background: A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive.
Methods: We genotyped this locus and explored interactions with known risk factors as potential sources of heterogeneity, which may explain the previously inconsistent replication. We included Caucasians with colorectal adenoma or colorectal cancer and controls from 4 studies (total 3,891 cases, 4,490 controls): the Women's Health Initiative (WHI); the Diet, Activity and Lifestyle Study (DALS); a Minnesota population-based case-control study (MinnCCS); and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). We used logistic regression to evaluate the association and test for gene-environment interactions.
Results: SNP rs719725 was statistically significantly associated with risk of colorectal cancer in WHI (OR per A allele 1.19; 95% CI, 1.01-1.40; P(trend) = 0.04), marginally associated with adenoma risk in PLCO (OR per A allele 1.11; 95% CI, 0.99-1.25; P(trend) = 0.07), and not associated in DALS and MinnCCS. Evaluating for gene-environment interactions yielded no consistent results across the studies. A meta-analysis of 17 studies (including these 4) gave an OR per A allele of 1.07 (95% CI, 1.03-1.12; P(trend) = 0.001).
Conclusions: Our results suggest the A allele for SNP rs719725 at locus 9p24 is positively associated with a small increase in risk for colorectal tumors. Environmental risk factors for colorectal cancer do not appear to explain heterogeneity across studies.
Impact: If this finding is supported by further replication and functional studies, it may highlight new pathways underlying colorectal neoplasia. Cancer Epidemiol Biomarkers Prev; 19(12); 3131-9. (C) 2010 AACR.
C1 [Kocarnik, Jonathan D.; Hutter, Carolyn M.; Hsu, Li; Beresford, Shirley A. A.; Makar, Karen W.; Prentice, Ross L.; Potter, John D.; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA.
[Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Duggan, David J.; Muehling, Jill] Translat Genom Res Inst, Genet Basis Human Dis Div, Phoenix, AZ USA.
[Caan, Bette J.] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA.
[Beresford, Shirley A. A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Rajkovic, Aleksandar] Univ Pittsburgh, Dept Obstet & Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Sarto, Gloria E.] Univ Wisconsin, Sch Med, Dept Obstet & Gynecol, Madison, WI USA.
[Marshall, James R.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Hammad, Nazik] Queens Univ, Dept Med Oncol, Canc Ctr SE Ontario, Kingston, ON, Canada.
[Wallace, Robert B.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA.
[Wallace, Robert B.] Univ Iowa, Coll Publ Hlth, Dept Internal Med, Iowa City, IA USA.
[Hayes, Richard B.] NYU, Dept Environm Med, Sch Med, Div Epidemiol, New York, NY 10016 USA.
RP Peters, U (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA.
EM upeters@fhcrc.org
OI Potter, John/0000-0001-5439-1500; Hayes, Richard/0000-0002-0918-661X
FU National Cancer Institute (NCI), National Institutes of Health (NIH),
U.S. Department of Health and Human Services (DHHS) [NIH R01 CA120582,
NIH K22 CA118421, NIH R01 CA48998, NIH R01 CA059045, NIH R25 CA094880,
NIH R01 AG14358, PO1 CA53996]; National Heart, Lung, and Blood
Institute, NIH, DHHS [N01WH22110, 24152, 32100-2, 32105-6, 32108-9,
32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221];
National Cancer Institute [R01 CA059045, R01 CA120582]; Division of
Cancer Epidemiology and Genetics; Division of Cancer Prevention,
National Cancer Institute, NIH, DHHS
FX This study was funded by National Cancer Institute (NCI), National
Institutes of Health (NIH), U.S. Department of Health and Human Services
(DHHS) awards NIH R01 CA120582 and NIH K22 CA118421 (Dr. Peters), NIH
R01 CA48998 (Dr. Slattery), NIH R01 CA059045 (Dr. Potter), NIH R25
CA094880 (Mr. Kocarnik), NIH K22 CA118421 (Dr. Hutter), NIH R01 AG14358
and PO1 CA53996 (Dr. Hsu). The WHI program is funded by the National
Heart, Lung, and Blood Institute, NIH, DHHS through contracts
N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115,
32118-32119, 32122, 42107-26, 42129-32, and 44221 (Dr. Caan, Dr.
Beresford, Dr. Rajkovic, Dr. Sarto, Dr. Wallace, Dr. Prentice). The
project described was supported by Award Numbers R01 CA059045 and R01
CA120582 from the National Cancer Institute. This research was also
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, NIH, DHHS.
NR 28
TC 17
Z9 17
U1 0
U2 5
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 2010
VL 19
IS 12
BP 3131
EP 3139
DI 10.1158/1055-9965.EPI-10-0878
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 694HP
UT WOS:000285285900014
PM 20978172
ER
PT J
AU Wolpin, BM
Kraft, P
Xu, MS
Steplowski, E
Olsson, ML
Arslan, AA
Bueno-De-Mesquita, HB
Gross, M
Helzlsouer, K
Jacobs, EJ
LaCroix, A
Petersen, G
Stolzenberg-Solomon, RZ
Zheng, W
Albanes, D
Allen, NE
Amundadottir, L
Austin, MA
Boutron-Ruault, MC
Buring, JE
Canzian, F
Chanock, SJ
Gaziano, JM
Giovannucci, EL
Hallmans, G
Hankinson, SE
Hoover, RN
Hunter, DJ
Hutchinson, A
Jacobs, KB
Kooperberg, C
Mendelsohn, JB
Michaud, DS
Overvad, K
Patel, AV
Sanchez, MJ
Sansbury, L
Shu, XO
Slimani, N
Tobias, GS
Trichopoulos, D
Vineis, P
Visvanathan, K
Virtamo, J
Wactawski-Wende, J
Watters, J
Yu, K
Zeleniuch-Jacquotte, A
Hartge, P
Fuchs, CS
AF Wolpin, Brian M.
Kraft, Peter
Xu, Mousheng
Steplowski, Emily
Olsson, Martin L.
Arslan, Alan A.
Bueno-de-Mesquita, H. Bas
Gross, Myron
Helzlsouer, Kathy
Jacobs, Eric J.
LaCroix, Andrea
Petersen, Gloria
Stolzenberg-Solomon, Rachael Z.
Zheng, Wei
Albanes, Demetrius
Allen, Naomi E.
Amundadottir, Laufey
Austin, Melissa A.
Boutron-Ruault, Marie-Christine
Buring, Julie E.
Canzian, Federico
Chanock, Stephen J.
Gaziano, J. Michael
Giovannucci, Edward L.
Hallmans, Goeran
Hankinson, Susan E.
Hoover, Robert N.
Hunter, David J.
Hutchinson, Amy
Jacobs, Kevin B.
Kooperberg, Charles
Mendelsohn, Julie B.
Michaud, Dominique S.
Overvad, Kim
Patel, Alpa V.
Sanchez, Maria-Jose
Sansbury, Leah
Shu, Xiao-Ou
Slimani, Nadia
Tobias, Geoffrey S.
Trichopoulos, Dimitrios
Vineis, Paolo
Visvanathan, Kala
Virtamo, Jarmo
Wactawski-Wende, Jean
Watters, Joanne
Yu, Kai
Zeleniuch-Jacquotte, Anne
Hartge, Patricia
Fuchs, Charles S.
TI Variant ABO Blood Group Alleles, Secretor Status, and Risk of Pancreatic
Cancer: Results from the Pancreatic Cancer Cohort Consortium
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID VON-WILLEBRAND-FACTOR; GENOME-WIDE ASSOCIATION; GENETIC-VARIANTS; GROUP
ANTIGENS; A-TRANSFERASE; LOCUS; DISEASE; SUSCEPTIBILITY; MUTATIONS;
SEQUENCE
AB Background: Subjects with non-O ABO blood group alleles have increased risk of pancreatic cancer. Glycosyltransferase activity is greater for the A(1) versus A(2) variant, whereas O01 and O02 variants are nonfunctioning. We hypothesized: 1) A(1) allele would confer greater risk than A(2) allele, 2) protective effect of the O allele would be equivalent for O01 and O02 variants, 3) secretor phenotype would modify the association with risk.
Methods: We determined ABO variants and secretor phenotype from single nucleotide polymorphisms in ABO and FUT2 genes in 1,533 cases and 1,582 controls from 12 prospective cohort studies. Adjusted odds ratios (OR) for pancreatic cancer were calculated using logistic regression.
Results: An increased risk was observed in participants with A(1) but not A(2) alleles. Compared with subjects with genotype O/O, genotypes A(2)/O, A(2)/A(1), A(1)/O, and A(1)/A(1) had ORs of 0.96 (95% CI, 0.72-1.26), 1.46 (95% CI, 0.98-2.17), 1.48 (95% CI, 1.23-1.78), and 1.71 (95% CI, 1.18-2.47). Risk was similar for O01 and O02 variant O alleles. Compared with O01/O01, the ORs for each additional allele of O02, A(1), and A(2) were 1.00 (95% CI, 0.87-1.14), 1.38 (95% CI, 1.20-1.58), and 0.96 (95% CI, 0.77-1.20); P-value, O01 versus O02 = 0.94, A(1) versus A(2) = 0.004. Secretor phenotype was not an effect modifier (P-interaction = 0.63).
Conclusions: Among participants in a large prospective cohort consortium, ABO allele subtypes corresponding to increased glycosyltransferase activity were associated with increased pancreatic cancer risk.
Impact: These data support the hypothesis that ABO glycosyltransferase activity influences pancreatic cancer risk rather than actions of other nearby genes on chromosome 9q34. Cancer Epidemiol Biomarkers Prev; 19(12); 3140-9. (C) 2010 AACR.
C1 [Wolpin, Brian M.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Wolpin, Brian M.; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Canzian, Federico] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA.
[Kraft, Peter; Xu, Mousheng; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Michaud, Dominique S.; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA.
[Olsson, Martin L.] Lund Univ, Div Hematol & Transfus Med, Dept Lab Med, Lund, Sweden.
[Arslan, Alan A.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA.
[Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA.
[Bueno-de-Mesquita, H. Bas; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY 10016 USA.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Gross, Myron] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Helzlsouer, Kathy] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Minneapolis, MN 55455 USA.
[Helzlsouer, Kathy] St Johns Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA.
[Jacobs, Eric J.; Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Jacobs, Eric J.; Visvanathan, Kala] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[LaCroix, Andrea; Patel, Alpa V.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Petersen, Gloria; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Stolzenberg-Solomon, Rachael Z.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Zheng, Wei; Albanes, Demetrius; Amundadottir, Laufey; Chanock, Stephen J.; Hoover, Robert N.; Hutchinson, Amy; Jacobs, Kevin B.; Mendelsohn, Julie B.; Tobias, Geoffrey S.; Yu, Kai; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Allen, Naomi E.; Shu, Xiao-Ou] Vanderbilt Univ, Div Epidemiol, Dept Med, Vanderbilt Epidemiol Ctr, Nashville, TN USA.
[Allen, Naomi E.; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Amundadottir, Laufey] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
[Austin, Melissa A.; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Boutron-Ruault, Marie-Christine] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Boutron-Ruault, Marie-Christine] Univ Washington, Inst Publ Hlth Genet, Sch Publ Hlth, Seattle, WA 98195 USA.
[Buring, Julie E.] INSERM, Villejuif, France.
[Buring, Julie E.] Inst Gustave Roussy, Villejuif, France.
[Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Phys Hlth Study, Boston, MA 02115 USA.
[Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Div Aging, Phys Hlth Study, Boston, MA 02115 USA.
[Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Phys Hlth Study, Boston, MA 02115 USA.
[Gaziano, J. Michael] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Giovannucci, Edward L.] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
[Hallmans, Goeran] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Hutchinson, Amy] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Jacobs, Kevin B.; Michaud, Dominique S.] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Overvad, Kim] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England.
[Sanchez, Maria-Jose] Aarhus Univ, Dept Epidemiol, Sch Publ Hlth, Aalborg, Denmark.
[Slimani, Nadia; Watters, Joanne] NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Trichopoulos, Dimitrios] Int Agcy Res Canc, F-69372 Lyon, France.
[Vineis, Paolo] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Virtamo, Jarmo] Univ London Imperial Coll Sci Technol & Med, MRC HPA Ctr Environm & Hlth, Sch Publ Hlth, London, England.
[Wactawski-Wende, Jean] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM bwolpin@partners.org
RI Boutron Ruault, Marie-Christine/G-3705-2013; Boutron,
Marie-Christine/K-8168-2013; Michaud, Dominique/I-5231-2014; Albanes,
Demetrius/B-9749-2015; Boutron-Ruault, Marie-Christine/H-3936-2014;
Amundadottir, Laufey/L-7656-2016; Tobias, Geoffrey/M-4135-2016
OI Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Amundadottir,
Laufey/0000-0003-1859-8971; Tobias, Geoffrey/0000-0002-2878-8253
FU NCI [R01CA034588, R01CA098661, CA105069, CA73790, P30CA016087, K07
CA140790, R01 CA82729, R01 CA70867]; National Institute of Environmental
Health Sciences [ES000260]; National Heart, Lung, and Blood Institute,
National Institutes of Health, U.S. Department of Health and Human
Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115,
32118-32119, 32122, 42107-26, 42129-32, 44221]; National Institutes of
Health [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]; National
Cancer Institute, National Institutes of Health [P01 CA87969, P01
CA55075, P50 CA127003, R01 CA124908]; Howard Hughes Medical Institute;
Intramural Research Program of National Cancer Institute (Division of
Cancer Epidemiology and Genetics); Intramural Research Program of the
Division of Cancer Epidemiology and Genetics; Division of Cancer
Prevention, National Cancer Institute, NIH, DHHS; National Cancer
Institute, Department of Health and Human Services [N01-CN-45165,
N01-RC-45035, N01-RC-37004, HHSN261201000006C]; European Commission
(DG-SANCO); International Agency for Research on Cancer (Denmark);
Danish Cancer Society (Denmark); Ligue contre le Cancer (France);
Societe 3M (France); Mutuelle Generale de l'Education Nationale
(France); Institut National de la Sante et de la Recherche Medicale
(France); Deutsche Krebshilfe (Germany); Deutsches
Krebsforschungszentrum (Germany); Federal Ministry of Education and
Research (Germany); Ministry of Health and Social Solidarity (Greece);
Stavros Niarchos Foundation (Greece); Hellenic Health Foundation
(Greece); Italian Association for Research on Cancer (AIRC) (Italy);
National Research Council (Italy); Dutch Ministry of Public Health,
Welfare and Sports (VWS); Netherlands Cancer Registry (NKR); LK Research
Funds (Zorg Onderzoek Nederland); Dutch Prevention Funds (Zorg Onderzoek
Nederland); Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research
Fund (WCRF) (The Netherlands); Statistics Netherlands (The Netherlands);
Health Research Fund (FIS) (Spain); Regional Governments of Andalucia,
Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (Spain)
[RD06/0020]; Swedish Cancer Society (Sweden); Swedish Scientific Council
(Sweden); Regional Government of Skane and Vasterbotten (Sweden); Cancer
Research UK (United Kingdom); Medical Research Council (United Kingdom);
Stroke Association (United Kingdom); British Heart Foundation (United
Kingdom); Department of Health, Food Standards Agency (United Kingdom);
Wellcome Trust (United Kingdom); National Institute of Aging
[5U01AG018033]; American Cancer Society
FX The NYU Women's Health Study is supported by research grants
R01CA034588, R01CA098661, center grant P30CA016087 from the NCI, and the
center grant ES000260 from the National Institute of Environmental
Health Sciences.; The WHI program is funded by the National Heart, Lung,
and Blood Institute, National Institutes of Health, U.S. Department of
Health and Human Services through contracts N01WH22110, 24152, 32100-2,
32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26,
42129-32, and 44221. The authors thank the WHI investigators and staff
for their dedication, and the study participants for making the program
possible. A full listing of WHI investigators is available. (54).;
P.H.S. was supported by grants CA 97193, CA 34944, CA 40360, HL 26490,
and HL 34595 from the National Institutes of Health.; The NHS, HPFS, and
WHS at Harvard were supported by the National Cancer Institute, National
Institutes of Health (Grants No. P01 CA87969, P01 CA55075, P50 CA127003,
R01 CA124908). Brian Wolpin, MD, MPH, was supported by NCI K07 CA140790,
an American Society of Clinical Oncology Career Development Award, and a
Howard Hughes Medical Institute Early Career Physician-Scientist Award.;
The Shanghai Men's Health Study was supported by the National Cancer
Institute extramural research grant [R01 CA82729]. The Shanghai Women's
Health Study was supported by the National Cancer Institute extramural
research grant [R01 CA70867] and, partially for biological sample
collection, by the Intramural Research Program of National Cancer
Institute (Division of Cancer Epidemiology and Genetics).; PLCO 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, NIH, DHHS. The authors thank Drs.
Christine Berg and Philip Prorok, Division of Cancer Prevention,
National Cancer Institute, the Screening Center investigators and staff
of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening
Trial, Mr. Tom Riley and staff, Information Management Services, Inc.,
Ms. Barbara O'Brien and staff, Westat, Inc., Mr. Tim Sheehy and staff,
DNA Extraction and Staging Laboratory, SAIC-Frederick, Inc, and Ms.
Jackie King and staff, BioReliance, Inc. Most importantly, we
acknowledge the study participants for their contributions to making
this study possible.; The ATBC Study was supported by U.S. Public Health
Service contractsN01-CN-45165, N01-RC-45035, N01-RC-37004, and
HHSN261201000006C from the National Cancer Institute, Department of
Health and Human Services, and by funding from the Intramural Research
Program of the National Cancer Institute.; For the EPIC cohorts, all
coauthors coordinated the initial recruitment and management of the
studies. All authors contributed to the final paper. The authors thank
all of the participants who took part in this research and the funders
and support and technical staff who made this study possible. The
coordination of EPIC is financially supported by the European Commission
(DG-SANCO) and the International Agency for Research on Cancer. The
national cohorts are supported by Danish Cancer Society (Denmark); Ligue
contre le Cancer, Societe 3M, Mutuelle Generale de l'Education
Nationale, Institut National de la Sante et de la Recherche Medicale
(France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and
Federal Ministry of Education and Research (Germany); Ministry of Health
and Social Solidarity, Stavros Niarchos Foundation and Hellenic Health
Foundation (Greece); Italian Association for Research on Cancer (AIRC)
and National Research Council (Italy); Dutch Ministry of Public Health,
Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research
Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland),
World Cancer Research Fund (WCRF), Statistics Netherlands (The
Netherlands); Health Research Fund (FIS), Regional Governments of
Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC
(RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council
and Regional Government of Skane and Vasterbotten (Sweden); Cancer
Research UK, Medical Research Council, Stroke Association, British Heart
Foundation, Department of Health, Food Standards Agency, and Wellcome
Trust (United Kingdom).; CLUE II was supported by National Institute of
Aging grant (5U01AG018033) and National Cancer Institute grants
(CA105069, CA73790). The authors express their appreciation to the
participants of the CLUE II cohort and thank the staff at the George W.
Comstock Center for Public Health Research and Prevention for their
dedication and contributions to the study: Judy Hoffman-Bolton, Clara
Krumpe, Kitty Spoonire, and Betty Miner.; The Cancer Prevention Study II
Nutrition Cohort is supported by the American Cancer Society. The
authors thank all of the men and women in the Cancer Prevention Study II
Nutrition Cohort for their many years of dedicated participation in the
study.; This project has been funded in whole or in part with federal
funds from the National Cancer Institute, National Institutes of Health,
under Contract No. HHSN261200800001E. The content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 53
TC 39
Z9 41
U1 0
U2 9
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 2010
VL 19
IS 12
BP 3140
EP 3149
DI 10.1158/1055-9965.EPI-10-0751
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 694HP
UT WOS:000285285900015
PM 20971884
ER
PT J
AU Fang, SY
Pinney, SM
Bailey-Wilson, JE
de Andrade, MA
Li, YF
Kupert, E
You, M
Schwartz, AG
Yang, P
Anderson, MW
Amos, CI
AF Fang, Shenying
Pinney, Susan M.
Bailey-Wilson, Joan E.
de Andrade, Mariza A.
Li, Yafang
Kupert, Elena
You, Ming
Schwartz, Ann G.
Yang, Ping
Anderson, Marshall W.
Amos, Christopher I.
TI Ordered Subset Analysis Identifies Loci Influencing Lung Cancer Risk on
Chromosomes 6q and 12q
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GROWTH-FACTOR-I; HUMAN BREAST-CANCER; H-CADHERIN CDH13; COMPLEX TRAITS;
PROGNOSTIC-SIGNIFICANCE; SUSCEPTIBILITY LOCUS; LINKAGE ANALYSIS;
FAMILIAL RISK; ALLELIC LOSS; MUCINS MUC1
AB Background: Genetic susceptibility for cancer can differ substantially among families. We use trait-related covariates to identify a genetically homogeneous subset of families with the best evidence for linkage in the presence of heterogeneity.
Methods: We performed a genome-wide linkage screen in 93 families. Samples and data were collected by the familial lung cancer recruitment sites of the Genetic Epidemiology of Lung Cancer Consortium. We estimated linkage scores for each family by the Markov chain Monte Carlo procedure using SimWalk2 software. We used ordered subset analysis (OSA) to identify genetically homogenous families by ordering families based on a disease-associated covariate. We performed permutation tests to determine the relationship between the trait-related covariate and the evidence for linkage.
Results: A genome-wide screen for lung cancer loci identified strong evidence for linkage to 6q23-25 and suggestive evidence for linkage to 12q24 using OSA, with peak logarithm of odds (LOD) scores of 4.19 and 2.79, respectively. We found other chromosomes also suggestive for linkages, including 5q31-q33, 14q11, and 16q24.
Conclusions: Our OSA results support 6q as a lung cancer susceptibility locus and provide evidence for disease linkage on 12q24. This study further increased our understanding of the inheritability for lung cancer. Validation studies using larger sample size are needed to verify the presence of several other chromosomal regions suggestive of an increased risk for lung cancer and/or other cancers.
Impact: OSA can reduce genetic heterogeneity in linkage study and may assist in revealing novel susceptibility loci. Cancer Epidemiol Biomarkers Prev; 19(12); 3157-66. (C) 2010 AACR.
C1 [Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Unit 1340, Houston, TX 77030 USA.
[Pinney, Susan M.; Kupert, Elena; Anderson, Marshall W.] Univ Cincinnati, Cincinnati, OH USA.
[Bailey-Wilson, Joan E.] NHGRI, Baltimore, MD USA.
[de Andrade, Mariza A.; Yang, Ping] Mayo Clin, Coll Med, Rochester, MN USA.
[You, Ming] Washington Univ, St Louis, MO USA.
[Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
RP Amos, CI (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Unit 1340, 1155 Pressler St, Houston, TX 77030 USA.
EM camos@mdanderson.org
OI Bailey-Wilson, Joan/0000-0002-9153-2920
FU National Institutes of Health [UO1CA076293, P30ES06096, P30CA016772,
R01CA133996, RO1CA060691, RO1CA87895, P30ES007789, P50CA70907,
NO1PC35145]; National Cancer Institute; National Human Genome Research
Institute; National Institute of Environmental Health Sciences
[P30ES007784]
FX This work was supported in part by the National Institutes of Health
grants UO1CA076293, P30ES06096, P30CA016772, R01CA133996, RO1CA060691,
RO1CA87895, P30ES007789, P50CA70907, and NO1PC35145, the intramural
programs of the National Cancer Institute, and the National Human Genome
Research Institute. This publication was made possible by grant
P30ES007784 from the National Institute of Environmental Health
Sciences.
NR 40
TC 4
Z9 4
U1 0
U2 3
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 2010
VL 19
IS 12
BP 3157
EP 3166
DI 10.1158/1055-9965.EPI-10-0792
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 694HP
UT WOS:000285285900017
PM 21030603
ER
PT J
AU Frankel, TL
Burns, W
Riley, J
Morgan, RA
Davis, JL
Hanada, K
Quezado, M
Rosenberg, SA
Royal, RE
AF Frankel, Timothy L.
Burns, William
Riley, John
Morgan, Richard A.
Davis, Jeremy L.
Hanada, Kenichi
Quezado, Martha
Rosenberg, Steven A.
Royal, Richard E.
TI Identification and characterization of a tumor infiltrating
CD56(+)/CD16(-) NK cell subset with specificity for pancreatic and
prostate cancer cell lines
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE Natural killer cells; Pancreatic cancer; Immunotherapy; Anti-CTLA-4
ID NATURAL-KILLER-CELLS; APOPTOSIS-INDUCING LIGAND; PERIPHERAL-BLOOD
LYMPHOCYTES; METASTATIC MELANOMA; IMMUNOTHERAPY; EXPRESSION; ACTIVATION;
CARCINOMAS; RECEPTOR; THERAPY
AB In a recent clinical trial, a patient exhibited regression of several pancreatic cancer metastases following the administration of the immune modulator Ipilimumab (anti-CTLA-4 antibody). We sought to characterize the immune cells responsible for this regression. Tumor infiltrating lymphocytes (TIL-2742) and an autologous tumor line (TC-2742) were expanded from a regressing metastatic lesion excised from this patient. Natural killer (NK) cells predominated in the TIL (92% CD56(+)) with few T cells (12% CD3(+)). A majority (88%) of the NK cells were CD56(bright)CD16(-). TIL-2742 secreted IFN-gamma and GM-CSF following co-culture with TC-2742 and major histocompatibility complex mismatched pancreatic tumor lines. After sorting TIL-2742, the purified CD56(+)CD16(-)CD3(-) subset showed reactivity similar to TIL-2742 while the CD56(-)CD16(-)CD3(+) cells exhibited no tumor recognition. In co-culture assays, TIL-2742 and the NK subset expressed high reactivity to several pancreatic and prostate cancer cell lines and could lyse the autologous tumor as well as pancreas and prostate cancer lines. Reactivity was partially abrogated by blockade of TRAIL. We thus identified a unique subset of NK cells (CD56(bright)CD16(dim)) isolated from a regressing metastatic pancreatic cancer in a patient responding to Ipilimumab. This represents the first report of CD56(+)CD16(-) NK cells with apparent specificity for pancreatic and prostate cancer cell lines and associated with tumor regression following the treatment with an immune modulating agent.
C1 [Frankel, Timothy L.; Burns, William; Riley, John; Morgan, Richard A.; Davis, Jeremy L.; Hanada, Kenichi; Rosenberg, Steven A.; Royal, Richard E.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Quezado, Martha] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Royal, RE (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, 1515 Holcombe Blvd,Unit 444, Houston, TX 77098 USA.
EM rroyal@mdanderson.org
RI Hanada, Ken-ichi/L-2481-2013
OI Hanada, Ken-ichi/0000-0003-2959-1257
NR 34
TC 9
Z9 12
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD DEC
PY 2010
VL 59
IS 12
BP 1757
EP 1769
DI 10.1007/s00262-010-0897-y
PG 13
WC Oncology; Immunology
SC Oncology; Immunology
GA 654RC
UT WOS:000282184700001
PM 20734041
ER
PT J
AU Li, QF
Tang, JA
Liu, QR
Shi, SL
Chen, XF
AF Li, Qi-Fu
Tang, Jian
Liu, Qing-Rong
Shi, Song-Lin
Chen, Xiang-Feng
TI Localization and Altered Expression of Nucleophosmin in the Nuclear
Matrix During the Differentiation of Human Hepatocarcinoma SMMC-7721
Cells Induced by HMBA
SO CANCER INVESTIGATION
LA English
DT Article
DE Nucleophosmin; Nuclear matrix; Hepatocarcinoma cell; Cell
differentiation
ID TUMOR-SUPPRESSOR PROTEIN; RETINOIC ACID; PROSTATE-CANCER; HL-60 CELLS;
HELA-CELLS; APOPTOSIS; NPM; ACTIVATION; PATHWAY; B23
AB Nucleophosmin (NPM1) is frequently upregulated and mutated in various tumor cells. To investigate the mechanism of induced differentiation of tumor cells, the nuclear matrix of human hepatocarcinoma SMMC-7721 cells induced by hexamethylene bisacetamide (HMBA) was selectively extracted and subjected to proteomic methodologies. We confirmed that NPM1 existed in nuclear matrix proteins and downregulated after HMBA treatment. By using immunogold electromicroscopy, we found that NPM1 was localized on nuclear matrix-intermediate filaments. Our study also revealed the colocalization between NPM1 and products of oncogenes or tumor surppresor genes including c-Fos, c-Myc, p53, and Rb by using laser scanning confocal microscopy in SMMC-7721 cells.
C1 [Li, Qi-Fu; Tang, Jian; Shi, Song-Lin; Chen, Xiang-Feng] Xiamen Univ, Key Lab, Minist Educ Cell Biol & Tumor Cell Engn, Sch Life Sci, Xiamen 361005, Peoples R China.
[Liu, Qing-Rong] NIDA, Mol Neurobiol Branch, IRP, DHSS, Baltimore, MD USA.
RP Li, QF (reprint author), Xiamen Univ, Key Lab, Minist Educ Cell Biol & Tumor Cell Engn, Sch Life Sci, Xiamen 361005, Peoples R China.
EM chifulee@xmu.edu.cn
RI Li, QF/G-4604-2010; Liu, Qing-Rong/A-3059-2012
OI Liu, Qing-Rong/0000-0001-8477-6452
FU National Natural Science Foundation of China [30470877]
FX This study was supported by the National Natural Science Foundation of
China (grant no. 30470877).
NR 24
TC 2
Z9 3
U1 1
U2 4
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 0735-7907
J9 CANCER INVEST
JI Cancer Invest.
PD DEC
PY 2010
VL 28
IS 10
BP 1004
EP 1012
DI 10.3109/07357900902918452
PG 9
WC Oncology
SC Oncology
GA 680GH
UT WOS:000284219900004
PM 20690796
ER
PT J
AU Goodman, PJ
Tangen, CM
Kristal, AR
Thompson, IM
Lucia, MS
Platz, EA
Figg, WD
Hoque, A
Hsing, A
Neuhouser, ML
Parnes, HL
Reichardt, JKV
Santella, RM
Till, C
Lippman, SM
AF Goodman, Phyllis J.
Tangen, Catherine M.
Kristal, Alan R.
Thompson, Ian M.
Lucia, M. Scott
Platz, Elizabeth A.
Figg, William D.
Hoque, Ashraful
Hsing, Ann
Neuhouser, Marian L.
Parnes, Howard L.
Reichardt, Juergen K. V.
Santella, Regina M.
Till, Cathee
Lippman, Scott M.
TI Transition of a Clinical Trial into Translational Research: The Prostate
Cancer Prevention Trial Experience
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID MODELING APPROACH; FINASTERIDE; RISK; SUSCEPTIBILITY; DISEASE; BIAS; MEN
AB Large clinical trials provide a tremendous opportunity to integrate correlative, comprehensive biological studies with invaluable repositories of biospecimens and clinical and other data from the trial. The Prostate Cancer Prevention Trial (PCPT) was a phase III randomized, double-blind, placebo-controlled clinical trial of finasteride in 18,882 men. Clinical data and blood and tissue specimens were collected at baseline and throughout the study, offering an opportunity to create a program project to investigate hypotheses related to the biology underlying the PCPT findings as well as the etiology and risk of prostate cancer. The transition of the randomized PCPT into this translational and epidemiologic scientific investigation required extensive planning and coordination. Five individual but interrelated projects were brought together with the underlying program theme of the genetic, metabolic, and environmental factors associated with the risks of overall and high-grade prostate cancer and how these factors affected the efficacy of finasteride in preventing cancer. All projects with serum-based measures use a single, shared, nested case-control sample of participants so that each subject provides a more complete biomarker and genetic profile for the evaluation of joint effects of these factors. Strengths of this program include the following: 1) the control group contains only men who are negative for biopsy-detected cancer, 2) the statistical methods to evaluate associations of risk factors with disease are shared across all projects, 3) the large number of cancer cases with fully characterized genetic, metabolic, and behavioral exposures, 4) a central pathology core histopathologically classified the prostate cancer, and 5) cancer cases identified during the PCPT reflect the characteristics of cases currently being detected in the prostate-specific antigen screening era, leading to contemporary and highly relevant results. This article describes the comprehensive methodology and multidisciplinary collaborations, both national and international, essential to a major risk-modeling research program. We provide a framework for doing collaborative research in an international setting structured around a common theme of a clinical trial. Cancer Prev Res; 3(12); 1523-33. (C) 2010 AACR.
C1 [Goodman, Phyllis J.; Tangen, Catherine M.; Till, Cathee] Fred Hutchinson Canc Res Ctr, SW Oncol Grp Stat Ctr, Seattle, WA 98109 USA.
[Kristal, Alan R.; Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, Seattle, WA 98109 USA.
[Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Lucia, M. Scott] Univ Colorado Denver, Sch Med, Aurora, CO USA.
[Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Figg, William D.; Hsing, Ann; Parnes, Howard L.] NCI, Bethesda, MD 20892 USA.
[Hoque, Ashraful; Lippman, Scott M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Reichardt, Juergen K. V.] Univ Sydney, Sydney, NSW 2006, Australia.
[Santella, Regina M.] Columbia Univ, New York, NY USA.
RP Goodman, PJ (reprint author), Fred Hutchinson Canc Res Ctr, SW Oncol Grp Stat Ctr, 1100 Fairview Ave N,M3-C102, Seattle, WA 98109 USA.
EM pgoodman@fhcrc.org
RI Figg Sr, William/M-2411-2016;
OI Kristal, Alan/0000-0002-7329-1617; Reichardt,
Juergen/0000-0001-6458-2773
FU National Cancer Institute, National Institutes of Health [CA37429,
P01CA108964]
FX This work was funded by the National Cancer Institute, National
Institutes of Health (CA37429 and P01CA108964). The content of this work
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
NR 21
TC 13
Z9 13
U1 0
U2 0
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 2010
VL 3
IS 12
BP 1523
EP 1533
DI 10.1158/1940-6207.CAPR-09-0256
PG 11
WC Oncology
SC Oncology
GA 692XO
UT WOS:000285189400005
PM 21149329
ER
PT J
AU Hendrix, A
Westbroek, W
Bracke, M
De Wever, O
AF Hendrix, An
Westbroek, Wendy
Bracke, Marc
De Wever, Olivier
TI An Ex(o)citing Machinery for Invasive Tumor Growth
SO CANCER RESEARCH
LA English
DT Review
ID CANCER-CELL INVASION; EXOCYTOSIS; SECRETION; GTPASES; TRAFFICKING;
HSP90-ALPHA; EXPRESSION; PROTEOMICS; EXOSOMES; PATHWAY
AB Cancer cells communicate with the environment through delivery of surface proteins, release of soluble factors (growth factors and cytokines), and sophisticated nanovehicles (exosomes) for establishment of invasive tumor growth. This communication occurs in part through constitutive exocytosis, regulated exocytosis, or release of intraluminal vesicles, and is modulated by small Rab GTPases, the master regulators of vesicle traffic. We studied Rab GTPases implicated in regulated exocytosis and showed a unique role for Rab27B in invasive tumor growth. Emerging evidence indicates that various exocytic routes are implemented by cancer cells to relay crucial information for fostering growth, migration, and matrix degradation. Cancer Res; 70(23); 9533-7. (C) 2010 AACR.
C1 [Hendrix, An; Bracke, Marc; De Wever, Olivier] Ghent Univ Hosp, Lab Expt Canc Res, Dept Radiat Oncol & Expt Canc Res, B-9000 Ghent, Belgium.
[Westbroek, Wendy] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
RP De Wever, O (reprint author), Ghent Univ Hosp, Lab Expt Canc Res, Dept Radiat Oncol & Expt Canc Res, De Pintelaan 185, B-9000 Ghent, Belgium.
EM olivier.dewever@ugent.be
RI de wever, olivier/J-3094-2013
OI de wever, olivier/0000-0002-5453-760X
FU Fund for Scientific Research Flanders (FWO, Belgium); Special Research
Fund (BOF, Ghent University, Belgium); National Human Genome Research
Institute
FX O. De Wever was supported by a postdoctoral grant from Fund for
Scientific Research Flanders (FWO, Belgium), A. Hendrix by a
postdoctoral grant from Special Research Fund (BOF, Ghent University,
Belgium), and W. Westbroek by the Intramural Research Program of the
National Human Genome Research Institute.
NR 35
TC 57
Z9 57
U1 1
U2 10
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 2010
VL 70
IS 23
BP 9533
EP 9537
DI 10.1158/0008-5472.CAN-10-3248
PG 5
WC Oncology
SC Oncology
GA 690YJ
UT WOS:000285045900001
PM 21098711
ER
PT J
AU Antoniou, AC
Beesley, J
McGuffog, L
Sinilnikova, OM
Healey, S
Neuhausen, SL
Ding, YC
Rebbeck, TR
Weitzel, JN
Lynch, HT
Isaacs, C
Ganz, PA
Tomlinson, G
Olopade, OI
Couch, FJ
Wang, XS
Lindor, NM
Pankratz, VS
Radice, P
Manoukian, S
Peissel, B
Zaffaroni, D
Barile, M
Viel, A
Allavena, A
Dall'Olio, V
Peterlongo, P
Szabo, CI
Zikan, M
Claes, K
Poppe, B
Foretova, L
Mai, PL
Greene, MH
Rennert, G
Lejbkowicz, F
Glendon, G
Ozcelik, H
Andrulis, IL
Thomassen, M
Gerdes, AM
Sunde, L
Cruger, D
Jensen, UB
Caligo, M
Friedman, E
Kaufman, B
Laitman, Y
Milgrom, R
Dubrovsky, M
Cohen, S
Borg, A
Jernstrom, H
Lindblom, A
Rantala, J
Stenmark-Askmalm, M
Melin, B
Nathanson, K
Domchek, S
Jakubowska, A
Lubinski, J
Huzarski, T
Osorio, A
Lasa, A
Duran, M
Tejada, MI
Godino, J
Benitez, J
Hamann, U
Kriege, M
Hoogerbrugge, N
van der Luijt, RB
van Asperen, CJ
Devilee, P
Meijers-Heijboer, EJ
Blok, MJ
Aalfs, CM
Hogervorst, F
Rookus, M
Cook, M
Oliver, C
Frost, D
Conroy, D
Evans, DG
Lalloo, F
Pichert, G
Davidson, R
Cole, T
Cook, J
Paterson, J
Hodgson, S
Morrison, PJ
Porteous, ME
Walker, L
Kennedy, MJ
Dorkins, H
Peock, S
Godwin, AK
Stoppa-Lyonnet, D
de Pauw, A
Mazoyer, S
Bonadona, V
Lasset, C
Dreyfus, H
Leroux, D
Hardouin, A
Berthet, P
Faivre, L
Loustalot, C
Noguchi, T
Sobol, H
Rouleau, E
Nogues, C
Frenay, M
Venat-Bouvet, L
Hopper, JL
Daly, MB
Terry, MB
John, EM
Buys, SS
Yassin, Y
Miron, A
Goldgar, D
Singer, CF
Dressler, AC
Gschwantler-Kaulich, D
Pfeiler, G
Hansen, TVO
Jnson, L
Agnarsson, BA
Kirchhoff, T
Offit, K
Devlin, V
Dutra-Clarke, A
Piedmonte, M
Rodriguez, GC
Wakeley, K
Boggess, JF
Basil, J
Schwartz, PE
Blank, SV
Toland, AE
Montagna, M
Casella, C
Imyanitov, E
Tihomirova, L
Blanco, I
Lazaro, C
Ramus, SJ
Sucheston, L
Karlan, BY
Gross, J
Schmutzler, R
Wappenschmidt, B
Engel, C
Meindl, A
Lochmann, M
Arnold, N
Heidemann, S
Varon-Mateeva, R
Niederacher, D
Sutter, C
Deissler, H
Gadzicki, D
Preisler-Adams, S
Kast, K
Schonbuchner, I
Caldes, T
de la Hoya, M
Aittomaki, K
Nevanlinna, H
Simard, J
Spurdle, AB
Holland, H
Chen, XQ
Platte, R
Chenevix-Trench, G
Easton, DF
AF Antoniou, Antonis C.
Beesley, Jonathan
McGuffog, Lesley
Sinilnikova, Olga M.
Healey, Sue
Neuhausen, Susan L.
Ding, Yuan Chun
Rebbeck, Timothy R.
Weitzel, Jeffrey N.
Lynch, Henry T.
Isaacs, Claudine
Ganz, Patricia A.
Tomlinson, Gail
Olopade, Olufunmilayo I.
Couch, Fergus J.
Wang, Xianshu
Lindor, Noralane M.
Pankratz, Vernon S.
Radice, Paolo
Manoukian, Siranoush
Peissel, Bernard
Zaffaroni, Daniela
Barile, Monica
Viel, Alessandra
Allavena, Anna
Dall'Olio, Valentina
Peterlongo, Paolo
Szabo, Csilla I.
Zikan, Michal
Claes, Kathleen
Poppe, Bruce
Foretova, Lenka
Mai, Phuong L.
Greene, Mark H.
Rennert, Gad
Lejbkowicz, Flavio
Glendon, Gord
Ozcelik, Hilmi
Andrulis, Irene L.
Thomassen, Mads
Gerdes, Anne-Marie
Sunde, Lone
Cruger, Dorthe
Jensen, Uffe Birk
Caligo, Maria
Friedman, Eitan
Kaufman, Bella
Laitman, Yael
Milgrom, Roni
Dubrovsky, Maya
Cohen, Shimrit
Borg, Ake
Jernstroem, Helena
Lindblom, Annika
Rantala, Johanna
Stenmark-Askmalm, Marie
Melin, Beatrice
Nathanson, Kate
Domchek, Susan
Jakubowska, Ania
Lubinski, Jan
Huzarski, Tomasz
Osorio, Ana
Lasa, Adriana
Duran, Mercedes
Tejada, Maria-Isabel
Godino, Javier
Benitez, Javier
Hamann, Ute
Kriege, Mieke
Hoogerbrugge, Nicoline
van der Luijt, Rob B.
van Asperen, Christi J.
Devilee, Peter
Meijers-Heijboer, E. J.
Blok, Marinus J.
Aalfs, Cora M.
Hogervorst, Frans
Rookus, Matti
Cook, Margaret
Oliver, Clare
Frost, Debra
Conroy, Don
Evans, D. Gareth
Lalloo, Fiona
Pichert, Gabriella
Davidson, Rosemarie
Cole, Trevor
Cook, Jackie
Paterson, Joan
Hodgson, Shirley
Morrison, Patrick J.
Porteous, Mary E.
Walker, Lisa
Kennedy, M. John
Dorkins, Huw
Peock, Susan
Godwin, Andrew K.
Stoppa-Lyonnet, Dominique
de Pauw, Antoine
Mazoyer, Sylvie
Bonadona, Valerie
Lasset, Christine
Dreyfus, Helene
Leroux, Dominique
Hardouin, Agnes
Berthet, Pascaline
Faivre, Laurence
Loustalot, Catherine
Noguchi, Tetsuro
Sobol, Hagay
Rouleau, Etienne
Nogues, Catherine
Frenay, Marc
Venat-Bouvet, Laurence
Hopper, John L.
Daly, Mary B.
Terry, Mary B.
John, Esther M.
Buys, Saundra S.
Yassin, Yosuf
Miron, Alexander
Goldgar, David
Singer, Christian F.
Dressler, Anne Catharina
Gschwantler-Kaulich, Daphne
Pfeiler, Georg
Hansen, Thomas V. O.
Jnson, Lars
Agnarsson, Bjarni A.
Kirchhoff, Tomas
Offit, Kenneth
Devlin, Vincent
Dutra-Clarke, Ana
Piedmonte, Marion
Rodriguez, Gustavo C.
Wakeley, Katie
Boggess, John F.
Basil, Jack
Schwartz, Peter E.
Blank, Stephanie V.
Toland, Amanda Ewart
Montagna, Marco
Casella, Cinzia
Imyanitov, Evgeny
Tihomirova, Laima
Blanco, Ignacio
Lazaro, Conxi
Ramus, Susan J.
Sucheston, Lara
Karlan, Beth Y.
Gross, Jenny
Schmutzler, Rita
Wappenschmidt, Barbara
Engel, Christoph
Meindl, Alfons
Lochmann, Magdalena
Arnold, Norbert
Heidemann, Simone
Varon-Mateeva, Raymonda
Niederacher, Dieter
Sutter, Christian
Deissler, Helmut
Gadzicki, Dorothea
Preisler-Adams, Sabine
Kast, Karin
Schoenbuchner, Ines
Caldes, Trinidad
de la Hoya, Miguel
Aittomaeki, Kristiina
Nevanlinna, Heli
Simard, Jacques
Spurdle, Amanda B.
Holland, Helene
Chen, Xiaoqing
Platte, Radka
Chenevix-Trench, Georgia
Easton, Douglas F.
CA Ontario Canc Genetics Network
SWE-BRCA
HEBON
EMBRACE
GEMO
Breast Canc Family Registry
kConFab
CIMBA
TI Common Breast Cancer Susceptibility Alleles and the Risk of Breast
Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk
Prediction
SO CANCER RESEARCH
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ESTROGEN-RECEPTOR; LOCI; VARIANTS
AB The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR - 1.10, 95% CI: 1.03-1.18, P - 0.006 and HR - 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P 7 = 10 x (11) - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42%
C1 [Antoniou, Antonis C.; McGuffog, Lesley; Cook, Margaret; Oliver, Clare; Frost, Debra; Peock, Susan] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
[Beesley, Jonathan; Healey, Sue; Spurdle, Amanda B.; Holland, Helene; Chen, Xiaoqing] Queensland Inst Med Res, Brisbane, Qld, Australia.
[Sinilnikova, Olga M.] Univ Lyon 1, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Ctr Hosp, F-69365 Lyon, France.
[Neuhausen, Susan L.; Ding, Yuan Chun] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA.
[Rebbeck, Timothy R.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Rebbeck, Timothy R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Lynch, Henry T.] Creighton Univ, Omaha, NE 68178 USA.
[Weitzel, Jeffrey N.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
[Tomlinson, Gail] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Olopade, Olufunmilayo I.; Easton, Douglas F.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN USA.
[Pankratz, Vernon S.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Radice, Paolo; Peterlongo, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Unit Genet Susceptibil Canc, Dept Expt Oncol & Mol Med, Milan, Italy.
[Radice, Paolo; Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy.
[Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predict Med, Milan, Italy.
[Barile, Monica] IEO, Div Canc Prevent & Genet, Milan, Italy.
[Viel, Alessandra] IRCCS, CRO, Div Expt Oncol 1, Aviano, PN, Italy.
[Allavena, Anna] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy.
[Dall'Olio, Valentina] Cogentech, Consortium Genom Technol, Milan, Italy.
[Szabo, Csilla I.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA.
[Zikan, Michal] Charles Univ Prague, Fac Med 1, Dept Biochem & Expt Oncol, Prague, Czech Republic.
[Claes, Kathleen; Poppe, Bruce] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Mai, Phuong L.; Greene, Mark H.] US Natl Canc Inst, Clin Genet Branch, Rockville, MD USA.
[Rennert, Gad; Lejbkowicz, Flavio] Technion Israel Inst Technol, Carmel Med Ctr, Haifa, Israel.
[Rennert, Gad; Lejbkowicz, Flavio] Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel.
[Glendon, Gord; Andrulis, Irene L.] OCGN, Toronto, ON, Canada.
[Ozcelik, Hilmi; Andrulis, Irene L.] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Samuel Lunenfeld Res Inst, New York, NY 10029 USA.
[Ozcelik, Hilmi; Andrulis, Irene L.] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark.
[Gerdes, Anne-Marie] Rigshosp, Dept Clin Genet, Odense, Denmark.
[Sunde, Lone] Aalborg Hosp, Dept Clin Genet, Aalborg, Denmark.
[Cruger, Dorthe] Vejle Hosp, Dept Clin Genet, Velje, Denmark.
[Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark.
[Caligo, Maria] Univ Pisa, Div Surg Mol & Ultrastruct Pathol, Dept Oncol, Pisa, Italy.
[Caligo, Maria] Pisa Univ Hosp, Pisa, Italy.
[Friedman, Eitan; Laitman, Yael; Milgrom, Roni; Dubrovsky, Maya; Cohen, Shimrit] Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, Tel Hashomer, Israel.
[Kaufman, Bella] Sheba Med Ctr, Inst Oncol, Tel Hashomer, Israel.
[Borg, Ake; Jernstroem, Helena] Lund Univ, Dept Oncol, Lund, Sweden.
[Lindblom, Annika; Rantala, Johanna] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Stenmark-Askmalm, Marie] Linkoping Univ, Dept Oncol, Linkoping, Sweden.
[Melin, Beatrice] Umea Univ, Dept Radiat Sci, Umea, Sweden.
[Nathanson, Kate; Domchek, Susan] Univ Penn, Philadelphia, PA 19104 USA.
[Jakubowska, Ania; Lubinski, Jan; Huzarski, Tomasz] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland.
[Osorio, Ana] Spanish Natl Canc Res Ctr, Human Genet Grp, Human Canc Genet Programme, Madrid, Spain.
[Lasa, Adriana] Hosp Santa Creu & Sant Pau, Genet Serv, Barcelona, Spain.
[Duran, Mercedes] Univ Valladolid, Inst Biol & Mol Genet, IBGM UVA, Valladolid, Spain.
[Tejada, Maria-Isabel] Cruces Hosp Barakaldo, Mol Genet Lab, Dept Biochem, Bizkaia, Spain.
[Godino, Javier] Univ Lozano Blesa, Hosp Clin, Oncol Serv, Zaragoza, Spain.
[Benitez, Javier] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Genotyping Unit, Madrid, Spain.
[Hamann, Ute] Deutsch Krebsforschungszentrum, Mol Genet Breast Canc, D-6900 Heidelberg, Germany.
[Kriege, Mieke] Daniel Denhoed Canc Ctr, Erasmus MC, Dept Med Oncol, Family Canc Clin, Rotterdam, Netherlands.
[Hoogerbrugge, Nicoline] Radboud Univ Nijmegen, Nijmegen Med Ctr, Hereditary Canc Clin, NL-6525 ED Nijmegen, Netherlands.
[van der Luijt, Rob B.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[van Asperen, Christi J.] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, Dept Pathol, NL-2300 RA Leiden, Netherlands.
[Meijers-Heijboer, E. J.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
[Blok, Marinus J.] Univ Med Ctr, Dept Genet & Cell Biol, Maastricht, Netherlands.
[Aalfs, Cora M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands.
[Hogervorst, Frans] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands.
[Rookus, Matti] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands.
[Conroy, Don] Univ Cambridge, Dept Oncol, Cambridge, England.
[Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Pichert, Gabriella] Guys & St Thomas NHS Fdn Trust, London, England.
[Davidson, Rosemarie] Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland.
[Cole, Trevor] Birmingham Womens Hosp Healthcare NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England.
[Cook, Jackie] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England.
[Paterson, Joan] Addenbrookes Hosp, Dept Clin Genet, E Anglian Reg Genet Serv, Cambridge, England.
[Hodgson, Shirley] Univ London, Dept Clin Genet, St Georges Hosp, London, England.
[Morrison, Patrick J.] Belfast City Hosp, Northern Ireland Reg Genet Ctr, Belfast BT9 7AD, Antrim, North Ireland.
[Porteous, Mary E.] Western Gen Hosp, SE Scotland Reg Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland.
[Walker, Lisa] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England.
[Kennedy, M. John] St James Hosp, Canc Genet Program, Hope Directorate, Dublin, Ireland.
[Dorkins, Huw] Kennedy Galton Ctr, NW Thames Reg Genet Serv, Harrow, Middx, England.
[Godwin, Andrew K.; Daly, Mary B.] Fox Chase Canc Ctr, Dept Med Oncol, Womens Canc Program, Philadelphia, PA 19111 USA.
[Stoppa-Lyonnet, Dominique; de Pauw, Antoine] Univ Paris 05, INSERM, U509, Serv Genet Oncol,Inst Curie, Paris, France.
[Mazoyer, Sylvie] Univ Lyon 1, CNRS, Ctr Leon Berard, Equipe Labellisee LIGUE 2008,UMR5201, F-69365 Lyon, France.
[Bonadona, Valerie; Lasset, Christine] Univ Lyon 1, CNRS, UMR5558, F-69365 Lyon, France.
[Bonadona, Valerie; Lasset, Christine] Ctr Leon Berard, Unite Prevent & Epidemiol Genet, F-69373 Lyon, France.
[Dreyfus, Helene; Leroux, Dominique] CHU Grenoble, Dept Genet, F-38043 Grenoble, France.
[Dreyfus, Helene; Leroux, Dominique] Univ Grenoble, Inst Albert Bonniot, Grenoble, France.
[Hardouin, Agnes; Berthet, Pascaline] Ctr Francois Baclesse, F-14021 Caen, France.
[Faivre, Laurence] Ctr Hosp Univ Dijon, Ctr Genet, Dijon, France.
[Faivre, Laurence; Loustalot, Catherine] Ctr Lutte Canc Georges Francois Leclerc, Dijon, France.
[Noguchi, Tetsuro; Sobol, Hagay] INSERM, Inst Paoli Calmettes, UMR599, Dept Oncol Genet, F-13258 Marseille, France.
[Rouleau, Etienne] Ctr Rene Huguenin, INSERM, U735, St Cloud, France.
[Frenay, Marc] Ctr Antoine Lacassagne, F-06054 Nice, France.
[Venat-Bouvet, Laurence] Ctr Hosp Univ Limoges, Dept Oncol, Limoges, France.
[Terry, Mary B.] Columbia Univ, New York, NY USA.
[Hopper, John L.] Univ Melbourne, Melbourne, Vic, Australia.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[John, Esther M.] No Calif Canc Ctr, Fremont, CA USA.
[John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA.
[Yassin, Yosuf; Miron, Alexander] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Goldgar, David] Univ Utah, Dept Dermatol, Salt Lake City, UT USA.
[Singer, Christian F.; Dressler, Anne Catharina; Gschwantler-Kaulich, Daphne; Pfeiler, Georg] Med Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria.
[Hansen, Thomas V. O.; Jnson, Lars] Univ Copenhagen, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark.
[Agnarsson, Bjarni A.] Univ Hosp, Dept Pathol, Reykjavik, Iceland.
[Agnarsson, Bjarni A.] Univ Iceland, Sch Med, Reykjavik, Iceland.
[Kirchhoff, Tomas; Offit, Kenneth; Devlin, Vincent; Dutra-Clarke, Ana] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA.
[Piedmonte, Marion] Roswell Pk Canc Inst, GOG Stat & Data Ctr, Buffalo, NY 14263 USA.
[Rodriguez, Gustavo C.] NorthShore Univ Hlth Syst, Evanston NW Healthcare, Evanston, IL USA.
[Wakeley, Katie] Tufts Univ, New England Med Ctr, Boston, MA 02111 USA.
[Boggess, John F.] Univ N Carolina, Chapel Hill, NC USA.
[Schwartz, Peter E.] Yale Univ, Sch Med, New Haven, CT USA.
[Basil, Jack] St Elizabeth Hosp, Edgewood, KY USA.
[Blank, Stephanie V.] NYU, Sch Med, New York, NY USA.
[Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med & Mol Virol, Div Human Canc Genet, Columbus, OH 43210 USA.
[Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Dept Immunol & Med Genet, Div Human Canc Genet, Columbus, OH 43210 USA.
[Montagna, Marco; Casella, Cinzia] IRCCS, Ist Oncol Veneto, Immunol & Mol Oncol Unit, Padua, Italy.
[Tihomirova, Laima] Latvian Biomed Res & Study Ctr, Riga, Latvia.
[Imyanitov, Evgeny] NN Petrov Inst Oncol, St Petersburg, Russia.
[Blanco, Ignacio; Lazaro, Conxi] Catalan Inst Oncol IDIBELL, Hereditary Canc Program, Barcelona, Spain.
[Ramus, Susan J.] Univ London Imperial Coll Sci Technol & Med, Gynaecol Oncol Unit, UCL EGA Inst Womens Hlth, London, England.
[Sucheston, Lara] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Karlan, Beth Y.; Gross, Jenny] Cedars Sinai Med Ctr, Womens Canc Res Inst, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Schmutzler, Rita; Wappenschmidt, Barbara] Univ Cologne, Ctr Familial Breast & Ovarian Canc, Dept Obstet & Gynaecol, Cologne, Germany.
[Schmutzler, Rita; Wappenschmidt, Barbara] Univ Cologne, CIO, Cologne, Germany.
[Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany.
[Meindl, Alfons; Lochmann, Magdalena] Tech Univ Munich, Klinikum Rechts Isar, Dept Obstet & Gynaecol, Div Tumor Genet, D-8000 Munich, Germany.
[Arnold, Norbert] Univ Kiel, Dept Obstet & Gynaecol, Univ Hosp Schleswig Holstein, Kiel, Germany.
[Heidemann, Simone] Univ Kiel, Inst Human Genet, Univ Hosp Schleswig Holstein, Kiel, Germany.
[Varon-Mateeva, Raymonda] Campus Virchow Klinikum, Charite Berlin, Inst Human Genet, Berlin, Germany.
[Niederacher, Dieter] Univ Dusseldorf, Dept Obstet & Gynaecol, Div Mol Genet, Univ Hosp Dusseldorf, Dusseldorf, Germany.
[Sutter, Christian] Univ Heidelberg, Inst Human Genet, Div Mol Diagnost, Heidelberg, Germany.
[Deissler, Helmut] Univ Hosp Ulm, Dept Obstet & Gynaecol, Ulm, Germany.
[Gadzicki, Dorothea] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany.
[Preisler-Adams, Sabine] Univ Hosp Muenster, Inst Human Genet, Munster, Germany.
[Kast, Karin] Tech Univ Dresden, Dept Obstet & Gynaecol, Univ Hosp Carl Gustav Carus, Dresden, Germany.
[Schoenbuchner, Ines] Univ Wurzburg, Inst Human Genet, Div Med Genet, Wurzburg, Germany.
[Caldes, Trinidad; de la Hoya, Miguel] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain.
[Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland.
[Aittomaeki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland.
[Simard, Jacques] Ctr Hosp Univ Quebec, Canada Res Chair Oncogenet, Canc Genom Lab, Quebec City, PQ, Canada.
[Simard, Jacques] Univ Laval, Quebec City, PQ, Canada.
[Spurdle, Amanda B.; Holland, Helene; Chen, Xiaoqing] Familial Breast Canc Peter MacCallum Canc Ctr, Kathleen Cuningham Consortium Res, Melbourne, Vic, Australia.
RP Antoniou, AC (reprint author), Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England.
EM antonis@srl.cam.ac.uk
RI Osorio, Ana/I-4324-2014; Ehrencrona, Hans/M-5619-2014; Jakubowska,
Anna/O-8050-2014; GLADIEFF, Laurence/O-5129-2014; Ligtenberg,
Marjolijn/N-9666-2013; manoukian, siranoush/E-7132-2017; Peissel,
Bernard/E-8187-2017; Oosterwijk, Jan C./G-5770-2011; Arnold,
Norbert/E-3012-2010; Lester, Jenny/B-5933-2012; Toland,
Amanda/E-4202-2011; montagna, marco/E-2225-2012; Leroux,
Dominique/G-7309-2014; Hereditario, Cancer/E-3311-2012; M Isabel,
Tejada/E-2394-2012; Andrulis, Irene/E-7267-2013; Sunde,
Lone/H-7402-2013; Hoogerbrugge, Nicoline/O-1016-2013; Radice,
Paolo/O-3119-2013; Blanco, Ignacio/D-2565-2013; Spurdle,
Amanda/A-4978-2011;
OI Osorio, Ana/0000-0001-8124-3984; Ehrencrona, Hans/0000-0002-5589-3622;
GLADIEFF, Laurence/0000-0002-6980-9719; Ligtenberg,
Marjolijn/0000-0003-1290-1474; manoukian, siranoush/0000-0002-6034-7562;
Peissel, Bernard/0000-0001-9233-3571; Nordling,
Margareta/0000-0002-4047-4994; Eeles, Rosalind/0000-0002-3698-6241;
Nathanson, Katherine/0000-0002-6740-0901; TEJADA,
Maria-Isabel/0000-0002-7334-1864; Arnold, Norbert/0000-0003-4523-8808;
montagna, marco/0000-0002-4929-2150; Blanco,
Ignacio/0000-0002-7414-7481; VENAT-BOUVET, Laurence/0000-0002-0716-2550;
Evans, Gareth/0000-0002-8482-5784; Ramus, Susan/0000-0003-0005-7798;
Spurdle, Amanda/0000-0003-1337-7897; Sunde, Lone/0000-0002-8479-165X;
Kleibl, Zdenek/0000-0003-2050-9667; Nevanlinna,
Heli/0000-0002-0916-2976; Kirchhoff, Tomas/0000-0002-9055-2364
FU Cancer Research UK; Associazione Italiana per la Ricerca sul Cancro
FX The Consortium of Investigators of Modifiers of BRCA1/2 is supported by
grants from Cancer Research UK. All study-specific grants are listed in
the acknowledgments section.
NR 26
TC 94
Z9 95
U1 4
U2 21
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 2010
VL 70
IS 23
BP 9742
EP 9754
DI 10.1158/0008-5472.CAN-10-1907
PG 13
WC Oncology
SC Oncology
GA 690YJ
UT WOS:000285045900024
PM 21118973
ER
PT J
AU Bauer, EM
Qin, Y
Miller, TW
Bandle, RW
Csanyi, G
Pagano, PJ
Bauer, PM
Schnermann, J
Roberts, DD
Isenberg, JS
AF Bauer, Eileen M.
Qin, Yan
Miller, Thomas W.
Bandle, Russell W.
Csanyi, Gabor
Pagano, Patrick J.
Bauer, Philip M.
Schnermann, Jurgen
Roberts, David D.
Isenberg, Jeff S.
TI Thrombospondin-1 supports blood pressure by limiting eNOS activation and
endothelial-dependent vasorelaxation
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Thrombospondin-1; eNOS; CD47; Vasorelaxation; Blood pressure
ID VASCULAR SMOOTH-MUSCLE; INTEGRIN-ASSOCIATED PROTEIN; NITRIC-OXIDE
SYNTHASE; CELL RESPONSES; IN-VIVO; L-NAME; CA2+; ACETYLCHOLINE;
RELAXATION; PLATELET
AB Thrombospondin-1 (TSP1), via its necessary receptor CD47, inhibits nitric oxide (NO)-stimulated soluble guanylate cyclase activation in vascular smooth muscle cells, and TSP1-null mice have increased shear-dependent blood flow compared with wild-type mice. Yet, the endothelial basement membrane should in theory function as a barrier to diffusion of soluble TSP1 into the arterial smooth muscle cell layer. These findings suggested that endothelial-dependent differences in blood flow in TSP1-null mice may be the result of direct modulation of endothelial NO synthase (eNOS) activation by circulating TSP1. Here we tested the hypothesis that TSP1 inhibits eNOS activation and endothelial-dependent arterial relaxation.
Acetylcholine (ACh)-stimulated activation of eNOS and agonist-driven calcium transients in endothelial cells were inhibited by TSP1. TSP1 also inhibited eNOS phosphorylation at serine(1177). TSP1 treatment of the endothelium of wild-type and TSP1-null but not CD47-null arteries inhibited ACh-stimulated relaxation. TSP1-null vessels demonstrated greater endothelial-dependent vasorelaxation compared with the wild type. Conversely, TSP1-null arteries demonstrated less vasoconstriction to phenylephrine compared with the wild type, which was corrected upon inhibition of eNOS. In TSP1-null mice, intravenous TSP1 blocked ACh-stimulated decreases in blood pressure, and both intravenous TSP1 and a CD47 agonist antibody acutely elevated blood pressure in mice.
TSP1, via CD47, inhibits eNOS activation and endothelial-dependent arterial relaxation and limits ACh-driven decreases in blood pressure. Conversely, intravenous TSP1 and a CD47 antibody increase blood pressure. These findings suggest that circulating TSP1, by limiting endogenous NO production, functions as a pressor agent supporting blood pressure.
C1 [Bauer, Eileen M.; Csanyi, Gabor; Pagano, Patrick J.; Isenberg, Jeff S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15260 USA.
[Isenberg, Jeff S.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA.
[Pagano, Patrick J.; Isenberg, Jeff S.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA.
[Bauer, Philip M.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA.
[Qin, Yan; Schnermann, Jurgen] NIDDKD, Kidney Dis Branch, Bethesda, MD 20892 USA.
[Miller, Thomas W.; Bandle, Russell W.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Isenberg, JS (reprint author), Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15260 USA.
EM jsi5@pitt.edu
RI Roberts, David/A-9699-2008; Miller, Thomas/G-1215-2011
OI Roberts, David/0000-0002-2481-2981; Miller, Thomas/0000-0001-8645-2785
FU NIH [K22 CA128616]; NIH, NCI, Center for Cancer Research; NIDDK
FX NIH grant K22 CA128616 (J.S.I.) and Intramural Research Program of the
NIH, NCI, Center for Cancer Research (D.D.R.), and NIDDK (J.S.).
NR 45
TC 44
Z9 45
U1 2
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
EI 1755-3245
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD DEC
PY 2010
VL 88
IS 3
BP 471
EP 481
DI 10.1093/cvr/cvq218
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 676OX
UT WOS:000283923000013
PM 20610415
ER
PT J
AU Stuelten, CH
Salomon, D
AF Stuelten, Christina H.
Salomon, David
TI miR-31 in cancer: Location matters
SO CELL CYCLE
LA English
DT Editorial Material
ID SATB2; FIBROBLASTS; EXPRESSION
C1 [Stuelten, Christina H.; Salomon, David] NCI, NIH, Bethesda, MD 20892 USA.
RP Stuelten, CH (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM chrisstu@mail.nih.gov
NR 9
TC 6
Z9 6
U1 1
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 2010
VL 9
IS 23
BP 4608
EP 4609
DI 10.4161/cc.9.23.13928
PG 2
WC Cell Biology
SC Cell Biology
GA 688ES
UT WOS:000284833200004
PM 21260945
ER
PT J
AU Shen, WX
Ahmad, F
Hockman, S
Ma, J
Omi, H
Raghavachari, N
Manganiello, V
AF Shen, Weixing
Ahmad, Faiyaz
Hockman, Steven
Ma, John
Omi, Hitoshi
Raghavachari, Nalini
Manganiello, Vincent
TI Female infertility in PDE3A(-/-) mice Polo-like kinase 1 (Plk1) may be a
target of protein kinase A (PKA) and involved in meiotic arrest of
oocytes from PDE3A(-/-) mice
SO CELL CYCLE
LA English
DT Article
DE mice oocytes; PDE3A; cAMP; PKA; polo-like kinase 1; centrosome; prophase
arrested
ID HISTONE H3 PHOSPHORYLATION; CELL-CYCLE ARREST; MOUSE OOCYTE;
SUBCELLULAR-LOCALIZATION; CYTOPLASMIC ACCUMULATION; CHROMOSOME
CONDENSATION; CDC25B PHOSPHATASE; SPINDLE CHECKPOINT; INHIBITORY KINASE;
XENOPUS OOCYTES
AB Mechanisms of cAMP/PKA-induced meiotic arrest in oocytes are not completely identified. In cultured, G(2)/M-arrested PDE3A(-/-) murine oocytes, elevated PKA activity was associated with inactivation of Cdc2 and Plk1, and inhibition of phosphorylation of histone H3 (S10) and of dephosphorylation of Cdc25B (S323) and Cdc2 (Thr14/Tyr15). In cultured WT oocytes, PKA activity was transiently reduced and then increased to that observed in PDE3A(-/-) oocytes; Cdc2 and Plk1 were activated, phosphorylation of histone H3 (S10) and dephosphorylation of Cdc25B (S323) and Cdc2 (Thr14/Tyr15) were observed. In WT oocytes, PKAc were rapidly translocated into nucleus, and then to the spindle apparatus, but in PDE3A(-/-) oocytes, PKAc remained in the cytosol. Plk1 was reactivated by incubation of PDE3A(-/-) oocytes with PKA inhibitor, Rp-cAMPS. PDE3A was co-localized with Plk1 in WT oocytes, and co-immunoprecipitated with Plk1 in WT ovary and Hela cells. PKAc phosphorylated rPlk1 and Hela cell Plk1 and inhibited Plk1 activity in vitro. Our results suggest that PKA-induced inhibition of Plk1 may be critical in oocyte meiotic arrest and female infertility in PDE3A(-/-) mice.
C1 [Shen, Weixing; Ahmad, Faiyaz; Hockman, Steven; Ma, John; Omi, Hitoshi; Manganiello, Vincent] NHLBI, TMB, NIH, Bethesda, MD 20892 USA.
[Raghavachari, Nalini] NHLBI, Genom Core Facil, PVMB, NIH, Bethesda, MD 20892 USA.
RP Manganiello, V (reprint author), NHLBI, TMB, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM manganiv@nhlbi.nih.gov
FU NHLBI
FX This research was funded by the NHLBI Intramural Research Program.
NR 82
TC 9
Z9 11
U1 1
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 2010
VL 9
IS 23
BP 4720
EP 4734
DI 10.4161/cc.9.23.14090
PG 15
WC Cell Biology
SC Cell Biology
GA 688ES
UT WOS:000284833200022
PM 21099356
ER
PT J
AU Won, M
Park, KA
Byun, HS
Sohn, KC
Kim, YR
Jeon, J
Hong, JH
Park, J
Seok, JH
Kim, JM
Yoon, WH
Jang, IS
Shen, HM
Liu, ZG
Hur, GM
AF Won, M.
Park, K. A.
Byun, H. S.
Sohn, K-C
Kim, Y-R
Jeon, J.
Hong, J. H.
Park, J.
Seok, J. H.
Kim, J. M.
Yoon, W-H
Jang, I-S
Shen, H. M.
Liu, Z. G.
Hur, G. M.
TI Novel anti-apoptotic mechanism of A20 through targeting ASK1 to suppress
TNF-induced JNK activation
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
DE TNF receptor; JNK; NF-kappa B; apoptosis; cellular signaling
ID NF-KAPPA-B; ZINC-FINGER PROTEIN; ALPHA-INDUCED APOPTOSIS; NECROTIC
CELL-DEATH; DEPENDENT ACTIVATION; SIGNAL-TRANSDUCTION; FAMILY PROTEINS;
MAP KINASES; UBIQUITINATION; INHIBITION
AB The zinc-finger protein A20 has crucial physiological functions as a dual inhibitor of nuclear factor-kappa B (NF-kappa B) activation and apoptosis in tumor necrosis factor (TNF) receptor 1 signaling pathway. Although the molecular basis for the anti-NF-kappa B function of A20 has been well elucidated, the anti-apoptotic function of A20 is largely unknown. Here, we report a novel mechanism underlying the anti-apoptotic function of A20: A20 blocks TNF-induced apoptosis through suppression of c-jun N-terminal kinase (JNK) by targeting apoptosis signal-regulating kinase1 (ASK1). First, the ectopic expression of A20 drastically inhibits TNF-induced JNK activation and apoptosis in multiple cell types including those deficient of NF-kappa B activation. Unexpectedly, the blunting effect of A20 on TNF-induced JNK activation is not mediated by affecting the TNFR1 signaling complex formation. Instead, A20 interacts with ASK1, an important MAPKK kinase in the JNK signaling cascade. More importantly, overexpression of wild-type A20, but not of mutant A20 (ZnF4; C624A, C627A), promotes degradation of the ASK1 through the ubiquitin-proteasome system. Taken together, the results from this study reveal a novel anti-apoptotic mechanism of A20 in TNF signaling pathway: A20 binds to ASK1 and mediates ASK1 degradation, leading to suppression of JNK activation and eventually blockage of apoptosis. Cell Death and Differentiation (2010) 17, 1830-1841; doi:10.1038/cdd.2010.47; published online 7 May 2010
C1 [Won, M.; Park, K. A.; Byun, H. S.; Kim, Y-R; Jeon, J.; Hong, J. H.; Park, J.; Seok, J. H.; Hur, G. M.] Chungnam Natl Univ, Daejeon Reg Canc Ctr, Infect Signaling Network Res Ctr, Dept Pharmacol,Res Inst Med Sci,Coll Med, Taejon 301131, South Korea.
[Sohn, K-C] Chungnam Natl Univ, Coll Med, Dept Dermatol, Taejon 301131, South Korea.
[Kim, J. M.] Chungnam Natl Univ, Coll Med, Dept Pathol, Taejon 301131, South Korea.
[Yoon, W-H] Chungnam Natl Univ, Coll Med, Dept Biochem, Taejon 301131, South Korea.
[Jang, I-S] Chungnam Natl Univ, Coll Med, Dept Surg, Taejon 301131, South Korea.
[Shen, H. M.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol & Publ Hlth, Singapore 117595, Singapore.
[Liu, Z. G.] NCI, Cell & Cellular Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hur, GM (reprint author), Chungnam Natl Univ, Daejeon Reg Canc Ctr, Infect Signaling Network Res Ctr, Dept Pharmacol,Res Inst Med Sci,Coll Med, 6 Munhwa Dong, Taejon 301131, South Korea.
EM gmhur@cnu.ac.kr
RI SHEN, Han-Ming/B-5942-2011
OI SHEN, Han-Ming/0000-0001-7369-5227
FU Ministry of Science & Technology in Korea [FG06-2-17]; MEST
[20090079064]; Infection Signaling Network Research Center at Chungnam
National University [R13-2007-020-01002-0]; National R&D Program for
Cancer Control Ministry of Health & Welfare, Repubic of Korea [0720560]
FX We thank Dr. H Ichijo for ASK1-/- MEFs. This work was supported by Grant
FG06-2-17 of the 21C Frontier Functional Human Genome Project from the
Ministry of Science & Technology in Korea, by the grant 20090079064 from
NRF of Korea grant funded by the MEST, by the Infection Signaling
Network Research Center (R13-2007-020-01002-0) at Chungnam National
University, and a grant from the National R&D Program for Cancer Control
Ministry of Health & Welfare, Repubic of Korea (No. 0720560).
NR 42
TC 35
Z9 36
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD DEC
PY 2010
VL 17
IS 12
BP 1830
EP 1841
DI 10.1038/cdd.2010.47
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 680CI
UT WOS:000284209600004
PM 20448643
ER
PT J
AU Moore, NM
Calcagno, AM
Hanlon, S
Nagahara, LA
Kuhn, NZ
AF Moore, Nicole M.
Calcagno, Anna Maria
Hanlon, Sean
Nagahara, Larry A.
Kuhn, Nastaran Z.
TI Physical Sciences-Oncology Centers: Bridging Engineers and Oncologists
for a New Perspective on Fighting Cancer
SO CELLULAR AND MOLECULAR BIOENGINEERING
LA English
DT Editorial Material
ID GROWTH
C1 [Moore, Nicole M.; Calcagno, Anna Maria; Hanlon, Sean; Nagahara, Larry A.; Kuhn, Nastaran Z.] NCI, Ctr Strateg Sci Initiat, Off Phys Sci Oncol, Bethesda, MD 20892 USA.
RP Kuhn, NZ (reprint author), NCI, Ctr Strateg Sci Initiat, Off Phys Sci Oncol, Bethesda, MD 20892 USA.
EM nastaran.kuhn@nih.gov
RI Calcagno, Anna Maria/A-5617-2012;
OI Calcagno, Anna Maria/0000-0002-0804-2753
NR 8
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1865-5025
J9 CELL MOL BIOENG
JI Cell. Mol. Bioeng.
PD DEC
PY 2010
VL 3
IS 4
BP 334
EP 336
DI 10.1007/s12195-010-0144-9
PG 3
WC Cell & Tissue Engineering; Biophysics; Cell Biology
SC Cell Biology; Biophysics
GA 693GB
UT WOS:000285211500002
ER
PT J
AU Butkiewicz, D
Krzesniak, M
Vaitiekunaite, R
Sikora, B
Bowman, ED
Harris, CC
Rusin, M
AF Butkiewicz, Dorota
Krzesniak, Malgorzata
Vaitiekunaite, Rasa
Sikora, Bozena
Bowman, Elise D.
Harris, Curtis C.
Rusin, Marek
TI A functional analysis of G23A polymorphism and the alternative splicing
in the expression of the XPA gene
SO CELLULAR & MOLECULAR BIOLOGY LETTERS
LA English
DT Article
DE Single nucleotide polymorphism; XPA; Kozak sequence; Alternative
splicing; Cancer risk; Reporter assay
ID NUCLEOTIDE EXCISION-REPAIR; PIGMENTOSUM GROUP-A; CELL LUNG-CANCER;
XERODERMA-PIGMENTOSUM; DNA-REPAIR; HUMAN TISSUES; RISK; TRANSLATION;
POPULATION; PROTEIN
AB The XPA gene has a commonly occurring polymorphism (G23A) associated with cancer risk. This study assessed the functional significance of this polymorphism, which is localised near the translation start codon. Lymphoblastoid cell lines with alternative homozygous genotypes showed no significant differences in their XPA levels. The luciferase reporter assay detected no functional difference between the two sequences. Unexpectedly, we found that the alternatively spliced form of XPA mRNA lacked a part of exon 1. Only the reading frame downstream of codon Met59 was preserved. The alternative mRNA is expressed in various human tissues. The analysis of the 5'cDNA ends showed similar transcription start sites for the two forms. The in vitro expression of the alternative XPA labelled with the red fluorescent protein (mRFP) showed a lack of preferential nuclear accumulation of the XPA isoform. The biological role of the alternative XPA mRNA form remains to be elucidated.
C1 [Butkiewicz, Dorota; Krzesniak, Malgorzata; Vaitiekunaite, Rasa; Sikora, Bozena; Rusin, Marek] Maria Sklodowska Curie Mem Canc Ctr, Dept Tumor Biol, PL-44101 Gliwice, Poland.
[Bowman, Elise D.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
[Butkiewicz, Dorota; Krzesniak, Malgorzata; Vaitiekunaite, Rasa; Sikora, Bozena; Rusin, Marek] Inst Oncol, Gliwice Branch, PL-44101 Gliwice, Poland.
RP Rusin, M (reprint author), Maria Sklodowska Curie Mem Canc Ctr, Dept Tumor Biol, Wybrzeze Armii Krajowej 15, PL-44101 Gliwice, Poland.
EM rusinm@rocketmail.com
FU Polish State Committee for Scientific Research (KBN) [4P05A 062 17,
3P04A 004 23]; Polish-American M. Sklodowska-Curie Fund [MZ/HHS-97-313];
Department of Tumour Biology [9/2000]; National Cancer Institute -
Office for International Affairs, NIH, Bethesda, MD, USA
FX The authors would like to thank Mrs. Iwona Matuszczyk and Ms. Helena
Paterak for their excellent technical assistance. The editorial
assistance of Mrs. Dorothea Dudek-Creaven is also appreciated. The study
was supported by the Polish State Committee for Scientific Research
(KBN) grant no. 4P05A 062 17 and grant no. 3P04A 004 23, Polish-American
M. Sklodowska-Curie Fund grant no. MZ/HHS-97-313, UICC Fellowship Award
9/2000 to Marek Rusin and Fellowship Program at Department of Tumour
Biology, supported by the National Cancer Institute - Office for
International Affairs, NIH, Bethesda, MD, USA to Rasa Vaitiekunaite.
NR 41
TC 4
Z9 4
U1 0
U2 1
PU VERSITA
PI WARSAW
PA SOLIPSKA 14A-1, 02-482 WARSAW, POLAND
SN 1425-8153
J9 CELL MOL BIOL LETT
JI Cell. Mol. Biol. Lett.
PD DEC
PY 2010
VL 15
IS 4
BP 611
EP 629
DI 10.2478/s11658-010-0032-2
PG 19
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 654NM
UT WOS:000282175000008
PM 20865363
ER
PT J
AU Ahmad, IM
Mustafa, EH
Mustafa, NH
Tahtamouni, LH
Abdalla, MY
AF Ahmad, Iman M.
Mustafa, Ebtihal H.
Mustafa, Noor H.
Tahtamouni, Lubna H.
Abdalla, Maher Y.
TI 2DG enhances the susceptibility of breast cancer cells to doxorubicin
SO CENTRAL EUROPEAN JOURNAL OF BIOLOGY
LA English
DT Article
DE 2DG; Doxorubicin; Oxidative stress; Breast cancer; GSH; BSO
ID CARCINOMA MCF-7/ADR CELLS; HUMAN TUMOR-CELLS; OXIDATIVE STRESS; GLUCOSE
DEPRIVATION; GLUTATHIONE DISULFIDE; CYCLE PROGRESSION; HUMAN HEAD;
2-DEOXY-D-GLUCOSE; CYTOTOXICITY; ADRIAMYCIN
AB 2DG causes cytotoxicity in cancer cells by disrupting thiol metabolism while Doxorubicin (DOX) induces cytotoxicity in tumor cells by generating reactive oxygen species (ROS). Here we examined the combined cytotoxic action of 2DG and DOX in rapidly dividing T47D breast cancer cells vs. slowly growing MCF-7 breast cancer cells. T47D cells exposed to the combination of 2DG/DOX significantly decreased cell survival compared to controls, while 2DG/DOX had no effect on MCF-7 cells. 2DG/DOX also disrupted the oxidant status of T47D treated cells, decreased intracellular total glutathione and increased glutathione disulfide (%GSSG) compared to MCF-7 cells. Lipid peroxidation increased in T47D cells treated with 2DG and/or DOX, but not in MCF-7 cells. T47D cells were significantly protected by NAC, indicating that the combined treatment exerts its action by increasing ROS production and disrupting antioxidant stores. When we inhibited glutathione synthesis with BSO, T47D cells became more sensitive to 2DG/DOX-induced cytotoxicity, but NAC significantly reversed this cytotoxic effect. Finally, 2DG/DOX, and BSO significantly increased the %GSSG in T47D cells, an effect which was also reversed by NAC. Our results suggest that exposure of rapidly dividing breast cancer cells to 2DG/DOX enhances cytotoxicity via oxidative stress and via disruptions to thiol metabolism.
C1 [Ahmad, Iman M.] Hashemite Univ, Dept Radiog, Allied Hlth Sci Fac, Al Zarqa 13115, Jordan.
[Mustafa, Ebtihal H.; Mustafa, Noor H.; Tahtamouni, Lubna H.; Abdalla, Maher Y.] Hashemite Univ, Dept Biol Sci & Biotechnol, Fac Sci, Al Zarqa 13115, Jordan.
[Abdalla, Maher Y.] NCI, Vaccine Branch, Ctr Canc Res, Natl Naval Med Ctr, Bethesda, MD 20889 USA.
RP Ahmad, IM (reprint author), Hashemite Univ, Dept Radiog, Allied Hlth Sci Fac, Al Zarqa 13115, Jordan.
EM abdallamy@mail.nih.gov
FU The Deanship of Research and Graduate Studies; The Hashemite University
FX This work was supported by a grant from The Deanship of Research and
Graduate Studies, The Hashemite University.
NR 47
TC 5
Z9 5
U1 1
U2 3
PU VERSITA
PI WARSAW
PA SOLIPSKA 14A-1, 02-482 WARSAW, POLAND
SN 1895-104X
J9 CENT EUR J BIOL
JI Cent. Eur. J. Biol.
PD DEC
PY 2010
VL 5
IS 6
BP 739
EP 748
DI 10.2478/s11535-010-0060-y
PG 10
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 653WE
UT WOS:000282127800001
ER
PT J
AU Kravitz, DJ
Kriegeskorte, N
Baker, CI
AF Kravitz, Dwight J.
Kriegeskorte, Nikolaus
Baker, Chris I.
TI High-Level Visual Object Representations Are Constrained by Position
SO CEREBRAL CORTEX
LA English
DT Article
DE behavior; fMRI; object recognition; position invariance; vision
ID INFERIOR TEMPORAL CORTEX; INFEROTEMPORAL CORTEX; RETINAL POSITION;
RECOGNITION; INVARIANCE; MACAQUE; SHAPE; TRANSLATION; NEURONS;
INFORMATION
AB It is widely assumed that high-level visual object representations are position-independent (or invariant). While there is sensitivity to position in high-level object-selective cortex, position and object identity are thought to be encoded independently in the population response such that position information is available across objects and object information is available across positions. Contrary to this view, we show, with both behavior and neuroimaging, that visual object representations are position-dependent (tied to limited portions of the visual field). Behaviorally, we show that the effect of priming an object was greatly reduced with any change in position (within- or between-hemifields), indicating nonoverlapping representations of the same object across different positions. Furthermore, using neuroimaging, we show that object-selective cortex is not only highly sensitive to object position but also the ability to differentiate objects based on its response is greatly reduced across different positions, consistent with the observed behavior and the receptive field properties observed in macaque object-selective neurons. Thus, even at the population level, the object information available in response of object-selective cortex is constrained by position. We conclude that even high-level visual object representations are position-dependent.
C1 [Kravitz, Dwight J.; Kriegeskorte, Nikolaus; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Kravitz, DJ (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
EM kravitzd@mail.nih.gov
RI Kravitz, Dwight/B-8430-2012;
OI Kriegeskorte, Nikolaus/0000-0001-7433-9005; Baker,
Chris/0000-0001-6861-8964
FU National Institute of Mental Health
FX National Institute of Mental Health Intramural Research Program.
NR 37
TC 80
Z9 80
U1 0
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD DEC
PY 2010
VL 20
IS 12
BP 2916
EP 2925
DI 10.1093/cercor/bhq042
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 679LG
UT WOS:000284162300014
PM 20351021
ER
PT J
AU Meister, IG
Foltys, H
Gallea, C
Hallett, M
AF Meister, Ingo G.
Foltys, Henrik
Gallea, Cecile
Hallett, Mark
TI How the Brain Handles Temporally Uncoupled Bimanual Movements
SO CEREBRAL CORTEX
LA English
DT Article
DE coordination; fMRI; functional connectivity; hand movement
ID SEQUENTIAL FINGER MOVEMENTS; CEREBRAL-BLOOD-FLOW; CORPUS-CALLOSUM;
FUNCTIONAL MRI; MOTOR AREAS; PARIETAL LOBE; MEDIAL WALL; COORDINATION;
CORTEX; ACTIVATION
AB Whereas the cerebral representation of bimanual spatial coordination has been subject to prior research, the networks mediating bimanual temporal coordination are still unclear. The present study used functional imaging to investigate cerebral networks mediating temporally uncoupled bimanual finger movements. Three bimanual tasks were designed for the execution of movements with different timing and amplitude, with same timing but different amplitude, and with same timing and amplitude. Functional magnetic resonance imaging results showed an increase of activation within right premotor and dorsolateral prefrontal, bilateral inferior parietal, basal ganglia, and cerebellum areas related to temporally uncoupled bilateral finger movements. Further analyses showed a decrease of connectivity between homologous primary hand motor regions. In contrast, there was an increase of connectivity between motor regions and anterior cingulate, premotor and posterior parietal regions during bimanual movements that were spatially or both temporally and spatially uncoupled, compared with bimanual movements that were both spatially and temporally coupled. These results demonstrate that the extent of bihemispheric coupling of M1 areas is related to the degree of temporal synchronization of bimanual finger movements. Furthermore, inferior parietal and premotor regions play a key role for the implementation not only of spatial but also of temporal movement parameters in bimanual coordination.
C1 [Meister, Ingo G.] Univ Hosp Cologne, Dept Neurol, D-50924 Cologne, Germany.
[Foltys, Henrik; Gallea, Cecile; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Foltys, Henrik] Rhein Westfal TH Aachen, Dept Neurol, D-52074 Aachen, Germany.
RP Meister, IG (reprint author), Univ Hosp Cologne, Dept Neurol, Kerpener Str 62, D-50924 Cologne, Germany.
EM igmeister@gmx.de
RI Meister, Ingo/A-3642-2008
FU University of Aachen; Medical Faculty of the University of Aachen;
National Institute of Neurological Disorders and Stroke, National
Institutes of Health; Deutsche Forschungsgemeinschaft (German Research
Organisation) [ME 2104/3-1]
FX "Rotationsprogramm'' of the Medical Faculty of the University of Aachen
to H.F.; Interdisziplinares Zentrum fur Klinische Forschung of the
Medical Faculty of the University of Aachen and the Intramural Program
of the National Institute of Neurological Disorders and Stroke, National
Institutes of Health; Deutsche Forschungsgemeinschaft (German Research
Organisation, grant ME 2104/3-1 to I.G.M.).
NR 47
TC 10
Z9 10
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD DEC
PY 2010
VL 20
IS 12
BP 2996
EP 3004
DI 10.1093/cercor/bhq048
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 679LG
UT WOS:000284162300021
PM 20356959
ER
PT J
AU Bharate, SB
Thompson, CM
AF Bharate, Sandip B.
Thompson, Charles M.
TI Antimicrobial, Antimalarial, and Antileishmanial Activities of Mono- and
Bis-quaternary Pyridinium Compounds
SO CHEMICAL BIOLOGY & DRUG DESIGN
LA English
DT Letter
DE antileishmanial; antimalarial; antimicrobial; biological threats;
pyridinium oximes
ID RECOMBINANT HUMAN ACETYLCHOLINESTERASE; INHIBITED ELECTRIC-EEL;
PLASMODIUM-FALCIPARUM; ANTIPARASITIC COMPOUNDS; REACTIVATION POTENCY;
HEALTHY-VOLUNTEERS; OXIMES; SALTS; TOLERANCE; MOLECULES
AB Pyridinium-based oxime compounds have been utilized worldwide as antidotes following exposure to anticholinesterase agents. In the event of combined chemical and biological incident, it is of vital importance to know the ability of antidotes to provide additional protection against biological threats. This paper reports results of in vitro antimicrobial and antiprotozoal activities of a series of quaternary pyridinium oximes against a number of lower pathogenicity BSL-1 and 2 agents. In general, our compound panel had little to no antimicrobial action except for thiophene- and benzothiophene-substituted monoquaternary pyridinium compounds 21 and 24 that showed moderate antibacterial activity against Staphylococus aureus and methicillin-resistant S. aureus with IC(50) values ranging from 12.2 to 17.7 mu g/mL. Compounds 21 and 24 also exhibited antileishmanial activity against Leishmania donovani with IC(50) values of 19 and 18 mu g/mL, respectively. Another monoquaternary pyridinium compound with a bromobutyl side chain 17 showed antimalarial activity against both a chloroquine sensitive and resistant strains of Plasmodium falciparum with IC(50) values of 3.7 and 4.0 mu g/mL, respectively. None of the bisquaternary pyridinium compounds showed antimicrobial or antiprotozoal activity. None of the compounds showed cytotoxic effects toward mammalian kidney fibroblasts. Results of this study indicate that the pyridinium compounds, some of which are already in use as antidotes, do not have significant antimicrobial and antiprotozoal activities and cannot be relied upon for additional protection in the event of combined chemical-biological incident.
C1 [Bharate, Sandip B.; Thompson, Charles M.] Univ Montana, Dept Biomed & Pharmaceut Sci, NIH COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA.
[Thompson, Charles M.] ATERIS Technol LLC, Missoula, MT 59802 USA.
RP Thompson, CM (reprint author), Univ Montana, Dept Biomed & Pharmaceut Sci, NIH COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA.
EM charles.thompson@umontana.edu
FU NCRR NIH HHS [P20 RR015583-10, P20 RR015583, P20-RR015583]; NIAID NIH
HHS [AI 27094, R01 AI027094-19, R01 AI027094]; NIEHS NIH HHS [R43
ES016392, U01-ES016102, U01 ES016102, R43 ES016392-02, U01 ES016102-03];
NINDS NIH HHS [P30-NS055022, U44 NS058229, P30 NS055022, P30
NS055022-02, U44 NS058229-02]
NR 30
TC 8
Z9 8
U1 0
U2 5
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1747-0277
J9 CHEM BIOL DRUG DES
JI Chem. Biol. Drug Des.
PD DEC
PY 2010
VL 76
IS 6
BP 546
EP 551
DI 10.1111/j.1747-0285.2010.01035.x
PG 6
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 679OF
UT WOS:000284170000011
PM 21040494
ER
PT J
AU Lam, CSP
Liu, XA
Yang, QO
Larson, MG
Pencina, MJ
Aragam, J
Redfield, MM
Benjamin, EJ
Vasan, RS
AF Lam, Carolyn S. P.
Liu, Xuan
Yang, Qiong
Larson, Martin G.
Pencina, Michael J.
Aragam, Jayashri
Redfield, Margaret M.
Benjamin, Emelia J.
Vasan, Ramachandran S.
TI Familial Aggregation of Left Ventricular Geometry and Association With
Parental Heart Failure The Framingham Heart Study
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE echocardiography; remodeling; risk factors
ID MYOCARDIAL-INFARCTION; GENDER-DIFFERENCES; MASS; HYPERTROPHY; DISEASE;
HYPERTENSION; RISK; ECHOCARDIOGRAPHY; THERAPY; OBESITY
AB Background-Data regarding the familial aggregation of left ventricular (LV) geometry and its relations to parental heart failure (HF) are limited.
Methods and Results-We evaluated concordance of LV geometry within 1093 nuclear families in 5758 participants of the original (parents) (n=2351) and offspring (n=3407) cohorts of the Framingham Heart Study undergoing routine echocardiography in mid-to late adulthood. LV geometry was categorized based on cohort-and sex-specific 80th percentile cutoffs of LV mass and relative wall thickness (RWT) into normal (both <80th percentile), concentric remodeling (LV mass <80th percentile; RWT >80th percentile), concentric hypertrophy (both >80th percentile), and eccentric hypertrophy (LV mass >80th percentile; RWT <80th percentile). Within nuclear families, LV geometry was concordant among related pairs (parent-child, sibling-sibling) (P=0.0015) but not among unrelated spousal pairs (P=0.60), a finding that remained unchanged after adjusting for clinical covariates known to influence LV remodeling (age, systolic blood pressure, body mass index), excluding individuals with prevalent HF and myocardial infarction, and varying the thresholds for defining LV geometry. The prevalence of abnormal LV geometry was higher in family members of affected individuals, with recurrence risks of 1.4 for concentric remodeling (95% CI, 1.2 to 1.7) and eccentric hypertrophy (95% CI, 1.1 to 1.8) and 3.9 (95% CI, 3.2 to 4.6) for concentric hypertrophy. In a subset of 1497 offspring, we observed an association between parental HF (n=458) and eccentric hypertrophy in offspring (P<0.0001).
Conclusions-Our investigation of a 2-generational community-based sample demonstrates familial aggregation of LV geometry, with the greatest recurrence risk for concentric LV geometry, and establishes an association between eccentric LV geometry and parental HF. (Circ Cardiovasc Genet. 2010;3:492-498.)
C1 [Lam, Carolyn S. P.; Larson, Martin G.; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Liu, Xuan; Yang, Qiong; Pencina, Michael J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Aragam, Jayashri] Harvard Univ, Sch Med, Boston, MA USA.
[Lam, Carolyn S. P.; Redfield, Margaret M.] Mayo Clin, Rochester, MN USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA.
RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
EM vasan@bu.edu
RI Yang, Qiong/G-5438-2014;
OI Larson, Martin/0000-0002-9631-1254; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336
FU National Heart, Lung, and Blood Institute [N01-HC-25195]; [6R01-NS
17950]; [R01HL080124]
FX This work was supported by National Heart, Lung, and Blood Institute
contract N01-HC-25195 and grants 6R01-NS 17950 and R01HL080124 (to Dr
Vasan).
NR 36
TC 12
Z9 13
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD DEC
PY 2010
VL 3
IS 6
BP 492
EP 498
DI 10.1161/CIRCGENETICS.110.941088
PG 7
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 694KG
UT WOS:000285295600003
PM 20884845
ER
PT J
AU van Loon, JE
Leebeek, FWG
Deckers, JW
Dippel, DWJ
Poldermans, D
Strachan, DP
Tang, WH
O'Donnell, CJ
Smith, NL
de Maat, MPM
AF van Loon, Janine E.
Leebeek, Frank W. G.
Deckers, Jaap W.
Dippel, Diederik W. J.
Poldermans, Don
Strachan, David P.
Tang, Weihong
O'Donnell, Christopher J.
Smith, Nicholas L.
de Maat, Moniek P. M.
TI Effect of Genetic Variations in Syntaxin-Binding Protein-5 and
Syntaxin-2 on von Willebrand Factor Concentration and Cardiovascular
Risk
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE von Willebrand factor; genetics; STX2; STXBP5; cardiovascular diseases
ID VONWILLEBRAND-FACTOR; FACTOR-VIII; THROMBOSIS; EXOCYTOSIS; SECRETION;
ARTERIAL; TWIN; AGE
AB Background-Elevated von Willebrand factor (VWF) plasma levels are associated with an increased risk of cardiovascular disease. A meta-analysis of genomewide association studies on VWF identified novel candidate genes, that is, syntaxin-binding protein 5 (STXBP5) and syntaxin 2 (STX2), which are possibly involved in the secretion of VWF. We investigated whether VWF antigen levels (VWF:Ag), VWF collagen-binding activity (VWF:CB) and the risk of arterial thrombosis are affected by common genetic variations in these genes.
Methods and Results-In 463 young white subjects (men <= 45 years of age and women <= 55 years of age), who were included 1 to 3 months after a first event of arterial thrombosis, and 406 control subjects, we measured VWF:Ag and VWF:CB. Nine haplotype tagging single-nucleotide polymorphisms of STXBP5 and STX2 were selected and subsequently analyzed using linear regression with additive genetic models adjusted for age, sex, and ABO blood group. The minor alleles of rs9399599 and rs1039084 in STXBP5 were associated with lower VWF plasma levels and activity, whereas the minor allele of rs7978987 in STX2 was associated with higher VWF plasma levels and activity. The minor alleles of the single-nucleotide polymorphisms in STX2 were associated with a reduced risk of arterial thrombosis (rs1236: odds ratio, 0.73 [95% confidence interval, 0.59, 0.89]; rs7978987: odds ratio, 0.81 [95% confidence interval, 0.65, 1.00]; rs11061158:odds ratio, 0.69 [95% confidence interval, 0.55, 0.88]).
Conclusions-Genetic variability in STXBP5 and STX2 affects both VWF concentration and activity in young individuals with premature arterial thrombosis. Furthermore, in our study, genetic variability in STX2 is associated with the risk of arterial thrombosis. However, at this point, the underlying mechanism remains unclear. (Circ Cardiovasc Genet. 2010; 3:507-512.)
C1 [van Loon, Janine E.; Leebeek, Frank W. G.; de Maat, Moniek P. M.] Erasmus Univ, Med Ctr, Dept Hematol, NL-3000 CA Rotterdam, Netherlands.
[Deckers, Jaap W.] Erasmus Univ, Med Ctr, Dept Cardiol, NL-3000 CA Rotterdam, Netherlands.
[Dippel, Diederik W. J.] Erasmus Univ, Med Ctr, Dept Neurol, NL-3000 CA Rotterdam, Netherlands.
Erasmus Univ, Med Ctr, Dept Vasc Surg, NL-3000 CA Rotterdam, Netherlands.
[Poldermans, Don] Erasmus Univ, Med Ctr, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands.
[Strachan, David P.] St Georges Univ London, Div Community Hlth Sci, London, England.
[Tang, Weihong] Univ Minnesota, Div Biostat Epidemiol & Community Hlth, Minneapolis, MN USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA.
[Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
RP de Maat, MPM (reprint author), Erasmus Univ, Med Ctr, Dept Hematol, Room L-431,POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM m.demaat@erasmusmc.nl
FU Netherlands Heart Foundation [2007B159]; Thrombosis Foundation Holland
[2010-3]
FX This work was supported by a grant of the Netherlands Heart Foundation
(2007B159) and the Thrombosis Foundation Holland (2010-3).
NR 18
TC 22
Z9 22
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD DEC
PY 2010
VL 3
IS 6
BP 507
EP 512
DI 10.1161/CIRCGENETICS.110.957407
PG 6
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 694KG
UT WOS:000285295600005
PM 21156930
ER
PT J
AU Yang, QO
Kottgen, A
Dehghan, A
Smith, AV
Glazer, NL
Chen, MH
Chasman, DI
Aspelund, T
Eiriksdottir, G
Harris, TB
Launer, L
Nalls, M
Hernandez, D
Arking, DE
Boerwinkle, E
Grove, ML
Li, M
Kao, WHL
Chonchol, M
Haritunians, T
Li, G
Lumley, T
Psaty, BM
Shlipak, M
Hwang, SJ
Larson, MG
O'Donnell, CJ
Upadhyay, A
van Duijn, CM
Hofman, A
Rivadeneira, F
Stricker, B
Uitterlinden, AG
Pare, G
Parker, AN
Ridker, PM
Siscovick, DS
Gudnason, V
Witteman, JC
Fox, CS
Coresh, J
AF Yang, Qiong
Koettgen, Anna
Dehghan, Abbas
Smith, Albert V.
Glazer, Nicole L.
Chen, Ming-Huei
Chasman, Daniel I.
Aspelund, Thor
Eiriksdottir, Gudny
Harris, Tamara B.
Launer, Lenore
Nalls, Michael
Hernandez, Dena
Arking, Dan E.
Boerwinkle, Eric
Grove, Megan L.
Li, Man
Kao, W. H. Linda
Chonchol, Michel
Haritunians, Talin
Li, Guo
Lumley, Thomas
Psaty, Bruce M.
Shlipak, Michael
Hwang, Shih-Jen
Larson, Martin G.
O'Donnell, Christopher J.
Upadhyay, Ashish
van Duijn, Cornelia M.
Hofman, Albert
Rivadeneira, Fernando
Stricker, Bruno
Uitterlinden, Andre G.
Pare, Guillaume
Parker, Alex N.
Ridker, Paul M.
Siscovick, David S.
Gudnason, Vilmundur
Witteman, Jacqueline C.
Fox, Caroline S.
Coresh, Josef
TI Multiple Genetic Loci Influence Serum Urate Levels and Their
Relationship With Gout and Cardiovascular Disease Risk Factors
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE uric acid; gout; cardiovascular diseases; risk factors; genome-wide
association study; Mendelian randomization analysis
ID GENOME-WIDE ASSOCIATION; BLOOD-PRESSURE; URIC-ACID; TRANSPORTER;
EPIDEMIOLOGY; PROTEIN; VARIANT; ABCG2
AB Background-Elevated serum urate levels can lead to gout and are associated with cardiovascular risk factors. We performed a genome-wide association study to search for genetic susceptibility loci for serum urate and gout and investigated the causal nature of the associations of serum urate with gout and selected cardiovascular risk factors and coronary heart disease (CHD).
Methods and Results-Meta-analyses of genome-wide association studies (GWAS) were performed in 5 population-based cohorts of the Cohorts for Heart and Aging Research in Genome Epidemiology consortium for serum urate and gout in 28 283 white participants. The effect of the most significant single-nucleotide polymorphism at all genome-wide significant loci on serum urate was added to create a genetic urate score. Findings were replicated in the Women's Genome Health Study (n=22 054). Single-nucleotide polymorphisms at 8 genetic loci achieved genome-wide significance with serum urate levels (P=4x10(-8) to 2x10(-242) in SLC22A11, GCKR, R3HDM2-INHBC region, RREB1, PDZK1, SLC2A9, ABCG2, and SLC17A1). Only 2 loci (SLC2A9, ABCG2) showed genome-wide significant association with gout. The genetic urate score was strongly associated with serum urate and gout (odds ratio, 12.4 per 100 mu mol/L; P=3x10(-39)) but not with blood pressure, glucose, estimated glomerular filtration rate, chronic kidney disease, or CHD. The lack of association between the genetic score and the latter phenotypes also was observed in the Women's Genome Health Study.
Conclusions-The genetic urate score analysis suggested a causal relationship between serum urate and gout but did not provide evidence for one between serum urate and cardiovascular risk factors and CHD. (Circ Cardiovasc Genet. 2010;3:523-530.)
C1 [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Yang, Qiong; Chen, Ming-Huei; Hwang, Shih-Jen; Larson, Martin G.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Koettgen, Anna; Li, Man; Kao, W. H. Linda; Coresh, Josef] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21287 USA.
[Dehghan, Abbas; van Duijn, Cornelia M.; Hofman, Albert; Stricker, Bruno; Witteman, Jacqueline C.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Smith, Albert V.; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Glazer, Nicole L.; Li, Guo] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Glazer, Nicole L.; Li, Guo; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Harris, Tamara B.; Launer, Lenore] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Boerwinkle, Eric; Grove, Megan L.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol, Houston, TX USA.
[Arking, Dan E.] Johns Hopkins Med Inst, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
[Kao, W. H. Linda; Coresh, Josef] Johns Hopkins Univ, Dept Med, Baltimore, MD 21287 USA.
[Chonchol, Michel] Univ Colorado Denver & Hlth Sci Ctr, Div Renal Dis & Hypertens, Aurora, CO USA.
[Haritunians, Talin] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
Grp Hlth, Ctr Hlth Studies, Seattle, WA USA.
[Shlipak, Michael] Univ Calif San Francisco, Div Gen Internal Med, San Francisco VA Med Ctr, San Francisco, CA 94143 USA.
[Chen, Ming-Huei] Boston Univ, Dept Neurol, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Upadhyay, Ashish] Boston Med Ctr, Renal Sect, Boston, MA USA.
Boston Univ, Sch Med, Boston, MA 02118 USA.
[Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Siscovick, David S.] Univ Washington, Dept Med & Epidemiol, Seattle, WA 98195 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Coresh, Josef] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
[Chasman, Daniel I.; Pare, Guillaume; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Nalls, Michael; Hernandez, Dena] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA.
[Parker, Alex N.] Amgen Inc, Cambridge, MA USA.
RP Coresh, J (reprint author), Johns Hopkins Univ, Dept Epidemiol, 2024 E Monument,Ste 2-630, Baltimore, MD 21287 USA.
EM coresh@jhu.edu
RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Kottgen,
Anna/D-2920-2012; Li, Guo/E-5613-2012; Yang, Qiong/G-5438-2014;
Gudnason, Vilmundur/K-6885-2015; Rivadeneira, Fernando/O-5385-2015;
Smith, Albert/K-5150-2015
OI Dehghan, Abbas/0000-0001-6403-016X; Aspelund, Thor/0000-0002-7998-5433;
Gudnason, Vilmundur/0000-0001-5696-0084; Rivadeneira,
Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845
FU National Institutes of Health, NIA; NIH [N01-AG-12100,
HHSN268200625226C]; NIA; Hjartavernd (the Icelandic Heart Association);
Althingi (the Icelandic Parliament); NHLBI [N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022,
R01HL087641, R01HL59367, R01HL086694, U01 HL080295, R01 HL087652, R01
AG027002, HL 043851]; National Human Genome Research Institute (NHGRI)
[U01HG004402]; NIH Roadmap for Medical Research; Donald W. Reynolds
Clinical Cardiovascular Research Center; National Center for Research
Resources (NCRR) [UL1 RR 025005, M01RR00069]; National Institute of
Diabetes and Digestive and Kidney Diseases [DK063491]; NHLBI's FHS
[N01-HC-25195]; Erasmus Medical Center; Erasmus University Rotterdam;
The Netherlands Organization for Scientific Research (NOW); The
Netherlands Organization for Health Research and Development; Research
Institute for Diseases in the Elderly; The Netherlands Heart Foundation;
Ministry of Education, Culture and Science; Ministry of Health Welfare
and Sports; European Commission; Municipality of Rotterdam; NWO
[175.010.2005.011, 911.03.012, 918-76-619]; The Netherlands Genomics
Initiative/NWO; National Cancer Institute [CA 047988]; Amgen, Inc.;
[UL1RR025005]; [R01DK076770]; [K01DK067207]; [N01-HC-85079];
[N01-HC-85086]; [N01-HC-35129]; [N01-HC-15103]; [N01 HC-55222];
[N01-HC-75150]; [N01-HC-45133]; [N02-HL-6-4278]
FX We acknowledge the essential role of the CHARGE consortium in
development and support of this manuscript. CHARGE members include The
Netherland's RS), the National Heart, Lung, and Blood Institute's
(NHLBI's) FHS, the CHS, the NHLBI's ARIC, and the Icelandic Heart
Association's and National Institute on Aging's (NIA's) Iceland AGES
Reykjavik Study. This research was supported in part by the Intramural
Research Program of the National Institutes of Health, NIA.; The AGES
study has been funded by NIH contract N01-AG-12100, the NIA Intramural
Research Program, Hjartavernd (the Icelandic Heart Association), and the
Althingi (the Icelandic Parliament). The ARIC study is carried out as a
collaborative study supported by NHLBI contracts N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022, R01HL087641, R01HL59367, and R01HL086694; National Human
Genome Research Institute (NHGRI) contract U01HG004402; and NIH contract
HHSN268200625226C. Infrastructure was partly supported by grant number
UL1RR025005, a component of the NIH and NIH Roadmap for Medical
Research. Drs Coresh, Kottgen, and Man Li are supported by R01DK076770
and Dr Arking by a Donald W. Reynolds Clinical Cardiovascular Research
Center grant. Dr Kao was supported by K01DK067207 and Dr Coresh by
R01DK076770. The project described was supported by grant number UL1 RR
025005 from the National Center for Research Resources (NCRR), a
component of the NIH and NIH Roadmap for Medical Research, and its
contents are solely the responsibility of the authors and do not
necessarily represent the official view of NCRR or NIH. Information on
NCRR is available at www.ncrr.nih.gov. Information on Re-engineering the
Clinical Research Enterprise can be obtained from
http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp.
The CHS was supported by contract numbers N01-HC-85079 through
N01-HC-85086, N01-HC-35129, N01-HC-15103, N01 HC-55222, N01-HC-75150,
N01-HC-45133 and grant numbers U01 HL080295, R01 HL087652, and R01
AG027002 from NHLBI. Genotyping was supported, in part, by NCRR grant
M01RR00069 and National Institute of Diabetes and Digestive and Kidney
Diseases grant DK063491. The FHS was supported by the NHLBI's FHS
(N01-HC-25195), and Affymetrix genotyping was supported by contract
N02-HL-6-4278. The RS is supported by the Erasmus Medical Center and
Erasmus University Rotterdam; The Netherlands Organization for
Scientific Research (NOW); The Netherlands Organization for Health
Research and Development; the Research Institute for Diseases in the
Elderly; The Netherlands Heart Foundation; the Ministry of Education,
Culture and Science; the Ministry of Health Welfare and Sports; the
European Commission; and the Municipality of Rotterdam. Support for
genotyping was provided by the NWO (175.010.2005.011, 911.03.012) and
Research Institute for Diseases in the Elderly. This study was further
supported by The Netherlands Genomics Initiative/NWO project number
050-060-810. Dr Dehghan is supported by a grant from NWO (vici,
918-76-619). The WGHS was supported by the NHLBI (HL 043851) and the
National Cancer Institute (CA 047988). Collaborative scientific and
genotyping support was provided by Amgen, Inc.; Dr Yang has received
research grant support from the NHLBI for the FHS. Dr Kottgen has
ownership interest in a pending patent for ABCG2 urate transport used in
the treatment of gout. Dr Smith has received research grant support for
genetics of diabetes and thermophidic bacteria from the Iceland Research
Council. Dr Chasman has received research grant support from NIH for the
Women's Health Study (R01 HL080467, Buring PI); PARC (U01 HL069757,
Krauss PI); PRE-DETERMINE (R01 HL091069, Albert PI); Genetics of AMD
(R01 EY017362, Schaumberg PI); Genetics of Migraine (R01 NS061836, Kurth
PI); and Gene Networks GWAS (R01 submitted, Chasman PI). Dr Boerwinkle
has received grant support from NIH/NHLBI, NIH/NHGRI, and NIH/National
Institute of General Medical Sciences. Dr Chonchol has received NIH
research grant support from R01, "Vitamin D and Dialysis"; R01,
"Adiporectin and Dialysis"; and U01, "BP and CKD." Dr Ridker has
received research grant support from NHLBI; Amgen, Inc; and Celera and
other research support from Amgen, Inc. Dr Coresh has received research
grant support from NIH for the ARIC cohort and ARIC kidney disease and
related conditions including genetics studies and has ownership interest
in a pending patent on using ABCG2 to treat hyperuricemia. Dr Parker is
an employee of Amgen, Inc. Drs Dehghan, Glazer, Chen, Aspelund, Harris,
Launer, Nalls, Arking, Kao, Haritunians, Lumley, Psaty, Shlipak, Hwang,
Larson, O'Donnell, Upadhyay, van Dujin, Hofman, Rivadeneira, Stricker,
Uitterlinden, Pare, Siscovick, Gudnason, Witteman, and Fox and Mss
Eiriksdottir, Hernandez, Grove, M. Li, and G. Li have no conflicts to
disclose.
NR 25
TC 134
Z9 150
U1 5
U2 20
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD DEC
PY 2010
VL 3
IS 6
BP 523
EP 530
DI 10.1161/CIRCGENETICS.110.934455
PG 8
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 694KG
UT WOS:000285295600007
PM 20884846
ER
PT J
AU Kelly, TN
Hixson, JE
Rao, DC
Mei, H
Rice, TK
Jaquish, CE
Shimmin, LC
Schwander, K
Chen, CS
Liu, DP
Chen, JC
Bormans, C
Shukla, P
Farhana, N
Stuart, C
Whelton, PK
He, JA
Gu, DF
AF Kelly, Tanika N.
Hixson, James E.
Rao, Dabeeru C.
Mei, Hao
Rice, Treva K.
Jaquish, Cashell E.
Shimmin, Lawrence C.
Schwander, Karen
Chen, Chung-Shuian
Liu, Depei
Chen, Jichun
Bormans, Concetta
Shukla, Pramila
Farhana, Naveed
Stuart, Colin
Whelton, Paul K.
He, Jiang
Gu, Dongfeng
TI Genome-Wide Linkage and Positional Candidate Gene Study of Blood
Pressure Response to Dietary Potassium Intervention The Genetic
Epidemiology Network of Salt Sensitivity Study
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE blood pressure; potassium; genetics
ID HUMAN ESSENTIAL-HYPERTENSION; TYPE-1 RECEPTOR GENE; LOCI;
SUPPLEMENTATION; POLYMORPHISMS; ASSOCIATION; GENSALT; SCAN;
METAANALYSIS; VARIANTS
AB Background-Genetic determinants of blood pressure (BP) response to potassium, or potassium sensitivity, are largely unknown. We conducted a genome-wide linkage scan and positional candidate gene analysis to identify genetic determinants of potassium sensitivity.
Methods and Results-A total of 1906 Han Chinese participants took part in a 7-day high-sodium diet followed by a 7-day high-sodium plus potassium dietary intervention. BP measurements were obtained at baseline and after each intervention using a random-zero sphygmomanometer. Significant linkage signals (logarithm of odds [LOD] score, >3) for BP responses to potassium were detected at chromosomal regions 3q24-q26.1, 3q28, and 11q22.3-q24.3. Maximum multipoint LOD scores of 3.09 at 3q25.2 and 3.41 at 11q23.3 were observed for absolute diastolic BP (DBP) and mean arterial pressure (MAP) responses, respectively. Linkage peaks of 3.56 at 3q25.1 and 3.01 at 11q23.3 for percent DBP response and 3.22 at 3q25.2, 3.01 at 3q28, and 4.48 at 11q23.3 for percent MAP response also were identified. Angiotensin II receptor, type 1 (AGTR1), single-nucleotide polymorphism rs16860760 in the 3q24-q26.1 region was significantly associated with absolute and percent systolic BP responses to potassium (P=0.0008 and P=0.0006, respectively). Absolute (95% CI) systolic BP responses for genotypes C/C, C/T, and T/T were -3.71 (-4.02 to -3.40), -2.62 (-3.38 to -1.85), and 1.03 (-3.73 to 5.79) mm Hg, respectively, and percent responses (95% CI) were -3.07 (-3.33 to -2.80), -2.07 (-2.74 to -1.41), and 0.90 (-3.20 to 4.99), respectively. Similar trends were observed for DBP and MAP responses.
Conclusions-Genetic regions on chromosomes 3 and 11 may harbor important susceptibility loci for potassium sensitivity. Furthermore, the AGTR1 gene was a significant predictor of BP responses to potassium intake.
C1 [Kelly, Tanika N.; Mei, Hao; Chen, Chung-Shuian; He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
[He, Jiang] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
[Hixson, James E.; Shimmin, Lawrence C.; Bormans, Concetta; Shukla, Pramila; Farhana, Naveed; Stuart, Colin] Univ Texas Sch Publ Hlth, Dept Epidemiol, Houston, TX USA.
[Rao, Dabeeru C.; Rice, Treva K.; Schwander, Karen] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Jaquish, Cashell E.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA.
[Liu, Depei] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100730, Peoples R China.
Peking Union Med Coll, Beijing 100021, Peoples R China.
[Chen, Jichun; Gu, Dongfeng] Chinese Acad Med Sci, Fuwai Hosp, Beijing 100037, Peoples R China.
Chinese Natl Ctr Cardiovasc Dis Control & Res, Beijing, Peoples R China.
[Whelton, Paul K.] Loyola Univ Hlth Syst & Med Ctr, Off President, Maywood, IL USA.
[Gu, Dongfeng] Chinese Acad Med Sci, Div Populat Genet & Prevent, Cardiovasc Inst, Beijing 100037, Peoples R China.
RP Gu, DF (reprint author), Chinese Acad Med Sci, Div Populat Genet & Prevent, Cardiovasc Inst, 167 Beilishi Rd, Beijing 100037, Peoples R China.
EM gudongfeng@vip.sina.com
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda [U01HL072507, R01HL087263, R01HL090682]; Eunice Kennedy
Shriver National Institute of Child Health & Human Development
[K12HD043451]
FX The Genetic Epidemiology Network of Salt Sensitivity is supported by
research grants (U01HL072507, R01HL087263, and R01HL090682) from the
National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Md. Dr Kelly and the project described were supported
by Award Number K12HD043451 from the Eunice Kennedy Shriver National
Institute of Child Health & Human Development. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the Eunice Kennedy Shriver National Institute of Child
Health & Human Development or the National Institutes of Health.
Upsher-Smith Laboratories, Maple Grove, Minn, has provided Klor-Con M20
potassium tablets for the GenSalt study.
NR 34
TC 5
Z9 7
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD DEC
PY 2010
VL 3
IS 6
BP 539
EP 547
DI 10.1161/CIRCGENETICS.110.940635
PG 9
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 694KG
UT WOS:000285295600009
PM 20861505
ER
PT J
AU Baccarelli, A
Rienstra, M
Benjamin, EJ
AF Baccarelli, Andrea
Rienstra, Michiel
Benjamin, Emelia J.
TI Cardiovascular Epigenetics Basic Concepts and Results From Animal and
Human Studies
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE DNA methylation; histones; risk factors; cardiovascular diseases
ID DNA METHYLATION; GENE PROMOTER; DISEASE; BLOOD; HYPERHOMOCYSTEINEMIA;
ATHEROSCLEROSIS; HYPERTENSION; HOMOCYSTEINE; EXPOSURE
C1 [Baccarelli, Andrea] Harvard Univ, Sch Publ Hlth, Lab Environm Epigenet, Exposure Epidemiol & Risk Program,Landmark Ctr, Boston, MA 02115 USA.
[Rienstra, Michiel] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Rienstra, Michiel; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Rienstra, Michiel; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Rienstra, Michiel] Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA.
RP Baccarelli, A (reprint author), Harvard Univ, Sch Publ Hlth, Lab Environm Epigenet, Exposure Epidemiol & Risk Program,Landmark Ctr, Room 415E W,POB 15677,401 Pk Dr, Boston, MA 02115 USA.
EM abaccare@hsph.harvard.edu
OI Baccarelli, Andrea/0000-0002-3436-0640; Benjamin,
Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X
FU The Netherlands Organization for Scientific Research [825.09.020];
National Institutes of Health [1R01HL092577, 1RC1HL101056, 1R01HL102214,
R01AG028321]; Baccarelli [ES000002, 1R21ES019773]
FX Dr Rienstra is supported by a grant from The Netherlands Organization
for Scientific Research (Rubicon grant 825.09.020). This work was
supported by grants from the National Institutes of Health to Drs
Benjamin (1R01HL092577, 1RC1HL101056, 1R01HL102214, R01AG028321) and
Baccarelli (ES000002, 1R21ES019773).
NR 23
TC 73
Z9 78
U1 2
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD DEC
PY 2010
VL 3
IS 6
BP 567
EP 573
DI 10.1161/CIRCGENETICS.110.958744
PG 7
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 694KG
UT WOS:000285295600012
PM 21156932
ER
PT J
AU Fabsitz, RR
McGuire, A
Sharp, RR
Puggal, M
Beskow, LM
Biesecker, LG
Bookman, E
Burke, W
Burchard, EG
Church, G
Clayton, EW
Eckfeldt, JH
Fernandez, CV
Fisher, R
Fullerton, SM
Gabriel, S
Gachupin, F
James, C
Jarvik, GP
Kittles, R
Leib, JR
O'Donnell, C
O'Rourke, PP
Rodriguez, LL
Schully, SD
Shuldiner, AR
Sze, RKF
Thakuria, JV
Wolf, SM
Burke, GL
AF Fabsitz, Richard R.
McGuire, Amy
Sharp, Richard R.
Puggal, Mona
Beskow, Laura M.
Biesecker, Leslie G.
Bookman, Ebony
Burke, Wylie
Burchard, Esteban Gonzalez
Church, George
Clayton, Ellen Wright
Eckfeldt, John H.
Fernandez, Conrad V.
Fisher, Rebecca
Fullerton, Stephanie M.
Gabriel, Stacey
Gachupin, Francine
James, Cynthia
Jarvik, Gail P.
Kittles, Rick
Leib, Jennifer R.
O'Donnell, Christopher
O'Rourke, P. Pearl
Rodriguez, Laura Lyman
Schully, Sheri D.
Shuldiner, Alan R.
Sze, Rebecca K. F.
Thakuria, Joseph V.
Wolf, Susan M.
Burke, Gregory L.
TI Ethical and Practical Guidelines for Reporting Genetic Research Results
to Study Participants Updated Guidelines From a National Heart, Lung,
and Blood Institute Working Group
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE consent; genetics; ethics; research genetics; risk prediction;
single-nucleotide polymorphism genetics
ID INCIDENTAL FINDINGS; CLINICAL-RESEARCH; RECOMMENDATIONS; DISCLOSURE;
MEDICINE; BIOBANKS; RETURN; LEGAL; DUTY
AB In January 2009, the National Heart, Lung, and Blood Institute convened a 28-member multidisciplinary Working Group to update the recommendations of a 2004 National Heart, Lung, and Blood Institute Working Group focused on Guidelines to the Return of Genetic Research Results. Changes in the genetic and societal landscape over the intervening 5 years raise multiple questions and challenges. The group noted the complex issues arising from the fact that technological and bioinformatic progress has made it possible to obtain considerable information on individuals that would not have been possible a decade ago. Although unable to reach consensus on a number of issues, the working group produced 5 recommendations. The working group offers 2 recommendations addressing the criteria necessary to determine when genetic results should and may be returned to study participants, respectively. In addition, it suggests that a time limit be established to limit the duration of obligation of investigators to return genetic research results. The group recommends the creation of a central body, or bodies, to provide guidance on when genetic research results are associated with sufficient risk and have established clinical utility to justify their return to study participants. The final recommendation urges investigators to engage the broader community when dealing with identifiable communities to advise them on the return of aggregate and individual research results. Creation of an entity charged to provide guidance to institutional review boards, investigators, research institutions, and research sponsors would provide rigorous review of available data, promote standardization of study policies regarding return of genetic research results, and enable investigators and study participants to clarify and share expectations for the handling of this increasingly valuable information with appropriate respect for the rights and needs of participants. (Circ Cardiovasc Genet. 2010;3:574-580.)
C1 [McGuire, Amy] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA.
[Sharp, Richard R.] Cleveland Clin, Dept Bioeth, Cleveland, OH 44106 USA.
[Beskow, Laura M.] Duke Univ, Duke Inst Genome Sci & Policy, Durham, NC USA.
[Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA.
[Bookman, Ebony] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA.
[Burke, Wylie; Fullerton, Stephanie M.] Univ Washington, Dept Bioeth & Humanities, Seattle, WA 98195 USA.
[Burchard, Esteban Gonzalez] Univ Calif San Francisco, Pulm & Crit Care Div, San Francisco, CA 94143 USA.
[Church, George] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Clayton, Ellen Wright] Vanderbilt Univ, Sch Law, Ctr Biomed Eth & Soc, Nashville, TN 37240 USA.
[Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Fernandez, Conrad V.] Dalhousie Univ, Dept Pediat, IWK Hlth Ctr, Halifax, NS, Canada.
[Gabriel, Stacey] Broad Inst, Boston, MA USA.
[Gachupin, Francine] SW Tribal Epidemiol Ctr, Albuquerque, NM USA.
[James, Cynthia] Johns Hopkins Univ, Div Med Cardiol, Baltimore, MD USA.
[Jarvik, Gail P.] Univ Washington, Div Med Genet, Sch Med, Seattle, WA 98195 USA.
[Kittles, Rick] Univ Illinois, Coll Med, Chicago, IL USA.
[Leib, Jennifer R.] Hlth Futures LLC, Washington, DC USA.
[O'Donnell, Christopher] NHLBI, Framingham Heart Study, Framingham, MA USA.
[O'Rourke, P. Pearl] Partners Hlth Care Syst Inc, Hlth Res Affairs, Boston, MA USA.
[Rodriguez, Laura Lyman] NHGRI, Off Policy Commun & Educ, Bethesda, MD 20892 USA.
[Schully, Sheri D.] NCI, Epidemiol & Genet Res Program, Bethesda, MD 20892 USA.
[Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Sze, Rebecca K. F.] Charles B Wang Community Hlth Ctr, New York, NY USA.
[Wolf, Susan M.] Univ Minnesota, Sch Law, Sch Med, Ctr Bioeth,Consortium Law & Value Hlth Environm &, Minneapolis, MN 55455 USA.
[Burke, Gregory L.] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Fabsitz, Richard R.] NHLBI, Epidemiol Branch, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Fabsitz, RR (reprint author), NHLBI, Epidemiol Branch, Div Cardiovasc Sci, Rockledge 2 Bldg,Room 10204,6701 Rockledge Dr,MSC, Bethesda, MD 20892 USA.
EM fabsitzr@nhlbi.nih.gov
RI Jarvik, Gail/N-6476-2014;
OI Jarvik, Gail/0000-0002-6710-8708; Clayton, Ellen/0000-0002-0308-4110
FU National Heart, Lung, and Blood Institute; BCM Clinical and
Translational Research Program; Baylor Annual Fund; State of Washington
Life Sciences Discovery fund; [HG003178]; [RR024128]; [HG004603]
FX Funding for participation in the Working Group meeting was provided by
the National Heart, Lung, and Blood Institute. Individual work on this
report has been in part supported by HG003178 (Dr Wolf); BCM Clinical
and Translational Research Program and the Baylor Annual Fund (Dr
McGuire); Northwest Institute of Genetic Medicine which is supported in
part by the State of Washington Life Sciences Discovery fund (Dr
Jarvik); RR024128 (Dr Beskow); and HG004603 (Dr Clayton). The authors
acknowledge the members of the Working Group Planning Committee: Weiniu
Gan, Alan Michelson, Dina Paltoo, George Papanicolaou, and Phyliss
Sholinsky.
NR 32
TC 186
Z9 186
U1 3
U2 20
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD DEC
PY 2010
VL 3
IS 6
BP 574
EP 580
DI 10.1161/CIRCGENETICS.110.958827
PG 7
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 694KG
UT WOS:000285295600013
ER
PT J
AU Truong, HHM
Sim, MS
Dillon, M
Uittenbogaart, CH
Dickover, R
Plaeger, SF
Bryson, YJ
AF Truong, Hong-Ha M.
Sim, Myung S.
Dillon, Maryanne
Uittenbogaart, Christel H.
Dickover, Ruth
Plaeger, Susan F.
Bryson, Yvonne J.
TI Correlation of Immune Activation during Late Pregnancy and Early
Postpartum with Increases in Plasma HIV RNA, CD4/CD8 T Cells, and Serum
Activation Markers
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; VIRAL LOAD;
ANTIRETROVIRAL THERAPY; TRANSMISSION; INFECTION; TYPE-1; WOMEN;
EXPRESSION; CD4(+)
AB A previously observed rise in the plasma viral load postpartum in both treated and untreated HIV-positive women remains unexplained. Virological and immunological markers were evaluated in HIV-negative controls and HIV-positive pregnant women with and without antiretroviral treatment. Plasma HIV RNA, CD4/CD8 T cells, and serum activation markers were sequentially measured during the third trimester, at delivery, and 2 to 8 weeks postpartum in a cohort of HIV-positive pregnant women (n = 96) enrolled in a maternal-fetal HIV transmission study and a control group of HIV-negative pregnant women (n = 28). Mean plasma HIV RNA (P = 0.003) increased from delivery to postpartum, and mean CD4 T cells (P = 0.002) and serum beta 2-microglobulin (P < 0.0001) increased from the third trimester through postpartum among the HIV-positive women. Mean CD8 T cells increased from the third trimester through postpartum in women receiving zidovudine (ZDV) and in those not treated (P < 0.05) but remained stable in those on highly active antiretroviral therapy (HAART) and the HIV-negative controls. Increases in serum beta 2-microglobulin were correlated with increases in HIV RNA (P = 0.01). HIV-positive pregnant women showed postpartum increases in plasma HIV RNA, CD4 T cells, and serum beta 2-microglobulin regardless of the treatment regimen. The rise in CD4 T cells and beta 2-microglobulin was also observed in HIV-negative pregnant women, suggesting hormonal changes and/or labor-induced cytokines may contribute to immune activation. Immune activation correlated with increased plasma HIV RNA in postpartum women despite treatment, although HAART appeared to blunt the effect. The observed rise in plasma HIV RNA postpartum, which correlated with markers of immune activation, may have implications for enhanced transmission to infants through early breast-feeding and to sexual partners.
C1 [Bryson, Yvonne J.] Univ Calif Los Angeles, Div Infect Dis, Dept Pediat, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Truong, Hong-Ha M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Plaeger, Susan F.] NIAID, Bethesda, MD 20892 USA.
RP Bryson, YJ (reprint author), Univ Calif Los Angeles, Div Infect Dis, Dept Pediat, David Geffen Sch Med, 10833 Le Conte Ave,MDCC 22-442, Los Angeles, CA 90095 USA.
EM ybryson@mednet.ucla.edu
FU National Institutes of Health [R0132440, R01-HD30629, UCLA CFAR
AI028697]; Pediatric AIDS Clinical Trials Group [U01-AI27550]; Clinical
Research Center [M01-RR00865]; University of California [F01-LA-0930]
FX Funding for this study was provided by the National Institutes of Health
(R0132440, R01-HD30629, and UCLA CFAR AI028697), Pediatric AIDS Clinical
Trials Group (U01-AI27550), Clinical Research Center (M01-RR00865), and
Universitywide AIDS Research Program of the University of California
Research (Postdoctoral Research Fellowship Award to Hong-Ha M. Truong
[F01-LA-0930]).
NR 28
TC 5
Z9 5
U1 0
U2 1
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 2010
VL 17
IS 12
BP 2024
EP 2028
DI 10.1128/CVI.00088-10
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 686HC
UT WOS:000284686400028
PM 20980480
ER
PT J
AU Goldstein, DS
AF Goldstein, David S.
TI Catecholamines 101
SO CLINICAL AUTONOMIC RESEARCH
LA English
DT Review
DE Catecholamine; Norepinephrine; Epinephrine; Dopamine; Autonomic
ID CONGESTIVE-HEART-FAILURE; NEUROGENIC ORTHOSTATIC HYPOTENSION;
BETA-HYDROXYLASE DEFICIENCY; SYMPATHETIC-NERVOUS-SYSTEM; PERFORMANCE
LIQUID-CHROMATOGRAPHY; POSTURAL TACHYCARDIA SYNDROME; FAMILIAL
DYSAUTONOMIA; PLASMA-LEVELS; ELECTROCHEMICAL DETECTION; NOREPINEPHRINE
SPILLOVER
AB This review of clinical catecholamine neurochemistry is based on the Streeten Memorial Lecture at the 19th annual meeting of the American Autonomic Society and lectures at a satellite of the 6th Congress of the International Society of Autonomic Neuroscience. Here I provide historical perspective, describe sources and meanings of plasma levels of catecholamines and their metabolites, present a model of a sympathetic noradrenergic neuron that conveys how particular aspects of sympathetic nervous function affect plasma levels of catecholamines and their metabolites, and apply the model to understand plasma neurochemical patterns associated with some drugs and disease states.
C1 Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
RP Goldstein, DS (reprint author), Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, 10 Ctr Dr MSC 1620,9000 Rockville Pike,Bldg 10,Rm, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU Intramural NIH HHS [Z99 NS999999]
NR 133
TC 22
Z9 22
U1 3
U2 14
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0959-9851
EI 1619-1560
J9 CLIN AUTON RES
JI Clin. Auton. Res.
PD DEC
PY 2010
VL 20
IS 6
BP 331
EP 352
DI 10.1007/s10286-010-0065-7
PG 22
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 691LL
UT WOS:000285081200001
PM 20623313
ER
PT J
AU Dunleavy, K
Piekarz, RL
Zain, J
Janik, JE
Wilson, WH
O'Connor, OA
Bates, SE
AF Dunleavy, Kieron
Piekarz, Richard L.
Zain, Jasmine
Janik, John E.
Wilson, Wyndham H.
O'Connor, Owen A.
Bates, Susan E.
TI New Strategies in Peripheral T-Cell Lymphoma: Understanding Tumor
Biology and Developing Novel Therapies
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; PROTEASOME INHIBITOR BORTEZOMIB; PHASE-II TRIAL;
HISTONE DEACETYLASE INHIBITOR; ANTI-CD30 MONOCLONAL-ANTIBODY; HIGH-DOSE
CHEMOTHERAPY; GENE-EXPRESSION; DEPSIPEPTIDE FR901228; DENILEUKIN
DIFTITOX; COMPLETE REMISSION
AB Peripheral T-cell lymphomas (PTCL) constitute a group of heterogeneous diseases that are uncommon, representing, in Western countries, only approximately 10% of all non-Hodgkin lymphomas. They are typically associated with a poor prognosis compared with their B-cell counterparts and are much less well understood with respect to tumor biology, owing to their rarity and biologic heterogeneity, and to the fact that characteristic cytogenetic abnormalities are few compared with B-cell lymphomas. Although the outcome for patients with anaplastic large cell lymphoma (ALCL), particularly anaplastic lymphoma kinase (ALK)-positive ALCL, is good, other types of PTCLs are associated with a poor prognosis, even with aggressive anthracycline-based chemotherapy. In this respect, there is a need for new approaches in these diseases, and this review focuses on and explores recent experience with novel therapies in PTCL. Clin Cancer Res; 16(23); 5608-17. (C)2010 AACR.
C1 [Dunleavy, Kieron; Piekarz, Richard L.; Janik, John E.; Wilson, Wyndham H.; Bates, Susan E.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Zain, Jasmine; O'Connor, Owen A.] NYU, Inst Canc, NYU Langone Med Ctr, New York, NY USA.
RP Dunleavy, K (reprint author), NCI, Ctr Canc Res, Bldg 10,Room 12N226,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dunleavk@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 86
TC 14
Z9 16
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD DEC 1
PY 2010
VL 16
IS 23
BP 5608
EP 5617
DI 10.1158/1078-0432.CCR-09-1995
PG 10
WC Oncology
SC Oncology
GA 690XU
UT WOS:000285044200002
PM 21138864
ER
PT J
AU Lockman, PR
Mittapalli, RK
Taskar, KS
Rudraraju, V
Gril, B
Bohn, KA
Adkins, CE
Roberts, A
Thorsheim, HR
Gaasch, JA
Huang, SY
Palmieri, D
Steeg, PS
Smith, QR
AF Lockman, Paul R.
Mittapalli, Rajendar K.
Taskar, Kunal S.
Rudraraju, Vinay
Gril, Brunilde
Bohn, Kaci A.
Adkins, Chris E.
Roberts, Amanda
Thorsheim, Helen R.
Gaasch, Julie A.
Huang, Suyun
Palmieri, Diane
Steeg, Patricia S.
Smith, Quentin R.
TI Heterogeneous Blood-Tumor Barrier Permeability Determines Drug Efficacy
in Experimental Brain Metastases of Breast Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; ALPHA-AMINOISOBUTYRIC-ACID; IN-VIVO;
P-GLYCOPROTEIN; DIETHYLENETRIAMINEPENTAACETIC ACID; TISSUE DISTRIBUTION;
CARBOXYLIC-ACID; CNS METASTASES; NUDE-MICE; CHEMOTHERAPY
AB Purpose: Brain metastases of breast cancer appear to be increasing in incidence, confer significant morbidity, and threaten to compromise gains made in systemic chemotherapy. The blood-tumor barrier (BTB) is compromised in many brain metastases; however, the extent to which this influences chemotherapeutic delivery and efficacy is unknown. Herein, we answer this question by measuring BTB passive integrity, chemotherapeutic drug uptake, and anticancer efficacy in vivo in two breast cancer models that metastasize preferentially to brain.
Experimental Design: Experimental brain metastasis drug uptake and BTB permeability were simultaneously measured using novel fluorescent and phosphorescent imaging techniques in immune-compromised mice. Drug-induced apoptosis and vascular characteristics were assessed using immunofluorescent microscopy.
Results: Analysis of over 2,000 brain metastases from two models (human 231-BR-Her2 and murine 4T1-BR5) showed partial BTB permeability compromise in greater than 89% of lesions, varying in magnitude within and between metastases. Brain metastasis uptake of C-14-paclitaxel and C-14-doxorubicin was generally greater than normal brain but less than 15% of that of other tissues or peripheral metastases, and only reached cytotoxic concentrations in a small subset (similar to 10%) of the most permeable metastases. Neither drug significantly decreased the experimental brain metastatic ability of 231-BR-Her2 tumor cells. BTB permeability was associated with vascular remodeling and correlated with overexpression of the pericyte protein desmin.
Conclusions: This work shows that the BTB remains a significant impediment to standard chemotherapeutic delivery and efficacy in experimental brain metastases of breast cancer. New brain permeable drugs will be needed. Evidence is presented for vascular remodeling in BTB permeability alterations. Clin Cancer Res; 16(23); 5664-78. (C)2010 AACR.
C1 [Lockman, Paul R.; Mittapalli, Rajendar K.; Taskar, Kunal S.; Rudraraju, Vinay; Bohn, Kaci A.; Adkins, Chris E.; Roberts, Amanda; Thorsheim, Helen R.; Smith, Quentin R.] Texas Tech Univ Hlth Sci Ctr, Dept Pharmaceut Sci, Canc Biol Ctr, Amarillo, TX 79106 USA.
[Gril, Brunilde; Palmieri, Diane; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD USA.
[Gaasch, Julie A.] W Texas A&M Univ, Dept Life Earth & Environm Sci, Canyon, TX USA.
[Huang, Suyun] Univ Texas Houston, MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA.
RP Lockman, PR (reprint author), Texas Tech Univ Hlth Sci Ctr, Dept Pharmaceut Sci, Canc Biol Ctr, 1406 Coulter, Amarillo, TX 79106 USA.
EM paul.lockman@ttuhsc.edu
RI Palmieri, Diane/B-4258-2015
FU Department of Defense [W81XWH-062-0033]; NINDS/NIH [R01 NS052484];
National Cancer Institute
FX Intramural Program of the National Cancer Institute (P.S.S., D.P.),
grant W81XWH-062-0033 from the Department of Defense Breast Cancer
Research Program (P.S.S., Q.R.S., P.R.L., S.H., and D.P.), and grant R01
NS052484 from NINDS/NIH (Q.R.S.).
NR 79
TC 186
Z9 188
U1 3
U2 22
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 2010
VL 16
IS 23
BP 5664
EP 5678
DI 10.1158/1078-0432.CCR-10-1564
PG 15
WC Oncology
SC Oncology
GA 690XU
UT WOS:000285044200008
PM 20829328
ER
PT J
AU Pan, YC
Li, CF
Ko, CY
Pan, MH
Chen, PJ
Tseng, JT
Wu, WC
Chang, WC
Huang, AM
Sterneck, E
Wang, JM
AF Pan, Yen-Chun
Li, Chien-Feng
Ko, Chiung-Yuan
Pan, Min-Hsiung
Chen, Pei-Jung
Tseng, Joseph T.
Wu, Wen-Chun
Chang, Wen-Chang
Huang, A-Mei
Sterneck, Esta
Wang, Ju-Ming
TI CEBPD Reverses RB/E2F1-Mediated Gene Repression and Participates in
HMDB-Induced Apoptosis of Cancer Cells
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID BINDING-PROTEIN-DELTA; ACTIVATED-RECEPTOR-GAMMA; TERMINAL ADIPOCYTE
DIFFERENTIATION; MAMMARY EPITHELIAL-CELLS; EPIDERMAL-GROWTH-FACTOR;
C/EBP-DELTA; TRANSCRIPTION FACTOR; ANTICANCER DRUGS; BREAST-CANCER;
GADD153 EXPRESSION
AB Purpose: Recent evidence indicates that a tumor suppressor gene CEBPD (CCAAT/enhancer-binding protein delta) is downregulated in many cancers including cervical cancer, which provides a therapeutic potential associated with its reactivation. However, little is known for CEBPD activators and the effect of reactivation of CEBPD transcription upon anticancer drug treatment. In this study, we identified a novel CEBPD activator, 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB). The purpose of this study is to characterize the mechanism of HMDB-induced CEBPD activation and its potential effect in cancer therapy.
Experimental Design: Methylation-specific PCR assay, reporter assay, and chromatin immunoprecipitation (ChIP) assay were performed to dissect the signaling pathway of HMDB-induced CEBPD transcription. Furthermore, a consequence of HMDB-induced CEBPD expression was linked with E2F1 and retinoblastoma (RB), which discloses the scenario of CEBPD, E2F1, and RB bindings and transcriptional regulation on the promoters of proapoptotic genes, PPARG2 and GADD153. Finally, the anticancer effect of HMDB was examined in xenograft mice.
Results: We demonstrate that CEBPD plays an essential role in HMDB-mediated apoptosis of cancer cells. HMDB up-regulates CEBPD transcription through the p38/CREB pathway, thus leading to transcriptional activation of PPARG2 and GADD153. Furthermore, increased level of CEBPD attenuates E2F1-induced cancer cell proliferation and partially rescues RB/E2F1-mediated repression of PPARG2 and GADD153 transcription. Moreover, HMDB treatment attenuates the growth of A431 xenografts in severe combined immunodeficient mice mice.
Conclusions: These results clearly demonstrate that HMDB kills cancer cells through activation of CEBPD pathways and suggest that HMDB can serve as a superior chemotherapeutic agent with limited potential for adverse side effects. Clin Cancer Res; 16(23); 5770-80. (C)2010 AACR.
C1 [Pan, Yen-Chun; Chen, Pei-Jung; Wu, Wen-Chun; Chang, Wen-Chang; Wang, Ju-Ming] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 70101, Taiwan.
[Li, Chien-Feng] Chi Mei Med Ctr, Dept Pathol, Tainan, Taiwan.
[Ko, Chiung-Yuan; Chang, Wen-Chang; Wang, Ju-Ming] Natl Kaohsiung Marine Univ, Ctr Gene Regulat & Signal Transduct Res, Kaohsiung, Taiwan.
[Pan, Min-Hsiung] Natl Kaohsiung Marine Univ, Dept Seafood Sci, Kaohsiung, Taiwan.
[Tseng, Joseph T.; Wang, Ju-Ming] Kaohsiung Med Univ, Inst Bioinformat & Biosignal Transduct, Coll Biosci & Biotechnol, Kaohsiung, Taiwan.
[Huang, A-Mei] Kaohsiung Med Univ, Grad Inst Biochem, Dept Med, Kaohsiung, Taiwan.
[Sterneck, Esta] NCI, Ctr Canc Res, Frederick, MD 21701 USA.
RP Wang, JM (reprint author), Natl Cheng Kung Univ, Inst Biosignal Transduct, Coll Biosci & Biotechnol, Tainan 70101, Taiwan.
RI wang, ju-ming/A-1875-2011;
OI Pan, Min-Hsiung/0000-0002-5188-7030
FU NSC [96-2320-B-006-044-MY2]; NCKU (Taiwan) [C007]
FX This work was supported in part by NSC grant 96-2320-B-006-044-MY2 and
by NCKU landmark grant C007 (Taiwan). Fund for Open Access publication
was provided by the NCKU landmark grant C007.
NR 49
TC 19
Z9 19
U1 2
U2 8
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 2010
VL 16
IS 23
BP 5770
EP 5780
DI 10.1158/1078-0432.CCR-10-1025
PG 11
WC Oncology
SC Oncology
GA 690XU
UT WOS:000285044200017
PM 20971808
ER
PT J
AU Nguyen, GH
Schetter, AJ
Chou, DB
Bowman, ED
Zhao, RH
Hawkes, JE
Mathe, EA
Kumamoto, K
Zhao, YQ
Budhu, A
Hagiwara, N
Wang, XW
Miyashita, M
Casson, AG
Harris, CC
AF Nguyen, Giang Huong
Schetter, Aaron J.
Chou, David B.
Bowman, Elise D.
Zhao, Ronghua
Hawkes, Jason E.
Mathe, Ewy A.
Kumamoto, Kensuke
Zhao, Yiqiang
Budhu, Anuradha
Hagiwara, Nobutoshi
Wang, Xin Wei
Miyashita, Masao
Casson, Alan G.
Harris, Curtis C.
TI Inflammatory and MicroRNA Gene Expression as Prognostic Classifier of
Barrett's-Associated Esophageal Adenocarcinoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; CANCER; METAPLASIA; DIFFERENTIATION; CYTOKINE;
PROGRESSION; SURVIVAL; TUMORS; INTERLEUKIN-18; SIGNATURE
AB Purpose: Esophageal cancer is one of the most aggressive and deadly forms of cancer; highlighting the need to identify biomarkers for early detection and prognostic classification. Our recent studies have identified inflammatory gene and microRNA signatures derived from tumor and nontumor tissues as prognostic biomarkers of hepatocellular, lung, and colorectal adenocarcinoma. Here, we examine the relationship between expression of these inflammatory genes and micro RNA (miRNA) expression in esophageal adenocarcinoma and patient survival.
Experimental Design: We measured the expression of 23 inflammation-associated genes in tumors and adjacent normal tissues from 93 patients (58 Barrett's and 35 Sporadic adenocarcinomas) by quantitative reverse transcription-polymerase chain reaction. These data were used to build an inflammatory risk model, based on multivariate Cox regression, to predict survival in a training cohort (n = 47). We then determined whether this model could predict survival in a cohort of 46 patients. Expression data for miRNA-375 were available for these patients and was combined with inflammatory gene expression.
Results: IFN-gamma, IL-1 alpha, IL-8, IL-21, IL-23, and proteoglycan expression in tumor and nontumor samples were each associated with poor prognosis based on Cox regression [(Z-score)>1.5] and therefore were used to generate an inflammatory risk score (IRS). Patients with a high IRS had poor prognosis compared with those with a low IRS in the training (P = 0.002) and test (P = 0.012) cohorts. This association was stronger in the group with Barrett's history. When combining with miRNA-375, the combined IRS/miR signature was an improved prognostic classifier than either one alone.
Conclusion: Transcriptional profiling of inflammation-associated genes and miRNA expression in resected esophageal Barrett's-associated adenocarcinoma tissues may have clinical utility as predictors of prognosis. Clin Cancer Res; 16(23); 5824-34. (C)2010 AACR.
C1 [Nguyen, Giang Huong; Schetter, Aaron J.; Bowman, Elise D.; Hawkes, Jason E.; Mathe, Ewy A.; Kumamoto, Kensuke; Zhao, Yiqiang; Budhu, Anuradha; Wang, Xin Wei; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Nguyen, Giang Huong; Chou, David B.; Hawkes, Jason E.] Howard Hughes Med Inst, Howard Hughes Med Inst Natl Inst Hlth, Chevy Chase, MD 20815 USA.
[Schetter, Aaron J.] NCI, Canc Prevent Fellowship Program, Off Director, NIH, Bethesda, MD 20892 USA.
[Chou, David B.] NIAID, Mucosal Immun Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Zhao, Ronghua; Casson, Alan G.] Univ Saskatchewan, Dept Surg, Saskatoon, SK, Canada.
[Zhao, Yiqiang] Peking Univ, Beijing 100871, Peoples R China.
[Hagiwara, Nobutoshi; Miyashita, Masao] Nippon Med Sch, Dept Surg, Tokyo 113, Japan.
RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 3068, Bethesda, MD 20892 USA.
EM curtis_harris@nih.gov
RI Wang, Xin/B-6162-2009;
OI Hawkes, Jason E./0000-0001-5870-181X
FU Howard Hughes Medical Institute; Office of the Director, National Cancer
Institute, National Institutes of Health; Nova Scotia Health Research
Foundation; National Cancer Institute of Canada; Canadian Cancer
Society; National Cancer Institute, Center for Cancer Research at the
National Institutes of Health
FX Intramural Research Program of the National Cancer Institute, Center for
Cancer Research at the National Institutes of Health. G. H. Nguyen, D.
B. Chou, and J. E. Hawkes were supported by the Howard Hughes Medical
Institute Grant for Graduate Medical Education. A. J. Schetter was
supported by the Cancer Prevention Fellowship Program, Office of the
Director, National Cancer Institute, National Institutes of Health. A.
G. Casson was supported by the Nova Scotia Health Research Foundation
and the National Cancer Institute of Canada with funds from the Canadian
Cancer Society.
NR 46
TC 45
Z9 47
U1 1
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD DEC 1
PY 2010
VL 16
IS 23
BP 5824
EP 5834
DI 10.1158/1078-0432.CCR-10-1110
PG 11
WC Oncology
SC Oncology
GA 690XU
UT WOS:000285044200022
PM 20947516
ER
PT J
AU Davis, JL
Theoret, MR
Zheng, ZL
Lamers, CHJ
Rosenberg, SA
Morgan, RA
AF Davis, Jeremy L.
Theoret, Marc R.
Zheng, Zhili
Lamers, Cor H. J.
Rosenberg, Steven A.
Morgan, Richard A.
TI Development of Human Anti-Murine T-Cell Receptor Antibodies in Both
Responding and Nonresponding Patients Enrolled in TCR Gene Therapy
Trials
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID TUMOR-INFILTRATING LYMPHOCYTES; VERSUS-HOST-DISEASE; CANCER REGRESSION;
IMMUNE-RESPONSE; OVARIAN-CANCER; PHASE-I; RECOGNITION; ANTIGEN;
IMMUNOTHERAPY; TRANSDUCTION
AB Purpose: Immune responses to gene-modified cells are a concern in the field of human gene therapy, as they may impede effective treatment. We conducted 2 clinical trials in which cancer patients were treated with lymphocytes genetically engineered to express murine T-cell receptors (mTCR) specific for tumor-associated antigens p53 and gp100.
Experimental Design: Twenty-six patients treated with autologous lymphocytes expressing mTCR had blood and serum samples available for analysis. Patient sera were assayed for the development of a humoral immune response. Adoptive cell transfer characteristics were analyzed to identify correlates to immune response.
Results: Six of 26 (23%) patients' posttreatment sera exhibited specific binding of human anti-mTCR antibodies to lymphocytes transduced with the mTCR. Antibody development was found in both responding and nonresponding patients. The posttreatment sera of 3 of these 6 patients mediated a 60% to 99% inhibition of mTCR activity as measured by a reduction in antigen-specific interferon-gamma release. Detailed analysis of posttreatment serum revealed that antibody binding was beta-chain specific in 1 patient whereas it was alpha-chain specific in another.
Conclusions: A subset of patients treated with mTCR-engineered T cells developed antibodies directed to the mTCR variable regions and not to the constant region domains common to all mTCR. Overall, the development of a host immune response was not associated with the level of transduced cell persistence or response to therapy. In summary, patients treated with mTCR can develop an immune response to gene-modified cells in a minority of cases, but this may not affect clinical outcome. Clin Cancer Res; 16(23); 5852-61. (C)2010 AACR.
C1 [Davis, Jeremy L.; Theoret, Marc R.; Zheng, Zhili; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lamers, Cor H. J.] Daniel Denhoed Canc Ctr, Erasmus MC, Dept Med Oncol, Rotterdam, Netherlands.
RP Morgan, RA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,CRC,Room 3-5940, Bethesda, MD 20892 USA.
EM rmorgan@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 29
TC 47
Z9 49
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD DEC 1
PY 2010
VL 16
IS 23
BP 5852
EP 5861
DI 10.1158/1078-0432.CCR-10-1280
PG 10
WC Oncology
SC Oncology
GA 690XU
UT WOS:000285044200025
PM 21138872
ER
PT J
AU Pencina, MJ
D'Agostino, RB
Vasan, RS
AF Pencina, Michael J.
D'Agostino, Ralph B.
Vasan, Ramachandran S.
TI Statistical methods for assessment of added usefulness of new biomarkers
SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE
LA English
DT Review
DE calibration; discrimination; integrated discrimination improvement; net
reclassification improvement; reclassification; risk prediction
ID C-REACTIVE PROTEIN; CARDIOVASCULAR RISK PROFILE; ROC CURVE; FRAMINGHAM;
SCORE; PREDICTION; DISEASE; RECLASSIFICATION; DISCRIMINATION; CLASSIFIER
AB The discovery and development of new biomarkers continues to be an exciting and promising field. Improvement in prediction of risk of developing disease is one of the key motivations in these pursuits. Appropriate statistical measures are necessary for drawing meaningful conclusions about the clinical usefulness of these new markers. In this review, we present several novel metrics proposed to serve this purpose. We use reclassification tables constructed on the basis of clinically meaningful disease risk categories to discuss the concepts of calibration, risk separation, risk discrimination, and risk classification accuracy. We discuss the notion that the net reclassification improvement (NRI) is a simple yet informative way to summarize information contained in risk reclassification tables. In the absence of meaningful risk categories, we suggest a 'category-less' version of the NRI and integrated discrimination improvement as metrics to summarize the incremental value of new biomarkers. We also suggest that predictiveness curves be preferred to receiver operating characteristic curves as visual descriptors of a statistical model's ability to separate predicted probabilities of disease events. Reporting of standard metrics, including measures of relative risk and the c statistic, is still recommended. These concepts are illustrated with a risk prediction example using data from the Framingham Heart Study. Clin Chem Lab Med 2010; 48:1703-11.
C1 [Pencina, Michael J.] Boston Univ, Dept Biostat, Framingham Heart Study, Harvard Clin Res Inst, Boston, MA 02215 USA.
[D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Pencina, Michael J.; D'Agostino, Ralph B.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Pencina, MJ (reprint author), Boston Univ, Dept Biostat, Framingham Heart Study, Harvard Clin Res Inst, 111 Cummington St, Boston, MA 02215 USA.
EM mpencina@bu.edu; vasan@bu.edu
OI Ramachandran, Vasan/0000-0001-7357-5970
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]
FX National Heart, Lung, and Blood Institute's Framingham Heart Study;
contract/grant number: N01-HC-25195.
NR 35
TC 147
Z9 148
U1 2
U2 13
PU WALTER DE GRUYTER & CO
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 1434-6621
J9 CLIN CHEM LAB MED
JI Clin. Chem. Lab. Med.
PD DEC
PY 2010
VL 48
IS 12
BP 1703
EP 1711
DI 10.1515/CCLM.2010.340
PG 9
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 685JI
UT WOS:000284624600004
PM 20716010
ER
PT J
AU Ocean, AJ
Polite, B
Christos, P
Horvath, L
Hamilton, A
Matulich, D
Chen, HX
Sparano, JA
Kindler, HL
AF Ocean, Allyson J.
Polite, Blase
Christos, Paul
Horvath, Lisa
Hamilton, Anne
Matulich, Daniel
Chen, Helen X.
Sparano, Joseph A.
Kindler, Hedy L.
TI Cetuximab is Associated With Excessive Toxicity When Combined With
Bevacizumab Plus mFOLFOX6 in Metastatic Colorectal Carcinoma
SO CLINICAL COLORECTAL CANCER
LA English
DT Article
DE KRAS mutation; Oxaliplatin; Vascular endothelial growth factor
ID GROWTH-FACTOR RECEPTOR; PHASE-II TRIAL; 1ST-LINE TREATMENT; CANCER;
OXALIPLATIN; FLUOROURACIL; LEUCOVORIN; IRINOTECAN; CHEMOTHERAPY;
COMBINATION
AB Background: The bevacizumab-cetuximab combination has shown promising activity in chemotherapy-refractory metastatic colorectal cancer (mCRC). We sought to determine the safety and efficacy of cetuximab added to bevacizumab plus standard mFOLFOX6 (modified 5-fluorouracil [5-FU]/eucovorin/oxaliplatin) as first-line therapy for mCRC. Patients and Methods: Sixty-six patients received cetuximab (400 mg/m(2) loading dose, then 250 mg/m(2) weekly intravenously [I.V.]) plus bevacizumab 5 mg/kg and mFOLFOX6 chemotherapy every 2 weeks. The primary endpoint was toxicity. Results: The most common grade 3-4 events included diarrhea (14%), fatigue (14%), neuropathy (12%), venous thrombosis (9%), acneiform rash (8%), and desquamation (8%). A protocol-defined prohibitive adverse event occurred in 4 patients (6%), including 2 treatment-associated deaths. Thirty-seven patients (56%) discontinued therapy before disease progression because of either toxicity (n = 19; 29%) or patient withdrawal (n = 18; 27%). Twenty-eight of 37 patients (76%) who discontinued therapy before disease progression did so because of cetuximab-associated toxicity. Conclusion: Although the addition of cetuximab to bevacizumab plus mFOLFOX6 was not associated with excessive life-threatening toxicity, many patients discontinued therapy because of cetuximab-associated toxicity. Taken together with the results of recently reported phase Ill trials, cetuximab should not be used concurrently with bevacizumab and infusional 5-FU, leucovorin, and oxaliplatin chemotherapy for the treatment of mCRC.
C1 [Sparano, Joseph A.] Albert Einstein Coll Med, Montefiore Med Ctr, Weiler Div, Dept Oncol, Bronx, NY 10461 USA.
[Polite, Blase] Univ Chicago, Chicago, IL 60637 USA.
[Horvath, Lisa; Hamilton, Anne; Chen, Helen X.] Univ Sydney, Sydney, NSW 2006, Australia.
[Kindler, Hedy L.] Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA.
[Ocean, Allyson J.; Christos, Paul; Matulich, Daniel] New York Canc Consortium, New York, NY USA.
[Ocean, Allyson J.; Christos, Paul; Matulich, Daniel] Univ Chicago, Phase Consortium 2, Weill Cornell Med Coll, New York, NY USA.
RP Sparano, JA (reprint author), Albert Einstein Coll Med, Montefiore Med Ctr, Weiler Div, Dept Oncol, 2 South ,Rm 47,1825 Eastchester Rd, Bronx, NY 10461 USA.
EM jsparano@montefiore.org
FU National Institute of Health, National Cancer Institute [N01-CM-62204,
N01-CM-62201]; Genentech, Inc.
FX The authors acknowledge the late Dr. Scott Wadler, our colleague and
friend, who conceived of and designed this trial, and founded the New
York Cancer Consortium. He will be remembered for his skills as a
clinician, a scholar, and a mentor. Supported by a contract from the
National Institute of Health, National Cancer Institute (N01-CM-62204
[PI: Joseph A. Sparano]) and N01-CM-62201 [PI: Everett Vokes]).; Dr.
Ocean is a member of the Speaker's Bureau for Eli Lilly and Company,
Genentech, Inc., and sanofi-aventis U.S. Dr. Polite is a member of the
Speaker's Bureau for sanofi-aventis U.S. Dr. Polite has received
honoraria from sanofi-aventis U.S. Dr. Kindler has received research
funding from Genentech, Inc. and served as a consultant for Roche and
Genentech, Inc. Dr. Sparano has served as a consultant for Genentech and
sanofi-aventis U.S. The remaining authors report no potential conflicts
of interest.
NR 20
TC 5
Z9 5
U1 0
U2 0
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 2010
VL 9
IS 5
BP 290
EP 296
DI 10.3816/CCC.2010.n.042
PG 7
WC Oncology
SC Oncology
GA 695UU
UT WOS:000285398900004
PM 21208843
ER
PT J
AU Lee, PA
Gollenberg, AL
Hediger, ML
Himes, JH
Zhang, ZW
Louis, GMB
AF Lee, Peter A.
Gollenberg, Audra L.
Hediger, Mary L.
Himes, John H.
Zhang, Zhiwei
Louis, Germaine M. Buck
TI Luteinizing hormone, testosterone and inhibin B levels in the
peripubertal period and racial/ethnic differences among boys aged 6-11
years: analyses from NHANES III, 1988-1994
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID FOLLICLE-STIMULATING-HORMONE; NUTRITION EXAMINATION SURVEY; SECONDARY
SEXUAL CHARACTERISTICS; 3RD NATIONAL-HEALTH; BODY-MASS INDEX; PUBERTAL
STAGE; SERUM; SECRETION; ESTRADIOL; CHILDREN
AB P>Objective
To determine whether the initial physical findings of puberty are accompanied by hormonal evidence of pubertal activation of the hypothalamic-pituitary-gonadal (HPG) axis and whether racial/ethnic differences exist, we have analysed hormone levels in relation to age, onset of puberty and race/ethnicity.
Design
Cross-sectional analysis of luteinizing hormone (LH), testosterone (T) and inhibin B from banked sera from a representative sample of US boys aged 6 center dot 0-11 center dot 99 years who participated in the National Health and Nutrition Examination Survey (NHANES) III.
Patients
Eight hundred and twenty-eight boys having sera including 228 non-Hispanic white (NHW), 266 non-Hispanic black (NHB), 288 Mexican-American (MA) and 46 'other'.
Measurements
Using analysis of variance and linear regression techniques, concentrations of LH, T and inhibin B were compared by race/ethnicity for all boys and pubertal status (Tanner's Staging 1, 2 and 3+) for boys aged 8 years and older. Receiver operating curves were utilized to identify cut-points predictive of pubertal HPG status.
Results
Mean hormones levels progressively increased with age. Receiver operating characteristic (ROC) curves indicate hormones are consistent with pubertal onset as indicated by Tanner stage 2, except for T and genital stage 2. Inhibin B and LH levels increased significantly by genital stage after adjusting for age and race/ethnicity, while LH and T concentrations increased significantly across pubic hair stages. Levels of inhibin B were significantly higher for NHB boys compared with other racial/ethnic groups.
Conclusions
In these cross-sectional findings, hormone levels rise gradually as boys approach the peripubertal age, whereas an abrupt rise was not associated with the onset of physical changes of puberty.
C1 [Lee, Peter A.] Penn State Coll Med, Milton S Hershey Med Ctr, Dept Pediat, Hershey, PA 17033 USA.
[Lee, Peter A.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA.
[Gollenberg, Audra L.; Hediger, Mary L.; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD USA.
[Himes, John H.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Zhang, Zhiwei] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD USA.
RP Lee, PA (reprint author), Penn State Coll Med, Milton S Hershey Med Ctr, Dept Pediat, Hershey, PA 17033 USA.
EM plee@psu.edu
OI Buck Louis, Germaine/0000-0002-1774-4490
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development
FX Support with intramural funding from the Eunice Kennedy Shriver National
Institute of Child Health & Human Development.
NR 27
TC 5
Z9 7
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0300-0664
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD DEC
PY 2010
VL 73
IS 6
BP 744
EP 751
DI 10.1111/j.1365-2265.2010.03866.x
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 681ND
UT WOS:000284321700009
PM 20825425
ER
PT J
AU Crocker, MK
Kaplowitz, P
AF Crocker, Melissa K.
Kaplowitz, Paul
TI Treatment of paediatric hyperthyroidism but not hypothyroidism has a
significant effect on weight
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID BODY-MASS INDEX; THYROID-HORMONE; GRAVES-DISEASE; CHILDREN; MYXEDEMA;
OBESITY; THYROTOXICOSIS; ADOLESCENTS; OVERWEIGHT; THYROXINE
AB P>Objective
Thyroid hormones are involved in metabolic regulation, but the degree to which they affect body weight and body mass index (BMI) in children is unclear. We examined the effect of hypo- and hyperthyroidism on weight and BMI at the time of diagnosis and after appropriate treatment.
Design
Prospective and retrospective case series.
Patients
Children referred for thyroid dysfunction were enrolled prospectively if their total or free T4 was elevated with TSH < 0 center dot 05 mIU/ml (N = 57) or if they had a subnormal total or free T4 and TSH > 20 (N = 29).
Results
Almost all patients had at least 2 classic signs or symptoms including goitre, but hyperthyroid patients had more symptoms. Mean BMI z scores at the time of diagnosis did not significantly differ between the two groups. Males with hyperthyroidism complained of weight loss more frequently and had a lower pretreatment BMI z score than hyperthyroid females. Hypothyroid patients lost a minimal amount of weight by the first follow-up (mean of 0 center dot 3 kg) and on average gained weight by the second follow-up visit. In contrast hyperthyroid patients gained a mean of 3 center dot 4 kg at the first follow-up visit and a mean of 7 center dot 1 kg by the second.
Conclusions
Correction of hypothyroidism resulted in minimal weight loss, suggesting that hypothyroidism does not cause significant weight gain in children. In contrast, correction of the hyperthyroid state had a somewhat greater impact on weight status. These results are consistent with prior reports but surprising given the opposite metabolic effects of hypo- and hyperthyroidism.
C1 [Kaplowitz, Paul] Childrens Natl Med Ctr, Dept Endocrinol, Washington, DC 20010 USA.
[Crocker, Melissa K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Kaplowitz, P (reprint author), Childrens Natl Med Ctr, Dept Endocrinol, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM PKaplowi@cnmc.org
FU NIH, NICHD
FX Dr Crocker is supported by the Intramural Research Program of the NIH,
NICHD.
NR 24
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0300-0664
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD DEC
PY 2010
VL 73
IS 6
BP 752
EP 759
DI 10.1111/j.1365-2265.2010.03877.x
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 681ND
UT WOS:000284321700010
PM 20874768
ER
PT J
AU Madan, RA
Gulley, JL
AF Madan, Ravi A.
Gulley, James L.
TI The Current and Emerging Role of Immunotherapy in Prostate Cancer
SO CLINICAL GENITOURINARY CANCER
LA English
DT Review
DE Cancer Vaccine; Treatment
ID IMMUNOLOGICAL SELF-TOLERANCE; ANDROGEN-DEPRIVATION THERAPY; REGULATORY
T-CELLS; COMBINATION THERAPY; SIPULEUCEL-T; ANTITUMOR-ACTIVITY;
IMMUNE-RESPONSES; CUTTING EDGE; LUNG-CANCER; TUMOR-CELLS
AB Recent phase III trial results have demonstrated the effectiveness of sipuleucel-T, a therapeutic cancer vaccine, in the treatment of metastatic prostate cancer. Yet, despite the survival benefit of sipuleucel-T, questions remain about how immunologic agents can be used in the treatment of metastatic prostate cancer. The primary issue confounding researchers and practitioners about the benefits of sipuleucel-T is the lack of effect on time to progression. It may be helpful to note that recent phase II data from a different therapeutic prostate cancer vaccine (Prostvac), as well as phase III data from an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking agent in metastatic melanoma, also show improved survival without short-term changes in disease progression. Furthermore, mathematical tumor growth models provide some insight into the fact that immunologic therapies do allow for continued tumor growth, but at a slower rate, thus prolonging survival. This understanding can help to clarify the role of the newly approved sipuleucel-T in the treatment of metastatic prostate cancer. It is also possible that appropriate sequencing of therapies could further improve the clinical course for such patients. Additional clinical trials will further our understanding of the role of therapeutic cancer vaccines and add new agents to the armamentarium of therapy for patients with prostate cancer.
C1 [Madan, Ravi A.; Gulley, James L.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Madan, Ravi A.; Gulley, James L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Madan, RA (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU National Cancer Institute, Center for Cancer Research, National
Institutes of Health
FX Financial support was provided by the Intramural Research Program of the
National Cancer Institute, Center for Cancer Research, National
Institutes of Health. The authors thank Bonnie L. Casey for her
editorial assistance in the preparation of this manuscript.
NR 75
TC 8
Z9 9
U1 1
U2 4
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1558-7673
J9 CLIN GENITOURIN CANC
JI Clin. Genitourin. Cancer
PD DEC
PY 2010
VL 8
IS 1
BP 10
EP 16
DI 10.3816/CGC.2010.n.002
PG 7
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 700KV
UT WOS:000285738600002
PM 21208850
ER
PT J
AU Dembele, B
Coulibaly, YI
Dolo, H
Konate, S
Coulibaly, SY
Sanogo, D
Soumaoro, L
Coulibaly, ME
Doumbia, SS
Diallo, AA
Traore, SF
Keita, AD
Fay, MP
Nutman, TB
Klion, AD
AF Dembele, Benoit
Coulibaly, Yaya I.
Dolo, Housseini
Konate, Siaka
Coulibaly, Siaka Y.
Sanogo, Dramane
Soumaoro, Lamine
Coulibaly, Michel E.
Doumbia, Salif Seriba
Diallo, Abdallah A.
Traore, Sekou F.
Keita, Adama Diaman
Fay, Michael P.
Nutman, Thomas B.
Klion, Amy D.
TI Use of High-Dose, Twice-Yearly Albendazole and Ivermectin to Suppress
Wuchereria bancrofti Microfilarial Levels
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID LYMPHATIC FILARIASIS; DIETHYLCARBAMAZINE; COMBINATION; ELIMINATION;
EFFICACY; SAFETY
AB (See the editorial commentary by Kazura, on pages 1236-1237.)
Background. Annual mass treatment with albendazole and ivermectin is the mainstay of current strategies to interrupt transmission of Wuchereria bancrofti in Africa. More-effective microfilarial suppression could potentially reduce the time necessary to interrupt transmission, easing the economic burden of mass treatment programs in countries with limited resources.
Methods. To determine the effect of increased dose and frequency of albendazole-ivermectin treatment on microfilarial clearance, 51 W. bancrofti microfilaremic residents of an area of W. bancrofti endemicity in Mali were randomized to receive 2 doses of annual, standard-dose albendazole-ivermectin therapy (400 mg and 150 mg/kg;) n = 26 or 4 doses of twice-yearly, increased-dose albendazole-ivermectin therapy (800 mg and 400 mg/kg; n = 25).
Results. Although microfilarial levels decreased significantly after therapy in both groups, levels were significantly lower in the high-dose, twice-yearly group at 12, 18, and 24 months. Furthermore, there was complete clearance of detectable microfilariae at 12 months in the 19 patients in the twice-yearly therapy group with data available at 12 months, compared with 9 of 21 patients in the annual therapy group (P < .001, by Fisher's exact test). This difference between the 2 groups was sustained at 18 and 24 months, with no detectable microfilariae in the patients receiving twice-yearly treatment. Worm nests detectable by ultrasonography and W. bancrofti circulating antigen levels, as measured by enzyme-linked immunosorbent assay, were decreased to the same degree in both groups at 24 months, compared with baseline.
Conclusions. These findings suggest that increasing the dosage and frequency of albendazole-ivermectin treatment enhances suppression of microfilariae but that this effect may not be attributable to improved adulticidal activity.
C1 [Nutman, Thomas B.; Klion, Amy D.] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Dembele, Benoit; Coulibaly, Yaya I.; Dolo, Housseini; Konate, Siaka; Coulibaly, Siaka Y.; Sanogo, Dramane; Soumaoro, Lamine; Coulibaly, Michel E.; Doumbia, Salif Seriba; Diallo, Abdallah A.; Traore, Sekou F.] Univ Bamako, Filariasis Unit, Fac Med Pharm & Dent, Bamako, Mali.
[Keita, Adama Diaman] Hosp Point G, Dept Radiol, Bamako, Mali.
[Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Klion, AD (reprint author), NIH, Parasit Dis Lab, Bldg 50,Rm 6351, Bethesda, MD 20892 USA.
EM aklion@nih.gov
OI Klion, Amy/0000-0002-4986-5326; Fay, Michael P./0000-0002-8643-9625
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases; Task Force for Global Health
FX Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases, and the Task
Force for Global Health (to A.D.K.).
NR 19
TC 12
Z9 12
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD DEC 1
PY 2010
VL 51
IS 11
BP 1229
EP 1235
DI 10.1086/657063
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 675RZ
UT WOS:000283850200003
PM 21039220
ER
PT J
AU Oliveira, R
Krauss, M
Essama-Bibi, S
Hofer, C
Harris, DR
Tiraboschi, A
de Souza, R
Marques, H
Succi, R
Abreu, T
Della Negra, M
Hazra, R
Mofenson, LM
Siberry, GK
AF Oliveira, Ricardo
Krauss, Margot
Essama-Bibi, Suzanne
Hofer, Cristina
Harris, D. Robert
Tiraboschi, Adriana
de Souza, Ricardo
Marques, Heloisa
Succi, Regina
Abreu, Thalita
Della Negra, Marinella
Hazra, Rohan
Mofenson, Lynne M.
Siberry, George K.
CA NISDI Pediat Study Group 2010
TI Viral Load Predicts New World Health Organization Stage 3 and 4 Events
in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy,
Independent of CD4 T Lymphocyte Value
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RESOURCE-LIMITED SETTINGS; HIV-1-INFECTED
CHILDREN; DISEASE PROGRESSION; VIROLOGICAL FAILURE; MORTALITY; INFANTS;
ADULTS; METAANALYSIS; OUTCOMES
AB Background. Many resource-limited countries rely on clinical and immunological monitoring without routine virological monitoring for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). We assessed whether HIV load had independent predictive value in the presence of immunological and clinical data for the occurrence of new World Health Organization (WHO) stage 3 or 4 events (hereafter, WHO events) among HIV-infected children receiving HAART in Latin America.
Methods. The NISDI (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative) Pediatric Protocol is an observational cohort study designed to describe HIV-related outcomes among infected children. Eligibility criteria for this analysis included perinatal infection, age ! 15 years, and continuous HAART for >= 6 months. Cox proportional hazards modeling was used to assess time to new WHO events as a function of immunological status, viral load, hemoglobin level, and potential confounding variables; laboratory tests repeated during the study were treated as time-varying predictors.
Results. The mean duration of follow-up was 2.5 years; new WHO events occurred in 92 (15.8%) of 584 children. In proportional hazards modeling, most recent viral load 15000 copies/mL was associated with a nearly doubled risk of developing a WHO event (adjusted hazard ratio, 1.81; 95% confidence interval, 1.05-3.11; P = 033), even after adjustment for immunological status defined on the basis of CD4 T lymphocyte value, hemoglobin level, age, and body mass index.
Conclusions. Routine virological monitoring using the WHO virological failure threshold of 5000 copies/mL adds independent predictive value to immunological and clinical assessments for identification of children receiving HAART who are at risk for significant HIV-related illness. To provide optimal care, periodic virological monitoring should be considered for all settings that provide HAART to children.
C1 [Hazra, Rohan; Mofenson, Lynne M.; Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA.
[Oliveira, Ricardo; Hofer, Cristina; Abreu, Thalita] Univ Fed Rio de Janeiro, Inst Puericultura & Pediat Martagao Gesteira, Rio De Janeiro, Brazil.
[Tiraboschi, Adriana] Univ Sao Paulo, Fac Med Ribeirao Preto, Sao Paulo, Brazil.
[Marques, Heloisa] Univ Sao Paulo, Fac Med Sao Paulo, Sao Paulo, Brazil.
[Succi, Regina] Univ Fed Sao Paulo, Sao Paulo, Brazil.
[Della Negra, Marinella] Inst Infectol Emilio Ribas, Sao Paulo, Brazil.
[de Souza, Ricardo] Univ Caxias Sul, Serv Municipal Infectol, Caxias Do Sul, Brazil.
[Krauss, Margot; Essama-Bibi, Suzanne; Harris, D. Robert] WESTAT Corp, Rockville, MD 20850 USA.
RP Siberry, GK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, 6100 Execut Blvd,Room 4B11H, Bethesda, MD 20892 USA.
EM siberryg@mail.nih.gov
RI Mussi-Pinhata, Marisa/G-6568-2012;
OI Mofenson, Lynne/0000-0002-2818-9808
FU NICHD [HHSN267200800001C, N01-HD-8-0001]
FX NICHD (contract HHSN267200800001C, control N01-HD-8-0001).
NR 28
TC 12
Z9 12
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD DEC 1
PY 2010
VL 51
IS 11
BP 1325
EP 1333
DI 10.1086/657119
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 675RZ
UT WOS:000283850200018
PM 21039218
ER
PT J
AU Bleyer, AJ
Zivna, M
Hulkova, H
Hodanova, K
Vyletal, P
Sikora, J
Zivny, J
Sovova, J
Hart, TC
Adams, JN
Elleder, M
Kapp, K
Haws, R
Cornell, LD
Kmoch, S
Hart, PS
AF Bleyer, A. J.
Zivna, M.
Hulkova, H.
Hodanova, K.
Vyletal, P.
Sikora, J.
Zivny, J.
Sovova, J.
Hart, T. C.
Adams, J. N.
Elleder, M.
Kapp, K.
Haws, R.
Cornell, L. D.
Kmoch, S.
Hart, P. S.
TI Clinical and molecular characterization of a family with a dominant
renin gene mutation and response to treatment with fludrocortisone
SO CLINICAL NEPHROLOGY
LA English
DT Article
DE anemia; children; fludrocortisone; hyperuricemia; renin mutation
ID ERYTHROID PROGENITORS; ANGIOTENSIN; PATHOGENESIS; EXPRESSION; PROTEIN
AB Background: A family was identified with autosomal dominant inheritance of anemia, polyuria, hyperuricemia, and chronic kidney disease. Mutational analysis revealed a novel heterozygous mutation c. 58T > C resulting in the amino acid substitution of cysteine for arginine in the preprorenin signal sequence (p.cys20Arg) occurring in all affected members. Methods: Effects of the identified mutation were characterized using in vitro and in vivo studies. Affected individuals were clinically characterized before and after administration of fludrocortisone. Results: The mutation affects endoplasmic reticulum co-translational translocation and post-translational processing, resulting in massive accumulation of non-glycosylated preprorenin in the cytoplasm. This affects expression of intra-renal RAS components and leads to ultrastructural damage of the kidney. Affected individuals suffered from anemia, hyperuricemia, decreased urinary concentrating ability, and progressive chronic kidney disease. Treatment with fludrocortisone in an affected 10-year-old child resulted in an increase in blood pressure and estimated glomerular filtration rate. Conclusions: A novel REN gene mutation resulted in an alteration in the amino acid sequence of the renin signal sequence and caused childhood anemia, polyuria, and kidney disease. Treatment with fludrocortisone improved renal function in an affected child. Nephrologists should consider REN mutational analysis in families with autosomal dominant inheritance of chronic kidney disease, especially if they suffer from anemia, hyperuricemia, and polyuria in childhood.
C1 [Bleyer, A. J.] Wake Forest Univ, Bowman Gray Sch Med, Nephrol Sect, Winston Salem, NC 27157 USA.
[Zivna, M.; Hodanova, K.; Vyletal, P.; Elleder, M.; Kmoch, S.] Charles Univ Prague, Fac Med 1, Ctr Appl Genom, Prague, Czech Republic.
[Zivna, M.; Hulkova, H.; Hodanova, K.; Vyletal, P.; Sikora, J.; Sovova, J.; Elleder, M.; Kmoch, S.] Charles Univ Prague, Fac Med 1, Inst Inherited Metab Disorders, Prague, Czech Republic.
[Zivny, J.] Charles Univ Prague, Fac Med 1, Inst Pathophysiol, Prague, Czech Republic.
[Hart, T. C.] NIDCR, Human Craniofacial Genet Sect, NIH, Bethesda, MD USA.
[Adams, J. N.; Hart, P. S.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Kapp, K.] Univ Heidelberg, ZMBH Ctr Mol Biol Heidelberg, Heidelberg, Germany.
[Cornell, L. D.] Mayo Clin, Dept Lab Med & Pathol, Div Anat Pathol, Rochester, MN USA.
RP Bleyer, AJ (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Nephrol Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM ableyer@wfubmc.edu
RI Vyletal, Petr/F-4771-2017; Sikora, Jakub /F-4842-2017
OI Vyletal, Petr/0000-0002-9357-1237; Sikora, Jakub /0000-0003-4104-2023
FU Ministry of Education of the Czech Republic [MSM0021620806,
1M6837805002]
FX The authors would like to thank Vicki Robins, R.N. for her important
contributions to this investigation. This work was supported by
institutional grants provided by the Ministry of Education of the Czech
Republic (projects MSM0021620806, and 1M6837805002).
NR 18
TC 11
Z9 13
U1 1
U2 7
PU DUSTRI-VERLAG DR KARL FEISTLE
PI DEISENHOFEN-MUENCHEN
PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY
SN 0301-0430
J9 CLIN NEPHROL
JI Clin. Nephrol.
PD DEC
PY 2010
VL 74
IS 6
BP 411
EP 422
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA 703QO
UT WOS:000285995200001
PM 21084044
ER
PT J
AU Momeni, P
Wickremaratchi, MM
Bell, J
Arnold, R
Beer, R
Hardy, J
Revesz, T
Neal, JW
Morris, HR
AF Momeni, Parastoo
Wickremaratchi, Mirdhu M.
Bell, Jason
Arnold, Richard
Beer, Roger
Hardy, John
Revesz, Tamas
Neal, James W.
Morris, Huw R.
TI Familial early onset frontotemporal dementia caused by a novel S356T
MAPT mutation, initially diagnosed as schizophrenia
SO CLINICAL NEUROLOGY AND NEUROSURGERY
LA English
DT Article
DE Tau; MAPT; Frontotemporal dementia; Early onset dementia
ID LOBAR DEGENERATION; PREVALENCE; FTDP-17
AB Autosomal dominant frontotemporal dementia (FTD) due to mutations in the MAPT gene is referred to as FTD with parkinsonism linked to chromosome 17 with tau pathology (FTDP-17T) Typically the disease begins in the sixth decade of life We report a novel exon 12 mutation in MAPT(S356T) in a family with an exceptionally early age at onset (27 and 29 years) causing familial behavioural variant frontotemporal dementia Both the proband and the proband s father were initially diagnosed as having schizophrenia Pathological examination showed frontotemporal lobar degeneration with extensive neuronal and glial tau deposition This mutation is one of a small group of MAPT mutations (including P301S G335V and S352L) that cause very early onset FTDP-17T It is likely that the early age at onset reflects a marked pathogenic effect of the mutation involving a disturbance of microtubule binding tau phosphorylation or a major acceleration of tau aggregation (C) 2010 Elsevier B V All rights reserved
C1 [Momeni, Parastoo] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Neurogenet Lab, Lubbock, TX 79430 USA.
[Wickremaratchi, Mirdhu M.; Morris, Huw R.] Cardiff Univ, Sch Med, Dept Neurol, Cardiff CF14 4XN, S Glam, Wales.
[Bell, Jason] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Hardy, John; Revesz, Tamas] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Neal, James W.] Cardiff Univ, Sch Med, Dept Neurolopathol, Cardiff CF14 4XN, S Glam, Wales.
[Morris, Huw R.] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF14 4XN, S Glam, Wales.
RP Morris, HR (reprint author), Cardiff Univ, Univ Wales Hosp, Sch Med Neurol C4, Dept Neurol, Cardiff CF14 4XN, S Glam, Wales.
RI Morris, Huw/B-8527-2008; turton, miranda/F-4682-2011; Hardy,
John/C-2451-2009; Revesz, Tamas/A-8732-2010
OI Morris, Huw/0000-0002-5473-3774; Revesz, Tamas/0000-0003-2501-0259
FU Ipsen Fund; Parkinson's disease society [8047]
FX MMW was sponsored by the Ipsen Fund and the Parkinson's disease society
(grant 8047) We are grateful to members of the family for participating
in this study We are grateful to Drs Ian Burgess and Abigail Ekin-Wood
for helpful advice on the manuscript
NR 10
TC 15
Z9 15
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0303-8467
J9 CLIN NEUROL NEUROSUR
JI Clin. Neurol. Neurosurg.
PD DEC
PY 2010
VL 112
IS 10
BP 917
EP 920
DI 10.1016/j.clineuro.2010.07.015
PG 4
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 689GV
UT WOS:000284916500017
PM 20708332
ER
PT J
AU Ho, MK
Goldman, D
Heinz, A
Kaprio, J
Kreek, MJ
Li, MD
Munafo, MR
Tyndale, RF
AF Ho, M. K.
Goldman, D.
Heinz, A.
Kaprio, J.
Kreek, M. J.
Li, M. D.
Munafo, M. R.
Tyndale, R. F.
TI Breaking Barriers in the Genomics and Pharmacogenetics of Drug Addiction
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID OPIOID-RECEPTOR GENE; NICOTINIC ACETYLCHOLINE-RECEPTOR;
ALCOHOL-DEPENDENT PATIENTS; DYNAMIN 1 GENE; FUNCTIONAL POLYMORPHISM;
COST-EFFECTIVENESS; SMOKING-CESSATION; OPIATE ADDICTION; WIDE
ASSOCIATION; EXPRESSION
AB Drug addiction remains a substantial health issue with limited treatment options currently available. Despite considerable advances in the understanding of human genetic architecture, the genetic underpinning of complex disorders remains elusive. On the basis of our current understanding of neurobiology, numerous candidate genes have been implicated in the etiology and response to treatment for different addictions. Genome-wide association (GWA) studies have also identified novel targets. However, replication of these studies is often lacking, and this complicates interpretation. The situation is expected to improve as issues such as phenotypic characterization, the apparent "missing heritability," the identification of functional variants, and possible gene-environment (G x E) interactions are addressed. In addition, there is growing evidence that genetic information can be useful in refining the choice of addiction treatment. As genetic testing becomes more common in the practice of medicine, a variety of ethical and practical challenges, some of which are unique to drug addiction, will also need to be considered.
C1 [Ho, M. K.; Tyndale, R. F.] Univ Toronto, Ctr Addict & Mental Hlth, Dept Psychiat Pharmacol & Toxicol, Toronto, ON, Canada.
[Goldman, D.] NIAAA, NIH, Bethesda, MD USA.
[Heinz, A.] Charite, Dept Psychiat & Psychotherapy, D-13353 Berlin, Germany.
[Kaprio, J.] Univ Helsinki, Inst Mol Med, Helsinki, Finland.
[Kaprio, J.] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.
[Kaprio, J.] Natl Inst Hlth & Welf, Helsinki, Finland.
[Kreek, M. J.] Rockefeller Univ, Lab Biol Addict Dis, New York, NY 10021 USA.
[Li, M. D.] Univ Virginia, Sch Med, Dept Psychiat & Neurobehav Sci, Charlottesville, VA 22908 USA.
[Munafo, M. R.] Univ Bristol, Dept Expt Psychol, Bristol, Avon, England.
RP Tyndale, RF (reprint author), Univ Toronto, Ctr Addict & Mental Hlth, Dept Psychiat Pharmacol & Toxicol, Toronto, ON, Canada.
EM r.tyndale@utoronto.ca
RI Goldman, David/F-9772-2010;
OI Goldman, David/0000-0002-1724-5405; Kaprio, Jaakko/0000-0002-3716-2455;
Munafo, Marcus/0000-0002-4049-993X
FU Canadian Institutes of Health Research [MOP86471]; Intramural NIH HHS
[Z01 AA000280-18]; NCRR NIH HHS [UL1 RR024143]; NIDA NIH HHS [P60
DA005130, DA 0220830, DA012844, DA012854, DA013783, P60-DA005130, R01
DA012844, R01 DA012854, R01 DA013783, R56 DA012854, U01 DA020830]; NIMH
NIH HHS [R01 MH076537, R01 MH079880, R01-MH79880, R21 MH097639]
NR 50
TC 29
Z9 31
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD DEC
PY 2010
VL 88
IS 6
BP 779
EP 791
DI 10.1038/clpt.2010.175
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 684BR
UT WOS:000284522500019
PM 20981002
ER
PT J
AU Blanco, I
Beritze, N
Arguelles, M
Carcaba, V
Fernandez, F
Janciauskiene, S
Oikonomopoulou, K
de Serres, FJ
Fernandez-Bustillo, E
Hollenberg, MD
AF Blanco, Ignacio
Beritze, Nana
Argueelles, Mario
Carcaba, Victoriano
Fernandez, Fernando
Janciauskiene, Sabina
Oikonomopoulou, Katerina
de Serres, Frederick J.
Fernandez-Bustillo, Enrique
Hollenberg, Morley D.
TI Abnormal overexpression of mastocytes in skin biopsies of fibromyalgia
patients
SO CLINICAL RHEUMATOLOGY
LA English
DT Article
DE Alpha 1-antitrypsin; Fibromyalgia; Mast cell; Skin biopsy; Tryptase
ID HUMAN MAST-CELLS; ALPHA-1-ANTITRYPSIN; CLASSIFICATION; CRITERIA;
DEFICIENCY; DIAGNOSIS; IGG
AB Formalin-fixed, paraffin-embedded skin tissue sections were collected from a matched cohort of 63 fibromyalgia syndrome (FMS) patients and 49 volunteers from the general population with both alpha1-antitrypsin (AAT) normal and deficiency variants. These tissues were examined for the expression of the broad-spectrum inhibitor AAT, the serine proteinases elastase and tryptase, the proinflammatory cytokines MCP-1 and TNF alpha, the endothelium biomarker VEGF, and the inflammation/nociception-related receptor PAR(2). The most relevant finding of the study was a significantly increased number of mast cells (MCs) in the papillary dermis of all FMS patients (greater than or equal to five to 14 per microscopic high power field) compared to zero to one in controls (p<0.001). MCs strongly stained with tryptase, AAT and PAR(2) antibodies, exhibited a spindle-like shape and were uniformly distributed around blood vessels and appendages. MCP-1 and VEGF expressed weak/moderate positivity in most samples, with a higher expression in controls than in FMS patients (p<0.001 and 0.051, respectively). No differences in elastase and TNF alpha were found between both groups. Moreover, no histological differences were found between samples from AAT deficiency and normal AAT phenotypes. Our results indicate that FMS is a MC-associated condition. MCs are present in skin and mucosal surfaces throughout the human body, and are easily stimulated by a number of physical, psychological, and chemical triggers to degranulate, releasing several proinflammatory products which are able to generate nervous peripheral stimuli causing CNS hypersensitivity, local, and systemic symptoms. Our findings open new avenues of research on FMS mechanisms and will benefit the diagnosis of patients and the development of therapeutics.
C1 [Blanco, Ignacio; Carcaba, Victoriano] Valle Nalon Hosp, Dept Internal Med, Sama De Langreo 33920, Principado Astu, Spain.
[Beritze, Nana; Argueelles, Mario] Cabuenes Hosp, Dept Pathol, Gijon, Principado Astu, Spain.
[Fernandez, Fernando] Valle Nalon Hosp, Dept Surg, Sama De Langreo 33920, Principado Astu, Spain.
[Janciauskiene, Sabina] Hannover Med Sch, Dept Resp Med, D-30625 Hannover, Germany.
[Oikonomopoulou, Katerina] Univ Calgary, Dept Physiol & Pharmacol, Calgary, AB, Canada.
[Oikonomopoulou, Katerina] Univ Calgary, Dept Med, Calgary, AB, Canada.
[de Serres, Frederick J.] Ctr Evaluat Risks Human Reprod, Natl Inst Environm Hlth Sci, MD EC32, Res Triangle Pk, NC 27709 USA.
[Fernandez-Bustillo, Enrique] Cent Univ Hosp Asturias, Biostat Unit, Oviedo 33006, Principado Astu, Spain.
[Hollenberg, Morley D.] Med Univ Calgary, Fac Med Calgary, Dept Physiol & Pharmacol, Calgary, AB T2N 4N1, Canada.
RP Blanco, I (reprint author), Valle Nalon Hosp, Dept Internal Med, Sama De Langreo 33920, Principado Astu, Spain.
EM ignablanco@yahoo.com; nanarus@terra.es;
mario.arguelles@sespa.princast.es; victoriano.carcaba@sespa.princast.es;
frfernando@telecable.es; SabinaJanciauskiene@gmail.com;
oikoa@mail.med.upenn.edu; deserres@bellsouth.net; efbustillo@hca.es;
mhollenb@ucalgary.ca
OI Blanco, Ignacio/0000-0002-7414-7481
FU Alberta Heritage Foundation for Medical Research (AHFMR); Canadian
Institutes of Health Research
FX We would like to thank every patient and volunteer who participated in
this study, providing us with their clinical data and biopsy samples. We
also acknowledge the technical work for the preparation of the
paraffin-embedded tissues samples by Dr. Francisco Dominguez and
laboratory technicians at the Valle del Nalon Hospital, Asturias, Spain;
and the immunohistochemical work performed by Ms. Mercedes Acha
(Cabuenes Hospital, Gijon, Spain). Furthermore, we are indebted to Dr.
Eleftherios P. Diamandis (Mount Sinai Hospital, Toronto) for sharing
vital reagents and ideas for the completion of this work. Finally, we
are grateful to Ms. Jimena Blanco Fueyo (UNESCO; MA/BA Universite de
Geneve) for the English editing of this manuscript. This study has been
endorsed by the Spanish National Health Institute Carlos III and the
Biohealth Research Office (OIB) of the Principado de Asturias, Spain (IB
and VC). KO is a recipient of an Alberta Heritage Foundation for Medical
Research (AHFMR) Postdoctoral Fellowship for whom operating funds were
provided by a grant to MDH by the Canadian Institutes of Health
Research.
NR 27
TC 42
Z9 42
U1 0
U2 2
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0770-3198
EI 1434-9949
J9 CLIN RHEUMATOL
JI Clin. Rheumatol.
PD DEC
PY 2010
VL 29
IS 12
BP 1403
EP 1412
DI 10.1007/s10067-010-1474-7
PG 10
WC Rheumatology
SC Rheumatology
GA 684KA
UT WOS:000284547600010
PM 20428906
ER
PT J
AU Korn, EL
Dodd, LE
Freidlin, B
AF Korn, Edward L.
Dodd, Lori E.
Freidlin, Boris
TI Measurement error in the timing of events: effect on survival analyses
in randomized clinical trials
SO CLINICAL TRIALS
LA English
DT Article
ID PROGRESSION-FREE SURVIVAL
AB Background Presence of measurement error in the outcome can complicate the interpretation of a randomized clinical trial. The Oncologic Drugs Advisory Committee of the US Food and Drug Administration voted against recommending approval of bevacizumab for the initial treatment of metastatic breast cancer; one of their major concerns was the presence of a large amount of nondifferential measurement error in the evaluation of progression-free survival, the primary outcome of the randomized clinical trial E2100.
Purpose To investigate the effects of nondifferential measurement error in time-to-event outcomes on the conclusions of a proportional hazards analysis of a randomized clinical trial.
Methods Simulations were performed showing effects of measurement error on the estimated treatment effect (hazard ratio) in a clinical trial. In some simulations, the measurement error structure from E2100 data was approximated; for other simulations, larger or smaller measurement error was considered.
Results The bias in estimating the hazard ratio was very small using measurement error and a hazard ratio similar to E2100. Even with a larger nondifferential measurement error, the bias remained small when the hazard ratio was in a range commonly seen in clinical trials. There was no or little effect on the variability of the estimated treatment effect.
Limitations Because of censoring issues, retrospective evaluation of the measurement error structure from a completed trial is difficult. Although our simulations cover a range of plausible measurement error values, in theory, a trial could have much larger measurement error than we considered. Differential measurement error is only briefly considered.
Conclusions Nondifferential measurement error due to variability in estimating time-to-event outcomes will typically not be a major concern in randomized clinical trials. Clinical Trials 2010; 7: 626-633. http://ctj.sagepub.com
C1 [Korn, Edward L.; Freidlin, Boris] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
[Dodd, Lori E.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
RP Korn, EL (reprint author), NCI, Biometr Res Branch, EPN 8129,MSC 7434, Bethesda, MD 20892 USA.
EM korne@ctep.nci.nih.gov
NR 15
TC 9
Z9 9
U1 2
U2 6
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
J9 CLIN TRIALS
JI Clin. Trials
PD DEC
PY 2010
VL 7
IS 6
BP 626
EP 633
DI 10.1177/1740774510382801
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 691QE
UT WOS:000285095100003
PM 20819840
ER
PT J
AU Hunsberger, S
Albert, PS
Dodd, L
AF Hunsberger, Sally
Albert, Paul S.
Dodd, Lori
TI Analysis of progression-free survival data using a discrete time
survival model that incorporates measurements with and without
diagnostic error
SO CLINICAL TRIALS
LA English
DT Article
ID PROPORTIONAL HAZARDS MODELS; MISMEASURED OUTCOMES
AB Background In cancer studies progression-free survival (PFS) is becoming a very important endpoint in the development of new therapeutic agents. Two methods of determining progression are typically used: (1) the local radiologist evaluates scans and (2) scans are reviewed by an independent blinded (central) reviewer. The second method is considered to be the reference standard but is expensive, time consuming, and logistically difficult. The first method has measurement error associated with it, but, it is less expensive and easier to obtain.
Purpose This article explores a new
method for analyzing PFS data. Methods When PFS data using the test with measurement error are analyzed, inferences about covariate effects may be invalid due to bias. A sampling strategy is evaluated where data are collected on a subset of subjects using the reference test and on all subjects using the test that has error. The strategy is designed to maintain valid inferences while requiring the more expensive or difficult test on a small proportion of patients. In the analysis of the data we incorporate subject-specific and time-dependent covariates into the diagnostic errors (sensitivity and specificity) of the tests. We also propose a modeling formulation that accounts for unobserved covariate affects on diagnostic error through a shared random effect. We explore the effect of different diagnostic test properties on inference via simulation and use the methodology to analyze a renal cancer example.
Results The simulations show inference is correct when a subset of measurements without error are collected.
Limitations When the sensitivity and specificity of the local review is low a large fraction of centrally reviewed tests are needed to have high efficiency.
Conclusions When designing a study where PFS is the primary endpoint collecting centrally reviewed data on a subset of patients may provide a valid an more feasible approach than collecting centrally reviewed data on all patients. Clinical Trials 2010; 7: 634-642. http://ctj.sagepub.com
C1 [Hunsberger, Sally] NCI, Biostat Res Branch, Rockville, MD USA.
[Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD USA.
[Dodd, Lori] NIAID, Rockville, MD USA.
RP Hunsberger, S (reprint author), NCI, Biostat Res Branch, Rockville, MD USA.
EM sallyh@ctep.nci.nih.gov
NR 13
TC 2
Z9 2
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
J9 CLIN TRIALS
JI Clin. Trials
PD DEC
PY 2010
VL 7
IS 6
BP 634
EP 642
DI 10.1177/1740774510384887
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 691QE
UT WOS:000285095100004
PM 21109582
ER
PT J
AU Read, JS
AF Read, Jennifer S.
TI Prevention of Mother-to-Child Transmission of HIV: Antiretroviral
Strategies
SO CLINICS IN PERINATOLOGY
LA English
DT Article
DE Mother-to-child transmission; HIV-1; Prevention; Antiretrovirals
ID HUMAN-IMMUNODEFICIENCY-VIRUS; LOW-BIRTH-WEIGHT; PERSISTENT MITOCHONDRIAL
DYSFUNCTION; RANDOMIZED CONTROLLED-TRIAL; INFECTED WOMEN; PERINATAL
TRANSMISSION; UNINFECTED CHILDREN; PREGNANT-WOMEN; PRETERM BIRTH;
CONGENITAL-ABNORMALITIES
AB The World Health Organization's Strategic Approaches to the Prevention of HIV Infection in Infants includes 4 components: primary prevention of HIV-1 infection; prevention of unintended pregnancies among HIV-1-infected women; prevention of transmission of HIV-1 infection from mothers to children; and provision of ongoing support, care, and treatment to HIV-1-infected women and their families. This review focuses on antiretrovirals for secondary prevention of HIV-1 infection-prevention of HIV-1 transmission from an HIV-1-infected woman to her child. Antiretroviral strategies to prevent the mother-to-child transmission of HIV-1 in nonbreastfeeding populations comprise antiretroviral treatment of HIV-1-infected pregnant women needing antiretrovirals for their own health, antiretroviral prophylaxis for HIV-1-infected pregnant women not yet meeting criteria for treatment, and antiretroviral prophylaxis for infants of HIV-1-infected mothers. The review primarily addresses antiretroviral strategies for nonbreastfeeding, HIV-1-infected women and their infants in resource-rich settings, such as the United States. Antiretroviral strategies to prevent antepartum, intrapartum, and early postnatal transmission in resource-poor settings are also addressed, albeit more briefly.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA.
RP Read, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Execut Bldg,Room 4B11C,6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA.
EM JENNIFER_READ@NIH.GOV
NR 59
TC 9
Z9 9
U1 0
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0095-5108
J9 CLIN PERINATOL
JI Clin. Perinatol.
PD DEC
PY 2010
VL 37
IS 4
BP 765
EP +
DI 10.1016/j.clp.2010.08.007
PG 13
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 697AQ
UT WOS:000285485400007
PM 21078449
ER
PT J
AU Legardy-Williams, JK
Jamieson, DJ
Read, JS
AF Legardy-Williams, Jennifer K.
Jamieson, Denise J.
Read, Jennifer S.
TI Prevention of Mother-to-Child Transmission of HIV: The Role of Cesarean
Delivery
SO CLINICS IN PERINATOLOGY
LA English
DT Article
DE Mother-to-child transmission; Cesarean delivery; HIV; Prevention
ID HUMAN-IMMUNODEFICIENCY-VIRUS; FRENCH PERINATAL COHORT; INFECTED WOMEN;
VERTICAL TRANSMISSION; POSTPARTUM MORBIDITY; ANTIRETROVIRAL THERAPY;
RESPIRATORY MORBIDITY; HIV-1-INFECTED WOMEN; RUPTURED MEMBRANES; VAGINAL
DELIVERY
AB The risk of mother-to-child transmission (MTCT) of HIV can be reduced through cesarean delivery prior to the onset of labor and prior to rupture of the membranes (elective cesarean delivery [ECD]). As a result of this evidence, the American College of Obstetricians and Gynecologists and the Department of Health and Human Services Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission developed guidelines recommending ECD for HIV-infected women with plasma viral loads of more than 1000 copies/mL. Since the release of the recommendations, an increase in ECD has been seen among HIV-infected women in the United States. This article discusses the evidence on efficacy of ECD, current recommendations in the United States, and risks and morbidity related to ECD. Although the benefit of ECD in preventing MTCT of HIV is substantial, some questions remain. Specifically, the benefit of ECD for women with very low viral loads or for women using combination antiretroviral regimens is unclear, as is the timeframe after onset of labor or rupture of membranes within which ECD will still confer preventive benefits.
C1 [Legardy-Williams, Jennifer K.; Jamieson, Denise J.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA.
[Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA.
RP Legardy-Williams, JK (reprint author), Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway,MS-K-34, Atlanta, GA 30341 USA.
EM jlegardy@cdc.gov
NR 58
TC 7
Z9 9
U1 0
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0095-5108
J9 CLIN PERINATOL
JI Clin. Perinatol.
PD DEC
PY 2010
VL 37
IS 4
BP 777
EP +
DI 10.1016/j.clp.2010.08.013
PG 10
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 697AQ
UT WOS:000285485400008
PM 21078450
ER
PT J
AU Dundr, M
Misteli, T
AF Dundr, Miroslav
Misteli, Tom
TI Biogenesis of Nuclear Bodies
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID MAMMALIAN-CELL NUCLEUS; SIMPLEX-VIRUS TYPE-1; PRE-RIBOSOMAL-RNA; LIVE
HUMAN-CELLS; CAJAL BODIES; IN-VIVO; SPLICING FACTORS; COILED BODIES;
REPLICATION COMPARTMENTS; MUTATIONAL ANALYSIS
AB The nucleus is unique amongst cellular organelles in that it contains a myriad of discrete suborganelles. These nuclear bodies are morphologically and molecularly distinct entities, and they host specific nuclear processes. Although the mode of biogenesis appears to differ widely between individual nuclear bodies, several common design principles are emerging, particularly, the ability of nuclear bodies to form de novo, a role of RNA as a structural element and self-organization as a mode of formation. The controlled biogenesis of nuclear bodies is essential for faithful maintenance of nuclear architecture during the cell cycle and is an important part of cellular responses to intra-and extracellular events.
C1 [Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
[Dundr, Miroslav] Rosalind Franklin Univ Med & Sci, Dept Cell Biol, N Chicago, IL 60064 USA.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mirek.dundr@rosalindfranklin.edu; mistelit@mail.nih.gov
FU Intramural NIH HHS [Z01 BC010309-10]
NR 86
TC 102
Z9 105
U1 0
U2 10
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 2010
VL 2
IS 12
AR a000711
DI 10.1101/cshperspect.a000711
PG 15
WC Cell Biology
SC Cell Biology
GA 688RB
UT WOS:000284868600001
PM 21068152
ER
PT J
AU Evans, AN
Henning, T
Gelsleichter, J
Nunez, BS
AF Evans, Andrew N.
Henning, Toni
Gelsleichter, James
Nunez, B. Scott
TI Molecular classification of an elasmobranch angiotensin receptor:
Quantification of angiotensin receptor and natriuretic peptide receptor
mRNAs in saltwater and freshwater populations of the Atlantic stingray
SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR
BIOLOGY
LA English
DT Article
DE Angiotensin receptor; Elasmobranch; Natriuretic peptides; Natriuretic
peptide receptor; Osmoregulation; Renin-angiotensin system
ID SHARK RECTAL GLAND; II TYPE-1 RECEPTOR; ST JOHNS RIVER; DASYATIS-SABINA;
SQUALUS-ACANTHIAS; EURYHALINE ELASMOBRANCH; SCYLIORHINUS-CANICULA;
ONCORHYNCHUS-MYKISS; AT(1) RECEPTOR; RAINBOW-TROUT
AB Among the most conserved osmoregulatory hormone systems in vertebrates are the renin-angiotensin system (RAS) and the natriuretic peptides (NPs). We examined the RAS and NP system in the euryhaline Atlantic stingray, Dasyatis sabina (Lesueur). To determine the relative sensitivity of target organs to these hormonal systems, we isolated cDNA sequences encoding the D. sabina angiotensin receptor (AT) and natriuretic peptide type-B receptor (NPR-B). We then determined the tissue-specific expression of their mRNAs in saltwater D. sabina from local Texas waters and an isolated freshwater population in Lake Monroe, Florida. AT mRNA was most abundant in interrenal tissue from both populations. NPR-B mRNA was most abundant in rectal gland tissue from both populations, and also highly abundant in the kidney of saltwater D. sabina. This study is the first to report the sequence of an elasmobranch angiotensin receptor, and phylogenetic analysis indicates that the D. sabina receptor is more similar to AT(1) vs. AT(2) proteins. This classification is further supported by molecular analysis of AT(1) and AT(2) proteins demonstrating conservation of AT(1)-specific amino acid residues and motifs in D. sabina AT. Molecular classification of the elasmobranch angiotensin receptor as an AT(1)-like protein provides fundamental insight into the evolution of the vertebrate RAS. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Evans, Andrew N.; Henning, Toni] Univ Texas Marine Sci Inst, Port Aransas, TX 78373 USA.
[Gelsleichter, James] Mote Marine Lab, Sarasota, FL 34236 USA.
[Nunez, B. Scott] Lee Coll, Baytown, TX 77522 USA.
RP Evans, AN (reprint author), NICHHD, 10 Ctr Dr,Rm 1-3272, Bethesda, MD 20892 USA.
EM evansan@mail.nih.gov
OI Evans, Andrew/0000-0002-5366-9942
FU National Science Foundation [GK-12]; University of Texas Marine Science
Institute; NSF [IBN-0416454]; Coastal Conservation Association of Texas
FX ANE was supported in part by a National Science Foundation GK-12
Fellowship and an E.J. Lund Graduate Fellowship from the University of
Texas Marine Science Institute. A Coastal Conservation Association of
Texas Fellowship awarded to ANE also supported this research. Collection
of freshwater stingray samples was supported by NSF grant #IBN-0416454
to JG. This study represents a portion of the research conducted as
partial fulfillment of a Doctorate of Philosophy in Marine Science from
the University of Texas at Austin (ANE). The authors declare that there
is no conflict of interest that would prejudice the impartiality of this
scientific work.
NR 85
TC 5
Z9 5
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1096-4959
J9 COMP BIOCHEM PHYS B
JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol.
PD DEC
PY 2010
VL 157
IS 4
BP 423
EP 431
DI 10.1016/j.cbpb.2010.09.006
PG 9
WC Biochemistry & Molecular Biology; Zoology
SC Biochemistry & Molecular Biology; Zoology
GA 682ZP
UT WOS:000284441800014
PM 20869458
ER
PT J
AU Xue, ZY
Long, LR
Antani, S
Neve, L
Zhu, YY
Thoma, GR
AF Xue, Zhiyun
Long, L. Rodney
Antani, Sameer
Neve, Leif
Zhu, Yaoyao
Thoma, George R.
TI A unified set of analysis tools for uterine cervix image segmentation
SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS
LA English
DT Article
DE Uterine cervix image; Image segmentation; Segmentation evaluation;
Web-accessible system
ID VALIDATION; RETRIEVAL; ALGORITHM; REGIONS; TRUTH
AB Segmentation is a fundamental component of many medical image-processing applications and It has long been recognized as a challenging problem In this paper we report our research and development efforts on analyzing and extracting clinically meaningful regions from uterine cervix Images in a large database created for the study of cervical cancer In addition to proposing new algorithms we also focus on developing open source tools which are in synchrony with the research objectives These efforts have resulted in three Web-accessible tools which address three important and Interrelated sub-topics in medical image segmentation respectively the Boundary Marking Tool (BMT) Cervigram Segmentation Tool (CST) and Multi-Observer Segmentation Evaluation System (MOSES) The BMT is for manual segmentation typically to collect ground truth Image regions from medical experts The CST is for automatic segmentation and MOSES is for segmentation evaluation These tools are designed to be a unified set in which data can be conveniently exchanged They have value not only for improving the reliability and accuracy of algorithms of uterine cervix image segmentation but also promoting collaboration between biomedical experts and engineers which are crucial to medical image-processing applications Although the CST is designed for the unique characteristics of cervigrams the BMT and MOSES are very general and extensible and can be easily adapted to other biomedical image collections Published by Elsevier Ltd
C1 [Xue, Zhiyun; Long, L. Rodney; Antani, Sameer; Neve, Leif; Thoma, George R.] Natl Lib Med, Bethesda, MD USA.
[Zhu, Yaoyao] Lehigh Univ, Bethlehem, PA 18015 USA.
RP Xue, ZY (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD USA.
OI Antani, Sameer/0000-0002-0040-1387
FU National Institutes of Health (NIH); National Library of Medicine (NLM);
Lister Hill National Center for Biomedical Communications (LHNCBC)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH) National Library of Medicine (NLM)
and Lister Hill National Center for Biomedical Communications (LHNCBC)
NR 39
TC 3
Z9 3
U1 1
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-6111
EI 1879-0771
J9 COMPUT MED IMAG GRAP
JI Comput. Med. Imaging Graph.
PD DEC
PY 2010
VL 34
IS 8
BP 593
EP 604
DI 10.1016/j.compmedimag.2010.04.002
PG 12
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 684RK
UT WOS:000284566800001
PM 20510585
ER
PT J
AU Hicks, C
Sweeney, D
Danner, R
Eichacker, P
Suffredini, A
Feng, J
Sun, JF
Behrend, E
Solomon, S
Natanson, C
AF Hicks, Caitlin
Sweeney, Daniel
Danner, Robert
Eichacker, Peter
Suffredini, Anthony
Feng, Jing
Sun, Junfeng
Behrend, Ellen
Solomon, Steven
Natanson, Charles
TI ADRENAL FUNCTION IN A CANINE MODEL OF BACTERIAL PNEUMONIA-INDUCED SEPTIC
SHOCK
SO CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT 40th Critical Care Congress
CY JAN 15-19, 2011
CL San Diego, CA
SP Soc Crit Care Med
C1 [Hicks, Caitlin; Sweeney, Daniel; Danner, Robert; Eichacker, Peter; Suffredini, Anthony; Feng, Jing; Sun, Junfeng; Solomon, Steven; Natanson, Charles] NIH, Bethesda, MD 20892 USA.
[Behrend, Ellen] Auburn Univ, Auburn, AL 36849 USA.
RI Hicks, Caitlin/E-8849-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD DEC
PY 2010
VL 38
IS 12
SU S
MA 186
BP U52
EP U52
PG 1
WC Critical Care Medicine
SC General & Internal Medicine
GA 684BA
UT WOS:000284520800172
ER
PT J
AU Hicks, C
Sweeney, D
Danner, R
Eichacker, P
Surfredini, A
Feng, J
Sun, JF
Behrend, E
Solomon, S
Natanson, C
AF Hicks, Caitlin
Sweeney, Daniel
Danner, Robert
Eichacker, Peter
Surfredini, Anthony
Feng, Jing
Sun, Junfeng
Behrend, Ellen
Solomon, Steven
Natanson, Charles
TI CORTICOSTEROID THERAPY IS BENEFICIAL IN HIGH-BUT NOT LOW-SEVERITY SEPTIC
SHOCK IN A CANINE MODEL OF BACTERIAL PNEUMONIA
SO CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT 40th Critical Care Congress
CY JAN 15-19, 2011
CL San Diego, CA
SP Soc Crit Care Med
C1 [Hicks, Caitlin; Sweeney, Daniel; Danner, Robert; Eichacker, Peter; Surfredini, Anthony; Feng, Jing; Sun, Junfeng; Solomon, Steven; Natanson, Charles] NIH, Bethesda, MD 20892 USA.
[Behrend, Ellen] Auburn Univ, Auburn, AL 36849 USA.
RI Hicks, Caitlin/E-8849-2012
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD DEC
PY 2010
VL 38
IS 12
SU S
MA 189
BP U53
EP U53
PG 1
WC Critical Care Medicine
SC General & Internal Medicine
GA 684BA
UT WOS:000284520800177
ER
PT J
AU Hicks, C
Sweeney, D
Danner, R
Eichacker, P
Suffredini, A
Feng, J
Sun, J
Behrend, E
Solomon, S
Natanson, C
AF Hicks, Caitlin
Sweeney, Daniel
Danner, Robert
Eichacker, Peter
Suffredini, Anthony
Feng, Jing
Sun, Junfeng
Behrend, Ellen
Solomon, Steven
Natanson, Charles
TI LACK OF BENEFIT FROM DEXAMETHASONE ADDED TO MINERALOCORTICOID THERAPY IN
A CANINE MODEL OF BACTERIAL PNEUMONIA
SO CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
CT 40th Critical Care Congress
CY JAN 15-19, 2011
CL San Diego, CA
SP Soc Crit Care Med
C1 [Hicks, Caitlin; Sweeney, Daniel; Danner, Robert; Eichacker, Peter; Suffredini, Anthony; Feng, Jing; Sun, Junfeng; Solomon, Steven; Natanson, Charles] NIH, Bethesda, MD 20892 USA.
[Behrend, Ellen] Auburn Univ, Auburn, AL 36849 USA.
RI Hicks, Caitlin/E-8849-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD DEC
PY 2010
VL 38
IS 12
SU S
MA 185
BP U52
EP U52
PG 1
WC Critical Care Medicine
SC General & Internal Medicine
GA 684BA
UT WOS:000284520800173
ER
PT J
AU Hurley, JH
AF Hurley, James H.
TI The ESCRT complexes
SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Review
ID MULTIVESICULAR BODY PATHWAY; EPIDERMAL-GROWTH-FACTOR; UBIQUITIN-BINDING
DOMAINS; LEUKEMIA-VIRUS TYPE-1; ENDOSOMAL SORTING COMPLEX; RECEPTOR
DOWN-REGULATION; LATE-BUDDING DOMAINS; AAA-ATPASE VPS4; TUMOR
SUSCEPTIBILITY GENE-101; VESICULAR-STOMATITIS-VIRUS
AB The ESCRT machinery consists of the peripheral membrane protein complexes ESCRT-0, -I, -II, -III, and Vps4-Vta1, and the ALIX homodimer. The ESCRT system is required for degradation of unneeded or dangerous plasma membrane proteins; biogenesis of the lysosome and the yeast vacuole; the budding of most membrane enveloped viruses; the membrane abscission step in cytokinesis; macroautophagy; and several other processes. From their initial discovery in 2001-2002, the literature on ESCRTs has grown exponentially. This review will describe the structure and function of the six complexes noted above and summarize current knowledge of their mechanistic roles in cellular pathways and in disease. 25 dB HL) between the two surveys, for 500, 1000, 2000, and 4000 Hz, and for their four-frequency average.
Results: Across age and sex groups, median thresholds were lower (better) in the 1999-2004 survey at 500, 3000, 4000, and 6000 Hz (8000 Hz was not tested in the 1959-1962 survey). For both men and women, the prevalence of hearing impairment was significantly lower in 1999-2004 at 500, 2000, and 4000 Hz, but not at 1000 Hz.
Conclusions: For men and women of a specific age, high-frequency hearing thresholds were lower (better) in 1999-2004 than in 1959-1962. The prevalences of hearing impairment were also lower in the recent survey. Differences seen at 500 Hz may be attributable at least in part to changes in standards for ambient noise in audiometry. The National Health and Nutrition Examination Survey 1999-2004 distributions are offered as a possible replacement for Annex B in ISO-1999 and ANSI S3.44.
C1 [Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders, NIDCD, Epidemiol & Stat Program, NIH, Bethesda, MD 20892 USA.
[Dobie, Robert A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Otolaryngol Head & Neck Surg, San Antonio, TX USA.
[Themann, Christa L.; Murphy, William J.] NIOSH, Ctr Dis Control & Prevent, Hearing Loss Prevent Team, Cincinnati, OH 45226 USA.
RP Hoffman, HJ (reprint author), Natl Inst Deafness & Other Commun Disorders, NIDCD, Epidemiol & Stat Program, NIH, Suite 400A,EPS Bldg,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM hoffmanh@nidcd.nih.gov
OI dobie, robert/0000-0003-3833-1772
FU NIDCD; NCHS
FX The NHANES 1999-2004 audiometric data collection was funded with NIDCD
research contract funds via an interagency agreement between NIDCD and
NCHS. NIOSH provided funding for the audiometric testing equipment,
training and monitoring of technicians, and editing of preliminary data
files and had a separate interagency agreement with NCHS. Audiometric
testing was conducted in the field by health technicians employed by
WESTAT, Inc., under contract with NCHS.
NR 42
TC 39
Z9 41
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0196-0202
J9 EAR HEARING
JI Ear Hear.
PD DEC
PY 2010
VL 31
IS 6
BP 725
EP 734
DI 10.1097/AUD.0b013e3181e9770e
PG 10
WC Audiology & Speech-Language Pathology; Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Otorhinolaryngology
GA 673IK
UT WOS:000283652700001
PM 20683190
ER
PT J
AU Hoye, BJ
Munster, VJ
Nishiura, H
Klaassen, M
Fouchier, RAM
AF Hoye, Bethany J.
Munster, Vincent J.
Nishiura, Hiroshi
Klaassen, Marcel
Fouchier, Ron A. M.
TI Surveillance of Wild Birds for Avian Influenza Virus
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID A VIRUSES; DISEASE SURVEILLANCE; MIGRATORY WATERFOWL; AQUATIC BIRDS;
DUCKS; INFECTION; ECOLOGY; PARAMYXOVIRUSES; PREVALENCE
AB Recent demand for increased understanding of avian influenza virus in its natural hosts, together with the development of high-throughput diagnostics has heralded a new era in wildlife disease surveillance However survey design sampling and interpretation in the context of host populations still present major challenges We critically reviewed current surveillance to distill a series of considerations pertinent to avian influenza virus surveillance in wild birds including consideration of what when where and how many to sample in the context of survey objectives Recognizing that wildlife disease surveillance is logistically and financially constrained we discuss pragmatic alternatives for achieving probability-based sampling schemes that capture this host pathogen system We recommend hypothesis-driven surveillance through standardized local surveys that are in turn strategically compiled over broad geographic areas Rethinking the use of existing surveillance infrastructure can thereby greatly enhance our global understanding of avian influenza and other zoonotic diseases
C1 [Hoye, Bethany J.; Klaassen, Marcel] Netherlands Inst Ecol, Nieuwersluis, Netherlands.
[Munster, Vincent J.; Fouchier, Ron A. M.] Erasmus MC, Rotterdam, Netherlands.
[Munster, Vincent J.] NIH, Hamilton, MT USA.
[Nishiura, Hiroshi] Univ Utrecht, Utrecht, Netherlands.
[Nishiura, Hiroshi] Japan Sci & Technol Agcy, Saitama, Japan.
[Klaassen, Marcel] Deakin Univ, Waurn Ponds, Vic, Australia.
RP Hoye, BJ (reprint author), Netherlands Inst Ecol NIOO KNAW, Rijksstraatweg 6, NL-3631 AC Nieuwersluis, Netherlands.
RI Hoye, Bethany/A-4486-2010; Klaassen, Marcel/B-4325-2008; Fouchier,
Ron/A-1911-2014;
OI Hoye, Bethany/0000-0001-9502-5582; Klaassen, Marcel/0000-0003-3907-9599;
Fouchier, Ron/0000-0001-8095-2869; Nishiura,
Hiroshi/0000-0003-0941-8537; Munster, Vincent/0000-0002-2288-3196
FU Netherlands Organisation for Scientific Research [851 40 073, 851 40
074]; European Union [044490]; Japan Science and Technology Precursory
Re search for Embryonic Science and Technology; National Institutes of
Health [NIAIDNIH HHSN266200700010C]
FX This study was supported through the Bird Health programme within the
International Polar Year by the Netherlands Organisation for Scientific
Research (grant nos 851 40 073 and 851 40 074), European Union Framework
six program NewFlu Bird (044490) Japan Science and Technology Precursory
Re search for Embryonic Science and Technology program and the
Intramural Research Program of the National Institutes of Health,
contract NIAIDNIH HHSN266200700010C This is publication 4876 of the
Netherlands Institute of Ecology (NIOO-KNAW)
NR 38
TC 57
Z9 58
U1 1
U2 35
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD DEC
PY 2010
VL 16
IS 12
BP 1827
EP 1834
DI 10.3201/eid1612.100589
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 690TM
UT WOS:000285031100001
PM 21122209
ER
PT J
AU Sheng, ZM
Chertow, DS
Morens, DM
Taubenberger, JK
AF Sheng, Zong-Mei
Chertow, Daniel S.
Morens, David M.
Taubenberger, Jeffery K.
TI Fatal 1918 Pneumonia Case Complicated by Erythrocyte Sickling
SO EMERGING INFECTIOUS DISEASES
LA English
DT Letter
ID CELL TRAIT
C1 [Taubenberger, Jeffery K.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Taubenberger, JK (reprint author), NIAID, Infect Dis Lab, NIH, 33 North Dr,MSC 3203, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [ZIA AI000995-04]
NR 10
TC 1
Z9 1
U1 0
U2 0
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD DEC
PY 2010
VL 16
IS 12
BP 2000
EP 2001
DI 10.3201/eid1612.101376
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 690TM
UT WOS:000285031100034
PM 21122243
ER
PT J
AU Sharifi, N
Gulley, JL
Dahut, WL
AF Sharifi, Nima
Gulley, James L.
Dahut, William L.
TI An update on androgen deprivation therapy for prostate cancer
SO ENDOCRINE-RELATED CANCER
LA English
DT Review
ID GONADOTROPIN-RELEASING-HORMONE; RANDOMIZED CONTROLLED-TRIAL; INHIBITOR
ABIRATERONE ACETATE; PREVENT BONE LOSS; I CLINICAL-TRIAL; CARDIOVASCULAR
MORTALITY; KETOCONAZOLE THERAPY; ANTITUMOR-ACTIVITY; INTERIM ANALYSIS;
ANTIGEN DECLINE
AB Androgen deprivation therapy (ADT) with gonadal testosterone depletion is the frontline treatment for advanced prostate cancer. Other hormonal interventions have a role in the treatment of prostate cancer. We sought to examine systematically the evidence for hormonal interventions in prostate cancer, risks of ADT, and interventions that mitigate these risks. Search results for therapeutic studies were focused primarily on randomized controlled clinical trials, and the Jadad scale criteria were used to evaluate the quality of these studies. Four trials of the efficacy of intermittent ADT versus continuous ADT were included. One randomized study analysis and six postrandomization analyses were included on the effects of ADT on cardiovascular mortality. Seven randomized controlled trials of pharmacologic interventions were included for the treatment of metabolic effects due to ADT. One randomized trial of GnRH antagonist versus GnRH agonist was included. Six phase I/II clinical trials of secondary hormonal therapies with novel mechanisms of action were included. Randomized studies completed to date indicate that intermittent ADT might be equivalent to continuous ADT. Although adverse effects of ADT include risk factors for cardiovascular disease, effects on cardiovascular mortality are uncertain. Bone loss and increased risk of fracture may be effectively treated with pharmacologic interventions. Benefits of ADT must be balanced with a consideration of the risks. Endocrine-Related Cancer (2010) 17 R305-R315
C1 [Sharifi, Nima] Univ Texas SW Med Ctr Dallas, Div Hematol & Oncol, Dept Internal Med, Dallas, TX 75390 USA.
[Gulley, James L.; Dahut, William L.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gulley, James L.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Sharifi, N (reprint author), Univ Texas SW Med Ctr Dallas, Div Hematol & Oncol, Dept Internal Med, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM nima.sharifi@utsouthwestern.edu
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU Howard Hughes Medical Institute; Prostate Cancer Foundation; U.S. Army
Medical Research and Materiel Command [PC80193]; Center for Cancer
Research, National Cancer Institute, National Institutes of Health
FX This work was supported in part by a Howard Hughes Medical Institute
Physician-Scientist Early Career Award, an award from the Prostate
Cancer Foundation and from grant number PC80193 from the U.S. Army
Medical Research and Materiel Command to N Sharifi and the Intramural
Research Program of the Center for Cancer Research, National Cancer
Institute, National Institutes of Health.
NR 76
TC 50
Z9 50
U1 4
U2 8
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD DEC
PY 2010
VL 17
IS 4
BP R305
EP R315
DI 10.1677/ERC-10-0187
PG 11
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA 683QJ
UT WOS:000284490000005
PM 20861285
ER
PT J
AU Stojilkovic, SS
Tabak, J
Bertram, R
AF Stojilkovic, Stanko S.
Tabak, Joel
Bertram, Richard
TI Ion Channels and Signaling in the Pituitary Gland
SO ENDOCRINE REVIEWS
LA English
DT Review
ID GONADOTROPIN-RELEASING-HORMONE; RAT ANTERIOR-PITUITARY;
CYCLASE-ACTIVATING POLYPEPTIDE; PROTEIN-KINASE-C;
GAMMA-AMINOBUTYRIC-ACID; VOLTAGE-GATED CA2+; FOLLICULO-STELLATE CELLS;
CA2+-ACTIVATED K+ CHANNELS; SECRETING ADENOMA CELLS; CYTOSOLIC-FREE
CALCIUM
AB Endocrine pituitary cells are neuronlike; they express numerous voltage-gated sodium, calcium, potassium, and chloride channels and fire action potentials spontaneously, accompanied by a rise in intracellular calcium. In some cells, spontaneous electrical activity is sufficient to drive the intracellular calcium concentration above the threshold for stimulus-secretion and stimulus-transcription coupling. In others, the function of these action potentials is to maintain the cells in a responsive state with cytosolic calcium near, but below, the threshold level. Some pituitary cells also express gap junction channels, which could be used for intercellular Ca2+ signaling in these cells. Endocrine cells also express extracellular ligand-gated ion channels, and their activation by hypothalamic and intrapituitary hormones leads to amplification of the pacemaking activity and facilitation of calcium influx and hormone release. These cells also express numerous G protein-coupled receptors, which can stimulate or silence electrical activity and action potential-dependent calcium influx and hormone release. Other members of this receptor family can activate calcium channels in the endoplasmic reticulum, leading to a cell type-specific modulation of electrical activity. This review summarizes recent findings in this field and our current understanding of the complex relationship between voltage-gated ion channels, ligand-gated ion channels, gap junction channels, and G protein-coupled receptors in pituitary cells. (Endocrine Reviews 31: 845-915, 2010)
C1 [Stojilkovic, Stanko S.] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Tabak, Joel] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA.
[Bertram, Richard] Florida State Univ, Dept Math, Tallahassee, FL 32306 USA.
[Bertram, Richard] Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA.
[Bertram, Richard] Florida State Univ, Program Mol Biophys, Tallahassee, FL 32306 USA.
RP Stojilkovic, SS (reprint author), NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bldg 49,Room6A-36,49 Convent Dr, Bethesda, MD 20892 USA.
EM stankos@helix.nih.gov
OI Tabak, Joel/0000-0002-0588-957X
FU National Institutes of Health (NIH) [DA19356, DK43200]; National
Institute of Child Health and Human Development
FX J.T. and R.B. were supported by National Institutes of Health (NIH)
Grants DA19356 and DK43200. S.S.S. was supported by an NIH grant from
the Intramural Research Program of the National Institute of Child
Health and Human Development.
NR 752
TC 63
Z9 63
U1 1
U2 20
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0163-769X
J9 ENDOCR REV
JI Endocr. Rev.
PD DEC
PY 2010
VL 31
IS 6
BP 845
EP 915
DI 10.1210/er.2010-0005
PG 71
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 690YY
UT WOS:000285047800003
PM 20650859
ER
PT J
AU Cservenak, M
Bodnar, I
Usdin, TB
Palkovits, M
Nagy, GM
Dobolyi, A
AF Cservenak, Melinda
Bodnar, Ibolya
Usdin, Ted B.
Palkovits, Miklos
Nagy, Gyoergy M.
Dobolyi, Arpad
TI Tuberoinfundibular Peptide of 39 Residues Is Activated during Lactation
and Participates in the Suckling-Induced Prolactin Release in Rat
SO ENDOCRINOLOGY
LA English
DT Article
ID MILK-EJECTION REFLEX; STIMULUS-INDUCED RELEASE; NERVOUS-SYSTEM;
PARATHYROID-HORMONE-2 RECEPTOR; PERIPEDUNCULAR NUCLEUS; SOMATOSENSORY
SYSTEMS; DOPAMINERGIC-NEURONS; MATERNAL-BEHAVIOR; SEXUAL-BEHAVIOR;
SPINAL-CORD
AB Tuberoinfundibular peptide of 39 residues (TIP39) and the PTH-2 receptor (PTH2R) constitute a peptide receptor neuromodulator system. Based on the abundance of TIP39 fibers and axonal terminals as well as PTH2R-containing neurons and their processes in the hypothalamic para-and periventricular and arcuate nuclei TIP39 has been suggested to play a role in neuroendocrine regulation. We showed previously that TIP39 expression decreased dramatically by adulthood. In the present study, using in situ hybridization histochemistry, real-time RT-PCR, and immunohistochemistry, we found that TIP39 mRNA and peptide expression levels are markedly elevated in the posterior intralaminar complex of the thalamus (PIL) of lactating dams, one of the three locations of TIP39-containing cell bodies in the brain. In addition, in mother rats, these TIP39 neurons showed Fos expression in response to pup exposure. Transection of TIP39 fibers originating in the PIL resulted in an ipsilateral disappearance of TIP39 immunoreactivity throughout the mediobasal hypothalamus of mother rats, suggesting that TIP39 fibers there arise from the PIL. To elucidate the function of TIP39 activation in dams, mothers separated from their pups for 4h on postpartum d 9 received injection of a PTH2R antagonist into the lateral ventricle 5 min before returning the pups. Blood samples were taken seven times during the experimental period through jugular cannulae. The PTH2R antagonist administered in two different concentrations markedly inhibited suckling-induced elevation of plasma prolactin levels in a dose-dependent manner. These results suggest that TIP39 neurons in the PIL may regulate suckling-induced prolactin release in rat dams. (Endocrinology 151: 5830-5840, 2010)
C1 [Dobolyi, Arpad] Semmelweis Univ, Dept Anat Histol & Embryol, Neuromorphol Lab, H-1094 Budapest, Hungary.
[Cservenak, Melinda; Palkovits, Miklos; Dobolyi, Arpad] Hungarian Acad Sci, Dept Anat Histol & Embryol, Neuromorphol & Neuroendocrine Res Lab, H-1094 Budapest, Hungary.
[Bodnar, Ibolya; Nagy, Gyoergy M.] Hungarian Acad Sci, Dept Human Morphol & Dev Biol, H-1094 Budapest, Hungary.
[Usdin, Ted B.] NIMH, Sect Fundamental Neurosci, Bethesda, MD 20892 USA.
RP Dobolyi, A (reprint author), Semmelweis Univ, Dept Anat Histol & Embryol, Neuromorphol Lab, Tuzolto Utca 58, H-1094 Budapest, Hungary.
EM dobolyi@ana.sote.hu
RI Palkovits, Miklos/F-2707-2013;
OI Palkovits, Miklos/0000-0003-0578-0387
FU Bolyai Janos Fellowship [NFM-OTKA NNF78219, NKTH-OTKA K67646, OTKA
NK72929, OTKA K81522]; NIMH
FX This work was supported by Bolyai Janos Fellowship Grants, NFM-OTKA
NNF78219 and NKTH-OTKA K67646 for A. D., OTKA NK72929 for M. P., OTKA
K81522 for G.M.N., and NIMH IRP for T.B.U.
NR 45
TC 19
Z9 19
U1 0
U2 3
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD DEC
PY 2010
VL 151
IS 12
BP 5830
EP 5840
DI 10.1210/en.2010-0767
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 683QH
UT WOS:000284489800027
PM 20861230
ER
PT J
AU Backus, GS
Howden, R
Fostel, J
Bauer, AK
Cho, HY
Marzec, J
Peden, DB
Kleeberger, SR
AF Backus, Gillian S.
Howden, Reuben
Fostel, Jennifer
Bauer, Alison K.
Cho, Hye-Youn
Marzec, Jacqui
Peden, David B.
Kleeberger, Steven R.
TI Protective Role of Interleukin-10 in Ozone-Induced Pulmonary
Inflammation
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE air pollution; gene array; IL-10; inflammation; lung; ozone; pulmonary
ID NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; INDUCED LUNG INFLAMMATION;
GENE-EXPRESSION; FACTOR-ALPHA; KAPPA-B; COSTIMULATORY MOLECULES;
ALVEOLAR MACROPHAGES; CYTOKINE SIGNALING-3; AIRWAY INFLAMMATION
AB BACKGROUND: The mechanisms underlying ozone (O(3))-induced pulmonary inflammation remain unclear. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators.
OBJECTIVES: We investigated the molecular mechanisms underlying interleuken-10 (IL-10)-mediated attenuation of O(3)-induced pulmonary inflammation in mice.
METHODS: Il10-deficient (Il10(-/-)) and wild-type (Il10(+/+)) mice were exposed to 0.3 ppm O(3) or filtered air for 24, 48, or 72 hr. Immediately after exposure, differential cell counts and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also used global mRNA expression analyses of lung tissue with Ingenuity Pathway Analysis to identify patterns of gene expression through which IL-10 modifies O(3)-induced inflammation.
RESULTS: Mean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10(-/-) mice than in Il10(+/+) mice after exposure to O(3) at all time points tested. O(3)-enhanced nuclear NF-kappa B translocation was elevated in the lungs of Il10(-/-) compared with Il10(+/+) mice. Gene expression analyses revealed several IL-10-dependent and O(3)-dependent mediators, including macro-phage inflammatory protein 2, cathepsin E, and serum amyloid A3.
CONCLUSIONS: Results indicate that IL-10 protects against O(3)-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several genetic targets through which IL-10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O(3)-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals.
C1 [Backus, Gillian S.; Fostel, Jennifer; Cho, Hye-Youn; Marzec, Jacqui; Kleeberger, Steven R.] Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Howden, Reuben] Univ N Carolina, Dept Kinesiol, Charlotte, NC 28223 USA.
[Bauer, Alison K.] Michigan State Univ, Dept Pathobiol & Diagnost Invest, Ctr Integrat Toxicol, E Lansing, MI 48824 USA.
[Peden, David B.] Univ N Carolina, Sch Med, Dept Pediat, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC USA.
[Peden, David B.] Univ N Carolina, Sch Med, Div Immunol & Infect Dis, Chapel Hill, NC USA.
RP Kleeberger, SR (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,Bldg 101,MD 201, Res Triangle Pk, NC 27709 USA.
EM kleeber1@niehs.nih.gov
FU Division of Intramural Research, National Institute of Environmental
Health Sciences (NIEHS), National Institutes of Health, Department of
Health and Human Services; NIEHS [R01ES012706]
FX This work was supported by the Division of Intramural Research, National
Institute of Environmental Health Sciences (NIEHS), National Institutes
of Health, Department of Health and Human Services. D.B.P. was supported
by a grant from NIEHS (R01ES012706).
NR 48
TC 22
Z9 22
U1 0
U2 1
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD DEC
PY 2010
VL 118
IS 12
BP 1721
EP 1727
DI 10.1289/ehp.1002182
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 692YB
UT WOS:000285190700026
PM 20826374
ER
PT J
AU Hosgood, HD
Boffetta, P
Greenland, S
Lee, YCA
McLaughlin, J
Seow, A
Duell, EJ
Andrew, AS
Zaridze, D
Szeszenia-Dabrowska, N
Rudnai, P
Lissowska, J
Fabianova, E
Mates, D
Bencko, V
Foretova, L
Janout, V
Morgenstern, H
Rothman, N
Hung, RJ
Brennan, P
Lan, Q
AF Hosgood, H. Dean, III
Boffetta, Paolo
Greenland, Sander
Lee, Yuan-Chin Amy
McLaughlin, John
Seow, Adeline
Duell, Eric J.
Andrew, Angeline S.
Zaridze, David
Szeszenia-Dabrowska, Neonila
Rudnai, Peter
Lissowska, Jolanta
Fabianova, Eleonora
Mates, Dana
Bencko, Vladimir
Foretova, Lenka
Janout, Vladimir
Morgenstern, Hal
Rothman, Nathaniel
Hung, Rayjean J.
Brennan, Paul
Lan, Qing
TI In-Home Coal and Wood Use and Lung Cancer Risk: A Pooled Analysis of the
International Lung Cancer Consortium
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE coal; lung cancer; pooled; risk factor; wood
ID INDOOR AIR-POLLUTION; UPPER AERODIGESTIVE TRACT; SMOKE EXPOSURE;
PULMONARY-DISEASE; CHINESE-WOMEN; SOLID FUELS; XUAN-WEI; COOKING;
METAANALYSIS; HEALTH
AB BACKGROUND: Domestic fuel combustion from cooking and heating is an important public health issue because roughly 3 billion people are exposed worldwide. Recently, the International Agency for Research on Cancer classified indoor emissions from household coal combustion as a human carcinogen (group 1) and from biomass fuel (primarily wood) as a probable human carcinogen (group 2A).
OBJECTIVES: We pooled seven studies from the International Lung Cancer Consortium (5,105 cases and 6,535 controls) to provide further epidemiological evaluation of the association between in-home solid-fuel use, particularly wood, and lung cancer risk.
METHODS: Using questionnaire data, we classified subjects as predominant solid-fuel users (e. g., coal, wood) or nonsolid-fuel users (e.g., oil, gas, electricity). Unconditional logistic regression was used to estimate the odds ratios (ORs) and to compute 95% confidence intervals (CIs), adjusting for age, sex, education, smoking status, race/ethnicity, and study center.
RESULTS: Compared with nonsolid-fuel users, predominant coal users (OR = 1.64; 95% CI, 1.49-1.81), particularly coal users in Asia (OR = 4.93; 95% CI, 3.73-6.52), and predominant wood users in North American and European countries (OR = 1.21; 95% CI, 1.06-1.38) experienced higher risk of lung cancer. The results were similar in never-smoking women and other subgroups.
CONCLUSIONS: Our results are consistent with previous observations pertaining to in-home coal use and lung cancer risk, support the hypothesis of a carcinogenic potential of in-home wood use, and point to the need for more detailed study of factors affecting these associations.
C1 [Hosgood, H. Dean, III] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA.
[Boffetta, Paolo; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Greenland, Sander; Lee, Yuan-Chin Amy] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[McLaughlin, John; Hung, Rayjean J.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Seow, Adeline] Natl Univ Singapore, Singapore 117548, Singapore.
[Duell, Eric J.] Catalan Inst Oncol, Canc Epidemiol Res Programme, Unit Nutr Environm & Canc, Barcelona, Spain.
[Andrew, Angeline S.] Dartmouth Med Sch, Norris Cotton Canc Ctr, Lebanon, NH USA.
[Andrew, Angeline S.] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH USA.
[Zaridze, David] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia.
[Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Dept Epidemiol, Lodz, Poland.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
[Lissowska, Jolanta] Maria Sklodowska Curie Inst Oncol, Warsaw, Poland.
[Lissowska, Jolanta] Ctr Canc, Warsaw, Poland.
[Fabianova, Eleonora] Specialized State Hlth Inst, Dept Occupat Hlth, Banska Bystrica, Slovakia.
[Mates, Dana] Inst Hyg Publ Hlth Hlth Serv & Management, Bucharest, Romania.
[Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Foretova, Lenka] Masaryk Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Janout, Vladimir] Palacky Univ, Fac Med, Dept Prevent Med, CR-77147 Olomouc, Czech Republic.
[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.
[Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
RP Hosgood, HD (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,EPS 8120,MCS 7240, Bethesda, MD 20892 USA.
EM hosgoodd@mail.nih.gov
RI Szeszenia-Dabrowska, Neonila/F-7190-2010; Hung, Rayjean/A-7439-2013;
McLaughlin, John/E-4577-2013; Zaridze, David/K-5605-2013; Janout,
Vladimir/M-5133-2014;
OI Duell, Eric J/0000-0001-5256-0163; mates, dana/0000-0002-6219-9807;
Lissowska, Jolanta/0000-0003-2695-5799
FU National Cancer Institute, U.S. National Institutes of Health (NIH)
[N01-CO-12400]; European Commission [IC15-CT96-0313]; Polish State
Committee for Scientific Research
[SPUB-M-COPERNICUS/P-05/DZ-30/99/2000]; Ministry of Health of the Czech
Republic [MZ0 MOU 2005]; U.S. National Institutes of Health [DA11386,
CA90833, ES 011667]; Ann Fitzpatrick Alper Research Program for
Environmental Genomics; Canadian Cancer Society; Canadian Institutes for
Health Research; Singapore National Medical Research Council; U.S.
National Center for Research Resources [P20RR018787]
FX The Xuanwei1 and Xuanwei2 studies were funded by the Intramural Research
Program of the National Cancer Institute, U.S. National Institutes of
Health (NIH; N01-CO-12400); the Central and Eastern Europe study, by the
European Commission's INCO-Copernicus Programme (contract
IC15-CT96-0313), Polish State Committee for Scientific Research (grant
SPUB-M-COPERNICUS/P-05/DZ-30/99/2000), and a grant from the Ministry of
Health of the Czech Republic (MZ0 MOU 2005); the California study, by
the U.S. National Institutes of Health (grants DA11386, CA90833, ES
011667) and Ann Fitzpatrick Alper Research Program for Environmental
Genomics; the Toronto study, by the Canadian Cancer Society and Canadian
Institutes for Health Research; the Singapore study, by the Singapore
National Medical Research Council; and the New England study, by the
U.S. National Center for Research Resources (grant P20RR018787).
NR 44
TC 37
Z9 37
U1 3
U2 15
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD DEC
PY 2010
VL 118
IS 12
BP 1743
EP 1747
DI 10.1289/ehp.1002217
PG 5
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 692YB
UT WOS:000285190700029
PM 20846923
ER
PT J
AU Gollenberg, AL
Hediger, ML
Lee, PA
Himes, JH
Louis, GMB
AF Gollenberg, Audra L.
Hediger, Mary L.
Lee, Peter A.
Himes, John H.
Louis, Germaine M. Buck
TI Association between Lead and Cadmium and Reproductive Hormones in
Peripubertal U.S. Girls
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE heavy metals; inhibin B; luteinizing hormone; NHANES; puberty
ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; BLOOD LEAD;
ENVIRONMENTAL-FACTORS; UNITED-STATES; PUBERTAL DEVELOPMENT;
LUTEINIZING-HORMONE; METAL INTERACTIONS; US POPULATION; PB EXPOSURE
AB BACKGROUND: Lead (Pb) and cadmium (Cd) are known reproductive toxicants thought to disrupt hormone production throughout sensitive developmental windows, although this has not been previously examined in nationally representative peripubertal children.
OBJECTIVES: We examined the association between blood Pb and urinary Cd concentrations and the reproductive hormones inhibin B and luteinizing hormone (LH) in girls 6-11 years of age who participated in the cross-sectional Third National Health and Nutrition Examination Survey (NHANES III) (1988-1994).
METHODS: Pb (micrograms per deciliter) was measured in whole blood, and Cd was measured in urine (nanograms per milliliter). Inhibin B (picograms per milliliter) and LH (milli-International units per milliliter) were measured in residual sera for 705 girls. Survey logistic regression was used to estimate associations with pubertal onset based on inhibin B concentration > 35 pg/mL or LH concentration > 0.4 mIU/mL, and multinomial logistic regression was used to estimate the association between Pb and increasing categories of hormone concentrations.
RESULTS: High Pb (>= 5 mu g/dL) was inversely associated with inhibin B > 35 pg/mL [odds ratio (OR) = 0.26; 95% confidence interval (CI), 0.11-0.60; compared with Pb < 1 mu g/dL]. At 10 and 11 years of age, girls with low Pb (< 1 mu g/dL) had significantly higher inhibin B than did girls with moderate (1-4.99 mu g/dL) or high Pb (>= 5 mu g/dL). In the subsample of 260 girls with levels of inhibin B above the level of detection and using survey regression modeling, inhibin B levels were lower among girls with both high Pb and high Cd (beta = -0.52; 95% CI, -0.09 to -1.04) than among girls with high Pb alone (beta = -0.35; 95% CI, -0.13 to -0.57), relative to girls with low Pb and low Cd.
CONCLUSIONS: Higher Pb was inversely associated with inhibin B, a marker of follicular development, and estimated effects suggestive of pubertal delays appeared to be stronger in the context of higher Cd concentrations. These data underscore the importance of Pb and Cd as reproductive toxicants for young girls.
C1 [Gollenberg, Audra L.; Hediger, Mary L.; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Lee, Peter A.] Penn State Coll Med, Dept Pediat, Hershey, PA USA.
[Himes, John H.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
RP Hediger, ML (reprint author), 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM hedigerm@exchange.nih.gov
OI Buck Louis, Germaine/0000-0002-1774-4490
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This work was supported by the intramural research program, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
NR 52
TC 24
Z9 24
U1 1
U2 16
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD DEC
PY 2010
VL 118
IS 12
BP 1782
EP 1787
DI 10.1289/ehp.1001943
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 692YB
UT WOS:000285190700035
PM 20675266
ER
PT J
AU Birnbaum, LS
Bergman, A
AF Birnbaum, Linda S.
Bergman, Ake
TI Brominated and Chlorinated Flame Retardants: The San Antonio Statement
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
ID PBDES
C1 [Birnbaum, Linda S.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Birnbaum, Linda S.] NIH, NTP, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Bergman, Ake] Stockholm Univ, Dept Mat & Environm Chem, S-10691 Stockholm, Sweden.
[Bergman, Ake] Stockholm Univ, Environm Chem Unit, S-10691 Stockholm, Sweden.
RP Birnbaum, LS (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM birnbaumls@niehs.nih.gov; ake.bergman@mmk.su.se
OI Bergman, Ake/0000-0003-3403-093X
NR 15
TC 16
Z9 16
U1 1
U2 12
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD DEC
PY 2010
VL 118
IS 12
BP A514
EP A515
DI 10.1289/ehp.1003088
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 692YB
UT WOS:000285190700001
PM 21123139
ER
PT J
AU Patlolla, AK
Hussain, SM
Schlager, JJ
Patlolla, S
Tchounwou, PB
AF Patlolla, Anita K.
Hussain, Saber M.
Schlager, John J.
Patlolla, Srikant
Tchounwou, Paul B.
TI Comparative Study of the Clastogenicity of Functionalized and
Nonfunctionalized Multiwalled Carbon Nanotubes in Bone Marrow Cells of
Swiss-Webster Mice
SO ENVIRONMENTAL TOXICOLOGY
LA English
DT Article
DE multiwalled; carbon; nanotubes; bone marrow cells; leukocytes;
Swiss-Webster mice; chromosomal aberrations; micronucleus formation;
mitotic index; Comet assay; DNA damage
ID HUMAN LYMPHOBLASTOID-CELLS; DNA-DAMAGE; PULMONARY TOXICITY; OXIDATIVE
STRESS; EPITHELIAL-CELLS; IN-VITRO; CYTOTOXICITY; NANOMATERIALS;
GENOTOXICITY; PARTICLES
AB The development of nanotechnologies may lead to environmental release of nanomaterials that are potentially harmful to human health Among the nanomaterials multiwalled carbon nanotubes (MWCNTs) are already commercialized in various products which can be in direct contact with populations However few studies address their potential toxicity Although a few reports on the cytotoxicity of carbon nanotubes (CNTs) have been published very little is known about their toxicity or genotoxicity in mammalian cells We have for the first time compared the clastogenic/genotoxic potential of functionalized and nonfunctionalized MWCNTs in bone marrow cells of Swiss-Webster mice using mitotic index (MI) chromosome aberrations (CA) micronuclei (MN) formation, and DNA damage in leukocytes as toxicologic endpoints Six groups of five male mice, each weighing similar to 30 +/- 2 g, were administered intraperitoneally once a day for five days with doses of 0 25 0 5, 0 75 mg/kg body weight (BW) of functionalized and nonfunctionalized MWCNTs Four vehicle control groups (negative) and a positive control group (carbon black) were also made of 5 mice each Chromosome and micronuclei from bone marrow cells and comet slides from leukocytes were examined following standard protocols The results demonstrated that MWCNTs exposure significantly increased (P < 0 05) the number of structural chromosomal aberrations the frequency of micro-nucleated cells and the level of DNA damage, and decreased the mitotic index in treated groups compared to control groups MWCNTs were shown to be toxic at sufficiently high concentrations, however purified functionalized MWCNTs had a higher clastogenic/genotoxic potential compared to nonfunctionalized form of MWCNT The results of our study suggest that exposure to MWCNT has the potential to cause genetic damage Hence, careful monitoring should be done with respect to designing/synthesizing biocompatible carbon nanomaterials Further characterization of their systemic toxicity genotoxicity and carcinogenicity is also essential (C) 2010 Wiley Periodicals Inc Environ Toxicol 25 608-621 2010
C1 [Patlolla, Anita K.; Tchounwou, Paul B.] Jackson State Univ, Mol Toxicol Res Lab, NIH, RCMI,Ctr Environm Hlth, Jackson, MS 39217 USA.
[Hussain, Saber M.; Schlager, John J.] USAF, Res Lab Wright Patterson AFB, Dayton, OH USA.
[Patlolla, Srikant] Emory Univ, Atlanta, GA 30322 USA.
RP Patlolla, AK (reprint author), Jackson State Univ, Mol Toxicol Res Lab, NIH, RCMI,Ctr Environm Hlth, 1400 Lynch St,Box 18540, Jackson, MS 39217 USA.
FU Air Forces Research Laboratory [FA8650 07 1 6851]; National Institutes
of Health RCMI Center for Environmental Health at Jackson State
University [5G12RR01349 12]
FX Contract grant sponsor Air Forces Research Laboratory/Wright Patter son
AFB; Contract grant number FA8650 07 1 6851; Contract grant sponsor
National Institutes of Health RCMI Center for Environmental Health at
Jackson State University; Contract grant number 5G12RR01349 12
NR 47
TC 41
Z9 44
U1 1
U2 8
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1520-4081
J9 ENVIRON TOXICOL
JI Environ. Toxicol.
PD DEC
PY 2010
VL 25
IS 6
BP 608
EP 621
DI 10.1002/tox.20621
PG 14
WC Environmental Sciences; Toxicology; Water Resources
SC Environmental Sciences & Ecology; Toxicology; Water Resources
GA 686GC
UT WOS:000284683800009
PM 20549644
ER
PT J
AU Paul, KB
Hedge, JM
DeVito, MJ
Crofton, KM
AF Paul, Katie B.
Hedge, Joan M.
DeVito, Michael J.
Crofton, Kevin M.
TI DEVELOPMENTAL TRICLOSAN EXPOSURE DECREASES MATERNAL AND NEONATAL
THYROXINE IN RATS
SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
LA English
DT Article
DE Endocrine disruptors; Developmental toxicity; Mammals; Triclosan
ID PERSONAL CARE PRODUCTS; THYROID-HORMONE DISRUPTION; IN-VIVO EXPOSURE;
WASTE-WATER; SHORT-TERM; EARLY-PREGNANCY; POLYCHLORINATED-BIPHENYLS;
NONSTEROIDAL ESTROGEN; DIPHENYL ETHERS; BRAIN
AB Disruption of maternal thyroid hormones during fetal developmental may result in irreversible neurological consequences in offspring The present study tested the hypothesis that perinatal triclosan exposure of dams decreases thyroxine in dams and offspring prior to weaning Pregnant Long Evans rats received triclosan by oral gavage (0-300 mg/kg/d) in corn oil from gestational day (GD)6 through postnatal day (PND)21 Serum was obtained from pups on PND4 14 and 21 and from dams on PND22 Serum thyroxine (T4) was reduced 31% in dams on PND22 In pups a unique pattern of hypothyroxinemia was observed serum T4 decreased 27% in PND4 pups with no significant reduction observed on PND14 or PND21 Comparable reductions of approximately 30% in serum T4 at 300 mg/kg/d for dams and PND4 neonates and a lack of effect at PND14 and PND21 suggest that toxicokinetic or toxicodynamic factors may have contributed to a reduced exposure or a reduced toxicological response during the lactation period Environ Toxicol Chem 2010 29 2840-2844 (C) 2010 SETAC
C1 [Paul, Katie B.; Crofton, Kevin M.] Univ N Carolina, Chapel Hill, NC 27515 USA.
[Hedge, Joan M.; Crofton, Kevin M.] US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA.
[DeVito, Michael J.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA.
RP Crofton, KM (reprint author), Univ N Carolina, Chapel Hill, NC 27515 USA.
RI Crofton, Kevin/J-4798-2015
OI Crofton, Kevin/0000-0003-1749-9971
FU PhRMA Foundation; EPA/UNC [CR833237]; National Institute of
Environmental Health Science [T32 ES07126]
FX This manuscript has been reviewed by the National Health and
Environmental Effects Research Laboratory U S Environmental Protection
Agency and approved for publication Mention of trade names or commercial
products does not constitute endorsement or recommendation for use The
authors thank David Ross and Kateland Grant for assistance during animal
sacrifice Ram Ramabhadran Sid Hunter William Mundy Tammy Stoker Doug
Wolf and Leah Zorrilla are gratefully acknowledged for comments on an
earlier version of this manuscript Triclosan was a generous gift from
James Plautz and Lisa Navarro of Ciba Specialty Chemicals Raw data files
can be obtained by contacting the corresponding author K B Paul was
funded by a PhRMA Foundation Predoctoral Pharmacology/Toxicology
Fellowship the EPA/UNC Toxicology Research Program Training Agreement
(CR833237) and the National Institute of Environmental Health Science
Training Grant (T32 ES07126) during this work
NR 43
TC 31
Z9 33
U1 7
U2 22
PU SETAC PRESS
PI PENSACOLA
PA 1010 N 12TH AVE, PENSACOLA, FL 32501-3367 USA
SN 0730-7268
J9 ENVIRON TOXICOL CHEM
JI Environ. Toxicol. Chem.
PD DEC
PY 2010
VL 29
IS 12
BP 2840
EP 2844
DI 10.1002/etc.339
PG 5
WC Environmental Sciences; Toxicology
SC Environmental Sciences & Ecology; Toxicology
GA 686FW
UT WOS:000284683200026
PM 20954233
ER
PT J
AU Yang, HH
Gong, J
Zhang, J
Wang, ML
Yang, J
Wu, GZ
Quan, WL
Gong, HM
Szu, SC
AF Yang, H. H.
Gong, J.
Zhang, J.
Wang, M. L.
Yang, J.
Wu, G. Z.
Quan, W. L.
Gong, H. M.
Szu, S. C.
TI An outbreak of Salmonella Paratyphi A in a boarding school: a
community-acquired enteric fever and carriage investigation
SO EPIDEMIOLOGY AND INFECTION
LA English
DT Article
DE Community epidemics; community outbreaks; enteric bacteria; Salmonella
Paratyphi; serology
ID TYPHOID-FEVER; SEROVAR PARATYPHI; MAJOR CAUSE; CARRIERS; VACCINE;
CHILDREN; EFFICACY; ASIA; EMERGENCE; INFECTION
AB Salmonella Paratyphi A (SPA) is rapidly becoming a common cause of enteric fever in South East Asia. A large outbreak of SPA occurred in a boarding middle school in China in 2004. There were 394 suspected cases; 95.5% were students. The highest incidence was in the youngest children (7th grade). Forty-four of 151 (29%) blood cultures and 4/54 (7.4%) rectal swabs were positive for SPA; three were from kitchen workers. The geometric mean levels of serum IgG anti-lipopolysaccharide (anti-LPS) from patients was higher than from healthy individuals [35.25 vs. 5.20 ELISA units (EU), P<0.001]. A kitchen worker with a positive rectal swab, negative blood culture and a high level of serum IgG anti-LPS (529.65 EU), was identified as a possible SPA carrier. No SPA was isolated from water or food samples. A survey of students' habits indicated drinking unboiled water as being the main reason for contracting the disease. Hand washing was the second most important factor. A food handler with possible SPA carriage could also have been a risk factor. Attention to maintaining a safe water supply, enhancing food-handler hygiene and proper hand washing can help to prevent similar outbreaks in the future.
C1 [Szu, S. C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Yang, H. H.; Gong, J.; Zhang, J.; Wang, M. L.; Yang, J.] Guangxi Ctr Dis Control & Prevent, Nanning, Guangxi, Peoples R China.
[Wu, G. Z.; Quan, W. L.; Gong, H. M.] Lingchuan Ctr Dis Control & Prevent, Lingchuan, Guangxi, Peoples R China.
RP Szu, SC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bldg 6,Room 1A6,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM szus@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development, National Institutes of Health, USA; Guangxi Center of
Disease Control and Prevention at Nanning, Guangxi, China
FX We thank the Clinical Microbiology Laboratory, Clinical Center, NIH, USA
for verification of SPA isolates, Steven Hunt and Lingyun Zhou for
technical help in serological assays, and Rachel Schneerson and John B.
Robbins for helpful discussion and review of the manuscript. The work
was supported by the intramural research of the Eunice Kennedy Shriver
National Institute of Child Health & Human Development, National
Institutes of Health, USA and by the Guangxi Center of Disease Control
and Prevention at Nanning, Guangxi, China.
NR 41
TC 3
Z9 3
U1 0
U2 1
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0950-2688
J9 EPIDEMIOL INFECT
JI Epidemiol. Infect.
PD DEC
PY 2010
VL 138
IS 12
BP 1765
EP 1774
DI 10.1017/S0950268810001986
PG 10
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 677SK
UT WOS:000284011900013
PM 20800009
ER
PT J
AU Patlolla, A
Knighten, B
Tchounwou, P
AF Patlolla, Anita
Knighten, Brionna
Tchounwou, Paul
TI MULTI-WALLED CARBON NANOTUBES INDUCE CYTOTOXICITY, GENOTOXICITY AND
APOPTOSIS IN NORMAL HUMAN DERMAL FIBROBLAST CELLS
SO ETHNICITY & DISEASE
LA English
DT Article; Proceedings Paper
CT 11th RCMI International Symposium on Health Disparities
CY DEC 01-04, 2008
CL Univ Hawai Manoa, Honolulu, HI
HO Univ Hawai Manoa
DE Multi-walled Carbon Nanotubes; Human Dermal Fibroblast; DNA; Annexin V;
Cytotoxicity
ID HEALTH-RISKS; IN-VITRO; KAPPA-B; NANOMATERIALS; TOXICITY; KERATINOCYTES;
DEPENDENCE; FULLERENE; EXPOSURE; SAFETY
AB Multi-walled carbon nanotubes (MWCNT) have won enormous popularity in nanotechnology. Due to their unusual, one dimensional, hollow nanostructure and unique physicochemical properties they are highly desirable for use within the commercial, environmental and medical sectors. Despite their wide application, little information is known concerning their impact on human health and the environment. While nanotechnology looms large with commercial promise and potential benefit, an equally large issue is the evaluation of potential effects on humans and other biological systems. Our research is focused on cellular response to purified MWCNT in normal human dermal fibroblast cells (NHDF). Three doses (40, 200, 400 mu g/mL) of MWCNT and control (tween-80+0.9% saline) were used in this study. Following exposure to MWCNT, cytotoxicity, genotoxicity and apoptosis assays were performed using standard protocols. Our results demonstrated a dose-dependent toxicity with MWCNT. It was found to be toxic and induced massive loss of cell viability through DNA damage and programmed cell-death of all doses compared to control. Our results demonstrate that carbon nanotubes indeed can be very toxic at sufficiently high concentrations and that careful monitoring of toxicity studies is essential for risk assessment. (Ethn Dis. 2010;20[Suppl 1]:S1-65-S1-72)
C1 [Patlolla, Anita; Knighten, Brionna; Tchounwou, Paul] Jackson State Univ, Mol Toxicol Res Lab, NIH Ctr Environm Hlth, Jackson, MS 39217 USA.
RP Patlolla, A (reprint author), Jackson State Univ, Mol Toxicol Lab, NIH RCMI Ctr Environm Hlth, Jackson, MS 39217 USA.
EM anita.k.patlolla@jsums.edu
NR 34
TC 21
Z9 22
U1 0
U2 6
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
J9 ETHNIC DIS
JI Ethn. Dis.
PD WIN
PY 2010
VL 20
IS 1
SU 1
BP 65
EP 72
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 576XR
UT WOS:000276183900014
ER
PT J
AU Yedjou, CG
Tchounwou, CK
Haile, S
Edwards, F
Tchounwou, PB
AF Yedjou, Clement G.
Tchounwou, Christine K.
Haile, Samuel
Edwards, Falicia
Tchounwou, Paul B.
TI N-ACETYL-CYSTEINE PROTECTS AGAINST DNA DAMAGE ASSOCIATED WITH LEAD
TOXICITY IN HEPG(2) CELLS
SO ETHNICITY & DISEASE
LA English
DT Article; Proceedings Paper
CT 11th RCMI International Symposium on Health Disparities
CY DEC 01-04, 2008
CL Univ Hawai Manoa, Honolulu, HI
HO Univ Hawai Manoa
DE Lead; Cytotoxicity; Genotoxicity; N-Acetyl-Cysteine; HepG(2) Cells
ID GENOTOXICITY; STRESS
AB Lead toxicity has been associated with its ability to interact and damage DNA. However, its molecular mechanisms of action are not fully understood. In vitro studies in our laboratory indicated that lead nitrate (PbNO3) induces cytotoxicity and oxidative stress to human liver carcinoma (HepG(2)) cells in a dose-dependent manner. In this research, we hypothesized that n-acetyl-cysteine (NAC), a known antioxidant compound, affords protection against lead-induced cell death associated with genotoxic damage. To test this hypothesis, HepG(2) cells were treated either with a physiologic dose of NAC, NAC plus PbNO3, or PbNO3 alone, followed by incubation in humidified 5% CO2 incubator at 37 degrees C for 48 hr. The cell viability was determined by trypan blue exclusion test. The degree of DNA damage was detected by micro gel electrophoresis (comet) assay. Our results showed that lead exposure induces a substantial cytotoxicity as well as a significant genotoxicity to HepG(2) cells. However, co-treatment with a physiologic dose (500 mu M) of NAC slightly increases cell viability, and significantly reduced (P<.05) the degree of DNA damage. Hence, NAC treatment may be a promising therapeutic candidate for chemoprevention against lead toxicity, based on its ability to scavenge free radicals. (Ethn Dis. 2010; 20[Suppl 1]:S1-101-S1-103)
C1 [Yedjou, Clement G.] Jackson State Univ, Dept Biol, Cell & Toxicogen Res Lab, RCMI Ctr Environm Hlth,Coll Sci Engn & Technol, Jackson, MS 39217 USA.
RP Yedjou, CG (reprint author), Jackson State Univ, Dept Biol, Cell & Toxicogen Res Lab, RCMI Ctr Environm Hlth,Coll Sci Engn & Technol, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA.
EM clement.yedjou@jsums.edu
NR 15
TC 5
Z9 6
U1 0
U2 0
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
J9 ETHNIC DIS
JI Ethn. Dis.
PD WIN
PY 2010
VL 20
IS 1
SU 1
BP 101
EP 103
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 576XR
UT WOS:000276183900021
ER
PT J
AU Lyons-Abbott, S
Sackett, DL
Wloga, D
Gaertig, J
Morgan, RE
Werbovetz, KA
Morrissette, NS
AF Lyons-Abbott, Sally
Sackett, Dan L.
Wloga, Dorota
Gaertig, Jacek
Morgan, Rachel E.
Werbovetz, Karl A.
Morrissette, Naomi S.
TI alpha-Tubulin Mutations Alter Oryzalin Affinity and Microtubule Assembly
Properties To Confer Dinitroaniline Resistance
SO EUKARYOTIC CELL
LA English
DT Article
ID YEAST SACCHAROMYCES-CEREVISIAE; PURPURATUS SPINDLE TUBULIN;
STATHMIN-LIKE DOMAIN; BETA-TUBULIN; TETRAHYMENA-THERMOPHILA; KNOCKOUT
HETEROKARYONS; HERBICIDE RESISTANCE; ALVEOLATE EVOLUTION;
TOXOPLASMA-GONDII; GENE REPLACEMENT
AB Plant and protozoan microtubules are selectively sensitive to dinitroanilines, which do not disrupt vertebrate or fungal microtubules. Tetrahymena thermophila is an abundant source of dinitroaniline-sensitive tubulin, and we have modified the single T. thermophila alpha-tubulin gene to create strains that solely express mutant alpha-tubulin in functional dimers. Previous research identified multiple alpha-tubulin mutations that confer dinitroaniline resistance in the human parasite Toxoplasma gondii, and when two of these mutations (L136F and I252L) were introduced into T. thermophila, they conferred resistance in these free-living ciliates. Purified tubulin heterodimers composed of L136F or I252L alpha-tubulin display decreased affinity for the dinitroaniline oryzalin relative to wild-type T. thermophila tubulin. Moreover, the L136F substitution dramatically reduces the critical concentration for microtubule assembly relative to the properties of wild-type T. thermophila tubulin. Our data provide additional support for the proposed dinitroaniline binding site on alpha-tubulin and validate the use of T. thermophila for expression of genetically homogeneous populations of mutant tubulins for biochemical characterization.
C1 [Lyons-Abbott, Sally; Morrissette, Naomi S.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA.
[Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Integrat & Med Biophys, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Wloga, Dorota; Gaertig, Jacek] Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA.
[Morgan, Rachel E.; Werbovetz, Karl A.] Ohio State Univ, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA.
RP Morrissette, NS (reprint author), Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA.
EM nmorriss@uci.edu
RI Werbovetz, Karl/E-4290-2011; Gaertig, Jacek/F-1553-2010; Wloga,
Dorota/R-4078-2016
FU NIH [AI067981]; NSF [MBC-0639934]; Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX Research presented in this paper was supported by NIH grant AI067981
(N.S.M.), NSF grant MBC-0639934 (J.G.), and by funds from the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (D.L.S.).
NR 79
TC 12
Z9 13
U1 1
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1535-9778
J9 EUKARYOT CELL
JI Eukaryot. Cell
PD DEC
PY 2010
VL 9
IS 12
BP 1825
EP 1834
DI 10.1128/EC.00140-10
PG 10
WC Microbiology; Mycology
SC Microbiology; Mycology
GA 688UP
UT WOS:000284879700003
PM 20870876
ER
PT J
AU Diniz, SN
Pendeloski, KPT
Morgun, A
Chepelev, I
Gerbase-DeLima, M
Shulzhenko, N
AF Diniz, Susana N.
Pendeloski, Karen P. T.
Morgun, Andrey
Chepelev, Iouri
Gerbase-DeLima, Maria
Shulzhenko, Natalia
TI Tissue-specific expression of IL-15RA alternative splicing transcripts
and its regulation by DNA methylation
SO EUROPEAN CYTOKINE NETWORK
LA English
DT Article
DE IL-15RA; alternative splicing; DNA methylation; 5-azacitidine
ID RECEPTOR-ALPHA-CHAIN; CELL-DIFFERENTIATION; GENE-EXPRESSION;
INTERLEUKIN-15; CYTOKINE; BINDING; REJECTION; CHROMATIN; CLEAVAGE;
BIOLOGY
AB The human IL-15RA gene encoding the alpha chain of the IL-15 receptor is expressed in a variety of immune and non-immune cell types from different tissues, and generates multiple splicing events of functional importance. We aimed to evaluate expression of IL-15RA transcripts generated by alternative usage of transcription start site (Var1 and Var2) and by deletion of exon 3 (Del3), exon 2 (Del2), or both (Del2,3) in different human tissues. Since a CpG island was found near to the IL-15RA gene transcription start site, we also investigated the role of DNA methylation on the expression of IL-15RA full-length and alternative transcripts fragments in peripheral blood mononuclear cells (PBMC). IL-15RA transcription of functional (full-length and del 3) and non-functional (del 2 and del 2,3) variants was detected in many tissues, however, the number of different IL-15RA transcripts variants detected in each tissue did not correlate with the level of gene expression. IL-15RA transcript variants Var1 and Var2 presented similar expression levels in different human tissues. However, we found a distinct expression profile of functional and non-functional IL-15RA transcripts fragments. A preferential expression of transcripts that bind IL-15 compared to IL-15 non-binding transcripts was seen in the tissues investigated. When PBMC cultures were treated with 5-azacitidine (AZA), a DNA methyltransferase inhibitor, we detected a significant increase in IL-15RA copy number. Only alternative exon skipping events of Var1 (Del 2, Del 3 and Del 2, 3) were altered by AZA treatment, which is consistent with the CpG island localization in the regulatory region 5' upstream of the transcription start site of Var1 and not of Var2. Therefore, this work shows a broad expression pattern of functional IL-15RA splicing forms and suggests a regulatory role of DNA methylation in IL-15RA transcript Var1 expression in mononuclear cells.
C1 [Diniz, Susana N.; Pendeloski, Karen P. T.; Morgun, Andrey; Gerbase-DeLima, Maria; Shulzhenko, Natalia] Fed Univ Sao Paulo UNIFESP, Div Immunogenet, Sao Paulo, Brazil.
[Diniz, Susana N.] Bandeirante Univ Sao Paulo UNIBAN, Dept Pharm, Sao Paulo, SP, Brazil.
[Morgun, Andrey; Shulzhenko, Natalia] NIAID, Ghost Lab, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Chepelev, Iouri] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Diniz, SN (reprint author), Av Diogenes Ribeiro de Lima,2991-74 Alto da Lapa, Sao Paulo, Brazil.
EM dinizsusana@gmail.com
RI Gerbase-DeLima, Maria/K-2515-2015
FU AFIP (Associacao Fundo de Incentivo a Psicofarmacologia)
FX The Brazilian agency AFIP (Associacao Fundo de Incentivo a
Psicofarmacologia) provided fellowships for SND and KPTP.
NR 37
TC 4
Z9 5
U1 0
U2 1
PU JOHN LIBBEY EUROTEXT LTD
PI MONTROUGE
PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE
SN 1148-5493
J9 EUR CYTOKINE NETW
JI Eur. Cytokine Netw.
PD DEC
PY 2010
VL 21
IS 4
BP 308
EP 318
DI 10.1684/ecn.2010.0218
PG 11
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 695YL
UT WOS:000285408800012
PM 21097393
ER
PT J
AU Patel, RS
Su, SY
Neeland, IJ
Ahuja, A
Veledar, E
Zhao, JY
Helgadottir, A
Holm, H
Gulcher, JR
Stefansson, K
Waddy, S
Vaccarino, V
Zafari, AM
Quyyumi, AA
AF Patel, Riyaz S.
Su, Shaoyong
Neeland, Ian J.
Ahuja, Ayushi
Veledar, Emir
Zhao, Jinying
Helgadottir, Anna
Holm, Hilma
Gulcher, Jeffrey R.
Stefansson, Kari
Waddy, Salina
Vaccarino, Viola
Zafari, A. Maziar
Quyyumi, Arshed A.
TI The chromosome 9p21 risk locus is associated with angiographic severity
and progression of coronary artery disease
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Atherosclerosis; angiography; coronary disease; genetics; genomics; 9p21
ID MYOCARDIAL-INFARCTION; INTRACRANIAL ANEURYSM; GENETIC-VARIATION;
VARIANT; ATHEROSCLEROSIS; SUSCEPTIBILITY; METAANALYSIS; REPLICATION;
POPULATIONS; STIFFNESS
AB We tested the hypothesis that the 9p21 risk locus promotes atherosclerosis by examining the association between rs10757278 and coronary artery disease (CAD) severity and progression determined by semi-quantitative angiographic scores.
The rs10757278 single nucleotide polymorphism (SNP) was genotyped as the marker for the 9p21 locus in 2334 Caucasian patients undergoing cardiac catheterization (mean age 63, male 67%). Angiographic CAD was assessed using two semi-quantitative scoring systems with one estimating severity (Gensini) and the other extent (Sullivan). A subset of 308 patients who underwent two or more coronary angiograms at least 6 months apart were examined for net change in Gensini and Sullivan scores over time to determine the rate of CAD progression by genotype and were further classified as 'progressors' or 'non-progressors' based on absolute change per year in angiographic severity score. We replicated the association between the rs10757278 SNP and myocardial infarction and binary (presence/absence) angiographic classifications of CAD. Furthermore, we observed a significant additive association with this SNP, and both severity and extent of CAD using angiographic scores, after adjustment for age, gender, body mass index, traditional cardiovascular risk factors, myocardial infarction, and statin use (Gensini P = 0.016, Sullivan P = 0.005). In addition, there was a significant linear association with CAD progression before and after adjustment for covariates (Gensini P = 0.023, Sullivan P = 0.003) with homozygotes for the risk variant having three-fold greater odds of CAD progression compared with the referent group.
The 9p21 risk locus is associated with angiographically defined severity, extent, and progression of CAD, suggesting a role for this locus in influencing atherosclerosis and its progression.
C1 [Patel, Riyaz S.; Su, Shaoyong; Neeland, Ian J.; Ahuja, Ayushi; Veledar, Emir; Vaccarino, Viola; Zafari, A. Maziar; Quyyumi, Arshed A.] Emory Univ, Sch Med, Div Cardiol, Emory Univ Hosp, Atlanta, GA 30322 USA.
[Patel, Riyaz S.] Cardiff Univ, Dept Med, Cardiff, S Glam, Wales.
[Zhao, Jinying] Univ Oklahoma, Dept Biostat & Epidemiol, Oklahoma City, OK USA.
[Helgadottir, Anna] Univ Oxford, Dept Cardiovasc Med, Oxford, England.
[Holm, Hilma; Gulcher, Jeffrey R.; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
[Waddy, Salina] NINDS, NIH, Bethesda, MD 20892 USA.
[Zafari, A. Maziar] Atlanta Vet Affairs Med Ctr, Decatur, GA USA.
RP Quyyumi, AA (reprint author), Emory Univ, Sch Med, Div Cardiol, Emory Univ Hosp, 1364 Clifton Rd,4th Floor,Suite D403C, Atlanta, GA 30322 USA.
EM aquyyum@emory.edu
RI Library, Woodruff Health/A-6096-2012; Veledar, Emir/K-2808-2012
OI Veledar, Emir/0000-0002-3831-5433
FU American Heart Association; Robert W. Woodruff Health Sciences Center;
Emory Heart and Vascular Center; NIH [UL1 RR025008, R01HL089650-02];
Emory Neuroscience NINDS Core Facilities [P30NS055077]
FX This work was supported by the American Heart Association (Post-doctoral
Fellowship for R. S. P.), Robert W. Woodruff Health Sciences Center
Fund, Emory Heart and Vascular Center Funds, and was supported in part
by NIH grant UL1 RR025008 from the Clinical and Translational Science
Award program, NIH grant R01HL089650-02, and from the Emory Neuroscience
NINDS Core Facilities grant P30NS055077.
NR 28
TC 48
Z9 52
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD DEC
PY 2010
VL 31
IS 24
BP 3017
EP 3023
DI 10.1093/eurheartj/ehq272
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 696BC
UT WOS:000285415900014
PM 20729229
ER
PT J
AU Celi, FS
Brychta, RJ
Linderman, JD
Butler, PW
Alberobello, AT
Smith, S
Courville, AB
Lai, EW
Costello, R
Skarulis, MC
Csako, G
Remaley, A
Pacak, K
Chen, KY
AF Celi, Francesco S.
Brychta, Robert J.
Linderman, Joyce D.
Butler, Peter W.
Alberobello, Anna Teresa
Smith, Sheila
Courville, Amber B.
Lai, Edwin W.
Costello, Rene
Skarulis, Monica C.
Csako, Gyorgy
Remaley, Alan
Pacak, Karel
Chen, Kong Y.
TI Minimal changes in environmental temperature result in a significant
increase in energy expenditure and changes in the hormonal homeostasis
in healthy adults
SO EUROPEAN JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID BROWN ADIPOSE-TISSUE; MILD COLD; PHYSICAL-ACTIVITY; HUMANS; OBESITY;
DIET; THERMOGENESIS; DEIODINASE; METABOLISM; CAFFEINE
AB Objective: Resting energy expenditure (EE) is a major contributor to the total EE and thus plays an important role in body weight regulation. Adaptive thermogenesis is a major component of EE in rodents, but little is known on the effects of exposure of humans to mild and sustainable reduction in environmental temperature.
Design: To characterize the dynamic changes in continuously measured resting EE, substrate utilization, and hormonal axes simultaneously in response to mild reduction in environmental temperature, we performed a cross-over intervention.
Methods: Twenty-five volunteers underwent two 12-h recordings of EE in whole room indirect calorimeters at 24 and 19 degrees C with simultaneous measurement of spontaneous movements and hormonal axes.
Results: Exposure to 19 degrees C resulted in an increase in plasma and urine norepinephrine levels (P < 0.0001), and a 5.96% (P < 0.001) increase in EE without significant changes in spontaneous physical activity. Exposure to the lower temperature resulted in a significant increase in free fatty acid levels (P < 0.01), fasting insulin levels (P < 0.05), and a marginal decrease in postprandial glucose levels. A small but significant (P < 0.002) increase in serum free thyroxine and urinary free cortisol (P < 0.05) was observed at 19 degrees C.
Conclusions: Our observations indicate that exposure to 19 degrees C, a mild and tolerable cold temperature, results in a predictable increase in EE driven by a sustained rise in catecholamine and the activation of counter-regulatory mechanisms.
C1 [Celi, Francesco S.; Brychta, Robert J.; Linderman, Joyce D.; Butler, Peter W.; Alberobello, Anna Teresa; Smith, Sheila; Skarulis, Monica C.; Chen, Kong Y.] NIDDK, Clin Endocrinol Branch, Bethesda, MD 20892 USA.
[Butler, Peter W.; Lai, Edwin W.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod & Adult Endocrinol Branch, Bethesda, MD 20892 USA.
[Courville, Amber B.; Costello, Rene; Csako, Gyorgy; Remaley, Alan] NIH, Dept Lab Med, Ctr Clin, CRC, Bethesda, MD 20892 USA.
RP Celi, FS (reprint author), NIDDK, Clin Endocrinol Branch, Bldg 10,RM 6-3940,10 Ctr Dr,MSC 1613, Bethesda, MD 20892 USA.
EM fc93a@nih.gov
OI Chen, Kong/0000-0002-0306-1904
FU NIDDK [Z01-DK047057-02, Z01-DK071013-02]; Clinical Center, NIH
FX This work was supported by the Intramural Research Program of the NIDDK
programs Z01-DK047057-02, Z01-DK071013-02, and the Clinical Center, NIH.
NR 38
TC 28
Z9 28
U1 2
U2 8
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0804-4643
EI 1479-683X
J9 EUR J ENDOCRINOL
JI Eur. J. Endocrinol.
PD DEC
PY 2010
VL 163
IS 6
BP 863
EP 872
DI 10.1530/EJE-10-0627
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 678RR
UT WOS:000284098400003
PM 20826525
ER
PT J
AU Wang, WY
Lee, ET
Howard, BV
Fabsitz, RR
Devereux, RB
MacCluer, JW
Laston, S
Comuzzie, AG
Shara, NM
Welty, TK
AF Wang, Wenyu
Lee, Elisa T.
Howard, Barbara V.
Fabsitz, Richard R.
Devereux, Richard B.
MacCluer, Jean W.
Laston, Sandra
Comuzzie, Anthony G.
Shara, Nawar M.
Welty, Thomas K.
TI Models of population-based analyses for data collected from large
extended families
SO EUROPEAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Correlated outcomes; Marginal models; Family study; Large and
inter-related extended families
ID LINEAR MIXED MODELS; CARDIOVASCULAR-DISEASE; VARIANCE-COMPONENTS;
PEDIGREE ANALYSIS; AMERICAN-INDIANS; ASSOCIATION; RISK; EXTENSIONS;
INFERENCE; LINKAGE
AB Large studies of extended families usually collect valuable phenotypic data that may have scientific value for purposes other than testing genetic hypotheses if the families were not selected in a biased manner. These purposes include assessing population-based associations of diseases with risk factors/covariates and estimating population characteristics such as disease prevalence and incidence. Relatedness among participants however, violates the traditional assumption of independent observations in these classic analyses. The commonly used adjustment method for relatedness in population-based analyses is to use marginal models, in which clusters (families) are assumed to be independent (unrelated) with a simple and identical covariance (family) structure such as those called independent, exchangeable and unstructured covariance structures. However, using these simple covariance structures may not be optimally appropriate for outcomes collected from large extended families, and may under- or over-estimate the variances of estimators and thus lead to uncertainty in inferences. Moreover, the assumption that families are unrelated with an identical family structure in a marginal model may not be satisfied for family studies with large extended families. The aim of this paper is to propose models incorporating marginal models approaches with a covariance structure for assessing population-based associations of diseases with their risk factors/covariates and estimating population characteristics for epidemiological studies while adjusting for the complicated relatedness among outcomes (continuous/categorical, normally/non-normally distributed) collected from large extended families. We also discuss theoretical issues of the proposed models and show that the proposed models and covariance structure are appropriate for and capable of achieving the aim.
C1 [Wang, Wenyu; Lee, Elisa T.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK 73190 USA.
[Howard, Barbara V.; Shara, Nawar M.] MedStar Hlth Res Inst, Washington, DC USA.
[Fabsitz, Richard R.] NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA.
[Devereux, Richard B.] Cornell Univ, Med Ctr, New York, NY 10021 USA.
[MacCluer, Jean W.; Laston, Sandra; Comuzzie, Anthony G.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA.
[Welty, Thomas K.] Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA.
RP Wang, WY (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, POB 26901, Oklahoma City, OK 73190 USA.
EM wenyu-wang@ouhsc.edu
FU National Heart, Lung, and Blood Institute [U01-HL41642, U01-HL41652,
U01-HL41654, U01-HL65520, U01-HL65521]
FX This study was supported by cooperative agreement grants (No.
U01-HL41642, U01-HL41652, U01-HL41654, U01-HL65520, and U01-HL65521)
from the National Heart, Lung, and Blood Institute. The authors wish to
thank the Indian Health Service hospitals and clinics at each center,
the directors of the Strong Heart Study clinics, Betty Jarvis, Dr.
Tauqeer Ali, Marcia O'Leary, Dr. Marie Russell, Bert Lewis, and their
staffs. The opinions expressed in this paper are those of the authors
and do not necessarily reflect those of the Indian Health Service.
NR 26
TC 3
Z9 3
U1 1
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0393-2990
J9 EUR J EPIDEMIOL
JI Eur. J. Epidemiol.
PD DEC
PY 2010
VL 25
IS 12
BP 855
EP 865
DI 10.1007/s10654-010-9512-y
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 703IJ
UT WOS:000285971300002
PM 20882324
ER
PT J
AU Lan, Q
Au, WY
Chanock, S
Tse, J
Wong, KF
Shen, M
Siu, LP
Yuenger, J
Yeager, M
Hosgood, HD
Purdue, MP
Liang, R
Rothman, N
AF Lan, Qing
Au, Wing-Yan
Chanock, Stephen
Tse, Jovic
Wong, Kit-fai
Shen, Min
Siu, L. P.
Yuenger, Jeff
Yeager, Meredith
Hosgood, Howard Dean, III
Purdue, Mark P.
Liang, Raymond
Rothman, Nathaniel
TI Genetic susceptibility for chronic lymphocytic leukemia among Chinese in
Hong Kong
SO EUROPEAN JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE genetic polymorphism; chronic lymphocytic leukemia; Chinese
ID LYMPHOPROLIFERATIVE DISORDERS; 6P25.3; RISK
AB The genetic basis of chronic lymphocytic leukemia (CLL) has not been fully elucidated to date. Although it is the most common haematological malignancy in Caucasians, it is uncommon among Asians. A recent genome-wide scan of CLL in Caucasians, which was carried out in the UK, identified six variants showing strong association. We attempted to replicate these findings in 71 patients with CLL and 1273 controls in Hong Kong Chinese. Three of the six variants were significantly associated with CLL. The rs872071 variant (Odds Ratio (95% Confidence Interval) = 1.78 (1.25-2.53), P = 0.0013) in the IRF4 gene region showed the strongest association, similar to that reported in the UK study. Polymorphisms in SP140 and ACOXL were also associated with risk of CLL. Further, the mean allele frequencies of the six variants were moderately (59%) to extremely (0.5%) lower in the Chinese population compared with Caucasians. These results suggest that variants in three loci may contribute to risk of CLL among Chinese.
C1 [Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Au, Wing-Yan; Tse, Jovic; Liang, Raymond] Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China.
[Wong, Kit-fai; Siu, L. P.] Queen Elizabeth Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Yuenger, Jeff; Yeager, Meredith] NCI Core Genotyping Facil, Gaithersburg, MD USA.
RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, MSC 7240,6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA.
EM qingl@mail.nih.gov
RI Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
FU NIH, NCI; Hong Kong University
FX Supported in part by the intramural research program of the NIH, NCI and
the Hong Kong University Carol Chau Ting Tong Research Fund.
NR 14
TC 24
Z9 24
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0902-4441
J9 EUR J HAEMATOL
JI Eur. J. Haematol.
PD DEC
PY 2010
VL 85
IS 6
BP 492
EP 495
DI 10.1111/j.1600-0609.2010.01518.x
PG 4
WC Hematology
SC Hematology
GA 679MN
UT WOS:000284165600004
PM 20731705
ER
PT J
AU Ashida, S
Koehly, LM
Roberts, JS
Chen, CA
Hiraki, S
Green, RC
AF Ashida, Sato
Koehly, Laura M.
Roberts, J. Scott
Chen, Clara A.
Hiraki, Susan
Green, Robert C.
TI The role of disease perceptions and results sharing in psychological
adaptation after genetic susceptibility testing: the REVEAL Study
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE susceptibility genetic testing; AD; APOE; results disclosure;
communication; risk perceptions
ID NONPOLYPOSIS COLORECTAL-CANCER; TERM-CARE INSURANCE; ALZHEIMERS-DISEASE;
1ST-DEGREE RELATIVES; RISK-ASSESSMENT; IMPACT; FAMILY; COMMUNICATION;
BRCA1/2; ADJUSTMENT
AB This study evaluates the extent to which psychological adaptation (validated measures of depressive symptoms, anxiety, and test-specific distress) after genetic susceptibility testing is influenced by changes in beliefs about Alzheimer's disease (AD) and sharing of test results with others. Adult children of AD patients (N=269) from a randomized clinical trial involving genetic testing for apolipoprotein E (APOE) provided information before, as well as 6 weeks and 12 months after results disclosure. The levels of adaptation varied highly among participants at 12-month assessment. Participants who learned that they were epsilon 4 negative (lower risk) had a reduction in perceived risk and concern about developing AD compared with those who learned that they were epsilon 4 positive. Those who received results through an extended educational protocol (three in-person visits) had a larger decline in AD concern than those in a condensed protocol (educational brochure and two in-person visits). Increase in AD concern 6 weeks after disclosure was associated with increase in depression scores (b=0.20, P<0.01) and anxiety levels (b=0.20, P<0.01), and higher distress associated with AD genetic testing (b=0.18, P=0.02) 1 year after testing. Increase in perceived risk (b=0.16, P=0.04) was also associated with higher AD genetic testing distress. Sharing the test results with health professionals and friends (but not family) was associated with decrease in depression (b=-0.11, P=0.05) and anxiety levels (b=-0.16, P<0.01), respectively after a year. Enhancing discussion with regard to risks and concerns about AD during pretesting counseling and obtaining support through sharing the results after testing may help facilitate test recipients' long-term psychological adaptation. European Journal of Human Genetics (2010) 18, 1296-1301; doi: 10.1038/ejhg.2010.119; published online 28 July 2010
C1 [Ashida, Sato; Koehly, Laura M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[Roberts, J. Scott] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA.
[Chen, Clara A.] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA.
[Hiraki, Susan; Green, Robert C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Green, Robert C.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Green, Robert C.] Boston Univ, Sch Med, Dept Med Genet, Boston, MA 02118 USA.
RP Ashida, S (reprint author), NHGRI, Social & Behav Res Branch, 31 Ctr Dr,B1B37C, Bethesda, MD 20892 USA.
EM ashidas@mail.nih.gov
FU ELSI Branch of the National Human Genome Research Institute; National
Institute on Aging [R01 HG/AG02213, R01 AG09029, K24 AG027841]; National
Human Genome Research Institute at the National Institutes of Health;
Boston University Alzheimer's Disease Center [P50 AG13846]
FX The REVEAL Study was funded by the ELSI Branch of the National Human
Genome Research Institute and the National Institute on Aging (R01
HG/AG02213 and R01 AG09029). Additional support was provided by an NIA
Mentoring Award to Dr Green (K24 AG027841), the Boston University
Alzheimer's Disease Center (P50 AG13846) and Boston University General
Clinical Research Center (GCRC) (M01 RR00533). The completion of this
article was supported by the Intramural Research Program of the National
Human Genome Research Institute at the National Institutes of Health.
Other REVEAL investigators include: Lindsay A Farrer, PhD, Department of
Neurology and Medicine (Genetics Program), Boston University School of
Medicine and Biostatistics, Boston University School of Public Health;
Robert Stern, PhD, Department of Neurology, Boston University School of
Medicine; L Adrienne Cupples, PhD, Department of Epidemiology and
Biostatistics, Boston University School of Public Health; Anil Nair, MD,
Department of Neurology, Boston University School of Medicine; Erin
Linnenbringer, MS, CGC, Department of Health Behavior and Health
Education, University of Michigan School of Public Health; Thomas
Obisesan, MD, MPH, Department of Medicine, Howard University Hospital,
Washington, DC; Grace-Ann Fasaye, ScM, CGC, Department of Medicine,
Howard University Hospital, Washington, DC; Charmaine Royal, PhD,
National Human Genome Center, Howard University, Washington, DC; Melissa
Barber, ScM, Memory and Aging Center, Case Western Reserve
University/University Hospitals of Cleveland Memory and Aging,
Cleveland, OH; Peter Whitehouse, MD, Memory and Aging Center, Case
Western Reserve University/University Hospitals of Cleveland Memory and
Aging, Cleveland, OH; Normal Relkin, MD, PhD, Department of Neurology,
Weill Medical College of Cornell University, New York, NY; Elana Cox,
MS, CGC, Department of Neurology, Weill Medical College of Cornell
University, New York, NY; Lisa Ravdin, PhD, Department of Neurology and
Neuroscience, Weill Medical College of Cornell University, New York, NY;
Robert Cook-Deegan at Duke University.
NR 42
TC 21
Z9 23
U1 4
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 2010
VL 18
IS 12
BP 1296
EP 1301
DI 10.1038/ejhg.2010.119
PG 6
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 682CF
UT WOS:000284376800006
PM 20664629
ER
PT J
AU Tucci, A
Nalls, MA
Houlden, H
Revesz, T
Singleton, AB
Wood, NW
Hardy, J
Paisan-Ruiz, C
AF Tucci, Arianna
Nalls, Mike A.
Houlden, Henry
Revesz, Tamas
Singleton, Andrew B.
Wood, Nicholas W.
Hardy, John
Paisan-Ruiz, Coro
TI Genetic variability at the PARK16 locus
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE PARK16 locus; genetics; association studies
ID IDIOPATHIC PARKINSONS-DISEASE; GENOME-WIDE ASSOCIATION; ALPHA-SYNUCLEIN;
RISK-FACTORS; LRRK2 GENE; SUSCEPTIBILITY; ACCURACY
AB Parkinson's disease (PD) is a complex neurodegenerative disease which is clinically heterogeneous and pathologically consists of loss of dopaminergic neurons in the substantia nigra and intracytoplasmic neuronal inclusions containing alpha-synuclein aggregations known as Lewy bodies. Although the majority of PD is idiopathic, pathogenic mutations in several mendelian genes have been successfully identified through linkage analyses. To identify susceptibility loci for idiopathic PD, several genome-wide association studies (GWAS) within different populations have recently been conducted in both idiopathic and familial forms of PD. These analyses have confirmed SNCA and MAPT as loci harboring PD susceptibility. In addition, the GWAS identified several other genetic loci suggestively associated with the risk of PD; among these, only one was replicated by two different studies of European and Asian ancestries. Hence, we investigated this novel locus known as PARK16 for coding mutations in a large series of idiopathic pathologically proven PD cases, and also conducted an association study in a case-control cohort from the United Kingdom. An association between a novel RAB7L1 mutation, c.379-12insT, and disease (P-value=0.0325) was identified. Two novel coding variants present only in the PD cohort were also identified within the RAB7L1 (p.K157R) and SLC41A1 (p.A350V) genes. No copy number variation analyses have yet been performed within this recently identified locus. We concluded that, although both coding variants and risk alleles within the PARK16 locus seem to be rare, further molecular analyses within the PARK16 locus and within different populations are required in order to examine its biochemical role in the disease process. European Journal of Human Genetics (2010) 18, 1356-1359; doi: 10.1038/ejhg.2010.125; published online 4 August 2010
C1 [Tucci, Arianna; Houlden, Henry; Revesz, Tamas; Wood, Nicholas W.; Hardy, John; Paisan-Ruiz, Coro] UCL Inst Neurol, Dept Mol Neurosci, London, England.
[Tucci, Arianna; Houlden, Henry; Revesz, Tamas; Wood, Nicholas W.; Hardy, John; Paisan-Ruiz, Coro] UCL Inst Neurol, Reta Lila Weston Inst, London, England.
[Nalls, Mike A.; Singleton, Andrew B.] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Paisan-Ruiz, C (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl, New York, NY 10029 USA.
EM cpaisan@gmail.com
RI Paisan-Ruiz, Coro/C-2912-2009; Singleton, Andrew/C-3010-2009; Hardy,
John/C-2451-2009; Houlden, Henry/C-1532-2008; Wood,
Nicholas/C-2505-2009; Revesz, Tamas/A-8732-2010
OI Houlden, Henry/0000-0002-2866-7777; Wood, Nicholas/0000-0002-9500-3348;
Revesz, Tamas/0000-0003-2501-0259
FU Medical Research Council (MRC) [G108/638, G0802760]; Michael J Fox
Foundation; NIHR UCLH/UCL Comprehensive Biomedical Research Centre; NIH,
National Institute on Aging [AG000957-07]
FX We thank all patients who participated in this study and all families
who supported the donation of tissue for research. We also thank The
Medical Research Council (MRC; HH: MRC fellowships G108/638 and G0802760
and JH: start-up funds) and The Michael J Fox Foundation (HH and CPR)
for support. This study was also supported by the NIHR UCLH/UCL
Comprehensive Biomedical Research Centre. MAN and ABS were partly
supported in this research by the Intramural Research Program of the
NIH, National Institute on Aging (AG000957-07 (2009) Assessment of
Candidate Loci in Neurological diseases).
NR 23
TC 34
Z9 39
U1 0
U2 2
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 2010
VL 18
IS 12
BP 1356
EP 1359
DI 10.1038/ejhg.2010.125
PG 4
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 682CF
UT WOS:000284376800017
PM 20683486
ER
PT J
AU Smrz, D
Iwaki, S
McVicar, DW
Metcalfe, DD
Gilfillan, AM
AF Smrz, Daniel
Iwaki, Shoko
McVicar, Daniel W.
Metcalfe, Dean D.
Gilfillan, Alasdair M.
TI TLR-mediated signaling pathways circumvent the requirement for DAP12 in
mast cells for the induction of inflammatory mediator release
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE DAP12; Fc epsilon RI; KIT; Mast cells; TLR
ID PROTEIN-TYROSINE KINASE; TOLL-LIKE RECEPTORS; CUTTING EDGE; ADAPTERS
DAP12; MYELOID CELLS; FCR-GAMMA; ACTIVATION; RESPONSES; SYK;
PHOSPHORYLATION
AB TLR, expressed on the surface of mast cells, respond to a variety of bacterial and viral components to induce and enhance high-affinity IgE receptor-mediated cytokine production. Recent reports have indicated that specific TLR-dependent responses in macrophages and dendritic cells are regulated by the ITAM-containing molecule, DAP12. When phosphorylated, DAP12 recruits Syk, which is a critical molecule for mast cell activation. We therefore examined whether DAP12 similarly regulates TLR-mediated responses in mast cells. DAP12 was confirmed to be expressed in both human and mouse mast cells and, upon phosphorylation, to recruit Syk. However, although TLR agonists induced cytokine production, and synergistically enhanced high-affinity IgE receptor-mediated cytokine production, surprisingly, they failed to increase DAP12 phosphorylation in mouse bone marrow-derived mast cells (BMMC). Furthermore, normal TLR-mediated responses were observed in DAP12(-/-) BMMC. However, DAP12 phosphorylation and subsequent Syk recruitment were observed in BMMC following Con A-induced aggregation of mannose-glycosylated receptors, and these responses, together with Con A-induced degranulation, were substantially reduced in the DAP12(-/-) BMMC. These data demonstrate that TLR have differential requirements for DAP12 for their function in different cell types and that the inability of TLR to influence mast cell degranulation may be linked to their inability to utilize DAP12 to recruit Syk.
C1 [Smrz, Daniel; Iwaki, Shoko; Metcalfe, Dean D.; Gilfillan, Alasdair M.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[McVicar, Daniel W.] Natl Canc Inst Frederick, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD USA.
RP Gilfillan, AM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C206,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA.
EM agilfillan@niaid.nih.gov
RI McVicar, Daniel/G-1970-2015; Smrz, Daniel/D-4853-2014
OI Smrz, Daniel/0000-0003-0143-8744
FU Division of Intramural Research of NIAID; NCI within the National
Institutes of Health
FX This work was supported by the Division of Intramural Research of NIAID
and NCI within the National Institutes of Health. We thank Drs.
Toshiyuki Takei and Wayne Yokoyama for providing DAP12-deficient
animals.
NR 42
TC 11
Z9 11
U1 0
U2 0
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD DEC
PY 2010
VL 40
IS 12
BP 3557
EP 3569
DI 10.1002/eji.201040573
PG 13
WC Immunology
SC Immunology
GA 693YV
UT WOS:000285262200029
PM 21108475
ER
PT J
AU Romagnoli, R
Baraldi, PG
Cara, CL
Hamel, E
Basso, G
Bortolozzi, R
Viola, G
AF Romagnoli, Romeo
Baraldi, Pier Giovanni
Cara, Carlota Lopez
Hamel, Ernest
Basso, Giuseppe
Bortolozzi, Roberta
Viola, Giampietro
TI Synthesis and biological evaluation of 2-(3 ',4 ',5
'-trimethoxybenzoyl)-3-aryl/arylaminobenzo[b]thiophene derivatives as a
novel class of antiproliferative agents
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Microtubules; Benzo[b]thiophene; Apoptosis
ID TUBULIN-BINDING-AGENTS; CELL-DEATH; MICROTUBULE DYNAMICS; MEDICINAL
CHEMISTRY; CANCER-THERAPY; APOPTOSIS; UPDATE; MITOCHONDRIA; DRUGS; BCL-2
AB The biological importance of microtubules in mitosis, as well as in interphase, makes them an interesting target for the development of anticancer agents. Small molecules such as benzo[b]thiophenes are attractive as inhibitors of tubulin polymerization. Thus, a new class of compounds that incorporated the structural motif of the 2-(3',4',5'-trimethoxybenzoyl)-3-aryl/arylamino benzo[b]thiophene molecular skeleton, with electron-donating (Me, OMe, SMe or OEt) or electron-withdrawing (F and Cl) substituents on the B-ring, was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization and cell cycle effects. The most promising compound in this series was 2-(3',4',5'-trimethoxybenzoyl)-3-(4'-ethoxyphenyl)-benzo[b]thiophene (4e), which significantly inhibited cancer cell growth at submicromolar concentrations, especially against HeLa and Jurkat cells, and interacted with tubulin. As determined by flow cytometric analysis, 4e caused G2/M phase arrest and apoptosis in a time and concentration-dependent manner. The block in G2/M was correlated with increased expression of cyclin 131 and phosphorylation of cdc25c. Moreover, 4e perturbed mitochondrial membrane potential and caused activation of caspase-3 and cleavage of poly(ADP-rybose)polymerase (PARP), events that are involved in 4e-induced apoptosis. (C) 2010 Elsevier Masson SAS. All rights reserved.
C1 [Romagnoli, Romeo; Baraldi, Pier Giovanni; Cara, Carlota Lopez] Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
[Basso, Giuseppe; Bortolozzi, Roberta; Viola, Giampietro] Univ Padua, Dipartimento Pediat, Lab Oncoematol, I-35131 Padua, Italy.
RP Romagnoli, R (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, Via Fossato di Mortara 17-19, I-44100 Ferrara, Italy.
EM rmr@unife.it; giampietro.viola.1@unipd.it
RI Viola, Giampietro/I-4095-2012; Bortolozzi, Roberta/D-4950-2015;
LOPEZ-CARA, LUISA CARLOTA/F-9686-2014; Romagnoli, Romeo/G-9887-2015;
Baraldi, Pier Giovanni/B-7933-2017;
OI Viola, Giampietro/0000-0001-9329-165X; Bortolozzi,
Roberta/0000-0002-3357-4815; LOPEZ-CARA, LUISA
CARLOTA/0000-0003-1142-6448; BASSO, GIUSEPPE/0000-0002-2634-9302
FU Intramural NIH HHS [Z99 CA999999]
NR 46
TC 14
Z9 15
U1 0
U2 4
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD DEC
PY 2010
VL 45
IS 12
BP 5781
EP 5791
DI 10.1016/j.ejmech.2010.09.038
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 697AM
UT WOS:000285485000029
PM 20933308
ER
PT J
AU Luo, XA
Oyugi, DA
Lin, CW
Izevbigie, EB
Lee, KS
AF Luo, Xuan
Oyugi, Daniel A.
Lin, Cuiwu
Izevbigie, Ernest B.
Lee, Ken S.
TI Isolation and characterization of the antibreast carcinoma cell growth
components of Vernonia amygdalina extracts
SO EXPERIMENTAL BIOLOGY AND MEDICINE
LA English
DT Article
DE anticancer; Vernonia amygdalina; steroid glucoside; active components;
chromatography
ID POSSIBLE MEDICINAL-PLANT; SESQUITERPENE LACTONES; WILD CHIMPANZEES;
STEROID GLUCOSIDES; BITTER; LEAVES; DEL; CONSTITUENTS; FRACTIONS
AB Vernonia amygdalina (VA) is widely used for medicinal and food purposes in tropical Africa. Many health benefits (antioxidant, antimicrobial, anticancer activities and more) of VA extracts have been reported. The mechanisms of actions have also been described. We have previously reported that VA extracts elicited growth inhibitory activities in human estrogen receptor-positive (ER(+)) cells (MCF-7 cells) and ductal carcinoma cells (BT-549) in vitro. The active components in the organic solvent (chloroform)-extracted VA have been previously determined. However, the active components in the ethanolic extracts of VA have not been previously studied. Hence, the objectives of this study are to isolate and characterize the active components of the ethanolic extracts of VA using liquid liquid extraction, thin layer chromatography and column techniques. Fractionation of the ethanolic extracts of VA yielded three fractions named Al, A2 and A3, and A2 retained the DNA synthesis-inhibitory activity of the extracts. Subsequent fractionation of A2 yielded fraction A2B whose activity was 16 and three times more potent than the ethanolic fraction and fraction A2, respectively. The treatment of cells with 100 mu g/mL of either the ethanolic VA extracts, fraction A2 or fraction A2B resulted in a 23% (P<0.01), 86% (P<0.0001) and 97% (P<0.0001) inhibition of DNA synthesis compared with vehicle-treated controls, respectively. Further purification of A2B by high-speed countercurrent chromatography and confirmed by spectroscopic analysis revealed that the major active components of A2B (65% by weight) were steroid glucosides.
C1 [Oyugi, Daniel A.; Izevbigie, Ernest B.] Jackson State Univ, Dept Biol, Jackson, MS 39217 USA.
[Luo, Xuan; Lee, Ken S.] Jackson State Univ, Dept Chem & Biochem, Jackson, MS 39217 USA.
[Oyugi, Daniel A.] Howard Univ, Dept Biol, Washington, DC 20059 USA.
[Lin, Cuiwu] Guangxi Univ, Sch Chem & Chem Engn, Nanning 530004, Guangxi, Peoples R China.
[Izevbigie, Ernest B.] Jackson State Univ, NIH, Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA.
[Izevbigie, Ernest B.] Jackson State Univ, Lab Cellular Signaling Phytoceut & Canc Prevent &, Coll Sci Engn & Technol, Jackson, MS 39217 USA.
RP Izevbigie, EB (reprint author), Jackson State Univ, Dept Biol, 1400 JR Lynch St,POB 18540, Jackson, MS 39217 USA.
EM ernest.b.izevbigie@jsums.edu
FU National Center for Research Resources [G12RR013459]; National Science
Foundation [CHE-0821357]
FX Our appreciation also goes to Joseph L Bryant DVM (University of
Maryland School of Medicine, Baltimore, MD, USA) and Alphonsus Obayuwana
(MD of the Department and Obstetrics and Gynecology, St Vincent Medical
Center, Toledo, OH, USA) for their technical assistance. The project was
supported by the National Center for Research Resources grant no.
G12RR013459 and the National Science Foundation grant no. CHE-0821357.
NR 30
TC 3
Z9 4
U1 3
U2 11
PU SOC EXPERIMENTAL BIOLOGY MEDICINE
PI MAYWOOD
PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA
SN 1535-3702
J9 EXP BIOL MED
JI Exp. Biol. Med.
PD DEC
PY 2010
VL 235
IS 12
BP 1472
EP 1478
DI 10.1258/ebm.2010.010124
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 702OW
UT WOS:000285905000011
PM 20962014
ER
PT J
AU Qian, HH
Alexander, KR
Ripps, H
AF Qian, Haohua
Alexander, Kenneth R.
Ripps, Harris
TI Harmonic analysis of the cone flicker ERG of rabbit
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE electroretinogram; flicker ERG; rabbit; cone pathway; pharmacology;
sinusoidal stimuli; frequency response
ID MAMMALIAN RETINA; IN-VIVO; B-WAVE; ELECTRORETINOGRAM; RESPONSES;
AMPLITUDE; TOXICITY; KINETICS; ROD
AB Harmonic analysis was used to characterize the rabbit flicker ERG elicited by sinusoidally modulated full-field stimuli under light-adapted conditions. The frequency-response function for fundamental amplitude, derived from Fourier analysis of the ERG waveforms, exhibited two limbs, with an amplitude minimum at approximately 30 Hz, and a high-frequency region peaking at around 45 Hz and extending to more than 100 Hz at higher adapting levels. At low frequencies (< 20 Hz), the fundamental response amplitude was independent of mean luminance (Weber law behavior), whereas the response amplitude at high stimulus frequencies varied nonlinearly with mean luminance. At low frequencies, intravitreal administration of L-AP4, which blocks ON-pathway activity, reduced the fundamental response amplitude and produced a phase shift. On the other hand, PDA, which reduces OFF-pathway activity, had a minimal effect on both the response amplitude and phase at low frequencies. At high frequencies, L-AP4 increased the fundamental response amplitude at low mean luminances, whereas PDA had only a small effect on amplitude and phase. Both pharmacologic agents removed the minimum in the amplitude-frequency function as well as the abrupt change in phase at stimulus frequencies near 30 Hz. The results suggest that there is a nonlinear interaction between ON- and OFF-pathway activity over the entire stimulus frequency range examined in this study. These findings provide a basis for formulating protocols to evaluate the effect of pharmacologic agents and/or disease on the cone flicker ERG of rabbit. Published by Elsevier Ltd.
C1 [Qian, Haohua; Alexander, Kenneth R.; Ripps, Harris] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA.
[Qian, Haohua; Ripps, Harris] Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60612 USA.
[Qian, Haohua] Univ Illinois, Dept Biol Sci, Chicago, IL 60612 USA.
[Alexander, Kenneth R.] Univ Illinois, Dept Psychol, Chicago, IL 60612 USA.
[Alexander, Kenneth R.] Univ Illinois, Dept Bioengn, Chicago, IL 60612 USA.
[Ripps, Harris] Marine Biol Lab, Woods Hole, MA 02543 USA.
RP Qian, HH (reprint author), NEI, MSC 4403,9000 Rockville Pike,49 Convent Dr,Bldg 4, Bethesda, MD 20892 USA.
EM haohua.qian@nih.gov
FU Joyce Schroeder Fund; NIH [EY008301, EY01792]; RPB; Research to Prevent
Blindness, Inc.
FX The authors thank Ms. Tara Nguyen for her excellent technical support.
This work was supported by a grant from the Joyce Schroeder Fund (HQ),
NIH research grant EY008301 (KRA), NIH core grant EY01792, RPB Senior
Scientific Investigator Award (HR) and an unrestricted departmental
award from Research to Prevent Blindness, Inc.
NR 30
TC 4
Z9 4
U1 3
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD DEC
PY 2010
VL 91
IS 6
BP 811
EP 817
DI 10.1016/j.exer.2010.10.005
PG 7
WC Ophthalmology
SC Ophthalmology
GA 693IT
UT WOS:000285218500005
PM 20974130
ER
PT J
AU Kittipatarin, C
Li, WQ
Durum, SK
Khaled, AR
AF Kittipatarin, Christina
Li, Wenqing
Durum, Scott K.
Khaled, Annette R.
TI Cdc25A-driven proliferation regulates CD62L levels and lymphocyte
movement in response to interleukin-7
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID NAIVE T-CELLS; IN-VIVO; L-SELECTIN; IL-7; HOMEOSTASIS; SURVIVAL; CDC25A;
RECEPTOR; FOXO1; IMMUNODEFICIENCY
AB Objective Interleukin-7 (IL-7) is a multifunctional cytokine and a promising immunotherapeutic agent However, because transient T-cell depletion is an immediate outcome of IL-7 administration at supraphysiological doses, we investigated the mechanism by which the IL-7 proliferative signal transduced through Cdc25A, a key activator of cyclin-dependent kinases, could modulate lymphocyte movement
Materials and Methods Employing novel methods of manipulating Cdc25A gene expression, combined with in vitro and in vivo evaluation of IL-7 application, we assessed the expression of activation and homing markers and identified the mechanism by which IL-7 could induce T-cell expansion and alter lymphocyte motility
Results Constitutively active Cdc25A drove T-cell proliferation Independently of IL-7 and resulted in an activated phenotype (CD69(hi), CD44(hi)) Conversely, inhibition of Cdc25A resulted in decreased proliferation, reduced expression of activation markers, and upregulation of the lymph node homing molecule, CD62L, which promoted cell adhesion when engaged by ligand We found that IL-7 prevented the nuclear translocation of the transcription factor, Foxo1, in a manner dependent on the activity of Cdc25A, resulting in decreased levels of CD62L In vivo administration of 1L-7 decreased lymph node cellularity, while treatment with IL-7, premixed with a neutralizing IL-7 antibody (M25), increased total lymph node cells with more nuclear Foxo1 detected in cells from mice receiving IL-7 + M25
Conclusions These results are consistent with the model that IL-7 drives Cdc25A-mediated T-cell proliferation, which prevents the nuclear translocation of Foxo1, leading to reduced expression of CD62L and the migration of T cells into circulation (C) 2010 ISEH - Society for Hematology and Stem Cells Published by Elsevier Inc
C1 [Kittipatarin, Christina; Khaled, Annette R.] Univ Cent Florida, Burnett Sch Biomed Sci, Coll Med, Orlando, FL 32827 USA.
[Li, Wenqing; Durum, Scott K.] NCI, Frederick, MD 21701 USA.
RP Khaled, AR (reprint author), Univ Cent Florida, Burnett Sch Biomed Sci, Coll Med, 6900 Lake Nona Blvd, Orlando, FL 32827 USA.
FU NIH [F31GM073565, CA109524RO1]
FX This study was supported by a National Institutes of Health
(NIH)/National Institute of General Medical Sciences Predoctoral
Fellowship F31GM073565 (C K) and an NIH/National Cancer Institute grant
CA109524RO1 (A R K) from the NIH
NR 39
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD DEC
PY 2010
VL 38
IS 12
BP 1143
EP 1156
DI 10.1016/j.exphem.2010.08.010
PG 14
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 689ZC
UT WOS:000284968600004
PM 20831893
ER
PT J
AU Akhavan, AA
Mirhendi, H
Khamesipour, A
Alimohammadian, MH
Rassi, Y
Bates, P
Kamhawi, S
Valenzuela, JG
Arandian, MH
Abdoli, H
Jalali-zand, N
Jafari, R
Shareghi, N
Ghanei, M
Yaghoobi-Ershadi, MR
AF Akhavan, Amir Ahmad
Mirhendi, Hossein
Khamesipour, Ali
Alimohammadian, Mohammad Hossein
Rassi, Yavar
Bates, Paul
Kamhawi, Shaden
Valenzuela, Jesus G.
Arandian, Mohammad Hossein
Abdoli, Hamid
Jalali-zand, Niloufar
Jafari, Reza
Shareghi, Niloufar
Ghanei, Maryam
Yaghoobi-Ershadi, Mohammad Reza
TI Leishmania species: Detection and identification by nested PCR assay
from skin samples of rodent reservoirs
SO EXPERIMENTAL PARASITOLOGY
LA English
DT Article
DE Leishmania major; Leishmania gerbilli; Leishmania turanica; Rodent;
Rhombomys opimus; Cutaneous leishmaniasis; Nested PCR; Iran
ID ZOONOTIC CUTANEOUS LEISHMANIASIS; RHOMBOMYS-OPIMUS; IRAN; INFECTIONS;
NUCLEAR; HOSTS; FOCI
AB Many rodent species act as reservoir hosts of zoonotic cutaneous leishmaniasis in endemic areas. In the present study a simple and reliable assay based on nested PCR was developed for the detection and identification of Leishmania parasites from rodent skin samples. We designed Leishmania-specific primers that successfully amplified ITS regions of Leishmania major, Leishmania gerbilli and Leishmania turanica using nested PCR. Out of 95 field collected Rhombomys opimus, 21 were positive by microscopic examination and 48 by nested PCR. The percentage of gerbils infected with L. major, L gerbilli and L turanica was 3.2%, 1.1% and 27.4%, respectively. In 15.8% of the rodents, we found mixed natural infections by L. major and L turanica, 1.1% by L major and L gerbilli, and 2.1% by the three species. We concluded that this method is simple and reliable for detecting and identifying Leishmania species circulating in rodent populations. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Akhavan, Amir Ahmad; Rassi, Yavar; Yaghoobi-Ershadi, Mohammad Reza] Univ Tehran Med Sci, Sch Publ Hlth, Dept Med Entomol & Vector Control, Tehran, Iran.
[Mirhendi, Hossein] Univ Tehran Med Sci, Sch Publ Hlth, Dept Med Parasitol & Mycol, Tehran, Iran.
[Khamesipour, Ali] Univ Tehran Med Sci, Ctr Res & Training Skin Dis & Leprosy, Tehran, Iran.
[Alimohammadian, Mohammad Hossein] Pasteur Inst Iran, Dept Immunol, Tehran, Iran.
[Bates, Paul] Univ Lancaster, Sch Hlth & Med, Div Biomed & Life Sci, Lancaster, England.
[Kamhawi, Shaden; Valenzuela, Jesus G.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Arandian, Mohammad Hossein; Abdoli, Hamid; Jalali-zand, Niloufar; Jafari, Reza; Shareghi, Niloufar; Ghanei, Maryam] Univ Tehran Med Sci, Publ Hlth Res Inst, Esfahan Hlth Training & Res Ctr, Tehran, Iran.
RP Yaghoobi-Ershadi, MR (reprint author), Univ Tehran Med Sci, Sch Publ Hlth, Dept Med Entomol & Vector Control, Tehran, Iran.
EM yaghoobi.reza@gmail.com
OI Bates, Paul/0000-0001-6861-5421
FU Research deputy of Tehran University of Medical Sciences [3025]
FX This research was supported by Research deputy of Tehran University of
Medical Sciences, Project No. 3025. We are very grateful to Dr. P.
Parvizi, Pasteur Institute of Iran, who provides us with the standard
strains of L. turanica and L. gerbilli and also Mr. D. lravani and Ms.
M. Vaziri, Pasteur Institute of Iran for their technical assistance in
this project. We also thank Dr. M. Jeddi-Tehrani, Avicenna Research
Institute, ACECR, for his valuable comment on the molecular experiments.
NR 24
TC 31
Z9 36
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4894
J9 EXP PARASITOL
JI Exp. Parasitol.
PD DEC
PY 2010
VL 126
IS 4
BP 552
EP 556
DI 10.1016/j.exppara.2010.06.003
PG 5
WC Parasitology
SC Parasitology
GA 654IJ
UT WOS:000282161400018
PM 20566364
ER
PT J
AU Bianco, C
Salomon, DS
AF Bianco, Caterina
Salomon, David S.
TI Targeting the embryonic gene Cripto-1 in cancer and beyond
SO EXPERT OPINION ON THERAPEUTIC PATENTS
LA English
DT Review
DE cancer vaccines; Cripto-1; degenerative muscle diseases; humanized mAbs;
neurodegenerative diseases
ID MAMMARY EPITHELIAL-CELLS; DIFFERENTIAL IMMUNOHISTOCHEMICAL DETECTION;
CARCINOMA-CELLS; COLON-CANCER; STEM-CELLS; ANTISENSE OLIGONUCLEOTIDES;
PARKINSONS-DISEASE; GROWTH-INHIBITION; BREAST-CANCER; SIGNALING PATHWAY
AB Importance of the field: Emerging evidence has clearly implicated an inappropriate activation of embryonic regulatory genes during cell transformation in adult tissues. An example of such a case is the embryonic gene Cripto-1. Cripto-1 is critical for embryonic development and is considered a marker of undifferentiated embryonic stem cells. Critpo-1 is expressed at low levels in adult tissues, but is re-expressed at a high frequency in a number of different types of human carcinomas, therefore, representing an attractive therapeutic target in cancer.
Area covered in this review: This review surveys different approaches that have been used to target Cripto-1 in cancer as reflected by the relevant patent literature as well as peer-reviewed publications. Potential involvement and targeting of Cripto-1 in neurodegenerative and degenerative muscle diseases are also discussed.
What the reader will gain: The reader will gain an overview of different mAbs, vaccines or oligonucleotides antisense targeting Cripto-1. A humanized anti-Cripto-1 antibody is currently being tested in a Phase I clinical trial in cancer patients.
Take home message: Targeting Cripto-1 in human tumors has the potential to eliminate not only differentiated cancer cells but also destroy an undifferentiated subpopulation of cancer cells with stem-like characteristics that support tumor initiation and self-renewal.
C1 [Bianco, Caterina; Salomon, David S.] NCI, NIH, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA.
RP Bianco, C (reprint author), NCI, NIH, Mammary Biol & Tumorigenesis Lab, 37 Convent Dr,Bldg 37,Room 1112, Bethesda, MD 20892 USA.
EM Biancoc@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 86
TC 15
Z9 16
U1 0
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1354-3776
J9 EXPERT OPIN THER PAT
JI Expert Opin. Ther. Patents
PD DEC
PY 2010
VL 20
IS 12
BP 1739
EP 1749
DI 10.1517/13543776.2010.530659
PG 11
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 681YR
UT WOS:000284361100007
PM 21073352
ER
PT J
AU Yuditskaya, S
Suffredini, AF
Kato, GJ
AF Yuditskaya, Susan
Suffredini, Anthony F.
Kato, Gregory J.
TI The proteome of sickle cell disease: insights from exploratory proteomic
profiling
SO EXPERT REVIEW OF PROTEOMICS
LA English
DT Review
DE 2D-DIGE; apolipoprotein; cytoskeleton; exploratory proteomics; lipid
rafts; MALDI-TOF; oxidative stress; pulmonary hypertension; SELDI-TOF;
sickle cell disease
ID ACUTE-PHASE RESPONSE; GLUTATHIONE-PEROXIDASE LEVELS;
HIGH-DENSITY-LIPOPROTEINS; TANDEM MASS-SPECTROMETRY; APOLIPOPROTEIN-A-I;
RED-BLOOD-CELLS; PULMONARY-HYPERTENSION; ERYTHROCYTE-MEMBRANE; OXIDATIVE
DAMAGE; CONJUGATING/LIGATING ACTIVITY
AB The expanding realm of exploratory proteomics has added a unique dimension to the study of the complex pathophysiology involved in sickle cell disease. A review of proteomic studies published on sickle cell erythrocytes and plasma shows trends of upregulation of antioxidant proteins, an increase in cytoskeletal defects, an increase in protein repair and turnover components, a decrease in lipid raft proteins and apolipoprotein dysregulation. Many of these findings are consistent with the pathophysiology of sickle cell disease, including high oxidant burden, resulting in damage to cytoskeletal and other proteins, and erythrocyte rigidity. More unexpected findings, such as a decrease in lipid raft components and apolipoprotein dysregulation, offer previously unexplored targets for future investigation and potential therapeutic intervention. Exploratory proteomic profiling is a valuable source of hypothesis generation for the cellular and molecular pathophysiology of sickle cell disease.
C1 [Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Kato, GJ (reprint author), NHLBI, Sickle Cell Vasc Dis Sect, Cardiovasc & Pulm Branch, NIH, 9000 Rockville Pike,MSC 1476,Bldg 10 CRC,Room 5-5, Bethesda, MD 20892 USA.
EM gkato@mail.nih.gov
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU Division of Intramural Research of the National Heart, Lung and Blood
Institute (MD, USA); Clinical Center of the NIH (MD, USA); NIH
[1ZIAHL006014-01]
FX The authors are supported by funds from the Division of Intramural
Research of the National Heart, Lung and Blood Institute (MD, USA) and
the Clinical Center of the NIH (MD, USA). Gregory J Kato has received
funding from the NIH (grant number 1ZIAHL006014-01). The authors have no
other relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 111
TC 11
Z9 11
U1 0
U2 2
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1478-9450
J9 EXPERT REV PROTEOMIC
JI Expert Rev. Proteomics
PD DEC
PY 2010
VL 7
IS 6
BP 833
EP 848
DI 10.1586/EPR.10.88
PG 16
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 693ME
UT WOS:000285227400010
PM 21142886
ER
PT J
AU Yang, XR
Liang, XY
Pfeiffer, RM
Wheeler, W
Maeder, D
Burdette, L
Yeager, M
Chanock, S
Tucker, MA
Goldstein, AM
AF Yang, Xiaohong Rose
Liang, Xueying
Pfeiffer, Ruth M.
Wheeler, William
Maeder, Dennis
Burdette, Laurie
Yeager, Meredith
Chanock, Stephen
Tucker, Margaret A.
Goldstein, Alisa M.
TI Associations of 9p21 variants with cutaneous malignant melanoma, nevi,
and pigmentation phenotypes in melanoma-prone families with and without
CDKN2A mutations
SO FAMILIAL CANCER
LA English
DT Article
DE Melanoma; Nevi; Chromosome 9p21; SNP; CDKN2A
ID METHYLTHIOADENOSINE PHOSPHORYLASE GENE; GENOME-WIDE ASSOCIATION;
IRON-REGULATORY GENES; GERM-LINE MUTATIONS; TUMOR-SUPPRESSOR;
HEPATOCELLULAR-CARCINOMA; RISK; CANCER; POLYMORPHISMS; LINKAGE
AB Chromosome 9p21 has been implicated in the pathogenesis of cutaneous malignant melanoma (CMM). In addition to CDKN2A, the major known high-risk susceptibility gene for CMM, recent studies suggest that other 9p21 genes may be involved in melanoma/nevi development. To identify 9p21 variants that influence susceptibility to CMM and number of nevi in CMM-prone families with and without CDKN2A mutations, we analyzed 562 individuals (183 CMM) from 53 families (23 CDKN2A+, 30 CDKN2A-) for 233 tagging SNPs in 21 genes at 9p21. Single SNP- and gene-based regression analyses were used to assess the risk of CMM, nevi count, skin complexion, and tanning ability associated with these SNPs and genes. We found that SNP rs7023329 in the MTAP gene was associated with number of nevi (P (trend) = 0.003) confirming a recent finding by a genome-wide association study. In addition, three SNPs in the ACO1 gene, rs7855483 (P (trend) = 0.002), rs17288067 (P (trend) = 0.0009), and rs10813813 (P (trend) = 0.005), showed the strongest associations with CMM risk. None of the examined 9p21 SNPs was associated with skin complexion, whereas two SNPs, rs10964862 in IFNW1 (P (trend) = 0.003), and rs13290968 in TUSC1 (P (trend) = 0.0006), were associated with tanning ability. Gene-based analyses suggested that the ACO1 gene was significantly associated with CMM (P = 0.0004); genes IFNW1 (P = 0.002) and ACO1 (P = 0.0002) were significantly associated with tanning ability. Our findings are consistent with recent proposals that additional 9p21 genes may contribute to CMM susceptibility in CMM-prone families. These genetic variants may, at least partially, exert their effects through nevi and tanning ability.
C1 [Yang, Xiaohong Rose] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA.
[Yang, Xiaohong Rose; Liang, Xueying; Pfeiffer, Ruth M.; Maeder, Dennis; Chanock, Stephen; Tucker, Margaret A.; Goldstein, Alisa M.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Wheeler, William] Informat Management Serv Inc, Rockville, MD USA.
[Burdette, Laurie; Yeager, Meredith] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Yang, XR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM royang@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011; Tucker, Margaret/B-4297-2015
FU NIH, NCI, DCEG
FX We are indebted to the participating families, whose generosity and
cooperation have made this study possible. We also acknowledge the
contributions to this work that were made by Virginia Pichler, Deborah
Zametkin, and Mary Fraser. This research was supported by the Intramural
Research Program of the NIH, NCI, DCEG.
NR 49
TC 20
Z9 20
U1 1
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1389-9600
J9 FAM CANCER
JI Fam. Cancer
PD DEC
PY 2010
VL 9
IS 4
BP 625
EP 633
DI 10.1007/s10689-010-9356-3
PG 9
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 679JH
UT WOS:000284157200021
PM 20574843
ER
PT J
AU Hewitt, SC
Kissling, GE
Fieselman, KE
Jayes, FL
Gerrish, KE
Korach, KS
AF Hewitt, Sylvia C.
Kissling, Grace E.
Fieselman, Karen E.
Jayes, Friederike L.
Gerrish, Kevin E.
Korach, Kenneth S.
TI Biological and biochemical consequences of global deletion of exon 3
from the ER alpha gene
SO FASEB JOURNAL
LA English
DT Article
DE estrogen receptor; uterus; knockout
ID ESTROGEN-RECEPTOR-ALPHA; KNOCKOUT MICE; GROWTH-FACTOR; REPRODUCTIVE
PHENOTYPES; VASCULAR INJURY; CROSS-TALK; IN-VIVO; MOUSE; BONE;
SPECIFICITY
AB To address issues resulting from alpha estrogen receptor-knockout (alpha ERKO) residual N-terminal truncated estrogen receptor alpha, and to allow tissue-selective deletion of ER alpha, we generated loxP-flanked exon 3 mice. Initial characterization of global sox2 cre-derived exon 3-deleted Ex3 alpha ERKO mice indicated no ER alpha protein in uterine tissue and recapitulation of previously described female phenotypes, confirming successful ablation of ER alpha. Body weights of Ex3 alpha ERKO female mice were 1.4-fold higher than wild-tupe (WT) females and comparable to WT males. Microarray indicated the Ex3 alpha ERKO uterus is free of residual estrogen responses. RT-PCR showed Nr4a1 is increased 41-fold by estrogen in WT and 7.4-fold in alpha ERKO, and not increased in Ex3 alpha ERKO. Nr4a1, Cdkn1a, and c-fos transcripts were evaluated in WT and Ex3 alpha ERKO mice following estrogen, IGF1, or EGF injections. All 3 were increased by all treatments in WT. None were increased by estrogen in Ex3 alpha ERKO. Nr4a1 increased 24.5- and 14.7-fold, Cdkn1a increased 14.2- and 12.3-fold, and c-fos increased 20.9-fold and 16.2-fold after IGF1 and EGF treatments, respectively, in the Ex3 alpha ERKO mice, confirming that growth factor regulation is independent of ER alpha. Our Ex3 alpha ER alpha model will be useful in studies of complete or selective ablation of ER alpha in target tissues.-Hewitt, S. C., Kissling, G. E., Fieselman, K. E., Jayes, F. L., Gerrish, K. E., Korach, K. S. Biological and biochemical consequences of global deletion of exon 3 from the ER alpha gene. FASEB J. 24, 4660-4667 (2010). www.fasebj.org
C1 [Hewitt, Sylvia C.; Fieselman, Karen E.; Jayes, Friederike L.; Korach, Kenneth S.] NIEHS, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
[Kissling, Grace E.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Hewitt, SC (reprint author), 111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM curtiss@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU U.S. National Institutes of Health, National Institute of Environmental
Health Sciences [Z01ES 70065]
FX The authors thank David Monroy for breeding expertise and for collecting
animal weights; the National Institute of Environmental Health Sciences
(NIEHS) Microarray Core for microarray studies and analysis; the NIEHS
Histology Core for tissue sample preparation; Dr. Manas K. Ray and Mr.
Greg Scott (NIEHS Knockout Mice Core) for generating the floxed Ex3 ER
alpha mice; Comparative Medicine Branch surgeons James Clark, Page
Myers, and David Goulding for ovariectomies and implanting osmotic
pumps; and Karina Rodriguez for the hormone assays. This research was
supported (in part) by the Intramural Research Program of the U.S.
National Institutes of Health, National Institute of Environmental
Health Sciences project number Z01ES 70065.
NR 25
TC 55
Z9 56
U1 0
U2 3
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD DEC
PY 2010
VL 24
IS 12
BP 4660
EP 4667
DI 10.1096/fj.10-163428
PG 8
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 688BO
UT WOS:000284824400007
PM 20667977
ER
PT J
AU Lao, QZ
Kobrinsky, E
Liu, Z
Soldatov, NM
AF Lao, Qi Zong
Kobrinsky, Evgeny
Liu, Zhuo
Soldatov, Nikolai M.
TI Oligomerization of Ca-v beta subunits is an essential correlate of Ca2+
channel activity
SO FASEB JOURNAL
LA English
DT Article
DE protein-protein interaction; high-order protein complexes; calcium
channel regulation; calcium signaling
ID GATED CALCIUM-CHANNELS; FUNCTIONAL-PROPERTIES; ALKALINE-PHOSPHATASE;
HEART-CELLS; MODULATION; EXPRESSION; BRAIN; HETEROGENEITY; HYPERTENSION;
NEURONS
AB Voltage-gated calcium channels conduct Ca2+ ions in response to membrane depolarization. The resulting transient increase in cytoplasmic free calcium concentration is a critical trigger for the initiation of such vital responses as muscle contraction and transcription. L-type Ca(v)1.2 calcium channels are complexes of the pore-forming alpha(1C) subunit associated with cytosolic Ca-v beta subunits. All major Ca-v beta s share a highly homologous membrane associated guanylate kinaselike (MAGUK) domain that binds to alpha(1C) at the alpha-interaction domain (AID), a short motif in the linker between transmembrane repeats I and II. In this study we show that Ca-v beta subunits form multimolecular homoand heterooligomeric complexes in human vascular smooth muscle cells expressing native calcium channels and in Cos7 cells expressing recombinant Ca(v)1.2 channel subunits. Ca-v beta s oligomerize at the alpha(1C) subunits residing in the plasma membrane and bind to the AID. However, Ca-v beta oligomerization occurs independently on the association with alpha(1C). Molecular structures responsible for Ca-v beta oligomerization reside in 3 regions of the guanylate kinase subdomain of MAGUK. An augmentation of Ca-v beta homooligomerization significantly increases the calcium current density, while heterooligomerization may also change the voltagedependence and inactivation kinetics of the channel. Thus, oligomerization of Ca-v beta subunits represents a novel and essential aspect of calcium channel regulation.-Lao, Q. Z., Kobrinsky, E., Liu, Z., Soldatov, N. M. Oligomerization of Ca-v beta subunits is an essential correlate of Ca2+ channel activity. FASEB J. 24, 5013-5023 (2010). www. fasebj. org
C1 [Lao, Qi Zong; Kobrinsky, Evgeny; Liu, Zhuo; Soldatov, Nikolai M.] NIA, NIH, Baltimore, MD 21224 USA.
RP Soldatov, NM (reprint author), Humgenex Inc, 3105 Starner Court, Kensington, MD 20895 USA.
EM soldatovn.humgenex@verizon.net
FU National Institute on Aging [Z01 AG000294-08]
FX This work was supported by the National Institute on Aging Intramural
Research Program (Z01 AG000294-08 to N.M.S.).
NR 40
TC 8
Z9 8
U1 0
U2 4
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD DEC
PY 2010
VL 24
IS 12
BP 5013
EP 5023
DI 10.1096/fj.10-165381
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 688BO
UT WOS:000284824400039
PM 20732952
ER
PT J
AU Fenton, AK
Hobley, L
Butan, C
Subramaniam, S
Sockett, RE
AF Fenton, Andrew K.
Hobley, Laura
Butan, Carmen
Subramaniam, Sriram
Sockett, Renee E.
TI A coiled-coil-repeat protein 'Ccrp' in Bdellovibrio bacteriovorus
prevents cellular indentation, but is not essential for vibroid cell
morphology
SO FEMS MICROBIOLOGY LETTERS
LA English
DT Article
DE Bdellovibrio bacteriovorus; Ccrp; cytoskeleton; intermediate filament
ID ESCHERICHIA-COLI; CLONING VECTORS; LIFE-CYCLE; IV PILI; GROWTH;
STREPTOMYCES; PREDATION; DYNAMICS
AB Bdellovibrio bacteriovorus are small, vibroid, predatory bacteria that grow within the periplasmic space of a host Gram-negative bacterium. The intermediate-filament (IF)-like protein crescentin is a member of a broad class of IF-like, coiled-coil-repeat-proteins (CCRPs), discovered in Caulobacter crescentus, where it contributes to the vibroid cell shape. The B. bacteriovorus genome has a single ccrp gene encoding a protein with an unusually long, stutter-free, coiled-coil prediction; the inactivation of this did not alter the vibriod cell shape, but caused cell deformations, visualized as chiselled insets or dents, near the cell poles and a general 'creased' appearance, under the negative staining preparation used for electron microscopy, but not in unstained, frozen, hydrated cells. Bdellovibrio bacteriovorus expressing 'teal' fluorescent protein (mTFP), as a C-terminal tag on the wild-type Ccrp protein, did not deform under negative staining, suggesting that the function was not impaired. Localization of fluorescent Ccrp-mTFP showed some bias to the cell poles, independent of the cytoskeleton, as demonstrated by the addition of the MreB-specific inhibitor A22. We suggest that the Ccrp protein in B. bacteriovorus contributes as an underlying scaffold, similar to that described for the CCRP protein FilP in Streptomyces coelicolor, preventing cellular indentation, but not contributing to the vibroid shape of the B. bacteriovorus cells.
C1 [Sockett, Renee E.] Univ Nottingham, QMC, Inst Genet, Sch Biol,Med Sch, Nottingham NG7 2UH, England.
[Butan, Carmen; Subramaniam, Sriram] NCI, Cell Biol Lab, CCR, Bethesda, MD 20892 USA.
RP Sockett, RE (reprint author), Univ Nottingham, QMC, Inst Genet, Sch Biol,Med Sch, Derby Rd, Nottingham NG7 2UH, England.
EM liz.sockett@nottingham.ac.uk
FU BBSRC; HFSP grant [RGP57/2005]; NIH
FX We thank C.J. Wagner for her initial identification of a coiled-coil
containing protein in Bdellovibrio, Cezar Khusugaria for advice and
assistance with the cryoelectron microscopy on the Tecnai Polara TEM and
Marilyn Whitworth for technical assistance. This study was funded by a
BBSRC PhD Studentship for A. K. F. to R. E. S., HFSP grant RGP57/2005 to
R. E. S. for L. H. and NIH core funding to S. S. for C. B. A. K. F.
carried out the majority of the experiments, designed parts of the
experimental programme including the mTFP fusions and coauthored the
paper. L. H. constructed the Bd2345::Kn B. bacteriovorus control strain,
assisted with TEM analysis and critically read the manuscript. C. B. and
A. K. F. carried out cryoelectron microscopic analysis under the
supervision of S. S., and R. E. S. designed the experimental programme,
supervised the research, coauthored and revised the paper.
NR 24
TC 3
Z9 3
U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0378-1097
J9 FEMS MICROBIOL LETT
JI FEMS Microbiol. Lett.
PD DEC
PY 2010
VL 313
IS 2
BP 89
EP 95
DI 10.1111/j.1574-6968.2010.02125.x
PG 7
WC Microbiology
SC Microbiology
GA 682AM
UT WOS:000284367900001
PM 20977494
ER
PT J
AU Wickner, RB
Shewmaker, F
Edskes, H
Kryndushkin, D
Nemecek, J
McGlinchey, R
Bateman, D
Winchester, CL
AF Wickner, Reed B.
Shewmaker, Frank
Edskes, Herman
Kryndushkin, Dmitry
Nemecek, Julie
McGlinchey, Ryan
Bateman, David
Winchester, Chia-Lin
TI Prion amyloid structure explains templating: how proteins can be genes
SO FEMS YEAST RESEARCH
LA English
DT Review
DE prion; amyloid; in-register parallel structure
ID BETA-SHEET STRUCTURE; NUCLEAR-MAGNETIC-RESONANCE; YEAST SUP35 PROTEIN;
HET-S PRION; GERSTMANN-STRAUSSLER SYNDROME; CREUTZFELDT-JAKOB-DISEASE;
FUNGUS PODOSPORA-ANSERINA; SACCHAROMYCES-CEREVISIAE; IN-VITRO; SCRAPIE
AGENT
AB The yeast and fungal prions determine heritable and infectious traits, and are thus genes composed of protein. Most prions are inactive forms of a normal protein as it forms a self-propagating filamentous beta-sheet-rich polymer structure called amyloid. Remarkably, a single prion protein sequence can form two or more faithfully inherited prion variants, in effect alleles of these genes. What protein structure explains this protein-based inheritance? Using solid-state nuclear magnetic resonance, we showed that the infectious amyloids of the prion domains of Ure2p, Sup35p and Rnq1p have an in-register parallel architecture. This structure explains how the amyloid filament ends can template the structure of a new protein as it joins the filament. The yeast prions [PSI+] and [URE3] are not found in wild strains, indicating that they are a disadvantage to the cell. Moreover, the prion domains of Ure2p and Sup35p have functions unrelated to prion formation, indicating that these domains are not present for the purpose of forming prions. Indeed, prion-forming ability is not conserved, even within Saccharomyces cerevisiae, suggesting that the rare formation of prions is a disease. The prion domain sequences generally vary more rapidly in evolution than does the remainder of the molecule, producing a barrier to prion transmission, perhaps selected in evolution by this protection.
C1 [Wickner, Reed B.; Shewmaker, Frank; Edskes, Herman; Kryndushkin, Dmitry; Nemecek, Julie; McGlinchey, Ryan; Bateman, David; Winchester, Chia-Lin] NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA.
EM wickner@helix.nih.gov
FU National Institute of Diabetes Digestive and Kidney Diseases of the
National Institutes of Health
FX We were fortunate to be able to collaborate with Rob Tycko (NIDDK, NIH)
in our ssNMR studies. This work was supported by the Intramural Program
of the National Institute of Diabetes Digestive and Kidney Diseases of
the National Institutes of Health.
NR 119
TC 38
Z9 40
U1 1
U2 8
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1567-1356
J9 FEMS YEAST RES
JI FEMS Yeast Res.
PD DEC
PY 2010
VL 10
IS 8
BP 980
EP 991
DI 10.1111/j.1567-1364.2010.00666.x
PG 12
WC Biotechnology & Applied Microbiology; Microbiology; Mycology
SC Biotechnology & Applied Microbiology; Microbiology; Mycology
GA 674GR
UT WOS:000283725500004
PM 20726897
ER
PT J
AU Ardiani, A
Higgins, JP
Hodge, JW
AF Ardiani, Andressa
Higgins, Jack P.
Hodge, James W.
TI Vaccines based on whole recombinant Saccharomyces cerevisiae cells
SO FEMS YEAST RESEARCH
LA English
DT Review
DE therapeutic vaccine; yeast vaccine; immunotherapy; carcinoembryonic
antigen; Saccharomyces cerevisiae; antitumor activity
ID YEAST-BASED IMMUNOTHERAPY; T-LYMPHOCYTE RESPONSES; C VIRUS-INFECTION;
CARCINOEMBRYONIC ANTIGEN; PROSTATE-CANCER; DENDRITIC CELLS;
DOUBLE-BLIND; CHEMOTHERAPY; RADIATION; THERAPY
AB The ultimate goal of therapeutic vaccines is to activate and exploit the patient's own immune system to vigorously and dynamically seek and eradicate established malignant or virally infected cells. Therapeutic vaccines also offer the potential for preventing disease recurrence. Saccharomyces cerevisiae-based vaccines, where the yeast is engineered to express viral or tumor antigens, represent an ideal therapeutic approach due to their ability to stimulate tumor- or viral-specific CD4+ and CD8+ T-cell responses that are capable of reducing disease burden. This review describes preclinical and clinical studies supporting the development of S. cerevisiae-based therapeutic vaccines for the treatment of cancer and viral diseases, as well as multimodal strategies in which therapeutic vaccines are combined with cytotoxic drugs to achieve a greater clinical response.
C1 [Ardiani, Andressa; Higgins, Jack P.; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hodge, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B13,MSC 1750, Bethesda, MD 20892 USA.
EM jh241@nih.gov
RI Hodge, James/D-5518-2015
OI Hodge, James/0000-0001-5282-3154
NR 50
TC 29
Z9 29
U1 0
U2 8
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1567-1356
J9 FEMS YEAST RES
JI FEMS Yeast Res.
PD DEC
PY 2010
VL 10
IS 8
BP 1060
EP 1069
DI 10.1111/j.1567-1364.2010.00665.x
PG 10
WC Biotechnology & Applied Microbiology; Microbiology; Mycology
SC Biotechnology & Applied Microbiology; Microbiology; Mycology
GA 674GR
UT WOS:000283725500010
PM 20707820
ER
PT J
AU Beall, S
Brenner, C
Segars, J
AF Beall, Stephanie
Brenner, Carol
Segars, James
TI Oocyte maturation failure: a syndrome of bad eggs
SO FERTILITY AND STERILITY
LA English
DT Article
DE Oocyte maturation; oocyte arrest; meiotic arrest; sterility
ID METAPHASE-I ARREST; PROTEIN-KINASE-II; CYCLIN B1 DEGRADATION; MOUSE
OOCYTES; MEIOTIC MATURATION; PROMOTING FACTOR; XENOPUS OOCYTES;
CELL-CYCLE; MEIOSIS-I; PARTHENOGENETIC ACTIVATION
AB To show that disruption of meiotic competence results in cell cycle arrest, and the production of immature oocytes that are not capable of fertilization. Through an extensive review of animal studies and clinical case reports, we define the syndrome of oocyte maturation failure as a distinct oocyte disorder, present a classification system based on clinical parameters, and discuss the potential molecular origins for the disease. (Fertil Steril (R) 2010;94:2507-13. (C) 2010 by American Society for Reproductive Medicine.)
C1 [Brenner, Carol; Segars, James] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Beall, Stephanie] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Nashville, TN 37232 USA.
RP Segars, J (reprint author), NICHD, Program Reprod & Adult Endocrinol, NIH, Bldg 10,CRC 1E-3140,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM segarsj@mail.nih.gov
FU Intramural NIH HHS [Z01 HD008737-07, Z01 HD008737-08]; NCRR NIH HHS [R21
RR021881-03, R21 RR021881-02, R21 RR021881-01, R21 RR021881-04]; NICHD
NIH HHS [R03 HD046553-02, R03 HD046553-01A1, R03 HD046553-02S1, R03
HD046553-03]
NR 81
TC 16
Z9 18
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD DEC
PY 2010
VL 94
IS 7
BP 2507
EP 2513
DI 10.1016/j.fertnstert.2010.02.037
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 684TV
UT WOS:000284573700007
PM 20378111
ER
PT J
AU McCarthy-Keith, DM
Schisterman, EF
Robinson, RD
O'Leary, K
Lucidi, RS
Armstrong, AY
AF McCarthy-Keith, Desiree M.
Schisterman, Enrique F.
Robinson, Randal D.
O'Leary, Kathleen
Lucidi, Richard S.
Armstrong, Alicia Y.
TI Will decreasing assisted reproduction technology costs improve
utilization and outcomes among minority women?
SO FERTILITY AND STERILITY
LA English
DT Article
DE ART utilization; ethnic disparity; infertility
ID IN-VITRO FERTILIZATION; INSURANCE MANDATES; RACIAL DISPARITIES;
AFRICAN-AMERICAN; WHITE WOMEN; BLACK-WOMEN; INFERTILITY; CARE; SERVICES;
COVERAGE
AB Objective: To evaluate assisted reproduction technology (ART) usage and outcomes in minority women seeking care at enhanced access, military ART programs.
Design: Retrospective cohort.
Setting: Federal ART programs.
Patient(s): Two thousand fifty women undergoing first cycle, fresh, nondonor ART from 2000 to 2005.
Intervention(s): None.
Main Outcome Measure(s): Rate of ART use, clinical pregnancy rate, live birth rate.
Result(s): African American women had an almost fourfold increased use of ART and Hispanic women had decreased use. Clinical pregnancy rates were significantly lower for African American women compared with white women (46.1% vs. 52.6%, relative risk [RR] 0.88; 95% confidence interval [CI], 0.78-0.99) as were live birth rates (33.7%. vs. 45.7%, RR 0.74; 95% CI, 0.63-0.91).
Conclusion(s): Economics appear to influence ART use by African American women but not Hispanic women. Despite increased use by African American women, outcomes in this group were worse when compared with Caucasian women. Improving access through decreased cost may increase use by some but not all minority groups. Improved access may not translate into improved outcomes in some ethnic groups. (Fertil Steril (R) 2010; 94: 2587-9. (C) 2010 by American Society for Reproductive Medicine.)
C1 [McCarthy-Keith, Desiree M.; Armstrong, Alicia Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[McCarthy-Keith, Desiree M.; Armstrong, Alicia Y.] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Schisterman, Enrique F.; O'Leary, Kathleen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Robinson, Randal D.] Brooke Army Med Ctr, San Antonio Uniformed Serv Hlth Educ Consortium, Wilford Hall Med Ctr, San Antonio, TX USA.
[Lucidi, Richard S.] Tripler Army Med Ctr, Honolulu, HI 96859 USA.
RP Armstrong, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bldg 10,CRC Room 1E-1-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA.
EM armstroa@mail.nih.gov
OI Schisterman, Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX Supported in part by the Program in Reproductive and Adult
Endocrinology, Eunice Kennedy Shriver National Institute of Child Health
and Human Development.
NR 20
TC 17
Z9 17
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD DEC
PY 2010
VL 94
IS 7
BP 2587
EP 2589
DI 10.1016/j.fertnstert.2010.02.021
PG 3
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 684TV
UT WOS:000284573700021
PM 20356585
ER
PT J
AU Banks, NK
Norian, JM
Bundorf, MK
Henne, MB
AF Banks, Nicole K.
Norian, John M.
Bundorf, M. Kate
Henne, Melinda B.
TI Insurance mandates, embryo transfer, outcomes-the link is tenuous
SO FERTILITY AND STERILITY
LA English
DT Editorial Material
DE Health insurance mandates; embryo transfer; multiple births; IVF
outcomes
ID ASSISTED-REPRODUCTIVE-TECHNOLOGY; IN-VITRO FERTILIZATION; MULTIPLE
BIRTHS; COVERAGE; NUMBER; IMPACT
AB To examine the relationship between state insurance mandate status and the number of embryos transferred in assisted reproductive technology cycles, we conducted a retrospective analysis of clinics reporting to the publicly available national Society for Assisted Reproductive Technology registry. We found that clinics in states with comprehensive mandates transferred between 0.210 and 0.288 fewer embryos per cycle depending upon patient age, and were more likely to transfer fewer embryos than recommended for older women; however, the relationship between state mandate status and clinic birth and multiple birth rates varied by age group. (Fertil Steril (R) 2010; 94:2776-9. (C) 2010 by American Society for Reproductive Medicine.)
C1 [Henne, Melinda B.] Walter Reed Army Med Ctr, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Washington, DC 20307 USA.
[Bundorf, M. Kate] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Norian, John M.; Henne, Melinda B.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
[Norian, John M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, NIH, Bethesda, MD USA.
[Banks, Nicole K.] Georgetown Univ Hosp, Washington, DC 20007 USA.
RP Henne, MB (reprint author), Walter Reed Army Med Ctr, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, 6900 Georgia Ave NW,Bldg 1,Room A226, Washington, DC 20307 USA.
EM Melinda.Henne@amedd.army.mil
NR 21
TC 6
Z9 6
U1 0
U2 3
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 2010
VL 94
IS 7
BP 2776
EP 2779
DI 10.1016/j.fertnstert.2010.05.037
PG 4
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 684TV
UT WOS:000284573700067
PM 20579988
ER
PT J
AU Tong, ZB
Sullivan, SD
Lawless, LM
Vanderhoof, V
Zachman, K
Nelson, LM
AF Tong, Zhi-Bin
Sullivan, Shannon D.
Lawless, Lindsey M.
Vanderhoof, Vien
Zachman, Keith
Nelson, Lawrence M.
TI Five mutations of mitochondrial DNA polymerase-gamma (POLG) are not a
prevalent etiology for spontaneous 46,XX primary ovarian insufficiency
SO FERTILITY AND STERILITY
LA English
DT Editorial Material
DE Primary ovarian insufficiency; premature ovarian failure; DNA
polymerase-gamma; mitochondrial DNA
ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; AUTOSOMAL-DOMINANT;
MALE-INFERTILITY; FAILURE; DISEASE; CYCLE; MTDNA; GENE
AB The study objective was to determine if mutations in mitochondrial DNA polymerase gamma (POLG) are associated with spontaneous 46,XX primary ovarian insufficiency (sPOI) using restriction fragment length polymorphism analysis of genomic DNA. Of 201 women with 46,XX sPOI analyzed, we found only one case (0.5%, 95% confidence interval 0-3%) of heterozygosity for a POLG mutation, suggesting that this is not a common genetic etiology for this form of infertility. (Fertil Steril (R) 2010;94:2932-4. (c) 2010 by American Society for Reproductive Medicine.)
C1 [Tong, Zhi-Bin; Sullivan, Shannon D.; Lawless, Lindsey M.; Vanderhoof, Vien; Zachman, Keith; Nelson, Lawrence M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Integrat Reprod Med Grp, Intramural Res Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Sullivan, SD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Integrat Reprod Med Grp, Intramural Res Program Reprod & Adult Endocrinol, NIH, CRC 1-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA.
EM sullivsh@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999, ZIA HD000633-19]
NR 19
TC 9
Z9 10
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD DEC
PY 2010
VL 94
IS 7
BP 2932
EP 2934
DI 10.1016/j.fertnstert.2010.06.049
PG 3
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 684TV
UT WOS:000284573700112
PM 20701905
ER
PT J
AU Hulin-Curtis, SL
Petit, D
Figg, WD
Hsing, AW
Reichardt, JKV
AF Hulin-Curtis, Sarah L.
Petit, Dominique
Figg, W. Douglas
Hsing, Ann W.
Reichardt, Juergen K. V.
TI Finasteride metabolism and pharmacogenetics: new approaches to
personalized prevention of prostate cancer
SO FUTURE ONCOLOGY
LA English
DT Review
DE androgen; CYP3A4; finasteride; haplotype; personalized medicine;
pharmacogenetics; prostate cancer; single nucleotide polymorphism;
SRD5A2; UGT1A
ID LIPID-LOWERING THERAPY; UDP-GLUCURONOSYLTRANSFERASES; CLINICAL
PRESENTATION; FUTURE-DIRECTIONS; AFRICAN-AMERICAN; GENETIC VARIANT;
5-ALPHA-REDUCTASE INHIBITORS; INTRAEPITHELIAL NEOPLASIA; LINKAGE
DISEQUILIBRIUM; BIOCHEMICAL GENETICS
AB Incidences of prostate cancer in most countries are increasing owing to better detection methods; however, prevention with the use of finasteride, a very effective steroid 5 alpha-reductase type II inhibitor, has been met with mixed success. A wide interindividual variation in response exists and is thought to be due to heritable factors. This article summarizes the literature that attempts to elucidate the molecular mechanisms of finasteride in terms of its metabolism, excretion and interaction with endogenous steroid molecules. We describe previously reported genetic variations of steroid-metabolizing genes and their potential association with finasteride efficacy. Based on the literature, we outline directions of research that may contribute to understanding the interindividual variation in finasteride prevention and to the future development of personalized medicine.
C1 [Hulin-Curtis, Sarah L.; Petit, Dominique; Reichardt, Juergen K. V.] Univ Sydney, Bosch Inst, Camperdown, NSW, Australia.
[Figg, W. Douglas] NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
[Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Reichardt, JKV (reprint author), James Cook Univ, Sch Pharm & Mol Sci, Townsville, Qld, Australia.
EM juergen.reichardt@jcu.edu.au
OI Reichardt, Juergen/0000-0001-6458-2773
FU National Cancer Institute (NCI) [PO1 CA108964, 1]; NIH, NCI, Division of
Cancer Epidemiology and Genetics, USA
FX This work was supported in part by National Cancer Institute (NCI) grant
PO1 CA108964 (project 1) to Juergen KV Reichardt who is also a Medical
Foundation Fellow at the University of Sydney. This work was also
supported by the Intramural Research Program of the NIH, NCI, Division
of Cancer Epidemiology and Genetics, USA. The authors have no other
relevant affiliations or financial involvement with any organization or
entity with a financial interest in or financial conflict with the
subject matter or materials discussed in the manuscript apart from those
disclosed. No writing assistance was utilized in the production of this
manuscript.
NR 131
TC 5
Z9 5
U1 0
U2 3
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1479-6694
J9 FUTURE ONCOL
JI Future Oncol.
PD DEC
PY 2010
VL 6
IS 12
BP 1897
EP 1913
DI 10.2217/FON.10.149
PG 17
WC Oncology
SC Oncology
GA 849BP
UT WOS:000297100400014
PM 21142863
ER
PT J
AU Brant, LJ
Ferrucci, L
Sheng, SL
Concin, H
Zonderman, AB
Kelleher, CC
Longo, DL
Ulmer, H
Strasak, AM
AF Brant, Larry J.
Ferrucci, Luigi
Sheng, Shan L.
Concin, Hans
Zonderman, Alan B.
Kelleher, Cecily C.
Longo, Dan L.
Ulmer, Hanno
Strasak, Alexander M.
TI Gender Differences in the Accuracy of Time-Dependent Blood Pressure
Indices for Predicting Coronary Heart Disease: A Random-Effects Modeling
Approach
SO GENDER MEDICINE
LA English
DT Article
DE blood pressure indices; coronary heart disease; epidemiology; gender;
prospective study; random effects models
ID CARDIOVASCULAR RISK-FACTORS; INCREASED PULSE PRESSURE; MIDDLE-AGED MEN;
MYOCARDIAL-INFARCTION; WAVE VELOCITY; WOMEN; HYPERTENSION; FAILURE;
DECLINE; ADULTS
AB Background: Previous studies on blood pressure (BP) indices as a predictor of coronary heart disease (CHD) have provided equivocal results and generally relied on Cox proportional hazards regression methodology, with age and sex accounting for most of the predictive capability of the model.
Objective: The aim of the present study was to use serially collected BP measurements to examine age- and gender-related differences in BP indices for predicting CHD.
Methods: The predictive accuracy of time-dependent BP indices for CHD was investigated using a method of risk prediction based on posterior probabilities calculated from mixed-effects regression to utilize intraindividual differences in serial BP measurements according to age changes within gender groups. Data were collected prospectively from 2 community-dwelling cohort studies in the United States (Baltimore Longitudinal Study of Aging [BLSA]) and Europe (Vorarlberg Health Monitoring and Promotion Program [VHM&PP]).
Results: The study comprised 152,633 participants (aged 30-74 years) and 610,061 BP measurements. During mean follow-up of 7.5 years, 2457 nonfatal and fatal CHD events were observed. In both study populations, pulse pressure (PP) and systolic blood pressure (SBP) performed best as individual predictors of CHD in women (area under the receiver operating characteristic curve [AUC(ROC)] was between 0.83 and 0.85 for PP, and between 0.77 and 0.81 for SBP). Mean arterial pressure (MAP) and diastolic blood pressure (DBP) performed better for men (AUC(ROC) = 0.67 and 0.65 for MAP and DBP, respectively, in the BLSA; AUC(ROC) = 0.77 and 0.75 in the VHM&PP) than for women (AUC(ROC) = 0.60 for both MAP and DBP in the BLSA; AUC(ROC) = 0.75 and 0.52, respectively, in the VHM&PP). The degree of discrimination in both populations was overall greater but more varied for all BP indices for women (AUC(ROC) estimates between 0.85 [PP in the VHM&PP] and 0.52 [DBP in the VHM&PP]) than for men (AUC(ROC) estimates between 0.78 [MAP + PP in the VHM&PP] and 0.63 [PP in the BLSA]).
Conclusion: Our findings indicate differences in discrimination between women and men in the accuracy of longitudinally collected BP measurements for predicting CHD, implicating the usefulness of gender-specific BP indices to assess individual CHD risk. (Gend Med. 2010;7:616-627) (C) 2010 Elsevier HS Journals, Inc.
C1 [Ulmer, Hanno; Strasak, Alexander M.] Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, A-6020 Innsbruck, Austria.
[Brant, Larry J.; Sheng, Shan L.; Zonderman, Alan B.] NIA, Res Resources Branch, Baltimore, MD 21224 USA.
[Ferrucci, Luigi; Longo, Dan L.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Concin, Hans] Agcy Prevent & Social Med, Bregenz, Austria.
[Kelleher, Cecily C.] Univ Coll Dublin, Sch Publ Hlth Physiotherapy & Populat Sci, Dublin 2, Ireland.
RP Strasak, AM (reprint author), Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Schoepfstr 41, A-6020 Innsbruck, Austria.
EM alexander.strasak@i-med.ac.at
RI vhmpp, aks/F-9756-2012; Ulmer, Hanno/C-3488-2011;
OI Ulmer, Hanno/0000-0001-5911-1002; Zonderman, Alan B/0000-0002-6523-4778
FU National Institute on Aging Intramural Research Program
FX This research has been funded by the National Institute on Aging
Intramural Research Program (L.J. Brant, PI). The authors have indicated
that they have no conflicts of interest regarding the content of the
article. All authors contributed equally to the study.
NR 34
TC 1
Z9 1
U1 0
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 1550-8579
J9 GENDER MED
JI Gend. Med.
PD DEC
PY 2010
VL 7
IS 6
BP 616
EP 627
DI 10.1016/j.genm.2010.11.005
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 711DM
UT WOS:000286567300008
PM 21195361
ER
PT J
AU Zhang, DP
Aravind, L
AF Zhang, Dapeng
Aravind, L.
TI Identification of novel families and classification of the C2 domain
superfamily elucidate the origin and evolution of membrane targeting
activities in eukaryotes
SO GENE
LA English
DT Article
DE C2 domain; Evolution; Remote homology detection; Membranes; Lipid
recognition; Cytoskeleton
ID MULTIPLE SEQUENCE ALIGNMENTS; MECKEL-SYNDROME; ACTIN CYTOSKELETON;
CRYSTAL-STRUCTURE; PHOSPHOINOSITIDE 3-KINASES; COMPARATIVE GENOMICS;
STRUCTURE PREDICTION; SECONDARY STRUCTURE; DISTANT HOMOLOGY;
BINDING-PROTEIN
AB Eukaryotes contain an elaborate membrane system, which bounds the cell itself, nuclei, organelles and transient intracellular structures, such as vesicles. The emergence of this system was marked by an expansion of a number of structurally distinct classes of lipid-binding domains that could throw light on the early evolution of eukaryotic membranes. The C2 domain is a useful model to understand these events because it is one of the most prevalent eukaryotic lipid-binding domains deployed in diverse functional contexts. Most studies have concentrated on C2 domains prototyped by those in protein kinase C (PKC-C2) isoforms that bind lipid in a calcium-dependent manner. While two other distinct families of C2 domains, namely those in PI3K-C2 and FTEN-C2 are also recognized, a complete picture of evolutionary relationships within the C2 domain superfamily is lacking. We systematically studied this superfamily using sequence profile searches, phylogenetic and phyletic-pattern analysis and structure-prediction. Consequently, we identified several distinct families of C2 domains including those respectively typified by 12 domains in the Aida (axin interactor, dorsalization associated) proteins, B9 proteins (e.g. Mks1 (Xbx-7), Stumpy (Tza-1) and Tza-2) involved in centrosome migration and ciliogenesis, Dock180/Zizimin proteins which are Rac/CDC42 GDP exchange factors, the EEIG1/Sym-3. EHBP1 and plant RPG/PMI1 proteins involved in endocytotic recycling and organellar positioning and an apicomplexan family. We present evidence that the last eukaryotic common ancestor (LECA) contained at least 10 C2 domains belonging to 6 well-defined families. Further, we suggest that this pre-LECA diversification was linked to the emergence of several quintessentially eukaryotic structures, such as membrane repair and vesicular trafficking system, anchoring of the actin and tubulin cytoskeleton to the plasma and vesicular membranes, localization of small GTPases to membranes and lipid-based signal transduction. Subsequent lineage-specific expansions of Zizimin-type C2 domains and functionally linked CDC42/Rac GTPases occurred independently in eukaryotes that evolved active amoeboid motility. While two lipid-binding regions are likely to be shared by majority of C2 domains, the actual constellation of lipid-binding residues (predominantly basic) are distinct in each family potentially reflective of the functional and biochemical diversity of these domains. Importantly, we show that the calcium-dependent membrane interaction is a derived feature limited to the PKC-C2 domains. Our identification of novel C2 domains offers new insights into interaction between both the microtubular and microfilament cytoskeleton and cellular membranes. Published by Elsevier B.V.
C1 [Zhang, Dapeng; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM aravind@ncbi.nlm.nih.gov
FU NIH; National Library of Medicine at the National Institutes of Health,
USA
FX The first author would like to thank S. Abhiman for his help in data
analysis and M. DiPetta for her assistance in analyzing initial sequence
alignment of the NT-C2 domains. We also thank L.M. Iyer for suggestions
on the manuscript. This work is supported by the NIH Postdoctoral
Visiting Fellowship and the intramural funds of the National Library of
Medicine at the National Institutes of Health, USA.
NR 94
TC 47
Z9 49
U1 4
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1119
J9 GENE
JI Gene
PD DEC 1
PY 2010
VL 469
IS 1-2
BP 18
EP 30
DI 10.1016/j.gene.2010.08.006
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 683FA
UT WOS:000284455900003
PM 20713135
ER
PT J
AU Kopplin, LJ
Igo, RP
Wang, Y
Sivakumaran, TA
Hagstrom, SA
Peachey, NS
Francis, PJ
Klein, ML
SanGiovanni, JP
Chew, EY
Pauer, GJT
Sturgill, GM
Joshi, T
Tian, L
Xi, Q
Henning, AK
Lee, KE
Klein, R
Klein, BEK
Iyengar, SK
AF Kopplin, L. J.
Igo, R. P., Jr.
Wang, Y.
Sivakumaran, T. A.
Hagstrom, S. A.
Peachey, N. S.
Francis, P. J.
Klein, M. L.
SanGiovanni, J. P.
Chew, E. Y.
Pauer, G. J. T.
Sturgill, G. M.
Joshi, T.
Tian, L.
Xi, Q.
Henning, A. K.
Lee, K. E.
Klein, R.
Klein, B. E. K.
Iyengar, S. K.
TI Genome-wide association identifies SKIV2L and MYRIP as protective
factors for age-related macular degeneration
SO GENES AND IMMUNITY
LA English
DT Article
DE macular degeneration; association testing; melanosome trafficking
ID COMPLEMENT FACTOR-H; RETINAL-PIGMENT EPITHELIUM; BLUE MOUNTAINS EYE;
BEAVER DAM EYE; MYOSIN-VIIA; FACTOR-B; COMPONENT 2; CHINESE POPULATION;
10-YEAR INCIDENCE; 5-YEAR INCIDENCE
AB Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. We conducted a genome-wide association study in a series of families enriched for AMD and completed a meta-analysis of this new data with results from reanalysis of an existing study of a late-stage case-control cohort. We tested the top findings for replication in 1896 cases and 1866 controls and identified two novel genetic protective factors for AMD. In addition to the complement factor H (CFH) (P = 2.3 x 10(-64)) and age-related maculopathy susceptibility 2 (ARMS2) (P = 1.2 x 10(-60)) loci, we observed a protective effect at rs429608, an intronic SNP in SKIV2L (P=5.3 x 10(-15)), a gene near the complement component 2 (C2)/complement factor B (BF) locus, that indicates the protective effect may be mediated by variants other than the C2/BF variants previously studied. Haplotype analysis at this locus identified three protective haplotypes defined by the rs429608 protective allele. We also identified a new potentially protective effect at rs2679798 in MYRIP (P=2.9 x 10(-4)), a gene involved in retinal pigment epithelium melanosome trafficking. Interestingly, MYRIP was initially identified in the family-based scan and was confirmed in the case-control set. From these efforts, we report the identification of two novel protective factors for AMD and confirm the previously known associations at CFH, ARMS2 and C3. Genes and Immunity (2010) 11, 609-621; doi: 10.1038/gene.2010.39; published online 23 September 2010
C1 [Igo, R. P., Jr.; Wang, Y.; Sivakumaran, T. A.; Joshi, T.; Tian, L.; Xi, Q.; Iyengar, S. K.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Kopplin, L. J.; Iyengar, S. K.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA.
[Hagstrom, S. A.; Peachey, N. S.; Pauer, G. J. T.] Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA.
[Hagstrom, S. A.; Peachey, N. S.] Case Western Reserve Univ, Lerner Coll Med, Cleveland Clin, Dept Ophthalmol, Cleveland, OH 44106 USA.
[Peachey, N. S.; Sturgill, G. M.] Vet Affairs Med Ctr, Res Serv, Cleveland, OH USA.
[Francis, P. J.; Klein, M. L.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
[SanGiovanni, J. P.; Chew, E. Y.] NEI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
[Henning, A. K.] EMMES Corp, Rockville, MD USA.
[Lee, K. E.; Klein, R.; Klein, B. E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA.
RP Iyengar, SK (reprint author), Case Western Reserve Univ, Dept Epidemiol & Biostat, Wolstein Res Bldg,Room 1315,2103 Cornell Rd, Cleveland, OH 44106 USA.
EM ski@case.edu
RI Peachey, Neal/G-5533-2010
FU National Eye Institute [EY015810, U10EY06594, EY015286, EY13438,
EY10605, T32 EY07157, T32 GM07250]; National Institute of General
Medical Sciences [GM28356]; Research to Prevent Blindness; Foundation
Fighting Blindness, Columbia, MD; Macular Degeneration Center; Goodall
Macular Degeneration Fund; Casey Eye Institute; Research to Prevent
Blindness, New York, NY; Department of Ophthalmology, Case Western
Reserve University (CWRU) School of Medicine and Cleveland Clinic Lerner
College of Medicine of CWRU; Gene Expression and Genotyping Facility of
the Comprehensive Cancer Center at CWRU; University Hospitals of
Cleveland [P30CA43703]; Genotyping Core Facility at CWRU; National
Center for Research Resources [RR03655]; National Center for Research
Resources (NCRR), a component of the National Institutes of Health [UL1
RR024989]; NIH roadmap for Medical Research
FX This study was supported by the NIH grants EY015810, U10EY06594,
EY015286, EY13438 and EY10605 from the National Eye Institute, training
grant T32 EY07157 to the Visual Sciences Training Program and T32
GM07250 to the Case Medical Scientist Training Program; US Public Health
Service research grants GM28356, from the National Institute of General
Medical Sciences; and by Senior Scientific Investigator Awards from
Research to Prevent Blindness (Dr R Klein and Dr B Klein), The
Foundation Fighting Blindness, Columbia, MD (Dr PJ Francis); the Macular
Degeneration Center Research Fund and the Goodall Macular Degeneration
Fund, Casey Eye Institute (Dr ML Klein), Research to Prevent Blindness,
New York, NY (unrestricted grants to Casey Eye Institute and a Career
Development Award to Dr PJ Francis) and unrestricted awards from
Research to Prevent Blindness (Department of Ophthalmology, Case Western
Reserve University (CWRU) School of Medicine and Cleveland Clinic Lerner
College of Medicine of CWRU), a VA Merit Review and a Center Grant from
Foundation Fighting Blindness. This study was also supported by the Gene
Expression and Genotyping Facility of the Comprehensive Cancer Center at
CWRU and University Hospitals of Cleveland (P30CA43703) and the
Genotyping Core Facility at CWRU. The results of this paper were
obtained by using the software package S.A.G.E., which is supported by a
US Public Health Service Resource Grant (RR03655) from the National
Center for Research Resources. This publication was made possible by the
CWRU/Cleveland Clinic CTSA Grant Number UL1 RR024989 from the National
Center for Research Resources (NCRR), a component of the National
Institutes of Health and NIH roadmap for Medical Research. Its contents
are solely the responsibility of the authors and do not necessarily
represent the official view of NCRR or NIH.
NR 85
TC 35
Z9 36
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1466-4879
J9 GENES IMMUN
JI Genes Immun.
PD DEC
PY 2010
VL 11
IS 8
BP 609
EP 621
DI 10.1038/gene.2010.39
PG 13
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 688TP
UT WOS:000284877100002
PM 20861866
ER
PT J
AU Tang, H
Siegmund, DO
Johnson, NA
Romieu, I
London, SJ
AF Tang, Hua
Siegmund, David O.
Johnson, Nicholas A.
Romieu, Isabelle
London, Stephanie J.
TI Joint Testing of Genotype and Ancestry Association in Admixed Families
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE TDT; genome-wide association studies; genetic admixture
ID DISEASE-GENE DISCOVERY; DENSITY ADMIXTURE MAP; LINKAGE DISEQUILIBRIUM;
ETHNIC-DIFFERENCES; MAPPING GENES; POPULATIONS; UYGHURS; RISK
AB Current genome-wide association studies (GWAS) often involve populations that have experienced recent genetic admixture. Genotype data generated from these studies can be used to test for association directly, as in a non-admixed population. As an alternative, these data can be used to infer chromosomal ancestry, and thus allow for admixture mapping. We quantify the contribution of allele-based and ancestry-based association testing under a family-design, and demonstrate that the two tests can provide non-redundant information. We propose a joint testing procedure, which efficiently integrates the two sources information. The efficiencies of the allele, ancestry and combined tests are compared in the context of a GWAS. We discuss the impact of population history and provide guidelines for future design and analysis of GWAS in admixed populations. Genet. Epidemiol. 34:783-791, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Tang, Hua] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
[Siegmund, David O.; Johnson, Nicholas A.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA.
[Romieu, Isabelle] Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico.
[London, Stephanie J.] NIEHS, Dept Hlth & Human Serv, Epidemiol Branch, NIH, Res Triangle Pk, NC USA.
RP Tang, H (reprint author), Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
EM huatang@stanford.edu
OI London, Stephanie/0000-0003-4911-5290
FU NIGMS [GM073059, HG000848]; Stanford Genome Training Program; Ric
Weiland Fellowship; National Institutes of Health, National Center for
Environmental Health at the Centers for Disease Control; National
Institute of Environmental Health Sciences [ZIA ES049019, ZIA ES025045];
National Council of Science and Technology [26206-M]
FX Contract grant sponsor: NIGMS; Contract grant numbers: GM073059;
HG000848; Contract grant sponsors: Stanford Genome Training Program and
the Ric Weiland Fellowship, National Institutes of Health, National
Center for Environmental Health at the Centers for Disease Control;
National Institute of Environmental Health Sciences; Contract grant
numbers: ZIA ES049019; ZIA ES025045; Contract grant sponsor: National
Council of Science and Technology; Contract grant number: 26206-M.
NR 29
TC 18
Z9 18
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
BP 783
EP 791
DI 10.1002/gepi.20520
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100002
PM 21031451
ER
PT J
AU Lobach, I
Fan, RZ
Carroll, RJ
AF Lobach, Iryna
Fan, Ruzong
Carroll, Raymond J.
TI Genotype-Based Association Mapping of Complex Diseases: Gene-Environment
Interactions with Multiple Genetic Markers and Measurement Error in
Environmental Exposures
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE gene-environment interactions; EM-algorithm; errors in variables;
linkage disequilibrium; pseudo-likelihood; semi-parametric methods
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; QUANTITATIVE TRAIT LOCI; HAPLOTYPE
RECONSTRUCTION; HUMAN GENOME; INFERENCE; MAP; INDEPENDENCE; CANCER; RISK
AB With the advent of dense single nucleotide polymorphism genotyping, population-based association studies have become the major tools for identifying human disease genes and for fine gene mapping of complex traits. We develop a genotype-based approach for association analysis of case-control studies of gene-environment interactions in the case when environmental factors are measured with error and genotype data are available on multiple genetic markers. To directly use the observed genotype data, we propose two genotype-based models: genotype effect and additive effect models. Our approach offers several advantages. First, the proposed risk functions can directly incorporate the observed genotype data while modeling the linkage disequilibrium information in the regression coefficients, thus eliminating the need to infer haplotype phase. Compared with the haplotype-based approach, an estimating procedure based on the proposed methods can be much simpler and significantly faster. In addition, there is no potential risk due to haplotype phase estimation. Further, by fitting the proposed models, it is possible to analyze the risk alleles/ variants of complex diseases, including their dominant or additive effects. To model measurement error, we adopt the pseudo-likelihood method by Lobach et al. [2008]. Performance of the proposed method is examined using simulation experiments. An application of our method is illustrated using a population-based case-control study of association between calcium intake with the risk of colorectal adenoma development. Genet. Epidemiol. 34:792-802, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Fan, Ruzong; Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA.
[Lobach, Iryna] NYU, Sch Med, Div Biostat, New York, NY USA.
[Fan, Ruzong] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Fan, Ruzong] NCI, Div Canc Control & Populat Sci, Surveillance Res Program, Rockville, MD USA.
RP Fan, RZ (reprint author), Texas A&M Univ, Dept Stat, 447 Blocker, College Stn, TX 77843 USA.
EM rfan@stat.tamu.edu
FU National Cancer Institute [R01-CA133996, R37-CA057030]; National
Institutes of Health; National Cancer Institute, MD Anderson Cancer
Center [R01-CA133996]
FX Contract grant sponsor: National Cancer Institute; Contract grant
numbers: R01-CA133996; R37-CA057030; Contract grant sponsor: National
Institutes of Health.; The research of Fan was supported by the National
Cancer Institute grant R01-CA133996 from MD Anderson Cancer Center (P.
I. C. Amos), where Fan spent his sabbatical during the 2008-2009
academic year; and a Research and Travel Support from the
Intergovernmental Personnel Act (IPA), National Institutes of Health, in
2010. The research of Carroll was supported by a grant from the National
Cancer Institute (R37-CA057030).
NR 22
TC 7
Z9 7
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
BP 792
EP 802
DI 10.1002/gepi.20523
PG 11
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100003
PM 21031455
ER
PT J
AU Merikangas, KR
Liang, KY
Elston, RC
AF Merikangas, Kathleen Ries
Liang, Kung-Yee
Elston, Robert C.
TI Contribution of Family Studies in the Era of Genome Wide Association and
Sequencing Studies
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Merikangas, Kathleen Ries] NIMH, Bethesda, MD USA.
[Liang, Kung-Yee] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Elston, Robert C.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
RI Liang, Kung-Yee/F-8299-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 169
BP 963
EP 964
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100178
ER
PT J
AU Sorant, AJM
Cai, JL
Sung, H
Kim, Y
Wilson, AF
AF Sorant, Alexa J. M.
Cai, Juanliang
Sung, Heejong
Kim, Yoonhee
Wilson, Alexander F.
TI TiledReg: Software Implementation of Tiled Regression
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society
CY OCT 10-12, 2010
CL Boston, MA
SP Int Genet Epidemiol Soc
C1 [Sorant, Alexa J. M.; Cai, Juanliang; Sung, Heejong; Kim, Yoonhee; Wilson, Alexander F.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Bethesda, MD USA.
NR 0
TC 2
Z9 2
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2010
VL 34
IS 8
MA 244
BP 984
EP 985
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 686TR
UT WOS:000284719100248
ER
PT J
AU Stein, KK
Nesmith, JE
Ross, BD
Golden, A
AF Stein, Kathryn K.
Nesmith, Jessica E.
Ross, Benjamin D.
Golden, Andy
TI Functional Redundancy of Paralogs of an Anaphase Promoting
Complex/Cyclosome Subunit in Caenorhabditis elegans Meiosis
SO GENETICS
LA English
DT Article
ID SPINDLE-ASSEMBLY CHECKPOINT; DEVELOPMENTAL DEFECTS; COMPLEX; MUTANTS;
IDENTIFICATION; COMPONENTS; METAPHASE; MITOSIS; YEAST
AB The anaphase promoting complex/cyclosome (APC/C) mediates the metaphase-to-anaphase transition by instructing the ubiquitination and turnover of key proteins at this stage of the cell cycle. We have recovered a gain-of-function allele in an APC5 subunit of the anaphase promoting complex/cyclosome. This finding led us to investigate further the role of APC5 in Caenorhabditis elegans, which contains two APC5 paralogs. We have shown that these two paralogs, such-1 and gfi-3, are coexpressed in the germline but have nonoverlapping expression patterns in other tissues. Depletion of such-1 or gfi-3 alone does not have a notable effect on the meiotic divisions; however, codepletion of these two factors results in meiotic arrest. In sum, the two C. elegans APC5 paralogs have a redundant function during the meiotic divisions.
C1 [Stein, Kathryn K.; Nesmith, Jessica E.; Ross, Benjamin D.; Golden, Andy] NIDDK, LBG, NIH, Bethesda, MD 20892 USA.
RP Golden, A (reprint author), NIDDK, LBG, NIH, 8 Ctr Dr,Bldg 8,Room 323, Bethesda, MD 20892 USA.
EM andyg@mail.nih.gov
FU National Institutes of Health (NIH), National Institute of Diabetes and
Digestive and Kidney Diseases; NIH National Center for Research
Resources
FX We thank Paula Fearon for critical reading of the manuscript and Risa
Kitagawa for the such-1(h1960) allele. We also thank Kevin O'Connell for
the "pedestal of rescue" technique for recovering transgenes from
ballistic transformations as well as his useful suggestions for the
manuscript. This research was supported by the Intramural Research
Program of the National Institutes of Health (NIH), National Institute
of Diabetes and Digestive and Kidney Diseases. Some nematode strains
used in this work were provided by the Caenorhabditis Genetics Center,
which is funded by the NIH National Center for Research Resources.
NR 24
TC 5
Z9 11
U1 0
U2 0
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
J9 GENETICS
JI Genetics
PD DEC
PY 2010
VL 186
IS 4
BP 1285
EP 1293
DI 10.1534/genetics.110.123463
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 694KP
UT WOS:000285297000017
PM 20944012
ER
PT J
AU Savage, SA
Bertuch, AA
AF Savage, Sharon A.
Bertuch, Alison A.
TI The genetics and clinical manifestations of telomere biology disorders
SO GENETICS IN MEDICINE
LA English
DT Review
DE telomere; telomere biology disorder; dyskeratosis congenita; bone marrow
failure; idiopathic pulmonary fibrosis
ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; NONCIRRHOTIC
PORTAL-HYPERTENSION; DOMINANT DYSKERATOSIS-CONGENITA; INTENSITY
CONDITIONING REGIMEN; HOYERAAL-HREIDARSSON-SYNDROME; DNA
METHYLTRANSFERASE GENE; SEVERE APLASTIC-ANEMIA; GASTRIC-CANCER RISK;
REVERSE-TRANSCRIPTASE
AB Telomere biology disorders are a complex set of illnesses defined by the presence of very short telomeres. Individuals with classic dyskeratosis congenita have the most severe phenotype, characterized by the triad of nail dystrophy, abnormal skin pigmentation, and oral leukoplakia. More significantly, these individuals are at very high risk of bone marrow failure, cancer, and pulmonary fibrosis. A mutation in one of six different telomere biology genes can be identified in 50-60% of these individuals. DKC1, TERC, TERT, NOP10, and NHP2 encode components of telomerase or a telomerase-associated factor and TINF2, a telomeric protein. Progressively shorter telomeres are inherited from generation to generation in autosomal dominant dyskeratosis congenita, resulting in disease anticipation. Up to 10% of individuals with apparently acquired aplastic anemia or idiopathic pulmonary fibrosis also have short telomeres and mutations in TERC or TERT. Similar findings have been seen in individuals with liver fibrosis or acute myelogenous leukemia. This report reviews basic aspects of telomere biology and telomere length measurement, and the clinical and genetic features of those disorders that constitute our current understanding of the spectrum of illness caused by defects in telomere biology. We also suggest a grouping schema for the telomere disorders. Genet Med 2010:12(12):753-764.
C1 [Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, NIH, Rockville, MD 20892 USA.
[Bertuch, Alison A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
RP Savage, SA (reprint author), NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, NIH, 6120 Execut Blvd,EPS-7018, Rockville, MD 20892 USA.
EM savagesh@mail.nih.gov
RI Savage, Sharon/B-9747-2015
OI Savage, Sharon/0000-0001-6006-0740
FU National Cancer Institute, National Institutes of Health
FX This work was supported, in part, by the intramural research program of
the National Cancer Institute, National Institutes of Health. The
authors thank the patients and families who have generously contributed
to our understanding of dyskeratosis congenita and telomere biology
disorders. They also thank Drs. Blanche Alter and Neelam Giri, National
Cancer Institute, for helpful discussions.
NR 132
TC 79
Z9 81
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD DEC
PY 2010
VL 12
IS 12
BP 753
EP 764
DI 10.1097/GIM.0b013e3181f415b5
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 692VJ
UT WOS:000285183500001
PM 21189492
ER
PT J
AU Hadley, DW
Ashida, S
Jenkins, JF
Martin, JC
Calzone, KA
Kuhn, NR
McBride, CM
Kirsch, IR
Koehly, LM
AF Hadley, Donald W.
Ashida, Sato
Jenkins, Jean F.
Martin, Jean C.
Calzone, Kathleen A.
Kuhn, Natalia R.
McBride, Colleen M.
Kirsch, Ilan R.
Koehly, Laura M.
TI Generation after generation: Exploring the psychological impact of
providing genetic services through a cascading approach
SO GENETICS IN MEDICINE
LA English
DT Article
DE genetic services; cascade genetic testing; social influence; genetic
test related distress and worry; HNPCC/Lynch syndrome
ID NONPOLYPOSIS COLORECTAL-CANCER; LYNCH-SYNDROME; FAMILIES;
SUSCEPTIBILITY; DISTRESS; RISK; COMMUNICATION; INFORMATION; DISCLOSURE;
MUTATIONS
AB Purpose: The provision of genetic services often occurs in a cascading fashion within families experiencing inherited diseases. This study examines whether previous family experiences with genetic services influences levels of psychological well-being of family members receiving services later. Methods: Two hundred ninety-seven persons from 38 families with Lynch syndrome completed questionnaires before receiving genetic services. Baseline levels of test-related distress, depressive symptoms, and cancer worries were assessed in relationship to the (1) amount of time elapsed since services were provided to the index case and (2) generation of the family member relative to the index case. Results: Family members in the same generation as the index case experienced significant increases in test-related distress (P = 0.003) and cancer worry (P = 0.001) with increasing time between receipt of genetic test results by the index case and provision of services to family members. Change in the number of depressive symptoms was not significant (P = 0.17). Conclusion: The provision of genetic services through a cascading approach significantly increases distress and worry among family members within the same generation as the index case who receive services at increasingly distant time intervals. Additional research is needed to explore social influences after the introduction of genetic services. Genet Med 2010:12(12):808-815.
C1 [Hadley, Donald W.] NHGRI, Social & Behav Res Branch, NIH, DHHS, Bethesda, MD 20892 USA.
[Jenkins, Jean F.] NHGRI, Off Director, Bethesda, MD 20892 USA.
[Calzone, Kathleen A.; Kirsch, Ilan R.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hadley, DW (reprint author), NHGRI, Social & Behav Res Branch, NIH, DHHS, 31 CENTER DR MSC 2073,Bldg 31,Room B1B37F, Bethesda, MD 20892 USA.
EM dhadley@mail.nih.gov
FU Intramural Research Programs of the National Human Genome Research
Institute [Z01HG000059-11]; National Cancer Institute at the National
Institutes of Health in Bethesda, Maryland
FX This research was supported by the Intramural Research Programs of the
National Human Genome Research Institute (Z01HG000059-11; PI: Koehly)
and the National Cancer Institute at the National Institutes of Health
in Bethesda, Maryland.
NR 33
TC 7
Z9 7
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD DEC
PY 2010
VL 12
IS 12
BP 808
EP 815
DI 10.1097/GIM.0b013e3181f69dbb
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 692VJ
UT WOS:000285183500007
PM 20921894
ER
PT J
AU Blank, SV
Christos, P
Curtin, JP
Goldman, N
Runowicz, CD
Sparano, JA
Liebes, L
Chen, HX
Muggia, FM
AF Blank, Stephanie V.
Christos, Paul
Curtin, John P.
Goldman, Noah
Runowicz, Carolyn D.
Sparano, Joseph A.
Liebes, Leonard
Chen, Helen X.
Muggia, Franco M.
TI Erlotinib added to carboplatin and paclitaxel as first-line treatment of
ovarian cancer: A phase II study based on surgical reassessment
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Ovarian cancer; Erlotinib; Carboplatin; Paclitaxel; Reassessment surgery
ID CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER;
GYNECOLOGIC-ONCOLOGY-GROUP; TYROSINE KINASE INHIBITOR; IMPROVED
SURVIVAL; STAGE-III; CARCINOMA; CISPLATIN; TRIAL; EXPRESSION
AB Background. The purpose of this study was to determine whether adding the anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to carboplatin/paclitaxel improved pathologic complete response (pCR) at reassessment surgery in epithelial ovarian, fallopian tube, or primary peritoneal cancers (OFPC).
Methods. Patients with stage III-IV OFPC initiated treatment within 12 weeks of initial cytoreductive surgery or, after histologic confirmation of diagnosis, neoadjuvantly. Treatment included paclitaxel (175 mg/m(2)) and carboplatin (AUC 6) every 3 weeks for up to 6 cycles, plus oral erlotinib 150 mg daily. The primary objective was to determine whether the pCR rate at reassessment surgery was at least 60% after optimal cytoreduction at initial surgery (< 1 cm residual disease), or at least 40% after suboptimal cytoreduction (at least 1 cm residual disease) using a two-stage design (alpha = 0.10, beta = 0.10).
Results. The study population included 56 patients with stage III-IV OFPC. EGFR gene amplification was present in 15% of the 20 tumors evaluated. Twenty-eight patients had protocol therapy after optimal cytoreduction (stratum l), 23 had protocol therapy either after suboptimal cytoreduction (stratum II), and 5 received neoadjuvant therapy prior to cytoreduction (stratum III Pathologic CR was confirmed in 8 patients (29%; 95% confidence intervals 13%, 49%) in stratum 1 and 3 patients (11%, 95% C.I. 2%, 28%) in stratum II, which did not meet the prespecified efficacy endpoint in either stratum.
Conclusions. Among unselected patients, erlotinib plus carboplatin-paclitaxel did not improve pCR rates compared with historical experience with carboplatin-paclitaxel alone in patients with stage III-IV OFPC. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Sparano, Joseph A.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Oncol, Bronx, NY 10467 USA.
[Blank, Stephanie V.; Curtin, John P.; Goldman, Noah] NYU, Dept Obstet & Gynecol, Div Gynecol Oncol, Sch Med, New York, NY 10016 USA.
[Christos, Paul] Cornell Univ, Div Biostat & Epidemiol, Dept Publ Hlth, Weill Med Coll, New York, NY 10021 USA.
[Runowicz, Carolyn D.] Univ Connecticut, Ctr Hlth, Div Gynecol Oncol, Neag Comprehens Canc Ctr, Farmington, CT USA.
[Liebes, Leonard; Muggia, Franco M.] NYU, Dept Med, Div Med Oncol, Sch Med, New York, NY 10016 USA.
[Chen, Helen X.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Sparano, JA (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Oncol, Bronx, NY 10467 USA.
EM jsparano@montefiore.org
OI Curtin, John/0000-0002-9370-5119; Muggia, Franco/0000-0003-0703-9146
FU NIH [M01-RR-00096, N01-CM-62204]; SAIC-Frederick, Inc. [23XS010A]; Lynne
Cohen Foundation
FX Supported by NIH M01-RR-00096, N01-CM-62204; SAIC-Frederick, Inc.
Contract 23XS010A; and the Lynne Cohen Foundation for Ovarian Cancer
Research.
NR 30
TC 26
Z9 27
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD DEC
PY 2010
VL 119
IS 3
BP 451
EP 456
DI 10.1016/j.ygyno.2010.08.008
PG 6
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 684NO
UT WOS:000284556800010
PM 20837357
ER
PT J
AU Lose, F
Nagle, CM
O'Mara, T
Batra, J
Bolton, KL
Song, HL
Ramus, SJ
Gentry-Maharaj, A
Menon, U
Gayther, SA
Pharoah, PDP
Kedda, MA
Spurdle, AB
AF Lose, Felicity
Nagle, Christina M.
O'Mara, Tracy
Batra, Jyotsna
Bolton, Kelly L.
Song, Honglin
Ramus, Susan J.
Gentry-Maharaj, Aleksandra
Menon, Usha
Gayther, Simon A.
Pharoah, Paul D. P.
Kedda, Mary-Anne
Spurdle, Amanda B.
TI Vascular endothelial growth factor gene polymorphisms and ovarian cancer
survival
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Vascular Endothelial Growth Factor; Ovarian cancer; Survival;
Polymorphisms
ID POPULATION GENOTYPE DATA; GENOME-WIDE ASSOCIATION; BREAST-CANCER;
PROSTATE-CANCER; VEGF; PROGNOSIS; STAGE; ANGIOGENESIS; RISK;
SUSCEPTIBILITY
AB Objectives. We sought to evaluate the effect of polymorphisms in the VEGF (Vascular Endothelial Growth Factor) gene on overall survival in ovarian cancer patients.
Methods. A sample of 319 women diagnosed with primary invasive epithelial ovarian cancer in Australia between 1985 and 1997, recruited as incident cases, were genotyped for four VEGF single nucleotide polymorphisms (three tagSNPs and one functional SNP) using the Sequenom MassARRAY platform. A SNP found to be associated with ovarian cancer survival in this sample set was then evaluated in two independent datasets in an attempt to replicate the association.
Results. VEGF tagSNPs rs3025033 and rs2146323 were not associated with ovarian cancer survival in the Australian sample. Ovarian cancer patients homozygous for tagSNP rs833068 or the functional SNP rs2010963 displayed significantly shortened overall survival in the Australian sample (HR 2.09, 95% CI 1.16-3.78). an effect most apparent in the first 5 years after diagnosis. This association was not replicated in two independent datasets.
Conclusions. Findings from this study provide no evidence that rs3025033 and rs2146323 VEGF polymorphisms are associated with ovarian cancer survival. Although homozygous carriers of the tagSNP rs833068 experienced significantly worse survival in our Australian dataset, we were unable to replicate this in two independent datasets. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Nagle, Christina M.] PO Royal Brisbane Hosp, Gynaecol Canc Grp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
[O'Mara, Tracy; Batra, Jyotsna; Kedda, Mary-Anne] Queensland Univ Technol, Hormone Dependent Canc Grp, Inst Hlth & Biomed Innovat, Brisbane, Qld 4059, Australia.
[Bolton, Kelly L.; Song, Honglin; Pharoah, Paul D. P.] Univ Cambridge, Strangeways Res Lab, Canc Res UK, Dept Oncol, Cambridge, England.
[Bolton, Kelly L.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A.] UCL, Dept Gynaecol Oncol, Inst Womens Hlth, London, England.
RP Nagle, CM (reprint author), PO Royal Brisbane Hosp, Gynaecol Canc Grp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
EM Christina.Nagle@qimr.edu.au
RI Menon, Usha/C-4716-2008; Batra, Jyotsna/B-4130-2011; O'Mara,
Tracy/M-7508-2016; Spurdle, Amanda/A-4978-2011
OI O'Mara, Tracy/0000-0002-5436-3232; Lose, Felicity/0000-0001-8337-3547;
Ramus, Susan/0000-0003-0005-7798; Spurdle, Amanda/0000-0003-1337-7897
FU NHMRC; PCFA; Australian Postgraduate Award; Institute of Health and
Biomedical Innovation; QLD Government; Cancer Research UK
FX We thank the patients and control subjects who participated so willingly
in our studies. We thank the SEARCH team and the Eastern Cancer
Registration and Information Centre. The results published here are in
part based upon data generated by The Cancer Genome Atlas Pilot Project
established by the NCI and NHGRI. Information about TCGA and the
investigators and institutions who constitute the TCGA research network
can be found at http://cancergenome.nih.gov. Amanda Spurdle is supported
by an NHMRC Senior Research Fellowship. Felicity Lose is supported by
PCFA funding, and Jyotsna Batra is an IHBI Fellow. Tracy O'Mara is
supported by Australian Postgraduate Award, Institute of Health and
Biomedical Innovation PhD top-up and QLD Government Smart State PhD
top-up award. Christina Nagle is supported by NHMRC Postdoctoral
Fellowship. _SEARCH is funded through a programme grant from Cancer
Research UK.
NR 38
TC 18
Z9 18
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD DEC
PY 2010
VL 119
IS 3
BP 479
EP 483
DI 10.1016/j.ygyno.2010.08.014
PG 5
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 684NO
UT WOS:000284556800014
PM 20832104
ER
PT J
AU Jukic, AMZ
Weinberg, CR
Wilcox, AJ
Baird, DD
AF Jukic, Anne Marie Z.
Weinberg, Clarice R.
Wilcox, Allen J.
Baird, Donna D.
TI Effects of early pregnancy loss on hormone levels in the subsequent
menstrual cycle
SO GYNECOLOGICAL ENDOCRINOLOGY
LA English
DT Article
DE Early pregnancy loss; pituitary gland; luteinising hormone
ID URINARY ESTROGEN; PROGESTERONE METABOLITES; OVULATION; RADIOIMMUNOASSAY;
PROBABILITY; CONCEPTION; WOMEN; TIME
AB Previous studies of hormone patterns after clinical miscarriage suggest reduced pituitary function. Hormonal effects of very early pregnancy loss (before 6 weeks gestation) have not been described. We used within-woman differences between menstrual cycles in urinary hormone measurements from women in the North Carolina Early Pregnancy Study to describe hormonal changes after very early pregnancy loss (n = 28 early losses; 80 non-conception comparison cycles). We found lower pre-ovulatory luteinising hormone and shorter luteal phase length after very early pregnancy loss, but the differences were non-significant (p > 0.3) and smaller than those reported in the spontaneous miscarriage literature. Consistent with the reduced pituitary function reported post-spontaneous miscarriage, we found a slower rate of oestrogen rise (p = 0.08). There was no evidence of lower mid-luteal steroid levels as has been suggested for post-spontaneous miscarriage cycles. Very early pregnancy losses do not appear to influence subsequent menstrual cycles to the same degree as spontaneous miscarriages.
C1 [Jukic, Anne Marie Z.; Wilcox, Allen J.; Baird, Donna D.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Weinberg, Clarice R.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Jukic, AMZ (reprint author), Mail Drop A3-05,POB 12233, Durham, NC 27709 USA.
EM jukica@niehs.nih.gov
RI Baird, Donna/D-5214-2017;
OI Baird, Donna/0000-0002-5544-2653; Wilcox, Allen/0000-0002-3376-1311
FU NIH, National Institute of Environmental Health Sciences
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences. We thank Dr.
Freya Kamel and Dr. Walter Rogan for their comments on an earlier draft
of this manuscript. We thank Dr. Robert McConnaghey for his support in
data management.
NR 15
TC 0
Z9 0
U1 2
U2 4
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 0951-3590
J9 GYNECOL ENDOCRINOL
JI Gynecol. Endocrinol.
PD DEC
PY 2010
VL 26
IS 12
BP 897
EP 901
DI 10.3109/09513590.2010.487601
PG 5
WC Endocrinology & Metabolism; Obstetrics & Gynecology
SC Endocrinology & Metabolism; Obstetrics & Gynecology
GA 678LI
UT WOS:000284075100009
PM 20504096
ER
PT J
AU Young, NS
AF Young, Neal S.
TI Telomere Biology and Telomere Diseases: Implications for Practice and
Research
SO HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM
LA English
DT Article
AB The recent recognition of genetic defects in telomeres and telomere repair in multiple human diseases has practical implications for hematologists and oncologists and their patients; consequences for future clinical research in hematology and other subspecialties; and even importance in the interpretation of animal experiments involving cell propagation. Telomere diseases include constitutional marrow failure as dyskeratosis congenita, some apparently acquired aplastic anemia, myelodysplasia and acute myeloid leukemia; pulmonary fibrosis; and hepatic nodular regenerative hyperplasia and cirrhosis. Accelerated telomere attrition is a likely pathophysiology of cancer arising from chronic inflammation. Telomerase can be modulated by sex hormones, which may explain the activity of androgens in marrow failure. Measurement of telomere length of peripheral blood leukocytes is a simple screening clinical assay. Detection of a mutation in a patient has implications for therapy, prognosis, monitoring, and genetic counseling. For research in hematology and oncology, telomere biology could be assessed as a risk for secondary malignancies and in graft-versus-host disease, for progression in a variety of blood cancers, and as potentially modifiable by hormone replacement strategies.
C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Young, NS (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr,Bldg 10 CRC 3-5140,MSC 1202, Bethesda, MD 20892 USA.
EM youngns@mail.nih.gov
NR 38
TC 20
Z9 23
U1 0
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 1520-4391
J9 HEMATOL-AM SOC HEMAT
JI Hematol.-Am. Soc. Hematol. Educ. Program
PD DEC
PY 2010
BP 30
EP 35
DI 10.1182/asheducation-2010.1.30
PG 6
WC Education, Scientific Disciplines; Hematology
SC Education & Educational Research; Hematology
GA V29PF
UT WOS:000208759600005
ER
PT J
AU Bevans, M
AF Bevans, Margaret
TI Health-Related Quality of Life Following Allogeneic Hematopoietic Stem
Cell Transplantation
SO HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM
LA English
DT Article
AB It is common knowledge that an allogeneic hematopoietic stem cell transplantation (HSCT) will have an enormous impact on the lives of transplant recipients and their families. Once an appropriate donor is identified, the curative potential of this treatment often drives the decision to proceed knowing that there will be intense physiologic toxicities and adverse effects on health-related quality of life (HRQL). Twenty-five years ago, HRQL was identified as an efficacy parameter in the evaluation of new anticancer drug therapy. Overall, the evidence suggests that an allogeneic HSCT has a significant impact on the overall HRQL of recipients, which is a result of decrements across all dimensions, including a significant symptom profile. The degree of impact on overall HRQL and the multiple dimensions varies across the transplant trajectory. Specific HRQL dimensions, such as physical function and symptoms, are easily incorporated into a clinician's assessment whereas other dimensions (eg, psychosocial) are less commonly integrated. The translation of HRQL results to improve clinical practice is not well established. Clinicians are often uncertain when to assess the scope of HRQL and how to interpret the information in a clinically meaningful way. The purpose of this review is to highlight the quality-of-life effects of allogeneic HSCT and discuss application into clinical practice.
C1 [Bevans, Margaret] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Bevans, M (reprint author), 10 Ctr Dr,MSC 1551,Room 2B13, Bethesda, MD 20892 USA.
EM mbevans@cc.nih.gov
NR 53
TC 11
Z9 11
U1 4
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 1520-4391
J9 HEMATOL-AM SOC HEMAT
JI Hematol.-Am. Soc. Hematol. Educ. Program
PD DEC
PY 2010
BP 248
EP 254
DI 10.1182/asheducation-2010.1.248
PG 7
WC Education, Scientific Disciplines; Hematology
SC Education & Educational Research; Hematology
GA V29PF
UT WOS:000208759600039
ER
PT J
AU Landgren, O
AF Landgren, Ola
TI Monoclonal Gammopathy of Undetermined Significance and Smoldering
Myeloma: New Insights into Pathophysiology and Epidemiology
SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM
LA English
DT Article
AB Routine screening for monoclonal gammopathy of undetermined significance (MGUS) is not indicated. Despite this fact, MGUS is a common finding in medical practice. Almost all individuals diagnosed with MGUS represent incidental cases diagnosed when physicians order serum protein electrophoresis, immunofixation, or both, as part of the work-up of a number of common symptoms and laboratory abnormalities. In the absence of reliable molecular predictors of outcome, the detection of an early precursor state typically imposes a complex situation for the patient and the responsible physician-usually, it leads to a lot of questions that lack clear answers. In the past years, several novel insights have been gained in the area of multiple myeloma (MM) precursor disease. This review focuses on results from recent investigations and discusses implications for diagnostic work-up, clinical management, and patient counseling. More specifically, it sheds light on the following commonly asked questions by patients and physicians: i) what is the risk of progression from precursor to full-blown MM, and are there ways to risk-stratify patients?; ii) is MM always preceded by a precursor state, and is there anything that could or should be done to delay or prevent progression?; and iii) why do some individuals develop MM precursor diseases, and is there a reason to screen the family?
C1 NCI, Multiple Myeloma Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Landgren, O (reprint author), NCI, Multiple Myeloma Sect, Med Oncol Branch, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 10 Room 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
FU National Cancer Institute of the National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Cancer Institute of the National Institutes of Health.
NR 70
TC 10
Z9 11
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 1520-4391
EI 1520-4383
J9 HEMATOL-AM SOC HEMAT
JI Hematol.-Am. Soc. Hematol. Educ. Program
PD DEC
PY 2010
BP 295
EP 302
DI 10.1182/asheducation-2010.1.295
PG 8
WC Education, Scientific Disciplines; Hematology
SC Education & Educational Research; Hematology
GA V29PF
UT WOS:000208759600047
ER
PT J
AU Clifford, RJ
Zhang, JH
Meerzaman, DM
Lyu, MS
Hu, Y
Cultraro, CM
Finney, RP
Kelley, JM
Efroni, S
Greenblum, SI
Nguyen, CV
Rowe, WL
Sharma, S
Wu, G
Yan, CH
Zhang, HG
Chung, YH
Kim, JA
Park, NH
Song, IH
Buetow, KH
AF Clifford, Robert J.
Zhang, Jinghui
Meerzaman, Daoud M.
Lyu, Myung-Soo
Hu, Ying
Cultraro, Constance M.
Finney, Richard P.
Kelley, Jenny M.
Efroni, Sol
Greenblum, Sharon I.
Nguyen, Cu V.
Rowe, William L.
Sharma, Sweta
Wu, Gang
Yan, Chunhua
Zhang, Hongen
Chung, Young-Hwa
Kim, Jeong A.
Park, Neung Hwa
Song, Il Han
Buetow, Kenneth H.
TI Genetic Variations at Loci Involved in the Immune Response Are Risk
Factors for Hepatocellular Carcinoma
SO HEPATOLOGY
LA English
DT Article
ID CHRONIC HEPATITIS-B; CORE PROTEIN; CANCER; GENOME; ASSOCIATION;
SUSCEPTIBILITY; HYBRIDIZATION; POLYMORPHISM; POPULATION; YEAR-2000
AB Primary liver cancer is the third most common cause of cancer-related death worldwide, with a rising incidence in Western countries Little is known about the genetic etiology of this disease To identify genetic factors associated with hepatocellular carcinoma (HCC) and liver cirrhosis (LC), we conducted a comprehensive, genome-wide variation analysis in a population of unrelated Asian individuals Copy number variation (CNV) and single nucleotide polymorphisms (SNPs) were assayed in peripheral blood with the high-density Affymetrix SNP6 0 microarray platform We used a two-stage discovery and replication design to control for overfitting and to validate observed results We identified a strong association with CNV at the T-cell receptor gamma and alpha loci (P < 1 x 10(-15)) in HCC cases when contrasted with controls This variation appears to be somatic in origin, reflecting differences between T-cell receptor processing in lymphocytes from individuals with liver disease and healthy individuals that is not attributable to chronic hepatitis virus infection Analysis of constitutional variation identified three susceptibility loci including the class II MHC complex, whose protein products present antigen to T-cell receptors and mediate immune surveillance Statistical analysis of biologic networks identified variation in the "antigen presentation and processing" pathway as being highly significantly associated with HCC (P = 1 x 10(-11)) SNP analysis identified two variants whose allele frequencies differ significantly between HCC and LC One of these (P = 174 X 10(-12)) lies in the PTEN homolog TPTE2 Conclusion. Combined analysis of CNV, individual SNPs, and pathways suggest that HCC susceptibility is mediated by germline factors affecting the immune response and differences in T-cell receptor processing (HEPATOLOGY 2010,52 2034-2043)
C1 [Clifford, Robert J.; Meerzaman, Daoud M.; Lyu, Myung-Soo; Cultraro, Constance M.; Kelley, Jenny M.; Nguyen, Cu V.; Sharma, Sweta; Zhang, Hongen; Buetow, Kenneth H.] NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA.
[Zhang, Jinghui; Hu, Ying; Finney, Richard P.; Greenblum, Sharon I.; Rowe, William L.; Wu, Gang; Yan, Chunhua; Buetow, Kenneth H.] NCI, Ctr Bioinformat & Informat Technol, Rockville, MD USA.
[Efroni, Sol] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, Ramat Gan, Israel.
[Chung, Young-Hwa; Kim, Jeong A.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Internal Med, Seoul, South Korea.
[Park, Neung Hwa] Univ Ulsan, Ulsan Univ Hosp, Coll Med, Dept Internal Med, Ulsan 680749, South Korea.
[Song, Il Han] Dankook Univ, Coll Med, Dept Internal Med, Cheonan, South Korea.
RP Clifford, RJ (reprint author), NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA.
RI Efroni, Sol/I-6752-2012
OI Efroni, Sol/0000-0001-7927-6349
FU National Institutes of Health (NIH) [Z01 CP 010139]
FX Supported by National Institutes of Health (NIH) intramural grant Z01 CP
010139
NR 38
TC 60
Z9 64
U1 0
U2 12
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD DEC
PY 2010
VL 52
IS 6
BP 2034
EP 2043
DI 10.1002/hep.23943
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 690RP
UT WOS:000285023700019
PM 21105107
ER
PT J
AU Zhang, XY
Tachibana, S
Wang, H
Hisada, M
Williams, GM
Gao, B
Sun, ZL
AF Zhang, Xiuying
Tachibana, Shingo
Wang, Hua
Hisada, Masayuki
Williams, George Melville
Gao, Bin
Sun, Zhaoli
TI Interleukin-6 Is an Important Mediator for Mitochondrial DNA Repair
After Alcoholic Liver Injury in Mice
SO HEPATOLOGY
LA English
DT Article
ID CHRONIC ETHANOL-CONSUMPTION; APOPTOSIS-INDUCING FACTOR; RAT-LIVER;
OXIDATIVE DAMAGE; CYTOCHROME-C; INDUCTION; DISEASE; HEPATOCYTES;
STEATOSIS; MORTALITY
AB We investigated the hypothesis that a prominent effect of chronic ethanol consumption is mitochondrial DNA (mtDNA) injury and compared this injury in IL-6 knockout (KO) and wild-type (WT) mice Ethanol feeding for 4 weeks resulted in steatosis and oxidative mtDNA damage (8-OHdG) in both IL-6KO and WT mice However, the WT mice were able to repair the injury by increased production of mtDNA repair enzymes (OGG-1, Neil 1) and check point (p21, p53) proteins and avoid the mtDNA mutations By contrast the IL-6 KO mice were unable to repair mtDNA resulting in deletions and diminished transcription of the mtDNA encoded protein cytochrome c oxidase subunit-I (COI) The mitochondrial injury was reflected by decreased membrane potential, reduced levels of ATP, and apoptosis-inducing factor (AIF)-induced apoptosis Conclusion IL-6 plays a critical role in allowing the liver to recover from significant mtDNA oxidation caused by alcohol The data suggests that IL-6 activates mtDNA repair enzymes and induces cell cycle arrest allowing time for mtDNA repair (HEPATOLOGY 2010,52 2137-2147)
C1 [Zhang, Xiuying; Tachibana, Shingo; Hisada, Masayuki; Williams, George Melville; Sun, Zhaoli] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
[Wang, Hua; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
RP Sun, ZL (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, 720 Rutland Ave,Ross 771, Baltimore, MD 21205 USA.
FU Bertram M Bernheim Research Fund; US National Institutes of Health
[AA018113]
FX This work was supported by the Bertram M Bernheim Research Fund and US
National Institutes of Health (AA018113)
NR 46
TC 23
Z9 25
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD DEC
PY 2010
VL 52
IS 6
BP 2137
EP 2147
DI 10.1002/hep.23909
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 690RP
UT WOS:000285023700029
PM 20931558
ER
PT J
AU Jimenez-Rojo, L
Ibarretxe, G
Aurrekoetxea, M
de Vega, S
Nakamura, T
Yamada, Y
Unda, F
AF Jimenez-Rojo, Lucia
Ibarretxe, Gaskon
Aurrekoetxea, Maitane
de Vega, Susana
Nakamura, Takashi
Yamada, Yoshihiko
Unda, Fernando
TI Epiprofin/Sp6: A new player in the regulation of tooth development
SO HISTOLOGY AND HISTOPATHOLOGY
LA English
DT Review
DE Odontogenesis; Supernumerary teeth; Ameloblast; Epiprofin/Sp6; Shh; Wnt;
BMP
ID TRANSCRIPTION FACTOR SP3; SUPERNUMERARY TEETH; TISSUE INTERACTIONS;
CELL-PROLIFERATION; DENTAL EPITHELIUM; MOUSE TOOTH; ENAMEL KNOT;
DIFFERENTIATION; GROWTH; MICE
AB Odontogenesis is governed by a complex network of intercellular signaling events between the dental epithelium and mesenchyme. This network leads to the progressive determination of tooth shape, and to the differentiation of these tissues into enamel-producing ameloblasts and dentin-producing odontoblasts respectively. Among the main signaling pathways involved in the regulation of tooth development, Bone Morphogenetic Protein (BMP), Sonic hedgehog (Shh) and Wingless-type MMTV integration site (Wnt) pathways have been reported to play significant roles. Recently, the phenotype of mice deficient in Epiprofin/Sp6 (Epfn) has been found to present striking dental abnormalities, including a complete lack of differentiated ameloblasts and consequently no enamel, highly altered molar cusp patterns and the formation of multiple supernumerary teeth. In this article, we review the interaction of Epfn with the BMP, Shh and Wnt pathways in the regulation of tooth development, based on the data obtained from the study of several genetically modified mice.
C1 [Ibarretxe, Gaskon; Aurrekoetxea, Maitane; Unda, Fernando] Univ Basque Country, Fac Med & Dent, Dept Cell Biol & Histol, Vizcaya, Spain.
[Jimenez-Rojo, Lucia] Ecole Polytech Fed Lausanne, ISREC Swiss Inst Expt Canc Res, NCCR Mol Oncol, Lausanne, Switzerland.
[de Vega, Susana; Nakamura, Takashi; Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
RP Unda, F (reprint author), Univ Basque Country, Fac Med & Dent, Dept Cell Biol & Histol, Vizcaya, Spain.
EM fernando.unda@ehu.es
RI Jimenez, Lucia/K-3377-2012; Nakamura, Takashi/P-7796-2016
OI Nakamura, Takashi/0000-0001-9904-1037
FU Basque Country University (UPV/EHU); Basque Country University; Jesus
Gangoiti Foundation
FX This work was supported by the Basque Country University (UPV/EHU).
L.J.R was supported by a fellowship from Basque Country University and
M. A was supported by Jesus Gangoiti Foundation and at this time is
supported by a fellowship of the University of the Basque Country.
NR 51
TC 11
Z9 12
U1 1
U2 6
PU F HERNANDEZ
PI MURCIA
PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN
SN 0213-3911
J9 HISTOL HISTOPATHOL
JI Histol. Histopath.
PD DEC
PY 2010
VL 25
IS 12
BP 1621
EP 1630
PG 10
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 657ZT
UT WOS:000282458900012
PM 20886441
ER
PT J
AU Calabrese, EJ
Mattson, MP
Calabrese, V
AF Calabrese, Edward J.
Mattson, Mark P.
Calabrese, Vittorio
TI Resveratrol commonly displays hormesis: Occurrence and biomedical
significance
SO HUMAN & EXPERIMENTAL TOXICOLOGY
LA English
DT Article
DE resveratrol; hormesis; hormetic; biphasic; U-shaped
ID BREAST-CANCER CELLS; HUMAN ENDOMETRIAL ADENOCARCINOMA; PARAOXONASE-1
GENE-EXPRESSION; ENDOTHELIAL PROGENITOR CELLS; ARYL-HYDROCARBON
RECEPTOR; BIPHASIC DOSE RESPONSES; BETA-AMYLOID TOXICITY;
GROWTH-FACTOR-II; IN-VITRO; RADIATION-HORMESIS
AB Resveratrol induces hormetic dose responses in a wide range of biological models, affecting numerous endpoints of biomedical and therapeutic significance. These responses were reported for numerous human tumor cell lines affecting breast, prostate, colon, lung, uterine and leukemia. In such cases, low concentrations of resveratrol enhanced tumor cell proliferation whereas higher concentrations were inhibitory. Similar resveratrol-induced biphasic dose responses were seen with several parasitic diseases, including Leishmaniasis and trichinella. Hormetic effects were also reported in animal models for cardiovascular induced injury, gastric lesions, ischemic stroke, Alzheimer's disease and osteoporosis. In these cases, there was often a protective effect at low doses but an adverse effect at higher doses, exacerbating the disease process/incidence. This analysis indicates that many effects induced by resveratrol are dependent on dose and that opposite effects occur at low and high doses, being indicative of a hormetic dose response. Despite consistent occurrence of hormetic dose responses of resveratrol in a wide range of biomedical models, epidemiologic and clinical trials are needed to assess the nature of its dose-response in humans.
C1 [Calabrese, Edward J.] Univ Massachusetts, Dept Publ Hlth, Amherst, MA 01003 USA.
[Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Calabrese, Vittorio] Univ Catania, Dept Chem, Biochem & Mol Biol Sect, Catania, Italy.
RP Calabrese, EJ (reprint author), Univ Massachusetts, Dept Publ Hlth, Morrill 1,N344, Amherst, MA 01003 USA.
EM edwardc@schoolph.umass.edu
RI Mattson, Mark/F-6038-2012
FU Air Force Office of Scientific Research, Air Force Material Command,
USAF [FA9550-07-1-0248]
FX Effort sponsored by the Air Force Office of Scientific Research, Air
Force Material Command, USAF, under grant number FA9550-07-1-0248.
NR 163
TC 78
Z9 79
U1 1
U2 18
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0960-3271
J9 HUM EXP TOXICOL
JI Hum. Exp. Toxicol.
PD DEC
PY 2010
VL 29
IS 12
BP 980
EP 1015
DI 10.1177/0960327110383625
PG 36
WC Toxicology
SC Toxicology
GA 687EU
UT WOS:000284762600002
PM 21115559
ER
PT J
AU Calabrese, EJ
Mattson, MP
Calabrese, V
AF Calabrese, Edward J.
Mattson, Mark P.
Calabrese, Vittorio
TI Dose response biology: The case of resveratrol
SO HUMAN & EXPERIMENTAL TOXICOLOGY
LA English
DT Article
DE resveratrol; hormesis; hormetic; dose response; biphasic; U-shaped;
adaptive response
ID THRESHOLD-MODEL; TOXICOLOGICAL LITERATURE; DATABASE; BECAME
AB Resveratrol often displays hormesis-like biphasic dose responses. This occurs in a broad range of biological models and for numerous endpoints of biomedical interest and public health concern. Recognition of the widespread occurrence of the hormetic nature of many of the responses of resveratrol is important on multiple levels. It can help optimize study design protocols by investigators, create a dose-response framework for better addressing dose-related biological complexities and assist in the development of public health and medical guidance with respect to considerations for what is an optimal dose not just for an agent such as resveratrol, but also for the plethora of agents that also act via hormetic mechanisms.
C1 [Calabrese, Edward J.] Univ Massachusetts, Dept Publ Hlth, Amherst, MA 01003 USA.
[Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Calabrese, Vittorio] Univ Catania, Dept Chem, Biochem & Mol Biol Sect, Catania, Italy.
RP Calabrese, EJ (reprint author), Univ Massachusetts, Dept Publ Hlth, Morrill 1,N344, Amherst, MA 01003 USA.
EM edwardc@schoolph.umass.edu
RI Mattson, Mark/F-6038-2012
NR 20
TC 25
Z9 25
U1 0
U2 11
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0960-3271
J9 HUM EXP TOXICOL
JI Hum. Exp. Toxicol.
PD DEC
PY 2010
VL 29
IS 12
BP 1034
EP 1037
DI 10.1177/0960327110383641
PG 4
WC Toxicology
SC Toxicology
GA 687EU
UT WOS:000284762600010
PM 21115567
ER
PT J
AU Zhang, LQ
Limberis, MP
Thompson, C
Antunes, MB
Luongo, C
Wilson, JM
Collins, PL
Pickles, RJ
AF Zhang, Liqun
Limberis, Maria P.
Thompson, Catherine
Antunes, Marcelo B.
Luongo, Cindy
Wilson, James M.
Collins, Peter L.
Pickles, Raymond J.
TI alpha-Fetoprotein Gene Delivery to the Nasal Epithelium of Nonhuman
Primates by Human Parainfluenza Viral Vectors
SO HUMAN GENE THERAPY
LA English
DT Article
ID CYSTIC-FIBROSIS PATIENTS; PHASE-I TRIAL; VIRUS TYPE-3; RESPIRATORY
EPITHELIA; AIRWAY EPITHELIUM; PROTEIN; CELLS
AB Over the last two decades, enormous effort has been focused on developing virus-based gene delivery vectors to target the respiratory airway epithelium as a potential treatment for cystic fibrosis (CF) lung disease. However, amongst other problems, the efficiency of gene delivery to the differentiated airway epithelial cells of the lung has been too low for clinical benefit. Although not a target for CF therapy, the nasal epithelium exhibits cellular morphology and composition similar to that of the lower airways, thus representing an accessible and relevant tissue target for evaluating novel and improved gene delivery vectors. We previously reported that replication-competent human parainfluenza virus (PIV)-based vectors efficiently deliver the cystic fibrosis transmembrane conductance regulator gene to sufficient numbers of cultured CF airway epithelial cells to completely correct the bioelectric function of CF cells to normal levels, resulting in restoration of mucus transport. Here, using an in vitro model of rhesus airway epithelium, we demonstrate that PIV mediates efficient gene transfer in rhesus epithelium as in the human counterpart. Naive rhesus macaques were inoculated intranasally with a PIV vector expressing rhesus macaque alpha-fetoprotein (rhAFP), and expression was monitored longitudinally. rhAFP was detected in nasal lavage fluid and in serum samples, indicating that PIV-mediated gene transfer was effective and that rhAFP was secreted into both mucosal and serosal compartments. Although expression was transient, lasting up to 10 days, it paralleled virus replication, suggesting that as PIV was cleared, rhAFP expression was lost. No adverse reactions or signs of discomfort were noted, and only mild, transient elevations of a small number of inflammatory cytokines were measured at the peak of virus replication. In summary, rhAFP proved suitable for monitoring in vivo gene delivery over time, and PIV vectors appear to be promising airway-specific gene transfer vehicles that warrant further development.
C1 [Zhang, Liqun; Thompson, Catherine; Pickles, Raymond J.] Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27759 USA.
[Limberis, Maria P.; Wilson, James M.] Univ Penn, Dept Pathol & Lab Med, Gene Therapy Program, Philadelphia, PA 19104 USA.
[Antunes, Marcelo B.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA.
[Luongo, Cindy; Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Pickles, Raymond J.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27759 USA.
RP Zhang, LQ (reprint author), Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, 7021 Thurston Bowles,CB 7248, Chapel Hill, NC 27759 USA.
EM liqun_zhang@med.unc.edu
RI Wilson, James/F-9220-2011
OI Wilson, James/0000-0002-9630-3131
FU National Institutes of Health [R01 HL77844, P01 HL051818, P30 DK065988,
P30 DK047757]; Cystic Fibrosis Foundation [ZHAN0310]; NIAID
FX The authors thank the UNC CF Center Tissue Culture Core for supplying
primary human bronchial epithelial cells and associated reagents, the
UNC CF Center Histology Core for histological assistance, and the
Clinical Proteomics Core Facility for performing the Luminex assays for
chemokine/cytokine measurements. The authors are grateful to Rebecca L.
Grant (University of Pennsylvania) for technical assistance in the
monkey experiments, and to Dr. Alice Tarantal (UC Davis) for providing
liver RNA from rhesus macaques. This work was supported by the National
Institutes of Health (R01 HL77844, P01 HL051818, P30 DK065988, P30
DK047757) and the Cystic Fibrosis Foundation (ZHAN0310). P. L. C. was
supported by the NIAID Intramural Program.
NR 20
TC 6
Z9 6
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD DEC
PY 2010
VL 21
IS 12
BP 1657
EP 1664
DI 10.1089/hum.2010.065
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 692WU
UT WOS:000285187400002
PM 20735256
ER
PT J
AU Sakuma, T
De Ravin, SS
Tonne, JM
Thatava, T
Ohmine, S
Takeuchi, Y
Malech, HL
Ikeda, Y
AF Sakuma, Toshie
De Ravin, Suk See
Tonne, Jason M.
Thatava, Tayaramma
Ohmine, Seiga
Takeuchi, Yasuhiro
Malech, Harry L.
Ikeda, Yasuhiro
TI Characterization of Retroviral and Lentiviral Vectors Pseudotyped with
Xenotropic Murine Leukemia Virus-Related Virus Envelope Glycoprotein
SO HUMAN GENE THERAPY
LA English
DT Article
ID EFFICIENT GENE-TRANSFER; STABLE PACKAGING CELLS; HIGH-TITER; INFECTIOUS
RETROVIRUS; SURFACE RECEPTOR; VSV-G; PROTEIN; TRANSDUCTION; THERAPY;
XMRV
AB Retroviral and lentiviral vectors are effective gene delivery vehicles that are being evaluated in clinical trials. Variations in the viral envelope (Env) glycoproteins, which are used to pseudotype retroviral or lentiviral vectors, can alter vector performance, including stability, titers, host range, and tissue tropism. Xenotropic murine leukemia virus (MLV)-related virus (XMRV) is a novel human retrovirus identified in patients with prostate cancer. XMRV targets XPR1 cell surface receptor, which is expressed in a broad range of human tissues including hematopoietic stem cells. Pseudotyping with XMRV Env would allow targeting of XPR1-expressing tissues. Here, we characterized XMRV Env-pseudotyped retroviral and lentiviral vectors. Although HIV and MLV vectors were poorly pseudotyped with wild-type XMRV Env, replacement of the C-terminal 11 amino acid residues in the transmembrane domain of XMRV Env with the corresponding 6 amino acid residues of amphotropic MLV Env (XMRV/R(ampho)) significantly increased XMRV Env-pseudotyped HIV and MLV vector titers. The transduction efficiency in human CD34(+) cells when using the XMRV/R(ampho)-pseudotyped HIV vector (10-20%) was comparable to that achieved when using the same infectious units of vesicular stomatitis virus G glycoprotein-pseudotyped vector (25%); thus the modified XMRV Env offers an alternative pseudotyping strategy for XPR1-mediated gene delivery.
C1 [Sakuma, Toshie; Tonne, Jason M.; Thatava, Tayaramma; Ohmine, Seiga; Ikeda, Yasuhiro] Mayo Clin, Dept Mol Med, Rochester, MN 55905 USA.
[De Ravin, Suk See; Malech, Harry L.] NIAID, Genet Immunotherapy Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Takeuchi, Yasuhiro] UCL, Windeyer Inst, Wohl Vir Ctr, Div Infect & Immun, London W1T 4JF, England.
RP Ikeda, Y (reprint author), Mayo Clin, Dept Mol Med, Guggenheim 18-11C,200 1st St SW, Rochester, MN 55905 USA.
EM ikeda.yasuhiro@mayo.edu
OI Malech, Harry/0000-0001-5874-5775
FU National Institutes of Health [R56AI074363]; Mayo Clinic Career
Development Project [CA91956-080013]; Mayo Foundation; Siebens Ph.D.
Training Fellowship
FX This work was supported by the National Institutes of Health
(R56AI074363), by Mayo Clinic Career Development Project in Prostate
SPORE grant CA91956-080013, and the Mayo Foundation (Y.I.), and by a
Siebens Ph.D. Training Fellowship (S.O.).
NR 38
TC 13
Z9 13
U1 0
U2 5
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD DEC
PY 2010
VL 21
IS 12
BP 1665
EP 1673
DI 10.1089/hum.2010.063
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 692WU
UT WOS:000285187400003
PM 20507233
ER
PT J
AU Kumari, D
Usdin, K
AF Kumari, Daman
Usdin, Karen
TI The distribution of repressive histone modifications on silenced FMR1
alleles provides clues to the mechanism of gene silencing in fragile X
syndrome
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID MENTAL-RETARDATION PROTEIN; EMBRYONIC STEM-CELLS; PREMUTATION MICE;
REPEAT EXPANSION; PROMOTER REGION; NONCODING RNAS; FISSION YEAST;
HETEROCHROMATIN; DNA; TRANSCRIPTION
AB Fragile X syndrome (FXS) is the most common heritable cause of intellectual disability and the most common known cause of autism. Most cases of FXS result from the expansion of a CGG. CCG repeat in the 5' UTR of the FMR1 gene that leads to gene silencing. It has previously been shown that silenced alleles are associated with histone H3 dimethylated at lysine 9 (H3K9Me2) and H3 trimethylated at lysine 27 (H3K27Me3), modified histones typical of developmentally repressed genes. We show here that these alleles are also associated with elevated levels of histone H3 trimethylated at lysine 9 (H3K9Me3) and histone H4 trimethylated at lysine 20 (H4K20Me3). All four of these modified histones are present on exon 1 of silenced alleles at levels comparable to that seen on pericentric heterochromatin. The two groups of histone modifications show a different distribution on fragile X alleles: H3K9Me2 and H3K27Me3 have a broad distribution, whereas H3K9Me3 and H4K20Me3 have a more focal distribution with the highest level of these marks being present in the vicinity of the repeat. This suggests that the trigger for gene silencing may be local to the repeat itself and perhaps involves a mechanism similar to that involved in the formation of pericentric heterochromatin.
C1 [Kumari, Daman; Usdin, Karen] NIDDK, Sect Gene Struct & Dis, Lab Mol & Cellular Biol, NIH, Bethesda, MD 20892 USA.
RP Usdin, K (reprint author), NIDDK, Sect Gene Struct & Dis, Lab Mol & Cellular Biol, NIH, Bldg 8,Room 2A19,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA.
EM ku@helix.nih.gov
FU NIDDK, National Institutes of Health, USA [DK057602]
FX This work was supported by a grant to K.U. from the Intramural Program
of NIDDK, National Institutes of Health, USA (grant number DK057602).
NR 68
TC 41
Z9 42
U1 0
U2 1
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 2010
VL 19
IS 23
BP 4634
EP 4642
DI 10.1093/hmg/ddq394
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 676QV
UT WOS:000283930200008
PM 20843831
ER
PT J
AU Kohonen-Corish, MRJ
Al-Aama, JY
Auerbach, AD
Axton, M
Barash, CI
Bernstein, I
Beroud, C
Burn, J
Cunningham, F
Cutting, GR
den Dunnen, JT
Greenblatt, MS
Kaput, J
Katz, M
Lindblom, A
Macrae, F
Maglott, D
Moslein, G
Povey, S
Ramesar, R
Richards, S
Seminara, D
Sobrido, MJ
Tavtigian, S
Taylor, G
Vihinen, M
Winship, I
Cotton, RGH
AF Kohonen-Corish, Maija R. J.
Al-Aama, Jumana Y.
Auerbach, Arleen D.
Axton, Myles
Barash, Carol Isaacson
Bernstein, Inge
Beroud, Christophe
Burn, John
Cunningham, Fiona
Cutting, Garry R.
den Dunnen, Johan T.
Greenblatt, Marc S.
Kaput, Jim
Katz, Michael
Lindblom, Annika
Macrae, Finlay
Maglott, Donna
Moeslein, Gabriela
Povey, Sue
Ramesar, Raj
Richards, Sue
Seminara, Daniela
Sobrido, Maria-Jesus
Tavtigian, Sean
Taylor, Graham
Vihinen, Mauno
Winship, Ingrid
Cotton, Richard G. H.
CA Contributors Human Variome Project
TI How to Catch All Those Mutations-The Report of the Third Human Variome
Project Meeting, UNESCO Paris, May 2010
SO HUMAN MUTATION
LA English
DT Editorial Material
DE mutation; variation; genomics; genetic disease
ID RECOMMENDATIONS
AB The third Human Variome Project (HVP) Meeting "Integration and Implementation" was held under UNESCO Patronage in Paris, France, at the UNESCO Headquarters May 10-14, 2010. The major aims of the HVP are the collection, curation, and distribution of all human genetic variation affecting health. The HVP has drawn together disparate groups, by country, gene of interest, and expertise, who are working for the common good with the shared goal of pushing the boundaries of the human variome and collaborating to avoid unnecessary duplication. The meeting addressed the 12 key areas that form the current framework of HVP activities: Ethics; Nomenclature and Standards; Publication, Credit and Incentives; Data Collection from Clinics; Overall Data Integration and Access-Peripheral Systems/Software; Data Collection from Laboratories; Assessment of Pathogenicity; Country Specific Collection; Translation to Healthcare and Personalized Medicine; Data Transfer, Databasing, and Curation; Overall Data Integration and Access-Central Systems; and Funding Mechanisms and Sustainability. In addition, three societies that support the goals and the mission of HVP also held their own Workshops with the view to advance disease-specific variation data collection and utilization: the International Society for Gastrointestinal Hereditary Tumours, the Micronutrient Genomics Project, and the Neurogenetics Consortium. Hum Mutat 31:1374-1381, 2010. (c) 2010 Wiley-Liss, Inc.
C1 [Kohonen-Corish, Maija R. J.] Univ NSW, St Vincents Clin Sch, Garvan Inst Med Res, Canc Res Program, Sydney, NSW 2010, Australia.
[Al-Aama, Jumana Y.] King Abdulaziz Univ, Dept Med Genet, Fac Med, Jeddah 21413, Saudi Arabia.
[Al-Aama, Jumana Y.] King Abdulaziz Univ, Princess Al Jawhara Ctr Excellence Res Hereditary, Jeddah 21413, Saudi Arabia.
[Auerbach, Arleen D.] Rockefeller Univ, Program Human Genet & Hematol, New York, NY 10021 USA.
[Axton, Myles] Nat Publishing Grp, New York, NY USA.
[Barash, Carol Isaacson] Boston Univ, Dept Philosophy Genet Eth & Policy Consulting, Boston, MA 02215 USA.
[Bernstein, Inge] Hvidovre Univ Hosp, Dept Surg Gastroenterol, Copenhagen, Denmark.
[Beroud, Christophe] Univ Montpellier 1, Hop Arnaud Villeneuve, Genet Mol Lab, INSERM,U827, Montpellier, France.
[Burn, John] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Cunningham, Fiona] EBI, Cambridge CB10 1SD, England.
[Cutting, Garry R.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA.
[den Dunnen, Johan T.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Greenblatt, Marc S.] Univ Vermont, Coll Med, Burlington, VT USA.
[Kaput, Jim] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR USA.
[Katz, Michael] March Dimes Fdn, White Plains, NY USA.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Macrae, Finlay] Dept Colorectal Med & Genet, Parkville, Vic, Australia.
[Macrae, Finlay] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Parkville, Vic, Australia.
[Maglott, Donna] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Moeslein, Gabriela] HELIOS St Josefs Hosp, Bochum, Germany.
[Povey, Sue] UCL, Div Life Sci, London, England.
[Ramesar, Raj] Univ Cape Town, Inst Infect Dis & Mol Med, Div Human Genet, MRC Human Genet Res Unit, ZA-7700 Rondebosch, South Africa.
[Richards, Sue] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Seminara, Daniela] NCI, Bethesda, MD 20892 USA.
[Sobrido, Maria-Jesus] Inst Hlth Carlos III, Ctr Biomed Network Res Rare Disorders CIBERER, Fdn Publ Galega Med Xenom, Madrid, Spain.
[Tavtigian, Sean] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT USA.
[Taylor, Graham] St James Univ Hosp, Leeds, W Yorkshire, England.
[Vihinen, Mauno] Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland.
[Vihinen, Mauno] Tampere Univ Hosp, Res Ctr, Tampere, Finland.
[Winship, Ingrid] Univ Melbourne, Royal Melbourne Hosp, Melbourne, Vic 3050, Australia.
[Cotton, Richard G. H.] Genom Disorders Res Ctr, Melbourne, Vic, Australia.
RP Kohonen-Corish, MRJ (reprint author), Univ NSW, St Vincents Clin Sch, Garvan Inst Med Res, Canc Res Program, 384 Victoria St, Sydney, NSW 2010, Australia.
EM m.corish@garvan.org.au
RI Ramesar, Raj/I-6941-2015; BEROUD, Christophe/A-8381-2008; Vihinen,
Mauno/A-8452-2012; LABO, U827/A-8632-2008
OI Ramesar, Raj/0000-0001-5688-1634; BEROUD,
Christophe/0000-0003-2986-8738; Axton, J. Myles/0000-0002-8042-4131;
Cunningham, Fiona/0000-0002-7445-2419; Auerbach,
Arleen/0000-0002-6911-8379; Winship, Ingrid/0000-0001-8535-6003;
Vihinen, Mauno/0000-0002-9614-7976;
FU NIDDK NIH HHS [R37 DK044003, R37 DK044003-21]
NR 7
TC 23
Z9 27
U1 1
U2 10
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD DEC
PY 2010
VL 31
IS 12
BP 1374
EP 1381
DI 10.1002/humu.21379
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 693VG
UT WOS:000285252900015
PM 20960468
ER
PT J
AU Zhu, JL
Hvidtjorn, D
Basso, O
Obel, C
Thorsen, P
Uldall, P
Olsen, J
AF Zhu, Jin Liang
Hvidtjorn, Dorte
Basso, Olga
Obel, Carsten
Thorsen, Poul
Uldall, Peter
Olsen, Jorn
TI Parental infertility and cerebral palsy in children
SO HUMAN REPRODUCTION
LA English
DT Article
DE cerebral palsy; infertility; infertility treatment; time to pregnancy;
Danish National Birth Cohort
ID IN-VITRO FERTILIZATION; NATIONAL BIRTH COHORT; ASSISTED CONCEPTION;
NEUROLOGICAL SEQUELAE; BORN; TWINS; VALIDATION; MORBIDITY; HEALTH; RISK
AB Children born after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have been reported to have a higher risk of cerebral palsy (CP), perhaps due to the higher frequency of preterm birth, multiple births or vanishing embryo in the pregnancies. However, it has been suggested that the underlying infertility may be part of the pathway. In this study, we examined whether untreated subfecundity (measured by time to pregnancy) or infertility treatment was associated with an increased risk of CP in the offspring.
Using the Danish National Birth Cohort (1997-2003), we compared children born after 0-2 months of waiting time to pregnancy (n = 35 848) with those born after a time to pregnancy of 3-5 months (n = 15 361), 6-12 months (n = 11 528) and > 12 months (n = 7387), as well as those born after IVF/ICSI (n = 3617), ovulation induction with or without intrauterine insemination (n = 3000), and unplanned pregnancies (n = 13 462). CP cases were identified through the Danish CP Register.
In total, 165 (0.18%) children were diagnosed with CP in the entire cohort. We found no significant association between time to pregnancy and the risk of CP in children conceived spontaneously. Children born after IVF/ICSI had an increased risk of CP, even after adjustment for preterm birth and multiplicity (hazard ratio 2.30, 95% confidence interval 1.12-4.73).
Subfecundity per se did not appear to be associated with the risk of CP in children, whereas being born after IVF/ICSI conferred an increased risk.
C1 [Zhu, Jin Liang; Hvidtjorn, Dorte; Obel, Carsten] Univ Aarhus, Danish Epidemiol Sci Ctr, Dept Epidemiol, Sch Publ Hlth, DK-8000 Aarhus C, Denmark.
[Basso, Olga] NIEHS, Dept Hlth & Human Serv, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Uldall, Peter] Univ Copenhagen Hosp, Rigshosp, DK-2100 Copenhagen, Denmark.
[Uldall, Peter] Inst Publ Hlth, Copenhagen, Denmark.
[Olsen, Jorn] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA.
RP Zhu, JL (reprint author), Univ Aarhus, Danish Epidemiol Sci Ctr, Dept Epidemiol, Sch Publ Hlth, Bartholins Alle 2, DK-8000 Aarhus C, Denmark.
EM zjl@soci.au.dk
RI Basso, Olga/E-5384-2010; Olsen, Jorn/F-8801-2015
OI Basso, Olga/0000-0001-9298-4921; Olsen, Jorn/0000-0001-7462-5140
FU Danish Medical Research Council [271-07-0402, 09-063477]; NIH, National
Institute of Environmental Health Sciences [Z01 ES044003]; Danish
Research Council for Health and Disease; Danish National Research
Foundation
FX This work was supported by grants from the Danish Medical Research
Council (271-07-0402 and 09-063477) and, in part, by the Intramural
program of the NIH, National Institute of Environmental Health Sciences
(Z01 ES044003). The work of Carsten Obel was funded by a grant from the
Danish Research Council for Health and Disease. The Danish National
Research Foundation has established the Danish Epidemiology Science
Centre that initiated and created the Danish National Birth Cohort. The
cohort is furthermore a result of a major grant from this Foundation.
Additional support for the Danish National Birth Cohort is obtained from
the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth
Defects Foundation, the Augustinus Foundation and the Health Foundation.
NR 23
TC 13
Z9 14
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD DEC
PY 2010
VL 25
IS 12
BP 3142
EP 3145
DI 10.1093/humrep/deq206
PG 4
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 685OH
UT WOS:000284637500029
PM 21045245
ER
PT J
AU Li, HL
Tang, QZ
Liu, C
Moon, M
Chen, MY
Yan, L
Bian, ZY
Zhang, Y
Wang, AB
Nghiem, MP
Liu, PP
AF Li, Hongliang
Tang, Qi-Zhu
Liu, Chen
Moon, Mark
Chen, Manyin
Yan, Ling
Bian, Zhou-Yan
Zhang, Yan
Wang, Ai-Bing
Nghiem, Mai P.
Liu, Peter P.
TI Cellular FLICE-Inhibitory Protein Protects Against Cardiac Remodeling
Induced by Angiotensin II in Mice
SO HYPERTENSION
LA English
DT Article
DE cFLIP; cardiac remodeling; ERK1/2; apoptosis
AB The development of cardiac hypertrophy in response to increased hemodynamic load and neurohormonal stress is initially a compensatory response that may eventually lead to ventricular dilatation and heart failure. Cellular FLICE-inhibitory protein (cFLIP) is a homologue of caspase 8 without caspase activity that inhibits apoptosis initiated by death receptor signaling. Previous studies showed that cFLIP expression was markedly decreased in the ventricular myocardium of patients with end-stage heart failure. However, the critical role of cFLIP on cardiac remodeling remains unclear. To specifically determine the role of cFLIP in pathological cardiac remodeling, we used heterozygote cFLIP(+/-) mice and transgenic mice with cardiac-specific overexpression of the human cFLIP(L) gene. Our results demonstrated that the cFLIP(+/-) mice were susceptible to cardiac hypertrophy and fibrosis through inhibition of mitogen-activated protein kinase kinase-extracellular signal-regulated kinase 1/2 signaling, whereas the transgenic mice displayed the opposite phenotype in response to angiotensin II stimulation. These studies indicate that cFLIP protein is a crucial component of the signaling pathway involved in cardiac remodeling and heart failure. (Hypertension. 2010;56:1109-1117.) . Online Data Supplement
C1 [Li, Hongliang; Tang, Qi-Zhu; Yan, Ling; Bian, Zhou-Yan; Zhang, Yan] Wuhan Univ, Dept Cardiol, Renmin Hosp, Wuhan 430060, Peoples R China.
[Li, Hongliang; Tang, Qi-Zhu; Yan, Ling; Bian, Zhou-Yan; Zhang, Yan] Wuhan Univ, Cardiovasc Res Inst, Wuhan 430060, Peoples R China.
[Liu, Chen] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Cardiol, Guangzhou 510275, Guangdong, Peoples R China.
[Moon, Mark; Chen, Manyin; Nghiem, Mai P.; Liu, Peter P.] Univ Toronto, Div Cardiol Heart & Stroke, Richard Lewar Ctr Excellence, Univ Hlth Network, Toronto, ON, Canada.
[Wang, Ai-Bing] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
RP Li, HL (reprint author), Wuhan Univ, Dept Cardiol, Renmin Hosp, JieFang Rd 238, Wuhan 430060, Peoples R China.
EM lihl@whu.edu.cn; peter.liu@utoronto.ca
FU Heart and Stroke Foundation of Ontario; Canadian Institutes of Health
Research; National Natural Science Foundation of China [30900524,
30972954]; Support Program for Disciplinary Leaders in Wuhan
[200951830561]; Fundamental Research Funds for the Central Universities
[3081013]; National Basic Research Program of China [2011CB503902]
FX This study was supported in part by grants from the Heart and Stroke
Foundation of Ontario, and the Canadian Institutes of Health Research,
and by the National Natural Science Foundation of China (grants 30900524
and 30972954) and supported by the Support Program for Disciplinary
Leaders in Wuhan (200951830561), the Fundamental Research Funds for the
Central Universities (3081013), and the National Basic Research Program
of China grant 2011CB503902.
NR 0
TC 19
Z9 19
U1 0
U2 0
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 2010
VL 56
IS 6
BP 1109
EP U221
DI 10.1161/HYPERTENSIONAHA.110.157412
PG 25
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 681KA
UT WOS:000284309800029
PM 20975036
ER
PT J
AU Koh, KK
Sakuma, I
Quon, MJ
AF Koh, Kwang Kon
Sakuma, Ichiro
Quon, Michael J.
TI Role of Renin-Angiotensin System Blockades in Reciprocal Relationship
Between Insulin Resistance and Endothelial Dysfunction
SO HYPERTENSION
LA English
DT Letter
ID ACTIVATION
C1 [Koh, Kwang Kon] Gachon Univ, Gil Hosp, Div Cardiol, Inchon, South Korea.
[Sakuma, Ichiro] Hokko Mem Clin, Dept Cardiovasc Med, Sapporo, Hokkaido, Japan.
[Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
RP Koh, KK (reprint author), Gachon Univ, Gil Hosp, Div Cardiol, Inchon, South Korea.
OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707
NR 5
TC 3
Z9 3
U1 0
U2 1
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 2010
VL 56
IS 6
BP E169
EP E169
DI 10.1161/HYPERTENSIONAHA.110.161869
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 681KA
UT WOS:000284309800001
PM 21059993
ER
PT J
AU Yao, JH
Chowdhury, AS
Aman, J
Summers, RM
AF Yao, Jianhua
Chowdhury, Ananda S.
Aman, Javed
Summers, Ronald M.
TI Reversible Projection Technique for Colon Unfolding
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Biomedical image processing
ID CT COLONOGRAPHY; VIRTUAL DISSECTION; VISUALIZATION; DEFORMATION
AB Colon unfolding provides an efficient way to navigate the colon in computed tomographic colonography (CTC). Most existing unfolding techniques only compute forward projections. When radiologists find abnormalities or conduct measurements on the unfolded view (which is often quicker and easier), it is difficult to locate the corresponding region on the 3-D view for further examination (which is more accurate and reliable). To address this, we propose a reversible projection technique for colon unfolding. The method makes use of advanced algorithms including rotation-minimizing frames, recursive ring sets, mesh skinning, and cylindrical projection. Both forward and reverse mapping can be computed for points on the colon surface. Therefore, it allows for detecting and measuring polyps on the unfolded view and mapping them back to the 3-D surface. We generated realistic colon simulation data incorporating most colon characteristics, such as curved centerline, variable distention, haustral folds, teniae coli, and colonic polyps. Our method was tested on both simulated data and data from 110 clinical CTC studies. The results showed submillimeter accuracy in simulated data and -0.23 +/- 1.67 mm in the polyp measurement using clinical CTC data. The major contributions of our technique are: 1) the use of a recursive ring set method to solve the centerline and surface correspondence problem; 2) reverse transformation from the unfolded view to the 3-D view; and 3) quantitative validation using a realistic colon simulation and clinical CTC polyp measurement.
C1 [Yao, Jianhua; Chowdhury, Ananda S.; Aman, Javed; Summers, Ronald M.] NIH, Bethesda, MD 20892 USA.
RP Yao, JH (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM jyao@cc.nih.gov; ananda.chowdhury@gmail.com
FU National Institutes of Health, Clinical Center
FX Manuscript received November 13, 2009; revised January 30, 2010, March
20, 2010, and May 10, 2010; accepted May 12, 2010. Date of publication
June 10, 2010; date of current version November 17, 2010. This work was
supported in part by the Intramural Research Program of the National
Institutes of Health, Clinical Center. Asterisk indicates corresponding
author.
NR 25
TC 8
Z9 8
U1 0
U2 1
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 2010
VL 57
IS 12
BP 2861
EP 2869
DI 10.1109/TBME.2010.2052255
PG 9
WC Engineering, Biomedical
SC Engineering
GA 681YH
UT WOS:000284360100008
PM 20542756
ER
PT J
AU Yang, HC
Yin, JC
Hu, CH
Cannata, J
Zhou, QF
Zhang, J
Chen, ZP
Shung, KK
AF Yang, Hao-Chung
Yin, Jiechen
Hu, Changhong
Cannata, Jonathan
Zhou, Qifa
Zhang, Jun
Chen, Zhongping
Shung, K. Kirk
TI A Dual-Modality Probe Utilizing Intravascular Ultrasound and Optical
Coherence Tomography for Intravascular Imaging Applications
SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL
LA English
DT Article
ID MR-ANGIOGRAPHY; SPIRAL CT; STENOSIS; PLAQUE; IVUS
AB We have developed a dual-modality biomedical imaging probe utilizing intravascular ultrasound (IVUS) and optical coherence tomography (OCT). It consists of an OCT probe, a miniature ultrasonic transducer and a fixed mirror. The mirror was mounted at the head of the hybrid probe 45 relative to the light and the ultrasound beams to change their propagation directions. The probe was designed to be able to cover a larger area in blood vessel by IVUS and then visualize a specific point at a much finer image resolution using OCT. To demonstrate both its feasibility and potential clinical applications, we used this ultrasound-guide OCT probe to image a rabbit aorta in vitro. The results offer convincing evidence that the complementary natures of these two modalities may yield beneficial results that could not have otherwise been obtained.
C1 [Yang, Hao-Chung; Hu, Changhong; Cannata, Jonathan; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, NIH, Transducer Resource Ctr, Los Angeles, CA 90089 USA.
[Yang, Hao-Chung; Hu, Changhong; Cannata, Jonathan; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
[Yin, Jiechen; Zhang, Jun; Chen, Zhongping] Univ Calif Irvine, Beckman Laser Inst, Irvine, CA USA.
[Yin, Jiechen; Zhang, Jun; Chen, Zhongping] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA USA.
RP Yang, HC (reprint author), Univ So Calif, NIH, Transducer Resource Ctr, Los Angeles, CA 90089 USA.
EM yangh@usc.edu
RI Zhang, Jun/A-1801-2014
FU NIH [P41-EB2182, CA-91717, EB-1090]; U.S. Air Force Office of Scientific
Research [FA9550-08-1-0384]
FX This work is based on research supported by NIH (P41-EB2182, CA-91717,
EB-1090) and the U.S. Air Force Office of Scientific Research, Medical
Free-Electron Laser Program FA9550-08-1-0384.
NR 18
TC 24
Z9 26
U1 0
U2 9
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0885-3010
EI 1525-8955
J9 IEEE T ULTRASON FERR
JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control
PD DEC
PY 2010
VL 57
IS 12
BP 2839
EP 2843
DI 10.1109/TUFFC.2010.1758
PG 5
WC Acoustics; Engineering, Electrical & Electronic
SC Acoustics; Engineering
GA 695GR
UT WOS:000285359100025
PM 21156380
ER
PT J
AU Martin, MP
Borecki, IB
Zhang, ZY
Nguyen, L
Ma, DD
Gao, XJ
Qi, Y
Carrington, M
Rader, JS
AF Martin, Maureen P.
Borecki, Ingrid B.
Zhang, Zhengyan
Nguyen, Loan
Ma, Duanduan
Gao, Xiaojiang
Qi, Ying
Carrington, Mary
Rader, Janet S.
TI HLA-Cw group 1 ligands for KIR increase susceptibility to invasive
cervical cancer
SO IMMUNOGENETICS
LA English
DT Article
DE Cervical neoplasia; HPV; HLA; KIR
ID ANTIGEN CLASS-I; HUMAN-PAPILLOMAVIRUS INFECTION; POPULATION
STRATIFICATION; NEOPLASIA; ASSOCIATION; DISEASE; ALLELES; RISK;
POLYMORPHISMS; EXPRESSION
AB Inherited genetic polymorphisms within immune response genes have been shown to associate with risk of invasive cervical cancer (ICC) and its immediate precursor, cervical intraepithelial neoplasia grade 3. Here, we used the transmission/disequilibrium test to detect disease-liability alleles and investigate haplotype transmission of KIR and HLA class I polymorphisms in a large family-based population of women with cervical cancer and their biological parents (359 trios). The effect of distinct human papillomavirus types was also explored. HLA-Cw group 1 (HLA-Cw alleles with asparagine at position 80), which serves as ligand for certain killer immunoglobulin-like receptors (KIR), was significantly overtransmitted in women with ICC (P = 0.04), and particularly in the subgroup of women infected with high risk HPV16 or 18 subtypes (P = 0.008). These data support the involvement of the HLA-C locus in modulating the risk of cervical neoplasia perhaps through its function as ligands for KIR, but functional studies are essential to confirm this hypothesis.
C1 [Martin, Maureen P.; Gao, Xiaojiang; Qi, Ying; Carrington, Mary] NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Zhang, Zhengyan; Nguyen, Loan; Rader, Janet S.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA.
[Carrington, Mary] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA.
[Carrington, Mary] Harvard Univ, Boston, MA 02114 USA.
[Borecki, Ingrid B.; Ma, Duanduan; Rader, Janet S.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
RP Rader, JS (reprint author), Med Coll Wisconsin, Dept Obstet & Gynecol, Milwaukee, WI 53226 USA.
EM jrader@mcw.edu
FU National Cancer Institute [5R01CA094141, 5R01CA095713]; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]; NIH,
National Cancer Institute, Center for Cancer Research
FX This work was supported by National Cancer Institute grants 5R01CA094141
and 5R01CA095713. This project has been funded in whole or in part with
federal funds from the National Cancer Institute, National Institutes of
Health, under Contract No. HHSN261200800001E. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. This research was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 33
TC 18
Z9 19
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0093-7711
J9 IMMUNOGENETICS
JI Immunogenetics
PD DEC
PY 2010
VL 62
IS 11-12
BP 761
EP 765
DI 10.1007/s00251-010-0477-5
PG 5
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 678YW
UT WOS:000284120700006
PM 20857097
ER
PT J
AU Chakravarty, S
AF Chakravarty, S.
TI Immunological underpinnings in the development of an attenuated
sporozoite vaccine to prevent and eliminate Plasmodium falciparum
malaria
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Congress of the British-Society-for-Immunology
CY DEC 06-10, 2010
CL Liverpool, ENGLAND
SP British Soc Immunol
C1 [Chakravarty, S.] Sanaria Inc, Attenuated Sporozoite Vaccine Lab, Rockville, MD USA.
[Chakravarty, S.] Sanaria Inc, Clin Dev Team, Rockville, MD USA.
[Chakravarty, S.] USN, Med Res Ctr, US Mil Malaria Vaccine Program, Silver Spring, MD USA.
[Chakravarty, S.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
[Chakravarty, S.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Chakravarty, S.] LUMC, Leiden Malaria Res Grp, Leiden, Netherlands.
[Chakravarty, S.] Columbia Univ, Med Ctr, New York, NY USA.
[Chakravarty, S.] Prot Potential LLC, Rockville, MD USA.
[Chakravarty, S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD DEC
PY 2010
VL 131
SU 1
BP 9
EP 9
PG 1
WC Immunology
SC Immunology
GA 689XL
UT WOS:000284964100024
ER
PT J
AU Hasnain, SZ
Evans, CM
Roy, M
Dickey, B
Wilson, M
Wynn, T
Grencis, RK
Thornton, DJ
AF Hasnain, S. Z.
Evans, C. M.
Roy, M.
Dickey, B.
Wilson, M.
Wynn, T.
Grencis, R. K.
Thornton, D. J.
TI Immunity to the enteric nematode Trichuris muris is dependent on the
Muc5ac mucin
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Congress of the British-Society-for-Immunology
CY DEC 06-10, 2010
CL Liverpool, ENGLAND
SP British Soc Immunol
C1 [Hasnain, S. Z.; Thornton, D. J.] Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester, Lancs, England.
[Hasnain, S. Z.] Univ Manchester, Manchester Immunol Grp, Manchester, Lancs, England.
[Evans, C. M.; Roy, M.; Dickey, B.] Univ Texas MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX 77030 USA.
[Wilson, M.] Natl Inst Med Res, Div Mol Immunol, London NW7 1AA, England.
[Wynn, T.] NIAID, Immunopathogenesis Sect, NIH, Bethesda, MD 20892 USA.
[Grencis, R. K.] Manchester Immunol Grp, Manchester, Lancs, England.
RI Hasnain, Sumaira /C-5047-2013; Hasnain, Sumaira/N-3412-2014
OI Hasnain, Sumaira/0000-0001-8577-8628
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD DEC
PY 2010
VL 131
SU 1
BP 49
EP 49
PG 1
WC Immunology
SC Immunology
GA 689XL
UT WOS:000284964100128
ER
PT J
AU Schewitz-Bowers, LP
Wei, L
Nussenblatt, RB
Dick, AD
Lee, RWJ
AF Schewitz-Bowers, L. P.
Wei, L.
Nussenblatt, R. B.
Dick, A. D.
Lee, R. W. J.
TI Dichotomy of IL-10 and IL-17 defines glucocorticoid responses in CD4+ T
cells
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Congress of the British-Society-for-Immunology
CY DEC 06-10, 2010
CL Liverpool, ENGLAND
SP British Soc Immunol
C1 [Schewitz-Bowers, L. P.; Dick, A. D.; Lee, R. W. J.] Univ Bristol, Sch Clin Sci, Bristol, Avon, England.
[Wei, L.; Nussenblatt, R. B.] NEI, NIH, Bethesda, MD 20892 USA.
RI Wei, Lai/D-1088-2014
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD DEC
PY 2010
VL 131
SU 1
BP 91
EP 92
PG 2
WC Immunology
SC Immunology
GA 689XL
UT WOS:000284964100278
ER
PT J
AU Comer, JE
Sturdevant, DE
Carmody, AB
Virtaneva, K
Gardner, D
Long, D
Rosenke, R
Porcella, SF
Hinnebusch, BJ
AF Comer, Jason E.
Sturdevant, Daniel E.
Carmody, Aaron B.
Virtaneva, Kimmo
Gardner, Donald
Long, Dan
Rosenke, Rebecca
Porcella, Stephen F.
Hinnebusch, B. Joseph
TI Transcriptomic and Innate Immune Responses to Yersinia pestis in the
Lymph Node during Bubonic Plague
SO INFECTION AND IMMUNITY
LA English
DT Article
ID A STREPTOCOCCUS TRANSCRIPTOME; PRIMARY PNEUMONIC PLAGUE;
T-CELL-ACTIVATION; V-ANTIGEN; MACROPHAGE ACTIVATION; PASTEURELLA PESTIS;
III SECRETION; RAT MODEL; VIRULENCE; SYSTEM
AB A delayed inflammatory response is a prominent feature of infection with Yersinia pestis, the agent of bubonic and pneumonic plague. Using a rat model of bubonic plague, we examined lymph node histopathology, transcriptome, and extracellular cytokine levels to broadly characterize the kinetics and extent of the host response to Y. pestis and how it is influenced by the Yersinia virulence plasmid (pYV). Remarkably, dissemination and multiplication of wild-type Y. pestis during the bubonic stage of disease did not induce any detectable gene expression or cytokine response by host lymph node cells in the developing bubo. Only after systemic spread had led to terminal septicemic plague was a transcriptomic response detected, which included upregulation of several cytokine, chemokine, and other immune response genes. Although an initial intracellular phase of Y. pestis infection has been postulated, a Th1-type cytokine response associated with classical activation of macrophages was not observed during the bubonic stage of disease. However, elevated levels of interleukin-17 (IL-17) were present in infected lymph nodes. In the absence of pYV, sustained recruitment to the lymph node of polymorphonuclear leukocytes (PMN, or neutrophils), the major IL-17 effector cells, correlated with clearance of infection. Thus, the ability to counteract a PMN response in the lymph node appears to be a major in vivo function of the Y. pestis virulence plasmid.
C1 [Comer, Jason E.; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Sturdevant, Daniel E.; Virtaneva, Kimmo; Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
[Carmody, Aaron B.] NIAID, Flow Cytometry Unit, Res Technol Sect, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
[Gardner, Donald; Long, Dan; Rosenke, Rebecca] NIAID, Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Hinnebusch, BJ (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM jhinnebusch@niaid.nih.gov
FU Division of Intramural Research, NIAID, NIH
FX This work was supported by the Division of Intramural Research, NIAID,
NIH.
NR 71
TC 32
Z9 34
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD DEC
PY 2010
VL 78
IS 12
BP 5086
EP 5098
DI 10.1128/IAI.00256-10
PG 13
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 680DW
UT WOS:000284213600012
PM 20876291
ER
PT J
AU Whitman, TJ
Herlihy, RK
Schlett, CD
Murray, PR
Grandits, GA
Ganesan, A
Brown, M
Mancuso, JD
Adams, WB
Tribble, DR
AF Whitman, Timothy J.
Herlihy, Rachel K.
Schlett, Carey D.
Murray, Patrick R.
Grandits, Greg A.
Ganesan, Anuradha
Brown, Maya
Mancuso, James D.
Adams, William B.
Tribble, David R.
TI Chlorhexidine-Impregnated Cloths to Prevent Skin and Soft-Tissue
Infection in Marine Recruits: A Cluster-Randomized, Double-Blind,
Controlled Effectiveness Trial
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Article
ID RESISTANT STAPHYLOCOCCUS-AUREUS; INTENSIVE-CARE-UNIT; BLOOD-STREAM
INFECTIONS; INTRANASAL MUPIROCIN; CLINICAL-TRIAL; NASAL CARRIAGE;
COLONIZATION; REDUCE; ERADICATION; SOLDIERS
AB BACKGROUND. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes skin and soft-tissue infection (SSTI) in military recruits.
OBJECTIVE. To evaluate the effectiveness of 2% chlorhexidine gluconate (CHG)-impregnated cloths in reducing rates of SSTI and S. aureus colonization among military recruits.
DESIGN. A cluster-randomized (by platoon), double-blind, controlled effectiveness trial.
SETTING. Marine Officer Candidate School, Quantico, Virginia, 2007.
PARTICIPANTS. Military recruits.
INTERVENTION. Application of CHG-impregnated or control (Comfort Bath; Sage) cloths applied over entire body thrice weekly.
MEASUREMENTS. Recruits were monitored daily for SSTI. Baseline and serial nasal and/or axillary swabs were collected to assess S. aureus colonization.
RESULTS. Of 1,562 subjects enrolled, 781 (from 23 platoons) underwent CHG-impregnated cloth application and 781 (from 21 platoons) underwent control cloth application. The rate of compliance (defined as application of 50% or more of wipes) at 2 weeks was similar (CHG group, 63%; control group, 67%) and decreased over the 6-week period. The mean 6-week SSTI rate in the CHG-impregnated cloth group was 0.094, compared with 0.071 in the control group (analysis of variance model rate difference, 0.025 +/- 0.016; P = .14). At baseline, 43% of subjects were colonized with methicillin-susceptible S. aureus (MSSA), and 2.1% were colonized with MRSA. The mean incidence of colonization with MSSA was 50% and 61% (P = .026) and with MRSA was 2.6% and 6.0% (P = .034) for the CHG-impregnated and control cloth groups, respectively.
CONCLUSIONS. CHG-impregnated cloths applied thrice weekly did not reduce rates of SSTI among recruits. S. aureus colonization rates increased in both groups but to a lesser extent in those assigned to the CHG-impregnated cloth intervention. Antecedent S. aureus colonization was not a risk factor for SSTI. Additional studies are needed to identify effective measures for preventing SSTI among military recruits.
C1 [Whitman, Timothy J.] Natl Naval Med Ctr, Dept Internal Med, Div Infect Dis, Bethesda, MD USA.
[Herlihy, Rachel K.; Schlett, Carey D.; Ganesan, Anuradha; Brown, Maya; Mancuso, James D.; Tribble, David R.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD USA.
[Murray, Patrick R.] NIH, Bethesda, MD 20892 USA.
[Adams, William B.] Marine Corps Base, Quantico, VA USA.
[Grandits, Greg A.] Univ Minnesota, Div Biostat, Minneapolis, MN USA.
RP Whitman, TJ (reprint author), Natl Naval Med Ctr, Dept Internal Med, Div Infect Dis, 8901 Rockville Pike, Bethesda, MD USA.
EM Timothy.Whitman@med.navy.mil
FU Infectious Disease Clinical Research Program [IDCRP-001]; Department of
Defense; National Institute of Allergy and Infectious Diseases, National
Institutes of Health [Y1-AI-5072]
FX Support for this work (IDCRP-001) was provided by the Infectious Disease
Clinical Research Program, a Department of Defense program executed
through the Uniformed Services University. This project was funded by
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health, under Inter-Agency Agreement Y1-AI-5072.
NR 36
TC 26
Z9 26
U1 0
U2 3
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD DEC
PY 2010
VL 31
IS 12
BP 1207
EP 1215
DI 10.1086/657136
PG 9
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 675PJ
UT WOS:000283842300001
PM 21028984
ER
PT J
AU Belay, ED
Schonberger, LB
Brown, P
Priola, SA
Chesebro, B
Will, RG
Asher, DM
AF Belay, Ermias D.
Schonberger, Lawrence B.
Brown, Paul
Priola, Suzette A.
Chesebro, Bruce
Will, Robert G.
Asher, David M.
TI Disinfection and Sterilization of Prion-Contaminated Medical Instruments
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Letter
ID CREUTZFELDT-JAKOB-DISEASE; DECONTAMINATION; ENCEPHALOPATHIES;
TRANSMISSION; INFECTIVITY; STEEL
C1 [Belay, Ermias D.; Schonberger, Lawrence B.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Priola, Suzette A.; Chesebro, Bruce] NIH, Hamilton, MT USA.
[Asher, David M.] US FDA, Silver Spring, MD USA.
[Will, Robert G.] United Kingdom Natl Creutzfeldt Jakob Dis Surveil, Edinburgh, Midlothian, Scotland.
RP Belay, ED (reprint author), 1600 Clifton Rd, Atlanta, GA 30333 USA.
EM EBelay@cdc.gov
RI Belay, Ermias/A-8829-2013
NR 15
TC 5
Z9 5
U1 1
U2 8
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD DEC
PY 2010
VL 31
IS 12
BP 1304
EP 1306
DI 10.1086/657579
PG 3
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 675PJ
UT WOS:000283842300018
PM 21047181
ER
PT J
AU Smith, LH
Wilbur, WJ
AF Smith, Larry H.
Wilbur, W. John
TI Finding related sentence pairs in MEDLINE
SO INFORMATION RETRIEVAL
LA English
DT Article
DE Machine learning; Related sentences
ID TRICHLOROETHYLENE; ALGORITHMS; RETRIEVAL
AB We explore the feasibility of automatically identifying sentences in different MEDLINE abstracts that are related in meaning. We compared traditional vector space models with machine learning methods for detecting relatedness, and found that machine learning was superior. The Huber method, a variant of Support Vector Machines which minimizes the modified Huber loss function, achieves 73% precision when the score cutoff is set high enough to identify about one related sentence per abstract on average. We illustrate how an abstract viewed in PubMed might be modified to present the related sentences found in other abstracts by this automatic procedure.
C1 [Smith, Larry H.; Wilbur, W. John] Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA.
RP Smith, LH (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM lsmith@ncbi.nlm.nih.gov
FU NIH; NLM; NCBI
FX This research was supported by the Intramural Research Program of the
NIH, NLM, and NCBI.
NR 35
TC 6
Z9 6
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1386-4564
J9 INFORM RETRIEVAL
JI Inf. Retr.
PD DEC
PY 2010
VL 13
IS 6
BP 601
EP 617
DI 10.1007/s10791-010-9126-8
PG 17
WC Computer Science, Information Systems
SC Computer Science
GA 682TF
UT WOS:000284425200001
ER
PT J
AU Luo, SJ
Johnson, WE
O'Brien, SJ
AF Luo, Shu-Jin
Johnson, Warren E.
O'Brien, Stephen J.
TI Applying molecular genetic tools to tiger conservation
SO INTEGRATIVE ZOOLOGY
LA English
DT Review
DE conservation genetics; mitochondrial DNA; microsatellite; subspecies;
tiger
ID PANTHERA-TIGRIS; DOMESTIC CAT; POPULATION-STRUCTURE; NUCLEAR GENOME;
AMUR TIGER; DNA; MICROSATELLITES; AMPLIFICATION; RADIATION; FELIDAE
AB The utility of molecular genetic approaches in conservation of endangered taxa is now commonly recognized. Over the past decade, conservation genetic analyses based on mitochondrial DNA sequencing and microsatellite genotyping have provided powerful tools to resolve taxonomy uncertainty of tiger subspecies, to define conservation units, to reconstruct phylogeography and demographic history, to examine the genetic ancestry of extinct subspecies, to assess population genetic status non-invasively, and to verify genetic background of captive tigers worldwide. The genetic status of tiger subspecies and populations and implications for developing strategies for the survival of this charismatic species both in situ and ex situ are discussed.
C1 [Luo, Shu-Jin] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China.
[Johnson, Warren E.; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
RP Luo, SJ (reprint author), Peking Univ, Sch Life Sci, 5 Yiheyuan Rd, Beijing 100871, Peoples R China.
EM luo.shujin@pku.edu.cn
RI Johnson, Warren/D-4149-2016
OI Johnson, Warren/0000-0002-5954-186X
NR 47
TC 7
Z9 7
U1 7
U2 66
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1749-4877
EI 1749-4869
J9 INTEGR ZOOL
JI Integr. Zool.
PD DEC
PY 2010
VL 5
IS 4
BP 351
EP 362
DI 10.1111/j.1749-4877.2010.00222.x
PG 12
WC Zoology
SC Zoology
GA 688LZ
UT WOS:000284852100008
PM 21392353
ER
PT J
AU Stockwin, LH
Yu, SX
Borgel, S
Hancock, C
Wolfe, TL
Phillips, LR
Hollingshead, MG
Newton, DL
AF Stockwin, Luke H.
Yu, Sherry X.
Borgel, Suzanne
Hancock, Chad
Wolfe, Tracy L.
Phillips, Lawrence R.
Hollingshead, Melinda G.
Newton, Dianne L.
TI Sodium dichloroacetate selectively targets cells with defects in the
mitochondrial ETC
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE glycolysis; mitochondria; dichloroacetate; electron transport chain;
pyruvate dehydrogenase kinase
ID CONTROLLED CLINICAL-TRIAL; CONGENITAL LACTIC-ACIDOSIS; INHIBITS CANCER
GROWTH; INDUCIBLE FACTOR-I; PYRUVATE-DEHYDROGENASE; APOPTOSIS;
INDUCTION; HYPOXIA; RESPIRATION; GLYCOLYSIS
AB The "Warburg effect," also termed aerobic glycolysis, describes the increased reliance of cancer cells on glycolysis for ATP production, even in the presence of oxygen. Consequently, there is continued interest in inhibitors of glycolysis as cancer therapeutics. One example is dichloroacetate (DCA), a pyruvate mimetic that stimulates oxidative phosphorylation through inhibition of pyruvate dehydrogenase kinase. In this study, the mechanistic basis for DCA anti-cancer activity was re-evaluated in vitro using biochemical, cellular and proteomic approaches. Results demonstrated that DCA is relatively inactive (IC(50) >= 17 mM, 48 hr), induces apoptosis only at high concentrations (>= 25 mM, 48 hr) and is not cancer cell selective. Subsequent 2D-PAGE proteomic analysis confirmed DCA-induced growth suppression without apoptosis induction. Furthermore, DCA depolarizes mitochondria and promotes reactive oxygen species (ROS) generation in all cell types. However, DCA was found to have selective activity against rho(0) cells [mitochondrial DNA (mtDNA) deficient] and to synergize with 2-deoxyglucose in complex IV deficient HCT116 p53(-/-) cells. DCA also synergized in vitro with cisplatin and topotecan, two antineoplastic agents known to damage mitochondrial DNA. These data suggest that in cells "hardwired" to selectively utilize glycolysis for ATP generation (e.g., through mtDNA mutations), the ability of DCA to force oxidative phosphorylation confers selective toxicity. In conclusion, although we provide a mechanism distinct from that reported previously, the ability of DCA to target cell lines with defects in the electron transport chain and to synergize with existing chemotherapeutics supports further preclinical development.
C1 [Stockwin, Luke H.; Yu, Sherry X.; Borgel, Suzanne; Hancock, Chad; Wolfe, Tracy L.; Newton, Dianne L.] SAIC Frederick Inc, Dev Therapeut Program, NCI Frederick, Biol Testing Branch, Frederick, MD 21702 USA.
[Phillips, Lawrence R.; Hollingshead, Melinda G.] Natl Canc Inst Frederick, Biol Testing Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD USA.
RP Newton, DL (reprint author), SAIC Frederick Inc, Dev Therapeut Program, NCI Frederick, Biol Testing Branch, Bldg 320,Room 9, Frederick, MD 21702 USA.
EM newtondianne@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Division of Cancer Treatment and Diagnosis of the
National Cancer Institute
FX Grant sponsor: This project has been funded in whole or in part with
federal funds from the National Cancer Institute, National Institutes of
Health; Grant number: HHSN261200800001E; Grant sponsor: This research
was supported [in part] by the Developmental Therapeutics Program in the
Division of Cancer Treatment and Diagnosis of the National Cancer
Institute
NR 40
TC 72
Z9 77
U1 2
U2 17
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD DEC 1
PY 2010
VL 127
IS 11
BP 2510
EP 2519
DI 10.1002/ijc.25499
PG 10
WC Oncology
SC Oncology
GA 672TJ
UT WOS:000283609500003
PM 20533281
ER
PT J
AU Ma, JD
Nguyen, ET
Tsunoda, SM
Greenberg, HE
Gorski, JC
Penzak, SR
Lee, LS
AF Ma, J. D.
Nguyen, E. T.
Tsunoda, S. M.
Greenberg, H. E.
Gorski, J. C.
Penzak, S. R.
Lee, L. S.
TI Assessment of oral midazolam limited sampling strategies to predict area
under the concentration time curve (AUC) during cytochrome P450 (CYP) 3A
baseline, inhibition and induction or activation
SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
DE CYP3A; limited sampling strategy; midazolam; phenotyping
ID IN-VIVO PROBE; PLASMA-CONCENTRATIONS; GRAPEFRUIT JUICE;
HEALTHY-SUBJECTS; DRUG; ADULTS; KETOCONAZOLE; PERFORMANCE; PLECONARIL;
BIOMARKER
AB A previous study reported a 2- and 3-timepoint limited sampling strategy (LSS) model accurately predicted oral midazolam area under the concentration time curve (AUC), and thus cytochrome P450 (CYP) 3A activity. Objective: This study evaluated whether the LSS models predict midazolam AUC during CYP3A baseline, inhibition and induction/activation. Materials and methods: Plasma midazolam concentrations from 106 healthy adults from 6 published studies were obtained where oral midazolam was co-administered alone or with ketoconazole, double-strength grapefruit juice, Ginkgo biloba extract, pleconaril, or rifampin. Observed and predicted midazolam AUCs were determined. Bias and precision of the LSS models were determined. Results: Contrasting results were observed for the 2- and 3-timepoint LSS models in accurately predicting midazolam AUC during baseline CYP3A conditions. With the exception of 1 study (single dose, double-strength grapefruit juice), the 2- and 3-timepoint LSS models did not accurately predict midazolam AUC during conditions of CYP3A inhibition and induction/activation. Conclusion: The previously reported 2- and 3-timepoint oral midazolam LSS models are not applicable to the evaluated conditions of CYP3A baseline, inhibition, and induction/activation.
C1 [Ma, J. D.; Nguyen, E. T.; Tsunoda, S. M.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
[Greenberg, H. E.] Clinilabs, New York, NY USA.
[Gorski, J. C.] Mylan Pharmaceut Inc, Morgantown, WV USA.
[Penzak, S. R.] NIH, Dept Pharm, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Ma, JD (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, 9500 Gilman Dr,MC 0714, La Jolla, CA 92093 USA.
EM joema@ucsd.edu
FU NIH [T32 RR023254]
FX We acknowledge Dr. Stephen D. Hall for providing the rifampin/midazolam
data. Supported in part by the NIH Institutional Research Training Grant
(T32 RR023254). Presented in part at the 2010 Annual Meeting of the
American Society for Clinical Pharmacology and Therapeutics, Atlanta,
GA, March 2010.
NR 31
TC 6
Z9 7
U1 0
U2 3
PU DUSTRI-VERLAG DR KARL FEISTLE
PI DEISENHOFEN-MUENCHEN
PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY
SN 0946-1965
J9 INT J CLIN PHARM TH
JI Int. J. Clin. Pharmacol. Ther.
PD DEC
PY 2010
VL 48
IS 12
BP 847
EP 853
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 695KK
UT WOS:000285368800008
PM 21084040
ER
PT J
AU Giedd, J
AF Giedd, J.
TI Neuroimaging of human development and neurodevelopmental disorders
SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
LA English
DT Meeting Abstract
CT 18th Biennial Meeting of the
International-Society-for-Developmental-Neuroscience
CY JUN 06-09, 2010
CL Estoril, PORTUGAL
SP Int Soc Dev Neurosci
C1 [Giedd, J.] NIMH, Bethesda, MD 20892 USA.
RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0736-5748
J9 INT J DEV NEUROSCI
JI Int. J. Dev. Neurosci.
PD DEC
PY 2010
VL 28
IS 8
SI SI
BP 640
EP 641
DI 10.1016/j.ijdevneu.2010.07.008
PG 2
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA 689YS
UT WOS:000284967600007
ER
PT J
AU Sun, JX
Zhang, Z
Zhang, C
Sakata, K
Lu, B
Sun, QQ
AF Sun, J. X.
Zhang, Z.
Zhang, C.
Sakata, K.
Lu, B.
Sun, Q. Q.
TI BDNF promoter-IV knock-in mice as a novel animal model for studying
shared mechanisms of Rett and autism
SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
LA English
DT Meeting Abstract
CT 18th Biennial Meeting of the
International-Society-for-Developmental-Neuroscience
CY JUN 06-09, 2010
CL Estoril, PORTUGAL
SP Int Soc Dev Neurosci
DE Rett; Autism; BDNF; GABA
C1 [Sun, J. X.; Zhang, Z.; Zhang, C.; Sun, Q. Q.] Univ Wyoming, Laramie, WY 82071 USA.
[Sakata, K.; Lu, B.] NICHD, Bethesda, MD USA.
RI Lu, Bai/A-4018-2012
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0736-5748
J9 INT J DEV NEUROSCI
JI Int. J. Dev. Neurosci.
PD DEC
PY 2010
VL 28
IS 8
SI SI
BP 689
EP 690
DI 10.1016/j.ijdevneu.2010.07.143
PG 2
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA 689YS
UT WOS:000284967600140
ER
PT J
AU Davis, MI
Puhl, HL
AF Davis, M. I.
Puhl, H. L.
TI The Nr4a1-EGFP mouse as a functional sensor of development and activity
in the extended striatum
SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
LA English
DT Meeting Abstract
CT 18th Biennial Meeting of the
International-Society-for-Developmental-Neuroscience
CY JUN 06-09, 2010
CL Estoril, PORTUGAL
SP Int Soc Dev Neurosci
DE Striatum patch-matrix; BDNF; Dopamine
C1 [Davis, M. I.; Puhl, H. L.] NIAAA, NIH, Bethesda, MD 20892 USA.
RI Davis, Margaret/F-4165-2010
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0736-5748
J9 INT J DEV NEUROSCI
JI Int. J. Dev. Neurosci.
PD DEC
PY 2010
VL 28
IS 8
SI SI
BP 694
EP 694
DI 10.1016/j.ijdevneu.2010.07.152
PG 1
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA 689YS
UT WOS:000284967600149
ER
PT J
AU Tanofsky-Kraff, M
Wilfley, DE
Young, JF
Mufson, L
Yanovski, SZ
Glasofer, DR
Salaita, CG
Schvey, NA
AF Tanofsky-Kraff, Marian
Wilfley, Denise E.
Young, Jami F.
Mufson, Laura
Yanovski, Susan Z.
Glasofer, Deborah R.
Salaita, Christine G.
Schvey, Natasha A.
TI A Pilot Study of Interpersonal Psychotherapy for Preventing Excess
Weight Gain in Adolescent Girls at-risk for Obesity
SO INTERNATIONAL JOURNAL OF EATING DISORDERS
LA English
DT Article
DE obesity prevention; interpersonal psychotherapy; adolescence; loss of
control eating
ID BINGE-EATING DISORDER; CONTROLLED-TRIAL; ADULT OBESITY; BODY-FAT;
OVERWEIGHT; CHILDREN; CHILDHOOD; EFFICACY; MODEL; INTERVENTION
AB Objective: Interpersonal psychotherapy (IPT) is effective at reducing binge episodes and inducing weight stabilization in obese adults with binge eating disorder.
Method: We piloted the administration of IPT to girls at-risk for excess weight gain (BMI 75(th)-97(th) percentile; IPT-WG) with and without loss of control (LOC) eating. Thirty-eight girls (12-17 years) were randomized to IPT-WG or a standard-of-care health education group.
Results: All 38 girls completed the programs and all follow-up visits through 6 months. Thirty-five of 38 returned for a complete assessment visit at 1 year. Among girls with baseline LOC (n = 20), those in IPT-WG experienced greater reductions in such episodes than girls in health education (p = .036). Regardless of LOC status, over 1 year girls in IPT-WG were less likely to increase their BMI as expected for their age and BMI percentile (p = .028).
Discussion: IPT-WG is feasible and acceptable to adolescent girls at-risk for adult obesity and may prevent excess weight gain over 1 year. (C) 2009 by Wiley Periodicals, Inc.
C1 [Tanofsky-Kraff, Marian; Schvey, Natasha A.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Tanofsky-Kraff, Marian; Yanovski, Susan Z.; Salaita, Christine G.; Schvey, Natasha A.] Eunice Kennedy Shriver Natl Inst Child Heath & Hu, Unit Growth & Obes, NIH, DHHS, Bethesda, MD USA.
[Wilfley, Denise E.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Young, Jami F.] Rutgers State Univ, Grad Sch Appl & Profess Psychol, Piscataway, NJ 08854 USA.
[Mufson, Laura; Glasofer, Deborah R.] Columbia Univ Coll Phys & Surg, Dept Psychiat, NY State Psychiat Inst, New York, NY 10032 USA.
[Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, NIH, DHHS, Bethesda, MD USA.
RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM mtanofsky@usuhs.mil
RI Young, Jami/A-1474-2011
FU NIH (NICHD) [Z01-HD-00641]; NIDDK [1R01DK080906-01A1]; USUHS [R072IC];
NCMHD
FX Supported by Z01-HD-00641 from NIH (Intramural Research Program of
NICHD); 1R01DK080906-01A1 from NIDDK; R072IC from USUHS; Supplemental
funding from NCMHD.
NR 45
TC 35
Z9 36
U1 4
U2 14
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0276-3478
J9 INT J EAT DISORDER
JI Int. J. Eating Disord.
PD DEC
PY 2010
VL 43
IS 8
BP 701
EP 706
DI 10.1002/eat.20773
PG 6
WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology
SC Psychology; Nutrition & Dietetics; Psychiatry
GA 684BX
UT WOS:000284523100004
PM 19882739
ER
PT J
AU Shomaker, LB
Tanofsky-Kraff, M
Elliott, C
Wolkoff, LE
Columbo, KM
Ranzenhofer, LM
Roza, CA
Yanovski, SZ
Yanovski, JA
AF Shomaker, Lauren B.
Tanofsky-Kraff, Marian
Elliott, Camden
Wolkoff, Laura E.
Columbo, Kelli M.
Ranzenhofer, Lisa M.
Roza, Caroline A.
Yanovski, Susan Z.
Yanovski, Jack A.
TI Salience of Loss of Control for Pediatric Binge Episodes: Does Size
Really Matter?
SO INTERNATIONAL JOURNAL OF EATING DISORDERS
LA English
DT Article
DE child; adolescent; binge eating; loss of control eating; obesity
ID EATING-DISORDER EXAMINATION; OVERWEIGHT CHILDREN; BULIMIC BEHAVIORS;
AFRICAN-AMERICAN; PUBERTAL CHANGES; OBJECTIVE BINGE; WEIGHT CONCERNS;
BODY-FAT; ADOLESCENTS; GIRLS
AB Objective: The subjective experience of loss of control (LOC) during eating, independent of overeating, may be a salient marker of disordered eating and risk for overweight in youth. However, few studies have directly tested this notion in an adequately powered sample.
Method: Three-hundred-sixty-seven youth (M +/- SD age = 12.7 +/- 2.8 y) were categorized as reporting objective binge eating (OBE; 12.5%), subjective binge eating (SBE; 11.4%), objective overeating without LOC (00; 18.5%), or no episodes (NE; 57.5%). Disordered eating attitudes, general psychopathology, and adiposity were assessed.
Results: Children with OBE and SBE generally did not differ in their disordered eating attitudes, emotional eating, eating in the absence of hunger, depressive and anxiety symptoms, or adiposity. However, both OBE and SBE youth had significantly greater disordered eating attitudes, emotional eating, eating in the absence of hunger, depressive and anxiety symptoms, and adiposity compared to those with OO or NE (ps < .05).
Discussion: For non-treatment-seeking youth, LOC during eating episodes, rather than episode size, appears to be the most salient marker of eating and weight problems. (C) 2009 by Wiley Periodicals, Inc.*
C1 [Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Elliott, Camden; Wolkoff, Laura E.; Columbo, Kelli M.; Ranzenhofer, Lisa M.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol MPS, Bethesda, MD 20814 USA.
[Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Elliott, Camden; Wolkoff, Laura E.; Columbo, Kelli M.; Ranzenhofer, Lisa M.; Roza, Caroline A.; Yanovski, Susan Z.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit 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), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol MPS, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM mtanofsky@usuhs.mil
OI Yanovski, Jack/0000-0001-8542-1637
FU NICHD, NIH [Z01-HD-00641]; NCMHD; OBSSR; USUHS [R072IC]; NICHD
[1F32HD056762]
FX Supported by Intramural Research Program, NIH, grant Z01-HD-00641 (to J.
Yanovski) from the NICHD, supplemental funding from NCMHD and OBSSR (to
J. Yanovski), USUHS grant R072IC (to M. Tanofsky-Kraff), and NICHD
National Research Service Award 1F32HD056762 (to L. Shomaker).
NR 52
TC 51
Z9 52
U1 1
U2 7
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0276-3478
J9 INT J EAT DISORDER
JI Int. J. Eating Disord.
PD DEC
PY 2010
VL 43
IS 8
BP 707
EP 716
DI 10.1002/eat.20767
PG 10
WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology
SC Psychology; Nutrition & Dietetics; Psychiatry
GA 684BX
UT WOS:000284523100005
PM 19827022
ER
PT J
AU Cook, MB
Akre, O
Forman, D
Madigan, MP
Richiardi, L
McGlynn, KA
AF Cook, Michael B.
Akre, Olof
Forman, David
Madigan, M. Patricia
Richiardi, Lorenzo
McGlynn, Katherine A.
TI A systematic review and meta-analysis of perinatal variables in relation
to the risk of testicular cancer-experiences of the son
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Review
DE Epidemiology; meta-analysis; pregnancy; review; systematic; testicular
neoplasms
ID GERM-CELL TUMORS; BIRTH-WEIGHT; UNITED-STATES; YOUNG MEN;
GESTATIONAL-AGE; INGUINAL-HERNIA; MATERNAL RECALL; MALES BORN;
CRYPTORCHIDISM; TESTIS
AB Background We undertook a systematic review and meta-analysis of perinatal variables in relation to testicular cancer risk, with a specific focus upon characteristics of the son.
Methods Literature databases Scopus, EMBASE, PubMed and Web of Science were searched using highly sensitive search strategies. Of 5865 references retrieved, 67 articles met the inclusion criteria, each of which was included in at least one perinatal analysis.
Results Random effects meta-analysis produced the following results for association with testicular cancer risk: birth weight [per kilogram, odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.88-1.01, I(2) = 12%], low birth weight (OR = 1.34, 95% CI 1.08-1.67, I(2) = 51%), high birth weight (OR = 1.05, 95% CI 0.96-1.14, I(2) = 0%), gestational age (per week, OR = 0.95, 95% CI 0.92-0.98, I(2) = 38%; low vs not, OR = 1.31, 95% CI 1.07-1.59, I(2) = 49%), cryptorchidism (OR = 4.30, 95% CI 3.62-5.11, I(2) = 44%), inguinal hernia (OR = 1.63, 95% CI 1.37-1.94, I(2) = 38%) and twinning (OR = 1.22, 95% CI 1.03-1.44, I(2) = 22%). Meta-analyses of the variables birth length, breastfeeding and neonatal jaundice did not provide evidence for an association with testicular cancer risk. When low birth weight was stratified by data ascertainment (record/registry vs self-report), only the category of self-report was indicative of an association. Meta-regression of data ascertainment (record/registry vs self-report) inferred that record-/registry-based studies were less supportive of an association with gestational age (per week = 0.97, 95% CI 0.94-1.00, I(2) = 29%; low vs not = 1.08, 95% CI 0.91-1.28, I(2) = 32%).
Conclusion In conclusion, this systematic review and meta-analysis finds evidence that cryptorchidism, inguinal hernia and twinning, and tentative evidence that birth weight and gestational age, are associated with risk of testicular cancer.
C1 [Cook, Michael B.; Madigan, M. Patricia; McGlynn, Katherine A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA.
[Akre, Olof] Karolinska Inst, Karolinska Sjukhuset, Stockholm, Sweden.
[Forman, David] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Canc Epidemiol Grp, Leeds, W Yorkshire, England.
[Richiardi, Lorenzo] Univ Turin, Dept Human Oncol & Biomed Sci, Canc Epidemiol Unit, Turin, Italy.
RP Cook, MB (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS,Suite 550,Room 5012, Rockville, MD 20852 USA.
EM cookmich@mail.nih.gov
RI Cook, Michael/A-5641-2009;
OI Cook, Michael/0000-0002-0533-7302; richiardi,
lorenzo/0000-0003-0316-9402
FU National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics
FX This research was funded by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics. The findings in this article reflect
the viewpoints of the authors and do not necessarily reflect the views
of the Department of Health and Human Services.
NR 101
TC 45
Z9 45
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD DEC
PY 2010
VL 39
IS 6
BP 1605
EP 1618
DI 10.1093/ije/dyq120
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 689TQ
UT WOS:000284952700029
PM 20660640
ER
PT J
AU Dou, ZH
Chen, RY
Xu, JH
Ma, Y
Jiao, JH
Durako, S
Zhao, Y
Zhao, DC
Fang, H
Zhang, FJ
AF Dou, Zhihui
Chen, Ray Y.
Xu, Jiahong
Ma, Ye
Jiao, Jin Hua
Durako, Stephen
Zhao, Yan
Zhao, Decai
Fang, Hua
Zhang, Fujie
TI Changing baseline characteristics among patients in the China National
Free Antiretroviral Treatment Program, 2002-09
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE China; HIV; national treatment program; baseline characteristics;
injection drug users; routine testing
ID HEPATITIS-C VIRUS; INJECTION-DRUG USERS; FORMER BLOOD-DONORS; RAPID
SCALE-UP; PLASMA/BLOOD DONORS; SOUTHERN CHINA; PUBLIC-HEALTH; HIV;
THERAPY; COINFECTION
AB Objective To improve HIV treatment in China by determining changes over time of patient characteristics (geographic, clinical and route of HIV infection) among patients enrolled in the China National Free Antiretroviral Treatment Program.
Methods Patients in the national treatment database from 1 June 2002 to 1 June 2009 were eligible. Patients were excluded if < 18 years old, not previously treatment-naive, missing initial treatment date or not initiated on triple drug therapy.
Results About 62 919 patients were included, located across 54.8% of counties/districts throughout mainland China; 86.4% were concentrated in 11.1% of counties/districts. Median age was 38 years, 41% female, 45.4% former plasma donors (FPDs), 33.9% sexually infected and 15.5% injection drug users (IDUs). Median baseline CD4 cell count was 129/mu l. In 2002, 100% of treated were FPDs with no CD4 cell counts. By 2009, 59% of the treated were sexually infected and 96% had baseline CD4 cell counts. Injection drug users remained a minority of those treated.
Conclusions Limited treatment resources can be focused on areas with more patients. Greater emphasis needs to be placed on earlier HIV diagnosis and treatment. New strategies must be identified to bring HIV-infected IDUs into treatment. Routine HIV testing would identify those at risk earlier.
C1 [Dou, Zhihui; Ma, Ye; Zhao, Yan; Zhao, Decai; Fang, Hua; Zhang, Fujie] Chinese Ctr Dis Control & Prevent, Div Treatment & Care, Natl Ctr AIDS STD Control & Prevent, Beijing 100050, Peoples R China.
[Chen, Ray Y.] US Embassy, NIAID, Natl Inst Hlth, Beijing, Peoples R China.
[Xu, Jiahong; Jiao, Jin Hua; Durako, Stephen] Westat Corp, Rockville, MD USA.
[Zhang, Fujie] Beijing Ditan Hosp, Beijing, Peoples R China.
RP Zhang, FJ (reprint author), Chinese Ctr Dis Control & Prevent, Div Treatment & Care, Natl Ctr AIDS STD Control & Prevent, 27 Nanwei Rd, Beijing 100050, Peoples R China.
EM zhang.fujie.t@gmail.com
OI Chen, Ray/0000-0001-6344-1442
FU Chinese National Antiretroviral Treatment Program; China Ministry of
Science and Technology (MOST) [973:2006CB504201]; US National Institutes
of Health [U2RTW06918-04S1, 1R03TW008203-01]
FX This work was supported by the Chinese National Antiretroviral Treatment
Program, and by the China Ministry of Science and Technology (MOST)
Chinese National Basic Research Program (973:2006CB504201). Preparation
of the manuscript was partly supported by US National Institutes of
Health Research Grants (U2RTW06918-04S1 and 1R03TW008203-01).
NR 36
TC 8
Z9 10
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD DEC
PY 2010
VL 39
SU 2
BP II56
EP II64
DI 10.1093/ije/dyq215
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 689TS
UT WOS:000284953100008
PM 21113038
ER
PT J
AU Gorsi, B
Ma, X
Chico, TJA
Srinivasan, A
Kramer, KL
Lui, F
Patient, R
Stringer, SE
AF Gorsi, B.
Ma, X.
Chico, T. J. A.
Srinivasan, A.
Kramer, K. L.
Lui, F.
Patient, R.
Stringer, S. E.
TI Sulf1 mediates zebrafish arterial venous identity
SO INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY
LA English
DT Meeting Abstract
CT Spring Meeting of the British-Society-for-Matrix-Biology
CY MAR 29-30, 2010
CL Univ Manchester, Manchester, ENGLAND
SP British Soc Matrix Biol
HO Univ Manchester
C1 [Gorsi, B.; Stringer, S. E.] Univ Manchester, Cardiovasc Med Fac Med & Human Sci, Manchester M13 9NT, Lancs, England.
[Ma, X.; Chico, T. J. A.] Univ Sheffield, MRC Ctr Dev & Biomed Genet, Sheffield, S Yorkshire, England.
[Srinivasan, A.; Kramer, K. L.] NHLBI, Natl Inst Hlth Bethesda Maryland, Bethesda, MD 20892 USA.
[Lui, F.; Patient, R.] Univ Oxford, Weatherall Inst Mol Med, Oxford, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0959-9673
J9 INT J EXP PATHOL
JI Int. J. Exp. Pathol.
PD DEC
PY 2010
VL 91
IS 6
BP A12
EP A12
PG 1
WC Pathology
SC Pathology
GA 684XV
UT WOS:000284589500010
ER
PT J
AU Basso, O
Pennell, ML
Chen, A
Longnecker, MP
AF Basso, O.
Pennell, M. L.
Chen, A.
Longnecker, M. P.
TI Mother's age at menarche and offspring size
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE age at menarche; body mass index; growth trajectory
ID BODY-MASS INDEX; SECULAR TRENDS; WEIGHT-GAIN; OBESITY; CHILDHOOD;
INFANCY; PUBERTY; GROWTH; OVERWEIGHT; SAMPLE
AB Objective: An individual's growth trajectory is, at least in part, inherited. Mother's early age at menarche has been associated with taller offspring height and greater body mass index (BMI) at age 9 years, suggesting that mother's age at menarche may be an intergenerational marker of growth. We examined the association between mother's age at menarche and childhood size at birth, and at ages 1, 3, 4, 7 and 8 years in the Collaborative Perinatal Project.
Subjects: We examined 128 636 measurements obtained from 31 474 Black and White children. We transformed the original measurements into z-scores. Child size was examined in mixed models, adjusted for center, child sex, race, socioeconomic index, child's exact age at measurement (in months), mother's age at recruitment and, depending on which measure was the outcome in the specific model, mother's height, pre-pregnancy weight or BMI.
Results: Compared with children whose mother had menarche at age 15 years or later, children whose mothers had age at menarche before age 12 years were taller from 1 year of age and had higher BMI, particularly at ages 7 and 8 years (0.17 and 0.19 z-score units, respectively).
Conclusions: Mothers' age at menarche is a modest predictor of their children's growth trajectory. The mechanism is likely to be heritable, although other explanations are possible. International Journal of Obesity (2010) 34, 1766-1771; doi:10.1038/ijo.2010.104; published online 15 June 2010
C1 [Basso, O.; Longnecker, M. P.] NIEHS, Epidemiol Branch, NIH, DHHS, Durham, NC USA.
[Pennell, M. L.] Ohio State Univ, Coll Publ Hlth, Div Biostat, Columbus, OH 43210 USA.
[Chen, A.] Univ Cincinnati, Coll Med, Dept Environm Hlth, Div Epidemiol & Biostat, Cincinnati, OH 45267 USA.
RP Basso, O (reprint author), McGill Univ, Royal Victoria Hosp, Dept Obstet & Gynecol, 687 Pine Ave W,Room F9-05, Montreal, PQ H3A 1A1, Canada.
EM olga.basso@mcgill.ca
RI Basso, Olga/E-5384-2010;
OI Basso, Olga/0000-0001-9298-4921; Longnecker, Matthew/0000-0001-6073-5322
FU NIH, National Institute of Environmental Health Sciences [Z01 ES049021]
FX This research was supported by the Intramural program of the NIH,
National Institute of Environmental Health Sciences (Z01 ES049021). We
thank Xuguang Guo for substantial help with statistical analysis, and
Clarice R Weinberg and Lea Cupul Uicab for suggestions on an earlier
draft.
NR 24
TC 7
Z9 7
U1 3
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0307-0565
J9 INT J OBESITY
JI Int. J. Obes.
PD DEC
PY 2010
VL 34
IS 12
BP 1766
EP 1771
DI 10.1038/ijo.2010.104
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 693RK
UT WOS:000285242900011
PM 20548308
ER
PT J
AU Theodore, S
Sharp, S
Zhou, JJ
Turner, T
Li, HZ
Miki, J
Ji, YM
Patel, V
Yates, C
Rhim, JS
AF Theodore, Shaniece
Sharp, Starlette
Zhou, Jianjun
Turner, Timothy
Li, Hongzhen
Miki, Jun
Ji, Youngmi
Patel, Vyomesh
Yates, Clayton
Rhim, Johng S.
TI Establishment and characterization of a pair of non-malignant and
malignant tumor derived cell lines from an African American prostate
cancer patient
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE African; American prostate cancer; non-malignant and malignant cell
lines
ID METASTASIS; GROWTH; BONE; PROFILE
AB Research into molecular and genetic mechanisms underlying prostate carcinogenesis in high-risk African American men would be greatly advanced by in vitro models of African American prostate tumors representing primary tumors However, the generation of immortalized primary African American prostate cancer cells that will accurately reflect the in situ characteristics of malignant epithelium is currently limited but is greatly needed We have successfully established immortalized cell lines of a pair of non-malignant and malignant tumors derived from an African American prostate cancel patient with HPV-16E6E7 (RC-77N/E and RC-77T1E) RC-77N/E and RC-77T1E cells are currently growing well at passage 40 Both cells exhibit epithelial morphology and are androgen sensitive The RC-77T/E cells produced tumors in SCID mice whereas the RC-77N/E cells produced no tumor in SCID mice These cells expressed androgen-regulated prostate-specific homobox gene, NKX 3 1, epithelial cell specific cytokeratn 8, androgen receptor (AR), prostate specific antigen (PSA), and p16 Chromosome analysis showed that both cell lines are similar near diploid human male (XY) with most chromosome counts in the 45-48 range However, RC-77T/E cell line has new marker chromosomes M1B=del/t(4,?)(q28,?), M5=16q+ in addition to those observed in the RC-77N1E cell line (M1=del(4)(q28q34)+hsr in some, M1A=t(4q,?),M2=der(9?),M2A=del(M2p-),M3=iso(?), M4=der(22?)) This is the first documented case of the establishment of pair of non-malignant and malignant tumors derived from an African American prostate cancer patient These models will provide novel tools to study the molecular and genetic mechanisms of prostate carcinogenesis, especially for high-risk African American men
C1 [Yates, Clayton] Tuskegee Univ, Dept Biol, Carver Res Fdn, Tuskegee, AL 36088 USA.
[Theodore, Shaniece; Sharp, Starlette; Zhou, Jianjun; Turner, Timothy; Yates, Clayton] Tuskegee Univ, Ctr Canc Res, Tuskegee, AL 36088 USA.
[Li, Hongzhen; Miki, Jun; Ji, Youngmi; Rhim, Johng S.] Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA.
[Patel, Vyomesh] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RP Yates, C (reprint author), Tuskegee Univ, Dept Biol, Carver Res Fdn, Rm 22, Tuskegee, AL 36088 USA.
FU National Institute of Health [U54 CA118623, RR-G12RR03059]; Department
of Defense Prostate Cancer Research Program [PC030694]; Department of
Defense [PC07397]
FX This study was supported by the National Institute of Health (U54
CA118623 and RR-G12RR03059 to T T and C Y), a Department of Defense
Prostate Cancer Research Program (PC030694 to J S R) and PC07397
(Department of Defense) to C Y
NR 18
TC 8
Z9 8
U1 0
U2 2
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 2010
VL 37
IS 6
BP 1477
EP 1482
DI 10.3892/ijo_00000800
PG 6
WC Oncology
SC Oncology
GA 689JA
UT WOS:000284922700013
PM 21042716
ER
PT J
AU Varma, R
Richman, EA
Ferris, FL
Bressler, NM
AF Varma, Rohit
Richman, Elaine A.
Ferris, Frederick L., III
Bressler, Neil M.
TI Use of Patient-Reported Outcomes in Medical Product Development: A
Report from the 2009 NEI/FDA Clinical Trial Endpoints Symposium
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID QUALITY-OF-LIFE; VISION-RELATED FUNCTION; ANGELES LATINO EYE; MACULAR
DEGENERATION; CATARACT-EXTRACTION; FUNCTIONAL STATUS; VISUAL-ACUITY;
GLAUCOMA; SURGERY; RANIBIZUMAB
C1 [Varma, Rohit] Doheny Eye Inst, Los Angeles, CA 90033 USA.
[Varma, Rohit] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA.
[Richman, Elaine A.] Richman Associates LLC, Baltimore, MD USA.
[Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA.
[Bressler, Neil M.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
RP Varma, R (reprint author), Doheny Eye Inst, Suite 4803,1450 San Pablo St, Los Angeles, CA 90033 USA.
EM rvarma@usc.edu
FU National Eye Institute [EY11753]; National Center on Minority Health and
Health Disparities, National Institutes of Health, Bethesda, MD
FX Supported by National Eye Institute Grant EY11753 and the National
Center on Minority Health and Health Disparities, National Institutes of
Health, Bethesda, MD.
NR 29
TC 18
Z9 19
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2010
VL 51
IS 12
BP 6095
EP 6103
DI 10.1167/iovs.10-5627
PG 9
WC Ophthalmology
SC Ophthalmology
GA 688GJ
UT WOS:000284837500002
PM 21123768
ER
PT J
AU Wong, WT
Kam, W
Cunningham, D
Harrington, M
Hammel, K
Meyerle, CB
Cukras, C
Chew, EY
Sadda, SR
Ferris, FL
AF Wong, Wai T.
Kam, Waynekid
Cunningham, Denise
Harrington, Molly
Hammel, Keri
Meyerle, Catherine B.
Cukras, Catherine
Chew, Emily Y.
Sadda, Srinivas R.
Ferris, Frederick L.
TI Treatment of Geographic Atrophy by the Topical Administration of OT-551:
Results of a Phase II Clinical Trial
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID VISUAL-ACUITY LOSS; MACULAR DEGENERATION; NATURAL-HISTORY; OXIDATIVE
DAMAGE; RISK-FACTORS; VITAMIN-E; AGE; DISEASE; AUTOFLUORESCENCE;
PATHOGENESIS
AB PURPOSE. To investigate the safety and preliminary efficacy of OT-551, a disubstituted hydroxylamine with antioxidant properties, for the treatment of geographic atrophy (GA), the advanced atrophic form of age-related macular degeneration (AMD).
METHODS. The study was a single-center, open-label phase II trial, enrolling 10 participants with bilateral GA. Topical 0.45% OT-551 was administered in one randomly assigned eye three times daily for 2 years. Safety measures were assessed by complete ophthalmic examination, fundus photography, and review of symptoms. The primary efficacy outcome measure was the change in best corrected visual acuity at 24 months. Secondary efficacy measures included changes in area of GA, contrast sensitivity, microperimetry measurements, and total drusen area from baseline.
RESULTS. Study drug was well tolerated and was associated with few adverse events. The mean change in BCVA at 2 years was +0.2 +/- 13.3 letters in the study eyes and -11.3 +/- 7.6 letters in fellow eyes (P = 0.0259). However, no statistically significant differences were found between the study and fellow eyes for all other secondary outcome measures.
CONCLUSIONS. OT-551 was well tolerated by study participants and was not associated with any serious adverse effects. Efficacy measurements in this small study indicate a possible effect in maintaining visual acuity. However, the absence of significant effects on other outcomes measures in this study suggests that OT-551, in the current concentration and mode of delivery, may have limited or no benefit as a treatment for GA (ClinicalTrials.gov number, NCT00306488). (Invest Ophthalmol Vis Sci. 2010;51:6131-6139) DOI:10.1167/iovs.10-5637
C1 [Wong, Wai T.; Meyerle, Catherine B.; Cukras, Catherine; Chew, Emily Y.; Ferris, Frederick L.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Wong, Wai T.; Kam, Waynekid] NEI, Off Sci Director, NIH, Bethesda, MD 20892 USA.
[Cunningham, Denise] NEI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Harrington, Molly; Hammel, Keri] EMMES Corp, Rockville, MD USA.
[Sadda, Srinivas R.] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Doheny Image Reading Ctr, Los Angeles, CA 90033 USA.
RP Wong, WT (reprint author), NEI, Div Epidemiol & Clin Applicat, NIH, 7 Mem Dr,Bldg 7,Room 217, Bethesda, MD 20892 USA.
EM wongw@xnei.nih.gov
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
FU National Eye Institute
FX Supported by the National Eye Institute Intramural Research Program.
NR 37
TC 39
Z9 41
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2010
VL 51
IS 12
BP 6131
EP 6139
DI 10.1167/iovs.10-5637
PG 9
WC Ophthalmology
SC Ophthalmology
GA 688GJ
UT WOS:000284837500007
PM 20574018
ER
PT J
AU Bai, YJ
Shi, ZH
Zhuo, YH
Liu, J
Malakhov, A
Ko, E
Burgess, K
Schaefer, H
Esteban, PF
Tessarollo, L
Saragovi, HU
AF Bai, Yujing
Shi, ZhiHua
Zhuo, Yehong
Liu, Jing
Malakhov, Andrey
Ko, Eunhwa
Burgess, Kevin
Schaefer, Henry
Esteban, Pedro F.
Tessarollo, Lino
Saragovi, H. Uri
TI In Glaucoma the Upregulated Truncated TrkC.T1 Receptor Isoform in Glia
Causes Increased TNF-alpha Production, Leading to Retinal Ganglion Cell
Death
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE PRODUCTION; INTRAOCULAR-PRESSURE;
MOUSE MODEL; IN-VIVO; NEUROTROPHIC RATIONALE; ALZHEIMERS-DISEASE;
GLUTAMATE LEVELS; DEGENERATION; INHIBITION
AB PURPOSE. Glaucoma is a distinct neuropathy characterized by the chronic and progressive death of retinal ganglion cells (RGCs). The etiology of RGC death remains unknown. Risk factors for glaucomatous RGC death are elevated intraocular pressure and glial production of tumor necrosis factor-alpha (TNF-alpha). Previously, the authors showed that glaucoma causes a rapid upregulation of a neurotrophin receptor truncated isoform lacking the kinase domain, TrkC.T1, in retina. Here they examined the biological role of TrkC.T1 during glaucoma progression.
METHODS. Rat and mouse models of chronic ocular hypertension were used. Immunofluorescence Western blot analysis and in situ mRNA hybridization were used to identify cells upregulating TrkC.T1. A genetic model of engineered mice lacking TrkC.T1 (TrkC.T1(-/-)) was used to validate a role for this receptor in glaucoma. Pharmacologic studies were conducted to evaluate intravitreal delivery of agonists or antagonists of TrkC. T1, compared with controls, during glaucoma. Surviving RGCs were quantified by retrograde-labeling techniques. Production of neurotoxic TNF-alpha and alpha 2 macroglobulin were quantified.
RESULTS. TrkC.T1 was upregulated in retinal glia, with a pattern similar to that of TNF-alpha. TrkC.T1(-/-) mice had normal retinas. However, during experimental glaucoma, TrkC.T1 (/) mice had lower rates of RGC death and produced less TNF-alpha than wild-type littermates. In rats with glaucoma, the pharmacologic use of TrkC antagonists delayed RGC death and reduced the production of retinal TNF-alpha.
CONCLUSIONS. TrkC.T1 is implicated in glaucomatous RGC death through the control of glial TNF-alpha production. Overall, the data point to a paracrine mechanism whereby elevated intraocular pressure upregulated glial TrkC.T1 expression in glia; TrkC.T1 controlled glial TNF-alpha production, and TNF-alpha caused RGC death. (Invest Ophthalmol Vis Sci. 2010; 51: 6639-6651) DOI:10.1167/iovs.10-5431
C1 [Bai, Yujing; Shi, ZhiHua; Saragovi, H. Uri] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada.
[Bai, Yujing; Zhuo, Yehong] Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China.
[Liu, Jing; Malakhov, Andrey; Ko, Eunhwa; Burgess, Kevin] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA.
[Schaefer, Henry; Esteban, Pedro F.; Tessarollo, Lino] NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Saragovi, H. Uri] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada.
[Saragovi, H. Uri] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
[Saragovi, H. Uri] McGill Univ, Ctr Canc, Montreal, PQ H3G 1Y6, Canada.
RP Saragovi, HU (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada.
EM uri.saragovi@mcgill.ca
RI Burgess, Kevin/B-5372-2015
OI Burgess, Kevin/0000-0001-6597-1842
FU Natural Scientific Foundation of China [30700928]; Guangdong Province
Universities and Colleges; National Institutes of Health [MH070040];
Robert A. Welch Foundation [A-1121]; National Institutes of
Health/National Cancer Institute; Canadian Institutes of Health Research
[192060-PT]
FX Supported by the Natural Scientific Foundation of China Grant 30700928;
Guangdong Province Universities and Colleges 2010 Pearl River Scholar
Funded Scheme (YZ); National Institutes of Health Grant MH070040; Robert
A. Welch Foundation Grant A-1121 (KB); the Intramural Research Program
of the National Institutes of Health/National Cancer Institute (PFE, HS,
LT); and Canadian Institutes of Health Research Grant 192060-PT (HUS).
NR 50
TC 24
Z9 24
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2010
VL 51
IS 12
BP 6639
EP 6651
DI 10.1167/iovs.10-5431
PG 13
WC Ophthalmology
SC Ophthalmology
GA 688GJ
UT WOS:000284837500072
PM 20574020
ER
PT J
AU Rao, RC
Tchedre, KT
Malik, MTA
Coleman, N
Fang, YA
Marquez, VE
Chen, DF
AF Rao, Rajesh C.
Tchedre, Kissaou T.
Malik, Muhammad Taimur A.
Coleman, Natasha
Fang, Yuan
Marquez, Victor E.
Chen, Dong Feng
TI Dynamic Patterns of Histone Lysine Methylation in the Developing Retina
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID NEURAL STEM-CELLS; GANGLION-CELLS; METHYLTRANSFERASE G9A; EARLY
EMBRYOGENESIS; AXON REGENERATION; GENE-EXPRESSION; NERVOUS-SYSTEM;
PROTEIN EZH2; CANCER-CELLS; DIFFERENTIATION
AB PURPOSE. Histone lysine methylation (HKM) is an important epigenetic mechanism that establishes cell-specific gene expression and functions in development. However, epigenetic control of retinal development is poorly understood. To study the roles of HKM in retinogenesis, the authors examined the dynamic changes of three HKM modifications and of two of their regulators, the histone methyltransferases (HMTases) Ezh2 and G9a, in the mouse retina.
METHODS. Retinal sections and lysates from embryonic day 16 through adult were processed for immunohistochemistry and immunoblotting using antibodies against various marks and HMTases. To further analyze the biological functions of HKM, the effects of small molecule inhibitors of HMTases were examined in vitro.
RESULTS. Methylation marks of trimethyl lysine 4 and 27 on histone H3 (H3K4me3 and H3K27me3) were detected primarily in differentiated retinal neurons in the embryonic and adult retina. In contrast, dimethyl lysine 9 on histone H3 (H3K9me2) was noted in early differentiating retinal ganglion cells but was lost after birth. The HMTases controlling H3K27me3, H3K9me2, Ezh2, and G9a were enriched in the inner embryonic retina during the period of active retinogenesis. Using the chemical inhibitors of Ezh2 and G9a, the authors reveal a role for HKM in regulating retinal neuron survival.
CONCLUSIONS. HKM is a dynamic and spatiotemporally regulated process in the developing retina. Epigenetic regulation of gene transcription by Ezh2- and G9a-mediated HKM plays crucial roles in retinal neuron survival and may represent novel epigenetic targets to enhance viability in retinal neurodegenerative diseases such as glaucoma. (Invest Ophthalmol Vis Sci. 2010;51:6784-6792) DOI:10.1167/iovs.09-4730
C1 [Chen, Dong Feng] Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA.
[Rao, Rajesh C.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Fang, Yuan] Fudan Univ, Eye & ENT Hosp, Shanghai 200433, Peoples R China.
[Marquez, Victor E.] NCI, Med Chem Lab, NIH, Frederick, MD 21701 USA.
RP Chen, DF (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA.
EM dongfeng.chen@schepens.harvard.edu
OI Rao, Rajesh/0000-0002-5776-8366
FU National Institutes of Health (NIH)/National Eye Institute (NEI)
[R01EY017641]; NIH/National Institute on Drug Abuse [R21DA024803];
Department of Defense [W81XWH-04-2-0008, W23RYX-9104-N603]; Department
of Veterans Affairs [1I01RX000110-01]; American Health Foundation (DFC);
NIH/National Cancer Institute Center for Cancer Research (VEM); NIH/NEI
[P30EY003790]
FX Supported by National Institutes of Health (NIH)/National Eye Institute
(NEI)Grant R01EY017641, NIH/National Institute on Drug Abuse Grant
R21DA024803, Department of Defense Grants W81XWH-04-2-0008 and
W23RYX-9104-N603, Department of Veterans Affairs Grant 1I01RX000110-01,
and the American Health Foundation (DFC); the Intramural Research
Program of the NIH/National Cancer Institute Center for Cancer Research
(VEM); NIH/NEI Grant P30EY003790; and a core grant to Schepens Eye
Research Institute.
NR 66
TC 15
Z9 20
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2010
VL 51
IS 12
BP 6784
EP 6792
DI 10.1167/iovs.09-4730
PG 9
WC Ophthalmology
SC Ophthalmology
GA 688GJ
UT WOS:000284837500090
PM 20671280
ER
PT J
AU Vogler, MA
Patterson, K
Kamemoto, L
Park, JG
Watts, H
Aweeka, F
Klingman, KL
Cohn, SE
AF Vogler, Mary A.
Patterson, Kristine
Kamemoto, Lori
Park, Jeong-Gun
Watts, Heather
Aweeka, Francesca
Klingman, Karin L.
Cohn, Susan E.
TI Contraceptive Efficacy of Oral and Transdermal Hormones When
Co-Administered With Protease Inhibitors in HIV-1-Infected Women:
Pharmacokinetic Results of ACTG Trial A5188
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV; hormonal contraceptive; lopinavir/ritonavir; pharmacokinetics
ID ANTIRETROVIRAL THERAPY; VENOUS THROMBOEMBOLISM; ETHINYL ESTRADIOL; HIV;
PATCH; MEDROXYPROGESTERONE; PARTICIPANTS; RITONAVIR
AB Background: Pharmacokinetic (PK) interactions between lopinavir/ritonavir (LPV/r) and transdermally delivered ethinyl estradiol (EE) and norelgestromin (NGMN) are unknown.
Methods: Using a standard noncompartmental PK analysis, we compared EE area under the time-concentration curve (AUC) and NGMN AUC during transdermal contraceptive patch administration in HIV-1-infected women on stable LPV/r to a control group of women not on highly active antiretroviral therapy (HAART). In addition, EE AUC after a single dose of a combination oral contraceptive pill including EE and norethindrone was measured before patch placement and was compared with patch EE AUC in both groups. Contraceptive effects on LPV/r PKs were estimated by measuring LPV/r AUC at baseline and during week 3 of patch administration.
Results: Eight women on LPV/r, and 24 women in the control group were enrolled. Patch EE median AUC02168 h was 45% lower at 6010.36 pg.h.mL(-1) in those on LPV/r versus 10911.42 pg.h.mL(-1) in those on no HAART (P = 0.064). Pill EE median AUC(0-48) hours was similarly 55% lower at 344.67 pg.h.mL(-1) in those on LPV/r versus 765.38 pg.h.mL(-1) in those on no HAART (P = 0.003). Patch NGMN AUC(0-168) (h) however, was 138.39 ng.h.mL(-1), 83% higher in the LPV/r group compared with the control AUC of 75.63 ng.h.mL(-1) (P = 0.036). After 3 weeks on the patch, LPVAUC(0-8) (h) decreased by 19%, (P = 0.156).
Conclusions: Although PKs of contraceptive EE and NGMN are significantly altered with LPV/r, the contraceptive efficacy of the patch is likely to be maintained. Larger studies are indicated to fully assess contraceptive efficacy versus risks of the transdermal contraceptive patch when co-administered with protease inhibitors.
C1 [Vogler, Mary A.] Weill Cornell Coll Med, Dept Med, Div Infect Dis, New York, NY USA.
[Patterson, Kristine] Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC USA.
[Kamemoto, Lori] Univ Hawaii, John A Burns Sch Med, Dept Obstet Gynecol & Womens Hlth, Honolulu, HI 96822 USA.
[Park, Jeong-Gun] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Park, Jeong-Gun] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA.
[Watts, Heather] CRMC NICHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
[Aweeka, Francesca] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA.
[Klingman, Karin L.] NIAID, DAIDS, NIH, DHHS, Bethesda, MD 20892 USA.
[Cohn, Susan E.] Northwestern Univ, Dept Med, Div Infect Dis, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Vogler, MA (reprint author), Cornell Univ, Weill Coll Med, 119 W 24th St, New York, NY 10011 USA.
EM mav9046@med.cornell.edu
FU National Institute of Allergy and Infectious Diseases; National
Institute of Child Health and Human Development [N01HD33345]
FX This research was supported in part by the Adult AIDS Clinical Trials
Group funded by the National Institute of Allergy and Infectious
Diseases, the Perinatal/Pediatric Clinical Trials network (N01HD33345)
funded by the National Institute of Child Health and Human Development,
and by Ortho-McNeill-Janssen Pharmaceuticals, Inc. who kindly provided
the transdermal patches and the birth control pills (eg, Ortho-Novum
1/35 pills) and funding for hormonal assays.
NR 35
TC 15
Z9 15
U1 1
U2 2
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 2010
VL 55
IS 4
BP 473
EP 482
DI 10.1097/QAI.0b013e3181eb5ff5
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 675RR
UT WOS:000283849100012
PM 20842042
ER
PT J
AU Lucas, GM
Clarke, W
Kagaayi, J
Atta, MG
Fine, DM
Laeyendecker, O
Serwadda, D
Chen, M
Wawer, MJ
Gray, RH
AF Lucas, Gregory M.
Clarke, William
Kagaayi, Joseph
Atta, Mohamed G.
Fine, Derek M.
Laeyendecker, Oliver
Serwadda, David
Chen, Michael
Wawer, Maria J.
Gray, Ronald H.
TI Decreased Kidney Function in a Community-based Cohort of HIV-Infected
and HIV-Negative Individuals in Rakai, Uganda
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE Africa; chronic kidney disease; cohort study; HIV infection; Uganda
ID GLOMERULAR-FILTRATION-RATE; RENAL-DISEASE; ANTIRETROVIRAL THERAPY; SERUM
CREATININE; AIDS-PREVENTION; RISK; TRIAL; POPULATION; EPIDEMIC; AFRICA
AB Background: High prevalences of reduced glomerular filtration rate (GFR) have been reported from HIV-infected individuals in sub-Saharan Africa when initiating antiretroviral therapy. However little is known about natural history HIV-related kidney disease or about background rates of reduced GFR in HIV-negative individuals in this region.
Methods: We estimated GFR from first and last available stored serum samples from 1202 HIV-infected and 664 age-matched and sex-matched HIV-negative individuals in a community-based cohort of HIV-infected and HIV-negative individuals in Rakai, Uganda, between 1994 and 2003. We assessed the prevalence and incidence of mildly (60-89 ml.min(-1).1.73 m(-2)) and moderately (< 60 ml.min(-1).1.73 m(-2)) reduced GFR using standard analytical methods.
Results: At baseline, 8.4% of HIV-infected and 4.7% of HIV-negative individuals had mildly or moderately reduced GFR (P = 0.002). During follow-up, the rates of decline to a lower GFR category were of 32.4 and 20.3 per 1000 person-years in HIV-infected and HIV-negative subjects, respectively (P = 0.019).
Conclusions: In an unselected community sample of HIV-infected individuals followed in Rakai, Uganda, before the availability of antiretroviral therapy, the prevalence of decreased GFR and the incidence of a decline in GFR category during follow-up were both significantly higher in HIV-infected subjects compared with HIV-negative subjects, although moderately reduced GFR was uncommon.
C1 [Lucas, Gregory M.; Clarke, William; Atta, Mohamed G.; Fine, Derek M.; Laeyendecker, Oliver] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
[Lucas, Gregory M.; Clarke, William; Atta, Mohamed G.; Fine, Derek M.; Laeyendecker, Oliver] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA.
[Kagaayi, Joseph] Uganda Virus Res Inst, Rakai Hlth Sci Program, Entebbe, Uganda.
[Laeyendecker, Oliver] NIAID, NIH, Bethesda, MD 20892 USA.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Chen, Michael; Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Lucas, GM (reprint author), 1830 E Monument St,Room 435A, Baltimore, MD 21287 USA.
EM glucas@jhmi.edu
RI Laeyendecker, Oliver/B-9331-2009; Lucas, Gregory/B-9225-2009;
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU Johns Hopkins Center on Global Health; Department of the Army
[DAMD17-98-2-8007]; National Institutes of Health [R01 A134826, R01
A134265, R01 DA018577]; National Institute of Child and Health
Development [5P30HD06826]; World Bank STI, Uganda; Henry M. Jackson
Foundation; Fogarty Foundation [5D43TW00010]; Bill and Melinda Gates
Institute for Population and Reproductive Health at Johns Hopkins
University; Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, NIH
FX Supported by a grant from the Johns Hopkins Center on Global Health. The
Rakai Project was funded through the Department of the Army, United
States Army Medical Research and Material Command Cooperative Agreement
DAMD17-98-2-8007; grants R01 A134826, R01 A134265, and R01 DA018577 from
the National Institutes of Health; grant 5P30HD06826 from the National
Institute of Child and Health Development; the World Bank STI Project,
Uganda; the Henry M. Jackson Foundation; grant 5D43TW00010 from the
Fogarty Foundation; and the Bill and Melinda Gates Institute for
Population and Reproductive Health at Johns Hopkins University.
Additional support was provided by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, NIH.
NR 20
TC 13
Z9 13
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 2010
VL 55
IS 4
BP 491
EP 494
DI 10.1097/QAI.0b013e3181e8d5a8
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 675RR
UT WOS:000283849100014
PM 20613548
ER
PT J
AU Shiels, MS
Cole, SR
Mehta, SH
Kirk, GD
AF Shiels, Meredith S.
Cole, Stephen R.
Mehta, Shruti H.
Kirk, Gregory D.
TI Lung Cancer Incidence and Mortality Among HIV-Infected and
HIV-Uninfected Injection Drug Users
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE cancer; drug users; lung; smoking; survival
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY;
UNITED-STATES; HAART ERA; RISK; AIDS; PEOPLE; INDIVIDUALS; SMOKING;
COHORT
AB Objectives: To examine the impact of HIV on lung cancer incidence and survival. Design: Prospective study of 2495 HIV-infected and HIV-uninfected injection drug users in Baltimore, MD.
Methods: Cancer data were obtained from the Maryland Cancer Registry. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer in 2 strata of packs of cigarettes smoked per day by HIV serostatus, and for mortality by HIV serostatus.
Results: HIV-infected participants had twice the risk (HR = 2.3; 95% CI: 1.1 to 5.1) of lung cancer. There was no evidence of an interaction between HIV and packs of cigarettes smoked per day (P interaction = 0.18). Compared with participants who smoked < 1.43 packs per day, among HIV-uninfected individuals lung cancer risk was 6 times greater (HR = 5.9; 95% CI: 2.1 to 17) and among HIV-infected individuals lung cancer risk was doubled (HR = 2.1; 95% CI: 0.63 to 6.8) in persons who smoked >= 1.43 per day. Additionally, HIV was associated with 4 times the risk of death (HR = 3.8; 95% CI: 0.92 to 15) in lung cancer cases.
Conclusions: HIV was associated with increased risk of lung cancer, after adjusting for smoking. However, no evidence was observed for synergistic effects of HIV and smoking. Further, HIV was associated with poorer lung cancer survival after accounting for cancer stage.
C1 [Shiels, Meredith S.; Mehta, Shruti H.; Kirk, Gregory D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Cole, Stephen R.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
RP Shiels, MS (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7059, Rockville, MD 20892 USA.
EM shielsms@mail.nih.gov
FU National Institute on Drug Abuse [R01 DA12568, R01 DA04334]; National
Heart, Lung and Blood Institute [R01 HL090483]; National Institutes of
Health [T32 CA009314]
FX Supported by Public Health Service Grants from the National Institute on
Drug Abuse: R01 DA12568, R01 DA04334, and the National Heart, Lung and
Blood Institute (R01 HL090483). Dr M.S.S. was supported by the National
Institutes of Health Research Service Award T32 CA009314.
NR 28
TC 39
Z9 39
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD DEC 1
PY 2010
VL 55
IS 4
BP 510
EP 515
DI 10.1097/QAI.0b013e3181f53783
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 675RR
UT WOS:000283849100018
PM 20838223
ER
PT J
AU Lambert, EY
Normand, JL
Volcow, ND
AF Lambert, Elizabeth Y.
Normand, Jacques L.
Volcow, Nora D.
TI Prevention and Treatment of HIV/AIDS Among Drug-Using Populations: A
Global Perspective INTRODUCTION
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Editorial Material
ID USERS; THERAPY; RISK
C1 [Lambert, Elizabeth Y.; Normand, Jacques L.; Volcow, Nora D.] NIDA, NIH, Rockville, MD USA.
RP Lambert, EY (reprint author), NIDA, NIH, 6001 Execut Blvd,Room 5146,MSC 9589, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 DA999999]
NR 18
TC 4
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD DEC 1
PY 2010
VL 55
SU 1
BP S1
EP S4
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 681SJ
UT WOS:000284337800001
PM 21045592
ER
PT J
AU Landgren, O
Waxman, AJ
AF Landgren, Ola
Waxman, Adam Justin
TI Multiple Myeloma Precursor Disease
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID UNDETERMINED SIGNIFICANCE MGUS; INDEPENDENT RISK-FACTOR; LIGHT-CHAIN
RATIO; MONOCLONAL GAMMOPATHY; WHOLE-BODY; IMAGING TECHNIQUES; WORKING
GROUP; PROGRESSION; DIAGNOSIS; PREVALENCE
AB Recent data indicate that multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma. Currently, multiple myeloma is a clinical diagnosis based on manifestations including hypercalcemia, renal failure, anemia, and bone lesions, whereas MGUS and smoldering myeloma are diagnosed based on laboratory abnormalities. Current clinical markers allow for more individualized risk stratification and counseling of these patients. However, there is a dearth of biomarkers and molecular imaging techniques capable of (1) accurately identifying patients with disease biology corresponding with high risk of progression; (2) elucidating the mechanism of transformation to multiple myeloma; and (3) forming a framework for development of targeted therapies. This case presentation and review discusses the current understanding of myeloma precursor disease and future opportunities for improving personalized management of patients with MGUS or smoldering myeloma, as well as the potential for developing early treatment strategies designed to delay and prevent development of multiple myeloma. JAMA. 2010;304(21):2397-2404 www.jama.com
C1 [Landgren, Ola] NCI, NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Landgren, O (reprint author), NCI, NIH, Ctr Canc Res, Med Oncol Branch, 900 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
FU National Cancer Institute of the National Institutes of Health
FX Research for this article was supported by the Intramural Research
Program of the National Cancer Institute of the National Institutes of
Health.
NR 48
TC 24
Z9 25
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD DEC 1
PY 2010
VL 304
IS 21
BP 2397
EP 2404
DI 10.1001/jama.2010.1713
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 687FH
UT WOS:000284763900021
PM 21119086
ER
PT J
AU Aberle, DR
Adams, AM
Berg, CD
Clapp, JD
Clingan, KL
Gareen, IF
Lynch, DA
Marcus, PM
Pinsky, PF
AF Aberle, Denise R.
Adams, Amanda M.
Berg, Christine D.
Clapp, Jonathan D.
Clingan, Kathy L.
Gareen, Ilana F.
Lynch, David A.
Marcus, Pamela M.
Pinsky, Paul F.
CA Natl Lung Screening Trial Res Team
TI Baseline Characteristics of Participants in the Randomized National Lung
Screening Trial
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SPIRAL COMPUTED-TOMOGRAPHY; CANCER RISK; DOSE CT; PROGRAM; SMOKERS;
PROJECT; WORKERS; CHEST
AB Background The National Lung Screening Trial (NLST), a randomized study conducted at 33 US sites, is comparing lung cancer mortality among persons screened with reduced dose helical computerized tomography and among persons screened with chest radiograph. In this article, we present characteristics of the study population.
Methods Eligible participants were aged 55-74 years and were current or former smokers with a cigarette smoking history of at least 30 pack-years. Randomization was stratified by site, sex, and age. To assess representativeness of the study population, demographic characteristics of individuals from the general population who met NLST age and smoking history inclusion criteria were obtained from the Tobacco Use Supplement of the US Census Bureau Current Population Surveys.
Results The NLST enrolled 53 456 persons, with 26 733 randomly assigned to chest radiograph screening and 26 723 to computerized tomography screening. Characteristics of the participants were as follows: 31 533 (59%) were men, 39 234 (73%) were younger than 65 years, 25 779 (48%) were current smokers, and 16 839 (32%) had a college or higher degree. Median cigarette exposure was 48 pack-years. Among Tobacco Use Supplement respondents who met NLST age and smoking history criteria, 59% were men, 65% were younger than 65 years, and 57% were current smokers. Median cigarette exposure among this group was 47 pack-years, and 14% had a college degree or higher.
Conclusion The NLST cohort has a distribution of sex and pack-year history that is similar to the component of the general US population that meets the major NLST eligibility criteria; however, NLST participants are younger, better educated, and less likely to be current smokers.
C1 [Lynch, David A.] Natl Jewish Hlth, Div Radiol, Denver, CO 80206 USA.
[Berg, Christine D.] NCI, Early Detect Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Adams, Amanda M.; Gareen, Ilana F.] Brown Univ, Dept Community Hlth, Ctr Stat Sci, Providence, RI 02912 USA.
[Clingan, Kathy L.] WESTAT Corp, Rockville, MD 20850 USA.
[Clapp, Jonathan D.] Informat Management Serv Inc, Rockville, MD USA.
[Aberle, Denise R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA.
RP Lynch, DA (reprint author), Natl Jewish Hlth, Div Radiol, 1400 Jackson St, Denver, CO 80206 USA.
EM lynchd@njhealth.org
RI Gareen, Ilana/I-2816-2014; Berg , Christine/K-1047-2014;
OI Gareen, Ilana/0000-0002-0457-5595; fishman, elliot/0000-0002-2567-1658;
Aberle, Denise/0000-0002-8858-3401
FU Division of Cancer Prevention, National Cancer Institute (NCI), National
Institutes of Health, Department of Health and Human Services; Cancer
Imaging Program, Division of Cancer Treatment and Diagnosis, NCI [U01
CA80098, CA79778]
FX This research was supported by contracts from the Division of Cancer
Prevention, National Cancer Institute (NCI), National Institutes of
Health, Department of Health and Human Services, and by grants (U01
CA80098 and CA79778) to support the American College of Radiology
Imaging Network (ACRIN) under a cooperative agreement with Cancer
Imaging Program, Division of Cancer Treatment and Diagnosis, NCI. The
NCI and ACRIN were actively involved in the design of the study and
collection of data, but the authors had full responsibility for the
analysis and interpretation of the data, the decision to submit the
manuscript for publication, and the writing of the manuscript.
NR 20
TC 85
Z9 85
U1 1
U2 3
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-. Natl. Cancer Inst.
PD DEC
PY 2010
VL 102
IS 23
BP 1771
EP 1779
DI 10.1093/jnci/djq434
PG 9
WC Oncology
SC Oncology
GA 689SU
UT WOS:000284950200008
ER
PT J
AU Gabay, O
Sanchez, C
Taboas, JM
AF Gabay, Odile
Sanchez, Christelle
Taboas, Juan M.
TI Update in cartilage bio-engineering (vol 77, pg 283, 2010)
SO JOINT BONE SPINE
LA English
DT Correction
C1 [Gabay, Odile] NIAMS, Cartilage Biol & Orthopaed Branch, Cartilage Genet Mol Grp, NIH, Bethesda, MD USA.
[Sanchez, Christelle] Univ Liege, Bone & Cartilage Res Unit, Liege, Belgium.
[Taboas, Juan M.] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Ctr Cellular & Mol Engn, Pittsburgh, PA 15261 USA.
RP Gabay, O (reprint author), NIAMS, Cartilage Biol & Orthopaed Branch, Cartilage Genet Mol Grp, NIH, Bethesda, MD USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
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 2010
VL 77
IS 6
BP 630
EP 630
DI 10.1016/j.jbspin.2010.09.017
PG 1
WC Rheumatology
SC Rheumatology
GA 691MU
UT WOS:000285085900040
ER
PT J
AU Marcus, MD
Baranowski, T
DeBar, LL
Edelstein, S
Kaufman, FR
Schneider, M
Siega-Riz, AM
Staten, MA
Virus, A
Yin, ZN
AF Marcus, Marsha D.
Baranowski, Tom
DeBar, Lynn L.
Edelstein, Sharon
Kaufman, Francine R.
Schneider, Margaret
Siega-Riz, Anna Maria
Staten, Myrlene A.
Virus, Amy
Yin, Zenong
TI Severe Obesity and Selected Risk Factors in a Sixth Grade Multiracial
Cohort: The HEALTHY Study
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Obesity; Hyperinsulinism; Glucose intolerance; Hyperlipidemia;
Hypertension
ID ADOLESCENTS; CHILDREN; OVERWEIGHT; TRENDS
AB The purpose of this study was to document the prevalence of severe obesity and associated risk in the HEALTHY cohort. A total of 6,365 students were assessed at school-based screenings. Results showed that 6.9% of students were severely obese. Severe obesity was associated with elevated cardiometabolic risk and race/ethnicity. Severe obesity is common and requires preventive intervention. (C) 2010 Society for Adolescent Health and Medicine. All rights reserved.
C1 [Marcus, Marsha D.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Baranowski, Tom] Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, ARS,USDA, Houston, TX 77030 USA.
[DeBar, Lynn L.] Kaiser Permanente, Ctr Hlth Res, Portland, OR USA.
[Edelstein, Sharon] George Washington Univ, Ctr Biostat, Rockville, MD USA.
[Kaufman, Francine R.] Univ So Calif, Keck Sch Med, Dept Pediat, Div Endocrinol, Los Angeles, CA 90033 USA.
[Schneider, Margaret] Univ Calif Irvine, Sch Social Sci, Dept Planning Policy & Design, Irvine, CA 92717 USA.
[Siega-Riz, Anna Maria] Univ N Carolina Sch Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Siega-Riz, Anna Maria] Univ N Carolina Sch Chapel Hill, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC USA.
[Staten, Myrlene A.] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA.
[Virus, Amy] Temple Univ, Sch Med, Ctr Obes Res & Educ, Philadelphia, PA 19122 USA.
[Yin, Zenong] Univ Texas San Antonio, Dept Hlth & Kinesiol, San Antonio, TX USA.
RP Marcus, MD (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA.
EM marcusmd@upmc.edu
OI Baranowski, Tom/0000-0002-0653-2222
FU NIDDK/NIH [U01-DK61230, U01-DK61249, U01-DK61231, U01-DK61223]
FX This work was completed with funding from NIDDK/NIH grant numbers
U01-DK61230, U01-DK61249, U01-DK61231, and U01-DK61223 to the STOPP-T2D
collaborative group, with additional support from the American Diabetes
Association.
NR 10
TC 17
Z9 18
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD DEC
PY 2010
VL 47
IS 6
BP 604
EP 607
DI 10.1016/j.jadohealth.2010.04.017
PG 4
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 683IP
UT WOS:000284469800011
PM 21094439
ER
PT J
AU Wallen, GR
Mitchell, SA
Melnyk, B
Fineout-Overholt, E
Miller-Davis, C
Yates, J
Hastings, C
AF Wallen, Gwenyth R.
Mitchell, Sandra A.
Melnyk, Bernadette
Fineout-Overholt, Ellen
Miller-Davis, Claiborne
Yates, Janice
Hastings, Clare
TI Implementing evidence-based practice: effectiveness of a structured
multifaceted mentorship programme
SO JOURNAL OF ADVANCED NURSING
LA English
DT Article
DE evidence-based practice; mentors; mentorship programme; nursing;
quasi-experiment
ID ANTICIPATED TURNOVER; ATTITUDE SIMILARITY; REGISTERED NURSES;
HEALTH-CARE; STRATEGIES; RETENTION; OUTCOMES; MODEL; SATISFACTION;
BELIEFS
AB P>Aim.
This paper is a report of the effectiveness of a structured multifaceted mentorship programme designed to implement evidence-based practice in a clinical research intensive environment.
Background.
Barriers to implementing evidence-based practice are well-documented in the literature. Evidence-based practice is associated with higher quality care and better patient outcomes than care that is steeped in tradition. However, the integration of evidence-based practice implementation into daily clinical practice remains inconsistent, and the chasm between research and bedside practice remains substantial.
Methods.
This quasi-experimental mixed methods study included three focused discussions with nursing leadership and shared governance staff as well as pre- (N = 159) and post-intervention (N = 99) questionnaires administered between June 2006 and February 2007. Online questionnaires included measures of organizational readiness, evidence-based practice beliefs, evidence-based practice implementation, job satisfaction, group cohesion and intent to leave nursing and the current job.
Results.
Participants in the evidence-based practice mentorship programme had a larger increase in perceived organizational culture and readiness for evidence-based practice and in evidence-based practice belief scores than those who did not participate. Qualitative findings suggested that leadership support of a culture for evidence-based practice and the dedication of resources for sustainability of the initiative needed to be a priority for engaging staff at all levels.
Conclusion.
These findings corroborate other studies showing that nurses' beliefs about evidence-based practice are significantly correlated with evidence-based practice implementation and that having a mentor leads to stronger beliefs and greater implementation by nurses as well as greater group cohesion, which is a potent predictor of nursing turnover rates.
C1 [Wallen, Gwenyth R.; Hastings, Clare] NIH, Nursing Serv, Ctr Clin, Bethesda, MD 20892 USA.
[Fineout-Overholt, Ellen] Arizona State Univ, Coll Nursing & Hlth Innovat, Ctr Advancement Evidence Based Practice, Phoenix, AZ USA.
[Hastings, Clare] NIH, Patient Care Serv, Ctr Clin, Bethesda, MD 20892 USA.
RP Wallen, GR (reprint author), NIH, Nursing Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM gwallen@cc.nih.gov
FU National Institutes of Health, Clinical Center
FX This study was funded by the National Institutes of Health, Clinical
Center Intramural Research Program.
NR 47
TC 61
Z9 62
U1 4
U2 23
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0309-2402
J9 J ADV NURS
JI J. Adv. Nurs.
PD DEC
PY 2010
VL 66
IS 12
BP 2761
EP 2771
DI 10.1111/j.1365-2648.2010.05442.x
PG 11
WC Nursing
SC Nursing
GA 681AA
UT WOS:000284277400017
PM 20825512
ER
PT J
AU Sutin, AR
Beason-Held, LL
Dotson, VM
Resnick, SM
Costa, PT
AF Sutin, Angelina R.
Beason-Held, Lori L.
Dotson, Vonetta M.
Resnick, Susan M.
Costa, Paul T., Jr.
TI The neural correlates of Neuroticism differ by sex prospectively mediate
depressive symptoms among older women
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Neuroticism; Depression; PET imaging; Hippocampus; Mediation; Sex
differences
ID CEREBRAL-BLOOD-FLOW; HIPPOCAMPAL FUNCTION; PERSONALITY-TRAITS;
GLUCOSE-METABOLISM; PREFRONTAL CORTEX; MAJOR DEPRESSION; 5-FACTOR MODEL;
PANIC DISORDER; BRAIN ACTIVITY; RESTING-STATE
AB Background: Mood disorders in old age increase the risk of morbidity and mortality for individuals and healthcare costs for society. Trait Neuroticism, a strong risk factor for such disorders into old age, shares common genetic variance with depression, but the more proximal biological mechanisms that mediate this connection are not well understood. Further, whether sex differences in the neural correlates of Neuroticism mirror sex differences in behavioral measures is unknown. The present research identifies sex differences in the stable neural activity associated with Neuroticism and tests whether this activity prospectively mediates Neuroticism and subsequent depressive symptoms.
Methods: A total of 100 (46 female) older participants (>55 years) underwent a resting-state PET scan twice, approximately two years apart, and completed measures of Neuroticism and depressive symptoms twice.
Results: Replicating at both time points, Neuroticism correlated positively with resting-state regional cerebral blood-flow activity in the hippocampus and midbrain in women and the middle temporal gyrus in men. For women, hippocampal activity mediated the association between Neuroticism at baseline and depressive symptoms at follow-up. The reverse mediational model was not significant.
Conclusions: Neuroticism was associated with stable neural activity in regions implicated in emotional processing and regulation for women but not men. Among women, Neuroticism prospectively predicted depressive symptoms through greater activity in the right hippocampus, suggesting one neural mechanism between Neuroticism and depression for women. Identifying responsible mechanisms for the association between Neuroticism and psychiatric disorders may help guide research on pharmacological interventions for such disorders across the lifespan. (C) 2010 Published by Elsevier B.V.
C1 [Sutin, Angelina R.; Beason-Held, Lori L.; Resnick, Susan M.; Costa, Paul T., Jr.] NIA, Lab Personal & Cognit, NIH, DHHS, Baltimore, MD 21224 USA.
[Dotson, Vonetta M.] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL 32611 USA.
RP Sutin, AR (reprint author), NIA, Lab Personal & Cognit, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sutina@mail.nih.gov
RI Dotson, Vonetta/K-6090-2015;
OI Dotson, Vonetta/0000-0002-3043-3320; Costa, Paul/0000-0003-4375-1712
FU NIH, National Institute on Aging; Revised NEO; [N01-AG-3-2124]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging and by Research and Development
Contract N01-AG-3-2124. The funding sources had no role in the design,
analysis, or interpretation of the data.; Paul Costa receives royalties
from the Revised NEO Personality Inventory. The other authors declare no
conflicts of interest.
NR 55
TC 5
Z9 5
U1 3
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD DEC
PY 2010
VL 127
IS 1-3
BP 241
EP 247
DI 10.1016/j.jad.2010.06.004
PG 7
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 692AJ
UT WOS:000285123600032
PM 20599276
ER
PT J
AU Prussin, C
Yin, YZ
Upadhyaya, B
AF Prussin, Calman
Yin, Yuzhi
Upadhyaya, Bhaskar
TI T(H)2 heterogeneity: Does function follow form?
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE T(H)2; heterogeneity; T cell; IL-5; differentiation; lineage
ID CD4(+) T-CELLS; FOLLICULAR HELPER-CELLS; AIRWAY INFLAMMATION; CYTOKINE
PRODUCTION; ALLERGIC DISEASES; IMMUNE-RESPONSES; T-HELPER-2 CELLS;
MEMORY CELLS; TH1 CELLS; TGF-BETA
AB T(H)2 immune responses are required for the 2 fundamental pathological processes characteristic of allergic disease: IgE-mediated hypersensitivity and eosinophilic inflammation. The 3 established T(H)2 cytokines, IL-4, IL-5, and IL-13, each play a nonredundant role in allergic disease pathology. The recent explosion of T-H subpopulations combined with the wide availability of polychromatic cytokine staining has facilitated the discovery of T(H)2 lineage heterogeneity. In this article we review T(H)2 heterogeneity and ask the following question: At what point do these subpopulations graduate from in vitro curiosities to immunologically robust therapeutic targets? We propose criteria to establish a T-cell subset as a biologically relevant entity and address the evidence to support these T(H)2 subpopulations having a unique function or specific contribution to allergic pathology or host defense. (J Allergy Clin Immunol 2010;126:1094-8.)
C1 [Prussin, Calman; Yin, Yuzhi; Upadhyaya, Bhaskar] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Prussin, C (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C207, Bethesda, MD 20892 USA.
EM cprussin@niaid.nih.gov
OI Prussin, Calman/0000-0002-3917-3326
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health; Division of Intramural Research, National
Institute of Allergy and Infectious Diseases
FX Supported by the National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Intramural Research Program.; Disclosure
of potential conflict of interest: C. Prussin, Y. Yin, and B. Upadhyaya
receive research support from the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases.
NR 47
TC 16
Z9 16
U1 0
U2 2
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 2010
VL 126
IS 6
BP 1094
EP 1098
DI 10.1016/j.jaci.2010.08.031
PG 5
WC Allergy; Immunology
SC Allergy; Immunology
GA 689RZ
UT WOS:000284947800002
PM 20951419
ER
PT J
AU Akin, C
Valent, P
Metcalfe, DD
AF Akin, Cem
Valent, Peter
Metcalfe, Dean D.
TI Mast cell activation syndrome: Proposed diagnostic criteria
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Mast cells; tryptase; histamine; mastocytosis; allergy; anaphylaxis;
urticaria
ID SYSTEMIC MASTOCYTOSIS; TRYPTASE LEVELS; ANAPHYLAXIS; KIT; DISORDERS; RI
AB The term mast cell activation syndrome (MCAS) is finding increasing use as a diagnosis for subjects who present with signs and symptoms involving the dermis, gastrointestinal track, and cardiovascular system frequently accompanied by neurologic complaints. Such patients often have undergone multiple extensive medical evaluations by different physicians in varied disciplines without a definitive medical diagnosis until the diagnosis of MCAS is applied. However, MCAS as a distinct clinical entity has not been generally accepted, nor do there exist definitive criteria for diagnosis. Based on current understanding of this disease "syndrome" and on what we do know about mast cell activation and resulting pathology, we will explore and propose criteria for its diagnosis. The proposed criteria will be discussed in the context of other disorders involving mast cells or with similar presentations and as a basis for further scientific study and validation. (J Allergy Clin Immunol 2010;126:1099-104.)
C1 [Metcalfe, Dean D.] NIAID, NIH, LAD, Bethesda, MD 20892 USA.
[Akin, Cem] Univ Michigan, Dept Internal Med, Div Allergy & Immunol, Ann Arbor, MI 48109 USA.
[Valent, Peter] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, Vienna, Austria.
RP Metcalfe, DD (reprint author), NIAID, NIH, LAD, Bldg 10-11C207,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA.
EM dmetcalfe@niaid.nih.gov
OI Akin, Cem/0000-0001-6301-4520
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases; Fonds zur Forderung der Wissenschaftlichen
Forschung in Osterreich (FWF) [P21173-B13, SFB-F01820]; Food Allergy
Initiative; Novartis; Bristol-Myers Squibb
FX Supported by the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, and grants #P21173-B13 and #SFB-F01820
of the Fonds zur Forderung der Wissenschaftlichen Forschung in
Osterreich (FWF).; Disclosure of potential conflict of interest: C. Akin
receives research support from the Food Allergy Initiative, has provided
legal consultation/expert witness testimony in cases related to
anaphylaxis, and is on the Medical Advisory Board for the Mastocytosis
Society. P. Valent receives research support from Novartis and
Bristol-Myers Squibb. D. D. Metcalfe receives research support from the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, and is a member of the Editorial Board for the
World Allergy Organization.
NR 29
TC 85
Z9 86
U1 1
U2 9
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 2010
VL 126
IS 6
BP 1099
EP U60
DI 10.1016/j.jaci.2010.08.035
PG 10
WC Allergy; Immunology
SC Allergy; Immunology
GA 689RZ
UT WOS:000284947800003
PM 21035176
ER
PT J
AU Boyce, JA
Assa'ad, A
Burks, AW
Jones, SM
Sampson, HA
Wood, RA
Plaut, M
Cooper, SF
Fenton, MJ
Arshad, SH
Bahna, SL
Beck, LA
Byrd-Bredbenner, C
Camargo, CA
Eichenfield, L
Furuta, GT
Hanifin, JM
Jones, C
Kraft, M
Levy, BD
Lieberman, P
Luccioli, S
McCall, KM
Schneider, LC
Simon, RA
Simons, FER
Teach, SJ
Yawn, BP
Schwaninger, JM
AF Boyce, Joshua A.
Assa'ad, Amal
Burks, A. Wesley
Jones, Stacie M.
Sampson, Hugh A.
Wood, Robert A.
Plaut, Marshall
Cooper, Susan F.
Fenton, Matthew J.
Arshad, S. Hasan
Bahna, Sami L.
Beck, Lisa A.
Byrd-Bredbenner, Carol
Camargo, Carlos A., Jr.
Eichenfield, Lawrence
Furuta, Glenn T.
Hanifin, Jon M.
Jones, Carol
Kraft, Monica
Levy, Bruce D.
Lieberman, Phil
Luccioli, Stefano
McCall, Kathleen M.
Schneider, Lynda C.
Simon, Ronald A.
Simons, F. Estelle R.
Teach, Stephen J.
Yawn, Barbara P.
Schwaninger, Julie M.
TI Guidelines for the Diagnosis and Management of Food Allergy in the
United States: Summary of the NIAID-Sponsored Expert Panel Report
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
C1 [Plaut, Marshall; Cooper, Susan F.; Fenton, Matthew J.; Schwaninger, Julie M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA.
[Boyce, Joshua A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy,Dept Med, Boston, MA 02115 USA.
[Assa'ad, Amal] Univ Cincinnati, Div Allergy & Immunol, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA.
[Jones, Stacie M.] Univ Arkansas Med Sci, Div Allergy & Immunol, Dept Pediat, Arkansas Childrens Hosp, Little Rock, AR 72205 USA.
[Sampson, Hugh A.] Mt Sinai Sch Med, Elliot & Roslyn Jaffe Food Allergy Inst, Div Allergy & Immunol, Dept Pediat, New York, NY USA.
[Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD USA.
[Arshad, S. Hasan] Univ Southampton, Sch Med, Southampton, Hants, England.
[Arshad, S. Hasan] St Marys Hosp, David Hide Asthma & Allergy Res Ctr, Newport, Wight, England.
[Arshad, S. Hasan] Southampton Univ Hosp NHS Trust, Southampton, Hants, England.
[Bahna, Sami L.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Allergy & Immunol Sect, Shreveport, LA 71105 USA.
[Beck, Lisa A.] Univ Rochester, Dept Dermatol, Med Ctr, Rochester, NY 14627 USA.
[Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Med, Div Rheumatol Allergy & Immunol,Massachusetts Gen, Boston, MA USA.
[Eichenfield, Lawrence] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA.
[Eichenfield, Lawrence] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Eichenfield, Lawrence] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA.
[Furuta, Glenn T.] Childrens Hosp Denver, Sect Pediat Gastroenterol Hepatol & Nutr, Digest Hlth Inst, Aurora, CO USA.
[Furuta, Glenn T.] Univ Colorado, Dept Pediat, Denver Sch Med, Aurora, CO USA.
[Furuta, Glenn T.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA.
[Hanifin, Jon M.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA.
[Jones, Carol] Allergy & Asthma Network Mothers Asthmat, Mclean, VA USA.
[Kraft, Monica] Duke Univ, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA.
[Levy, Bruce D.] Brigham & Womens Hosp, Partners Asthma Ctr, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Levy, Bruce D.] Harvard Univ, Sch Med, Boston, MA USA.
[Lieberman, Phil] Univ Tennessee, Dept Med, Div Allergy & Immunol, Coll Med, Memphis, TN 38104 USA.
[Luccioli, Stefano] US FDA, Off Food Addit Safety, College Pk, MD USA.
[McCall, Kathleen M.] Childrens Hosp Orange Cty, Orange, CA USA.
[Schneider, Lynda C.] Childrens Hosp Boston, Div Immunol, Boston, MA USA.
[Simon, Ronald A.] Scripps Clin, Div Allergy Asthma & Immunol, San Diego, CA USA.
[Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Pediat, Winnipeg, MB, Canada.
[Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Child Hlth & Immunol, Winnipeg, MB, Canada.
[Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA.
[Yawn, Barbara P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA.
[Yawn, Barbara P.] Univ Minnesota, Sch Med, Dept Family & Community Hlth, Minneapolis, MN 55455 USA.
RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 3105, Bethesda, MD 20892 USA.
EM fentonm@niaid.nih.gov
RI Byrd-Bredbenner, Carol/F-8064-2015
OI Byrd-Bredbenner, Carol/0000-0002-8010-3987
FU National Institutes of Health; GlaxoSmithKline; Food Allergy and
Anaphylaxis Network, Gerber, Mead Johnson; Dyax Corp; Food Allergy and
Anaphylaxis Network, Mead Johnson; National Peanut Board; Food Allergy
Initiative; National Institutes of Health (Division of Receipt and
Referral, National Institute of Allergy and Infectious Diseases,
National Center for Complementary and Alternative Medicine); Phadia AB;
Genentech; National Institutes of Health (National Institute of Allergy
and Infectious Diseases); National Institute of Health Research, UK;
American Academy of Allergy, Asthma, and Immunology; National Eczema
Association; US Department of Agriculture; Canned Food Alliance; New
Jersey Department of Health and Senior Services; Dey; Novartis;
Astellas; Ferndale; Johnson Johnson; Sinclair; Stiefel; Therapeutics
Inc.; American Gastrointestinal Association; ALZA; Astellas Pharma US,
Inc; Asubio Pharmaceuticals, Inc; Centocor, Inc; Corgentech; Nucryst
Pharmaceuticals; Seattle Genetics; Shionogi USA; Merck; Sepracor; Dey
Laboratories; Schering-Plough; AstraZenica; TEVA; Pfizer; MEDA; Alcon;
Intelliject; US Food and Drug Administration; AllerGen; Canadian
Allergy; Asthma and Immunology Foundation/Anaphylaxis Canada; Canadian
Institutes of Health Research; AstraZeneca Foundation; Aventis; Child
Health Center Board; CNMC Research Advisory Council; National
Association of Chain Drug Stores Foundation; National Institutes of
Health (National Institute of Allergy and Infectious Diseases; National
Heart, Lung, and Blood Institute); Novartis/Genentech; Robert Woods
Johnson Foundation; US Centers for Disease Control and Prevention; US
Public Health Service; Washington, DC, Department of Health
FX J. A. Boyce has served on the Advisory Board of GlaxoSmithKline. He has
served as a consultant and/or speaker for Altana, GlaxoSmithKline, and
Merck. He has received funding/grant support from the National
Institutes of Health.; A. Assa'ad holds, or is listed as an inventor on,
US patent application #10/566903, entitled "Genetic markers of food
allergy." She has served as a consultant for GlaxoSmithKline and as a
speaker for the American College of Allergy, Asthma, and Immunology, the
North East Allergy Society, the Virginia Allergy Society, the New
England Allergy Society, and the American Academy of Pediatrics. Dr
Assa'ad has received funding/grant support from GlaxoSmithKline.; A. W.
Burks holds, or is listed as an inventor on, multiple US patents related
to food allergy. He owns stock in Allertein and MastCell, Inc, and is a
minority stockholder in Dannon Co Probiotics. He has served as a
consultant for ActoGeniX NV, McNeil Nutritionals, Mead Johnson, and
Novartis. He has served on the speaker's bureau for EpiPen/Dey, LP, and
has served on the data monitoring committee for Genentech. He has served
on an expert panel for Nutricia. Dr Burks has received funding/grant
support from the Food Allergy and Anaphylaxis Network, Gerber, Mead
Johnson, and the National Institutes of Health.; S. M. Jones has served
as a speaker and grant reviewer and has served on the medical advisory
committee for the Food Allergy and Anaphylaxis Network. She has received
funding/grant support from Dyax Corp, the Food Allergy and Anaphylaxis
Network, Mead Johnson, the National Peanut Board, and the National
Institutes of Health.; H. A. Sampson holds, or is listed as an inventor
on, multiple US patents related to food allergy. He owns stock in
Allertein Therapeutics. He is the immediate past president of the
American Academy of Allergy, Asthma, and Immunology. He has served as a
consultant for Allertein Therapeutics, the American Academy of Allergy,
Asthma, and Immunology, the Food Allergy Initiative, and Schering
Plough. He has received funding/grant support for research projects from
the Food Allergy Initiative, the National Institutes of Health (Division
of Receipt and Referral, National Institute of Allergy and Infectious
Diseases, National Center for Complementary and Alternative Medicine),
and Phadia AB. He is a co-owner of Herbal Spring, LLC.; R. A. Wood has
served as a speaker/advisory board member for GlaxoSmithKline, Merck,
and Dey. He has received funding/grant support from Genentech and the
National Institutes of Health (National Institute of Allergy and
Infectious Diseases).; S. H. Arshad has received funding/grant support
from the National Institutes of Health and the National Institute of
Health Research, UK.; S. L. Bahna has received funding/grant support
from Genentech.; L. A. Beck has received funding/grant support from the
American Academy of Allergy, Asthma, and Immunology, the National Eczema
Association, and the National Institutes of Health.; C. Byrd-Bredbenner
owns stock in Johnson & Johnson. She has received funding/grant support
from the US Department of Agriculture, the Canned Food Alliance, and the
New Jersey Department of Health and Senior Services.; C. A. Camargo Jr
has consulted for Dey and Novartis. He has received funding/grant
support from a variety of government agencies and not-for-profit
research foundations, as well as Dey and Novartis.; L. Eichenfield has
received funding/grant support from a variety of not-for-profit
foundations, as well as Astellas, Ferndale, Johnson & Johnson, Novartis,
Sinclair, Stiefel, and Therapeutics Inc.; G. T. Furuta has served as a
consultant and/or speaker to Ception Therapeutics and TAP. He has
received funding/grant support from the American Gastrointestinal
Association and the National Institutes of Health.; J. M. Hanifin has
served as served as a consultant for ALZA, Anesiva, Inc, Barrier
Therapeutics, Inc, Milliken & Company, Nordic Biotech, Novartis
Pharmaceuticals Corporation, Shionogi USA, Taisho Pharmaceutical R&D,
Inc, Teikoku Pharma USA, Inc, UCB, York Pharma, ZARS, Inc, and
ZymoGenetics. He has served as an investigator or received research
funding from ALZA, Astellas Pharma US, Inc, Asubio Pharmaceuticals, Inc,
Centocor, Inc, Corgentech, Novartis, Nucryst Pharmaceuticals, Seattle
Genetics, and Shionogi USA.; M. Kraft has served as a consultant and/or
speaker for Astra-Zeneca, Genentech, GlaxoSmithKline, Merck, Novartis,
and Sepracor. She has received funding/grant support from Genentech,
GlaxoSmithKline, the National Institutes of Health and Novartis.; B. D.
Levy holds, or is listed as an inventor on, US patent applications
#20080064746 entitled "Lipoxins and aspirin-triggered lipoxins and their
stable analogs in the treatment of asthma and inflammatory airway
diseases" and #20080096961 entitled "Use of docosatrienes, resolvins and
their stable analogs in the treatment of airway diseases and asthma." He
owns stock in Resolvyx Pharmaceuticals. He has served as a consultant
for Bayer Healthcare and Resolvyx Pharmaceuticals. Dr Levy has received
funding/grant support from the National Institutes of Health.; P.
Lieberman has served as a consultant and/or speaker to Dey Laboratories,
Novartis, Schering-Plough, AstraZenica, Merck, TEVA, Pfizer, MEDA,
Alcon, Genentech, Intelliject, and the Food Allergy and Anaphylaxis
Network. He is past president of the American Academy of Allergy,
Asthma, and Immunology.; L. C. Schneider has served as a
consultant/clinical advisor for the Food Allergy Initiative. She has
received funding/grant support from a variety of not-for-profit research
foundations, as well as Novartis and the National Institutes of Health.;
R. A. Simon has served as a speaker for Dey Laboratories, Genentech,
GlaxoSmithKline, Merck, Novartis, and the US Food and Drug
Administration.; F. E. R. Simons holds a patent on "Fast-disintegrating
epinephrine tablets for sublingual administration." She is a
past-president of the American Academy of Allergy, Asthma, and
Immunology and of the Canadian Society of Allergy and Clinical
Immunology. She is a member of the advisory boards of Dey, Intelliject,
and ALK-Abello. She has received funding/grant support from AllerGen,
the Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis
Canada, and the Canadian Institutes of Health Research.; S. J. Teach has
served as a speaker for AstraZeneca. He has received funding/grant
support from the AstraZeneca Foundation, Aventis, the Child Health
Center Board, the CNMC Research Advisory Council, the National
Association of Chain Drug Stores Foundation, the National Institutes of
Health (National Institute of Allergy and Infectious Diseases; National
Heart, Lung, and Blood Institute), Novartis/Genentech, the Robert Woods
Johnson Foundation, the US Centers for Disease Control and Prevention,
the US Public Health Service, and the Washington, DC, Department of
Health.
NR 1
TC 399
Z9 409
U1 10
U2 37
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD DEC
PY 2010
VL 126
IS 6
BP 1105
EP 1118
DI 10.1016/j.jaci.2010.10.008
PG 14
WC Allergy; Immunology
SC Allergy; Immunology
GA 689RZ
UT WOS:000284947800005
PM 21134568
ER
PT J
AU White, SM
Rohani, P
Sait, SM
AF White, Steven M.
Rohani, Pejman
Sait, Steven M.
TI Modelling pulsed releases for sterile insect techniques: fitness costs
of sterile and transgenic males and the effects on mosquito dynamics
SO JOURNAL OF APPLIED ECOLOGY
LA English
DT Article
DE Aedes aegypti; biological control; dengue fever; fitness; population
cycles; RIDL; SIT; transgenic
ID LETHAL GENETIC SYSTEM; AEDES-AEGYPTI DIPTERA; POPULATION-DYNAMICS;
LARVAL COMPETITION; BIOLOGICAL-CONTROL; BORNE DISEASES; YELLOW-FEVER;
MALARIA; CULICIDAE; DOMINANT
AB 1. The development of transgenic technologies, coupled with sterile insect techniques (SIT), is being explored in relation to new approaches for the biological control of insect pests. Recent studies have shown that there are often fitness costs associated with transgenic insect strains, but the impact of these costs on their potential use in pest control is poorly understood.
2. In this paper, we explore the impact of an insect fitness cost on two control strategies (classical SIT and transgenic late-acting bisex lethality) using a stage-structured mathematical model, which is parameterized for the mosquito Aedes aegypti. Counter to the majority of studies, we use realistic pulsed release strategies and incorporate a fitness cost, which is manifested as a reduction in male mating competitiveness.
3. For both models we show that the level of control of a pest mosquito population is highly sensitive to the rate at which the transgenic or sterile males are released. Population control is more effective when smaller numbers of sterile/transgenic males are released more frequently than larger and less frequent releases.
4. If the wild-type mosquito population exhibits cycles of peaks and troughs in abundance, as is the case for many insect species, then high frequency releases of transgenic males not only reduce mosquito abundance, but they may dampen future pest outbreaks, whereas the use of SIT alone may have an adverse effect, causing an increase in mosquito abundance. Additionally, the timing of sterile/transgenic male release during the mosquito population cycle is critical in reducing pest outbreak levels.
5. In all cases, the reduced fitness of the sterile/transgenic males causes reductions in control, thus requiring more frequent or greater magnitude releases.
6. Synthesis and applications. The sterile insect technique is considered to be a valuable non-chemical tool for pest management. With the potential application of recent genetic developments to enhance the technique, it is becoming increasingly important to consider the wider ecological implications of this biological control strategy. Predicting the most efficient release strategies will be important in combating pest and vector insects as well as for limiting potential broader ecological effects. Although the focus of our models are based on the mosquito, A. aegypti, which can spread yellow fever, dengue fever and Chikungunya disease, our modelling approach and results can be applied more broadly to other species.
C1 [White, Steven M.; Sait, Steven M.] Univ Leeds, Fac Biol Sci, Inst Integrat & Comparat Biol, Leeds LS2 9JT, W Yorkshire, England.
[Rohani, Pejman] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP White, SM (reprint author), Ctr Ecol & Hydrol, Maclean Bldg,Benson Lane, Wallingford OX10 8BB, Oxon, England.
EM smwhit@ceh.ac.uk
OI White, Steven/0000-0002-3192-9969
FU NERC [NE/B503276/1]
FX This work was carried out as a result of an International Atomic Energy
Agency Co-ordinated Research Programme on 'Molecular technologies to
improve the effectiveness of the sterile insect technique' (UK/12529)
and we would like to thank Dr Gerald Franz and Dr Alan Robinson
accordingly. This work was also partly supported by NERC grant
NE/B503276/1 awarded to S.M.S. and P.R.
NR 61
TC 26
Z9 26
U1 5
U2 29
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-8901
J9 J APPL ECOL
JI J. Appl. Ecol.
PD DEC
PY 2010
VL 47
IS 6
BP 1329
EP 1339
DI 10.1111/j.1365-2664.2010.01880.x
PG 11
WC Biodiversity Conservation; Ecology
SC Biodiversity & Conservation; Environmental Sciences & Ecology
GA 677IQ
UT WOS:000283983200020
ER
PT J
AU Goldstein, DS
AF Goldstein, David S.
TI THE ROLE OF THE SYMPATHETIC NERVOUS SYSTEM-INFLUENCES OF SEX AND AGING
SO JOURNAL OF APPLIED PHYSIOLOGY
LA English
DT Letter
C1 NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, Bethesda, MD 20892 USA.
RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, Bethesda, MD 20892 USA.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 8750-7587
J9 J APPL PHYSIOL
JI J. Appl. Physiol.
PD DEC
PY 2010
VL 109
IS 6
BP 2005
EP 2006
PG 2
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 695FK
UT WOS:000285355800063
PM 21188816
ER
PT J
AU Shao, WH
Kuan, AP
Wang, C
Abraham, V
Waldman, MA
Vogelgesang, A
Wittenburg, G
Choudhury, A
Tsao, PY
Miwa, T
Eisenberg, RA
Cohen, PL
AF Shao, Wen-Hai
Kuan, Anita P.
Wang, Charlie
Abraham, Valsamma
Waldman, Meryl A.
Vogelgesang, Antje
Wittenburg, Gretel
Choudhury, Arpita
Tsao, Patricia Y.
Miwa, Takashi
Eisenberg, Robert A.
Cohen, Philip L.
TI Disrupted Mer receptor tyrosine kinase expression leads to enhanced MZ
B-cell responses
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE Apoptosis; Autoantibodies; Autoimmunity; Tolerance; MZ B cell
ID GRAFT-VERSUS-HOST; MARGINAL-ZONE; APOPTOTIC CELLS; ANTIBODY-RESPONSE;
H-CHAIN; MICE; CLEARANCE; DNA; TOLERANCE; LUPUS
AB Control of lymphocyte homeostasis is essential to ensure efficient immune responses and to prevent autoimmunity Splenic marginal zone B cells are Important producers of autoantibodies and are subject to stringent tolerance mechanisms to prevent autoimmunity In this paper we explore the role of the Mer tyrosine kinase (Mertk) in regulating autoreactive B cells This receptor tyrosine kinase serves to bind apoptotic cells to mediate their phagocytosis and to regulate subsequent cytokine production Mice lacking Mertk suffer from impaired apoptotic cell clearance and develop a lupus-like autoimmune syndrome Here we show that such Mertk-KO mice have expanded numbers of splenic marginal zone B cells Mertk-KO mice bearing a DNA-specific immunoglobulin heavy-chain transgene (3H9) produced anti-DNA antibodies that appeared to be secreted largely by marginal zone B cells Finally Mertk-KO mice developed greater antibody responses after NP-Ficoll immunization than their B6 counterparts Taken together our data show that Mertk has a major effect on the development of the marginal zone B-cell compartment Mertk is also important in establishing DNA-specific B-cell tolerance in 3H9 anti-DNA transgenic mice (c) 2010 Elsevier Ltd All rights reserved
C1 [Shao, Wen-Hai; Cohen, Philip L.] Temple Univ, Dept Med, Rheumatol Sect, Philadelphia, PA 19122 USA.
[Kuan, Anita P.; Wang, Charlie; Abraham, Valsamma; Vogelgesang, Antje; Wittenburg, Gretel; Choudhury, Arpita; Tsao, Patricia Y.; Eisenberg, Robert A.] Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA.
[Waldman, Meryl A.] NIDDKD, Bethesda, MD 20892 USA.
[Miwa, Takashi] Univ Penn, Dept Pharmacol, Ctr Expt Therapeut, Philadelphia, PA 19104 USA.
RP Cohen, PL (reprint author), 3322 N Broad St,Room 205, Philadelphia, PA 19140 USA.
FU National Institute of Dental and Craniofacial Research at the National
Institute of Health [R01DE017590]; United States Department of Veterans
Affairs
FX We are grateful for Dr Ziaur S M Rahman for critical reading of this
manuscript This work was supported by grants from the National Institute
of Dental and Craniofacial Research at the National Institute of Health
(Grant number R01DE017590) and the United States Department of Veterans
Affairs
NR 32
TC 13
Z9 13
U1 1
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
J9 J AUTOIMMUN
JI J. Autoimmun.
PD DEC
PY 2010
VL 35
IS 4
BP 368
EP 374
DI 10.1016/j.jaut.2010.08.001
PG 7
WC Immunology
SC Immunology
GA 684RT
UT WOS:000284567700010
PM 20822883
ER
PT J
AU Gilk, SD
Beare, PA
Heinzen, RA
AF Gilk, Stacey D.
Beare, Paul A.
Heinzen, Robert A.
TI Coxiella burnetii Expresses a Functional Delta 24 Sterol Reductase
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID INDUCED APOPTOSIS; OXIDATIVE STRESS; PHASE-I; Q-FEVER; CHOLESTEROL;
MACROPHAGES; CELLS; YEAST; BIOSYNTHESIS; LOCALIZATION
AB Coxiella burnetii, the etiological agent of human Q fever, occupies a unique niche inside the host cell, where it replicates in a modified acidic phagolysosome or parasitophorous vacuole (PV). The PV membrane is cholesterol-rich, and inhibition of host cholesterol metabolism negatively impacts PV biogenesis and pathogen replication. The precise source(s) of PV membrane cholesterol is unknown, as is whether the bacterium actively diverts and/or modifies host cell cholesterol or sterol precursors. C. burnetii lacks enzymes for de novo cholesterol biosynthesis; however, the organism encodes a eukaryote-like Delta 24 sterol reductase homolog, CBU1206. Absent in other prokaryotes, this enzyme is predicted to reduce sterol double bonds at carbon 24 in the final step of cholesterol or ergosterol biosynthesis. In the present study, we examined the functional activity of CBU1206. Amino acid alignments revealed the greatest sequence identity (51.7%) with a Delta 24 sterol reductase from the soil amoeba Naegleria gruberi. CBU1206 activity was examined by expressing the protein in a Saccharomyces cerevisiae erg4 mutant under the control of a galactose-inducible promoter. Erg4 is a yeast Delta 24 sterol reductase responsible for the final reduction step in ergosterol synthesis. Like Erg4-green fluorescent protein (GFP), a CBU1206-GFP fusion protein localized to the yeast endoplasmic reticulum. Heterologous expression of CBU1206 rescued S. cerevisiae erg4 sensitivity to growth in the presence of brefeldin A and cycloheximide and resulted in new synthesis of ergosterol. These data indicate CBU1206 is an active sterol reductase and suggest the enzyme may act on host sterols during C. burnetii intracellular growth.
C1 [Gilk, Stacey D.; Beare, Paul A.; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Heinzen, RA (reprint author), NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM rheinzen@niaid.nih.gov
FU 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 27
TC 16
Z9 16
U1 1
U2 5
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 2010
VL 192
IS 23
BP 6154
EP 6159
DI 10.1128/JB.00818-10
PG 6
WC Microbiology
SC Microbiology
GA 677LQ
UT WOS:000283994300006
PM 20870767
ER
PT J
AU Yu, H
Tu, K
Xie, L
Li, YY
AF Yu, Hui
Tu, Kang
Xie, Lu
Li, Yuan-Yuan
TI DIGOUT: VIEWING DIFFERENTIAL EXPRESSION GENES AS OUTLIERS
SO JOURNAL OF BIOINFORMATICS AND COMPUTATIONAL BIOLOGY
LA English
DT Article
DE Microarray; replication-lacking; differential expression genes; outliers
AB With regards to well-replicated two-conditional microarray datasets, the selection of differentially expressed (DE) genes is a well-studied computational topic, but for multi-conditional microarray datasets with limited or no replication, the same task is not properly addressed by previous studies. This paper adopts multivariate outlier analysis to analyze replication-lacking multi-conditional microarray datasets, finding that it performs significantly better than the widely used limit fold change (LFC) model in a simulated comparative experiment. Compared with the LFC model, the multivariate outlier analysis also demonstrates improved stability against sample variations in a series of manipulated real expression datasets. The reanalysis of a real non-replicated multi-conditional expression dataset series leads to satisfactory results. In conclusion, a multivariate outlier analysis algorithm, like DigOut, is particularly useful for selecting DE genes from non-replicated multi-conditional gene expression dataset.
C1 [Yu, Hui; Xie, Lu; Li, Yuan-Yuan] Shanghai Ctr Bioinformat Technol, Shanghai 200235, Peoples R China.
[Yu, Hui; Li, Yuan-Yuan] Chinese Acad Sci, Shanghai Inst Biol Sci, Bioinformat Ctr, Key Lab Syst Biol, Shanghai 200031, Peoples R China.
[Tu, Kang] NHLBI, NIH, Bethesda, MD USA.
RP Xie, L (reprint author), Shanghai Ctr Bioinformat Technol, 100 Qinzhou Rd, Shanghai 200235, Peoples R China.
EM yuhui@scbit.org; kang.tu@nih.gov; xielu@scbit.org; yyli@scbit.org
FU Shanghai Institutes for Biological Sciences; Chinese Academy of Sciences
[2008KIP207]; National Natural Science Foundation of China [30770497,
31070752, 31000380]; National Key Technologies RD Program [2007AA02Z331]
FX This work was supported by grants from Shanghai Institutes for
Biological Sciences, Chinese Academy of Sciences (2008KIP207), the
National Natural Science Foundation of China (30770497, 31070752,
31000380), and the National Key Technologies R&D Program (2007AA02Z331).
NR 45
TC 4
Z9 4
U1 0
U2 3
PU IMPERIAL COLLEGE PRESS
PI LONDON
PA 57 SHELTON ST, COVENT GARDEN, LONDON WC2H 9HE, ENGLAND
SN 0219-7200
J9 J BIOINFORM COMPUT B
JI J. Bioinform. Comput. Biol.
PD DEC
PY 2010
VL 8
SU 1
BP 161
EP 175
DI 10.1142/S0219720010005208
PG 15
WC Biochemical Research Methods; Computer Science, Interdisciplinary
Applications; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Computer Science; Mathematical &
Computational Biology
GA V20US
UT WOS:000208165500012
PM 21155026
ER
PT J
AU Devaiah, BN
Lu, HX
Gegonne, A
Sercan, Z
Zhang, HE
Clifford, RJ
Lee, MP
Singer, DS
AF Devaiah, Ballachanda N.
Lu, Hanxin
Gegonne, Anne
Sercan, Zeynep
Zhang, Hongen
Clifford, Robert J.
Lee, Maxwell P.
Singer, Dinah S.
TI Novel Functions for TAF7, a Regulator of TAF1-independent Transcription
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CLASS-II TRANSACTIVATOR; MHC CLASS-I; ACETYLTRANSFERASE ACTIVITY;
GENE-TRANSCRIPTION; BASAL PROMOTER; COMPLEX; CIITA; EXPRESSION;
TAF(II)250; TAT
AB The transcription factor TFIID components TAF7 and TAF1 regulate eukaryotic transcription initiation. TAF7 regulates transcription initiation of TAF1-dependent genes by binding to the acetyltransferase (AT) domain of TAF1 and inhibiting the enzymatic activity that is essential for transcription. TAF7 is released from the TAF1-TFIID complex upon completion of preinitiation complex assembly, allowing transcription to initiate. However, not all transcription is TAF1-dependent, and the role of TAF7 in regulating TAF1-independent transcription has not been defined. The IFN gamma-induced transcriptional co-activator CIITA activates MHC class I and II genes, which are vital for immune responses, in a TAF1-independent manner. Activation by CIITA depends on its intrinsic AT activity. We now show that TAF7 binds to CIITA and inhibits its AT activity, thereby repressing activated transcription. Consistent with this TAF7 function, siRNA-mediated depletion of TAF7 resulted in increased CIITA-dependent transcription. A more global role for TAF7 as a regulator of transcription was revealed by expression profiling analysis: expression of 30-40% of genes affected by TAF7 depletion was independent of either TAF1 or CIITA. Surprisingly, although TAF1-dependent transcripts were largely down-regulated by TAF7 depletion, TAF1-independent transcripts were predominantly up-regulated. We conclude that TAF7, until now considered only a TFIID component and regulator of TAF1-dependent transcription, also regulates TAF1-independent transcription.
C1 [Singer, Dinah S.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Zhang, Hongen; Clifford, Robert J.; Lee, Maxwell P.] NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA.
RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM dinah.singer@nih.gov
NR 34
TC 12
Z9 12
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD DEC
PY 2010
VL 285
IS 50
BP 38772
EP 38780
DI 10.1074/jbc.M110.173864
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 689PT
UT WOS:000284941300006
PM 20937824
ER
PT J
AU Kaur, S
Martin-Manso, G
Pendrak, ML
Garfield, SH
Isenberg, JS
Roberts, DD
AF Kaur, Sukhbir
Martin-Manso, Gema
Pendrak, Michael L.
Garfield, Susan H.
Isenberg, Jeff S.
Roberts, David D.
TI Thrombospondin-1 Inhibits VEGF Receptor-2 Signaling by Disrupting Its
Association with CD47
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; CELL RESPONSES;
VASCULAR HOMEOSTASIS; DEPENDENT ACTIVATION; ISCHEMIC TISSUE; TYPE-1
REPEATS; IN-VITRO; ANGIOGENESIS; MIGRATION
AB Thrombospondin-1 (TSP1) can inhibit angiogenic responses directly by interacting with VEGF and indirectly by engaging several endothelial cell TSP1 receptors. We now describe a more potent mechanism by which TSP1 inhibits VEGF receptor-2 (VEGFR2) activation through engaging its receptor CD47. CD47 ligation is known to inhibit downstream signaling targets of VEGFR2, including endothelial nitric-oxide synthase and soluble guanylate cyclase, but direct effects on VEGFR2 have not been examined. Based on FRET and co-immunoprecipitation, CD47 constitutively associated with VEGFR2. Ligation of CD47 by TSP1 abolished resonance energy transfer with VEGFR2 and inhibited phosphorylation of VEGFR2 and its downstream target Akt without inhibiting VEGF binding to VEGFR2. The inhibitory activity of TSP1 in large vessel and microvascular endothelial cells was replicated by a recombinant domain of the protein containing its CD47-binding site and by a CD47-binding peptide derived from this domain but not by the CD36-binding domain of TSP1. Inhibition of VEGFR2 phosphorylation was lost when CD47 expression was suppressed in human endothelial cells and in murine CD47-null cells. These results reveal that anti-angiogenic signaling through CD47 is highly redundant and extends beyond inhibition of nitric oxide signaling to global inhibition of VEGFR2 signaling.
C1 [Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Garfield, Susan H.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Isenberg, Jeff S.] Univ Pittsburgh, Vasc Med Inst, Dept Med, Pittsburgh, PA 15260 USA.
[Isenberg, Jeff S.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA.
RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Rm 2A33,10 Ctr Dr,MSC1500, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008; Martin Manso, Maria Gema/D-4612-2013
OI Roberts, David/0000-0002-2481-2981;
FU National Institutes of Health/NCI; National Institutes of Health
[CA128616]
FX This work was supported, in whole or in part, by the Intramural Research
Program of the National Institutes of Health/NCI (to D. D. R.) and by
National Institutes of Health Grant CA128616 (to J. S. I.).
NR 55
TC 73
Z9 74
U1 4
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 DEC
PY 2010
VL 285
IS 50
BP 38923
EP 38932
DI 10.1074/jbc.M110.172304
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 689PT
UT WOS:000284941300022
PM 20923780
ER
PT J
AU Assumpcao, TCF
Alvarenga, PH
Ribeiro, JMC
Andersen, JF
Francischetti, IMB
AF Assumpcao, Teresa C. F.
Alvarenga, Patricia H.
Ribeiro, Jose M. C.
Andersen, John F.
Francischetti, Ivo M. B.
TI Inhibits Platelet Aggregation, Vasoconstriction, and Angiogenesis
through Unique Binding Specificity for TXA(2), PGF(2 alpha), and
15(S)-HETE
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AORTIC ENDOTHELIAL-CELLS; BLOODSUCKING BUG; TRIATOMA-INFESTANS;
RHODNIUS-PROLIXUS; GLYCOPROTEIN-VI; GENE DISRUPTION; SALIVARY-GLANDS;
PROTEIN FAMILY; TICK SALIVA; COLLAGEN
AB Dipetalodipin (DPTL) is an 18 kDa protein cloned from salivary glands of the triatomine Dipetalogaster maxima. DPTL belongs to the lipocalin superfamily and has strong sequence similarity to pallidipin, a salivary inhibitor of collagen-induced platelet aggregation. DPTL expressed in Escherichia coli was found to inhibit platelet aggregation by collagen, U-46619, or arachidonic acid without affecting aggregation induced by ADP, convulxin, PMA, and ristocetin. An assay based on incubation of DPTL with small molecules (e. g. prostanoids, leukotrienes, lipids, biogenic amines) followed by chromatography, mass spectrometry, and isothermal titration calorimetry showed that DPTL binds with high affinity to carbocyclic TXA(2), TXA(2) mimetic (U-46619), TXB2, PGH(2) mimetic (U-51605), PGD(2), PGJ(2), and PGF(2 alpha). It also interacts with 15(S)-HETE, being the first lipocalin described to date to bind to a derivative of 15-lipoxygenase. Binding was not observed to other prostaglandins (e.g. PGE(1), PGE(2), 8-iso-PGF(2 alpha), prostacyclin), leukotrienes (e.g,. LTB4, LTC4, LTD4, LTE4), HETEs (e.g. 5(S)-HETE, 12(S)-HETE, 20-HETE), lipids (e.g. arachidonic acid, PAF), and biogenic amines (e.g. ADP, serotonin, epinephrine, norepinephrine, histamine). Consistent with its binding specificity, DPTL prevents contraction of rat uterus stimulated by PGF(2 alpha) and induces relaxation of aorta previously contracted with U-46619. Moreover, it inhibits angiogenesis mediated by 15(S)-HETE and did not enhance inhibition of collagen-induced platelet aggregation by SQ29548 (TXA(2) antagonist) and indomethacin. A3-D model for DPTL and pallidipin is presented that indicates the presence of a conserved Arg(39) and Gln(135) in the binding pocket of both lipocalins. Results suggest that DPTL blocks platelet aggregation, vasoconstriction, and angiogenesis through binding to distinct eicosanoids involved in inflammation.
C1 [Assumpcao, Teresa C. F.; Alvarenga, Patricia H.; Ribeiro, Jose M. C.; Andersen, John F.; Francischetti, Ivo M. B.] NIAID, Vector Biol Sect, LMVR, NIH, Bethesda, MD 20892 USA.
RP Francischetti, IMB (reprint author), NIAID, Vector Biol Sect, LMVR, NIH, 12735 Twinbrook Pkwy,Rm 2E-28, Bethesda, MD 20892 USA.
EM ifrancischetti@niaid.nih.gov
FU Division of Intramural Research, NIAID, National Institutes of Health
FX This work was supported, in whole or in part, by the Division of
Intramural Research, NIAID, National Institutes of Health.
NR 50
TC 20
Z9 20
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 DEC
PY 2010
VL 285
IS 50
BP 39001
EP 39012
DI 10.1074/jbc.M110.152835
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 689PT
UT WOS:000284941300030
PM 20889972
ER
PT J
AU Guo, Y
Au, WC
Shakoury-Elizeh, M
Protchenko, O
Basrai, M
Prinz, WA
Philpott, CC
AF Guo, Yan
Au, Wei-Chun
Shakoury-Elizeh, Minoo
Protchenko, Olga
Basrai, Munira
Prinz, William A.
Philpott, Caroline C.
TI Phosphatidylserine Is Involved in the Ferrichrome-induced Plasma
Membrane Trafficking of Arn1 in Saccharomyces cerevisiae
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TRANS-GOLGI NETWORK; UBIQUITIN-DEPENDENT TRAFFICKING; CROSS-PATHWAY
REGULATION; PHOSPHOLIPID METHYLATION; PROTEIN LOCALIZATION; INOSITOL
SYNTHESIS; GENETIC-ANALYSIS; BUDDING YEAST; PKH-KINASES; IRON UPTAKE
AB Arn1 is an integral membrane protein that mediates the uptake of ferrichrome, an important nutritional source of iron, in Saccharomyces cerevisiae. In the absence of ferrichrome, Arn1p is sorted directly from the trans-Golgi network to the vacuolar lumen for degradation. In the presence of low levels of ferrichrome, the siderophore binds to a receptor domain on Arn1, triggering the redistribution of Arn1 to the plasma membrane. When extracellular ferrichrome levels are high, Arn1 cycles between the plasma membrane and intracellular vesicles. To further understand the mechanisms of trafficking of Arn1p, we screened 4580 viable yeast deletion mutants for mislocalization of Arn1-GFP using synthetic genetic array technology. We identified over 100 genes required for trans-Golgi network-to-vacuole trafficking of Arn1-GFP and only two genes, SER1 and SER2, required for the ferrichrome-induced plasma membrane trafficking of Arn1-GFP. SER1 and SER2 encode two enzymes of the major serine biosynthetic pathway, and the Arn1 trafficking defect in the ser1 Delta strain was corrected with supplemental serine or glycine. Plasma membrane trafficking of Hxt3, a structurally related glucose transporter, was unaffected by SER1 deletion. Serine is required for the synthesis of multiple cellular components, including purines, sphingolipids, and phospholipids, but of these only phosphatidylserine corrected the Arn1 trafficking defects of the ser1 Delta strain. Strains with defects in phospholipid synthesis also exhibited alterations in Arn1p trafficking, indicating that the intracellular trafficking of some transporters is dependent on the phospholipid composition of the cellular membranes.
C1 [Guo, Yan; Shakoury-Elizeh, Minoo; Protchenko, Olga; Philpott, Caroline C.] NIDDK, Liver Dis Branch, Bethesda, MD 20892 USA.
[Prinz, William A.] NIDDK, Lab Cell Biol & Biochem, Bethesda, MD 20892 USA.
[Au, Wei-Chun; Basrai, Munira] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Philpott, CC (reprint author), Bldg 10 Rm 9B-16,10 Ctr Dr, Bethesda, MD 20892 USA.
EM carolinep@intra.niddk.nih.gov
FU National Institutes of Health (NIH), NIDDK, Intramural Research Program;
NCI, NIH
FX This work was supported, in whole or in part, by the National Institutes
of Health (NIH), NIDDK, Intramural Research Program (to Y. G., M. S.-E.,
O. P., W. A. P., and C. C. P.) and by NCI, NIH (to W.-C. A. and M. B.).
NR 42
TC 8
Z9 8
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD DEC
PY 2010
VL 285
IS 50
BP 39564
EP 39573
DI 10.1074/jbc.M110.177055
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 689PT
UT WOS:000284941300082
PM 20923770
ER
PT J
AU Hoi, YM
Wasserman, BA
Lakatta, EG
Steinman, DA
AF Hoi, Yiemeng
Wasserman, Bruce A.
Lakatta, Edward G.
Steinman, David A.
TI Effect of Common Carotid Artery Inlet Length on Normal Carotid
Bifurcation Hemodynamics
SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME
LA English
DT Article
ID BLOOD-FLOW; INTRACRANIAL ANEURYSMS; VESSEL MECHANICS; SHEAR-STRESS; CFD
MODELS; PATTERNS; WALL; MRI
AB Controversy exists regarding the suitability of fully developed versus measured inlet velocity profiles for image-based computational fluid dynamics (CFD) studies of carotid bifurcation hemodynamics. Here, we attempt to resolve this by investigating the impact of the reconstructed common carotid artery (CCA) inlet length on computed metrics of "disturbed" flow. Twelve normal carotid bifurcation geometries were reconstructed from contrast-enhanced angiograms acquired as part of the Vascular Aging-The Link That Bridges Age to Atherosclerosis study (VALIDATE). The right carotid artery lumen geometry was reconstructed from its brachiocephalic origin to well above the bifurcation, and the CCA was truncated objectively at locations one, three, five, and seven diameters proximal to where it flares into the bifurcation. Relative to the simulations carried out using the full CCA, models truncated at one CCA diameter strongly overestimated the amount of disturbed flow. Substantial improvement was offered by using three CCA diameters, with only minor further improvement using five CCA diameters. With seven CCA diameters, the amounts of disturbed flow agreed unambiguously with those predicted by the corresponding full-length models. Based on these findings, we recommend that image-based CFD models of the carotid bifurcation should incorporate at least three diameters of CCA length if fully developed velocity profiles are to be imposed at the inlet. The need for imposing measured inlet velocity profiles would seem to be relevant only for those cases where the CCA is severely truncated. [DOI: 10.1115/1.4002800]
C1 [Hoi, Yiemeng; Steinman, David A.] Univ Toronto, Dept Mech & Ind Engn, Biomed Simulat Lab, Toronto, ON M5S 3G8, Canada.
[Wasserman, Bruce A.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA.
[Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 20892 USA.
RP Hoi, YM (reprint author), Univ Toronto, Dept Mech & Ind Engn, Biomed Simulat Lab, Toronto, ON M5S 3G8, Canada.
RI Steinman, David/A-4258-2008
OI Steinman, David/0000-0002-7963-1168
FU Canadian Institutes of Health Research [MOP-62934]; National Institute
on Aging, NIH [NO1-AG-3-1003]; Heart and Stroke Foundation
FX This study was supported by Grant No. MOP-62934 from the Canadian
Institutes of Health Research. The VALIDATE study is supported by
Contract No. NO1-AG-3-1003 from the National Institute on Aging, NIH
and, in part, by the Intramural Research Program of the National
Institute on Aging, NIH. Y.H. and D.A.S. also acknowledge the support of
a Heart and Stroke Foundation Research Fellowship Award and Career
Investigator Award, respectively.
NR 27
TC 19
Z9 19
U1 0
U2 10
PU ASME-AMER SOC MECHANICAL ENG
PI NEW YORK
PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA
SN 0148-0731
J9 J BIOMECH ENG-T ASME
JI J. Biomech. Eng.-Trans. ASME
PD DEC
PY 2010
VL 132
IS 12
AR 121008
DI 10.1115/1.4002800
PG 6
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA 695ID
UT WOS:000285362900008
PM 21142322
ER
PT J
AU Wuchty, S
Zhang, A
Walling, J
Ahn, S
Li, AG
Quezado, M
Oberholtzer, C
Zenklusen, JC
Fine, HA
AF Wuchty, Stefan
Zhang, Alice
Walling, Jennifer
Ahn, Susie
Li, Aiguo
Quezado, Martha
Oberholtzer, Carl
Zenklusen, Jean-Claude
Fine, Howard A.
TI Gene pathways and subnetworks distinguish between major glioma subtypes
and elucidate potential underlying biology
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Classification; Gliomas; Subnetworks; Pathways
ID PROTEIN INTERACTION NETWORK; PHOSPHORYLATION NETWORKS; OLIGONUCLEOTIDE
ARRAYS; INTERACTION DATABASE; RESOURCE; DISCOVERY; REVEALS; CANCER;
PROGNOSIS; PROFILES
AB Molecular diagnostic tools are increasingly being used in an attempt to classify primary human brain tumors more accurately While methods that are based on the analysis of individual gene expression prove to be useful for diagnostic purposes, they are devoid of biological significance since tumorgenesis is a concerted deregulation of multiple pathways rather than single genes In a proof of concept, we utilize two large clinical data sets and show that the elucidation of enriched pathways and small differentially expressed sub-networks of protein interactions allow a reliable classification of glioblastomas and oligodendrogliomas Applying a feature selection method, we observe that an optimized subset of pathways and subnetworks significantly Improves the prediction accuracy By determining the enrichment of altered genes in pathways and subnetworks we show that optimized subsets of genes rarely seem to be a target of genomic alteration Our results suggest that groups of genes play a decisive role for the phenotype of the underlying tumor samples that can be utilized to reliably distinguish tumor types In the absence of enrichment of genes that are genomically altered we assume that genetic changes largely exert an indirect rather than direct regulatory influence on a number of tumor-defining regulatory networks. Published by Elsevier Inc
C1 [Wuchty, Stefan; Zhang, Alice; Walling, Jennifer; Ahn, Susie; Li, Aiguo; Zenklusen, Jean-Claude; Fine, Howard A.] Natl Inst Neurol Disorder & Stroke, Neurooncol Branch, NCI, NIH, Bethesda, MD 20894 USA.
[Quezado, Martha; Oberholtzer, Carl] Natl Inst Neurol Disorder & Stroke, Ctr Biomed Informat & Informat Technol, NCI, NIH, Bethesda, MD 20894 USA.
RP Fine, HA (reprint author), NCI, Neurooncol Branch, NIH, 9030 Old Georgetown Rd, Bethesda, MD 20892 USA.
NR 32
TC 6
Z9 6
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD DEC
PY 2010
VL 43
IS 6
BP 945
EP 952
DI 10.1016/j.jbi.2010.08.011
PG 8
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 690VM
UT WOS:000285036700010
PM 20828632
ER
PT J
AU Cao, YG
Cimino, JJ
Ely, J
Yu, H
AF Cao, Yong-gang
Cimino, James J.
Ely, John
Yu, Hong
TI Automatically extracting information needs from complex clinical
questions
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Natural language processing; Question answering; Question analysis;
Keyword extraction
ID HEALTH INFORMATION; PATIENT-CARE; MEDICAL LITERATURE; RETRIEVAL SYSTEMS;
ONLINE EVIDENCE; INTERNET; PHYSICIANS; KNOWLEDGE; QUALITY; ANSWER
AB Objective Clinicians pose complex clinical questions when seeing patients, and identifying the answers to those questions in a timely manner helps improve the quality of patient care We report here on two natural language processing models, namely, automatic topic assignment and keyword identification, that together automatically and effectively extract information needs from ad hoc clinical questions Our study is motivated in the context of developing the larger clinical question answering system Ask-HERMES (Hell) clinicians to Extract and aRrticulate Multimedia information for answering clinical quEstionS)
Design and measurements We developed supervised machine-learning systems to automatically assign predefined general categories (e g etiology, procedure, and diagnosis) to a question We also explored both supervised and unsupervised systems to automatically identify keywords that capture the main content of the question
Results We evaluated our systems on 4654 annotated clinical questions that were collected in practice We achieved an F1 score of 76 0% for the task of general topic classification and 58 0% for keyword extraction Our systems have been implemented into the larger question answering system AskHERMES. Our error analyses suggested that inconsistent annotation in our training data have hurt both question analysis tasks
Conclusion. Our systems, available at http //www askhermes org, can automatically extract information needs from both short (the number of word tokens <20) and long questions (the number of word tokens >20), and from both well-structured and ill-formed questions We speculate that the performance of general topic classification and keyword extraction can be further improved if consistently annotated data are made available (C) 2010 Elsevier Inc All rights reserved
C1 [Cao, Yong-gang; Yu, Hong] Univ Wisconsin, Milwaukee, WI 53201 USA.
[Cimino, James J.] NIH, CRC Hatfield Clin Res Ctr 10, Bethesda, MD 20892 USA.
[Ely, John] Univ Iowa, Carver Coll Med, Dept Family Med, Iowa City, IA 52242 USA.
RP Yu, H (reprint author), Univ Wisconsin, 2240 Hartford Ave,Enderis Hall 939, Milwaukee, WI 53211 USA.
OI Cimino, James/0000-0003-4101-1622
FU National Library of Medicine [1R01LM009836]; University of
Wisconsin-Milwaukee; MITAG
FX The authors acknowledge support from the National Library of Medicine,
Grant No 1R01LM009836, and from the University of Wisconsin-Milwaukee, a
MITAG grant Any opinions, findings, or recommendations are those of the
authors and do not necessarily reflect the views of the NIH and UWM
NR 87
TC 9
Z9 9
U1 0
U2 6
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 2010
VL 43
IS 6
BP 962
EP 971
DI 10.1016/j.jbi.2010.07.007
PG 10
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 690VM
UT WOS:000285036700012
PM 20670693
ER
PT J
AU Marcus, PM
Huang, GC
Beck, V
Miller, MJ
AF Marcus, Pamela M.
Huang, Grace C.
Beck, Vicki
Miller, Michael J.
TI The Impact of a Primetime Cancer Storyline: From Individual Knowledge
and Behavioral Intentions to Policy-level Changes
SO JOURNAL OF CANCER EDUCATION
LA English
DT Article
DE Primetime cancer storyline; Individual knowledge; Behavioral intentions
ID RACIAL-DIFFERENCES; BREAST-CANCER; CARE
AB We assessed the educational impact of a primetime network TV storyline that addressed cancer patient navigators. An online survey was administered after the episode aired. Exposed respondents saw the episode (n = 336); unexposed respondents did not (n = 211). Exposed respondents were more likely to report they would recommend a patient navigator (61% vs. 48%, p = 0.01). Clips of the episode were shown to raise awareness of patient navigators in a Congressional Committee meeting before the Patient Navigator Act was signed into law (2005). Entertainment education can have a positive impact on cancer knowledge and can contribute to policy-level decisions.
C1 [Marcus, Pamela M.; Miller, Michael J.] NCI, US Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Huang, Grace C.] USC Annenberg Norman Lear Ctr, Beverly Hills, CA USA.
RP Marcus, PM (reprint author), NCI, US Dept Hlth & Human Serv, NIH, 6130 Execut Blvd Suite,3131, Bethesda, MD 20892 USA.
EM marcusp@mail.nih.gov
NR 11
TC 3
Z9 3
U1 3
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-8195
J9 J CANCER EDUC
JI J. Cancer Educ.
PD DEC
PY 2010
VL 25
IS 4
BP 484
EP 489
DI 10.1007/s13187-010-0093-y
PG 6
WC Oncology; Education, Scientific Disciplines; Public, Environmental &
Occupational Health
SC Oncology; Education & Educational Research; Public, Environmental &
Occupational Health
GA 685UE
UT WOS:000284652800005
PM 20300910
ER
PT J
AU Bussard, KM
Venzon, DJ
Mastro, AM
AF Bussard, Karen M.
Venzon, David J.
Mastro, Andrea M.
TI Osteoblasts Are a Major Source of inflammatory Cytokines in the Tumor
Microenvironment of Bone Metastatic Breast Cancer
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE OSTEOBLAST; BREAST CANCER; IL-6; MCP-1; VEGF
ID ENDOTHELIAL GROWTH-FACTOR; COLONY-STIMULATING FACTOR; IN-VIVO;
CHEMOATTRACTANT PROTEIN-1; LUNG-CANCER; CELLS; RESORPTION; MCP-1;
DIFFERENTIATION; EXPRESSION
AB Metastatic breast cancer cells co-opt the cells of the bone to increase their production of inflammatory cytokines. Here, we sought to identify key cytokines expressed by osteoblasts in vitro anti in vivo in the presence of MDA-MB-231 metastatic breast cancer cells, including a bone-seeking variant. We hypothesized that osteoblast-derived cytokines increase in the presence of metastatic breast cancer cell conditioned medium (CM), act as chemoattractants for cancer cells, anti enhance osteoclast formation. We detected increases in the concentrations of osteoblast-derived IL-6, MCP-1, VEGF, MIP-2, and KC in vitro in culture supernatants from MC3T3-E1 cells in the presence of metastatic breast cancer cell CM and from cancer-bearing femurs ex vivo. A comparison of cancer cell- and osteoblast-derived cytokines revealed that while breast cancer cells expressed the same or equivalent cytokines as the osteoblasts, the breast cancer cells only produced picogram quantities of MCP-1; osteoblasts expressed nanogram amounts. Bone-derived MCP-1 increased in the proximal metaphysis, an area where breast cancer cells preferentially trafficked following intracardiac inoculation in athymic mice. An MDA-MB-231 bone-seeking variant was not different from parental lines. Osteoblast CM was a potent chemoattractant for metastatic breast cancer cells. Furthermore, culture supernatants of osteoblasts treated with breast cancer cell CM enhanced osteoclast formation. These findings suggest that bone metastatic breast cancer cells utilize osteoblast-derived cytokines to facilitate breast cancer cell colonization and survival upon arrival in the bone microenvironment. J. Cell. Biochem. 111: 1138-1148, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Mastro, Andrea M.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Bussard, Karen M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Venzon, David J.] NCI, Biostat & Data Management Sect, NIH, Rockville, MD 20892 USA.
RP Mastro, AM (reprint author), Penn State Univ, Dept Biochem & Mol Biol, 431 S Frear Bldg, University Pk, PA 16802 USA.
EM a36@psu.edu
OI Mastro, Andrea/0000-0003-2710-3360
FU U.S. Army Medical and Material Research Command Breast Cancer Program
[DAMD 17-02-1-0358, W81XWH-06-1-0432, W81XWH-06-1-0363,
W81XWH-08-1-0448]; National Foundation for Cancer Research, Center for
Metastasis Research; Susan G. Komen Breast Cancer Foundation
[BCTR0601044, BCTR104406]
FX Grant sponsor: U.S. Army Medical and Material Research Command Breast
Cancer Program; Grant numbers: DAMD 17-02-1-0358, W81XWH-06-1-0432,
W81XWH-06-1-0363; Grant sponsor: National Foundation for Cancer
Research, Center for Metastasis Research; Grant sponsor: The Susan G.
Komen Breast Cancer Foundation; Grant numbers: BCTR0601044, BCTR104406.;
The authors would like to thank Yu-chi Chen for her assistance with
graphing results. This work was supported by the U.S. Army Medical and
Materiel Research Command Breast Cancer Program (DAMD 17-02-1-0358,
W81XWH-06-1-0432, and W81XWH-08-1-0448 to A.M.M., and W81XWH-06-1-0363
to K.M.B.); National Foundation for Cancer Research, Center for
Metastasis Research; and The Susan G. Komen Breast Cancer Foundation
(BCTR0601044 and BCTR104406).
NR 43
TC 21
Z9 22
U1 0
U2 9
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD DEC 1
PY 2010
VL 111
IS 5
BP 1138
EP 1148
DI 10.1002/jcb.22799
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 703YH
UT WOS:000286017400009
PM 20683902
ER
PT J
AU Shen, DW
Ma, JC
Okabe, M
Zhang, GF
Xia, D
Gottesman, MM
AF Shen, Ding-Wu
Ma, Jichun
Okabe, Mitsunori
Zhang, Guofeng
Xia, Di
Gottesman, Michael M.
TI Elevated Expression of TMEM205, a Hypothetical Membrane Protein, Is
Associated With Cisplatin Resistance
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID OVARIAN-CARCINOMA CELLS; MULTIDRUG-RESISTANCE; IDENTIFICATION;
ACCUMULATION; CANCER; GENES; SENSITIVITY; MECHANISM;
CIS-DIAMMINEDICHLOROPLATINUM(II); LINES
AB Development of cisplatin resistance in cancer cells appears to be a consequence of multiple epigenetic alterations in genes involved in DNA damage repair, proto-oncogenes, apoptosis, transporters, transcription factors, etc. In this study, we found that expression of the hypothetical transmembrane protein TMEM205 (previously known as MBC3205) is associated with cisplatin resistance. TMEM205 was first detected by functional cloning from a retroviral cDNA library made from human cisplatin-resistant (CP-r) cells. TMEM205 is predicted to be a transmembrane protein, but its expression, localization, and function have not previously been investigated. A polyclonal antibody directed to the TMEM205 protein was raised in our laboratory. Using this antibody, it was demonstrated that this protein is located at the cell surface. Its expression is increased in our cisplatin-selected CP-r cell lines, as demonstrated by immunoblotting, confocal examination, and immuno-electron microscopy. Stable transfection of the TMEM205 gene confers resistance to cisplatin by approximately 2.5-fold. Uptake assays with Alexa Fluor-cisplatin showed reduced accumulation in CP-r KB-CP.3 and KB-CP.5 cells, and in TMEM205-transfected cells. Analysis of TMEM205 expression profiles in normal human tissues indicates a differential expression pattern with higher expression levels in the liver, pancreas, and adrenal glands. These results indicate that a novel mechanism for cisplatin resistance is mediated by TMEM205, and also suggest that overexpression of TMEM205 in CP-r cells may be valuable as a biomarker or target in cancer chemotherapy. J. Cell. Physiol. 225: 822-828, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Zhang, Guofeng] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA.
EM mgottesman@nih.gov
FU Intramural Research Program of the National Institutes of Health, the
National Cancer Institute; National Institute of Biomedical Imaging and
Bioengineering
FX This research was funded by the Intramural Research Program of the
National Institutes of Health, the National Cancer Institute and the
National Institute of Biomedical Imaging and Bioengineering. We would
like to thank George Leiman for editorial assistance, and Susan
Garfield, Poonam Mannan and Langston Lim in the Laboratory of
Experimental Carcinogenesis (NCI) for assistance with confocal analysis.
NR 20
TC 14
Z9 15
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0021-9541
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD DEC
PY 2010
VL 225
IS 3
BP 822
EP 828
DI 10.1002/jcp.22287
PG 7
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 679WI
UT WOS:000284191100022
PM 20589834
ER
PT J
AU Acosta, MT
Munasinghe, J
Pearl, PL
Gupta, M
Finegersh, A
Gibson, KM
Theodore, WH
AF Acosta, Maria T.
Munasinghe, Jeeva
Pearl, Phillip L.
Gupta, Maneesh
Finegersh, Andrey
Gibson, K. Michael
Theodore, William H.
TI Cerebellar Atrophy in Human and Murine Succinic Semialdehyde
Dehydrogenase Deficiency
SO JOURNAL OF CHILD NEUROLOGY
LA English
DT Article
DE succinic semialdehyde dehydrogenase deficiency; cerebellar atrophy
ID 4-HYDROXYBUTYRIC ACIDURIA; COGNITIVE FUNCTIONS; BRAIN; MICE; MRI;
SPECTROSCOPY; NUMBERS; AUTISM
AB Human succinic semialdehyde dehydrogenase deficiency, an autosomal recessive disorder of gamma-aminobutyric acid (GABA) catabolism, was modeled by a murine model sharing the phenotype of ataxia and seizures. Magnetic resonance imaging (MRI) with volumetry was obtained on 7 patients versus controls, and MRI with stereology was derived in 3 murine genotypes: null, wild-type, and heterozygous mutants. All patients had T1 hypointensity and T2 hyperintensity in globus pallidus, and 5 also had similar changes in subthalamic and cerebellar dentate nuclei. There was a trend for patients to have a smaller cerebellar vermis. Homozygous null mice had significantly lower total brain and cerebellar volumes than wild-types and heterozygotes. Stereology confirmed cerebellar atrophy and was otherwise normal in multiple regions. Cerebellar volume loss is present in the murine disorder with a trend for cerebellar atrophy in patients. Reduced cerebellar volume can reflect neurodegeneration and may be related to the clinical manifestations.
C1 [Acosta, Maria T.; Pearl, Phillip L.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
[Acosta, Maria T.; Pearl, Phillip L.; Finegersh, Andrey; Theodore, William H.] NINDS, Clin Epilepsy Sect, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Munasinghe, Jeeva] NINDS, Mouse Imaging Facil, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Gupta, Maneesh] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA.
[Gibson, K. Michael] Michigan Technol Univ, Dept Biol Sci, Houghton, MI 49931 USA.
RP Pearl, PL (reprint author), Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM ppearl@cnmc.org
FU NINDS Division of Intramural Research; NIH [NS 40270, HD 58553];
Pediatric Neurotransmitter Disease Association
FX The authors disclosed receipt of the following financial support for the
research and/or authorship of this article: The study was supported by
the NINDS Division of Intramural Research; NIH NS 40270 (Dr Gibson) and
HD 58553 (Dr Gibson, Dr Pearl); and the Pediatric Neurotransmitter
Disease Association (Dr Pearl).
NR 26
TC 6
Z9 6
U1 0
U2 2
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 2010
VL 25
IS 12
BP 1457
EP 1461
DI 10.1177/0883073810368137
PG 5
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 692IS
UT WOS:000285147100001
PM 20445195
ER
PT J
AU Lipska, KJ
De Rekeneire, N
Van Ness, PH
Johnson, KC
Kanaya, A
Koster, A
Strotmeyer, ES
Goodpaster, BH
Harris, T
Gill, TM
Inzucchi, SE
AF Lipska, Kasia J.
De Rekeneire, Nathalie
Van Ness, Peter H.
Johnson, Karen C.
Kanaya, Alka
Koster, Annemarie
Strotmeyer, Elsa S.
Goodpaster, Bret H.
Harris, Tamara
Gill, Thomas M.
Inzucchi, Silvio E.
TI Identifying Dysglycemic States in Older Adults: Implications of the
Emerging Use of Hemoglobin A1c
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID GLUCOSE CONTROL; BLOOD-GLUCOSE; HBA(1C); POPULATION; GLYCATION; A(1C);
RISK; AGE; PREVALENCE; HEALTH
AB Context: Hemoglobin A1c (A1c) was recently added to the diagnostic criteria for diabetes and prediabetes.
Objective: Our objective was to examine performance of A1c in comparison with fasting plasma glucose (FPG) in diagnosing dysglycemia in older adults.
Design and Setting: We conducted a cross-sectional analysis of data from the Health, Aging, and Body Composition study at yr 4 (2000-2001) when FPG and standardized A1c measurements were available.
Participants: Of 3075 persons (aged 70-79 yr, 48% men, 42% Black) at study entry, 1865 participants without known diabetes who had appropriate measures were included.
Main outcome measures: Sensitivity and specificity of A1c-based diagnoses were compared with those based on FPG and the proportion of participants identified with dysglycemia by each measure.
Results: Of all participants, 2.7 and 3.1% had undiagnosed diabetes by FPG >= 126 mg/dl and A1c >= 6.5%, respectively. Among the remaining participants, 21.1% had prediabetes by impaired fasting glucose (>= 100 mg/dl) and 22.2% by A1c >= 5.7%. Roughly one third of individuals with diabetes and prediabetes were identified by either FPG or A1c alone and by both tests simultaneously. Sensitivities and specificities of A1c compared with FPG were 56.9 and 98.4% for diabetes and 47.0 and 84.5% for prediabetes, respectively. Blacks and women were more likely to be identified with dysglycemia by A1c than FPG.
Conclusions: In this older population, we found considerable discordance between FPG- and A1c-based diagnosis of diabetes and prediabetes, with differences accentuated by race and gender. Broad implementation of A1c to diagnose dysglycemic states may substantially alter the epidemiology of these conditions in older Americans. (J Clin Endocrinol Metab 95: 5289-5295, 2010)
C1 [Lipska, Kasia J.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06520 USA.
[De Rekeneire, Nathalie; Van Ness, Peter H.; Gill, Thomas M.] Yale Univ, Sch Med, Sect Geriatr, New Haven, CT 06520 USA.
[Inzucchi, Silvio E.] Yale Univ, Sch Med, Endocrinol Sect, Dept Internal Med, New Haven, CT 06520 USA.
[Johnson, Karen C.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38163 USA.
[Kanaya, Alka] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Koster, Annemarie; Harris, Tamara] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Strotmeyer, Elsa S.; Goodpaster, Bret H.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Goodpaster, Bret H.] Univ Pittsburgh, Div Endocrinol & Metab, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
RP Lipska, KJ (reprint author), Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, POB 208088,333 Cedar St,SHM IE 61, New Haven, CT 06520 USA.
EM kasia.lipska@yale.edu
RI Koster, Annemarie/E-7438-2010; Strotmeyer, Elsa/F-3015-2014;
OI Strotmeyer, Elsa/0000-0002-4093-6036
FU National Institute on Aging (NIA) [N01-AG-6-2106, N01-AG-6-2101,
N01-AG-6-2103, K24AG021507]; Claude D. Pepper Older Americans
Independence Center at the Yale University School of Medicine
[2P30AG021342]; National Institutes of Health NIA; Novo Nordisk
FX The Health ABC Study has been supported by the National Institute on
Aging (NIA), contract numbers N01-AG-6-2106, N01-AG-6-2101, and
N01-AG-6-2103. This work was also supported in part by funding from the
Claude D. Pepper Older Americans Independence Center at the Yale
University School of Medicine (2P30AG021342) and in part by the
Intramural Research Program of the National Institutes of Health NIA.
T.M.G. is the recipient of an NIA Midcareer Investigator Award in
Patient-Oriented Research (K24AG021507).; Disclosure Summary: S.E.I.
served on the Advisory Panel for Amylin Pharmaceuticals, Merck, and
Takeda; received research support from Medtronic MiniMed and honoraria
from Novo Nordisk; consulted for Daiichi-Sankyo; and was an expert
witness for Eli Lilly. Other authors report no potential conflicts of
interests.
NR 33
TC 55
Z9 57
U1 0
U2 3
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 2010
VL 95
IS 12
BP 5289
EP 5295
DI 10.1210/jc.2010-1171
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 689PH
UT WOS:000284939800040
PM 20861123
ER
PT J
AU Chudova, D
Wilde, JI
Wang, ET
Wang, H
Rabbee, N
Egidio, CM
Reynolds, J
Tom, E
Pagan, M
Rigl, CT
Friedman, L
Wang, CC
Lanman, RB
Zeiger, M
Kebebew, E
Rosai, J
Fellegara, G
LiVolsi, VA
Kennedy, GC
AF Chudova, Darya
Wilde, Jonathan I.
Wang, Eric T.
Wang, Hui
Rabbee, Nusrat
Egidio, Camila M.
Reynolds, Jessica
Tom, Ed
Pagan, Moraima
Rigl, C. Ted
Friedman, Lyssa
Wang, C. Charles
Lanman, Richard B.
Zeiger, Martha
Kebebew, Electron
Rosai, Juan
Fellegara, Giovanni
LiVolsi, Virginia A.
Kennedy, Giulia C.
TI Molecular Classification of Thyroid Nodules Using High-Dimensionality
Genomic Data
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID FINE-NEEDLE-ASPIRATION; CHRONIC LYMPHOCYTIC THYROIDITIS;
GENE-EXPRESSION; UNDETERMINED SIGNIFICANCE; FOLLICULAR LESION; BENIGN;
TUMORS; CARCINOMA; IDENTIFICATION; DIAGNOSIS
AB Objective: We set out to develop a molecular test that distinguishes benign and malignant thyroid nodules using fine-needle aspirates (FNA).
Design: We used mRNA expression analysis to measure more than 247,186 transcripts in 315 thyroid nodules, comprising multiple subtypes. The data set consisted of 178 retrospective surgical tissues and 137 prospectively collected FNA samples. Two classifiers were trained separately on surgical tissues and FNAs. The performance was evaluated using an independent set of 48 prospective FNA samples, which included 50% with indeterminate cytopathology.
Results: Performance of the tissue-trained classifier was markedly lower in FNAs than in tissue. Exploratory analysis pointed to differences in cellular heterogeneity between tissues and FNAs as the likely cause. The classifier trained on FNA samples resulted in increased performance, estimated using both 30-fold cross-validation and an independent test set. On the test set, negative predictive value and specificity were estimated to be 96 and 84%, respectively, suggesting clinical utility in the management of patients considering surgery. Using in silico and in vitro mixing experiments, we demonstrated that even in the presence of 80% dilution with benign background, the classifier can correctly recognize malignancy in the majority of FNA samples.
Conclusions: The FNA-trained classifier was able to classify an independent set of FNAs in which substantial RNA degradation had occurred and in the presence of blood. High tolerance to dilution makes the classifier useful in routine clinical settings where sampling error may be a concern. An ongoing multicenter clinical trial will allow us to validate molecular test performance on a larger independent test set of prospectively collected thyroid FNAs. (J Clin Endocrinol Metab 95: 5296-5304, 2010)
C1 [Chudova, Darya; Wilde, Jonathan I.; Wang, Eric T.; Wang, Hui; Rabbee, Nusrat; Egidio, Camila M.; Reynolds, Jessica; Tom, Ed; Pagan, Moraima; Rigl, C. Ted; Friedman, Lyssa; Wang, C. Charles; Lanman, Richard B.; Kennedy, Giulia C.] Veracyte Inc, San Francisco, CA 94080 USA.
[Zeiger, Martha] Johns Hopkins Univ Hosp, Sch Med, Baltimore, MD 21287 USA.
[Kebebew, Electron] NCI, Bethesda, MD 20892 USA.
[Rosai, Juan; Fellegara, Giovanni] Ctr Diagnost Italiano, I-20147 Milan, Italy.
[LiVolsi, Virginia A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
RP Kennedy, GC (reprint author), Veracyte Inc, 7000 Shoreline,Court Suite 250, San Francisco, CA 94080 USA.
EM giuliakennedy@yahoo.com
OI Lanman, Richard/0000-0001-8122-4329
FU Veracyte
FX Disclosure Summary: J.I.W., E.T.W., H.W., C.M.E., J.R., E.T., C.T.R.,
L.F., C.C.W., R.B.L., and G.C.K. are employed by and have equity
interests in Veracyte. D.C. and M.P. consult for Veracyte. N.R. was
previously employed by Veracyte. M.Z., E.K., J.R., G.F., and V.A.L. have
received research support from Veracyte.
NR 29
TC 108
Z9 109
U1 0
U2 19
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 2010
VL 95
IS 12
BP 5296
EP 5304
DI 10.1210/jc.2010-1087
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 689PH
UT WOS:000284939800041
PM 20826580
ER
PT J
AU Legro, RS
Schlaff, WD
Diamond, MP
Coutifaris, C
Casson, PR
Brzyski, RG
Christman, GM
Trussell, JC
Krawetz, SA
Snyder, PJ
Ohl, D
Carson, SA
Steinkampf, MP
Carr, BR
McGovern, PG
Cataldo, NA
Gosman, GG
Nestler, JE
Myers, ER
Santoro, N
Eisenberg, E
Zhang, MZ
Zhang, HP
AF Legro, Richard S.
Schlaff, William D.
Diamond, Michael P.
Coutifaris, Christos
Casson, Peter R.
Brzyski, Robert G.
Christman, Gregory M.
Trussell, J. C.
Krawetz, Stephen A.
Snyder, Peter J.
Ohl, Dana
Carson, Sandra A.
Steinkampf, Michael P.
Carr, Bruce R.
McGovern, Peter G.
Cataldo, Nicholas A.
Gosman, Gabriella G.
Nestler, John E.
Myers, Evan R.
Santoro, Nanette
Eisenberg, Esther
Zhang, Meizhuo
Zhang, Heping
CA Reprod Med Network
TI Total Testosterone Assays in Women with Polycystic Ovary Syndrome:
Precision and Correlation with Hirsutism
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; SERUM TESTOSTERONE; CONSENSUS; CRITERIA;
HYPERANDROGENEMIA; CLOMIPHENE; METFORMIN; HORMONES; MARKERS; PCOS
AB Context: There is no standardized assay of testosterone in women. Liquid chromatography mass spectrometry (LC/MS) has been proposed as the preferable assay by an Endocrine Society Position Statement.
Objective: The aim was to compare assay results from a direct RIA with two LC/MS.
Design and Setting: We conducted a blinded laboratory study including masked duplicate samples at three laboratories-two academic (University of Virginia, RIA; and Mayo Clinic, LC/MS) and one commercial (Quest, LC/MS).
Participants and Interventions: Baseline testosterone levels from 596 women with PCOS who participated in a large, multicenter, randomized controlled infertility trial performed at academic health centers in the United States were run by varying assays, and results were compared.
Main Outcome Measure: We measured assay precision and correlation and baseline Ferriman-Gallwey hirsutism scores.
Results: Median testosterone levels were highest with RIA. The correlations between the blinded samples that were run in duplicate were comparable. The correlation coefficient (CC) between LC/MS at Quest and Mayo was 0.83 [95% confidence interval (Cl), 0.80-0.85], between RIA and LC/MS at Mayo was 0.79 (95% Cl, 0.76-0.82), and between RIA and LC/MS at Quest was 0.67 (95% Cl, 0.63-0.72). Interassay variation was highest at the lower levels of total testosterone (<= 50 ng/dl). The CC for Quest LC/MS was significantly different from those derived from the other assays. We found similar correlations between total testosterone levels and hirsutism score with the RIA (CC = 0.24), LC/MS at Mayo (CC = 0.15), or Quest (CC = 0.17).
Conclusions: A testosterone RIA is comparable to LC/MS assays. There is significant variability between LC/MS assays and poor precision with all assays at low testosterone levels. (J Clin Endocrinol Metab 95: 5305-5313, 2010)
C1 [Legro, Richard S.] Penn State Univ, Milton S Hershey Med Ctr, Dept Obstet & Gynecol, Penn State Coll Med, Hershey, PA 17033 USA.
[Schlaff, William D.; Santoro, Nanette] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80217 USA.
[Zhang, Meizhuo; Zhang, Heping] Yale Univ, Sch Publ Hlth, Collaborat Ctr Stat Sci, New Haven, CT 06510 USA.
[Carr, Bruce R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Diamond, Michael P.; Krawetz, Stephen A.] Wayne State Univ, Dept Obstet, Detroit, MI 48202 USA.
[Diamond, Michael P.; Krawetz, Stephen A.] Wayne State Univ, Dept Gynecol, Detroit, MI 48202 USA.
[Carson, Sandra A.] Baylor Coll Med, Houston, TX 77030 USA.
[Steinkampf, Michael P.] Univ Alabama, Birmingham, AL 35294 USA.
[Coutifaris, Christos; Snyder, Peter J.] Univ Penn, Philadelphia, PA 19104 USA.
[McGovern, Peter G.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA.
[Cataldo, Nicholas A.] Stanford Univ, Stanford, CA 94305 USA.
[Gosman, Gabriella G.] Univ Pittsburgh, Pittsburgh, PA 15208 USA.
[Nestler, John E.] Virginia Commonwealth Univ, Sch Med, Dept Med, Richmond, VA 23298 USA.
[Myers, Evan R.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27705 USA.
[Myers, Evan R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA.
[Casson, Peter R.] Univ Vermont, Dept Med & Obstet & Gynecol, Burlington, VT 05405 USA.
[Brzyski, Robert G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA.
[Christman, Gregory M.; Ohl, Dana] Univ Michigan, Reprod Sci Program, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Eisenberg, Esther] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Sci Branch, Bethesda, MD 20814 USA.
RP Legro, RS (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Dept Obstet & Gynecol, Penn State Coll Med, 500 Univ Dr,H103, Hershey, PA 17033 USA.
EM RSL1@psu.edu
OI Diamond, Michael/0000-0001-6353-4489
FU National Institutes of Health (NIH)/Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD) [U10 HD27049,
U10 HD38992, U10HD055925, U01 HD38997, U10 HD39005, U10 HD27011, U10
HD33172, U10 HD38988, U10 HD38998, U10 HD38999, U10 HD055936, U10
HD055942, U10 HD055944, U54HD29834]; General Clinical Research Center
[MO1RR00056, MO1RR10732, C06 RR016499]; Eisai, Inc.; Serono
FX This work was supported by National Institutes of Health (NIH)/Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD) Grants U10 HD27049 (to C.C.), U10 HD38992 (to R.S.L.),
U10HD055925 (to H.Z. and M.Z.), U01 HD38997 (to E.R.M.), U10 HD39005 (to
M.P.D.), U10 HD27011 (to S.A.C.), U10 HD33172 (to M.P.S.), U10 HD38988
(to B.R.C.), U10 HD38998 (to W.D.S.), U10 HD38999 (to P.M.G.), U10
HD055936 (to G.M.C.), U10 HD055942 (to R.G.B.), and U10 HD055944 (to
P.R.C.); U54HD29834 (to the University of Virginia Center for Research
in Reproduction Ligand Assay and Analysis Core of the Specialized
Cooperative Centers Program in Reproduction and Infertility Research);
General Clinical Research Center Grants MO1RR00056 (to the University of
Pittsburgh) and MO1RR10732 and construction grant C06 RR016499 (to
Pennsylvania State University). The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the NICHD or NIH.; Disclosure Summary: W.D.S., M.P.D., C.C., P.R.C.,
R.G.B., G.M.C., J.C.T., S.A.K., P.J.S., D.O., S.A.C., M.P.S., B.R.C.,
P.G.M., N.A.C., G.G.G., J.E.N., E.R.M., N.S., E.E., and M.Z. have
nothing to declare. H.Z. reports receiving consulting fees from Eisai,
Inc. R.S.L. reports lecture fees from Serono.
NR 23
TC 78
Z9 80
U1 0
U2 5
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 2010
VL 95
IS 12
BP 5305
EP 5313
DI 10.1210/jc.2010-1123
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 689PH
UT WOS:000284939800042
PM 20826578
ER
PT J
AU Wei, QX
Levens, ED
Stefansson, L
Nieman, LK
AF Wei, Qingxiang
Levens, Eric D.
Stefansson, Lilja
Nieman, Lynnette K.
TI Indian Hedgehog and Its Targets in Human Endometrium: Menstrual Cycle
Expression and Response to CDB-2914
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID MURINE UTERUS; MOUSE UTERUS; BETA-CATENIN; PROGESTERONE; GENE; ROLES
AB Context: Progesterone is critical for secretory endometrial differentiation in women, but its downstream mediators are poorly understood.
Objective: Our objective was to investigate endometrial expression of Indian Hedgehog (IHH) and genes involved in its signaling [smoothened (SMO), patched-1 (PTCH1), glioma-associated oncogene homolog 1 (GLI1), and GLI2] during the menstrual cycle and the effects of the selective progesterone receptor modulator CDB-2914 on its expression.
Design and Setting: Comparisons between normally cycling volunteers and women with symptomatic fibroids who received CDB-2914 or placebo were made at a clinical research center.
Patients and Interventions: Endometrial biopsy was performed on 34 volunteers, 17 additional women with fibroids.
Main Outcome Measures: Endometrial expression of IHH, SMO, PTCH1, GLI1, and GLI2 by in situ hybridization and/or RT-PCR and IHH, GLI1, and PTCH1 immunohistochemistry were evaluated.
Results: RT-PCR showed expression of IHH, SMO, PTCH1, GLI1, and GLI2, with significant increases in IHH (5.2-fold) and GLI1 (3.6-fold) in endometrium exposed to CDB-2914 compared with placebo. In situ hybridization showed IHH mRNA expression in glands and stroma that was stronger in secretory samples. Among volunteers, IHH and GLI1 immunohistochemistry scores were higher in the secretory than proliferative phase in the nuclei and cytoplasm of glands and stroma(P = 0.0002-0.04). Compared with follicular-phase controls, women exposed to CDB-2914 showed increased IHH expression in all compartments except stromal cytoplasm (P = 0.0199-0.0423); GLI1 was up-regulated in glandular nuclei and cytoplasm compared with both volunteers and women receiving placebo (P <= 0.0416).
Conclusions: The temporal increase in endometrial IHH and GLI1 during the secretory phase, and their modulation by CDB-2914, suggests progestin regulation and a potential role in endometrial differentiation and implantation. (J Clin Endocrinol Metab 95: 5330-5337, 2010)
C1 [Wei, Qingxiang; Levens, Eric D.; Stefansson, Lilja; Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Nieman, LK (reprint author), Bldg 10,CRC,Room 1-3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM niemanl@mail.nih.gov
FU National Institute of Child Health and Human Development, National
Institutes of Health (Bethesda, MD); Laboratoire HRA-Pharma, Paris,
France
FX This work was supported by the Program in Reproductive and Adult
Endocrinology, of the intramural program of National Institute of Child
Health and Human Development, National Institutes of Health (Bethesda,
MD), and by funds provided through a Cooperative Research and
Development Agreement with Laboratoire HRA-Pharma, Paris, France.
NR 22
TC 14
Z9 16
U1 1
U2 3
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 2010
VL 95
IS 12
BP 5330
EP 5337
DI 10.1210/jc.2010-0637
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 689PH
UT WOS:000284939800045
PM 20881264
ER
PT J
AU Liu, JK
Fox, CS
Hickson, DA
May, WD
Hairston, KG
Carr, JJ
Taylor, HA
AF Liu, Jiankang
Fox, Caroline S.
Hickson, DeMarc A.
May, Warren D.
Hairston, Kristen G.
Carr, J. Jeffery
Taylor, Herman A.
TI Impact of Abdominal Visceral and Subcutaneous Adipose Tissue on
Cardiometabolic Risk Factors: The Jackson Heart Study
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID BODY-FAT DISTRIBUTION; METABOLIC SYNDROME; AFRICAN-AMERICAN; WAIST
CIRCUMFERENCE; INSULIN ACTION; MASS INDEX; OLDER MEN; WOMEN;
ASSOCIATION; OBESITY
AB Objective: Obesity is a major driver of cardiometabolic risk. Abdominal visceral adipose tissue (VAT) and sc adipose tissue (SAT) may confer differential metabolic risk profiles. We investigated the relations of VAT and SAT with cardiometabolic risk factors in the Jackson Heart Study cohort.
Methods: Participants from the Jackson Heart Study (n = 2477; 64% women; mean age, 58 yr) underwent multidetector computed tomography, and the volumetric amounts of VAT and SAT were assessed between 2007 and 2009. Cardiometabolic risk factors were examined by sex in relation to VAT and SAT.
Results: Men had a higher mean volume of VAT(873vs. 793cm(3)) and a lower mean volume of SAT(1730 vs. 2659 cm3) than women (P = 0.0001). Per 1-SD increment in either VAT or SAT, we observed elevated levels of fasting plasma glucose and triglyceride, lower levels of high-density lipoprotein-cholesterol, and increased odds ratios for hypertension, diabetes, and metabolic syndrome. The effect size of VAT in women was larger than that of SAT [fasting plasma glucose, 5.51 +/- 1.0 vs. 3.36 +/- 0.9; triglyceride, 0.17 +/- 0.01 vs. 0.05 +/- 0.01; high-density lipoprotein-cholesterol, -5.36 +/- 0.4 vs. n -2.85 +/- 0.4; and odds ratio for hypertension, 1.62 (1.4-1.9) vs. 1.40 (1.2-1.6); diabetes, 1.82 (1.6-2.1) vs. 1.58 (1.4-1.8); and metabolic syndrome, 3.34 (2.8-4.0) vs. 2.06 (1.8-2.4), respectively; P < 0.0001 for difference between VAT and SAT]. Similar patterns were also observed in men. Furthermore, VAT remained associated with most risk factors even after accounting for body mass index (P ranging from 0.006-0.0001). The relationship of VAT to most risk factors was significantly different between women and men.
Conclusions: Abdominal VAT and SAT are both associated with adverse cardiometabolic risk factors, but VAT remains more strongly associated with these risk factors. The results from this study suggest that relations with cardiometabolic risk factors are consistent with a pathogenic role of abdominal adiposity in participants of African ancestry. (J Clin Endocrinol Metab 95: 5419-5426, 2010)
C1 [Liu, Jiankang; Hickson, DeMarc A.; May, Warren D.; Taylor, Herman A.] Jackson State Univ, Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39213 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, NHLBI, Framingham Heart Study, Boston, MA 01702 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Diabet, Dept Med, Boston, MA 01702 USA.
Harvard Univ, Sch Med, Boston, MA 01702 USA.
[Carr, J. Jeffery] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC 27157 USA.
[Hairston, Kristen G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA.
RP Liu, JK (reprint author), Jackson State Univ, Univ Mississippi, Med Ctr, Jackson Heart Study, 350 W Woodrow Wilson Dr, Jackson, MS 39213 USA.
EM jliu@umc.edu
RI Carr, John/A-1938-2012
OI Carr, John/0000-0002-4398-8237
FU National Heart, Lung, and Blood Institute; National Center on Minority
Health and Health Disparities; National Heart, Lung, and Blood Institute
[N01-HC-95170, N01-HC-95171, N01-C-95172]
FX The Jackson Heart Study is supported by the National Heart, Lung, and
Blood Institute and the National Center on Minority Health and Health
Disparities. Funding for H.A.T. was provided under contracts
N01-HC-95170, N01-HC-95171, and N01-C-95172 from the National Heart,
Lung, and Blood Institute and the National Center on Minority Health and
Health Disparities.
NR 28
TC 126
Z9 136
U1 0
U2 6
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 2010
VL 95
IS 12
BP 5419
EP 5426
DI 10.1210/jc.2010-1378
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 689PH
UT WOS:000284939800057
PM 20843952
ER
PT J
AU Yeung, EH
Zhang, CL
Mumford, SL
Ye, AJ
Trevisan, M
Chen, LW
Browne, RW
Wactawski-Wende, J
Schisterman, EF
AF Yeung, Edwina H.
Zhang, Cuilin
Mumford, Sunni L.
Ye, Aijun
Trevisan, Maurizio
Chen, Liwei
Browne, Richard W.
Wactawski-Wende, Jean
Schisterman, Enrique F.
TI Longitudinal Study of Insulin Resistance and Sex Hormones over the
Menstrual Cycle: The BioCycle Study
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID MARGINAL STRUCTURAL MODELS; PLACEBO-CONTROLLED TRIAL; POSTMENOPAUSAL
WOMEN; GLUCOSE-TOLERANCE; YOUNG-WOMEN; REPLACEMENT THERAPY; METABOLIC
SYNDROME; BINDING GLOBULIN; DOUBLE-BLIND; SENSITIVITY
AB Context: Conflicting findings have been reported regarding the effect of menstrual cycle phase and sex hormones on insulin sensitivity.
Objective: The aim was to determine the pattern of insulin resistance over the menstrual cycle and whether variations in sex hormones explain these patterns.
Design: The BioCycle study is a longitudinal study that measured hormones at different phases of the menstrual cycle. Participants had up to eight visits per cycle; each visit was timed using fertility monitors to capture sensitive windows of hormonal changes.
Setting: The study was conducted in the general community of the University at Buffalo (Buffalo, NY).
Participants: A total of 257 healthy, premenopausal women (age, 27 +/- 8 yr; body mass index, 24 +/- 4 kg/m(2)) participated in the study.
Main Outcome Measures: We measured fasting insulin, glucose, and insulin resistance by the homeostasis model of insulin resistance (HOMA-IR).
Results: Significant changes in HOMA-IR were observed over the menstrual cycle; from a midfollicular phase level of 1.35, levels rose to 1.59 during the early luteal phase and decreased to 1.55 in the late-luteal phase. HOMA-IR levels primarily reflected changes in insulin and not glucose. After adjustment for age, race, cycle, and other sex hormones, HOMA-IR was positively associated with estradiol (beta = 0.082; P < 0.001) and progesterone (beta = 0.025; P < 0.001), and inversely associated with FSH (adjusted beta = -0.040; P < 0.001) and SHBG (beta = -0.085; P < 0.001). LH was not associated with HOMA-IR. Further adjustment for BMI weakened the association with SHBG (beta = -0.057; P = 0.06) but did not affect other associations.
Conclusion: Insulin exhibited minor menstrual cycle variability. Estradiol and progesterone were positively associated with insulin resistance and should be considered in studies of insulin resistance among premenopausal women. (J Clin Endocrinol Metab 95: 5435-5442, 2010)
C1 [Yeung, Edwina H.; Zhang, Cuilin; Mumford, Sunni L.; Ye, Aijun; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Bethesda, MD 20892 USA.
[Trevisan, Maurizio] Univ Nevada Hlth Sci Syst, Las Vegas, NV 89103 USA.
[Chen, Liwei] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, Program Epidemiol, New Orleans, LA 70112 USA.
[Browne, Richard W.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14214 USA.
[Browne, Richard W.; Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, 6100 Execut Blvd,Room 7B03,MSC7510, Bethesda, MD 20892 USA.
EM schistee@mail.nih.gov
RI Perez , Claudio Alejandro/F-8310-2010; Yeung, Edwina/F-5992-2015;
OI Perez , Claudio Alejandro/0000-0001-9688-184X; Yeung,
Edwina/0000-0002-3851-2613; Schisterman, Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX This study was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 39
TC 29
Z9 30
U1 0
U2 5
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 2010
VL 95
IS 12
BP 5435
EP 5442
DI 10.1210/jc.2010-0702
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 689PH
UT WOS:000284939800059
PM 20843950
ER
PT J
AU Crompton, PD
Pierce, SK
Miller, LH
AF Crompton, Peter D.
Pierce, Susan K.
Miller, Louis H.
TI Advances and challenges in malaria vaccine development
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID PLASMODIUM-FALCIPARUM MALARIA; CIRCUMSPOROZOITE PROTEIN VACCINE;
TRANSMISSION-BLOCKING VACCINES; RANDOMIZED CONTROLLED-TRIAL; HUMORAL
IMMUNE-RESPONSES; CHONDROITIN SULFATE-A; PAPUA-NEW-GUINEA;
RED-BLOOD-CELLS; PHASE 2A TRIAL; NAIVE ADULTS
AB Malaria caused by Plasmodium falciparum remains a major public health threat, especially among children and pregnant women in Africa. An effective malaria vaccine would be a valuable tool to reduce the disease burden and could contribute to elimination of malaria in some regions of the world. Current malaria vaccine candidates are directed against human and mosquito stages of the parasite life cycle, but thus far, relatively few proteins have been studied for potential vaccine development. The most advanced vaccine candidate, RTS,S, conferred partial protection against malaria in phase II clinical trials and is currently being evaluated in a phase III trial in Africa. New vaccine targets need to be identified to improve the chances of developing a highly effective malaria vaccine. A better understanding of the mechanisms of naturally acquired immunity to malaria may lead to insights for vaccine development.
C1 [Miller, Louis H.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Crompton, Peter D.; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Miller, LH (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA.
RI Crompton, Peter/N-1130-2016
NR 126
TC 107
Z9 109
U1 0
U2 28
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD DEC
PY 2010
VL 120
IS 12
BP 4168
EP 4178
DI 10.1172/JCI44423
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 690AD
UT WOS:000284971400002
PM 21123952
ER
PT J
AU Moreth, K
Brodbeck, R
Babelova, A
Gretz, N
Spieker, T
Zeng-Brouwers, J
Pfeilschifter, J
Young, MF
Schaefer, RM
Schaefer, L
AF Moreth, Kristin
Brodbeck, Rebekka
Babelova, Andrea
Gretz, Norbert
Spieker, Tilmann
Zeng-Brouwers, Jinyang
Pfeilschifter, Josef
Young, Marian F.
Schaefer, Roland M.
Schaefer, Liliana
TI The proteoglycan biglycan regulates expression of the B cell
chemoattractant CXCL13 and aggravates murine lupus nephritis
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID TOLL-LIKE RECEPTORS; GROWTH-FACTOR-BETA; LYMPHOID ORGANS; DENDRITIC
CELLS; RENAL-DISEASE; GLOMERULAR EXPRESSION; DIABETIC-NEPHROPATHY;
CHEMOKINE CXCL13; MESANGIAL CELLS; HUMAN KIDNEY
AB CXCL13 is a key B cell chemoattractant and marker of disease activity in patients with SLE; however, the mechanism of its induction has not been identified yet. Here, we have shown that the proteoglycan biglycan triggers CXCL13 expression via TLR2/4 in macrophages and dendritic cells. In vivo, levels of biglycan were markedly elevated in the plasma and kidneys of human SLE patients and lupus-prone (MRL/lpr) mice. Overexpression of soluble biglycan in MRL/lpr mice raised plasma and renal levels of CXCL13 and caused accumulation of B cells with an enhanced B1/B cell ratio in the kidney, worsening of organ damage, and lbuminuria. Importantly, biglycan also triggered CXCL13 expression and B cell infiltration in the healthy kidney. Conversely, biglycan deficiency improved systemic and renal outcome in lupus-prone mice, with lower levels of autoantibodies, less enlargement of the spleen and lymph nodes, and reduction in renal damage and albuminuria. This correlated with a marked decline in circulating and renal CXCL13 and a reduction in the number of B cells in the kidney. Collectively, our results describe what we believe to be a novel mechanism for the regulation of CXCL13 by biglycan, a host-derived ligand for TLR2/4. Blocking biglycan-TLR2/4 interactions might be a promising strategy for the management of SLE and other B cell-mediated inflammatory disease entities.
C1 [Moreth, Kristin; Brodbeck, Rebekka; Babelova, Andrea; Zeng-Brouwers, Jinyang; Pfeilschifter, Josef; Schaefer, Liliana] Univ Frankfurt Klinikum, Pharmazentrum Frankfurt, Inst Allgemeine Pharmakol & Toxikol, ZAFES, D-60590 Frankfurt, Germany.
[Gretz, Norbert] Univ Heidelberg, Med Res Ctr, D-6800 Mannheim, Germany.
[Spieker, Tilmann] Univ Munster, Inst Pathol, Munster, Germany.
[Young, Marian F.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
[Schaefer, Roland M.] Univ Munster, Dept Internal Med D, Munster, Germany.
RP Schaefer, L (reprint author), Univ Frankfurt Klinikum, Pharmazentrum Frankfurt, Inst Allgemeine Pharmakol & Toxikol, ZAFES, Haus 74,3 108A,Theodor Stern Kai 7, D-60590 Frankfurt, Germany.
OI Schaefer, Liliana/0000-0002-3318-3005
FU Deutsche Forschungsgemeinschaft [SFB 815, A5, A7, SCHA 1082/2-1, GRK
1172]; Else Kroner-Fresenius-Stiftung; NIH/NIDCR
FX This work was supported by the Deutsche Forschungsgemeinschaft (SFB 815,
project A5 to L Schaefer and project A7 to J Pfeilschifter, SCHA
1082/2-1 to L Schaefer, GRK 1172 and Excellence Cluster ECCPS), Else
Kroner-Fresenius-Stiftung, and by the Intramural Research Program of
NIH/NIDCR (to M F Young) The excellent technical support of Riad Haceni
is highly appreciated We thank Chad Casey for his excellent work with
the graphic design
NR 64
TC 71
Z9 74
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
J9 J CLIN INVEST
JI J. Clin. Invest.
PD DEC
PY 2010
VL 120
IS 12
BP 4251
EP 4272
DI 10.1172/JCI42213
PG 22
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 690AD
UT WOS:000284971400014
PM 21084753
ER
PT J
AU Ha, SP
Klemen, ND
Kinnebrew, GH
Brandmaier, AG
Marsh, J
Hangoc, G
Palmer, DC
Restifo, NP
Cornetta, K
Broxmeyer, HE
Touloukian, CE
AF Ha, Sung P.
Klemen, Nicholas D.
Kinnebrew, Garrett H.
Brandmaier, Andrew G.
Marsh, Jon
Hangoc, Giao
Palmer, Douglas C.
Restifo, Nicholas P.
Cornetta, Kenneth
Broxmeyer, Hal E.
Touloukian, Christopher E.
TI Transplantation of mouse HSCs genetically modified to express a
CD4-restricted TCR results in long-term immunity that destroys tumors
and initiates spontaneous autoimmunity
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID CD4(+) T-CELLS; LARGE ESTABLISHED MELANOMA; LENTIVIRAL VECTORS;
HUMAN-LYMPHOCYTES; GENE-THERAPY; SELF-ANTIGEN; HOMEOSTATIC
PROLIFERATION; METASTATIC MELANOMA; NEGATIVE SELECTION; TRANSGENIC MICE
AB The development of effective cancer immunotherapies has been consistently hampered by several factors, including an inability to instigate long-term effective functional antitumor immunity. This is particularly true for immunotherapies that focus on the adoptive transfer of activated or genetically modified mature CD8(+) T cells. In this study, we sought to alter and enhance long-term host immunity by genetically modifying, then transplanting, mouse HSCs. We first cloned a previously identified tumor-reactive HLA-DR4-restricted CD4(+) TCR specific for the melanocyte differentiation antigen tyrosinase-related protein 1 (Tyrp1), then constructed both a high-expression lentivirus vector and a TCR-transgenic mouse expressing the genes encoding this TCR. Using these tools, we demonstrated that both mouse and human HSCs established durable, highefficiency TCR gene transfer following long-term transplantation into lethally irradiated mice transgenic for HLA-DR4. Recipients of genetically modified mouse HSCs developed spontaneous autoimmune vitiligo that was associated with the presence of a Th1-polarized memory effector CD4(+) T cell population that expressed the Tyrp1-specific TCR. Most importantly, large numbers of CD4(+) T cells expressing the Tyrp1-specific TCR were detected in secondary HLA-DR4-transgenic transplant recipients, and these mice were able to destroy subcutaneously administered melanoma cells without the aid of vaccination, immune modulation, or cytokine administration. These results demonstrate the creation of what we believe to be a novel translational model of durable lentiviral gene transfer that results in long-term effective immunity.
C1 [Ha, Sung P.; Klemen, Nicholas D.; Kinnebrew, Garrett H.; Brandmaier, Andrew G.; Marsh, Jon; Hangoc, Giao; Cornetta, Kenneth; Broxmeyer, Hal E.; Touloukian, Christopher E.] Indiana Univ, Sch Med, Dept Surg, Indianapolis, IN 46202 USA.
[Palmer, Douglas C.; Restifo, Nicholas P.] NCI, Bethesda, MD 20892 USA.
RP Touloukian, CE (reprint author), Indiana Univ, Sch Med, Dept Surg, 950 W Walnut St,Res Bldg 2,Room 302, Indianapolis, IN 46202 USA.
RI Restifo, Nicholas/A-5713-2008; Palmer, Douglas/B-9454-2008;
OI Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas
P./0000-0003-4229-4580
FU NIH [R01 RCA134014A]
FX Funding for this research project was supported by grant NIH R01
RCA134014A The authors would like to thank Steven A Rosenberg, Wolfgang
Leitner, and Keith Lillemoe for all their advice and support
NR 77
TC 16
Z9 16
U1 0
U2 2
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD DEC
PY 2010
VL 120
IS 12
BP 4273
EP 4288
DI 10.1172/JCI43274
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 690AD
UT WOS:000284971400015
PM 21084750
ER
PT J
AU Gallagher, PG
Steiner, LA
Liem, RI
Owen, AN
Cline, AP
Seidel, NE
Garrett, LJ
Bodine, DM
AF Gallagher, Patrick G.
Steiner, Laurie A.
Liem, Robert I.
Owen, Ashley N.
Cline, Amanda P.
Seidel, Nancy E.
Garrett, Lisa J.
Bodine, David M.
TI Mutation of a barrier insulator in the human ankyrin-1 gene is
associated with hereditary spherocytosis
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID ENHANCER-BLOCKING ACTIVITY; BETA-GLOBIN LOCUS; CHROMATIN INSULATORS;
DROSOPHILA-MELANOGASTER; NUCLEAR-ORGANIZATION; IN-VITRO; ALTERNATE
PROMOTER; DOMAIN BOUNDARIES; PROGENITOR CELLS; TRANSGENIC MICE
AB Defects of the ankyrin-1 gene are the most common cause in humans of hereditary spherocytosis, an inherited anemia that affects patients of all ethnic groups. In some kindreds, linked -108/-153 nucleotide substitutions have been found in the upstream region of the ankyrin gene promoter that is active in erythroid cells. In vivo, the ankyrin erythroid promoter and its upstream region direct position-independent, uniform expression, a property of barrier insulators. Using human erythroid cell lines and primary cells and transgenic mice, here we have demonstrated that a region upstream of the erythroid promoter is a barrier insulator in vivo in erythroid cells. The region exhibited both functional and structural characteristics of a barrier, including prevention of gene silencing in an in vivo functional assay, appropriate chromatin configuration, and occupancy by barrier- associated proteins. Fragments with the -108/-153 spherocytosis-associated mutations failed to function as barrier insulators in vivo and demonstrated perturbations in barrier-associated chromatin configuration. In transgenic mice, flanking a mutant -108/-153 ankyrin gene promoter with the well-characterized chicken HS4 barrier insulator restored position-independent, uniform expression at levels comparable to wild-type. These data indicate that an upstream region of the ankyrin-1 erythroid promoter acts as a barrier insulator and identify disruption of the barrier element as a potential pathogenetic mechanism of human disease.
C1 [Gallagher, Patrick G.; Steiner, Laurie A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA.
[Gallagher, Patrick G.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
[Liem, Robert I.; Owen, Ashley N.; Cline, Amanda P.; Seidel, Nancy E.; Garrett, Lisa J.; Bodine, David M.] NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Gallagher, PG (reprint author), Yale Univ, Sch Med, Dept Pediat, 333 Cedar St,POB 208064, New Haven, CT 06520 USA.
FU NIDDK [DK62039, HD000850]; National Human Genome Research Institute
FX Supported in part by NIDDK DK62039 (to PG Gallagher), HD000850 (to LA
Steiner), and intramural funds from the National Human Genome Research
Institute (to D M Bodine) The authors thank Bernard Forget, Yale
University, for critical manuscript review
NR 96
TC 15
Z9 17
U1 0
U2 2
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD DEC
PY 2010
VL 120
IS 12
BP 4453
EP 4465
DI 10.1172/JCI42240
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 690AD
UT WOS:000284971400031
PM 21099109
ER
PT J
AU Kennedy, AD
Porcella, SF
Martens, C
Whitney, AR
Braughton, KR
Chen, LA
Craig, CT
Tenover, FC
Kreiswirth, BN
Musser, JM
DeLeo, FR
AF Kennedy, Adam D.
Porcella, Stephen F.
Martens, Craig
Whitney, Adeline R.
Braughton, Kevin R.
Chen, Liang
Craig, Carly T.
Tenover, Fred C.
Kreiswirth, Barry N.
Musser, James M.
DeLeo, Frank R.
TI Complete Nucleotide Sequence Analysis of Plasmids in Strains of
Staphylococcus aureus Clone USA300 Reveals a High Level of Identity
among Isolates with Closely Related Core Genome Sequences
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID INDUCIBLE CLINDAMYCIN RESISTANCE; UNITED-STATES; ENTEROTOXIN-D;
INFECTIONS; EMERGENCE
AB A community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain known as pulsed-field type USA300 (USA300) is epidemic in the United States. Previous comparative whole-genome sequencing studies demonstrated that there has been recent clonal emergence of a subset of USA300 isolates, which comprise the epidemic clone. Although the core genomes of these isolates are closely related, the level of diversity among USA300 plasmids was not resolved. Inasmuch as these plasmids might contribute to significant gene diversity among otherwise closely related USA300 isolates, we performed de novo sequencing of endogenous plasmids from 10 previously characterized USA300 clinical isolates obtained from different geographic locations in the United States. All isolates tested contained small (2- to 3-kb) and/or large (27- to 30-kb) plasmids. The large plasmids encoded heavy metal and/or antimicrobial resistance elements, including those that confer resistance to cadmium, bacitracin, macrolides, penicillin, kanamycin, and streptothricin, although all isolates were sensitive to minocycline, doxycycline, trimethoprim-sulfamethoxazole, vancomycin, teicoplanin, and linezolid. One of the USA300 isolates contained an archaic plasmid that encoded staphylococcal enterotoxins R, J, and P. Notably, the large plasmids (27 to 28 kb) from 8 USA300 isolates-those that comprise the epidemic USA300 clone-were virtually identical (99% identity) and similar to a large plasmid from strain USA300_TCH1516 (a previously sequenced USA300 strain from Houston, TX). These plasmids are largely divergent from the 37-kb plasmid of FPR3757, the first sequenced USA300 strain. The high level of plasmid sequence identity among the majority of closely related USA300 isolates is consistent with the recent clonal emergence hypothesis for USA300.
C1 [Kennedy, Adam D.; Whitney, Adeline R.; Braughton, Kevin R.; Craig, Carly T.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Porcella, Stephen F.; Martens, Craig] NIAID, Rocky Mt Labs, Genom Unit, Res Technol Sect, Hamilton, MT 59840 USA.
[Chen, Liang; Kreiswirth, Barry N.] Univ Med & Dent New Jersey, Publ Hlth Res Inst, Newark, NJ 07103 USA.
[Tenover, Fred C.] Cepheid, Sunnyvale, CA USA.
[Musser, James M.] Methodist Hosp, Ctr Mol & Translat Human Infect Dis, Res Inst, Houston, TX 77030 USA.
[Musser, James M.] Methodist Hosp, Dept Pathol & Lab Med, Houston, TX 77030 USA.
RP DeLeo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM fdeleo@niaid.nih.gov
OI DeLeo, Frank/0000-0003-3150-2516
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 32
Z9 32
U1 0
U2 7
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 2010
VL 48
IS 12
BP 4504
EP 4511
DI 10.1128/JCM.01050-10
PG 8
WC Microbiology
SC Microbiology
GA 686JU
UT WOS:000284693400025
PM 20943864
ER
PT J
AU Schweizer, J
Lu, PS
Mahoney, CW
Berard-Bergery, M
Ho, M
Ramasamy, V
Silver, JE
Bisht, A
Labiad, Y
Peck, RB
Lim, J
Jeronimo, J
Howard, R
Gravitt, PE
Castle, PE
AF Schweizer, Johannes
Lu, Peter S.
Mahoney, Charles W.
Berard-Bergery, Marthe
Ho, Minh
Ramasamy, Valli
Silver, Jon E.
Bisht, Arnima
Labiad, Yassine
Peck, Roger B.
Lim, Jeanette
Jeronimo, Jose
Howard, Roslyn
Gravitt, Patti E.
Castle, Philip E.
TI Feasibility Study of a Human Papillomavirus E6 Oncoprotein Test for
Diagnosis of Cervical Precancer and Cancer
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID TRIAGE
AB In a feasibility study using a prototype, lateral-flow test for human papillomavirus type 16, 18, and/or 45 (HPV16/18/45) E6 oncoproteins, 51 of 75 (68%; 95% confidence interval [95% CI] of 56 to 78%) of HPV16/18/45 DNA-positive specimens from women with a diagnosis of CIN3+ (cervical intraepithelial neoplasia grade 3+ or cervical cancer) tested positive for HPV16/18/45 E6 oncoprotein. None of 16 (95% CI of 0 to 37%) HPV16/18/45 DNA-positive cervical specimens from women with a negative or CIN1 diagnosis tested positive for HPV16/18/45 E6 oncoprotein.
C1 [Schweizer, Johannes; Lu, Peter S.; Mahoney, Charles W.; Berard-Bergery, Marthe; Ho, Minh; Ramasamy, Valli; Silver, Jon E.; Bisht, Arnima; Labiad, Yassine] Arbor Vita Corp, Fremont, CA 94555 USA.
[Peck, Roger B.; Lim, Jeanette; Jeronimo, Jose] Program Appropriate Technol Hlth, Seattle, WA USA.
[Howard, Roslyn; Gravitt, Patti E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Gravitt, Patti E.] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Schweizer, J (reprint author), Arbor Vita Corp, 6611 Dumbarton Circle, Fremont, CA 94555 USA.
EM johannes.schweizer@arborvita.com
FU NIH, National Cancer Institute; NIH SBIR [2R43CA103383-01,
5R44CA121155-03, 5R43 AI068160-02]; Bill & Melinda Gates Foundation
FX P. E. Castle was supported (in part) by the Intramural Research Program
of the NIH, National Cancer Institute. The AV Avantage HPV E6 test
prototype development was a collaboration between Arbor Vita Corporation
and PATH and was funded by NIH SBIR grants 2R43CA103383-01,
5R44CA121155-03, and 5R43 AI068160-02 and by a PATH grant through the
START project, funded by the Bill & Melinda Gates Foundation.
NR 10
TC 24
Z9 26
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 2010
VL 48
IS 12
BP 4646
EP 4648
DI 10.1128/JCM.01315-10
PG 3
WC Microbiology
SC Microbiology
GA 686JU
UT WOS:000284693400055
PM 20926711
ER
PT J
AU Kaiser, LD
Melemed, AS
Preston, AJ
Ross, HAC
Niedzwiecki, D
Fyfe, GA
Gough, JM
Bushnell, WD
Stephens, CL
Mace, MK
Abrams, JS
Schilsky, RL
AF Kaiser, Lee D.
Melemed, Allen S.
Preston, Alaknanda J.
Ross, Hilary A. Chaudri
Niedzwiecki, Donna
Fyfe, Gwendolyn A.
Gough, Jacqueline M.
Bushnell, William D.
Stephens, Cynthia L.
Mace, M. Kelsey
Abrams, Jeffrey S.
Schilsky, Richard L.
TI Optimizing Collection of Adverse Event Data in Cancer Clinical Trials
Supporting Supplemental Indications
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID METASTATIC COLORECTAL-CANCER; CELL LUNG-CANCER; CISPLATIN PLUS
GEMCITABINE; PHASE-III TRIAL; BREAST-CANCER; RANDOMIZED-TRIAL;
POSTMENOPAUSAL WOMEN; FLUOROURACIL FAILURE; BEVACIZUMAB; IRINOTECAN
AB Purpose Although much is known about the safety of an anticancer agent at the time of initial marketing approval, sponsors customarily collect comprehensive safety data for studies that support supplemental indications. This adds significant cost and complexity to the study but may not provide useful new information. The main purpose of this analysis was to assess the amount of safety and concomitant medication data collected to determine a more optimal approach in the collection of these data when used in support of supplemental applications.
Methods Following a prospectively developed statistical analysis plan, we reanalyzed safety data from eight previously completed prospective randomized trials.
Results A total of 107,884 adverse events and 136,608 concomitant medication records were reviewed for the analysis. Of these, four grade 1 to 2 and nine grade 3 and higher events were identified as drug effects that were not included in the previously established safety profiles and could potentially have been missed using subsampling. These events were frequently detected in subsamples of 400 patients or larger. Furthermore, none of the concomitant medication records contributed to labeling changes for the supplemental indications.
Conclusion Our study found that applying the optimized methodologic approach, described herein, has a high probability of detecting new drug safety signals. Focusing data collection on signals that cause physicians to modify or discontinue treatment ensures that safety issues of the highest concern for patients and regulators are captured and has significant potential to relieve strain on the clinical trials system. J Clin Oncol 28:5046-5053. (C) 2010 by American Society of Clinical Oncology
C1 Genentech Inc, San Francisco, CA USA.
Eli Lilly, Indianapolis, IN USA.
GlaxoSmithKline Inc, Philadelphia, PA USA.
Novartis Pharma AG, Basel, Switzerland.
Duke Univ, Med Ctr, Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA.
Amer Soc Clin Oncol, Alexandria, VA USA.
NCI, Bethesda, MD 20892 USA.
[Schilsky, Richard L.] Univ Chicago, Div Biol, Canc & Leukemia Grp B, Chicago, IL 60637 USA.
RP Schilsky, RL (reprint author), Univ Chicago, Div Biol, Canc & Leukemia Grp B, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA.
EM rschilsk@medicine.bsd.uchicago.edu
NR 24
TC 8
Z9 8
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD DEC 1
PY 2010
VL 28
IS 34
BP 5046
EP 5053
DI 10.1200/JCO.2010.29.6608
PG 8
WC Oncology
SC Oncology
GA 686JR
UT WOS:000284693100015
PM 20921453
ER
PT J
AU Landgren, O
Pfeiffer, RM
Kristinsson, SY
Bjorkholm, M
AF Landgren, Ola
Pfeiffer, Ruth M.
Kristinsson, Sigurdur Y.
Bjorkholm, Magnus
TI Survival Patterns in Patients With Hodgkin's Lymphoma With a
Pre-Existing Hospital Discharge Diagnosis of Autoimmune Disease
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; SOLID-ORGAN
TRANSPLANTATION; RHEUMATOID-ARTHRITIS; LYMPHOPROLIFERATIVE DISORDERS;
1ST-DEGREE RELATIVES; CANCER-RISK; METHOTREXATE; IMMUNOSUPPRESSION;
SUSCEPTIBILITY
AB Purpose Autoimmune diseases (AIs) are associated with elevated risk for Hodgkin's lymphoma (HL); however, information on the interplay of AIs and HL on survival is sparse.
Patients and Methods We evaluated survival patterns for 7,414 patients with HL in relation to a pre-existing hospital discharge diagnosis of an AI. We also assessed survival patterns in relation to a prior AI diagnosis among 29,240 population-based matched controls.
Results Among female patients with HL with (v those without) a pre-existing AI, the 5-year and 10-year overall survival was 46.0% (63.3%) and 41.0% (51.9%); for males, the corresponding numbers were 48.5% (59.2%) and 43.6% (51.5%), respectively (P < .001). Among female controls with (v those without) a pre-existing AI, the 5-year and 10-year overall survival was 79.1% (90.2%) and 67.2% (83.3%); for males, the corresponding numbers were 82.5% (90.3%) and 68.6% (81.6%), respectively (P < .001). Female patients with HL with (v those without) a pre-existing AI had a 1.8-fold (range, 1.3- to 2.4-fold) increased relative risk of dying at 5 years of follow-up; for males, the corresponding excess relative risk of dying was 1.7-fold (range, 1.3- to 2.2-fold).
Conclusion Patients with HL have an overall excellent outcome from treatment but also pose some of the most complex challenges of cancer survivorship due to many late effects (eg, second malignancies, thyroid disease, cardiovascular disease, and altered reproductive and sexual function). Our finding that patients with HL with a hospital discharge diagnosis of an AI have a substantially higher risk of dying, emphasizes that underlying chronic diseases, such as AIs, should be high of the list of survivorship concerns for clinicians that treat HL. J Clin Oncol 28:5081-5087. (C) 2010 by American Society of Clinical Oncology
C1 [Landgren, Ola] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
Karolinska Univ Hosp Solna & Inst, Stockholm, Sweden.
RP Landgren, O (reprint author), NCI, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10-Room 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011; Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
FU Swedish Cancer Society, Stockholm County Council; Karolinska Institutet
Foundations; National Institutes of Health, National Cancer Institute
FX Supported by grants from the Swedish Cancer Society, Stockholm County
Council, the Karolinska Institutet Foundations, and the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute.
NR 53
TC 7
Z9 7
U1 0
U2 2
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 2010
VL 28
IS 34
BP 5081
EP 5087
DI 10.1200/JCO.2010.29.2243
PG 7
WC Oncology
SC Oncology
GA 686JR
UT WOS:000284693100020
PM 20940191
ER
PT J
AU Milano, MT
Li, HL
Gail, MH
Constine, LS
Travis, LB
AF Milano, Michael T.
Li, Huilin
Gail, Mitchell H.
Constine, Louis S.
Travis, Lois B.
TI Long-Term Survival Among Patients With Hodgkin's Lymphoma Who Developed
Breast Cancer: A Population-Based Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID LUNG-CANCER; YOUNG-WOMEN; PATHOLOGICAL ANALYSIS; 2ND MALIGNANCY;
RISK-FACTORS; FOLLOW-UP; DISEASE; RADIATION; CHEMOTHERAPY; RADIOTHERAPY
AB Purpose The increased risk of breast cancer (BC) among women receiving chest radiotherapy for Hodgkin's lymphoma (HL) is well-established. However, there are no large population-based studies that describe overall survival (OS) and cause-specific survival (CSS) compared with women with first primary BC.
Methods For 298 HL survivors who developed BC (HL-BC group) and 405,223 women with a first or only BC (BC-1 group), actuarial OS and CSS were compared, accounting for age, BC stage, hormone receptor status, sociodemographic status, radiation for HL, and other variables. All patients were derived from the population-based Surveillance, Epidemiology, and End Results program.
Results OS among patients with HL-BC was significantly inferior that of to patients with BC-1: 15-year OS was 48% versus 69% (P < .0001) for localized BC, and 33% versus 43% (P < .0001) for regional/distant BC. Patients with HL-BC had a significantly increased seven-fold risk (P < .0001) of death from other cancers (ie, not HL or BC) compared with patients with BC-1. Mortality from heart disease among patients with HL-BC with either localized or regional/distant disease was also significantly increased (hazard ratio = 2.22, P = .04; and hazard ratio = 4.28, P = .02, respectively) compared with patients with BC-1. Although 10-year BC-CSS was similar for patients with HL-BC and BC-1 with regional/distant disease, it was inferior for patients with localized BC (82% v 88%, respectively; P = .002).
Conclusion Women with HL may survive a subsequent diagnosis of BC, only to experience significant excesses of death from other primary cancers and cardiac disease. Greater awareness of screening for cardiac disease and subsequent primary cancers in patients with HL-BC is warranted. J Clin Oncol 28:5088-5096.(C) 2010 by American Society of Clinical Oncology
C1 [Milano, Michael T.] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA.
NCI, NIH, Rockville, MD USA.
RP Milano, MT (reprint author), Univ Rochester, Med Ctr, Dept Radiat Oncol, 601 Elmwood Ave,Box 647, Rochester, NY 14642 USA.
EM michael_milano@urmc.rochester.edu
NR 50
TC 31
Z9 31
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD DEC 1
PY 2010
VL 28
IS 34
BP 5088
EP 5096
DI 10.1200/JCO.2010.29.5683
PG 9
WC Oncology
SC Oncology
GA 686JR
UT WOS:000284693100021
PM 20975072
ER
PT J
AU DiazGranados, N
Ibrahim, LA
Brutsche, NE
Ameli, R
Henter, ID
Luckenbaugh, DA
Machado-Vieira, R
Zarate, CA
AF DiazGranados, Nancy
Ibrahim, Lobna A.
Brutsche, Nancy E.
Ameli, Rezvan
Henter, Ioline D.
Luckenbaugh, David A.
Machado-Vieira, Rodrigo
Zarate, Carlos A., Jr.
TI Rapid Resolution of Suicidal Ideation After a Single Infusion of an
N-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant
Major Depressive Disorder
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; ANTIDEPRESSANT TREATMENT;
EMERGENCY-DEPARTMENT; PSYCHIATRIC-PATIENTS; LITHIUM TREATMENT;
GENETIC-MARKERS; RATING-SCALE; RISK; THERAPY; INTERVENTION
AB Objective: Suicidal ideation is a medical emergency, especially when severe. Little research has been done on pharmacologic interventions that could address this problem. Ketamine, an N-methyl-D-aspartate antagonist, has been reported to have antidepressant effects within hours. We examined the effects of a single dose of ketamine on suicidal ideation in subjects with treatment-resistant major depressive disorder (MDD).
Method: Thirty-three subjects with DSM-IV-diagnosed MDD received a single open-label infusion of ketamine (0.5 mg/kg) and were rated at baseline and at 40, 80, 120, and 230 minutes postinfusion with the Scale for Suicide Ideation (SST), the Montgomery-Asberg Depression Rating Scale, the Hamilton Depression Rating Scale, and the Beck Depression Inventory. The study was conducted between October 2006 and January 2009.
Results: Suicidal ideation scores decreased significantly on the SSI as well as on the suicide subscales of other rating instruments within 40 minutes; these decreases remained significant through the first 4 hours postinfusion (P<.001). Ten subjects (30%) had an SSI score 4 at baseline; all these scores dropped below 4 (9 dropped by 40 minutes and 1 by 80 minutes). For those patients with a starting score below 4 on the SSI, only 1 reached a score of 4. Depression, anxiety, and hopelessness were significantly improved at all time points (P<.001).
Conclusions: Suicidal ideation in the context of MDD improved within 40 minutes of a ketamine infusion and remained improved for up to 4 hours postinfusion. Future studies with ketamine in suicidal ideation are warranted due to the potential impact on public health.
C1 NIMH, Expt Therapeut Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
Dept Human Hlth Serv, Bethesda, MD USA.
RP Zarate, CA (reprint author), CRC, 10 Ctr Dr,7 Southeast Unit,Room 7-3465, Bethesda, MD 20892 USA.
EM zaratec@intra.nimh.nih.gov
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190
FU NIMH; NARSAD
FX This study was supported by the Intramural Research Program at NIMH and
by NARSAD (Dr Zarate).
NR 42
TC 191
Z9 194
U1 2
U2 25
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD DEC
PY 2010
VL 71
IS 12
BP 1605
EP 1611
DI 10.4088/JCP.09m05327blu
PG 7
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 707OO
UT WOS:000286296100006
PM 20673547
ER
PT J
AU Blanco, C
Okuda, M
Markowitz, JC
Liu, SM
Grant, BF
Hasin, DS
AF Blanco, Carlos
Okuda, Mayumi
Markowitz, John C.
Liu, Shang-Min
Grant, Bridget F.
Hasin, Deborah S.
TI The Epidemiology of Chronic Major Depressive Disorder and Dysthymic
Disorder: Results From the National Epidemiologic Survey on Alcohol and
Related Conditions
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID COMORBIDITY SURVEY REPLICATION; DSM-IV ALCOHOL; COMPREHENSIVE
DEVELOPMENTAL MODEL; PSYCHIATRIC DIAGNOSTIC MODULES; BEHAVIORAL-ANALYSIS
SYSTEM; GENERAL-POPULATION SAMPLE; PROSPECTIVE FOLLOW-UP; UNITED-STATES;
PERSONALITY-DISORDERS; SOCIAL-CONSEQUENCES
AB Objective: To examine the prevalence of chronic major depressive disorder (CMDD) and dysthymic disorder, their sociodemographic correlates, patterns of 12-month and lifetime psychiatric comorbidity, lifetime risk factors, psychosocial functioning, and mental health service utilization.
Method: Face-to-face interviews were conducted in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (n = 43,093).
Results: The 12-month and lifetime prevalences were greater for CMDD (1.5% and 3.1%, respectively) than for dysthymic disorder (0.5% and 0.9%, respectively). Individuals with CMDD and dysthymic disorder shared most sociodemographic correlates and lifetime risk factors for major depressive disorder. Individuals with CMDD and dysthymic disorder had almost identically high rates of Axis I and Axis II comorbid disorders. However, individuals with CMDD received higher rates of all treatment modalities than individuals with dysthymic disorder.
Conclusions: Individuals with CMDD and dysthymic disorder share many sociodemographic correlates, comorbidity patterns, risk factors, and course. Individuals with chronic depressive disorders, especially those with dysthymic disorder, continue to face substantial unmet treatment needs. J Clin Psychiatry 2010;71(12):1645-1656 (C) Copyright 2010 Physicians Postgraduate Press, Inc.
C1 [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
[Blanco, Carlos; Hasin, Deborah S.] Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Blanco, Carlos; Okuda, Mayumi; Markowitz, John C.; Liu, Shang-Min; Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Hasin, Deborah S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10027 USA.
[Markowitz, John C.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3077,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA.
EM bgrant@willco.niaaa.nih.gov
RI Blanco, Carlos/I-4906-2013; Okuda, Mayumi/L-6210-2013
OI Blanco, Carlos/0000-0001-6187-3057; Okuda, Mayumi/0000-0002-3479-5599
FU Pfizer; GlaxoSmithKline; National Institute of Mental Health (NIMH)
[MH079078]; National Institutes of Health (NIH) [DA019606, DA020783,
DA023200, DA023973, MH076051, AA014223-03]; American Foundation for
Suicide Prevention; New York State Psychiatric Institute
FX Dr Blanco has received research grant/support from Pfizer and
GlaxoSmithKline. Dr Markowitz has received grant/research support from
the National Institute of Mental Health (NIMH) and receives minor
royalties from Oxford University Press, Basic Books, and American
Psychiatric Press. Drs Okuda, Grant, and Hasin and Ms Liu have no
personal affiliations or financial relationships with any commercial
interest to disclose relative to the article.; This study is supported
by National Institutes of Health (NIH) grants DA019606, DA020783,
DA023200, DA023973, and MH076051 (Dr Blanco); a grant from the American
Foundation for Suicide Prevention (Dr Blanco); NIMH grant MH079078 (Dr
Markowitz); NIH grant AA014223-03 (Dr Hasin); and the New York State
Psychiatric Institute (Drs Blanco, Hasin, and Markowitz).
NR 78
TC 34
Z9 35
U1 2
U2 10
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD DEC
PY 2010
VL 71
IS 12
BP 1645
EP 1656
DI 10.4088/JCP.09m05663gry
PG 12
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 707OO
UT WOS:000286296100011
PM 21190638
ER
PT J
AU Winhusen, TM
Somoza, EC
Brigham, GS
Liu, DS
Green, CA
Covey, LS
Croghan, IT
Adler, LA
Weiss, RD
Leimberger, JD
Lewis, DF
Dorer, EM
AF Winhusen, Theresa M.
Somoza, Eugene C.
Brigham, Gregory S.
Liu, David S.
Green, Carla A.
Covey, Lirio S.
Croghan, Ivana T.
Adler, Lenard A.
Weiss, Roger D.
Leimberger, Jeffrey D.
Lewis, Daniel F.
Dorer, Emily M.
TI Impact of Attention-Deficit/Hyperactivity Disorder (ADHD) Treatment on
Smoking Cessation Intervention in ADHD Smokers: A Randomized,
Double-Blind, Placebo-Controlled Trial
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID DEFICIT HYPERACTIVITY DISORDER; OROS METHYLPHENIDATE; CIGARETTE-SMOKING;
NICOTINE PATCH; ADULTS; ADOLESCENTS; CHILDREN; BUPROPION; STIMULANTS;
PREVALENCE
AB Objective: High smoking rates in adults with attention-deficit/hyperactivity disorder (ADHD) and nicotine's amelioration of ADHD suggest that effective ADHD treatment might facilitate abstinence in smokers with ADHD. The present study evaluated if using osmotic-release oral system methylphenidate (OROS-MPH) to treat ADHD enhances response to smoking cessation treatment in smokers with ADHD.
Method: A randomized, double-blind, placebo-controlled, 11-week trial with a 1-month follow-up was conducted at 6 clinical sites between December 2005 and January 2008. Adults (aged 18-55 years) meeting DSM-IV criteria for ADHD and interested in quitting smoking were randomly assigned to OROS-MPH titrated to 72 mg/d (n = 127) or placebo (n = 128). All participants received brief weekly individual smoking cessation counseling for 11 weeks and 21 mg/d nicotine patches starting on the smoking quit day (day 27) through study week 11. Outcome measures included prolonged smoking abstinence and DSM-IV ADHD Rating Scale (ADHD-RS) score.
Results: Of 255 randomly assigned participants, 204 (80%) completed the trial. Prolonged abstinence rates, 43.3% and 42.2%, for the OROS-MPH and placebo groups, respectively, did not differ significantly (OR = 1.1; 95% Cl, 0.63-1.79; P = .81). Relative to placebo, OROS-MPH evidenced a greater reduction in DSM-IV ADHD-RS score (P < .0001) and in cigarettes per day during the post-quit phase (P = .016). Relative to placebo, OROS-MPH increased blood pressure and heart rate to a statistically, but not clinically, significant degree (P < .05); medication discontinuation did not differ significantly between treatments.
Conclusions: Treatment for ADHD did not improve smoking cessation success; OROS-MPH, relative to placebo, effectively treated ADHD and was safe and generally well tolerated in this healthy sample of adult ADHD smokers. Trial Registration: clinical trials.gov Identifier: NCT00253747 J Clin Psychiatry 2010;71(12):1680-1688 (C) Copyright 2010 Physicians Postgraduate Press, Inc.
C1 [Winhusen, Theresa M.; Somoza, Eugene C.; Brigham, Gregory S.; Lewis, Daniel F.; Dorer, Emily M.] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45220 USA.
[Somoza, Eugene C.] Vet Affairs Med Ctr, Cincinnati, OH 45267 USA.
[Brigham, Gregory S.] Maryhaven, Columbus, OH USA.
[Liu, David S.] Ctr Clin Trials Network, Natl Inst Drug Abuse, Bethesda, MD USA.
[Green, Carla A.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA.
[Covey, Lirio S.] Columbia Univ, Med Ctr, New York State Psychiat Inst, New York, NY USA.
[Croghan, Ivana T.] Mayo Clin, Nicotine Res Program, Rochester, MN USA.
[Adler, Lenard A.] Vet Affairs New York Harbor Healthcare Syst, New York, NY USA.
[Weiss, Roger D.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Weiss, Roger D.] McLean Hosp, Alcohol & Drug Abuse Treatment Program, Belmont, MA 02178 USA.
[Leimberger, Jeffrey D.] Duke Clin Res Inst, Durham, NC USA.
RP Winhusen, TM (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, 3210 Jefferson Ave, Cincinnati, OH 45220 USA.
EM winhusen@carc.uc.edu
RI Green, Carla/D-2534-2017;
OI Green, Carla/0000-0002-0000-4381; Winhusen, Theresa/0000-0002-3364-0739;
Brigham, Gregory/0000-0003-1150-4493; Adler, Len/0000-0002-9812-8234
FU Abbott Laboratories; Cortex Pharmaceuticals; Bristol-Myers Squibb; Merck
and Co; Novartis Pharmaceuticals; Pfizer; Shire; Eli Lilly; Ortho
McNeil/Janssen/Johnson and Johnson; New River Pharmaceuticals; Cephalon;
National Institute of Drug Abuse; NYU; Winhusen; Somoza; Brigham; Liu;
Green; Covey; Croghan; Leimberger; National Institute on Drug Abuse
[U10-DA015831, K24 DA022288, U10-DA013035, U10-DA013046, U10-DA013036,
U10-DA013732]
FX Dr Adler is a consultant for Abbott Laboratories, Cortex
Pharmaceuticals, Novartis Pharmaceuticals, Pfizer, Shire, Eli Lilly,
Ortho McNeil/Janssen/Johnson and Johnson, New River Pharmaceuticals,
Cephalon, Merck, Organon, Sanofi-Aventis Pharmaceuticals, Psychogenics,
Mindsite, Major League Baseball, and Psychogenics; has received
grant/research support from Abbott Laboratories, Cortex Pharmaceuticals,
Bristol-Myers Squibb, Merck and Co, Novartis Pharmaceuticals, Pfizer,
Shire, Eli Lilly, Ortho McNeil/Janssen/Johnson and Johnson, New River
Pharmaceuticals, Cephalon, and the National Institute of Drug Abuse; is
a member of the speakers/advisory boards for Abbott Laboratories, Cortex
Pharmaceuticals, Novartis Pharmaceuticals, Pfizer, Shire, Eli Lilly,
Ortho McNeil/Janssen/Johnson and Johnson, New River Pharmaceuticals,
Cephalon, Merck, Organon, Sanofi-Aventis Pharmaceuticals, Eli Lilly, and
Shire; and has received royalty payments (as inventor) from NYU for
license of adult ADHD scales and training materials. Dr Weiss is a
consultant for Titan Pharmaceuticals and has received grant/research
support from Eli Lilly. Drs Winhusen, Somoza, Brigham, Liu, Green,
Covey, Croghan, and Leimberger and Mr Lewis and Ms Dorer have no
personal affiliations or financial relationships with any commercial
interest to disclose relative to the article.; This study was supported
by the following grants from the National Institute on Drug Abuse:
U10-DA015831 and K24 DA022288 to Harvard University (Dr Weiss);
U10-DA013035 to New York State Psychiatric Institute (Dr Nunes);
U10-DA013046 to New York University (Dr Rotrosen); U10-DA013036 to
Oregon Health and Science University (Dr McCarty); and U10-DA013732 to
the University of Cincinnati (Dr Somoza). The study medication and
matching placebo were provided by McNeil Consumer and Specialty
Pharmaceuticals at no cost.
NR 44
TC 52
Z9 52
U1 1
U2 4
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD DEC
PY 2010
VL 71
IS 12
BP 1680
EP 1688
DI 10.4088/JCP.09m05089gry
PG 9
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 707OO
UT WOS:000286296100015
PM 20492837
ER
PT J
AU Salvadore, G
Henter, ID
Zarate, CA
AF Salvadore, Giacomo
Henter, Ioline D.
Zarate, Carlos A., Jr.
TI Anticholinergic Mechanisms: A Forgotten Cause of the Switch Process in
Bipolar Disorder Reply
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Letter
C1 [Salvadore, Giacomo; Henter, Ioline D.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Program, Bethesda, MD 20892 USA.
RP Salvadore, G (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Program, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
NR 10
TC 0
Z9 0
U1 1
U2 1
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD DEC
PY 2010
VL 71
IS 12
BP 1699
EP 1700
DI 10.4088/JCP.10lr06389ayel
PG 2
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 707OO
UT WOS:000286296100020
ER
PT J
AU Siembab, VC
Smith, CA
Zagoraiou, L
Berrocal, MC
Mentis, GZ
Alvarez, F
AF Siembab, Valerie C.
Smith, Courtney A.
Zagoraiou, Laskaro
Berrocal, Maria C.
Mentis, George Z.
Alvarez, Francisco
TI Target Selection of Proprioceptive and Motor Axon Synapses on Neonatal
V1-Derived la Inhibitory lnterneurons and Renshaw Cells
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE spinal cord; VGLUT1; VAChT; development; calbindin; parvalbumin; la
afferent; motoneuron
ID RAT SPINAL-CORD; RECIPROCAL IA INHIBITION; VESICULAR GLUTAMATE
TRANSPORTERS; PRIMARY AFFERENT SYNAPSES; DORSAL-ROOT GANGLIA; V2-DERIVED
INTERNEURONS; POSTNATAL-DEVELOPMENT; RECURRENT INHIBITION;
LOCOMOTOR-ACTIVITY; EXPRESSION
AB The diversity of premotor interneurons in the mammalian spinal cord is generated from a few phylogenetically conserved embryonic classes of interneurons (V0, V1, V2, V3) Their mechanisms of diversification remain unresolved, although these are clearly important to understand motor circuit assembly in the spinal cord Some la inhibitory interneurons (IaINs) and all Renshaw cells (RCs) derive from embryonic V1 interneurons, however, in adult they display distinct functional properties and synaptic inputs, for example proprioceptive inputs preferentially target IaINs, while motor axons target RCs Previously, we found that both inputs converge on RCs in neonates, raising the possibility that proprioceptive (VGLUT1-positive) and motor axon synapses (VAChT-positive) initially target several different V1 interneurons populations and then become selected or deselected postnatally Alternatively, specific inputs might precisely connect only with predefined groups of V1 interneurons To test these hypotheses we analyzed synaptic development on Vi-derived IaINs and compared them to RCs of the same age and spinal cord levels V1-interneurons were labeled using genetically encoded lineage markers in mice The results show that although neonatal Vi-derived IaINs and RCs are competent to receive proprioceptive synapses, these synapses preferentially target the proximal somato-dendritic regions of IaINs and postnatally proliferate on IaINs, but not on RCs In contrast, cholinergic synapses on RCs are specifically derived from motor axons, while on IaINs they originate from Pitx2 V0c interneurons Thus, motor, proprioceptive, and even some interneuron inputs are biased toward specific subtypes of V1-interneurons Postnatal strengthening of these inputs is later superimposed on this initial preferential targeting 1 Comp Neurol 518 4675-4701, 2010 (C) 2010 Wiley Liss Inc
C1 [Siembab, Valerie C.; Smith, Courtney A.; Berrocal, Maria C.; Alvarez, Francisco] Wright State Univ, Dept Neurosci Cell Biol & Physiol, Boonshoft Sch Med, Dayton, OH 45435 USA.
[Zagoraiou, Laskaro] Columbia Univ, Howard Hughes Med Inst, Kavli Inst Brain Sci, Dept Neurosci, New York, NY 10032 USA.
[Mentis, George Z.] NINDS, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA.
RP Alvarez, F (reprint author), Wright State Univ, Dept Neurosci Cell Biol & Physiol, Boonshoft Sch Med, 3640 Colonel Glenn Highway, Dayton, OH 45435 USA.
RI Alvarez, Francisco/H-4929-2011
FU National Institutes of Health (NIH) [NS047357]; Wright State University;
NINDS [NS33245]; ALS
FX Grant sponsor National Institutes of Health (NIH) Grant number NS047357
(to F J A) Grant sponsors Biomedical Sciences PhD program at Wright
State University (to V CS) Intramural Funds of NINDS (to G Z M) Grant
from project ALS (to L Z) Grant sponsor NINDS Grant number NS33245 (to L
Z)
NR 73
TC 24
Z9 24
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9967
EI 1096-9861
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD DEC 1
PY 2010
VL 518
IS 23
BP 4675
EP 4701
DI 10.1002/cne.22441
PG 27
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA 677VQ
UT WOS:000284022500001
PM 20963823
ER
PT J
AU Ye, XG
Yu, YK
Altschul, SF
AF Ye, Xugang
Yu, Yi-Kuo
Altschul, Stephen F.
TI Compositional Adjustment of Dirichlet Mixture Priors
SO JOURNAL OF COMPUTATIONAL BIOLOGY
LA English
DT Article
DE algorithms; combinatorics; linear programming; machine learning;
statistics
ID ACID SUBSTITUTION MATRICES; MULTIPLE SEQUENCE ALIGNMENT; PROTEINS
AB Dirichlet mixture priors provide a Bayesian formalism for scoring alignments of protein profiles to individual sequences, which can be generalized to constructing scores for multiple-alignment columns. A Dirichlet mixture is a probability distribution over multinomial space, each of whose components can be thought of as modeling a type of protein position. Applied to the simplest case of pairwise sequence alignment, a Dirichlet mixture is equivalent to an implied symmetric substitution matrix. For alphabets of even size L, Dirichlet mixtures with L/2 components and symmetric substitution matrices have an identical number of free parameters. Although this suggests the possibility of a one-to-one mapping between the two formalisms, we show that there are some symmetric matrices no Dirichlet mixture can imply, and others implied by many distinct Dirichlet mixtures. Dirichlet mixtures are derived empirically from curated sets of multiple alignments. They imply "background'' amino acid frequencies characteristic of these sets, and should thus be non-optimal for comparing proteins with non-standard composition. Given a mixture Theta, we seek an adjusted Theta' that implies the desired composition, but that minimizes an appropriate relative-entropy-based distance function. To render the problem tractable, we fix the mixture parameter as well as the sum of the Dirichlet parameters for each component, allowing only its center of mass to vary. This linearizes the constraints on the remaining parameters. An approach to finding Theta' may be based on small consecutive parameter adjustments. The relative entropy of two Dirichlet distributions separated by a small change in their parameter values implies a quadratic cost function for such changes. For a small change in implied background frequencies, this function can be minimized using the Lagrange-Newton method. We have implemented this method, and can compositionally adjust to good precision a 20-component Dirichlet mixture prior for proteins in under half a second on a standard workstation.
C1 [Ye, Xugang; Yu, Yi-Kuo; Altschul, Stephen F.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Altschul, SF (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM altschul@ncbi.nlm.nih.gov
NR 21
TC 6
Z9 6
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1066-5277
J9 J COMPUT BIOL
JI J. Comput. Biol.
PD DEC
PY 2010
VL 17
IS 12
BP 1607
EP 1620
DI 10.1089/cmb.2010.0117
PG 14
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 692VT
UT WOS:000285184700002
PM 21128852
ER
PT J
AU Zhang, XN
Zhao, YD
Neumann, AU
AF Zhang, Xinan
Zhao, Yingdong
Neumann, Avidan U.
TI Partial Immunity and Vaccination for Influenza
SO JOURNAL OF COMPUTATIONAL BIOLOGY
LA English
DT Article
DE chi-square test of goodness of fit; influenza type A; mathematical
modeling
ID A VIRUS; EVOLUTION; DYNAMICS; HEMAGGLUTININ; TRANSMISSION; SWITZERLAND;
PATHOGENS; GENEVA; FLU
AB In this article, we estimated the basic reproductive numbers by mathematical modeling and computer simulation using the hospitalization data of influenza type A (H3N2) from the United States as provided by the Centers for Disease Control and Prevention (CDC) from the 2001 to 2006 influenza seasons, respectively. The mean value of basic reproductive number from the 2001-2002 to 2005-2006 influenza seasons is 1.2440, with a 95% confidence interval of 1.1170-1.3710. Our model predicts that the proportion of vaccination of susceptible is 20% and 60 million doses of vaccines should be prepared for each influenza season in the United States. The chi-square test of goodness of fit indicates that our model fits the data reasonably well.
C1 [Zhang, Xinan] Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.
[Zhao, Yingdong] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
[Neumann, Avidan U.] Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel.
RP Zhang, XN (reprint author), Cent China Normal Univ, Sch Math & Stat, Wuhan 430079, Peoples R China.
EM zhangxinan@hotmail.com
FU National Natural Science Foundation of China
FX This work is supported by the National Natural Science Foundation of
China. We thank Dr. Richard Simon in Biometric Research Branch of
National Cancer Institute, NIH, USA for initiating the project and
helpful discussions. We thank the reviewers very much for their valuable
opinions on the original manuscript.
NR 23
TC 2
Z9 3
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1066-5277
J9 J COMPUT BIOL
JI J. Comput. Biol.
PD DEC
PY 2010
VL 17
IS 12
BP 1689
EP 1696
DI 10.1089/cmb.2009.0003
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 692VT
UT WOS:000285184700006
PM 21128855
ER
PT J
AU Chun, YHP
Lu, Y
Hu, Y
Krebsbach, PH
Yamada, Y
Hu, JCC
Simmer, JP
AF Chun, Y. -H. P.
Lu, Y.
Hu, Y.
Krebsbach, P. H.
Yamada, Y.
Hu, J. C. -C.
Simmer, J. P.
TI Transgenic Rescue of Enamel Phenotype in Ambn Null Mice
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE amelogenin; ameloblastin; enamel; tooth
ID TOOTH GERMS; AMELOGENESIS IMPERFECTA; MOLECULAR EVIDENCE; SHEATH
PROTEINS; PORCINE ENAMEL; ANIMAL-MODEL; AMELOBLASTIN; EXPRESSION;
OVEREXPRESSION; SEQUENCES
AB Ameloblastin null mice fail to make an enamel layer, but the defects could be due to an absence of functional ameloblastin or to the secretion of a potentially toxic mutant ameloblastin. We hypothesized that the enamel phenotype could be rescued by the transgenic expression of normal ameloblastin in Ambn mutant mice. We established and analyzed 5 transgenic lines that expressed ameloblastin from the amelogenin (AmelX) promoter and identified transgenic lines that express virtually no transgene, slightly less than normal (Tg+), somewhat higher than normal (Tg++), and much higher than normal (Tg+++) levels of ameloblastin. All lines expressing detectable levels of ameloblastin at least partially recovered the enamel phenotype. When ameloblastin expression was only somewhat higher than normal, the enamel covering the molars and incisors was of normal thickness, had clearly defined rod and interrod enamel, and held up well in function. We conclude that ameloblastin is essential for dental enamel formation.
C1 [Chun, Y. -H. P.; Lu, Y.; Hu, Y.; Krebsbach, P. H.; Hu, J. C. -C.; Simmer, J. P.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
[Chun, Y. -H. P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA.
[Yamada, Y.] Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA.
RP Simmer, JP (reprint author), Univ Michigan, Dent Res Lab, 1210 Eisenhower Pl, Ann Arbor, MI 48108 USA.
EM jsimmer@umich.edu
FU USPHS [DE015846]
FX We thank Thom Saunders, PhD, and the University of Michigan Transgenic
Animal Model Core for generation of the transgenic mice. This research
was supported by USPHS Research Grant DE015846 (NIDCR/NIH). All authors
declare that there are no conflicting interests.
NR 32
TC 13
Z9 13
U1 0
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD DEC
PY 2010
VL 89
IS 12
BP 1414
EP 1420
DI 10.1177/0022034510379223
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 684EG
UT WOS:000284531100013
PM 20940352
ER
PT J
AU Goulding, EH
Hewitt, SC
Nakamura, N
Hamilton, K
Korach, KS
Eddy, EM
AF Goulding, Eugenia H.
Hewitt, Sylvia C.
Nakamura, Noriko
Hamilton, Katherine
Korach, Kenneth S.
Eddy, Edward M.
TI Ex3 alpha ERKO male infertility phenotype recapitulates the alpha ERKO
male phenotype
SO JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID ESTROGEN-RECEPTOR-ALPHA; MUTATION PROVIDES EVIDENCE; MALE
REPRODUCTIVE-SYSTEM; KNOCKOUT MICE; TARGETED DISRUPTION;
DUCTULI-EFFERENTES; LEYDIG-CELLS; NULL MICE; WILD-TYPE; IN-VIVO
AB Disruption of the Esr1 gene encoding estrogen receptor alpha (ER alpha) by insertion of a neomycin resistance gene (neo) into exon 2 (alpha ERKO mice) was shown previously to cause infertility in male mice. While full-length ER alpha protein was not expressed in alpha ERKO mice, alternative splicing resulted in the low-level expression of a truncated form lacking the N-terminus A/B domain and containing the DNA- and ligand-binding domains. Thus, it was unclear whether the reproductive phenotype in alpha ERKO males was only due to the lack of full-length ER alpha or was affected by the presence of the variant ER alpha isoform. The present study examined male mice with deletion of exon 3 of Esr1 gene, lacking the DNA-binding domain, and null for ER alpha (Ex3 alpha ERKO). Dilation of some seminiferous tubules was apparent in male Ex3 alpha ERKO mice as early as postnatal day 10 and was pronounced in all tubules from day 20 onward. At 6 weeks of age, sperm numbers and sperm motility were lower in Ex3 alpha ERKO mice than in wild-type (WT) mice, and the rete testis and efferent ductules were dilated. Mating studies determined that adult Ex3 alpha ERKO males were infertile and failed to produce copulatory plugs. Serum testosterone levels and Hsd17b3 and Cyp17a1 transcript levels were significantly higher, but serum estradiol, progesterone, LH, and FSH levels and Cyp19a1 transcript levels were not significantly different from those in WT mice. These results confirm and extend those seen in other studies on male mice with deletion of exon 3 of Esr1 gene. In addition, the reproductive phenotype of male Ex3 alpha ERKO mice recapitulated the phenotype of alpha ERKO mice, strongly suggesting that the alpha ERKO male infertility was not due to the presence of the DNA-binding domain in the truncated form of ER alpha and that full-length ER alpha is essential for maintenance of male fertility. Journal of Endocrinology (2010) 207, 281-288
C1 [Goulding, Eugenia H.; Nakamura, Noriko; Eddy, Edward M.] NIEHS, Gamete Biol Grp, NIH, Res Triangle Pk, NC 27709 USA.
[Hewitt, Sylvia C.; Hamilton, Katherine; Korach, Kenneth S.] NIEHS, Receptor Biol Grp, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
RP Eddy, EM (reprint author), NIEHS, Gamete Biol Grp, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM eddy@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU NIH, National Institute of Environmental Health Sciences [Z01ES70065,
Z01ES70076]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences, Z01ES70065 (K
S K), and Z01ES70076 (E M E).
NR 39
TC 14
Z9 15
U1 0
U2 2
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0022-0795
J9 J ENDOCRINOL
JI J. Endocrinol.
PD DEC
PY 2010
VL 207
IS 3
BP 281
EP 288
DI 10.1677/JOE-10-0290
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 683QM
UT WOS:000284490300004
PM 20833731
ER
PT J
AU Iwata-Okada, M
Okuyama, T
Kobayashi, S
Kawai, T
Horiuchi, Y
Kiyokawa, N
Li, XK
Fujimoto, J
Otsu, M
Kume, A
Ariga, T
Mizukami, T
Nunoi, H
Kuratsuji, T
Malech, HL
Kang, EM
Onodera, M
AF Iwata-Okada, Mayumi
Okuyama, Torayuki
Kobayashi, Shin-ichi
Kawai, Toshinao
Horiuchi, Yasuomi
Kiyokawa, Nobutaka
Li, Xiao-Kang
Fujimoto, Junichiro
Otsu, Makoto
Kume, Akihiro
Ariga, Tadashi
Mizukami, Tomoyuki
Nunoi, Hiroyuki
Kuratsuji, Tadatoshi
Malech, Harry L.
Kang, Elizabeth M.
Onodera, Masafumi
TI A REPORT OF THE PROGRESS FOR X-CGD GENE THERAPY IN JAPAN
SO JOURNAL OF GENE MEDICINE
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the Japan-Society-of-Gene-Therapy
CY JUL 09-11, 2009
CL Osaka, JAPAN
SP Japan Soc Gene Therapy
C1 [Iwata-Okada, Mayumi; Okuyama, Torayuki; Kobayashi, Shin-ichi; Kawai, Toshinao; Horiuchi, Yasuomi; Kiyokawa, Nobutaka; Li, Xiao-Kang; Fujimoto, Junichiro; Kuratsuji, Tadatoshi; Onodera, Masafumi] Univ Tokyo, Natl Ctr Child Hlth & Dev, Tokyo 1138654, Japan.
[Iwata-Okada, Mayumi] Univ Tokyo, Tokyo Metropolitan Higashiyamato Med Ctr Dev Mult, Tokyo 1138654, Japan.
[Otsu, Makoto] Univ Tokyo, Inst Med Sci, Tokyo 1138654, Japan.
[Kume, Akihiro] Jichi Med Univ, Shimotsuke, Tochigi, Japan.
[Ariga, Tadashi] Hokkaido Univ, Sapporo, Hokkaido 060, Japan.
[Mizukami, Tomoyuki; Nunoi, Hiroyuki] Miyazaki Univ, Miyazaki, Japan.
[Malech, Harry L.; Kang, Elizabeth M.] NIH, Bethesda, MD 20892 USA.
RI Ariga, Tadashi/A-4252-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1099-498X
J9 J GENE MED
JI J. Gene. Med.
PD DEC
PY 2010
VL 12
IS 12
BP 1057
EP 1057
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 694QC
UT WOS:000285311700111
ER
PT J
AU Phillips, KA
Berkenblit, GV
AF Phillips, Karran A.
Berkenblit, Gail V.
TI Training Residents in Outpatient HIV Care
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Letter
C1 [Phillips, Karran A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Berkenblit, Gail V.] Johns Hopkins Sch Med, Baltimore, MD USA.
RP Phillips, KA (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd,BRC 01B-616, Baltimore, MD 21224 USA.
EM phillipsk@nida.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD DEC
PY 2010
VL 25
IS 12
BP 1273
EP 1273
DI 10.1007/s11606-010-1522-7
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 690CN
UT WOS:000284978700005
PM 20882361
ER
PT J
AU Phillips, LR
Swartz, KJ
AF Phillips, L. Revell
Swartz, Kenton J.
TI Position and motions of the S4 helix during opening of the Shaker
potassium channel
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Article
ID DEPENDENT K+ CHANNEL; VOLTAGE-SENSOR; GATING CURRENTS; LIPID-MEMBRANE;
OPEN STATE; INTRACELLULAR GATE; ACTIVATION PATHWAY; TARANTULA TOXINS;
PORE DOMAIN; COOPERATIVITY
AB The four voltage sensors in voltage-gated potassium (Kv) channels activate upon membrane depolarization and open the pore. The location and motion of the voltage-sensing S4 helix during the early activation steps and the final opening transition are unresolved. We studied Zn(2+) bridges between two introduced His residues in Shaker Kv channels: one in the R1 position at the outer end of the S4 helix (R362H), and another in the S5 helix of the pore domain (A419H or F416H). Zn(2+) bridges readily form between R362H and A419H in open channels after the S4 helix has undergone its final motion. In contrast, a distinct bridge forms between R362H and F416H after early S4 activation, but before the final S4 motion. Both bridges form rapidly, providing constraints on the average position of S4 relative to the pore. These results demonstrate that the outer ends of S4 and S5 remain in close proximity during the final opening transition, with the S4 helix translating a significant distance normal to the membrane plane.
C1 [Phillips, L. Revell; Swartz, Kenton J.] Natl Inst Neurol Disorders & Stroke, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Swartz, KJ (reprint author), Natl Inst Neurol Disorders & Stroke, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
EM swartzk@ninds.nih.gov
FU NINDS, National Institutes of Health; National Institute of General
Medical Sciences PRAT
FX This work was supported by the Intramural Research Program of the NINDS,
National Institutes of Health, and a National Institute of General
Medical Sciences PRAT fellowship to L.R. Phillips.
NR 51
TC 10
Z9 10
U1 0
U2 2
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD DEC
PY 2010
VL 136
IS 6
BP 629
EP 644
DI 10.1085/jgp.201010517
PG 16
WC Physiology
SC Physiology
GA 688EG
UT WOS:000284832000005
PM 21115696
ER
PT J
AU Marshall, LJ
Dunham, L
Major, EO
AF Marshall, Leslie J.
Dunham, Lisa
Major, Eugene O.
TI Transcription factor Spi-B binds unique sequences present in the tandem
repeat promoter/enhancer of JC virus and supports viral activity
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; NUCLEAR FACTOR-I; LARGE
T-ANTIGEN; LATENT MEMBRANE-PROTEIN; CELL TYPE-SPECIFICITY; HEAVY-CHAIN
GENE; GLIAL-CELLS; REGULATORY REGION; BONE-MARROW; PUR-ALPHA
AB Progressive rnultifocal leukoencephalopathy (PML) is an often fatal demyelinating disease caused by lytic infection of oligodendrocytes with JC virus (iCV) The development of PML in non-immunosuppressed individuals is a growing concern with reports of mortality in patients treated with mAb therapies JCV can persist in the kidneys, lymphoid tissue and bone marrow JCV gene expression is restricted by non-coding viral regulatory region sequence variation and cellular transcription factors Because JCV latency has been associated with cells undergoing haematopoietic development, transcription factors previously reported as lymphoid specific may regulate JCV gene expression This study demonstrates that one such transcription factor, Spi-B, binds to sequences present in the JCV promoter/enhancer and may affect early virus gene expression in cells obtained from human brain tissue We identified four potential Spi-B-binding sites present in the promoter/enhancer elements of JCV sequences from PML variants and the non-pathogenic archetype Spi-B sites present in the promoter/enhancers of PML variants alone bound protein expressed in JCV susceptible brain and lymphoid-derived cell lines by electromobility shift assays Expression of exogenous Spi-B in semi- and non-permissive cells increased early viral gene expression Strikingly, mutation of the Spi-B core in a binding site unique to the Mad-4 variant was sufficient to abrogate viral activity in progenitor-derived astrocytes These results suggest that Spi-B could regulate JCV gene expression in susceptible cells, and may play an important role in JCV activity in the immune and nervous systems
C1 [Marshall, Leslie J.; Dunham, Lisa; Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA.
RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA.
NR 82
TC 29
Z9 29
U1 1
U2 1
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD DEC
PY 2010
VL 91
BP 3042
EP 3052
DI 10.1099/vir.0.023184-0
PN 12
PG 11
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 693JS
UT WOS:000285221000018
PM 20826618
ER
PT J
AU Teufel, A
Maass, T
Strand, S
Kanzler, S
Galante, T
Becker, K
Strand, D
Biesterfeld, S
Westphal, H
Galle, PR
AF Teufel, Andreas
Maass, Thorsten
Strand, Susanne
Kanzler, Stephan
Galante, Tiziana
Becker, Kevin
Strand, Dennis
Biesterfeld, Stefan
Westphal, Heiner
Galle, Peter R.
TI Liver-specific Ldb1 deletion results in enhanced liver cancer
development
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
ID LIM-HOMEODOMAIN PROTEINS; DOMAIN-BINDING PROTEIN;
HEPATOCELLULAR-CARCINOMA; GENE; TRANSCRIPTION; EXPRESSION; APOPTOSIS;
COFACTOR; LMO4; CELLS
AB Background 82 Aims LIM-domain-binding (Ldb) proteins have been demonstrated to be essential not only to key embryonic developmental processes but also to carcinogenesis We have previously demonstrated Ldb1 to be of high biological and developmental relevance as a targeted deletion of the Ldb1 gene in mice results in an embryonic lethal and pleiotropic phenotype
Methods We have now established a liver-specific Ldb1 knock Out to investigate the role of Ldb1 in carcinogenesis in particular in hepatocellular carcinoma (HCC) development in vivo
Results These mice demonstrated a significantly enhanced growth of liver cancer by means of tumor size and number advocating for an essential role of Ldb1 in HCC development In addition proliferation and resistance against apoptosis were increased In order to identify the functional disturbances due to a lack of Ldb1 we performed a 15 k mouse gene microarray expression analysis We found the Myc oncogene to be regulated in the microarray analysis and were able to further confirm this regulation by demonstrating an over-expression of its downstream target Cyclin D1 Furthermore we were able to demonstrate a down-regulation of the tumor suppressor p21 Finally the liver stem cell marker EpCAM was also identified to be over expressed in Ldb1(-/-) knock out mice
Conclusions We have established a significant role of Ldb1 in cancer development Furthermore we provided evidence for a myc/cyclin D1 p21 and EpCAM-dependent signalling to be key downstream regulators of this novel concept in HCC development (C) 2010 Published by Elsevier B V on behalf of the European Association for the Study of the Liver
C1 [Teufel, Andreas; Maass, Thorsten; Strand, Susanne; Kanzler, Stephan; Galante, Tiziana; Strand, Dennis; Galle, Peter R.] Johannes Gutenberg Univ Mainz, Dept Med 1, D-55101 Mainz, Germany.
[Becker, Kevin] NIA, Gene Express Unit, NIH, Bethesda, MD 20892 USA.
[Biesterfeld, Stefan] Univ Dusseldorf, Inst Cytopathol, D-4000 Dusseldorf, Germany.
[Westphal, Heiner] NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA.
RP Teufel, A (reprint author), Johannes Gutenberg Univ Mainz, Dept Med 1, Bldg 605,Langenbeckstr 1, D-55101 Mainz, Germany.
OI Becker, Kevin/0000-0002-6794-6656
FU German Research Foundation (Deutsche Forschungsgemeinschaft) Bonn
Germany [TE327/3-1]
FX This work was supported by the German Research Foundation (Deutsche
Forschungsgemeinschaft) Bonn Germany (TE327/3-1)
NR 34
TC 8
Z9 8
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD DEC
PY 2010
VL 53
IS 6
BP 1078
EP 1084
DI 10.1016/j.jhep.2010.05.027
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 689HF
UT WOS:000284918000016
PM 20828852
ER
PT J
AU Anderson, DE
McNeely, JD
Windham, BG
AF Anderson, D. E.
McNeely, J. D.
Windham, B. G.
TI Regular slow-breathing exercise effects on blood pressure and breathing
patterns at rest
SO JOURNAL OF HUMAN HYPERTENSION
LA English
DT Article
DE BP; breathing; tidal volume
ID END-TIDAL CO2; HYPERTENSION; DEVICE; WOMEN; SODIUM
AB Previous studies reported that a device-guided slow-breathing (DGB) exercise decreases resting blood pressure (BP) in hypertensive patients. This study investigated the effects of daily practice of DGB on (a) 24-h BP and breathing patterns in the natural environment, as well as (b) BP and breathing pattern during clinic rest. Altogether, 40 participants with pre-hypertension or stage 1 hypertension were trained to decrease breathing rate through DGB or to passively attend to breathing (control, CTL) during daily 15-min sessions. The participants practiced their breathing exercise at home for 4 weeks. The DGB (but not the CTL) intervention decreased clinic resting BP, mid-day ambulatory systolic BP (in women only) and resting breathing rate, and increased resting tidal volume. However, 24-h BP level was not changed by DGB or CTL interventions, nor was overnight breathing pattern. These findings are consistent with the conclusion that a short-term, autonomic mechanism mediated the observed changes in resting BP, but provided no evidence that regular DGB affected factors involved in long-term BP regulation. Additional research will be needed to determine whether 24-h BP can be lowered by a more prolonged intervention. Journal of Human Hypertension (2010) 24, 807-813; doi:10.1038/jhh.2010.18; published online 4 March 2010
C1 [Anderson, D. E.; McNeely, J. D.; Windham, B. G.] NIA, Clin Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Anderson, DE (reprint author), Univ Calif San Francisco, Osher Ctr Integrat Med, Campus Box 1726, San Francisco, CA 94143 USA.
EM Andersod@mail.nih.gov
FU NIH, National Institute on Aging
FX This research was solely supported by the Intramural Research Program of
the NIH, National Institute on Aging. The authors are indebted to Dr
Deborah Grady for calling our attention to the guided breathing device,
and to Drs Benjamin Gavish, S Mortesa Farasat and Margaret A Chesney for
review of the paper.
NR 22
TC 15
Z9 15
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9240
J9 J HUM HYPERTENS
JI J. Hum. Hypertens.
PD DEC
PY 2010
VL 24
IS 12
BP 807
EP 813
DI 10.1038/jhh.2010.18
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 682BQ
UT WOS:000284374100006
PM 20200548
ER
PT J
AU Wang, LY
Hou, LP
Li, HF
Chen, J
Kelly, TN
Jaquish, CE
Rao, DC
Hixson, JE
Hu, DS
Chen, CS
Gu, C
Chen, SF
Lu, XF
Whelton, PK
He, JA
Lu, FH
Huang, JF
Liu, DP
Gu, DF
AF Wang, Laiyuan
Hou, Liping
Li, Hongfan
Chen, Jing
Kelly, Tanika N.
Jaquish, Cashell E.
Rao, Dabeeru C.
Hixson, James E.
Hu, Dongsheng
Chen, Chung-Shiuan
Gu, Charles
Chen, Shufeng
Lu, Xiangfeng
Whelton, Paul K.
He, Jiang
Lu, Fanghong
Huang, Jianfeng
Liu, De-Pei
Gu, Dongfeng
CA GenSalt Collaborative Res Grp
TI Genetic variants in the renin-angiotensin system and blood pressure
reactions to the cold pressor test
SO JOURNAL OF HYPERTENSION
LA English
DT Article
DE blood pressure; cold pressor test; genetics; polymorphism;
renin-angiotensin system
ID CARDIOVASCULAR-DISEASE; ESSENTIAL-HYPERTENSION; STRESS; REACTIVITY;
ALPHA(2C)-ADRENOCEPTOR; POPULATION; RECEPTOR; CHINESE; VASOCONSTRICTION;
POLYMORPHISMS
AB Objectives The purpose of this study was to examine the association between genetic variants in the renin-angiotensin system and blood pressure (BP) responses to the cold pressor test (CPT).
Methods The CPT was conducted among 1998 Han Chinese participants. BP measurements were obtained before and after the CPT using a standard sphygmomanometer according to a standard protocol. The association between SNP genotypes and BP responses to the CPT was assessed using a mixed linear model.
Results Of 68 SNPs genotyped in six renin-angiotensin system genes, two were strongly associated with DBP responses to CPT (P <= 0.001; false discovery rate q value < 0.05): rs2006765 and rs943580 in the angiotensinogen (AGT) gene. Compared to C allele carriers of rs2006765, the TT homozygotes had a significantly decreased DBP response to the CPT. For participants with the TT genotype, percentage DBP responses were 5.68% (4.25-7.10%), compared to corresponding responses of 9.17% (8.66-9.68%) among participants with the CC+CT genotype. In addition, SNP rs4681443 of the angiotensin type 1 receptor (AGTR1) gene was significantly associated with percentage SBP responses to CPT (P <= 0.001; q-value < 0.05).
Conclusion Briefly, our study identified variants in the AGT and AGTR1 genes that may influence BP responses to CPT in the Han Chinese population. These results show that genetic variants in the renin-angiotensin system play an important role in BP responses to CPT and, therefore, in predicting future hypertension. J Hypertens 28:2422-2428 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Wang, Laiyuan; Hou, Liping; Li, Hongfan; Chen, Shufeng; Lu, Xiangfeng; Huang, Jianfeng; Gu, Dongfeng] Chinese Acad Med Sci, Cardiovasc Inst, Dept Evidence Based Med, Beijing 100037, Peoples R China.
[Wang, Laiyuan; Hou, Liping; Li, Hongfan; Chen, Shufeng; Lu, Xiangfeng; Huang, Jianfeng; Gu, Dongfeng] Chinese Acad Med Sci, Cardiovasc Inst, Div Populat Genet, Beijing 100037, Peoples R China.
[Wang, Laiyuan; Hou, Liping; Li, Hongfan; Chen, Shufeng; Lu, Xiangfeng; Huang, Jianfeng; Gu, Dongfeng] Chinese Acad Med Sci, Fu Wai Hosp, Beijing 100037, Peoples R China.
[Wang, Laiyuan; Hou, Liping; Li, Hongfan; Chen, Shufeng; Lu, Xiangfeng; Huang, Jianfeng; Liu, De-Pei; Gu, Dongfeng] Peking Union Med Coll, Beijing 100037, Peoples R China.
[Wang, Laiyuan] Chinese Natl Human Genome Ctr Beijing, Beijing, Peoples R China.
[Chen, Jing; Kelly, Tanika N.; Chen, Chung-Shiuan; He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
[Chen, Jing; He, Jiang] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
[Jaquish, Cashell E.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Rao, Dabeeru C.; Gu, Charles] Washington Univ, Sch Med, St Louis, MO USA.
[Hixson, James E.] Univ Texas Sch Publ Hlth, Houston, TX USA.
[Hu, Dongsheng] Zhengzhou Univ, Sch Publ Hlth, Zhengzhou, Henan, Peoples R China.
[Whelton, Paul K.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA.
[Lu, Fanghong] Shandong Acad Med Sci, Jinan, Shandong, Peoples R China.
[Liu, De-Pei] Chinese Acad Med Sci, Natl Lab Med Mol Biol, Inst Basic Med Sci, Beijing 100037, Peoples R China.
RP Gu, DF (reprint author), Chinese Acad Med Sci, Cardiovasc Inst, Dept Evidence Based Med, 167 Beilishi Rd, Beijing 100037, Peoples R China.
EM gudf@yahoo.com
RI Hou, Liping/G-1648-2011; Gu, Charles/A-7934-2010
OI Hou, Liping/0000-0003-3972-245X; Gu, Charles/0000-0002-8527-8145
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland [U01HL072507]
FX The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is
supported by a cooperative agreement project grant (U01HL072507) from
the National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland.
NR 37
TC 7
Z9 7
U1 0
U2 5
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 2010
VL 28
IS 12
BP 2422
EP 2428
DI 10.1097/HJH.0b013e32833ea74e
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 681IU
UT WOS:000284306000012
PM 20811292
ER
PT J
AU Garboczi, DN
Ghosh, P
Utz, U
Fan, QR
Biddison, WE
Wiley, DC
AF Garboczi, David N.
Ghosh, Partho
Utz, Ursula
Fan, Qing R.
Biddison, William E.
Wiley, Don C.
TI Structure of the complex between human T-cell receptor, viral peptide
and HLA-A2
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
AB Recognition by a T-cell antigen receptor (TCR) of peptide complexed with a major histo-compatibility complex (MHC) molecule occurs through variable loops in the TCR structure which bury almost all the available peptide and a much larger area of the MHC molecule. The TCR fits diagonally across the MHC peptide-binding site in a surface feature common to all class I and II MHC molecules, providing evidence that the nature of binding is general. A broadly applicable binding mode has implications for the mechanism of repertoire selection and the magnitude of alloreactions.
C1 [Garboczi, David N.; Ghosh, Partho; Fan, Qing R.; Wiley, Don C.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Garboczi, David N.; Ghosh, Partho; Fan, Qing R.; Wiley, Don C.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
[Utz, Ursula] Inst Rech Clin Montreal, Immunol Lab, Montreal, PQ H2W 1R7, Canada.
[Biddison, William E.] NINDS, Mol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
RP Wiley, DC (reprint author), Harvard Univ, Dept Mol & Cellular Biol, 7 Divin Ave, Cambridge, MA 02138 USA.
FU Department of the Army; Irvington Institute for Medical Research; HHMI
FX D.N.G. and P.G. contributed equally to this work. We thank A. Haykov, N.
Sinitskaya and R. Crouse for technical assistance, S.C. Harrison for
discussion , R.A. Mariuzza for V alpha 1934.4 coordinates, K.C. Garcia
and I.A. Wilson for making their manuscript available before
publication, members of our laboratory and the synchrotron staff for
help at CHESS, and D. Takemoto for help with figure. D.N.G. is supported
by a fellowship from the Department of the Army; no official endorsement
by the government should be inferred. P.G. was supported by the
Irvington Institute for Medical Research and the HMMI. D.C.W. is an
investigator of the HHMI, which supported this research.
NR 11
TC 0
Z9 0
U1 0
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD DEC 1
PY 2010
VL 185
IS 11
BP 134
EP 141
PG 8
WC Immunology
SC Immunology
GA 681KJ
UT WOS:000284311500002
ER
PT J
AU Laird, RM
Laky, K
Hayes, SM
AF Laird, Renee M.
Laky, Karen
Hayes, Sandra M.
TI Unexpected Role for the B Cell-Specific Src Family Kinase B Lymphoid
Kinase in the Development of IL-17-Producing gamma delta T Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID PROTEIN-TYROSINE KINASES; LISTERIA-MONOCYTOGENES INFECTION; ALPHA-BETA;
INTERFERON-GAMMA; INTERLEUKIN-7 RECEPTOR; TCR SIGNALS; IFN-GAMMA;
EXPRESSION; LINEAGE; MICE
AB The Ag receptors on alpha beta and gamma delta T cells differ not only in the nature of the ligands that they recognize but also in their signaling potential. We hypothesized that the differences in alpha beta- and gamma delta TCR signal transduction were due to differences in the intracellular signaling pathways coupled to these two TCRs. To investigate this, we used transcriptional profiling to identify genes encoding signaling molecules that are differentially expressed in mature alpha beta and gamma delta T cell populations. Unexpectedly, we found that B lymphoid kinase (Blk), a Src family kinase expressed primarily in B cells, is expressed in gamma delta T cells but not in alpha beta T cells. Analysis of Blk-deficient mice revealed that Blk is required for the development of IL-17-producing gamma delta T cells. Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. The Journal of Immunology, 2010, 185: 6518-6527.
C1 [Laird, Renee M.; Hayes, Sandra M.] SUNY Syracuse, Dept Microbiol & Immunol, Upstate Med Univ, Syracuse, NY 13210 USA.
[Laky, Karen] NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Hayes, SM (reprint author), SUNY Syracuse, Dept Microbiol & Immunol, Upstate Med Univ, 750 E Adams St, Syracuse, NY 13210 USA.
EM HayesSa@upstate.edu
FU Hendricks Fund for Medical Research; National Institutes of Health
[AI081068]
FX This work was supported by the Hendricks Fund for Medical Research and
National Institutes of Health Grant AI081068.
NR 55
TC 36
Z9 38
U1 1
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD DEC 1
PY 2010
VL 185
IS 11
BP 6518
EP 6527
DI 10.4049/jimmunol.1002766
PG 10
WC Immunology
SC Immunology
GA 681KJ
UT WOS:000284311500016
PM 20974990
ER
PT J
AU Zhang, HH
Song, KM
Rabin, RL
Hill, BJ
Perfetto, SP
Roederer, M
Douek, DC
Siegel, RM
Farber, JM
AF Zhang, Hongwei H.
Song, Kaimei
Rabin, Ronald L.
Hill, Brenna J.
Perfetto, Stephen P.
Roederer, Mario
Douek, Daniel C.
Siegel, Richard M.
Farber, Joshua M.
TI CCR2 Identifies a Stable Population of Human Effector Memory CD4(+) T
Cells Equipped for Rapid Recall Response
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CYTOMEGALOVIRUS-SPECIFIC CD4(+);
PRIMARY IMMUNE-RESPONSE; VIRUS TYPE-1 INFECTION; EPSTEIN-BARR-VIRUS;
LYMPH-NODE; L-SELECTIN; PHENOTYPIC CHARACTERIZATION; DIFFERENTIAL
REGULATION; INTERLEUKIN (IL)-2
AB Because T cells act primarily through short-distance interactions, homing receptors can identify colocalizing cells that serve common functions. Expression patterns for multiple chemokine receptors on CD4(+) T cells from human blood suggested a hierarchy of receptors that are induced and accumulate during effector/memory cell differentiation. We characterized CD4(+)CD45RO(+) T cells based on expression of two of these receptors, CCR5 and CCR2, the principal subsets being CCR5(-)CCR2(-) (similar to 70%), CCR5(+)CCR2(-) (similar to 25%), and CCR5(+)CCR2(+) (similar to 5%). Relationships among expression of CCR5 and CCR2 and CD62L, and the subsets' proliferation histories, suggested a pathway of progressive effector/memory differentiation from the CCR5(-)CCR2(-) to CCR5(+)CCR2(-) to CCR5(+)CCR2(+) cells. Sensitivity and rapidity of TCR-mediated activation, TCR signaling, and effector cytokine production by the subsets were consistent with such a pathway. The subsets also showed increasing responsiveness to IL-7, and the CCR5(+)CCR2(+) cells were CD127(bright) and invariably showed the greatest response to tetanus toxoid. CCR5(+)CCR2(+) cells also expressed the largest repertoire of chemokine receptors and migrated to the greatest number of chemokines. By contrast, the CCR5(+)CCR2(-) cells had the greatest percentages of regulatory T cells, activated/cycling cells, and CMV-reactive cells, and were most susceptible to apoptosis. Our results indicate that increasing memory cell differentiation can be uncoupled from susceptibility to death, and is associated with an increase in chemokine responsiveness, suggesting that vaccination (or infection) can produce a stable population of effector-capable memory cells that are highly enriched in the CCR5(+)CCR2(+) subset and ideally equipped for rapid recall responses in tissue. The Journal of Immunology, 2010, 185: 6646-6663.
C1 [Siegel, Richard M.; Farber, Joshua M.] NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
[Zhang, Hongwei H.; Song, Kaimei; Farber, Joshua M.] NIAID, Inflammat Biol Sect, Lab Mol Immunol, Bethesda, MD 20892 USA.
[Hill, Brenna J.; Douek, Daniel C.] NIAID, Human Immunol Sect, Bethesda, MD 20892 USA.
[Perfetto, Stephen P.; Roederer, Mario] NIAID, Vaccine Res Ctr, ImmunoTechnol Sect, Bethesda, MD 20892 USA.
[Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Farber, JM (reprint author), NIAMSD, Autoimmun Branch, NIH, Bldg 10,Room 11N-112,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jfarber@niaid.nih.gov
OI Siegel, Richard/0000-0001-5953-9893
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 80
TC 17
Z9 19
U1 0
U2 3
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 2010
VL 185
IS 11
BP 6646
EP 6663
DI 10.4049/jimmunol.0904156
PG 18
WC Immunology
SC Immunology
GA 681KJ
UT WOS:000284311500030
PM 20980630
ER
PT J
AU Dolan, BP
Knowlton, JJ
David, A
Bennink, JR
Yewdell, JW
AF Dolan, Brian P.
Knowlton, Jonathan J.
David, Alexandre
Bennink, Jack R.
Yewdell, Jonathan W.
TI RNA Polymerase II Inhibitors Dissociate Antigenic Peptide Generation
from Normal Viral Protein Synthesis: A Role for Nuclear Translation in
Defective Ribosomal Product Synthesis?
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MHC CLASS-I; MESSENGER-RNA; MAMMALIAN-CELLS; MAJOR SOURCE; VIRUS;
LOCALIZATION; DEGRADATION; COMPLEX; SYNTHETASES; MOLECULES
AB Following viral infection, cells rapidly present peptides from newly synthesized viral proteins on MHC class I molecules, likely from rapidly degraded forms of nascent proteins. The nature of these defective ribosomal products (DRiPs) remains largely undefined. Using inhibitors of RNA polymerase II that block influenza A virus neuraminidase (NA) mRNA export from the nucleus and inhibit cytoplasmic NA translation, we demonstrate a surprising disconnect between levels of NA translation and generation of SIINFEKL peptide genetically inserted into the NA stalk. A 33-fold reduction in NA expression is accompanied by only a 5-fold reduction in K-b-SIINFEKL complex cell-surface expression, resulting in a net 6-fold increase in the overall efficiency of Ag presentation. Although the proteasome inhibitor MG132 completely blocked K-b-SIINFEKL complex generation, we were unable to biochemically detect a MG132-dependent cohort of NA DRiPs relevant for Ag processing, suggesting that a minute population of DRiPs is a highly efficient source of antigenic peptides. These data support the idea that Ag processing uses compartmentalized translation, perhaps even in the nucleus itself, to increase the efficiency of the generation of class I peptide ligands. The Journal of Immunology, 2010, 185: 6728-6733.
C1 [Dolan, Brian P.; Knowlton, Jonathan J.; David, Alexandre; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
RP Yewdell, JW (reprint author), NIH, Room 2E13C1,Bldg 33, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
RI yewdell, jyewdell@nih.gov/A-1702-2012;
OI David, Alexandre/0000-0003-3365-1339
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases.
NR 34
TC 20
Z9 20
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 2010
VL 185
IS 11
BP 6728
EP 6733
DI 10.4049/jimmunol.1002543
PG 6
WC Immunology
SC Immunology
GA 681KJ
UT WOS:000284311500038
PM 21048111
ER
PT J
AU Tan, CY
Aziz, MK
Lovaas, JD
Vistica, BP
Shi, GP
Wawrousek, EF
Gery, I
AF Tan, Cuiyan
Aziz, Mehak K.
Lovaas, Jenna D.
Vistica, Barbara P.
Shi, Guangpu
Wawrousek, Eric F.
Gery, Igal
TI Antigen-Specific Th9 Cells Exhibit Uniqueness in Their Kinetics of
Cytokine Production and Short Retention at the Inflammatory Site
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID EFFECTOR T-CELLS; IL-9; DIFFERENTIATION; PLASTICITY; DISEASE;
EXPRESSION; SUBSETS; BETA; TH17; P40
AB Recently reported lines of Th9 cells, producing IL-9 and IL-10, were generated by polarization with IL-4 and TGF-beta and activation with Abs against CD3 and CD28. In this paper, we analyzed features of Th9 lines similarly polarized but activated by the "natural mode" (i.e., exposure of CD4 cells to their target Ag, hen egg lysozyme [HEL] and APCs). Main observations are the following: 1) both IL-9 and IL-10 were expressed by the line cells, but with strikingly different kinetics, with IL-9 being produced rapidly, reaching a peak on day 3 in culture and declining sharply thereafter, whereas IL-10 production increased gradually, resembling IL-4 and IL-17 production by their corresponding lineage cells; 2) reactivation of Th9, following expansion, triggered faster and higher production of both IL-9 and IL-10; 3) incubating Th9 cells in polarizing media specific for other phenotypes stimulated moderate levels of phenotype switching to Th1 or Th17 but a massive switching to Th2; 4) Th9 cells induced moderate inflammation in HEL-expressing recipient eyes but only when producing high levels of IL-9; and 5) IL-9-producing donor cells were detected in the blood of Th9 recipients but not in their inflamed eyes, suggesting that similar to findings in culture, exposure to HEL in these eyes arrested the IL-9 production in Th9 cells. Collectively, these data provide new information concerning Th9 cells and reveal their uniqueness, in particular with regard to the unusual production kinetics of IL-9 and the short retention of these cells in affected target tissues. The Journal of Immunology, 2010, 185: 6795-6801.
C1 [Tan, Cuiyan; Aziz, Mehak K.; Lovaas, Jenna D.; Vistica, Barbara P.; Shi, Guangpu; Gery, Igal] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Wawrousek, Eric F.] NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Gery, I (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N112,10 Ctr Dr, Bethesda, MD 20892 USA.
EM geryi@nei.nih.gov
FU National Eye Institute, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Eye Institute, National Institutes of Health.
NR 27
TC 54
Z9 63
U1 1
U2 10
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD DEC 1
PY 2010
VL 185
IS 11
BP 6795
EP 6801
DI 10.4049/jimmunol.1001676
PG 7
WC Immunology
SC Immunology
GA 681KJ
UT WOS:000284311500045
PM 20971929
ER
PT J
AU Zhao, AP
Urban, JF
Sun, R
Stiltz, J
Morimoto, M
Notari, L
Madden, KB
Yang, ZH
Grinchuk, V
Ramalingam, TR
Wynn, TA
Shea-Donohue, T
AF Zhao, Aiping
Urban, Joseph F., Jr.
Sun, Rex
Stiltz, Jennifer
Morimoto, Motoko
Notari, Luigi
Madden, Kathleen B.
Yang, Zhonghan
Grinchuk, Viktoriya
Ramalingam, Thirumalai R.
Wynn, Thomas A.
Shea-Donohue, Terez
TI Critical Role of IL-25 in Nematode Infection-Induced Alterations in
Intestinal Function
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID EPITHELIAL-CELL FUNCTION; NIPPOSTRONGYLUS-BRASILIENSIS INFECTION; TYPE-2
IMMUNITY; MAST-CELLS; IN-VIVO; IL-13; CYTOKINE; INTERLEUKIN-25;
INFLAMMATION; RESPONSES
AB IL-25 (IL-17E) is a member of the IL-17 cytokine family. IL-25-deficient mice exhibit impaired Th2 immunity against nematode infection, implicating IL-25 as a key component in mucosal immunity. The sources of IL-25 and mechanisms responsible for the induction of Th2 immunity by IL-25 in the gastrointestinal tract remain poorly understood. There is also little information on the regulation of IL-25 during inflammation or its role in gut function. In the current study, we investigated the regulation of IL-25 during Nippostrongylus brasiliensis infection and the contribution of IL-25 to the infection-induced alterations in intestinal function. We found that epithelial cells, but not immune cells, are the major source of IL-25 in the small intestine. N. brasiliensis infection-induced upregulation of IL-25 depends upon IL-13 activation of STAT6. IL-25(-/-) mice had diminished intestinal smooth muscle and epithelial responses to N. brasiliensis infection that were associated with an impaired Th2 protective immunity. Exogenous IL-25 induced characteristic changes similar to those after nematode infection but was unable to restore the impaired host immunity against N. brasiliensis infection in IL-13(-/-) mice. These data show that IL-25 plays a critical role in nematode infection-induced alterations in intestinal function that are important for host protective immunity, and IL-13 is the major downstream Th2 cytokine responsible for the IL-25 effects. The Journal of Immunology, 2010, 185: 6921-6929.
C1 [Zhao, Aiping; Stiltz, Jennifer; Notari, Luigi; Yang, Zhonghan; Grinchuk, Viktoriya; Shea-Donohue, Terez] Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA.
[Zhao, Aiping; Sun, Rex; Stiltz, Jennifer; Notari, Luigi; Yang, Zhonghan; Grinchuk, Viktoriya; Shea-Donohue, Terez] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Urban, Joseph F., Jr.] ARS, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA.
[Morimoto, Motoko] Miyagi Univ, Sch Food Agr Environm Sci, Sendai, Miyagi 982 0215, Japan.
[Madden, Kathleen B.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA.
[Ramalingam, Thirumalai R.; Wynn, Thomas A.] NIAID, Div Parasitol, NIH, Bethesda, MD 20892 USA.
RP Zhao, AP (reprint author), Univ Maryland, Sch Med, Mucosal Biol Res Ctr, 20 Penn St, Baltimore, MD 21201 USA.
EM azhao@mbrc.umaryland.edu
RI Wynn, Thomas/C-2797-2011;
OI Urban, Joseph/0000-0002-1590-8869
FU National Institutes of Health [R01-DK083418, R01-AI/DK49316]; U.S.
Department of Agriculture [1235-51000-055]
FX This work was supported by National Institutes of Health Grants
R01-DK083418 (to A.Z.) and R01-AI/DK49316 (to T.S.-D.) and by U.S.
Department of Agriculture Current Research Information System Project
No. 1235-51000-055 (to J.F.U.).
NR 34
TC 54
Z9 56
U1 0
U2 4
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 2010
VL 185
IS 11
BP 6921
EP 6929
DI 10.4049/jimmunol.1000450
PG 9
WC Immunology
SC Immunology
GA 681KJ
UT WOS:000284311500059
PM 20974983
ER
PT J
AU Chien, YW
Klugman, KP
Morens, DM
AF Chien, Yu-Wen
Klugman, Keith P.
Morens, David M.
TI Efficacy of Whole-Cell Killed Bacterial Vaccines in Preventing Pneumonia
and Death during the 1918 Influenza Pandemic
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID STREPTOCOCCUS; COLONIZATION; EPIDEMIOLOGY; PREPAREDNESS; VACCINATION;
INFECTIONS; CALIFORNIA; MORTALITY; PATHOGENS; DISEASE
AB Background. Most deaths in the 1918 influenza pandemic were caused by secondary bacterial pneumonia.
Methods. We performed a systematic review and reanalysis of studies of bacterial vaccine efficacy (VE) in preventing pneumonia and mortality among patients with influenza during the 1918 pandemic.
Results. A meta-analysis of 6 civilian studies of mixed killed bacterial vaccines containing pneumococci identified significant heterogeneity among studies and estimated VE at 34% (95% confidence interval [CI], 19%-47%) in preventing pneumonia and 42% (95% CI, 18%-59%) in reducing case fatality rates among patients with influenza, using random-effects models. Using fixed-effect models, the pooled VE from 3 military studies was 59% (95% CI, 43%-70%) for pneumonia and 70% (95% CI, 50%-82%) for case fatality. Military studies showed less heterogeneity and may provide more accurate results than civilian studies, given the potential biases in the included studies. Findings of 1 military study using hemolytic streptococci also suggested that there was significant protection.
Conclusions. Despite significant methodological problems, the systematic biases in these studies do not exclude the possibilities that whole-cell inactivated pneumococcal vaccines may confer cross-protection to multiple pneumococcal serotypes and that bacterial vaccines may play a role in preventing influenza-associated pneumonia.
C1 [Chien, Yu-Wen; Klugman, Keith P.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Morens, David M.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Klugman, KP (reprint author), Emory Univ, Rollins Sch Publ Hlth, 1518 Clifton Rd, Atlanta, GA 30322 USA.
EM kklugma@emory.edu
FU Pfizer Vaccines; GlaxoSmithKline
FX Potential conflicts of interest: K.P.K. has received consultant fees and
research support from Pfizer Vaccines and GlaxoSmithKline but received
no funding from industry for this analysis. All other authors report no
potential conflicts of interest.
NR 45
TC 19
Z9 21
U1 0
U2 5
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 2010
VL 202
IS 11
BP 1639
EP 1648
DI 10.1086/657144
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 675BU
UT WOS:000283799900005
PM 21028954
ER
PT J
AU Xi, LF
Koutsky, LA
Castle, PE
Edelstein, ZR
Hulbert, A
Schiffman, M
Kiviat, NB
AF Xi, Long Fu
Koutsky, Laura A.
Castle, Philip E.
Edelstein, Zoe R.
Hulbert, Ayaka
Schiffman, Mark
Kiviat, Nancy B.
TI Human Papillomavirus Type 16 Variants in Paired Enrollment and Follow-up
Cervical Samples: Implications for a Proper Understanding of
Type-Specific Persistent Infections
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID DNA
AB Prospective studies of the persistence of human papillomavirus (HPV) variants are rare and typically small. We sequenced HPV-16 variants in longitudinal pairs of specimens from 86 women enrolled in the ASCUS-LSIL Triage Study. A change of variants was identified in 4 women (4.7% [95% confidence interval, 1.3%-11.5%]). Among women with intervening HPV results (n=60), a variant switch occurred in 2 of 11 who had evidence of intervening negativity for HPV-16, compared with 1 of 49 who consistently tested positive (P=.11). These results suggest the possibility that rare misclassification of transient infections as persistent infections occurs in natural history studies of type-specific HPV infections.
C1 [Xi, Long Fu] Univ Washington, Dept Pathol, Harborview Med Ctr, Sch Med, Seattle, WA 98104 USA.
[Xi, Long Fu; Koutsky, Laura A.; Edelstein, Zoe R.] Univ Washington, Dept Epidemiol, Sch Publ Hlth & Community Med, Seattle, WA 98104 USA.
[Castle, Philip E.; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Xi, LF (reprint author), Univ Washington, Dept Pathol, Harborview Med Ctr, Sch Med, NJB Ste 1187,325 9th Ave, Seattle, WA 98104 USA.
EM longfu@u.washington.edu
FU Public Health Service [CA133569]
FX Financial support: Public Health Service (grant CA133569 to L.F.X.).
NR 15
TC 8
Z9 9
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD DEC 1
PY 2010
VL 202
IS 11
BP 1667
EP 1670
DI 10.1086/657083
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 675BU
UT WOS:000283799900008
PM 20977339
ER
PT J
AU Martin, MP
Qi, Y
Goedert, JJ
Hussain, SK
Kirk, GD
Hoots, WK
Buchbinder, S
Carrington, M
Thio, CL
AF Martin, Maureen P.
Qi, Ying
Goedert, James J.
Hussain, Shehnaz K.
Kirk, Gregory D.
Hoots, W. Keith
Buchbinder, Susan
Carrington, Mary
Thio, Chloe L.
TI IL28B Polymorphism Does Not Determine Outcomes of Hepatitis B Virus or
HIV Infection
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID C VIRUS; INTERFERON-LAMBDA; GENETIC-VARIATION; REPLICATION; CLEARANCE;
CELLS; MICE
AB An IL28B haplotype strongly determines the outcome of natural and interferon-alpha treated hepatitis C virus (HCV) infection. To assess whether the polymorphism marking the haplotype (rs12979860) also affects other interferon-alpha responsive chronic viral illnesses, namely hepatitis B virus (HBV) and human immunodeficiency virus (HIV) type 1 infections, we genotyped 226 individuals with HBV persistence, 384 with HBV recovery, and 2548 with or at high risk for HIV infection. The C/C genotype of rs12979860 was not associated with HBV recovery (odds ratio, 0.99), resistance to HIV infection (odds ratio, 0.97), or HIV disease progression (P>1.05). This IL28B single-nucleotide polymorphism affects the immune response to HCV but not to HBV or HIV.
C1 [Kirk, Gregory D.; Thio, Chloe L.] Johns Hopkins Univ, Baltimore, MD 21205 USA.
[Martin, Maureen P.; Qi, Ying; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, Frederick, MD 21701 USA.
[Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Hoots, W. Keith] NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA.
[Hussain, Shehnaz K.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Buchbinder, Susan] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Thio, CL (reprint author), Johns Hopkins Univ, 855 N Wolfe St,Ste 520, Baltimore, MD 21205 USA.
EM cthio@jhmi.edu
FU Burroughs Wellcome Fund; National Institute of Allergy and Infectious
Diseases; National Cancer Institute (NCI) [N02-CP-55504]; National
Heart, Lung and Blood Institute [UO1-AI-35042, 5-MO1-RR-00722 [GCRC],
UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613,
UO1-AI-35041]; RTI International; National Institute on Drug Abuse
[R01-DA-04334, R01-DA-12568]; Bureau of Maternal and Child Health and
Resources Development [MCJ-060570]; National Institute of Child Health
and Human Development [NO1-HD-4-3200]; Centers for Disease Control and
Prevention; National Institute of Mental Health; National Center for
Research Resources of the National Institutes of Health (NIH)
[MO1-RR06020]; Mount Sinai General Clinical Research Center, New York
[MO1-RR00071]; University of Iowa Clinical Research Center
[MO1-RR00059]; University of Texas Health Science Center, Houston
[MO1-RR02558]; NCI, NIH [N01-CO-12400]; NIH, NCI, Center for Cancer
Research; [R01-HD-4-1224]
FX The authors thank Abbott Laboratories for donating HBsAg and anti-HBs
kits and the cohort participants for making this study possible.; This
work was supported by the Investigators in the Pathogenesis of
Infectious Diseases Award from the Burroughs Wellcome Fund (C. L. T.).
Data in this study were collected by the Multicenter AIDS Cohort Study
(MACS), with centers (principal investigators) at the Johns Hopkins
University Bloomberg School of Public Health (Joseph B. Margolick, Lisa
Jacobson); Howard Brown Health Center and Northwestern University
Medical School (John Phair); University of California, Los Angeles
(Roger Detels); and University of Pittsburgh (Charles Rinaldo). The MACS
is funded by the National Institute of Allergy and Infectious Diseases,
with additional supplemental funding from the National Cancer Institute
(NCI) and the National Heart, Lung and Blood Institute (grants
UO1-AI-35042, 5-MO1-RR-00722 [GCRC], UO1-AI-35043, UO1-AI-37984,
UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, and UO1-AI-35041). Web site:
http://www.statepi.jhsph.edu/macs/macs.html.; The Multicenter Hemophilia
Cohort Study is supported by the NCI (contract N02-CP-55504 with RTI
International). The AIDS Link to Intravenous Experience (ALIVE) study is
supported by the National Institute on Drug Abuse (grants R01-DA-04334
and R01-DA-12568). The Hemophilia Growth and Development Study is
supported by the Bureau of Maternal and Child Health and Resources
Development (MCJ-060570), the National Institute of Child Health and
Human Development (NO1-HD-4-3200), the Centers for Disease Control and
Prevention, and the National Institute of Mental Health.; Additional
support has been provided by grants from the National Center for
Research Resources of the National Institutes of Health (NIH) to the New
York Hospital-Cornell Medical Center Clinical Research Center (grant
MO1-RR06020), Mount Sinai General Clinical Research Center, New York
(grant MO1-RR00071), University of Iowa Clinical Research Center
(MO1-RR00059), and University of Texas Health Science Center, Houston
(grant MO1-RR02558), and R01-HD-4-1224. This project has been funded in
whole or in part with federal funds from the NCI, NIH (contract
N01-CO-12400) and in part by the Intramural Research Program of the NIH,
NCI, Center for Cancer Research.
NR 15
TC 68
Z9 73
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD DEC 1
PY 2010
VL 202
IS 11
BP 1749
EP 1753
DI 10.1086/657146
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 675BU
UT WOS:000283799900019
PM 20977343
ER
PT J
AU Grubbs, R
Vugrek, O
Deisch, J
Wagner, C
Stabler, S
Allen, R
Baric, I
Rados, M
Mudd, SH
AF Grubbs, Randall
Vugrek, Oliver
Deisch, Jeremy
Wagner, Conrad
Stabler, Sally
Allen, Robert
Baric, Ivo
Rados, Marko
Mudd, S. Harvey
TI S-adenosylhomocysteine hydrolase deficiency: two siblings with fetal
hydrops and fatal outcomes
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Article
ID N-METHYLTRANSFERASE DEFICIENCY; RECEPTOR-BINDING PROTEIN; AHCY;
IDENTIFICATION; MUTATION; PATIENT
AB This paper reports the clinical and metabolic findings in two sibling sisters born with fetal hydrops and eventually found to have deficient S-adenosylhomocysteine hydrolase (AHCY) activity due to compound heterozygosity for two novel mutations, c.145C > T; p.Arg49Cys and c.257A > G; p.Asp86Gly. Clinically, the major abnormalities in addition to fetal hydrops (very likely due to impaired synthetic liver function) were severe hypotonia/myopathy, feeding problems, and respiratory failure. Metabolic abnormalities included elevated plasma S-adenosylhomocysteine, S-adenosylmethionine, and methionine, with hypoalbuminemia, coagulopathies, and serum transaminase elevation. The older sister died at age 25 days, but the definitive diagnosis was made only retrospectively. The underlying genetic abnormality was diagnosed in the second sister, but treatment by means of dietary methionine restriction and supplementation with phosphatidylcholine and creatine did not prevent her death at age 122 days. These cases extend the experience with AHCY deficiency in humans, based until now on only the four patients previously identified, and suggest that the deficiency in question may be a cause of fetal hydrops and developmental abnormalities of the brain.
C1 [Grubbs, Randall] Pediatrix Med Grp Texas, Ft Worth, TX USA.
[Vugrek, Oliver] Rudjer Boskovic Inst, Dept Mol Med, Zagreb, Croatia.
[Deisch, Jeremy] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Wagner, Conrad] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA.
[Stabler, Sally; Allen, Robert] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
[Baric, Ivo] Univ Zagreb, Univ Hosp Ctr, Sch Med, Dept Pediat, HR-10002 Zagreb, Croatia.
[Rados, Marko] Univ Zagreb, Univ Hosp Ctr, Dept Radiol, HR-10002 Zagreb, Croatia.
[Mudd, S. Harvey] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA.
[Rados, Marko] Univ Zagreb, Croatian Inst Brain Res, HR-10002 Zagreb, Croatia.
[Rados, Marko] Univ Zagreb, Zagreb Sch Med, HR-10002 Zagreb, Croatia.
RP Mudd, SH (reprint author), NIMH, Mol Biol Lab, Bldg 10,Room 2D46,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM muddh@mail.nih.gov
FU Ministry of Science, Education, and Sports, Republic of Croatia
[098-0000000-2463, 108-1081870-1885]
FX The authors thank Dr. Teodoro Bottiglieri for performing retrospectively
the assays listed in Table 1 for day-of-life 30 and Dr. Neil Buist for
advice on managing patient 2. This work was supported by grants
098-0000000-2463 (to OV) and 108-1081870-1885 (to IB) of the Ministry of
Science, Education, and Sports, Republic of Croatia
NR 17
TC 14
Z9 15
U1 0
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-8955
J9 J INHERIT METAB DIS
JI J. Inherit. Metab. Dis.
PD DEC
PY 2010
VL 33
IS 6
BP 705
EP 713
DI 10.1007/s10545-010-9171-x
PG 9
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 685RZ
UT WOS:000284647100011
PM 20852937
ER
PT J
AU Wolfe, LA
He, M
Vockley, J
Payne, N
Rhead, W
Hoppel, C
Spector, E
Gernert, K
Gibson, KM
AF Wolfe, Lynne A.
He, Miao
Vockley, Jerry
Payne, Nicole
Rhead, William
Hoppel, Charles
Spector, Elaine
Gernert, Kim
Gibson, K. Michael
TI Novel ETF dehydrogenase mutations in a patient with mild glutaric
aciduria type II and complex II-III deficiency in liver and muscle
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Article
AB We describe a 22-year-old male who developed severe hypoglycemia and lethargy during an acute illness at 4 months of age and subsequently grew and developed normally. At age 4 years he developed recurrent vomiting with mild hyperammonemia and dehydration requiring frequent hospitalizations. Glutaric aciduria Type II was suspected based upon biochemical findings and managed with cornstarch, carnitine and riboflavin supplements. He did not experience metabolic crises between ages 4-12 years. He experienced recurrent vomiting, mild hyperammonemia, and generalized weakness associated with acute illnesses and growth spurts. At age 18 years, he developed exercise intolerance and proximal muscle weakness leading to the identification of multiple acyl-CoA dehydrogenase and complex II/III deficiencies in both skeletal muscle and liver. Subsequent molecular characterization of the ETFDH gene revealed novel heterozygous mutations, p.G274X:c.820 G>T (exon 7) and p.P534L:c.1601 C>T (exon 12), the latter within the iron sulfur-cluster and predicted to affect ubiquinone reductase activity of ETFDH and the docking of ETF to ETFDH. Our case supports the concept of a structural interaction between ETFDH and other enzyme partners, and suggests that the conformational change upon ETF binding to ETFDH may play a key role in linking ETFDH to II/III super-complex formation.
C1 [Wolfe, Lynne A.; Vockley, Jerry; Payne, Nicole; Gibson, K. Michael] UPMC, Childrens Hosp, Dept Pediat, Div Med Genet, Pittsburgh, PA USA.
[Wolfe, Lynne A.] NHGRI, Undiagnosed Dis Program, Bethesda, MD 20892 USA.
[He, Miao] Emory Univ, Sch Med, Dept Human Genet, Decatur, GA 30033 USA.
[Vockley, Jerry; Gibson, K. Michael] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA.
[Vockley, Jerry; Gibson, K. Michael] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Rhead, William] Med Coll Wisconsin, Dept Pediat, Div Clin Genet, Milwaukee, WI 53226 USA.
[Hoppel, Charles] Case Western Reserve Univ, Louis Stokes Cleveland Dept Vet Affairs Med Ctr, Dept Med, Cleveland, OH 44106 USA.
[Spector, Elaine] UCD DNA Diagnost Lab, Aurora, CO USA.
[Gernert, Kim] Emory Univ, Sch Med, Atlanta, GA 30322 USA.
[Gibson, K. Michael] UPMC, Childrens Hosp, Dept Pathol, Pittsburgh, PA USA.
[Gibson, K. Michael] Michigan Technol Univ, Dept Biol Sci, Houghton, MI 49931 USA.
RP Gibson, KM (reprint author), Michigan Technol Univ, Dept Biol Sci, Room 740 DOW ESE Bldg,1400 Townsend Dr, Houghton, MI 49931 USA.
EM kmgibson@mtu.edu
OI Vockley, Jerry/0000-0002-8180-6457
FU NIDDK NIH HHS [R01 DK054936, R01 DK078775]
NR 21
TC 3
Z9 3
U1 1
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-8955
EI 1573-2665
J9 J INHERIT METAB DIS
JI J. Inherit. Metab. Dis.
PD DEC
PY 2010
VL 33
SU 3
BP S481
EP S487
DI 10.1007/s10545-010-9246-8
PG 7
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA V33ME
UT WOS:000209022100077
PM 21088898
ER
PT J
AU Khuddus, MA
Pepine, CJ
Handberg, EM
Merz, CNB
Sopko, G
Bavry, AA
Denardo, SJ
McGorray, SP
Smith, KM
Sharaf, BL
Nicholls, SJ
Nissen, SE
Anderson, RD
AF Khuddus, Matheen A.
Pepine, Carl J.
Handberg, Eileen M.
Merz, C. Noel Bairey
Sopko, George
Bavry, Anthony A.
Denardo, Scott J.
McGorray, Susan P.
Smith, Karen M.
Sharaf, Barry L.
Nicholls, Steven J.
Nissen, Steven E.
Anderson, R. David
TI An Intravascular Ultrasound Analysis in Women Experiencing Chest Pain in
the Absence of Obstructive Coronary Artery Disease: A Substudy from the
National Heart, Lung and Blood Institute-Sponsored Women's Ischemia
Syndrome Evaluation (WISE)
SO JOURNAL OF INTERVENTIONAL CARDIOLOGY
LA English
DT Article
ID COMPENSATORY ENLARGEMENT; MYOCARDIAL-INFARCTION; ATHEROSCLEROTIC
DISEASE; CARDIOVASCULAR EVENTS; CLINICAL PRESENTATION; IN-VIVO;
ANGIOGRAPHY; PROGRESSION; PREVALENCE; REGRESSION
AB Aims: Using intravascular ultrasound (IVUS), we sought to characterize coronary morphology in women with chest pain without major epicardial obstructive coronary artery disease (CAD). We have previously observed an unexpectedly high rate of adverse outcomes among women with chest pain and normal or insignificant obstructive CAD. Information about the presence and characteristics of coronary atherosclerosis in these women could provide insight into the mechanisms related to increased risk, as well as improved diagnosis, prevention, and treatment.
Methods: Women (n = 100) with suspected ischemia without obstructive CAD (> 50% stenosis) underwent IVUS of a left coronary segment with measurements by a core lab masked to clinical and angiographic findings.
Results: Angiograhic core lab analysis found 69.6% of patients had no (< 20%) and 30.4% had minimal (20-< 50%) CAD. IVUS segmental images were interpretable by the core lab in 92 women, with 19 (21%) having no atherosclerosis (intimal-medial thickness < 0.5 mm). In the remaining 73 women (79%), percent atheroma volume was 27 +/- 8% and mean maximum plaque thickness was 0.53 +/- 0.22 mm. Thirty-eight women with atherosclerosis (53%) had >= 30% of interrogated vessel involved. The average vessel involvement was 40%, and the maximum plaque thickness was 1.27 mm. The number of risk factors strongly correlated with percent atheroma volume (r = 0.53, P < 0.0001) and percent vessel involvement (r = 0.51, P < 0.0001), with the strongest independent predictor of both being age. Remodeling was assessed in 59/73 women (81%), and 73% had evidence of positive remodeling.
Conclusions: In symptomatic women without significant luminal obstructive CAD, we observed a high prevalence of atherosclerosis with positive remodeling and preserved lumen size. These findings may help explain increased risk and emphasize need for improved diagnostic and treatment options for women with concealed CAD. (J Interven Cardiol 2010;23:511-519).
C1 [Khuddus, Matheen A.; Pepine, Carl J.; Handberg, Eileen M.; Bavry, Anthony A.; Denardo, Scott J.; McGorray, Susan P.; Smith, Karen M.; Anderson, R. David] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA.
[Merz, C. Noel Bairey] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA.
[Sopko, George] NHLBI, Div Heart & Cardiovasc Dis, NIH, Bethesda, MD 20892 USA.
[Sharaf, Barry L.] Brown Univ, Rhode Isl Hosp, Div Cardiol, Providence, RI 02903 USA.
[Nicholls, Steven J.; Nissen, Steven E.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.
RP Anderson, RD (reprint author), Box 100277, Gainesville, FL 32610 USA.
EM david.anderson@medicine.ufl.edu
FU NCRR NIH HHS [M01 RR000425]; NHLBI NIH HHS [N01HV68163, N01 HV068161,
N01 HV068162, N01 HV068163, N01 HV068164, N01HV68162, T32 HL069751, U01
HL064829, U01 HL064829-05, U01 HL064924, U01 HL064924-05]
NR 37
TC 43
Z9 44
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0896-4327
J9 J INTERV CARDIOL
JI J. Interv. Cardiol.
PD DEC
PY 2010
VL 23
IS 6
BP 511
EP 519
DI 10.1111/j.1540-8183.2010.00598.x
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 688ZO
UT WOS:000284896600001
PM 21029178
ER
PT J
AU Dwivedi, P
Puzon, G
Tam, M
Langlais, D
Jackson, S
Kaplan, K
Siems, WF
Schultz, AJ
Xun, LY
Woodsd, A
Hill, HH
AF Dwivedi, Prabha
Puzon, Geoffery
Tam, Maggie
Langlais, Denis
Jackson, Shelley
Kaplan, Kimberly
Siems, William F.
Schultz, Albert J.
Xun, Luying
Woodsd, Amina
Hill, Herbert H., Jr.
TI Metabolic profiling of Escherichia coli by ion mobility-mass
spectrometry with MALDI ion source
SO JOURNAL OF MASS SPECTROMETRY
LA English
DT Article
DE ion mobility-mass spectrometry; metabolomics; Escherichia coli; MALDI;
ESI; peak capacity
AB Comprehensive metabolome analysis using mass spectrometry (MS) often results in a complex mass spectrum and difficult data analysis resulting from the signals of numerous small molecules in the metabolome. In addition, MS alone has difficulty measuring isobars and chiral, conformational and structural isomers. When a matrix-assisted laser desorption ionization (MALDI) source is added, the difficulty and complexity are further increased. Signal interference between analyte signals and matrix ion signals produced by MALDI in the low mass region (< 1500 Da) cause detection and/or identification of metabolites difficult by MS alone. However, ion mobility spectrometry (IMS) coupled with MS (IM-MS) provides a rapid analytical tool for measuring subtle structural differences in chemicals. IMS separates gas-phase ions based on their size-to-charge ratio. This study, for the first time, reports the application of MALDI to the measurement of small molecules in a biological matrix by ion mobility-time of flight mass spectrometry (IM-TOFMS) and demonstrates the advantage of ion-signal dispersion in the second dimension. Qualitative comparisons between metabolic profiling of the Escherichia coli metabolome by MALDI-TOFMS, MALDI-IM-TOFMS and electrospray ionization (ESI)-IM-TOFMS are reported. Results demonstrate that mobility separation prior to mass analysis increases peak-capacity through added dimensionality in measurement. Mobility separation also allows detection of metabolites in the matrix-ion dominated low-mass range (m/z < 1500 Da) by separating matrix signals from non-matrix signals in mobility space. Copyright (c) 2010 John Wiley & Sons, Ltd.
C1 [Dwivedi, Prabha; Tam, Maggie; Kaplan, Kimberly; Siems, William F.; Xun, Luying; Hill, Herbert H., Jr.] Washington State Univ, Pullman, WA 99164 USA.
[Puzon, Geoffery] CSIRO, Land & Water, Wembley, WA 6913, Australia.
[Langlais, Denis; Schultz, Albert J.] Ionwerks Inc, Houston, TX 77005 USA.
[Jackson, Shelley; Woodsd, Amina] NIDA IRP, NIH, Baltimore, MD 21224 USA.
RP Dwivedi, P (reprint author), Washington State Univ, Pullman, WA 99164 USA.
EM pdwivedi@wsu.edu
RI Puzon, Geoffrey/H-3667-2012
FU National Institute of Health [R21-DK070274]; National Institute on Drug
Abuse; NIDA [N44DA-3-7727, HHSN271200477384C]
FX This work was supported in part by grant from National Institute of
Health (Road Map Grant # R21-DK070274), National Institute on Drug Abuse
Intramural program for funding to A.S. Woods laboratory and NIH for NIDA
contracts # N44DA-3-7727 and HHSN271200477384C granted to Ionwerks for
instrument design and construction.
NR 104
TC 23
Z9 24
U1 2
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1076-5174
J9 J MASS SPECTROM
JI J. Mass Spectrom.
PD DEC
PY 2010
VL 45
IS 12
BP 1383
EP 1393
DI 10.1002/jms.1850
PG 11
WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA 703BM
UT WOS:000285949000002
PM 20967735
ER
PT J
AU Romero, R
Mazaki-Tovi, S
Vaisbuch, E
Kusanovic, JP
Chaiworapongsa, T
Gomez, R
Nien, JK
Yoon, BH
Mazor, M
Luo, JQ
Banks, D
Ryals, J
Beecher, C
AF Romero, Roberto
Mazaki-Tovi, Shali
Vaisbuch, Edi
Kusanovic, Juan Pedro
Chaiworapongsa, Tinnakorn
Gomez, Ricardo
Nien, Jyh Kae
Yoon, Bo Hyun
Mazor, Moshe
Luo, Jingqin
Banks, David
Ryals, John
Beecher, Chris
TI Metabolomics in premature labor: a novel approach to identify patients
at risk for preterm delivery
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Preterm labor; preterm delivery; intraamniotic inflammation; pregnancy;
amniocentesis; microbial invasion of the amniotic cavity; MIAC;
cytokines; chorioamnionitis; high-dimensional biology; omics sciences;
intraamniotic infection
ID HUMAN AMNIOTIC-FLUID; INFLAMMATORY RESPONSE SYNDROME; TANDEM
MASS-SPECTROMETRY; HIGH-DIMENSIONAL BIOLOGY; CERVICAL-VAGINAL FLUID;
BLOOD-CELL COUNT; ARACHIDONATE LIPOXYGENASE METABOLITES; ASSISTED
REPRODUCTIVE TECHNOLOGY; COMPREHENSIVE PROTEOMIC ANALYSIS;
MAGNETIC-RESONANCE-SPECTROSCOPY
AB Objective. Biomarkers for preterm labor (PTL) and delivery can be discovered through the analysis of the transcriptome (transcriptomics) and protein composition (proteomics). Characterization of the global changes in low-molecular weight compounds which constitute the 'metabolic network' of cells (metabolome) is now possible by using a 'metabolomics' approach. Metabolomic profiling has special advantages over transcriptomics and proteomics since the metabolic network is downstream from gene expression and protein synthesis, and thus more closely reflects cell activity at a functional level. This study was conducted to determine if metabolomic profiling of the amniotic fluid can identify women with spontaneous PTL at risk for preterm delivery, regardless of the presence or absence of intraamniotic infection/inflammation (IAI).
Study Design. Two retrospective cross-sectional studies were conducted, including three groups of pregnant women with spontaneous PTL and intact membranes: (1) PTL who delivered at term; (2) PTL without IAI who delivered preterm; and (3) PTL with IAI who delivered preterm. The first was an exploratory study that included 16, 19, and 20 patients in groups 1, 2, and 3, respectively. The second study included 40, 33, and 40 patients in groups 1, 2, and 3, respectively. Amniotic fluid metabolic profiling was performed by combining chemical separation (with gas and liquid chromatography) and mass spectrometry. Compounds were identified using authentic standards. The data were analyzed using discriminant analysis for the first study and Random Forest for the second.
Results. (1) In the first study, metabolomic profiling of the amniotic fluid was able to identify patients as belonging to the correct clinical group with an overall 96.3% (53/55) accuracy; 15 of 16 patients with PTL who delivered at term were correctly classified; all patients with PTL without IAI who delivered preterm neonates were correctly identified as such (19/19), while 19/20 patients with PTL and IAI were correctly classified. (2) In the second study, metabolomic profiling was able to identify patients as belonging to the correct clinical group with an accuracy of 88.5% (100/113); 39 of 40 patients with PTL who delivered at term were correctly classified; 29 of 33 patients with PTL without IAI who delivered preterm neonates were correctly classified. Among patients with PTL and IAI, 32/40 were correctly classified. The metabolites responsible for the classification of patients in different clinical groups were identified. A preliminary draft of the human amniotic fluid metabolome was generated and found to contain products of the intermediate metabolism of mammalian cells and xenobiotic compounds (e.g. bacterial products and Salicylamide).
Conclusion. Among patients with spontaneous PTL with intact membranes, metabolic profiling of the amniotic fluid can be used to assess the risk of preterm delivery in the presence or absence of infection/inflammation.
C1 [Romero, Roberto; Mazaki-Tovi, Shali; Vaisbuch, Edi; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Romero, Roberto; Mazaki-Tovi, Shali; Vaisbuch, Edi; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Gomez, Ricardo; Nien, Jyh Kae] Hosp Dr Sotero del Rio, CEDIP, Puente Alto, Chile.
[Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Mazor, Moshe] Soroka Univ Med Ctr, Beer Sheva, Israel.
[Luo, Jingqin] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Banks, David] Duke Univ, Deptment Stat Sci, Durham, NC USA.
[Ryals, John; Beecher, Chris] Metabolon Inc, Biochem & Technol, Durham, NC USA.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
RI Yoon, Bo Hyun/H-6344-2011;
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported, in part, by the Intramural Research Program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, NIH, DHHS.
NR 251
TC 74
Z9 76
U1 4
U2 28
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD DEC
PY 2010
VL 23
IS 12
BP 1344
EP 1359
DI 10.3109/14767058.2010.482618
PG 16
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 678LH
UT WOS:000284075000002
PM 20504069
ER
PT J
AU Durnwald, CP
Momirova, V
Rouse, DJ
Caritis, SN
Peaceman, AM
Sciscione, A
Varner, MW
Malone, FD
Mercer, BM
Thorp, JM
Sorokin, Y
Carpenter, MW
Lo, J
Ramin, SM
Harper, M
Spong, CY
AF Durnwald, Celeste P.
Momirova, Valerija
Rouse, Dwight J.
Caritis, Steve N.
Peaceman, Alan M.
Sciscione, Anthony
Varner, Michael W.
Malone, Fergal D.
Mercer, Brian M.
Thorp, John M., Jr.
Sorokin, Yoram
Carpenter, Marshall W.
Lo, Julie
Ramin, Susan M.
Harper, Margaret
Spong, Catherine Y.
CA Eunice Kennedy Shriver Natl Inst
TI Second trimester cervical length and risk of preterm birth in women with
twin gestations treated with 17-alpha hydroxyprogesterone caproate
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Preterm birth; cervical length; twin gestation
ID 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; MULTIPLE GESTATIONS; MOUSE MODEL;
DELIVERY; PROGESTERONE; PREDICTION; PREVENTION; CERCLAGE; TRIAL; AGE
AB Objective. To compare rates of preterm birth before 35 weeks based on cervical length measurement at 16-20 weeks in women with twin gestations who received 17-alpha hydroxyprogesterone caproate (17OHPC) or placebo.
Methods. This is a secondary analysis of a randomised, double-blind, placebo-controlled trial of twin gestations exposed to 17OHPC or placebo. Baseline transvaginal ultrasound evaluation of cervical length was performed prior to treatment assignment at 16-20 weeks. Cervical length measurements were categorised according to the 10th, 25th, 50th and 75th percentiles in the women studied. The effect of 17OHPC administration in women with a short (25th percentile) and long (75th percentile) cervix was evaluated.
Results. Of 661 twin gestations studied, 221 (33.4%) women enrolled at 11 centers underwent cervical length measurement. The 10th, 25th, 50th, 75th percentiles for cervical length at 16-20 weeks were 32, 36, 40 and 44 mm, respectively. The risk of preterm birth < 35 weeks was increased in women with a cervical length < 25th percentile (55.8 vs. 36.9%, p = 0.02). However, a cervical length > 75th percentile at this gestational age interval was not protective for preterm birth (36.5 vs. 42.9%, p = 0.42). Administration of 17OHPC did not reduce preterm birth before 35 weeks among those with either a short or a long cervix (64.3 vs. 45.8%, p = 0.18 and 38.1 vs. 35.5%, p = 0.85, respectively).
Conclusion. Women with twin gestations and a cervical length below the 25th percentile at 16-20 weeks had higher rates of preterm birth. In this subgroup of women, 17 OHPC did not prevent preterm birth before 35 weeks gestation. A cervical length above the 75th percentile at 16-20 weeks did not significantly reduce the risk of preterm birth in this high risk population.
C1 [Durnwald, Celeste P.] Ohio State Univ, Div Maternal Fetal Med, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
[Momirova, Valerija] George Washington Univ, Ctr Biostat, Dept Obstet & Gynecol, Washington, DC USA.
[Peaceman, Alan M.] Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
[Sciscione, Anthony] Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[Rouse, Dwight J.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
[Caritis, Steve N.] Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Obstet & Gynecol, Bethesda, MD USA.
[Varner, Michael W.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Malone, Fergal D.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
[Mercer, Brian M.] Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA.
[Thorp, John M., Jr.] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA.
[Sorokin, Yoram] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Carpenter, Marshall W.] Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA.
[Lo, Julie] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA.
[Ramin, Susan M.] Univ Texas Houston, Dept Obstet & Gynecol, Houston, TX USA.
[Harper, Margaret] Wake Forest Univ Hlth Sci, Dept Obstet & Gynecol, Winston Salem, NC USA.
RP Durnwald, CP (reprint author), Ohio State Univ, Div Maternal Fetal Med, Dept Obstet & Gynecol, 395 W 12th Ave, Columbus, OH 43210 USA.
EM celeste.durnwald@osumc.edu
RI Malone, Fergal/D-6233-2012; Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD27869, HD21410, HD40512, HD34136, HD34208, HD40485,
HD27915, HD40544, HD40560, HD27917, HD40500, HD34116, HD40545, HD27860,
HD36801]
FX The authors wish to acknowledge subcommittee members who contributed as
follows: Elizabeth Thom PhD (protocol development and statistical
analysis), Allison Northen RN and Margaret Cotroneo RN (protocol
development and coordination between clinical research centers). This
study was supported by grants from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (HD27869, HD21410,
HD40512, HD34136, HD34208, HD40485, HD27915, HD40544, HD40560, HD27917,
HD40500, HD34116, HD40545, HD27860, HD36801).
NR 17
TC 30
Z9 32
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD DEC
PY 2010
VL 23
IS 12
BP 1360
EP 1364
DI 10.3109/14767051003702786
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 678LH
UT WOS:000284075000003
PM 20441408
ER
PT J
AU Conde-Agudelo, A
Romero, R
AF Conde-Agudelo, Agustin
Romero, Roberto
TI Cervicovaginal fetal fibronectin for the prediction of spontaneous
preterm birth in multiple pregnancies: a systematic review and
meta-analysis
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Review
DE Multiple pregnancy; twin pregnancy; preterm labor; prematurity; twins
ID TWIN GESTATIONS; DIAGNOSTIC-TEST; CERVICAL LENGTH; UNITED-STATES;
DELIVERY; ACCURACY; RISK; BIAS; SYMPTOMS; TRENDS
AB Objective. To investigate the accuracy of cervicovaginal fetal fibronectin in predicting preterm birth in women with multiple pregnancies.
Methods. Systematic review and meta-analysis of predictive test accuracy. Cohort or cross-sectional studies were identified through searches in databases, reference lists, proceedings, and reviews. Study selection, quality assessment, and data extraction were performed. We constructed summary receiver operating characteristic curves and calculated pooled sensitivities and specificities using a bivariate, random-effects meta-regression model. We also calculated summary likelihood ratios and post-test probabilities of preterm birth.
Results. Fifteen studies (11 in asymptomatic women and 4 in women with symptoms of preterm labor) involving 1221 women with multiple pregnancies were included. Among asymptomatic women with multiple or twin pregnancies, the pooled sensitivities, specificities, and positive and negative likelihood ratios for predicting preterm birth before 32, 34, and 37 weeks' gestation ranged from 33% to 45%, 80% to 94%, 2.0 to 5.5, and 0.68 to 0.76, respectively. Among women with twin pregnancies and threatened preterm labor, the test was most accurate in predicting spontaneous preterm birth within 7 days of testing (pooled sensitivity, specificity, and positive and negative likelihood ratios of 85%, 78%, 3.9, and 0.20, respectively).
Conclusions. Cervicovaginal fetal fibronectin provides moderate to minimal prediction of preterm birth in women with multiple pregnancies. The test is most accurate in predicting spontaneous preterm birth within 7 days of testing in women with twin pregnancies and threatened preterm labor.
C1 [Conde-Agudelo, Agustin; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD USA.
[Conde-Agudelo, Agustin; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA.
RP Romero, R (reprint author), NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS,Hutzel Womens Hosp, Box 4,3990 John R, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
FU Perinatology Research Branch: Division of Intramural Research of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services
FX This research was supported by the Perinatology Research Branch:
Division of Intramural Research of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Department of Health and Human Services. We are very grateful to
Dr. Percy Pacora for his assistance in obtaining the articles. We would
like to thank Dr. Nathan Fox for assistance in providing unpublished
data from your study and for clarifications of other queries.
NR 44
TC 28
Z9 28
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD DEC
PY 2010
VL 23
IS 12
BP 1365
EP 1376
DI 10.3109/14767058.2010.499484
PG 12
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 678LH
UT WOS:000284075000004
PM 21067303
ER
PT J
AU Romero, R
Chaiworapongsa, T
Erez, O
Tarca, AL
Gervasi, MT
Kusanovic, JP
Mittal, P
Ogge, G
Vaisbuch, E
Mazaki-Tovi, S
Dong, Z
Kim, SK
Yeo, L
Hassan, SS
AF Romero, Roberto
Chaiworapongsa, Tinnakorn
Erez, Offer
Tarca, Adi L.
Gervasi, Maria Teresa
Kusanovic, Juan Pedro
Mittal, Pooja
Ogge, Giovanna
Vaisbuch, Edi
Mazaki-Tovi, Shali
Dong, Zhong
Kim, Sun Kwon
Yeo, Lami
Hassan, Sonia S.
TI An imbalance between angiogenic and anti-angiogenic factors precedes
fetal death in a subset of patients: results of a longitudinal study
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Soluble VEGF receptor-1; sFlt-1; soluble endoglin; placental growth
factor; mixed- effect model; fetal demise; stillbirth; pregnancy;
anti-angiogenic state
ID ENDOTHELIAL GROWTH-FACTOR; PLACENTAL OXIDATIVE STRESS;
FOR-GESTATIONAL-AGE; FACTOR RECEPTOR-1 CONCENTRATION; FETOCIDE REVERSES
PREECLAMPSIA; MATERNAL PLASMA-CONCENTRATIONS; POPULATION-BASED COHORT;
EARLY-PREGNANCY FAILURE; UTERINE ARTERY DOPPLER; TYROSINE KINASE-1
AB Objective. Women with a fetal death at the time of diagnosis have higher maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, than women with a normal pregnancy. An important question is whether these changes are the cause or consequence of fetal death. To address this issue, we conducted a longitudinal study and measured the maternal plasma concentrations of selective angiogenic and anti-angiogenic factors before the diagnosis of a fetal death. The anti-angiogenic factors studied were sVEGFR-1 and soluble endoglin (sEng), and the angiogenic factor, placental growth factor (P1GF).
Methods. This retrospective longitudinal nested case-control study included 143 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered a term infant with an appropriate weight for gestational age (n = 124); and (2) patients who had a fetal death (n = 19). Blood samples were collected at each prenatal visit, scheduled at 4-week intervals from the first trimester until delivery. Plasma concentrations of sVEGFR-1, sEng, and PlGF were determined by specific and sensitive ELISA. A linear mixed-effects model was used for analysis.
Results. (1) The average profiles of analyte concentrations as a function of gestational age for sVEGFR-1, sEng and PlGF were different between women destined to have a fetal death and those with a normal pregnancy after adjusting for covariates (p < 0.05); (2) Plasma sVEGFR-1 concentrations in patients destined to have a fetal death were significantly lower between 7 and 11 weeks of gestation and became significantly higher than those of women with a normal pregnancy between 20 and 37 weeks of gestation (p < 0.05); (3) Similarly, plasma sEng concentrations of women destined to have a fetal death were lower at 7 weeks of gestation (p = 0.04) and became higher than those of controls between 20 and 40 weeks of gestation (p < 0.05); (4) In contrast, plasma PlGF concentrations were higher among patients destined to develop a fetal death between 7 and 14 weeks of gestation and became significantly lower than those in the control group between 22 and 39 weeks of gestation (p < 0.05); (5) The ratio of PlGF/(sVEGFR-1 x sEng) was significantly higher in women destined to have a fetal death between 7 and 13 weeks of gestation (94-781%) and significantly lower (44-75%) than those in normal pregnant women between 20 and 40 weeks of gestation (p < 0.05); (6) Similar results were obtained when patients with a fetal death were stratified into those who were diagnosed before or after 37 weeks of gestation.
Conclusions. Fetal death is characterised by higher maternal plasma concentrations of PlGF during the first trimester compared to normal pregnancy. This profile changes into an anti-angiogenic one during the second and third trimesters.
C1 [Romero, Roberto; Chaiworapongsa, Tinnakorn; Erez, Offer; Tarca, Adi L.; Kusanovic, Juan Pedro; Mittal, Pooja; Ogge, Giovanna; Vaisbuch, Edi; Mazaki-Tovi, Shali; Dong, Zhong; Kim, Sun Kwon; Yeo, Lami; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Romero, Roberto; Chaiworapongsa, Tinnakorn; Erez, Offer; Tarca, Adi L.; Kusanovic, Juan Pedro; Mittal, Pooja; Ogge, Giovanna; Vaisbuch, Edi; Mazaki-Tovi, Shali; Dong, Zhong; Kim, Sun Kwon; Yeo, Lami; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Romero, Roberto; Chaiworapongsa, Tinnakorn; Erez, Offer; Kusanovic, Juan Pedro; Mittal, Pooja; Vaisbuch, Edi; Mazaki-Tovi, Shali; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA.
[Tarca, Adi L.] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA.
[Gervasi, Maria Teresa] Azienda Osped Padova, Dept Obstet & Gynecol, Padua, Italy.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
RI Ogge, Giovanna/G-6109-2011;
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported (in part) by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.
NR 116
TC 25
Z9 25
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD DEC
PY 2010
VL 23
IS 12
BP 1384
EP 1399
DI 10.3109/14767051003681121
PG 16
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 678LH
UT WOS:000284075000006
PM 20459337
ER
PT J
AU Gozalo, AS
Zerfas, PM
Starost, MF
Elkins, WR
Clarke, CL
AF Gozalo, Alfonso S.
Zerfas, Patricia M.
Starost, Matthew F.
Elkins, William R.
Clarke, Carol L.
TI Splenic angioleiomyoma in an owl monkey (Aotus nancymae)
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Article
DE cebidae; immunohistochemistry; neoplasia; non-human primate; spleen;
transmission electron microscopy; vascular leiomyoma
ID TUMORS
AB Background
An adult male owl monkey (Aotus nancymae) underwent a splenectomy. When the spleen was removed, a small, nodular mass slightly bulging over the splenic surface was noted.
Methods
The mass was examined by light and transmission electron microscopy and by immunohistochemistry.
Results
On light microscopy, the mass was well-circumscribed, non-encapsulated, and composed of haphazardly arranged smooth muscle bundles admixed with numerous small capillary-like structures containing blood. Immunohistochemical (IHC) staining revealed the tumor was strongly positive for smooth muscle actin yielding vascular smooth muscle bundles, and for Factor VIII, staining endothelial cells within the smooth muscle bundles. Transmission electron microscopy (TEM) showed a large portion of the cells to be atypical appearing smooth muscle and a few cells had structures resembling Weibel-Palade bodies indicating endothelial cells.
Conclusions
Based on cell morphology, by light and TEM, and IHC a final diagnosis of splenic angioleiomyoma was made. This is, to our knowledge, the first report of an angioleiomyoma in a non-human primate.
C1 [Gozalo, Alfonso S.] NIAID, Comparat Med Branch, NIH, SoBran Inc Govt Contractor, Bethesda, MD 20892 USA.
[Gozalo, Alfonso S.] SoBran Inc, Bethesda, MD USA.
[Zerfas, Patricia M.; Starost, Matthew F.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, NIH, SoBran Inc Govt Contractor, 9000 Rockville Pike,Bldg 14B S,Room 228, Bethesda, MD 20892 USA.
EM gozaloa@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases, Comparative Medicine Branch; Office of Research
Services; NIAID; Laboratory of Malaria Immunology and Vaccinology
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases, Comparative Medicine Branch, Laboratory of Malaria
Immunology and Vaccinology, the Office of Research Services, and a NIAID
contract to SoBran Inc. This study was funded by the Intramural Research
Program of the National Institutes of Health, National Institute of
Allergy and Infectious Diseases, Comparative Medicine Branch, and the
Office of Research Services.
NR 14
TC 5
Z9 5
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD DEC
PY 2010
VL 39
IS 6
BP 385
EP 388
DI 10.1111/j.1600-0684.2010.00425.x
PG 4
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 676XA
UT WOS:000283950800004
PM 20524955
ER
PT J
AU Natarajan, V
Kottilil, S
Hazen, A
Adelsberger, J
Murphy, AA
Polis, MA
Kovacs, JA
AF Natarajan, Ven
Kottilil, Shyam
Hazen, Allison
Adelsberger, Joseph
Murphy, Alison A.
Polis, Michael A.
Kovacs, Joseph A.
TI HCV in Peripheral Blood Mononuclear Cells Are Predominantly Carried on
the Surface of Cells in HIV/HCV Co-Infected Individuals
SO JOURNAL OF MEDICAL VIROLOGY
LA English
DT Article
DE HCV; HIV; extra hepatic HCV reservoir; NK cells
ID HEPATITIS-C; VIRUS HCV; REPLICATION; LIVER; ENTRY; RNA
AB HCV replication in extra-hepatic reservoirs has been suggested to occur in many tissues including PBMCs. A recent study showed evidence for compartmentalization and evolution of HCV in PBMCs. However, the cells that support HCV replication in PBMCs have not been identified. In this study we have fractionated the PBMC from HIV/HCV co-infected patients into T, monocytes, B and NK cells, and most of the HCV was located in CD3-cell fractions. Protease treatment of PBMCs to remove cell surface receptors resulted in the loss of HCV RNA suggesting that most of the HCV is present on the cell surface. PBMCs were treated by freeze-thaw nuclease method that would protect the HCV RNA in the virus but not the intracellular viral RNA. Data from this analysis support the conclusion that most of HCV is present on the cell surface. Even though the presence of minus strand RNA in PBMCs suggests that a low level HCV replication takes place within the PBMCs of HIV/HCV co-infected individuals, HCV in PBMC is present mainly on the surface of non-T cells, mostly on NK, monocytes and B cells. These results suggest a unique pathogenic role of NK, monocyte and B cells as carriers of HCV. J. Med. Virol. 82:2032-2037, 2010. (c) 2010 Wiley-Liss, Inc.
C1 [Kottilil, Shyam] NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Natarajan, Ven; Hazen, Allison; Adelsberger, Joseph] SAIC Frederick Inc, Mol Cell Biol Lab, Frederick, MD USA.
[Kovacs, Joseph A.] CC NIH, CCMD, Bethesda, MD USA.
RP Kottilil, S (reprint author), NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bldg10,Rm 11N204, Bethesda, MD 20892 USA.
EM skottilil@niaid.nih.gov
OI Polis, Michael/0000-0002-9151-2268
FU NIH (National Institute of Allergy and Infectious Diseases and NIH
Clinical Center); National Institute of Allergy and Infectious Diseases;
National Cancer Institute; National Institutes of Health
[HHSN261200800001E]; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]
FX Grant sponsor: Intramural Research Program of the NIH (National
Institute of Allergy and Infectious Diseases and NIH Clinical Center);
Grant sponsor: National Institute of Allergy and Infectious Diseases;
Grant sponsor: National Cancer Institute (Federal Funds); Grant sponsor:
National Institutes of Health; Grant number: HHSN261200800001E.; This
project has been funded in whole or in part with Federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
HHSN261200800001E.
NR 16
TC 20
Z9 20
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0146-6615
J9 J MED VIROL
JI J. Med. Virol.
PD DEC
PY 2010
VL 82
IS 12
BP 2032
EP 2037
DI 10.1002/jmv.21906
PG 6
WC Virology
SC Virology
GA 672ZY
UT WOS:000283628700007
PM 20981790
ER
PT J
AU Cohen, BE
AF Cohen, B. Eleazar
TI Amphotericin B Membrane Action: Role for Two Types of Ion Channels in
Eliciting Cell Survival and Lethal Effects
SO JOURNAL OF MEMBRANE BIOLOGY
LA English
DT Article
DE Amphotericin B; Ion channels; Sterol; Lipid rafts; Antifungal activity;
Antileishmanial activity; Lethal effects; Apoptosis
ID NITRIC-OXIDE SYNTHASE; POLYENE MACROLIDE ANTIBIOTICS; INDUCED
PERMEABILITY CHANGES; HUMAN-ERYTHROCYTE-MEMBRANES; ACTIVATED
PROTEIN-KINASE; PORE-FORMING TOXINS; NF-KAPPA-B; CANDIDA-ALBICANS;
SACCHAROMYCES-CEREVISIAE; SIGNALING PATHWAYS
AB The formation of aqueous pores by the polyene antibiotic amphotericin B (AmB) is at the basis of its fungicidal and leishmanicidal action. However, other types of nonlethal and dose-dependent biphasic effects that have been associated with the AmB action in different cells, including a variety of survival responses, are difficult to reconcile with the formation of a unique type of ion channel by the antibiotic. In this respect, there is increasing evidence indicating that AmB forms nonaqueous (cation-selective) channels at concentrations below the threshold at which aqueous pores are formed. The main foci of this review will be (1) to provide a summary of the evidence supporting the formation of cation-selective ion channels and aqueous pores by AmB in lipid membrane models and in the membranes of eukaryotic cells; (2) to discuss the influence of membrane parameters such as thickness fluctuations, the type of sterol present and the existence of sterol-rich specialized lipid raft microdomains in the formation process of such channels; and (3) to develop a cell model that serves as a framework for understanding how the intracellular K+ and Na+ concentration changes induced by the cation-selective AmB channels enhance multiple survival response pathways before they are overcome by the more sustained ion fluxes, Ca2+-dependent apoptotic events and cell lysis effects that are associated with the formation of AmB aqueous pores.
C1 NIAID, Div External Act, Bethesda, MD 20982 USA.
RP Cohen, BE (reprint author), NIAID, Div External Act, 6700B Rockledge Dr, Bethesda, MD 20982 USA.
EM ec17w@nih.gov
NR 170
TC 19
Z9 20
U1 0
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0022-2631
J9 J MEMBRANE BIOL
JI J. Membr. Biol.
PD DEC
PY 2010
VL 238
IS 1-3
BP 1
EP 20
DI 10.1007/s00232-010-9313-y
PG 20
WC Biochemistry & Molecular Biology; Cell Biology; Physiology
SC Biochemistry & Molecular Biology; Cell Biology; Physiology
GA 691FZ
UT WOS:000285067000001
PM 21085940
ER
PT J
AU Sack, MN
AF Sack, Michael N.
TI Rab4a signaling unmasks a pivotal link between myocardial homeostasis
and metabolic remodeling in the diabetic heart
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Editorial Material
ID INSULIN-RESISTANCE; MITOCHONDRIAL DYSFUNCTION; PPAR-ALPHA; MELLITUS;
CARDIOMYOPATHY; ACTIVATION; RECEPTOR; BETA
C1 NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
RP Sack, MN (reprint author), NHLBI, Ctr Mol Med, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z01 HL005102-04]
NR 19
TC 3
Z9 3
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD DEC
PY 2010
VL 49
IS 6
BP 908
EP 910
DI 10.1016/j.yjmcc.2010.09.002
PG 3
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 681GJ
UT WOS:000284299100003
PM 20840849
ER
PT J
AU Xie, ZH
Yang, ZO
Druey, KM
AF Xie, Zhihui
Yang, Zhao
Druey, Kirk M.
TI Phosphorylation of RGS13 by the Cyclic AMP-dependent Protein Kinase
Inhibits RGS13 Degradation
SO JOURNAL OF MOLECULAR CELL BIOLOGY
LA English
DT Article
DE RGS proteins; cAMP; protein kinase; phosphorylation
ID CANCER CELL-GROWTH; END RULE PATHWAY; TRANSCRIPTIONAL REGULATION;
REGULATOR; GENE; EXPRESSION; RECEPTOR; CREB; MECHANISM; RESPONSES
AB Regulators of G-protein signaling (RGS) proteins are scaffolds that control diverse signaling pathways by modulating signalosome formation and by accelerating the GTPase activity of heterotrimeric G proteins. Although expression of many RGS proteins is relatively low in quiescent cells, transcriptional and post-translational responses to environmental cues regulate both their abundance and activity. We found previously that RGS13, one of the smallest RGS proteins in the family, inhibited cyclic AMP-dependent protein kinase (PKA)-induced gene expression through interactions with the transcription factor cAMP-response element-binding (CREB) protein. Here, we show that PKA activation also leads to increased steady-state RGS13 expression through RGS13 phosphorylation, which inhibits RGS13 protein degradation. RGS13 turnover was significantly reduced in cells stimulated with cAMP, which was reversed by expression of the PKA-specific inhibitory peptide PKI. RGS13 phosphorylation was diminished by mutation of an N-terminal Thr residue (T41) identified as a phosphorylation site by mass spectrometry. Mutation of Thr41 in RGS13 to Ala (T41A) reduced steady-state RGS13 levels and its ability to inhibit M2 muscarinic receptor-mediated Erk phosphorylation compared with wild-type RGS13 by attenuating the protective effect of cAMP on RGS13 degradation. RGS13 underwent ubiquitylation, indicating that it is a likely target of the proteasome. These studies are the first to demonstrate post-translational mechanisms controlling the expression of RGS13. Stabilization of RGS13 through PKA-mediated phosphorylation could enhance RGS13 functions, providing negative feedback regulation that promotes cellular desensitization.
C1 [Xie, Zhihui; Yang, Zhao; Druey, Kirk M.] NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Druey, KM (reprint author), NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, 10 Ctr Dr,Room 11N242, Bethesda, MD 20892 USA.
EM kdruey@niaid.nih.gov
FU NIH, NIAID [AI000939-06 LAD]
FX This study was carried out as part of the authors' work for the National
Institute of Allergy and Infectious Diseases (NIAID). It supported by
the Intramural Research Program of the NIH, NIAID (grant no. AI000939-06
LAD).
NR 36
TC 10
Z9 10
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1674-2788
J9 J MOL CELL BIOL
JI J. Mol. Cell Biol.
PD DEC
PY 2010
VL 2
IS 6
BP 357
EP 365
DI 10.1093/jmcb/mjq031
PG 9
WC Cell Biology
SC Cell Biology
GA 709HM
UT WOS:000286429100008
PM 20974683
ER
PT J
AU Riminucci, M
Robey, PG
Saggio, I
Bianco, P
AF Riminucci, Mara
Robey, Pamela Gehron
Saggio, Isabella
Bianco, Paolo
TI Skeletal progenitors and the GNAS gene: fibrous dysplasia of bone read
through stem cells
SO JOURNAL OF MOLECULAR ENDOCRINOLOGY
LA English
DT Review
ID XL-ALPHA-S; STIMULATORY G-PROTEIN; MCCUNE-ALBRIGHT SYNDROME;
NUCLEOTIDE-BINDING PROTEIN; SHORT SPLICE VARIANTS; GS-ALPHA;
HEMATOPOIETIC MICROENVIRONMENT; PHOSPHATE HOMEOSTASIS; ACTIVATING
MUTATIONS; ADENYLYL-CYCLASE
AB Activating mutations of the GNAS gene, which causes fibrous dysplasia of bone (FD), lead to remarkable changes in the properties of skeletal progenitors, and it is these changes that mediate the pathological effect of this gene on bone. Mutated skeletal stem cells lose the ability to differentiate into adipocytes, and to maintain in situ, and transfer heterotopically, the hematopoietic microenvironment, leading to abnormal bone marrow histology in FD. They overexpress molecular effectors of osteoclastogenesis, thus promoting inappropriate bone resorption leading to fragility of FD bone. They express the phosphate-regulating hormone FGF-23 at normal levels, whose excess in the serum of FD patients correlates with the mass of osteogenic cells within FD lesions, leading to osteomalacia and deformity of the FD bone, and revealing that bone is an endocrine organ regulating renal handling of phosphate. Mechanisms of allelic selection and stem cell selection occur in mutated skeletal stem cells and contribute to the inherent diversity and evolution over time in FD. The definition of the etiological role of GNAS mutations marks the watershed between many decades of descriptive observation and the definition of cellular and molecular mechanisms that would explain and hopefully allow for a cure for the disease. Placing stem cells at center stage has permitted substantial advances in one decade, and promises more for the one to come.
C1 [Bianco, Paolo] Univ Roma La Sapienza, Div Pathol, Dept Mol Med, I-00161 Rome, Italy.
[Riminucci, Mara; Saggio, Isabella; Bianco, Paolo] Biomed Sci Pk San Raffaele, I-00128 Rome, Italy.
[Robey, Pamela Gehron] Natl Inst Dent & Craniofacial Res, Dept Hlth & Human Serv, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Saggio, Isabella] Univ Roma La Sapienza, Dept Genet & Mol Biol, I-00185 Rome, Italy.
[Saggio, Isabella] Inst Mol Biol & Pathol, Natl Res Council, I-00185 Rome, Italy.
RP Bianco, P (reprint author), Univ Roma La Sapienza, Div Pathol, Dept Mol Med, Viale Regina Elena 324, I-00161 Rome, Italy.
EM paolo.bianco@uniroma1.it
RI Robey, Pamela/H-1429-2011;
OI Robey, Pamela/0000-0002-5316-5576; saggio, isabella/0000-0002-9497-7415
FU Telethon [GGP09227]; Fondazione Roma; Ministry for University and
Research of Italy
FX The authors' work mentioned in this article was funded by Telethon
GGP09227, Fondazione Roma, and Ministry for University and Research of
Italy.
NR 73
TC 20
Z9 22
U1 0
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0952-5041
J9 J MOL ENDOCRINOL
JI J. Mol. Endocrinol.
PD DEC
PY 2010
VL 45
IS 6
BP 355
EP 364
DI 10.1677/JME-10-0097
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 684ZH
UT WOS:000284593300001
PM 20841428
ER
PT J
AU Meng, J
Wang, DL
Wang, PC
Jia, L
Chen, CY
Liang, XJ
AF Meng, Jie
Wang, Dong-liang
Wang, Paul C.
Jia, Lee
Chen, Chunying
Liang, Xing-Jie
TI Biomedical Activities of Endohedral Metallofullerene Optimized for
Nanopharmaceutics
SO JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
LA English
DT Article; Proceedings Paper
CT International Conference on NanoToxicology
CY SEP 17-19, 2008
CL Zhengzhou, PEOPLES R CHINA
SP Chinese Assoc Sci & Technol, Chinese Soc Toxicol, Natl Ctr Nanosciences & Technol China, Amer Assoc Chinese Toxicol, Inst High Energy Phy, Chinese Acad Sci (CAS)
DE Metallofullerenes; Nanoparticles; Toxicity; Nanopharmaceutics
ID MRI CONTRAST AGENTS; WATER-SOLUBLE METALLOFULLERENES; HEALTHY ADULT
MICE; OXIDATIVE STRESS; FUNCTIONALIZED FULLERENES; ENGINEERED
NANOMATERIALS; PHOTODYNAMIC THERAPY; CARBON NANOMATERIALS; INDUCED
APOPTOSIS; IN-VIVO
AB Endohedral metallofullerenes, a novel form of carbon-related nanomaterials, currently attract wide attention for their potential applications in biomedical fields such as therapeutic medicine. Most endohedral nnetallofullerenes are synthesized using C-60 or higher molecular weight fullerenes because of the limited interior volume of fullerene. It is known that the encapsulated metal atom has strong electronic interactions with the carbon cage in metallofullerenes. Gd@C-82 is one of the most important molecules in the metallofullerene family, known as Magnetic Resonance Imaging (MRI) contrast agent candidate for diagnostic imaging. Gadolinium endohedral metallofullerenol (e.g., Gd@C-82(OH)(22)) is a functionalized fullerene with gadolinium trapped inside carbon cage. Our group previously demonstrated that the distinctive chemical and physical properties of Gd@C-82(OH)(22) are dependent on the number and position of the hydroxyl groups on the fullerene cage. The present article summarizes our latest findings of biomedical effects of Gd@C-82(OH)(22) and gives rise to a connected flow of the existing knowledge and information from experts in the field. It briefly narrates the synthesis and physico-chemical properties of Gd@C-82(OH)(22). The polyhydroxylated nanoparticles exhibit the enhanced water solubility and high purity, and were tested as a MRI contrast agent. Gd@C-82(OH)(22) treatment inhibited tumor growth in tumor-bearing nude mice. Although the precise mechanisms of this action are not well defined, our in vitro data suggest involvements of improved immunity and antioxidation by Gd@C-82(OH)(22) and its size-based selective targeting to tumor site. The review critically analyzed the relevant data instead of fact-listing, and explained the potential for developing Gd@C-82(OH)(22) into a diagnostic or therapeutic agent.
C1 [Meng, Jie; Wang, Dong-liang; Chen, Chunying; Liang, Xing-Jie] Natl Ctr Nanosci & Technol China, Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China.
[Wang, Paul C.] Howard Univ, Dept Radiol, Lab Mol Imaging, Washington, DC 20060 USA.
[Jia, Lee] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, Rockville, MD 20852 USA.
RP Liang, XJ (reprint author), Natl Ctr Nanosci & Technol China, Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China.
FU NCI NIH HHS [2U54 CA091431-06A1, U54 CA091431, U54 CA091431-06A1]; NCRR
NIH HHS [G12 RR003048-23, 2G12RR003048, G12 RR003048, G12 RR003048-20S1]
NR 81
TC 15
Z9 16
U1 0
U2 27
PU AMER SCIENTIFIC PUBLISHERS
PI VALENCIA
PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA
SN 1533-4880
J9 J NANOSCI NANOTECHNO
JI J. Nanosci. Nanotechnol.
PD DEC
PY 2010
VL 10
IS 12
BP 8610
EP 8616
DI 10.1166/jnn.2010.2691
PG 7
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 672XQ
UT WOS:000283621400100
PM 21121373
ER
PT J
AU Whitson, EL
Thomas, CL
Henrich, CJ
Sayers, TJ
McMahon, JB
Mckee, TC
AF Whitson, Emily L.
Thomas, Cheryl L.
Henrich, Curtis J.
Sayers, Thomas J.
McMahon, James B.
McKee, Tawnya C.
TI Clerodane Diterpenes from Casearia arguta That Act As Synergistic TRAIL
Sensitizers
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID SYLVESTRIS SW FLACOURTIACEAE; ANTITUMOR PRINCIPLES; DEATH RECEPTORS;
RAIN-FOREST; CANCER; MEMBRANACEA; MECHANISMS; RESISTANCE; LEAVES; CELLS
AB Casearia arguta was investigated as part of the ongoing search for synergistic TRAIL (tumor necrosis factor-a-related apoptosis-inducing ligand) sensitizers. As a result of this study, argutins A-H, eight new highly oxygenated clerodane diterpenes, were isolated from the plant Casearia arguta collected in Guatemala. The modified Mosher ester method was utilized to establish the absolute configuration of argutins A and F. Each of the argutins showed varying levels of synergy with TRAIL. Argutin B showed the highest TRAIL sensitization; the synergistic effect of argutin B and TRAIL together was 3-fold greater than argutin B alone.
C1 [Whitson, Emily L.; Thomas, Cheryl L.; Henrich, Curtis J.; McMahon, James B.; McKee, Tawnya C.] NCI, Mol Targets Lab, Mol Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Henrich, Curtis J.; Sayers, Thomas J.] SAIC Frederick Inc, Frederick, MD 21702 USA.
[Sayers, Thomas J.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Mckee, TC (reprint author), NCI, Mol Targets Lab, Mol Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM mckeeta@mail.nih.gov
RI Sayers, Thomas/G-4859-2015
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX The authors would like to thank N. Marshall (NYBG), N. Trushell (NYBG),
D. Newman (NPB), and T. McCloud (NPSG) for collection, identification,
contract collection, and extraction of the plant material and the
Biophysics Resource of the Structural Biophysics Laboratory for
providing technical assistance with Q-TOF LC-MS experiments. This
project has been funded in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. This research
was supported in part by the Intramural Research Program of NIH,
National Cancer Institute, Center for Cancer Research.
NR 38
TC 27
Z9 27
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD DEC
PY 2010
VL 73
IS 12
BP 2013
EP 2018
DI 10.1021/np1004455
PG 6
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 697ZM
UT WOS:000285560000008
PM 21067210
ER
PT J
AU Luo, YQ
Mughal, MR
Ouyang, TGSX
Jiang, HY
Luo, WM
Yu, QS
Greig, NH
Mattson, MP
AF Luo, Yongquan
Mughal, Mohamed R.
Ouyang, Tae-Gen Son Xin
Jiang, Haiyang
Luo, Weiming
Yu, Qian-Sheng
Greig, Nigel H.
Mattson, Mark P.
TI Plumbagin promotes the generation of astrocytes from rat spinal cord
neural progenitors via activation of the transcription factor Stat3
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE ciliary neurotrophic factor; GFAP; neural progenitors; neurogenesis;
Stat3
ID NEUROEPITHELIAL STEM-CELLS; NEURONAL PRECURSORS; NEUROTROPHIC FACTOR;
OXIDATIVE STRESS; NERVOUS-SYSTEM; CYCLE ARREST; IN-VITRO;
DIFFERENTIATION; APOPTOSIS; PATHWAY
AB P>Plumbagin (5-hydroxy-2-methyl-1,4 naphthoquinone) is a naturally occurring low molecular weight lipophilic phytochemical derived from roots of plants of the Plumbago genus. Plumbagin has been reported to have several clinically relevant biological activities in non-neural cells, including anti-atherosclerotic, anticoagulant, anticarcinogenic, antitumor, and bactericidal effects. In a recent screen of a panel of botanical pesticides, we identified plumbagin as having neuroprotective activity. In this study, we determined if plumbagin could modify the developmental fate of rat E14.5 embryonic neural progenitor cells (NPC). Plumbagin exhibited no cytotoxicity when applied to cultured NPC at concentrations below 1 mu M. At a concentration of 0.1 mu M, plumbagin significantly enhanced the proliferation of NPC as indicated by a 17% increase in the percentage of cells incorporating bromo-deoxyuridine. Plumbagin at a concentration of 0.1 pM (but not 0.1 mu M), stimulated the production of astrocytes as indicated by increased GFAP expression. Plumbagin selectively induced the proliferation and differentiation of glial progenitor cells without affecting the proliferation or differentiation of neuron-restricted progenitors. Plumbagin (0.1 pM) rapidly activated the transcription factor signal transducer and activator of transcription 3 (Stat3) in NPC, and a Stat3 inhibitor peptide prevented both plumbagin-induced astrocyte formation and proliferation. These findings demonstrate the ability of a low molecular weight naturally occurring phytochemical to control the fate of glial progenitor cells by a mechanism involving the Stat3 signaling pathway.
C1 [Mattson, Mark P.] NIA, Neurosci Lab, BRC, Intramural Res Program, Baltimore, MD 21224 USA.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, BRC, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012
FU National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institute on Aging.
NR 53
TC 10
Z9 11
U1 0
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD DEC
PY 2010
VL 115
IS 6
BP 1337
EP 1349
DI 10.1111/j.1471-4159.2010.06780.x
PG 13
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 688ME
UT WOS:000284852600004
PM 20456019
ER
PT J
AU Rankin, ML
Sibley, DR
AF Rankin, Michele L.
Sibley, David R.
TI Constitutive phosphorylation by protein kinase C regulates D-1 dopamine
receptor signaling
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE cyclic AMP; D-1 dopamine receptor; desensitization; G protein coupling;
phosphorylation; protein kinase C
ID AGONIST-INDUCED DESENSITIZATION; ADENYLATE-CYCLASE; COUPLED RECEPTORS;
TRAFFICKING; D1; ERYTHROCYTES; LOCALIZATION; ACTIVATION; ARRESTINS;
MECHANISM
AB P>The D-1 dopamine receptor (D(1)DAR) is robustly phosphorylated by multiple protein kinases, yet the phosphorylation sites and functional consequences of these modifications are not fully understood. Here, we report that the D(1)DAR is phosphorylated by protein kinase C (PKC) in the absence of agonist stimulation. Phosphorylation of the D(1)DAR by PKC is constitutive in nature, can be induced by phorbol ester treatment or through activation of Gq-mediated signal transduction pathways, and is abolished by PKC inhibitors. We demonstrate that most, but not all, isoforms of PKC are capable of phosphorylating the receptor. To directly assess the functional role of PKC phosphorylation of the D(1)DAR, a site-directed mutagenesis approach was used to identify the PKC sites within the receptor. Five serine residues were found to mediate the PKC phosphorylation. Replacement of these residues had no effect on D(1)DAR expression or agonist-induced desensitization; however, G protein coupling and cAMP accumulation were significantly enhanced in PKC-null D(1)DAR. Thus, constitutive or heterologous PKC phosphorylation of the D(1)DAR dampens dopamine activation of the receptor, most likely occurring in a context-specific manner, mediated by the repertoire of PKC isozymes within the cell.
C1 [Rankin, Michele L.; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA.
RP Sibley, DR (reprint author), NINDS, Mol Neuropharmacol Sect, NIH, 5625 Fishers Lane,Room 4S-04,MSC 9405, Bethesda, MD 20892 USA.
EM sibley@helix.nih.gov
FU NINDS; NIMH, NIH
FX This research was supported in part by the Intramural Research Program
of NINDS and NIMH, NIH. M.L.R. was supported by an Intramural NINDS
Competitive Fellowship. We would like to thank the NINDS DNA Sequencing
Facility for generating all sequencing data used in this study. We would
also like to thank Dr. Varnitha Ramakrishana for the HEK293Tsa201 cells.
NR 44
TC 7
Z9 7
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD DEC
PY 2010
VL 115
IS 6
BP 1655
EP 1667
DI 10.1111/j.1471-4159.2010.07074.x
PG 13
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 688ME
UT WOS:000284852600031
PM 20969574
ER
PT J
AU Tabak, J
Shermann, A
Leng, G
AF Tabak, J.
Shermann, A.
Leng, G.
TI The Modern Box and Arrow Diagram
SO JOURNAL OF NEUROENDOCRINOLOGY
LA English
DT Editorial Material
C1 [Tabak, J.] Florida State Univ, Tallahassee, FL 32306 USA.
[Shermann, A.] NIDDK, NIH, Bethesda, MD USA.
[Leng, G.] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh, Midlothian, Scotland.
RP Tabak, J (reprint author), Florida State Univ, BRF 206, Tallahassee, FL 32306 USA.
EM joel@neuro.fsu.edu
RI Leng, Gareth/C-6688-2011; tabak, joel/K-1549-2013;
OI Leng, Gareth/0000-0002-2388-8466; Tabak, Joel/0000-0002-0588-957X
NR 4
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0953-8194
J9 J NEUROENDOCRINOL
JI J. Neuroendocrinol.
PD DEC
PY 2010
VL 22
IS 12
BP 1215
EP 1216
DI 10.1111/j.1365-2826.2010.02090.x
PG 2
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 682TK
UT WOS:000284425700002
PM 21054583
ER
PT J
AU Purohit, V
Rapaka, RS
Shurtleff, D
AF Purohit, Vishnudutt
Rapaka, Rao S.
Shurtleff, David
TI Mother-to-Child Transmission (MTCT) of HIV and Drugs of Abuse in
Post-Highly Active Antiretroviral Therapy (HAART) Era
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Review
DE HIV; HAART; MTCT; Drugs of abuse
ID IMMUNODEFICIENCY-VIRUS TYPE-1; BLOOD MONONUCLEAR PHAGOCYTES;
LOW-BIRTH-WEIGHT; CIGARETTE-SMOKING; MEDICATION ADHERENCE; MEDIATED
ENHANCEMENT; INFANT TRANSMISSION; TREATMENT OUTCOMES; ENDOTHELIAL-CELLS;
LIVER-MICROSOMES
AB In the pre-highly active antiretroviral therapy (HAART) era, prenatal "vertical" mother-to-child transmission (MTCT) of HIV was about 25% and exposure of pregnant mothers to drugs of abuse (illicit drugs and tobacco smoking) was a significant contributory factor of MTCT. However, with the introduction of HAART, the rate of MTCT of HIV has decreased to less that 2%. But, it is estimated that currently about 5.1% of pregnant women use illicit drugs and 16.4% smoke tobacco. The residual prevalence of MTCT is of concern and may be related to this continued prevalence of substance use among pregnant mothers. In this report, we review and present evidence that supports the hypothesis that drugs of abuse do have the potential to increase MTCT of HIV in the presence of HAART. Exposure to drugs of abuse during pregnancy may increase MTCT of HIV through a variety of mechanisms that are addressed in detail including possible damage to the placenta, induction of preterm birth, and increasing maternal plasma viral load though a variety of putative mechanisms such as: (a) promoting HIV replication in monocyte/macrophages; (b) increasing the expression of CCR5 receptors; (c) decreasing the expression of CCR5 receptor ligands; (d) increasing the expression of CXCR4 receptors; (e) increasing the expression of DC-SIGN; (f) impairing the efficacy of HAART through drug drug interaction; and (g) promoting HIV mutation and replication through non-adherence to HAART.
C1 [Purohit, Vishnudutt; Rapaka, Rao S.; Shurtleff, David] NIDA, Div Basic Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA.
RP Purohit, V (reprint author), NIDA, Div Basic Neurosci & Behav Res, NIH, 6001 Execut Blvd Room 4282,MSC 9555, Bethesda, MD 20892 USA.
EM vpurohit@nida.nih.gov
NR 93
TC 2
Z9 2
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 2010
VL 5
IS 4
BP 507
EP 515
DI 10.1007/s11481-010-9242-7
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 686YX
UT WOS:000284739500004
PM 20838913
ER
PT J
AU Hahn, G
Petermann, T
Havenith, MN
Yu, S
Singer, W
Plenz, D
Nikolic, D
AF Hahn, Gerald
Petermann, Thomas
Havenith, Martha N.
Yu, Shan
Singer, Wolf
Plenz, Dietmar
Nikolic, Danko
TI Neuronal Avalanches in Spontaneous Activity In Vivo
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID CORTICAL-NEURONS; VISUAL-CORTEX; CRITICALITY; NETWORKS; PATTERNS;
OSCILLATIONS; INTEGRATION; RESPONSES; DYNAMICS; RANGE
AB Hahn G, Petermann T, Havenith MN, Yu S, Singer W, Plenz D, Nikolic D. Neuronal avalanches in spontaneous activity in vivo. J Neurophysiol 104: 3312-3322, 2010. First published July 14, 2010; doi:10.1152/jn.00953.2009. Many complex systems give rise to events that are clustered in space and time, thereby establishing a correlation structure that is governed by power law statistics. In the cortex, such clusters of activity, called "neuronal avalanches," were recently found in local field potentials (LFPs) of spontaneous activity in acute cortex slices, slice cultures, the developing cortex of the anesthetized rat, and premotor and motor cortex of awake monkeys. At present, it is unclear whether neuronal avalanches also exist in the spontaneous LFPs and spike activity in vivo in sensory areas of the mature brain. To address this question, we recorded spontaneous LFPs and extracellular spiking activity with multiple 4 x 4 microelectrode arrays (Michigan Probes) in area 17 of adult cats under anesthesia. A cluster of events was defined as a consecutive sequence of time bins Delta t (1-32 ms), each containing at least one LFP event or spike anywhere on the array. LFP cluster sizes consistently distributed according to a power law with a slope largely above -1.5. In two thirds of the corresponding experiments, spike clusters also displayed a power law that displayed a slightly steeper slope of -1.8 and was destroyed by subsampling operations. The power law in spike clusters was accompanied with stronger temporal correlations between spiking activities of neurons that spanned longer time periods compared with spike clusters lacking power law statistics. The results suggest that spontaneous activity of the visual cortex under anesthesia has the properties of neuronal avalanches.
C1 [Hahn, Gerald; Havenith, Martha N.; Yu, Shan; Singer, Wolf; Nikolic, Danko] Max Planck Inst Brain Res, Dept Neurophysiol, D-60528 Frankfurt, Germany.
[Hahn, Gerald] CNRS, Unite Neurosci Informat & Complexite, Gif Sur Yvette, France.
[Petermann, Thomas; Yu, Shan; Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
[Singer, Wolf; Nikolic, Danko] Frankfurt Inst Adv Studies, Frankfurt, Germany.
RP Nikolic, D (reprint author), Max Planck Inst Brain Res, Dept Neurophysiol, Deutschordenstr 46, D-60528 Frankfurt, Germany.
EM danko.nikolic@gmail.com
RI Singer, Wolf/D-6874-2012;
OI Hahn, Gerald/0000-0002-7069-0639
FU Hertie Foundation; Max-Planck Society; Deutsche Forschungsgemeinschaft
[NI 708/2-1]; National Institute of Mental Health; European Community
[PITN-GA-2009-237955]
FX This work was supported by the Hertie Foundation, the Max-Planck
Society, a grant from Deutsche Forschungsgemeinschaft number NI 708/2-1,
the Division of the Intramural Research Program of the National
Institute of Mental Health, and the European Community's Seventh
Framework Program (FP7) under grant agreement number
PITN-GA-2009-237955.
NR 33
TC 61
Z9 62
U1 0
U2 8
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD DEC
PY 2010
VL 104
IS 6
BP 3312
EP 3322
DI 10.1152/jn.00953.2009
PG 11
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 695SK
UT WOS:000285392700036
PM 20631221
ER
PT J
AU Kim, E
Hyrc, KL
Speck, J
Lundberg, YW
Salles, FT
Kachar, B
Goldberg, MP
Warchol, ME
Ornitz, DM
AF Kim, Euysoo
Hyrc, Krzysztof L.
Speck, Judith
Lundberg, Yunxia W.
Salles, Felipe T.
Kachar, Bechara
Goldberg, Mark P.
Warchol, Mark E.
Ornitz, David M.
TI Regulation of Cellular Calcium in Vestibular Supporting Cells by
Otopetrin 1
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID AGE-RELATED-CHANGES; PIG INNER-EAR; GUINEA-PIG; OTOCONIAL MEMBRANE;
GLOBULAR SUBSTANCE; INTRACELLULAR CALCIUM; EXTRACELLULAR NUCLEOTIDES;
THAPSIGARGIN-RESISTANT; PURINERGIC RECEPTORS; HAIR-CELLS
AB Kim E, Hyrc KL, Speck J, Lundberg YW, Salles FT, Kachar B, Goldberg MP, Warchol ME, Ornitz DM. Regulation of cellular calcium in vestibular supporting cells by Otopetrin 1. J Neurophysiol 104: 3439-3450, 2010. First published June 16, 2010; doi:10.1152/jn.00525.2010. Otopetrin 1 (OTOP1) is a multitrans-membrane domain protein, which is essential for mineralization of otoconia, the calcium carbonate biominerals required for vestibular function, and the normal sensation of gravity. The mechanism driving mineralization of otoconia is poorly understood, but it has been proposed that supporting cells and a mechanism to maintain high concentrations of calcium are critical. Using Otop1 knockout mice and a utricular epithelial organ culture system, we show that OTOP1 is expressed at the apex of supporting cells and functions to increase cytosolic calcium in response to purinergic agonists, such as adenosine 5'-triphosphate (ATP). This is achieved by blocking mobilization of calcium from intracellular stores in an extracellular calcium-dependent manner and by mediating influx of extracellular calcium. These data support a model in which OTOP1 acts as a sensor of the extracellular calcium concentration near supporting cells and responds to ATP in the endolymph to increase intracellular calcium levels during otoconia mineralization.
C1 [Kim, Euysoo; Ornitz, David M.] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
[Hyrc, Krzysztof L.; Warchol, Mark E.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Speck, Judith; Warchol, Mark E.] Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA.
[Lundberg, Yunxia W.] Boys Town Natl Res Hosp, Dept Genet, Omaha, NE 68131 USA.
[Salles, Felipe T.; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD USA.
RP Ornitz, DM (reprint author), Washington Univ, Sch Med, Dept Dev Biol, Campus Box 8103,660 S Euclid Ave, St Louis, MO 63110 USA.
EM dornitz@wustl.edu
RI Salles, Felipe/H-7544-2013;
OI Ornitz, David/0000-0003-1592-7629
FU National Cancer Institute Cancer Center [P30 CA-91842]; National
Institutes of Health [DC-02236, NS-032636, NS-036265, DC-008603];
Washington University Digestive Diseases Research Core Center [P30
DK-052574]; Neuroscience Blueprint Core [P30 NS-057105]; Bakewell Family
Science Foundation; Microscopy and Digital Imaging (MDI) Core Grant [P30
DC-004665]; Ornitz family charitable trust
FX The Siteman Cancer Center is supported in part by an National Cancer
Institute Cancer Center Support Grant P30 CA-91842. This work was funded
by National Institutes of Health Grants DC-02236 to D. M. Ornitz,
NS-032636 and NS-036265 to M. P. Goldberg, DC-008603 to Y. W. Lundberg,
Washington University Digestive Diseases Research Core Center Grant P30
DK-052574 (microinjection of ES cells), Neuroscience Blueprint Core
Grant P30 NS-057105, Bakewell Family Science Foundation, Microscopy and
Digital Imaging (MDI) Core Grant P30 DC-004665, and the Ornitz family
charitable trust.
NR 56
TC 14
Z9 15
U1 1
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD DEC
PY 2010
VL 104
IS 6
BP 3439
EP 3450
DI 10.1152/jn.00525.2010
PG 12
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 695SK
UT WOS:000285392700046
PM 20554841
ER
PT J
AU Heiss, JD
Oldfield, EH
AF Heiss, John D.
Oldfield, Edward H.
TI Chiari malformation Type I Response
SO JOURNAL OF NEUROSURGERY-SPINE
LA English
DT Editorial Material
ID PATHOPHYSIOLOGY; SYRINGOMYELIA
C1 [Heiss, John D.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Oldfield, Edward H.] Univ Virginia Hlth Syst, Dept Neurosurg, Charlottesville, VA USA.
RP Heiss, JD (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1547-5654
J9 J NEUROSURG-SPINE
JI J. Neurosurg.-Spine
PD DEC
PY 2010
VL 13
IS 6
BP 728
EP 728
PG 1
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 684QS
UT WOS:000284565000013
ER
PT J
AU Heiss, JD
Suffredini, G
Smith, R
DeVroom, HL
Patronas, NJ
Butman, JA
Thomas, F
Oldfield, EH
AF Heiss, John D.
Suffredini, Giancarlo
Smith, Rene
DeVroom, Hetty L.
Patronas, Nicholas J.
Butman, John A.
Thomas, Francine
Oldfield, Edward H.
TI Pathophysiology of persistent syringomyelia after decompressive
craniocervical surgery
SO JOURNAL OF NEUROSURGERY-SPINE
LA English
DT Article
DE syringomyelia; therapeutics; radiography; physiology; Arnold-Chiari
malformation; Type I
ID CHIARI-I MALFORMATION; POSTERIOR-FOSSA DECOMPRESSION; ENDOSCOPIC 3RD
VENTRICULOSTOMY; FORAMEN MAGNUM; SYMPTOMATIC PATIENTS; CEREBELLAR
TONSILS; NATURAL-HISTORY; CRANIAL FOSSA; MANAGEMENT; HYDROCEPHALUS
AB Object. Craniocervical decompression for Chiari malformation Type I (CM-I) and syringomyelia has been reported to fail in 10%-40% of patients. The present prospective clinical study was designed to test the hypothesis that in cases in which syringomyelia persists after surgery, craniocervical decompression relieves neither the physiological block at the for amen magnum nor the mechanism of syringomyelia progression.
Methods. The authors prospectively evaluated and treated 16 patients with CM-I who had persistent syringomyelia despite previous craniocervical decompression. Testing before surgery included the following: I) clinical examination; 2) evaluation of the anatomy using T1-weighted MR imaging; 3) assessment of the syrinx and CSF velocity and flow using elm: phase-contrast MR imaging; and 4) appraisal of the lumbar and cervical subarachnoid pressures at rest, during a Valsalva maneuver, during jugular compression, and following the removal of CSF (CSF compliance measurement). During surgery, ultrasonography was performed to observe the motion of the cerebellar tonsils and syrinx walls; pressure measurements were obtained from the intracranial and lumbar intrathecal spaces. The surgical procedure involved enlarging the previous craniectomy and performing an expansile duraplasty with autologous pericranium. Three to 6 months after surgery, clinical examination. MR imaging, and CSF pressure recordings were repeated. Clinical examination and MR imaging studies were then repeated annually.
Results. Before reexploration, patients had a decreased size of the CSF pathways and a partial blockage in CSF transmission at the foramen magnum. Cervical subarachnoid pressure and pulse pressure were abnormally elevated. During surgery, ultrasonographic imaging demonstrated active pulsation of the cerebellar tonsils, with the tonsils descending during cardiac systole and concomitant narrowing of the upper pole of the syrinx. Three months after reoperation, patency of the CSF pathways was restored and pressure transmission was improved. The flow of syrinx fluid and the diameter of the syrinx decreased after surgery in 15 of 16 patients.
Conclusions. Persistent blockage of the CSF pathways at the foramen magnum resulted in increased pulsation of the cerebellar tensils, which acted on a partially enclosed cervical subarachnoid space to create elevated cervical CSF pressure waves, which in turn affected the external surface of the spinal cord to force CSF into the spinal cord through the Virchew-Robin spaces and to propel the syrinx fluid caudally, leading to syrinx progression. A surgical procedure that reestablished the CSF pathways at the foramen magnum reversed this pathophysiological mechanism and resolved syringomyelia. Elucidating the pathophysiology of persistent syringomyelia has implications for its primary and secondary treatment. (DOI: 10.3171/2010.6.SPINE10200)
C1 [Heiss, John D.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Oldfield, Edward H.] Univ Virginia Hlth Syst, Dept Neurosurg, Charlottesville, VA USA.
RP Heiss, JD (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,10-3D20,MSC 1414, Bethesda, MD 20892 USA.
EM heissj@ninds.nih.gov
RI Butman, John/A-2694-2008; Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU National Institute of Neurological Disorders and Stroke at the National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke at the National
Institutes of Health.
NR 58
TC 23
Z9 23
U1 1
U2 4
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1547-5654
J9 J NEUROSURG-SPINE
JI J. Neurosurg.-Spine
PD DEC
PY 2010
VL 13
IS 6
BP 729
EP 742
DI 10.3171/2010.6.SPINE10200
PG 14
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 684QS
UT WOS:000284565000014
PM 21121751
ER
PT J
AU Stumbo, PJ
Weiss, R
Newman, JW
Pennington, JA
Tucker, KL
Wiesenfeld, PL
Illner, AK
Klurfeld, DM
Kaput, J
AF Stumbo, Phyllis J.
Weiss, Rick
Newman, John W.
Pennington, Jean A.
Tucker, Katherine L.
Wiesenfeld, Paddy L.
Illner, Anne-Kathrin
Klurfeld, David M.
Kaput, Jim
TI Web-Enabled and Improved Software Tools and Data Are Needed to Measure
Nutrient Intakes and Physical Activity for Personalized Health Research
SO JOURNAL OF NUTRITION
LA English
DT Article
ID HEART-RATE-VARIABILITY; FOOD FREQUENCY QUESTIONNAIRE; DIETARY
ASSESSMENT; HUMAN METABOLOME; SYSTEMS BIOLOGY; HIGH-THROUGHPUT;
FATTY-ACIDS; IDENTIFICATION; NUTRIGENOMICS; CHALLENGES
AB Food intake physical activity (PA) and genetic makeup each affect health and each factor influences the impact of the other 2 factors Nutrigenomics describes interactions between genes and environment Knowledge about the interplay between environment and genetics would be improved if experimental designs included measures of nutrient intake and PA Lack of familiarity about how to analyze environmental variables and ease of access to tools and measurement instruments are 2 deterrents to these combined studies This article describes the state of the art for measuring food intake and PA to encourage researchers to make their tools better known and more available to workers in other fields Information presented was discussed during a workshop on this topic sponsored by the USDA NIH and FDA in the spring of 2009 J Nutr 140 2104-2115 2010
C1 [Stumbo, Phyllis J.] Univ Iowa, Inst Clin & Translat Sci, Iowa City, IA 52242 USA.
[Weiss, Rick] Viocare Inc, Princeton, NJ 08542 USA.
[Newman, John W.] ARS, USDA, Western Human Nutr Res Ctr, Davis, CA 95616 USA.
[Pennington, Jean A.] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA.
[Tucker, Katherine L.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA.
[Wiesenfeld, Paddy L.] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA.
[Illner, Anne-Kathrin] German Inst Human Nutr, Dept Epidemiol, D-14558 Potsdam, Nuthetal, Germany.
[Klurfeld, David M.] USDA ARS, Beltsville, MD 20705 USA.
[Kaput, Jim] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA.
RP Stumbo, PJ (reprint author), Univ Iowa, Inst Clin & Translat Sci, Iowa City, IA 52242 USA.
RI Tucker, Katherine/A-4545-2010;
OI Tucker, Katherine/0000-0001-7640-662X
FU FDA/National Center for Toxicological Research/Division of Personalized
Nutrition and Medicine NIH; USDA
FX Supported by FDA/National Center for Toxicological Research/Division of
Personalized Nutrition and Medicine NIH and USDA
NR 91
TC 16
Z9 16
U1 1
U2 4
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD DEC
PY 2010
VL 140
IS 12
BP 2104
EP 2115
DI 10.3945/jn.110.128371
PG 12
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 692AG
UT WOS:000285123300001
PM 20980656
ER
EF