FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Yi, L
Rosales, T
Rose, JJ
Chaudhury, B
Knutson, JR
Venkatesan, S
AF Yi, Ling
Rosales, Tilman
Rose, Jeremy J.
Chaudhury, Bhabhadeb
Knutson, Jay R.
Venkatesan, Sundararajan
TI HIV-1 Nef Binds a Subpopulation of MHC-I throughout Its Trafficking
Itinerary and Down-regulates MHC-I by Perturbing Both Anterograde and
Retrograde Trafficking
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FLUORESCENCE CORRELATION SPECTROSCOPY; VIRUS TYPE-1 NEF;
CROSS-CORRELATION SPECTROSCOPY; LIVING CELLS; ANTIGEN PRESENTATION;
ENDOCYTIC PATHWAY; PLASMA-MEMBRANE; CYTOPLASMIC TAIL; PHOTOBLEACHING
RECOVERY; SERINE PHOSPHORYLATION
AB The HIV protein Nef is thought to mediate immune evasion and promote viral persistence in part by down-regulating major histocompatibility complex class I protein (MHC-I or HLA-I) from the cell surface. Two different models have been proposed to explain this phenomenon as follows: 1) stimulation of MHC-I retrograde trafficking from and aberrant recycling to the plasma membrane, and 2) inhibition of anterograde trafficking of newly synthesized HLA-I from the endoplasmic reticulum to the plasma membrane. We show here that Nef simultaneously uses both mechanisms to down-regulate HLA-I in peripheral blood mononuclear cells or HeLa cells. Consistent with this, we found by using fluorescence correlation spectroscopy that a third of diffusing HLA-I at the endoplasmic reticulum, Golgi/trans-Golgi network, and the plasma membrane (PM) was associated with Nef. The binding of Nef was similarly avid for native HLA-I and recombinant HLA-I A2 at the PM. Nef binding to HLA-I at the PM was sensitive to specific inhibition of endocytosis. It was also attenuated by cyclodextrin disruption of PM lipid microdomain architecture, a change that also retarded lateral diffusion and induced large clusters of HLA-I. In all, our data support a model for Nef down-regulation of HLA-I that involves both major trafficking itineraries and persistent protein-protein interactions throughout the cell.
C1 [Venkatesan, Sundararajan] NIAID, MCBU, LMI, NIH, Bethesda, MD 20892 USA.
[Rosales, Tilman; Knutson, Jay R.] NHLBI, Opt Spect Sect, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Venkatesan, S (reprint author), NIAID, MCBU, LMI, NIH, Bldg 10,Rm 6A05, Bethesda, MD 20892 USA.
EM sv1s@nih.gov
FU National Institutes of Health, Division of Intramural Research, NIAID
FX This work was supported, in whole or in part, by National Institutes of
Health grant from Division of Intramural Research, NIAID.
NR 78
TC 19
Z9 21
U1 1
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 OCT 1
PY 2010
VL 285
IS 40
BP 30884
EP 30905
DI 10.1074/jbc.M110.135947
PG 22
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 653YS
UT WOS:000282135500055
PM 20622010
ER
PT J
AU Fitzkee, NC
Bax, A
AF Fitzkee, Nicholas C.
Bax, Ad
TI Facile measurement of H-1-N-15 residual dipolar couplings in larger
perdeuterated proteins
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE ARTSY; Catalytic core domain; HIV integrase; Quantitative J correlation;
TROSY; RDC
ID HIV-1 INTEGRASE; PULSE SEQUENCES; BIOLOGICAL MACROMOLECULES;
POLARIZATION TRANSFER; CRYSTAL-STRUCTURE; NMR-SPECTROSCOPY; CATALYTIC
DOMAIN; LIQUID-CRYSTAL; ACTIVE-SITE; CORE DOMAIN
AB We present a simple method, ARTSY, for extracting (1)J(NH) couplings and H-1-N-15 RDCs from an interleaved set of two-dimensional H-1-N-15 TROSY-HSQC spectra, based on the principle of quantitative J correlation. The primary advantage of the ARTSY method over other methods is the ability to measure couplings without scaling peak positions or altering the narrow line widths characteristic of TROSY spectra. Accuracy of the method is demonstrated for the model system GB3. Application to the catalytic core domain of HIV integrase, a 36 kDa homodimer with unfavorable spectral characteristics, demonstrates its practical utility. Precision of the RDC measurement is limited by the signal-to-noise ratio, S/N, achievable in the 2D TROSY-HSQC spectrum, and is approximately given by 30/(S/N) Hz.
C1 [Fitzkee, Nicholas C.; Bax, Ad] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM bax@nih.gov
FU NIDDK; NIH; Office of the Director, NIH
FX We thank Alexander Maltsev for the sample of perdeuterated GB3 and for
help in preparing the liquid crystalline solution for
IN50-212 measurement, and Lishan Yao for the protonated GB3
mutant. This work was supported in part by the Intramural Research
Program of the NIDDK, NIH, and by the Intramural AIDS-Targeted Antiviral
Program of the Office of the Director, NIH.
NR 39
TC 37
Z9 37
U1 1
U2 16
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD OCT
PY 2010
VL 48
IS 2
BP 65
EP 70
DI 10.1007/s10858-010-9441-9
PG 6
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA 659VW
UT WOS:000282596100001
PM 20694505
ER
PT J
AU Ahmet, I
Wan, RQ
Mattson, MP
Lakatta, EG
Talan, MI
AF Ahmet, Ismayil
Wan, Ruiqian
Mattson, Mark P.
Lakatta, Edward G.
Talan, Mark I.
TI Chronic Alternate-Day Fasting Results in Reduced Diastolic Compliance
and Diminished Systolic Reserve in Rats
SO JOURNAL OF CARDIAC FAILURE
LA English
DT Article
DE Diastolic dysfunction; heart failure; animal model; nutrition
ID LEFT ATRIAL VOLUME; CALORIC RESTRICTION; MINERALOCORTICOID RECEPTOR;
MYOCARDIAL-INFARCTION; DIETARY RESTRICTION; DISEASE; DYSFUNCTION;
IMPROVES; RISK; METABOLISM
AB Background: Based on animal experiments and limited data from the few human trials, alternate-day fasting (ADF) resulted in weight loss, prolonged life, reduced metabolic risk factors for diabetes and cardiovascular diseases, and reduced prevalence of age-related diseases. The present study is the first comprehensive examination of the long-term effects of ADF on general cardiovascular fitness in rats.
Methods and Results: Four-month-old male Sprague-Dawley rats were started on ADF or continued on ad libitum diets and followed for 6 months with serial echocardiography. A comprehensive hemodynamic evaluation including a combined dobutamine volume stress test was performed at the end of the study, and hearts were harvested for histological assessment. The 6-month-long ADF diet resulted in a 9% reduction (P<.01) of cardiomyocyte diameter and 3-fold increase in interstitial myocardial fibrosis. Left ventricular chamber size was not affected by ADF and ejection fraction was not reduced, but left atrial diameter was increased 16%, and the ratio of early (E) and late atrial (A) waves, in Doppler-measured mitral flow was reduced (P<.01). Pressure-volume loop analyses revealed a "stiff" heart during diastole in ADF rats, whereas combined dobutamine and volume loading showed a significant reduction in left ventricular diastolic compliance and a lack of increase in systolic pump function, indicating a diminished cardiac reserve.
Conclusion: Chronic ADF in rats results in development of diastolic dysfunction with diminished cardiac reserve. ADF is a novel and unique experimental model of diet-induced diastolic dysfunction. The deleterious effect of ADF in rats suggests that additional studies of ADF effects on cardiovascular functions in humans are warranted. (J Cardiac Fail 2010:16:843-853)
C1 [Ahmet, Ismayil; Lakatta, Edward G.; Talan, Mark I.] NIA, Cardiovasc Sci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Wan, Ruiqian; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Talan, MI (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM talanm@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012
FU National Institute on Aging
FX Fully funded by Intramural Research Program, National Institute on
Aging.
NR 33
TC 8
Z9 8
U1 1
U2 4
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 1071-9164
J9 J CARD FAIL
JI J. Card. Fail.
PD OCT
PY 2010
VL 16
IS 10
BP 843
EP 853
DI 10.1016/j.cardfail.2010.05.007
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 664XO
UT WOS:000282997500007
PM 20932467
ER
PT J
AU Fu, D
Wakabayashi, Y
Ido, Y
Lippincott-Schwartz, J
Arias, IM
AF Fu, Dong
Wakabayashi, Yoshiyuki
Ido, Yasuo
Lippincott-Schwartz, Jennifer
Arias, Irwin M.
TI Regulation of bile canalicular network formation and maintenance by
AMP-activated protein kinase and LKB1
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE AMPK; LKB1; Bile canaliculi; Polarity; Primary hepatocytes; Collagen
sandwich culture; P-glycoprotein; Tight junction
ID RAT HEPATOCYTES; CELL POLARITY; SANDWICH CONFIGURATION;
LIVER-REGENERATION; EPITHELIAL-CELLS; TIGHT JUNCTIONS; MYOSIN-II;
IN-VITRO; CULTURE; PHOSPHORYLATION
AB AMP-activated protein kinase (AMPK), a cellular metabolic sensor, is essential in energy regulation and metabolism. Hepatocyte polarization during liver development and regeneration parallels increased metabolism. The current study investigates the effects of AMPK and its upstream activator LKB1 on polarity and bile canalicular network formation and maintenance in collagen sandwich cultures of rat hepatocytes. Immunostaining for the apical protein ABCB1 and the tight junction marker occludin demonstrated that canalicular network formation is sequential and is associated with activation of AMPK and LKB1. AMPK and LKB1 activators accelerated canalicular network formation. Inhibition of AMPK or LKB1 by dominant-negative AMPK or kinase-dead LKB1 constructs blocked canalicular network formation. AICAR and 2-deoxyglucose, which activate AMPK, circumvented the inhibitory effect of kinase-dead LKB1 on canalicular formation, indicating that AMPK directly affects canalicular network formation. After the canalicular network was formed, inhibition of AMPK and LKB1 by dominant-negative AMPK or kinase-dead LKB1 constructs resulted in loss of canalicular network, indicating that AMPK and LKB1 also participate in network maintenance. In addition, activation of AMPK and LKB1 prevented low-Ca2+-mediated disruption of the canalicular network and tight junctions. These studies reveal that AMPK and its upstream kinase, LKB1, regulate canalicular network formation and maintenance.
C1 [Fu, Dong; Wakabayashi, Yoshiyuki; Lippincott-Schwartz, Jennifer; Arias, Irwin M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Ido, Yasuo] Boston Univ, Sch Med, Dept Med, Endocrinol Sect, Boston, MA 02118 USA.
RP Arias, IM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM ariasi@mail.nih.gov
RI Fu, Dong /J-1426-2012
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, US National Institutes of Health
FX The authors appreciate the advice and suggestions of Lewis Cantley
(Harvard Medical School, Boston, MA), Neil Ruderman (Boston University
School of Medicine, Boston, MA) and Reuben Shaw (The Salk Institute for
Biological Studies, La Jolla, CA). This project was supported by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, US National Institutes
of Health. Deposited in PMC for release after 12 months.
NR 49
TC 35
Z9 35
U1 2
U2 5
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD OCT 1
PY 2010
VL 123
IS 19
BP 3294
EP 3302
DI 10.1242/jcs.068098
PG 9
WC Cell Biology
SC Cell Biology
GA 651ER
UT WOS:000281908400010
PM 20826460
ER
PT J
AU Smyth, JT
Hwang, SY
Tomita, T
DeHaven, WI
Mercer, JC
Putney, JW
AF Smyth, Jeremy T.
Hwang, Sung-Yong
Tomita, Takuro
DeHaven, Wayne I.
Mercer, Jason C.
Putney, James W.
TI Activation and regulation of store-operated calcium entry
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Review
DE store-operated Ca2+entry; CRAC; calcium influx; calcium channel; STIM1;
STIM2; Orai1; Orai2; Orai3; TRPC
ID CAPACITATIVE CA2+ ENTRY; LIGHT-CHAIN KINASE; FAST CA2+-DEPENDENT
INACTIVATION; STROMAL INTERACTION MOLECULE-1; PLASMA MEMBRANE JUNCTIONS;
CRAC CHANNEL ACTIVATION; EMBRYONIC KIDNEY-CELLS; PAROTID ACINAR-CELLS;
ENDOPLASMIC-RETICULUM; TRPC CHANNELS
AB Introduction
I(CRAC)
Orais
STIM1
STIM2
STIM1, STIM2 and Ca2+ oscillations
TRPCs and SOCE
Conclusions
The process of store-operated Ca2+ entry (SOCE), whereby Ca2+ influx across the plasma membrane is activated in response to depletion of intracellular Ca2+ stores in the endoplasmic reticulum (ER), has been under investigation for greater than 25 years; however, only in the past 5 years have we come to understand this mechanism at the molecular level. A surge of recent experimentation indicates that STIM molecules function as Ca2+ sensors within the ER that, upon Ca2+ store depletion, rearrange to sites very near to the plasma membrane. At these plasma membrane-ER junctions, STIM interacts with and activates SOCE channels of the Orai family. The molecular and biophysical data that have led to these findings are discussed in this review, as are several controversies within this rapidly expanding field.
C1 [Smyth, Jeremy T.; Hwang, Sung-Yong; Tomita, Takuro; DeHaven, Wayne I.; Mercer, Jason C.; Putney, James W.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM putney@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences
FX Some of the research described in this review was supported by the
Intramural Program of the NIH, National Institute of Environmental
Health Sciences.
NR 146
TC 114
Z9 117
U1 0
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1582-1838
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD OCT
PY 2010
VL 14
IS 10
BP 2337
EP 2349
DI 10.1111/j.1582-4934.2010.01168.x
PG 13
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 672OS
UT WOS:000283596400001
PM 20807283
ER
PT J
AU Felici, A
Giubellino, A
Bottaro, DP
AF Felici, Angelina
Giubellino, Alessio
Bottaro, Donald P.
TI Gab1 Mediates Hepatocyte Growth Factor-Stimulated Mitogenicity and
Morphogenesis in Multipotent Myeloid Cells
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE HGF; MET; GAB1; SHP-2; MYELOID CELLS
ID TYROSINE-PHOSPHATASE SHP-2; ACTIVATED PROTEIN-KINASE; TRANSCRIPTION
FACTOR GATA-2; PLECKSTRIN HOMOLOGY DOMAIN; HEMATOPOIETIC STEM-CELLS;
SIGNAL-REGULATED KINASE; FACTOR RECEPTOR-BETA; GRB2 BINDING-SITE; C-MET;
DOCKING PROTEIN
AB Hepatocyte growth factor (HGF)-stimulated mitogenesis, motogenesis and morphogenesis in various cell types begins with activation of the Met receptor tyrosine kinase and the recruitment of intracellular adaptors and kinase substrates. The adapter protein Gab1 is a critical effector and substrate of activated Met, mediating morphogenesis, among other activities, in epithelial cells. To define its role downstream of Met in hematopoietic cells, Gab1 was expressed in the HGF-responsive, Gab1-negative murine myeloid cell line 32D. Interestingly, the adhesion and motility of Gab1-expressing cells were significantly greater than parental cells, independent of growth factor treatment. Downstream of activated Met, Gab1 expression was specifically associated with rapid Shp-2 recruitment and activation, increased mitogenic potency, suppression of GATA-1 expression and concomitant upregulation of GATA-2 transcription. In addition to enhanced proliferation, continuous culture of Gab1-expressing 32D cells in HGF resulted in cell attachment, filopodia extension and phenotypic changes suggestive of monocytic differentiation. Our results suggest that in myeloid cells, Gab1 is likely to enhance HGF mitogenicity by coupling Met to Shp-2 and GATA-2 expression, thereby potentially contributing to normal myeloid differentiation as well as oncogenic transformation. J. Cell. Biochem. 111: 310-321, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Felici, Angelina; Giubellino, Alessio; Bottaro, Donald P.] NCI, Urol Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA.
RP Bottaro, DP (reprint author), NCI, Urol Oncol Branch, CCR, NIH, Bldg 10 CRC W Rm 2-5239,10 Ctr Dr MSC 1107, Bethesda, MD 20892 USA.
EM dbottaro@helix.nih.gov
RI Bottaro, Donald/F-8550-2010;
OI Bottaro, Donald/0000-0002-5057-5334; Giubellino,
Alessio/0000-0002-5352-0662
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research, Bethesda, MD; NIH, National Cancer Institute, Center
for Cancer Research
FX Grant sponsor: Intramural Research Program of the National Institutes of
Health, National Cancer Institute, Center for Cancer Research, Bethesda,
MD.; We thank Dr. M. Sachs for the pBat-Flag-Gab1, Dr. B. Neel for the
pJ3Shp-2 Delta P and pJ3Shp-2CS expression vectors, Dr. G. Vande Woude
for recombinant human HGF, Dr. M. Udey for helpful comments, Mr. N.
Ellmore for technical assistance and Ms. V. Kapoor for FACS analysis.
This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 82
TC 10
Z9 11
U1 0
U2 2
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 OCT 1
PY 2010
VL 111
IS 2
BP 310
EP 321
DI 10.1002/jcb.22695
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 658HZ
UT WOS:000282482400007
PM 20506405
ER
PT J
AU Hartz, AMS
Mahringer, A
Miller, DS
Bauer, B
AF Hartz, Anika M. S.
Mahringer, Anne
Miller, David S.
Bauer, Bjoern
TI 17-beta-Estradiol: a powerful modulator of blood-brain barrier BCRP
activity
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE BCRP; blood-brain barrier; estrogen; nongenomic regulation; transport
ID CANCER-RESISTANCE-PROTEIN; PLACENTAL BEWO CELLS; NON-GENOMIC ACTIONS;
P-GLYCOPROTEIN; MICROVESSEL ENDOTHELIUM; MULTIDRUG TRANSPORTER;
HORMONAL-REGULATION; RESPONSE ELEMENT; UP-REGULATION; IN-VITRO
AB The ATP-driven efflux transporter, breast cancer resistance protein (BCRP), handles many therapeutic drugs, including chemotherapeutics, limiting their ability to cross the blood-brain barrier. This study provides new insight into rapid, nongenomic regulation of BCRP transport activity at the blood-brain barrier. Using isolated brain capillaries from rats and mice as an ex vivo blood-brain barrier model, we show that BCRP protein is highly expressed in brain capillary membranes and functionally active in intact capillaries. We show that nanomolar concentrations of 17-beta-estradiol (E2) rapidly reduced BCRP transport activity in the brain capillaries. This E2-mediated effect occurred within minutes and did not involve transcription, translation, or proteasomal degradation, indicating a nongenomic mechanism. Removing E2 after 1 h fully reversed the loss of BCRP activity. Experiments using agonists and antagonists for estrogen receptor (ER)alpha and ER beta and brain capillaries from ER alpha and ER beta knockout mice demonstrated that E2 could signal through either receptor to reduce BCRP transport function. We speculate that this nongenomic E2-signaling pathway could potentially be used for targeting BCRP at the blood-brain barrier, in brain tumors, and in brain tumor stem cells to improve chemotherapy of the central nervous system. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1742-1755; doi:10.1038/jcbfm.2010.36; published online 10 March 2010
C1 [Bauer, Bjoern] Univ Minnesota, Dept Pharmaceut Sci, Coll Pharm, Duluth, MN 55812 USA.
[Hartz, Anika M. S.] Univ Minnesota, Sch Med, Dept Biochem & Mol Biol, Duluth, MN 55812 USA.
[Mahringer, Anne] Univ Heidelberg, Inst Pharm & Mol Biotechnol, Div Pharmaceut Technol, Heidelberg, Germany.
[Miller, David S.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Bauer, B (reprint author), Univ Minnesota, Dept Pharmaceut Sci, Coll Pharm, 1110 Kirby Dr,232 Life Sci, Duluth, MN 55812 USA.
EM bjbauer@d.umn.edu
FU NIH, National Institute of Environmental Health Sciences; Whiteside
Institute for Clinical Research; UMN CoP; UMN
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (DSM), a
research grant from the Whiteside Institute for Clinical Research (AMSH
and BB), and UMN CoP startup funds (BB).
NR 45
TC 37
Z9 40
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2010
VL 30
IS 10
BP 1742
EP 1755
DI 10.1038/jcbfm.2010.36
PG 14
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 657AK
UT WOS:000282382200008
PM 20216549
ER
PT J
AU Revilla-Lopez, G
Jimenez, AI
Cativiela, C
Nussinov, R
Aleman, C
Zanuy, D
AF Revilla-Lopez, Guillermo
Jimenez, Ana I.
Cativiela, Carlos
Nussinov, Ruth
Aleman, Carlos
Zanuy, David
TI Conformational Profile of a Proline-Arginine Hybrid
SO JOURNAL OF CHEMICAL INFORMATION AND MODELING
LA English
DT Article
ID MOLECULAR-DYNAMICS; SIDE-CHAIN; PEPTIDE CONFORMATION; MEDICINAL
CHEMISTRY; FORCE-FIELD; ENERGY; PROTEINS; PREFERENCES; STABILITY;
ANALOGS
AB The intrinsic conformational preferences of a new nonproteinogenic amino acid have been explored by computational methods. This tailored molecule, named ((beta)Pro)Arg, is conceived as a replacement for arginine in bioactive peptides when the stabilization of folded turn-like conformations is required. The new residue features a proline skeleton that bears the guanidilated side chain of arginine at the C(beta) position of the five-membered pyrrolidine ring, in either a cis or a trans orientation with respect to the carboxylic acid. The conformational profiles of the N-acetyl-N '-methylamide derivatives of the cis and trans isomers of ((beta)Pro)Arg have been examined in the gas phase and in solution by B3LYP/6-3 I+G(d,p) calculations and molecular dynamics simulations. The main conformational features of both isomers represent a balance between geometric restrictions imposed by the five-membered pyrrolidine ring and the ability of the guanidilated side chain to interact with the backbone through hydrogen bonds. Thus, both cis- and trans-((beta)Pro)Arg exhibit a preference for the alpha(l), conformation as a consequence of the interactions established between the guanidinium moiety and the main-chain amide groups.
C1 [Revilla-Lopez, Guillermo; Aleman, Carlos; Zanuy, David] Univ Politecn Cataluna, ETS Engn Ind Barcelona, Dept Engn Quim, E-08028 Barcelona, Spain.
[Jimenez, Ana I.; Cativiela, Carlos] Univ Zaragoza, CSIC, Inst Ciencia Mat Aragon, Dept Quim Organ, E-50009 Zaragoza, Spain.
[Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel.
[Aleman, Carlos] Univ Politecn Cataluna, Ctr Res Nanoengn, E-08028 Barcelona, Spain.
RP Aleman, C (reprint author), Univ Politecn Cataluna, ETS Engn Ind Barcelona, Dept Engn Quim, Diagonal 647, E-08028 Barcelona, Spain.
EM carlos.aleman@upc.edu; david.zanuy@upc.edu
RI Zanuy, David/G-3930-2014
OI Zanuy, David/0000-0001-7704-2178
FU Ministerio de Educacion y Ciencia [CTQ2007-62245]; Gobierno de Aragon;
ICREA; National Cancer Institute; National Institutes of Health
[HHSN261200-800001E]; Center for Cancer Research
FX Gratitude is expressed to the Centre de Supercomputacio de Catalunya
(CESCA). We also acknowledge the National Cancer Institute for partial
allocation of computing time and staff support at the Advanced
Biomedical Computing Center of the Frederick Cancer Research and
Development Center. Classical calculations were partially carried out
using the high-performance computational capabilities of the Biowulf
PC/Linux cluster at the National Institutes of Health, Bethesda, MD
(http://biowulf.nih.gov). Financial support from the Ministerio de
Educacion y Ciencia (Ramon y Cajal contract for D.Z., Project
CTQ2007-62245), Gobierno de Aragon (research group E40), and Generalitat
de Catalunya (research group 2009 SGR 925; XRQTC; ICREA Academia prize
for excellence in research to C.A.) is gratefully acknowledged. This
project has been funded in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
HHSN261200-800001E. The content of this publication does not necessarily
reflect the view of the 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 49
TC 2
Z9 2
U1 1
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9596
J9 J CHEM INF MODEL
JI J. Chem Inf. Model.
PD OCT
PY 2010
VL 50
IS 10
BP 1781
EP 1789
DI 10.1021/ci100135f
PG 9
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science,
Information Systems; Computer Science, Interdisciplinary Applications
SC Pharmacology & Pharmacy; Chemistry; Computer Science
GA 668PX
UT WOS:000283283100003
PM 20886854
ER
PT J
AU Dong, Q
Cheng, ZQ
Chang, WH
Blackman, BE
Conte, FA
Hu, JX
Shoback, D
Miller, WL
AF Dong, Qing
Cheng, Zhiqiang
Chang, Wenhan
Blackman, Brigitte E.
Conte, Felix A.
Hu, Jianxin
Shoback, Dolores
Miller, Walter L.
TI Naturally-Occurring Mutation in the Calcium-Sensing Receptor Reveals the
Significance of Extracellular Domain Loop III Region for Class C
G-Protein-Coupled Receptor Function
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID NEONATAL SEVERE HYPERPARATHYROIDISM; FAMILIAL HYPOCALCIURIC
HYPERCALCEMIA; METABOTROPIC GLUTAMATE-RECEPTOR; CELL-SURFACE EXPRESSION;
HUMAN CA2+ RECEPTOR; SIGNAL-TRANSDUCTION; CA2+-SENSING RECEPTOR;
SECONDARY HYPERPARATHYROIDISM; ENDOPLASMIC-RETICULUM; LINKED
GLYCOSYLATION
AB Context: Inactivating mutations of the calcium-sensing receptor (CaSR) cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Most mutations are clustered in the N-terminal and Cys-rich regions of the extracellular domain (ECD) and seven-transmembrane domain. Disease-causing mutations are uncommon in the C terminus of ECD.
Objective: The aim of the study was to characterize the CaSR mutations causing neonatal severe hyperparathyroidism in a consanguineous family.
Methods: Parathyroid glands from the index patient were stained for CaSR protein. The CaSR gene was sequenced, mutations were recreated in CaSR cDNA, and HEK293 cells were transfected with the CaSR mutant expression vector. Cellular CaSR targeting was detected by immunoblotting and immunocytochemistry; CaSR activity was assayed by inositol phosphate accumulation, MAPK activation, and single-cell microfluorimetry.
Results: Immunocytochemistry showed reduced intracellular CaSR in patient parathyroids. An in-frame homozygous deletion/insertion mutation, c. 1031 > 1034 (delACAAinsT), replaced His344-Asn345 with a single Leu in CaSR loop III. The mutant reduced cell surface expression of CaSR in transfected HEK293 cells. Inositol phosphate accumulation, MAPK activation, and single-cell microfluorimetry revealed blunted signaling responses of the mutant receptor to changes in extracellular Ca2+ concentration.
Conclusion: Deletion of His344-Asn345 in the ECD loop III region affects cell surface targeting of CaSR in transfected cells and in affected parathyroid glands. Absence of conserved Asn345 may interfere with CaSR folding or glycosylation, leading to poor protein targeting to the cell membrane. This loss-of-function mutant indicates that the ECD loop III is required for CaSR activity. (J Clin Endocrinol Metab 95: E245-E252, 2010)
C1 [Dong, Qing; Conte, Felix A.; Miller, Walter L.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94121 USA.
[Cheng, Zhiqiang; Chang, Wenhan; Shoback, Dolores] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA.
[Cheng, Zhiqiang; Chang, Wenhan; Shoback, Dolores] Univ Calif San Francisco, Dept Obstet & Gynecol, San Francisco, CA 94121 USA.
[Blackman, Brigitte E.] Univ Calif San Francisco, Dept Reprod Sci, San Francisco, CA 94121 USA.
[Cheng, Zhiqiang; Chang, Wenhan; Shoback, Dolores] Dept Vet Affairs Med Ctr, Endocrine Res Unit, San Francisco, CA 94121 USA.
[Hu, Jianxin] NIDDKD, Mol Signalling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Dong, Q (reprint author), Univ Calif San Francisco, Dept Pediat, S672D,513 Parnassus Ave, San Francisco, CA 94143 USA.
EM dongq@peds.ucsf.edu
RI Miller, Walter/J-3696-2012
FU National Institutes of Health (NIH) [K08 DK064626]; Veterans Affairs
Merit Review; NIH/National Institute on Aging [R01AG21353-6]; National
Institute of Arthritis and Musculoskeletal and Skin Diseases
[R01AR055588]; NIH [R01 DK37922]
FX This work was supported by National Institutes of Health (NIH) Grant K08
DK064626 (to Q.D.); a Veterans Affairs Merit Review (to D.S.);
NIH/National Institute on Aging Grant R01AG21353-6 and National
Institute of Arthritis and Musculoskeletal and Skin Diseases Grant
R01AR055588 (to W.C. and D.S.); and NIH Grant R01 DK37922 (to W.L.M.).
NR 40
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Z9 3
U1 0
U2 2
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD OCT
PY 2010
VL 95
IS 10
BP E245
EP E252
DI 10.1210/jc.2010-0559
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 659NK
UT WOS:000282573300054
PM 20631026
ER
PT J
AU Perl, S
Kushner, JA
Buchholz, BA
Meeker, AK
Stein, GM
Hsieh, M
Kirby, M
Pechhold, S
Liu, EH
Harlan, DM
Tisdale, JF
AF Perl, S.
Kushner, J. A.
Buchholz, B. A.
Meeker, A. K.
Stein, G. M.
Hsieh, M.
Kirby, M.
Pechhold, S.
Liu, E. H.
Harlan, D. M.
Tisdale, J. F.
TI Significant Human beta-Cell Turnover Is Limited to the First Three
Decades of Life as Determined by in Vivo Thymidine Analog Incorporation
and Radiocarbon Dating
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID INSULIN REQUIREMENT; TRIMESTER
AB Aims: Diabetes mellitus results from an absolute or relative deficiency of insulin-producing pancreatic beta-cells. The turnover rate of adult human beta-cells remains unknown. We employed two techniques to examine adult human islet beta-cell turnover and longevity in vivo.
Methods: Subjects enrolled in National Institutes of Health clinical trials received thymidine analogs [iododeoxyuridine (IdU) or bromodeoxyuridine (BrdU)] 8 d to 4 yr prior to death. Archival autopsy samples from 10 patients (aged 17-74 yr) were employed to assess beta-cell turnover by scoring nuclear analog labeling within insulin-staining cells. Human adult beta-cell longevity was determined by estimating the cells' genomic DNA integration of atmospheric (14)C. DNA was purified from pancreatic islets isolated from cadaveric donors; whole islet prep DNA was obtained from a 15-yr-old donor, and purified beta-cell DNA was obtained from two donors (ages 48 and 80 yr). 14C levels were then determined using accelerator mass spectrometry. Cellular "birth date" was determined by comparing the subject's DNA (14)C content relative to a well-established (14)C atmospheric prevalence curve.
Results: In the two subjects less than 20 yr of age, 1-2% of the beta-cell nuclei costained for BrdU/IdU. No beta-cell nuclei costained in the eight patients more than 30 yr old. Consistent with the BrdU/IdU turnover data, beta-cell DNA (14)C content indicated that the "birth date" of cells occurred within the subject's first 30 yr of life.
Conclusions: Under typical circumstances, human beta-cells and their cellular precursors are established by young adulthood. (J Clin Endocrinol Metab 95: E234-E239, 2010)
C1 [Perl, S.; Pechhold, S.; Liu, E. H.; Harlan, D. M.] Natl Inst Diabet Digest & Kidney Dis NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA.
[Kushner, J. A.; Stein, G. M.] Univ Penn, Div Endocrinol & Diabet, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Buchholz, B. A.] Lawrence Livermore Natl Lab, Ctr Accelerator Mass Spectrometry, Livermore, CA 94550 USA.
[Meeker, A. K.] Johns Hopkins Med Inst, Dept Pathol, Div Genitourinary Pathol, Baltimore, MD 21287 USA.
[Kirby, M.] Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA.
[Perl, S.; Hsieh, M.; Kirby, M.; Tisdale, J. F.] NIDDK, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA.
[Perl, S.; Hsieh, M.; Kirby, M.; Tisdale, J. F.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Perl, S (reprint author), 10 Ctr Dr,Room 9N119, Bethesda, MD 20892 USA.
EM perls@nhlbi.nih.gov
RI Buchholz, Bruce/G-1356-2011
FU National Institute of Diabetes, Digestive, and Kidney Diseases at the
National Institutes of Health (NIH); NIH/National Center for Research
Resources [RR13461]; U.S. Department of Energy by Lawrence Livermore
National Laboratory [DE-AC52-07NA27344]
FX This work was supported in part by the intramural research program of
the National Institute of Diabetes, Digestive, and Kidney Diseases at
the National Institutes of Health (NIH) and NIH/National Center for
Research Resources (RR13461). This work was performed in part under the
auspices of the U.S. Department of Energy by Lawrence Livermore National
Laboratory under contract DE-AC52-07NA27344.
NR 14
TC 101
Z9 101
U1 0
U2 8
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD OCT
PY 2010
VL 95
IS 10
BP E234
EP E239
DI 10.1210/jc.2010-0932
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 659NK
UT WOS:000282573300052
PM 20660050
ER
PT J
AU Wan, ZH
Zhi, N
Wong, SS
Keyvanfar, K
Liu, DL
Raghavachari, N
Munson, PJ
Su, S
Malide, D
Kajigaya, S
Young, NS
AF Wan, Zhihong
Zhi, Ning
Wong, Susan
Keyvanfar, Keyvan
Liu, Delong
Raghavachari, Nalini
Munson, Peter J.
Su, Su
Malide, Daniela
Kajigaya, Sachiko
Young, Neal S.
TI Human parvovirus B19 causes cell cycle arrest of human erythroid
progenitors via deregulation of the E2F family of transcription factors
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID DNA-DAMAGE RESPONSE; NONSTRUCTURAL PROTEIN; GENE-EXPRESSION; INFECTIOUS
CLONE; P6 PROMOTER; NS1 PROTEIN; VIRUS; REPLICATION; APOPTOSIS;
PHOSPHORYLATION
AB Human parvovirus B19 (B19V) is the only human pathogenic parvovirus. It causes a wide spectrum of human diseases, including fifth disease (erythema infectiosum) in children and pure red cell aplasia in immunocompromised patients. B19V is highly erythrotropic and preferentially replicates in erythroid progenitor cells (EPCs). Current understanding of how B19V interacts with cellular factors to regulate disease progression is limited, due to a lack of permissive cell lines and animal models. Here, we employed a recently developed primary human CD36(+) EPC culture system that is highly permissive for B19V infection to identify cellular factors that lead to cell cycle arrest after B19V infection. We found that B19V exploited the E2F family of transcription factors by downregulating activating E2Fs (E2F1 to E2F3a) and upregulating repressive E2Fs (E2F4 to E2F8) in the primary CD36+ EPCs. B19V nonstructural protein 1 (NS1) was a key viral factor responsible for altering E2F1-E2F5 expression, but not E2F6-E2F8 expression. Interaction between NS1 and E2F4 or E2F5 enhanced the nuclear import of these repressive E2Fs and induced stable G(2) arrest. NS1-induced G(2) arrest was independent of p53 activation and increased viral replication. Downstream E2F4/E2F5 targets, which are potentially involved in the progression from G2 into M phase and erythroid differentiation, were identified by microarray analysis. These findings provide new insight into the molecular pathogenesis of B19V in highly permissive erythroid progenitors.
C1 [Wan, Zhihong; Zhi, Ning; Wong, Susan; Keyvanfar, Keyvan; Su, Su; Kajigaya, Sachiko; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Delong; Munson, Peter J.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Raghavachari, Nalini] NHLBI, Gene Express Core Facil, NIH, Bethesda, MD 20892 USA.
[Malide, Daniela] NHLBI, Light Microscopy Core Facil, NIH, Bethesda, MD 20892 USA.
RP Zhi, N (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10CRC,Rm 3E-5272,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM zhin@nhlbi.nih.gov
FU NIH
FX This work was supported by the NIH Intramural Research Program. We thank
Dong Joo Kim for help in preparing the manuscript.
NR 61
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U2 4
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 OCT
PY 2010
VL 120
IS 10
BP 3530
EP 3544
DI 10.1172/JCI41805
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 657DN
UT WOS:000282393200016
PM 20890043
ER
PT J
AU Elrod, JW
Wong, R
Mishra, S
Vagnozzi, RJ
Sakthievel, B
Goonasekera, SA
Karch, J
Gabel, S
Farber, J
Force, T
Brown, JH
Murphy, E
Molkentin, JD
AF Elrod, John W.
Wong, Renee
Mishra, Shikha
Vagnozzi, Ronald J.
Sakthievel, Bhuvana
Goonasekera, Sanjeewa A.
Karch, Jason
Gabel, Scott
Farber, John
Force, Thomas
Brown, Joan Heller
Murphy, Elizabeth
Molkentin, Jeffery D.
TI Cyclophilin D controls mitochondrial pore-dependent Ca2+ exchange,
metabolic flexibility, and propensity for heart failure in mice
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID PERMEABILITY TRANSITION PORE; ACTIVATED RECEPTOR-ALPHA; FATTY-ACID
OXIDATION; CELL-DEATH; RAT-HEART; CARDIAC DYSFUNCTION; RUTHENIUM RED;
CYCLOSPORINE; MEMBRANE; CHANNEL
AB Cyclophilin D (which is encoded by the Ppif gene) is a mitochondrial matrix peptidyl-prolyl isomerase known to modulate opening of the mitochondrial permeability transition pore (MPTP). Apart from regulating necrotic cell death, the physiologic function of the MPTP is largely unknown. Here we have shown that Ppif(-/-) mice exhibit substantially greater cardiac hypertrophy, fibrosis, and reduction in myocardial function in response to pressure overload stimulation than control mice. In addition, Ppif(-/-) mice showed greater hypertrophy and lung edema as well as reduced survival in response to sustained exercise stimulation. Cardiomyocyte-specific transgene expression of cyclophilin D in Ppif(-/-) mice rescued the enhanced hypertrophy, reduction in cardiac function, and rapid onset of heart failure following pressure overload stimulation. Mechanistically, the mal-adaptive phenotype phenotype in the hearts of Ppif(-/-) mice was associated with an alteration in MPTP-mediated Ca2+ efflux resulting in elevated levels of mitochondrial matrix Ca2+ and enhanced activation of Ca2+-dependent dehydrogenases. Elevated matrix Ca2+ led to increased glucose oxidation relative to fatty acids, thereby limiting the metabolic flexibility of the heart that is critically involved in compensation during stress. These findings suggest that the MPTP maintains homeostatic mitochondrial Ca2+ levels to match metabolism with alterations in myocardial workload, thereby suggesting a physiologic function for the MPTP.
C1 [Elrod, John W.; Goonasekera, Sanjeewa A.; Karch, Jason; Molkentin, Jeffery D.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Howard Hughes Med Inst, Dept Pediat, Cincinnati, OH 45229 USA.
[Wong, Renee; Gabel, Scott; Murphy, Elizabeth] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Mishra, Shikha; Brown, Joan Heller] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
[Vagnozzi, Ronald J.; Force, Thomas] Thomas Jefferson Univ, Ctr Translat Med, Philadelphia, PA 19107 USA.
[Vagnozzi, Ronald J.; Force, Thomas] Thomas Jefferson Univ, Div Cardiol, Philadelphia, PA 19107 USA.
[Sakthievel, Bhuvana; Farber, John] Thomas Jefferson Univ, Dept Pathol, Philadelphia, PA 19107 USA.
RP Molkentin, JD (reprint author), Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Howard Hughes Med Inst, Dept Pediat, 240 Albert Sabin Way,MLC 7020, Cincinnati, OH 45229 USA.
EM jeff.molkentin@cchmc.org
OI Force, Thomas/0000-0002-0450-8659; Elrod, John/0000-0003-3925-2224
FU NIH [5F32HL092737, HL62927, HL81104, HL80101]; Fondation Leducq; Howard
Hughes Medical Institute
FX The authors greatly appreciate the technical expertise of Allen York and
Michelle Sargent. This work was supported by grants from the NIH to J.W.
Elrod (5F32HL092737), J.D. Molkentin (HL62927, HL81104), and to J.H.
Brown (HL80101), as well as by an international grant in heart failure
research from the Fondation Leducq and the Howard Hughes Medical
Institute.
NR 46
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U1 2
U2 9
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 OCT
PY 2010
VL 120
IS 10
BP 3680
EP 3687
DI 10.1172/JCI43171
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 657DN
UT WOS:000282393200030
PM 20890047
ER
PT J
AU Russell, M
Silverman, A
Fleg, JL
Lee, ET
Mete, M
Weir, M
Wilson, C
Yeh, F
Howard, BV
Howard, WJ
AF Russell, Marie
Silverman, Angela
Fleg, Jerome L.
Lee, Elisa T.
Mete, Mihriye
Weir, Matthew
Wilson, Charlton
Yeh, Fawn
Howard, Barbara V.
Howard, Wm James
TI Achieving lipid targets in adults with type 2 diabetes: The Stop
Atherosclerosis in Native Diabetics Study
SO JOURNAL OF CLINICAL LIPIDOLOGY
LA English
DT Article
DE American Indians; Blood pressure; Cardiovascular disease; Carotid artery
intima media thickness; Lipids
ID CORONARY-HEART-DISEASE; BLOOD-PRESSURE; CONTROLLED-TRIAL; RISK-FACTORS;
MELLITUS; CHOLESTEROL; PREVENTION; SANDS; ATORVASTATIN; GUIDELINES
AB BACKGROUND: Although lipid management in diabetes is standard practice, goals often are neither met nor maintained. Strategies for achieving lower targets have not been explored. The Stop Atherosclerosis in Native Diabetics Study randomized patients with diabetes to standard versus aggressive lipid and blood pressure goals for 36 months.
OBJECTIVE: To report strategies used to achieve and maintain lipid goals and to report adverse events (AEs).
METHODS: Adults with type 2 diabetes and no history of cardiovascular disease (N = 499) were randomized to standard (low-density lipoprotein cholesterol [LDL-C] <= 100 mg/dL, non-high-density lipoprotein cholesterol [non-HDL-C] <= 130 mg/dL) or aggressive (LDL-C <= 70 mg/dL, non-HDL-C <= 100 mg/dL) targets. An algorithm was started with statin monotherapy, with intestinally acting agents added as required to reach LDL-C targets. Triglyceride [TG]-lowering agents were next used to reach non-HDL-C goals. Lipid management was performed by mid-level practitioners, with physician consultation, by the use of point-of-care lipid determinations.
RESULTS: On average, both groups achieved the LDL-C and non-HDL-C goals within 12 months and maintained them throughout the study. At 36 months, mean (SD) LDL-C and non-HDL-C were 72 (24) and 102 (29) mg/dL in the aggressive group (AGG) and 104 (20) and 138 (26) mg/dL, respectively, in the standard group (STD); systolic blood pressure targets were 115 and 130 mmHg, respectively. A total of 68% of participants reached target LDL-C for greater than 50% of the visits and 46% for greater than 75% of visits. At 36 months, the AGG averaged 1.5 lipid lowering medications and the STD 1.2. Statins were used in 91% and 68% of the AGG and STD; ezetimibe by 31% and 10%; fibrates by 8% and 18%. No serious AEs were observed; AEs occurred in 18% of the AGG and 14% of the STD.
CONCLUSION: Standard and aggressive lipid targets can be safely maintained in diabetic patients. Standardized algorithms, point-of-care lipid testing, and nonphysician providers facilitate care delivery. (C) 2010 National Lipid Association. All rights reserved.
C1 [Howard, Wm James] Washington Hosp Ctr, Washington, DC 20010 USA.
[Russell, Marie; Wilson, Charlton] Phoenix Indian Med Ctr, Phoenix, AZ USA.
[Silverman, Angela; Mete, Mihriye; Howard, Barbara V.] MedStar Hlth Res Inst, Hyattsville, MD USA.
[Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
[Lee, Elisa T.; Yeh, Fawn] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Weir, Matthew] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
RP Howard, WJ (reprint author), Washington Hosp Ctr, Rm 6A-126,110 Irving St NW, Washington, DC 20010 USA.
EM wm.james.howard@medstar.net
FU National Heart, Lung, and Blood Institute [U01-HL067031]; Merck/Schering
Plough; Pfizer; Astra Zeneca; Merck; Schering Plough
FX This work was supported by grant U01-HL067031 from the National Heart,
Lung, and Blood Institute. Dr. B.V. Howard has served on the advisory
boards of Merck/ Schering Plough and has received research support from
Merck/Schering Plough. Dr. Wm. J. Howard has received research support
as part of multicenter trials from Pfizer, Astra Zeneca, Merck, and
Schering Plough; has served as a consultant for Merck, Schering Plough,
and Pfizer; and has served on the speaker's bureau for Merck, Schering
Plough, Pfizer, Astra Zeneca, Abbott, and Daiichi Sankyo.
NR 18
TC 5
Z9 6
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1933-2874
J9 J CLIN LIPIDOL
JI J. Clin. Lipidol.
PD OCT
PY 2010
VL 4
IS 5
BP 435
EP 443
DI 10.1016/j.jacl.2010.07.007
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 672ES
UT WOS:000283566400021
PM 21076630
ER
PT J
AU Stevenson, LG
Drake, SK
Shea, YR
Zelazny, AM
Murray, PR
AF Stevenson, Lindsay G.
Drake, Steven K.
Shea, Yvonne R.
Zelazny, Adrian M.
Murray, Patrick R.
TI Evaluation of Matrix-Assisted Laser Desorption Ionization-Time of Flight
Mass Spectrometry for Identification of Clinically Important Yeast
Species
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID TRANSCRIBED SPACER REGIONS; RIBOSOMAL-RNA GENE; INVASIVE CANDIDIASIS;
SEQUENCE-ANALYSIS; BACTERIA; MANAGEMENT; MYCOBACTERIA; INFECTIONS;
CANDIDEMIA; SYSTEMS
AB We evaluated the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for the rapid identification of yeast species. Using Bruker Daltonics MALDI BioTyper software, we created a spectral database library with m/z ratios of 2,000 to 20,000 Da for 109 type and reference strains of yeast (44 species in 8 genera). The database was tested for accuracy by use of 194 clinical isolates (23 species in 6 genera). A total of 192 (99.0%) of the clinical isolates were identified accurately by MALDI-TOF MS. The MALDI-TOF MS-based method was found to be reproducible and accurate, with low consumable costs and minimal preparation time.
C1 [Stevenson, Lindsay G.; Drake, Steven K.; Shea, Yvonne R.; Zelazny, Adrian M.; Murray, Patrick R.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Murray, PR (reprint author), NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA.
EM Pmurray@cc.nih.gov
FU NIH Clinical Center; Department of Laboratory Medicine
FX This research was supported by the Intramural Research Program of the
NIH Clinical Center, Department of Laboratory Medicine.
NR 29
TC 125
Z9 135
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 OCT
PY 2010
VL 48
IS 10
BP 3482
EP 3486
DI 10.1128/JCM.00687-09
PG 5
WC Microbiology
SC Microbiology
GA 659CN
UT WOS:000282544700004
PM 20668126
ER
PT J
AU Keating, NL
Landrum, MB
Arora, NK
Malin, JL
Ganz, PA
van Ryn, M
Weeks, JC
AF Keating, Nancy L.
Landrum, Mary Beth
Arora, Neeraj K.
Malin, Jennifer L.
Ganz, Patricia A.
van Ryn, Michelle
Weeks, Jane C.
TI Cancer Patients' Roles in Treatment Decisions: Do Characteristics of the
Decision Influence Roles?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID BREAST-CANCER; HEALTH OUTCOMES; OLDER WOMEN; PARTICIPATION; CARE;
QUALITY; COMMUNICATION; PREFERENCES; INFORMATION; LIFE
AB Purpose
Patients with more active roles in decisions are more satisfied and may have better health outcomes. Younger and better educated patients have more active roles in decisions, but whether patients' roles in decisions differ by characteristics of the decision itself is unknown.
Patients and Methods
We surveyed a large, population-based cohort of patients with recently diagnosed lung or colorectal cancer about their roles in decisions regarding surgery, radiation therapy, and/or chemotherapy. We used multinomial logistic regression to assess whether characteristics of the decision, including evidence about the treatment's benefit, whether the decision was likely preference-sensitive (palliative therapy for metastatic cancer), and treatment modality, influenced patients' roles in that decision.
Results
Of 10,939 decisions made by 5,383 patients, 38.9% were patient controlled, 43.6% were shared, and 17.5% were physician controlled. When there was good evidence to support a treatment, shared control was greatest; when evidence was uncertain, patient control was greatest; and when there was no evidence for or evidence against a treatment, physician control was greatest (overall P < .001). Decisions about treatments for metastatic cancers tended to be more physician controlled than other decisions (P < .001).
Conclusion
Patients making decisions about treatments for which no evidence supports benefit and decisions about noncurative treatments reported more physician control, which suggests that patients may not want the responsibility of deciding on treatments that will not cure them. Better strategies for shared decision making may be needed when there is no evidence to support benefit of a treatment or when patients have terminal illnesses that cannot be cured.
C1 [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NCI, Bethesda, MD 20892 USA.
Univ Calif Los Angeles, W Los Angeles Vet Affairs Hlth Care Ctr, Los Angeles, CA USA.
Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
EM keating@hcp.med.harvard.edu
FU National Cancer Institute (NCI) [U01 CA093344, U01 CA 093332, U01
CA093324, U01 CA093348, U01 CA093329, U01 CA01013, U01 CA093339];
Department of Veterans Affairs [CRS 02-164]
FX Supported by Grants No. U01 CA093344 from the National Cancer Institute
(NCI) to the Statistical Coordinating Center; U01 CA 093332 from the
NCI-supported Primary Data Collection and Research Centers to DanaFarber
Cancer Institute/Cancer Research Network; U01 CA093324 to Harvard
Medical School/Northern California Cancer Center; U01 CA093348 to
RAND/University of California, Los Angeles; U01 CA093329 to the
University of Alabama at Birmingham; U01 CA01013 to the University of
Iowa; U01 CA093339 to the University of North Carolina; and by Grant No.
CRS 02-164 from the Department of Veterans Affairs to the Durham
Veterans Affairs Medical Center CRS 02-164.
NR 29
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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 OCT 1
PY 2010
VL 28
IS 28
BP 4364
EP 4370
DI 10.1200/JCO.2009.26.8870
PG 7
WC Oncology
SC Oncology
GA 655TP
UT WOS:000282272700037
PM 20713872
ER
PT J
AU Johnson, FM
Bekele, BN
Feng, L
Wistuba, I
Tang, XM
Tran, HT
Erasmus, JJ
Hwang, LL
Takebe, N
Blumenschein, GR
Lippman, SM
Stewart, DJ
AF Johnson, Faye M.
Bekele, B. Nebiyou
Feng, Lei
Wistuba, Ignacio
Tang, Xi Ming
Tran, Hai T.
Erasmus, Jeremy J.
Hwang, Li-Ling
Takebe, Naoko
Blumenschein, George R.
Lippman, Scott M.
Stewart, David J.
TI Phase II Study of Dasatinib in Patients With Advanced Non-Small-Cell
Lung Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID SRC-FAMILY KINASES; INHIBITOR DASATINIB; SOLID TUMORS; RECEPTOR;
EXPRESSION; ACTIVATION; ADENOCARCINOMA; CARCINOMA; INVASION; SURVIVAL
AB Purpose
Src family kinases (SFKs) promote cancer progression and are commonly expressed in non-small-cell lung cancer (NSCLC), but the clinical effects of SFK inhibition in NSCLC are unknown. We conducted a phase II trial of the SFK inhibitor dasatinib for advanced NSCLC. We tested the hypotheses that the activation of epidermal growth factor receptor (EGFR) or SFK or modulation of serum cytokines may predict a response to dasatinib.
Patients and Methods
Patients received dasatinib as first-line therapy. Response was measured by tumor size on computed tomography scans and by metabolic activity on positron emission tomography scans. Tissue samples taken before patients received dasatinib were tested for EGFR and Kras mutation and phosphorylated SFK expression.
Results
Thirty-four patients were enrolled. The overall disease control rate (partial responses plus stable disease) for dasatinib was 43%. One patient had a partial response to therapy. Eleven patients (32%) had a metabolic response to dasatinib. SFK activation and EGFR and Kras mutations in tumor tissue did not predict response to dasatinib. Significant toxicities included fatigue and dyspnea. The presence of a pleural effusion before dasatanib therapy predicted the development of a clinically significant effusion during therapy.
Conclusion
Dasatinib as a single agent had modest clinical activity that was lower than that generally observed in patients with NSCLC who receive chemotherapy. Pleural effusion was an expected and problematic toxicity that was successfully treated with steroids, diuretics, and dose interruptions. Marked activity in one patient and prolonged stable disease in four others suggested a potential subpopulation of patients with dasatinib-sensitive NSCLC.
C1 Univ Texas, Grad Sch Biomed Sci Houston, Houston, TX USA.
NCI, Bethesda, MD 20892 USA.
[Johnson, Faye M.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Unit 432, Houston, TX 77030 USA.
RP Johnson, FM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Unit 432, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM fmjohns@mdanderson.org
FU National Cancer Institute [N01 CM-62202]
FX Supported by Grant No. N01 CM-62202 from the National Cancer Institute's
Cancer Therapy Evaluation Program. Support for correlative laboratory
work was provided by The University of Texas Lung Specialized Program of
Research Excellence, Bristol-Myers Squibb, and the Commonwealth
Foundation for Cancer Research. Dasatinib was provided by Bristol-Myers
Squibb and the National Cancer Institute.
NR 40
TC 80
Z9 86
U1 0
U2 6
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 OCT
PY 2010
VL 28
IS 30
BP 4609
EP 4615
DI 10.1200/JCO.2010.30.5474
PG 7
WC Oncology
SC Oncology
GA 665SS
UT WOS:000283056400029
PM 20855820
ER
PT J
AU Kelly, RJ
Carter, C
Giaccone, G
AF Kelly, Ronan J.
Carter, Corey
Giaccone, Giuseppe
TI Personalizing Therapy in an Epidermal Growth Factor Receptor-Tyrosine
Kinase Inhibitor-Resistant Non-Small-Cell Lung Cancer Using PF-00299804
and Trastuzumab
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID PHASE-II TRIAL; DIMERIZATION INHIBITOR; OVEREXPRESSION; EXPRESSION;
GEFITINIB; CARCINOMA; GEMCITABINE; PERTUZUMAB; MUTATIONS; CISPLATIN
C1 [Kelly, Ronan J.; Giaccone, Giuseppe] NCI, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Carter, Corey] USN, Natl Med Ctr, Bethesda, MD 20084 USA.
RP Kelly, RJ (reprint author), NCI, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
NR 25
TC 31
Z9 32
U1 1
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 1
PY 2010
VL 28
IS 28
BP E507
EP E510
DI 10.1200/JCO.2010.29.3126
PG 4
WC Oncology
SC Oncology
GA 655TP
UT WOS:000282272700004
PM 20679607
ER
PT J
AU Zabor, EC
Klebanoff, M
Yu, K
Zhang, J
Nansel, T
Andrews, W
Schwebke, J
Jeffcoat, M
AF Zabor, Emily Craig
Klebanoff, Mark
Yu, Kai
Zhang, Jun
Nansel, Tonja
Andrews, William
Schwebke, Jane
Jeffcoat, Marjorie
TI Association between periodontal disease, bacterial vaginosis, and sexual
risk behaviours
SO JOURNAL OF CLINICAL PERIODONTOLOGY
LA English
DT Article
DE bacterial; bacterial infections; epidemiology; periodontal diseases;
sexual behaviour; vaginosis
ID LOW-BIRTH-WEIGHT; PRETERM BIRTH; ORAL SEX; PREGNANCY; DELIVERY;
INFECTION; RESPONSES; OUTCOMES; THERAPY
AB P>Background
Both periodontal disease and bacterial vaginosis may cause adverse pregnancy outcomes. This study evaluated the association between periodontal disease and bacterial vaginosis.
Materials and Methods
Data from 3569 women enrolled in the Longitudinal Study of Vaginal Flora were used. Periodontal disease, defined as greater than three sites with >= 4 mm attachment loss, was assessed by specially calibrated hygienists at baseline. Positive bacterial vaginosis status was based on a Nugent Gram stain score >= 7. Pairs of independent variables were compared with Pearson's chi 2 and risk ratios were calculated through log-binomial regression.
Results
Twenty-eight per cent of women with bacterial vaginosis had periodontal disease compared with 22% without , corresponding to 1.29 (95% CI: 1.13, 1.47) times greater risk of periodontal disease among women with bacterial vaginosis. In adjusted analysis the risk ratio dropped to 1.23 (95% CI: 1.08, 1.40). Receptive oral sex with an uncircumcised partner was associated with 1.28 times (95% CI: 0.97, 1.69) the risk for periodontal disease compared with receptive oral sex with a circumcised partner, though the association is not statistically significant.
Conclusions
In this population, there is a small but significant association between periodontal disease and bacterial vaginosis and a possible trend between receptive oral sex with an uncircumcised partner and periodontal disease.
C1 [Zabor, Emily Craig] Univ Minnesota, Div Biostat, Minneapolis, MN 55455 USA.
[Klebanoff, Mark; Yu, Kai; Zhang, Jun; Nansel, Tonja] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Andrews, William; Schwebke, Jane] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
[Jeffcoat, Marjorie] Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA.
RP Zabor, EC (reprint author), Univ Minnesota, Div Biostat, Mayo Bldg, Minneapolis, MN 55455 USA.
EM zabor008@umn.edu
OI Nansel, Tonja/0000-0002-8298-7595
FU NIH, NICHD [N01-HD-8-3293, Z01-HD002535-10]
FX The Longitudinal Study of Vaginal Flora was supported by intramural
funds (Z01-HD002535-10), and by contract (N01-HD-8-3293) from the NIH,
NICHD.
NR 30
TC 5
Z9 7
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0303-6979
J9 J CLIN PERIODONTOL
JI J. Clin. Periodontol.
PD OCT
PY 2010
VL 37
IS 10
BP 888
EP 893
DI 10.1111/j.1600-051X.2010.01593.x
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 647RM
UT WOS:000281636300003
PM 20636412
ER
PT J
AU Prosser, LA
Lee, SCK
Barbe, MF
VanSant, AF
Lauer, RT
AF Prosser, Laura A.
Lee, Samuel C. K.
Barbe, Mary F.
VanSant, Ann F.
Lauer, Richard T.
TI Trunk and hip muscle activity in early walkers with and without cerebral
palsy - A frequency analysis
SO JOURNAL OF ELECTROMYOGRAPHY AND KINESIOLOGY
LA English
DT Article
DE Cerebral palsy; Muscle; Trunk; Frequency; Gait
ID BALANCE CONTROL; SURFACE EMG; CHILDREN; GAIT; WALKING; ACTIVATION;
PATTERNS; ADOLESCENTS; RELIABILITY; STRATEGIES
AB Poor control of postural muscles is a primary impairment in cerebral palsy (CP), yet core trunk and hip muscle activity has not been thoroughly investigated. Frequency analysis of electromyographic (EMG) signals provides insight about the intensity and pattern of muscle activation, correlates with functional measures in CP, and is sensitive to change after intervention. The objective of this study was to investigate differences in trunk and hip muscle activation frequency in children with CP compared to children with similar amounts of walking experience and typical development (TD). EMG data from 31 children (15 with CP, 16 with TD) were recorded from 16 trunk and hip muscles bilaterally. A time-frequency pattern was generated using the continuous wavelet transform and instantaneous mean frequency (IMNF) was calculated at each interval of the gait cycle. Functional principal component analysis (PCA) revealed that IMNF was significantly higher in the CP group throughout the gait cycle for all muscles. Additionally, stride-to-stride variability was higher in the CP group. This evidence demonstrated altered patterns of trunk and hip muscle activation in CP, including increased rates of motor unit firing, increased number of recruited motor units, and/or decreased synchrony of motor units. These altered muscle activation patterns likely contribute to muscle fatigue and decreased biomechanical efficiency in children with CP. Published by Elsevier Ltd.
C1 [Prosser, Laura A.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
[Lee, Samuel C. K.] Shriners Hosp Children, Res Dept, Philadelphia, PA USA.
[Lee, Samuel C. K.] Univ Delaware, Phys Therapy Dept, Newark, DE USA.
[Barbe, Mary F.; VanSant, Ann F.; Lauer, Richard T.] Temple Univ, Dept Phys Therapy, Philadelphia, PA 19122 USA.
[Barbe, Mary F.] Temple Univ, Dept Anat, Philadelphia, PA 19122 USA.
[Barbe, Mary F.] Temple Univ, Dept Anat & Cell Biol, Philadelphia, PA 19122 USA.
[Lauer, Richard T.] Temple Univ, Dept Elect & Comp Engn, Philadelphia, PA 19122 USA.
RP Prosser, LA (reprint author), NIH, Dept Rehabil Med, Bldg 10 CRC,1-1469,10 Ctr Dr, Bethesda, MD 20892 USA.
EM laura.prosser@nih.gov
RI Prosser, Laura/C-1242-2009; Van Mulders, Benjamin/P-1241-2014
FU Section on Pediatrics; American Physical Therapy Association; NINDS
[R03NS048875]; NICHD [R01HD043859]; NIH Clinical Center
FX The authors thank Steve Capella and Jenny Lee for assistance with data
collection, and Diana Deshefy, DPT, Samuel Pierce, PT, PhD and Erin
Sheeder, DPT for assistance with participant recruitment. This work was
funded by a Clinical Research Grant to Dr. Prosser from the Section on
Pediatrics, American Physical Therapy Association, NINDS R03NS048875 to
Dr. Lauer, and NICHD R01HD043859 to Dr. Lee. This research was also
supported in part by the Intramural Research Program of the NIH Clinical
Center. Portions of this work were presented at the 2009 Annual Meeting
of the American Society of Biomechanics.
NR 46
TC 12
Z9 14
U1 2
U2 20
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1050-6411
J9 J ELECTROMYOGR KINES
JI J. Electromyogr. Kinesiol.
PD OCT
PY 2010
VL 20
IS 5
BP 851
EP 859
DI 10.1016/j.jelekin.2010.04.005
PG 9
WC Neurosciences; Physiology; Rehabilitation; Sport Sciences
SC Neurosciences & Neurology; Physiology; Rehabilitation; Sport Sciences
GA 634JD
UT WOS:000280576100010
PM 20472460
ER
PT J
AU Lu, SY
Pike, VW
AF Lu, Shuiyu
Pike, Victor W.
TI Synthesis of [F-18]xenon difluoride as a radiolabeling reagent from
[F-18]fluoride ion in a micro-reactor and at production scale
SO JOURNAL OF FLUORINE CHEMISTRY
LA English
DT Article
DE [F-18]Xenon difluoride; [F-18]Fluoride ion; Labeling agent;
Micro-reactor; Radiotracers
ID POSITRON-EMISSION-TOMOGRAPHY; F-18 XENON DIFLUORIDE; DIVALENT XENON;
FLUORINE-GAS; NO-CARRIER; PET; RADIOFLUORINATION; XEF2; ACETONITRILE;
CHLOROFORM
AB [F-18]Xenon difluoride ([F-18]XeF2), was produced by treating xenon difluoride with cyclotron-produced [F-18]fluoride ion to provide a potentially useful agent for labeling novel radiotracers with fluorine-18 (t(1/2) = 109.7 min) for imaging applications with positron emission tomography. Firstly, the effects of various reaction parameters, for example, vessel material, solvent, cation and base on this process were studied at room temperature. Glass vials facilitated the reaction more readily than polypropylene vials. The reaction was less efficient in acetonitrile than in dichloromethane. Cs+ or K+ with or without the cryptand. K 2.2.2, was acceptable as counter cation. The production of [F-18]XeF2 was retarded by K2CO3, suggesting that generation of hydrogen fluoride in the reaction milieu promoted the incorporation of fluorine-18 into xenon difluoride. Secondly, the effect of temperature was studied using a microfluidic platform in which [F-18]XeF2 was produced in acetonitrile at elevated temperature (>= 85 degrees C) over 94 s. These results enabled us to develop a method for obtaining [F-18]XeF2 on a production scale (up to 25 mCi) through reaction of [F-18]fluoride ion with xenon difluoride in acetonitrile at 90 degrees C for 10 min. [F-18]XeF2 was separated from the reaction mixture by distillation at 110 degrees C. Furthermore, [F-18]XeF2 was shown to be reactive towards substrates, such as 1-((trimethylsilyl)oxy)cyclohexene and fluorene. Published by Elsevier B.V.
C1 [Lu, Shuiyu; Pike, Victor W.] NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Lu, SY (reprint author), NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, NIH, 10 Ctr Dr,Room B3 C346, Bethesda, MD 20892 USA.
EM Shuiyu.Lu@mail.nih.gov
OI Lu, Shuiyu/0000-0003-0310-4318
FU National Institutes of Health (National Institute of Mental Health)
[Z01-MH-002793]
FX This research was supported by the Intramural Research Program (project
# Z01-MH-002793) of the National Institutes of Health (National
Institute of Mental Health). We are grateful to the NIH Clinical PET
Department for the production of fluorine-18. We also thank Professor C.
A. Ramsden (Keele University, UK) and Dr. F. I. Aigbirhio (Cambridge
University, UK) for their comments on the draft manuscript.
NR 57
TC 20
Z9 20
U1 2
U2 15
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 0022-1139
J9 J FLUORINE CHEM
JI J. Fluor. Chem.
PD OCT
PY 2010
VL 131
IS 10
BP 1032
EP 1038
DI 10.1016/j.jfluchem.2010.07.009
PG 7
WC Chemistry, Inorganic & Nuclear; Chemistry, Organic
SC Chemistry
GA 671CK
UT WOS:000283477300010
PM 20871806
ER
PT J
AU Okawa, H
Pahlberg, J
Rieke, F
Birnbaumer, L
Sampath, AP
AF Okawa, Haruhisa
Pahlberg, Johan
Rieke, Fred
Birnbaumer, Lutz
Sampath, Alapakkam P.
TI Coordinated control of sensitivity by two splice variants of G alpha(o)
in retinal ON bipolar cells
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Article
ID AII AMACRINE CELLS; METABOTROPIC GLUTAMATE-RECEPTOR; MAMMALIAN RETINA;
MOUSE RETINA; G-PROTEIN; LIGHT RESPONSE; ALPHA-SUBUNIT; DEPOLARIZING
BIPOLAR; GAMMA-SUBUNITS; DENDRITIC TIPS
AB The high sensitivity of scotopic vision depends on the efficient retinal processing of single photon responses generated by individual rod photoreceptors. At the first synapse in the mammalian retina, rod outputs are pooled by a rod "ON" bipolar cell, which uses a G-protein signaling cascade to enhance the fidelity of the single photon response under conditions where few rods absorb light. Here we show in mouse rod bipolar cells that both splice variants of the Go. subunit, G alpha(o1) and G alpha(o2), mediate light responses under the control of mGluR6 receptors, and their coordinated action is critical for maximizing sensitivity. We found that the light response of rod bipolar cells was primarily mediated by G alpha(o1), but the loss of G alpha(o2) caused a reduction in the light sensitivity. This reduced sensitivity was not attributable to the reduction in the total number of G(o) alpha subunits, or the altered balance of expression levels between the two splice variants. These results indicate that G alpha(o1) and G alpha(o2) both mediate a depolarizing light response in rod bipolar cells without occluding each other's actions, suggesting they might act independently on a common effector. Thus, G alpha(o2) plays a role in improving the sensitivity of rod bipolar cells through its action with G alpha(o1). The coordinated action of two splice variants of a single G. may represent a novel mechanism for the fine control of G-protein activity.
C1 [Okawa, Haruhisa; Sampath, Alapakkam P.] Univ So Calif, Grad Program Neurosci, Los Angeles, CA 90089 USA.
[Pahlberg, Johan; Sampath, Alapakkam P.] Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA.
[Sampath, Alapakkam P.] Univ So Calif, Dept Physiol & Biophys, Los Angeles, CA 90089 USA.
[Rieke, Fred] Univ Washington, Sch Med, Howard Hughes Med Inst, Seattle, WA 98195 USA.
[Rieke, Fred] Univ Washington, Sch Med, Dept Physiol & Biophys, Seattle, WA 98195 USA.
[Birnbaumer, Lutz] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Sampath, AP (reprint author), Univ So Calif, Grad Program Neurosci, Los Angeles, CA 90089 USA.
EM asampath@usc.edu
FU National Institutes of Health [EY17606, EY11850, Z01 ES101643]; Karl
Kirchgessner Foundation; McKnight Endowment Fund for Neurosciences
FX This work was supported by National Institutes of Health grants EY17606
(A.P. Sampath) and EY11850 (F. Rieke), the Intramural Research Program
of the National Institutes of Health Z01 ES101643 (L. Birnbaumer), the
Karl Kirchgessner Foundation (A.P. Sampath), and the McKnight Endowment
Fund for Neurosciences (A.P. Sampath).
NR 47
TC 19
Z9 19
U1 0
U2 1
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 OCT
PY 2010
VL 136
IS 4
BP 443
EP 454
DI 10.1085/jgp.201010477
PG 12
WC Physiology
SC Physiology
GA 688EB
UT WOS:000284831500005
PM 20837674
ER
PT J
AU Palmquist, AEL
Koehly, LM
Peterson, SK
Shegog, M
Vernon, SW
Gritz, ER
AF Palmquist, Aunchalee E. L.
Koehly, Laura M.
Peterson, Susan K.
Shegog, Margarette
Vernon, Sally W.
Gritz, Ellen R.
TI "The Cancer Bond": Exploring the Formation of Cancer Risk Perception in
Families with Lynch Syndrome
SO JOURNAL OF GENETIC COUNSELING
LA English
DT Article
DE Risk perception; Family communication; Genetic testing; Lynch Syndrome;
Genetic counseling
ID NONPOLYPOSIS COLORECTAL-CANCER; HEREDITARY COLON-CANCER; GENETIC
INFORMATION; COMMUNICATION; PREDISPOSITION; DISCLOSURE; MANAGEMENT;
BELIEFS; MEMBERS
AB This study explores the social context of hereditary cancer risk perception in three families, an African-American family, a Mexican-American family, and a Caucasian family, each with Lynch Syndrome documented by a mismatch repair gene mutation. Communication network assessments measured family communication about cancer experiences and genetic testing information among a total of 26 participants. Participant narratives were evaluated to gain insight into how family cancer experiences and genetic testing information have shaped perceptions of cancer risk. Analysis of communication networks indicated that some families discussed cancer experiences to a greater extent than genetic testing information, and vice-versa. Interviews elucidated that sharing both types of health information led participants to conceptualize linkages among a strong family history of cancer, genetic testing information, and cancer prevention strategies. Understanding how different types of family communication influence the formation of perceived hereditary disease risk may enhance efforts to tailor genetic counseling services for families.
C1 [Palmquist, Aunchalee E. L.] Yale Univ, MacMillan Ctr, New Haven, CT 06520 USA.
[Vernon, Sally W.] Univ Texas Houston, Sch Publ Hlth, Dept Epidemiol & Behav Sci, Houston, TX USA.
[Shegog, Margarette] Ohio State Univ, Sch Publ Hlth, Columbus, OH 43210 USA.
[Peterson, Susan K.; Gritz, Ellen R.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA.
[Palmquist, Aunchalee E. L.; Koehly, Laura M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
RP Palmquist, AEL (reprint author), Yale Univ, MacMillan Ctr, POB 208206, New Haven, CT 06520 USA.
EM aunchalee.palmquist@yale.edu
FU National Human Genome Research Institute, National Institutes of Health
[2R01HG1200-6, Z01HG200335-01]
FX This study was supported by the National Human Genome Research
Institute, National Institutes of Health (2R01HG1200-6, PI: ERG). This
research was also supported, in part, by the Intramural Research Program
of the National Human Genome Research Institute, National Institutes of
Health (Z01HG200335-01, PI: LMK). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NHGRI or NIH. This research was conducted as part
of the first author's postdoctoral work in the Social and Behavioral
Research Branch at the National Human Genome Research Institute. Dr.
Palmquist is currently a postdoctoral associate and lecturer at The
MacMillan Center, Yale University, New Haven, CT. We thank Sapna Kapoor
and Linda Solomon for their assistance with data collection, Mary
Fitzgerald and Heather Kitzman for their assistance in developing the
interview guide, and ABT Associates for their assistance in transcribing
the interviews. We extend our gratitude to our research participants for
their generous contribution to this study. Finally, we would like to
thank the anonymous reviewers for their invaluable suggestions regarding
the revision of this paper.
NR 37
TC 10
Z9 10
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1059-7700
J9 J GENET COUNS
JI J. Genet. Couns.
PD OCT
PY 2010
VL 19
IS 5
BP 473
EP 486
DI 10.1007/s10897-010-9299-8
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 654RA
UT WOS:000282184500005
PM 20401527
ER
PT J
AU Koppen, H
Palm-Meinders, I
Verschuren, M
Launer, L
van Buchem, M
Ferrari, M
Terwindt, G
Kruit, M
AF Koppen, H.
Palm-Meinders, I.
Verschuren, M.
Launer, L.
van Buchem, M.
Ferrari, M.
Terwindt, G.
Kruit, M.
TI Prevalence of diabetes, hypercholesterolemia and clinical stroke in
migraine patients after 9 years follow-up: results of the
population-based camera-2 study
SO JOURNAL OF HEADACHE AND PAIN
LA English
DT Meeting Abstract
C1 [Koppen, H.; Palm-Meinders, I.; van Buchem, M.; Ferrari, M.; Terwindt, G.; Kruit, M.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Koppen, H.] Haga Hosp, The Hague, Netherlands.
[Verschuren, M.] RIVM, Ctr Prevent & Hlth Serv Res, Bilthoven, Netherlands.
[Launer, L.] NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RI Kruit, Mark/K-2431-2012
OI Kruit, Mark/0000-0002-4319-834X
NR 0
TC 0
Z9 0
U1 1
U2 3
PU SPRINGER-VERLAG ITALIA SRL
PI MILAN
PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY
SN 1129-2369
EI 1129-2377
J9 J HEADACHE PAIN
JI J. Headache Pain
PD OCT
PY 2010
VL 11
SU 1
MA 266
BP S60
EP S60
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA V30BQ
UT WOS:000208791900167
ER
PT J
AU Palm-Meinders, IH
Koppen, H
Moonen, JME
Terwindt, GM
Launer, LJ
van Buchem, MA
Ferrari, MD
Kruit, MC
AF Palm-Meinders, I. H.
Koppen, H.
Moonen, J. M. E.
Terwindt, G. M.
Launer, L. J.
van Buchem, M. A.
Ferrari, M. D.
Kruit, M. C.
TI Progression of infratentorial hyperintense lesions in migraine: the
population-based camera-2 nine year follow-up MRI study
SO JOURNAL OF HEADACHE AND PAIN
LA English
DT Meeting Abstract
C1 [Palm-Meinders, I. H.; Koppen, H.; Moonen, J. M. E.; Terwindt, G. M.; van Buchem, M. A.; Ferrari, M. D.; Kruit, M. C.] Leiden Univ Med Ctr, Leiden, Netherlands.
[Koppen, H.] Haga Hosp, The Hague, Netherlands.
[Launer, L. J.] NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RI Kruit, Mark/K-2431-2012
OI Kruit, Mark/0000-0002-4319-834X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER-VERLAG ITALIA SRL
PI MILAN
PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY
SN 1129-2369
EI 1129-2377
J9 J HEADACHE PAIN
JI J. Headache Pain
PD OCT
PY 2010
VL 11
SU 1
MA 240
BP S50
EP S50
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA V30BQ
UT WOS:000208791900142
ER
PT J
AU Palm-Meinders, IH
Koppen, H
Terwindt, GM
Launer, LJ
Konishi, J
Bakkers, JTN
Hofman, PAM
Middelkoop, HAM
van Buchem, MA
Ferrari, MD
Kruit, MC
AF Palm-Meinders, I. H.
Koppen, H.
Terwindt, G. M.
Launer, L. J.
Konishi, J.
Bakkers, J. T. N.
Hofman, P. A. M.
Middelkoop, H. A. M.
van Buchem, M. A.
Ferrari, M. D.
Kruit, M. C.
TI Progression and consequences of brain lesions in migraine: the
population-based camera-2 nine year follow-up MRI study
SO JOURNAL OF HEADACHE AND PAIN
LA English
DT Meeting Abstract
C1 [Palm-Meinders, I. H.; Koppen, H.; Terwindt, G. M.; Konishi, J.; Middelkoop, H. A. M.; van Buchem, M. A.; Ferrari, M. D.; Kruit, M. C.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Koppen, H.] Haga Hosp, The Hague, Netherlands.
[Launer, L. J.] NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Bakkers, J. T. N.] Slingeland Ziekenhuis, Doetinchem, Netherlands.
[Hofman, P. A. M.] Univ Limburg, Acad Hosp Maastricht, Maastricht, Netherlands.
RI Kruit, Mark/K-2431-2012
OI Kruit, Mark/0000-0002-4319-834X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER-VERLAG ITALIA SRL
PI MILAN
PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY
SN 1129-2369
EI 1129-2377
J9 J HEADACHE PAIN
JI J. Headache Pain
PD OCT
PY 2010
VL 11
SU 1
MA 205
BP S42
EP S42
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA V30BQ
UT WOS:000208791900118
ER
PT J
AU Greten, TF
Korangy, F
AF Greten, Tim F.
Korangy, Firouzeh
TI Radiofrequency ablation for the treatment of HCC - Maybe much more than
simple tumor destruction?
SO JOURNAL OF HEPATOLOGY
LA English
DT Editorial Material
DE Immunotherapy; T cell; NK-cell
ID PHOTODYNAMIC THERAPY; CELLS
AB Background & Aims: Radiofrequency thermal ablation (RFA) is a minimally invasive technique used as standard local therapy of hepatocellular carcinoma and second-line treatment for metastatic liver tumors. Studies in preclinical models and in patients have shown that thermal destruction of tumor tissue can enhance anti-tumor cellular responses, but our knowledge of its impact on natural killer (NK) cells is still very limited.
Methods: Thirty-seven patients undergoing RFA for hepatocellular carcinoma were studied for peripheral blood lymphocytes counts followed by phenotypic and functional characterization of NK-cell population.
Results: Peripheral blood lymphocytes kinetics revealed an increased frequency and absolute number of NK-cells expressing higher levels of activatory along with reduced levels of inhibitory NK receptors, and increased functional NK-cell activity. A prevalent expansion of the CD3(-)CD56(dim) NK subset was observed compared to the CD3(-)CD56(bright) counterpart. Interferon-gamma production, anti-K562 cell-cytotoxicity, and antibody-dependent cell-cytotoxicity, appeared consistently increased in terms of both absolute activity and killing efficiency at 4 weeks after RFA, as compared to baseline. Interestingly, when recurrence-free survival was assessed in two groups of patients separated according to higher vs lower enhancement of cytotoxicity and/or interferon-gamma production, a significant difference was observed, thus suggesting a potential predictive role of NK functional assays on efficacy of RFA.
Conclusions: RFA can lead to stimulation of NK-cells with a more differentiated and proactivatory phenotypic profile with general increase of functional activities. This observation may be relevant Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Greten, Tim F.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Korangy, Firouzeh] Hannover Med Sch, Dept Gastroenterol Hepatol & Endokrinol, D-3000 Hannover, Germany.
RP Greten, TF (reprint author), NCI, Med Oncol Branch, NIH, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tim.greten@nih.gov
RI Greten, Tim/B-3127-2015
OI Greten, Tim/0000-0002-0806-2535
NR 7
TC 10
Z9 18
U1 1
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 OCT
PY 2010
VL 53
IS 4
BP 775
EP 776
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 660EM
UT WOS:000282622800026
PM 20619917
ER
PT J
AU Rai, G
Ray, S
Milton, J
Yang, J
Ren, P
Lempicki, R
Mage, RG
AF Rai, Geeta
Ray, Satyajit
Milton, Jacqueline
Yang, Jun
Ren, Ping
Lempicki, Richard
Mage, Rose G.
TI Gene Expression Profiles in a Rabbit Model of Systemic Lupus
Erythematosus Autoantibody Production
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID OLIGONUCLEOTIDE ARRAYS; AUTOIMMUNE-DISEASE; CELL DEPLETION; SLE;
INTERFERON; ANTIBODIES; PEPTIDE; BLOOD; SEQUENCE; DNA
AB We previously reported the establishment of a rabbit (Oryctolagus cuniculus) model in which peptide immunization led to production of lupus-like autoantibodies including anti-Sm, -RNP, -SS-A, -SS-B, and -dsDNA characteristic of those produced in systemic lupus erythematosus (SLE) patients. Some neurologic symptoms in the form of seizures and nystagmus were observed. The animals used in the previous and in the current study were from a National Institute of Allergy and Infectious Diseases colony of rabbits that were pedigreed, Ig-allotype defined, but not inbred. Their genetic heterogeneity may correspond to that found among patients of a given ethnicity. We extended the information about this rabbit model by microarray-based expression profiling. We first demonstrated that human expression arrays could be used with rabbit RNA to yield information on molecular pathways. We then designed a study evaluating gene expression profiles in eight groups of control and treated rabbits (47 rabbits in total). Genes significantly upregulated in treated rabbits were associated with NK cytotoxicity, Ag presentation, leukocyte migration, cytokine activity, protein kinases, RNA spliceosomal ribonucleoproteins, intracellular signaling cascades, and glutamate receptor activity. These results link increased immune activation with upregulation of components associated with neurologic and anti-RNP responses, demonstrating the utility of the rabbit model to uncover biological pathways related to SLE-induced clinical symptoms, including neuropsychiatric lupus. Our finding of distinct gene expression patterns in rabbits that made anti-dsDNA compared with those that only made other anti-nuclear Abs should be further investigated in subsets of SLE patients with different autoantibody profiles. The Journal of Immunology, 2010, 185: 4446-4456.
C1 [Rai, Geeta; Ray, Satyajit; Milton, Jacqueline; Mage, Rose G.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Yang, Jun; Ren, Ping; Lempicki, Richard] Natl Canc Inst Frederick, Sci Applicat Int Corp, Lab Bioinformat & Immunopathogenesis, Frederick, MD 21702 USA.
RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA.
EM rmage@niaid.nih.gov
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]
FX This work was supported by the intramural research program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases (http://www.niaid.nih.gov) and in part by federal
funds from the National Cancer Institute, National Institutes of Health,
under Contract HHSN261200800001E.
NR 66
TC 4
Z9 4
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD OCT 1
PY 2010
VL 185
IS 7
BP 4446
EP 4456
DI 10.4049/jimmunol.1001254
PG 11
WC Immunology
SC Immunology
GA 653BU
UT WOS:000282059500073
PM 20817871
ER
PT J
AU Royal, RE
Levy, C
Turner, K
Mathur, A
Hughes, M
Kammula, US
Sherry, RM
Topalian, SL
Yang, JC
Lowy, I
Rosenberg, SA
AF Royal, Richard E.
Levy, Catherine
Turner, Keli
Mathur, Aarti
Hughes, Marybeth
Kammula, Udai S.
Sherry, Richard M.
Topalian, Suzanne L.
Yang, James C.
Lowy, Israel
Rosenberg, Steven A.
TI Phase 2 Trial of Single Agent Ipilimumab (Anti-CTLA-4) for Locally
Advanced or Metastatic Pancreatic Adenocarcinoma
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE pancreatic cancer; immunotherapy; natural killer cells; ipilimumab;
CTLA-4; gastrointestinal malignancies
ID RANDOMIZED CONTROLLED-TRIAL; LYMPHOCYTE-ASSOCIATED ANTIGEN-4;
NATIONAL-CANCER-INSTITUTE; HIGH-DOSE INTERLEUKIN-2; CURATIVE RESECTION;
III TRIAL; ADJUVANT CHEMOTHERAPY; PERIAMPULLARY REGION; COOPERATIVE
GROUP; PROSTATE-CANCER
AB New, effective therapies are needed for pancreatic ductal adenocarcinoma. Ipilimumab can mediate an immunologic tumor regression in other histologies. This phase II trial evaluated the efficacy of Ipilimumab for advanced pancreatic cancer. Subjects were adults with locally advanced or metastatic pancreas adenocarcinoma with measurable disease, good performance status, and minimal comorbidities. Ipilimumab was administered intra-venously (3.0 mg/kg every 3 wk; 4 doses/course) for a maximum of 2 courses. Response rate by response evaluation criteria in solid tumors criteria and toxicity were measured. Twenty-seven subjects were enrolled (metastatic disease: 20 and locally advanced: 7) with median age of 55 years (27 to 68 y) and good performance status (26 with Eastern Cooperative Oncology Group performance status = 0 to 1). Three subjects experienced >= grade 3 immune-mediated adverse events (colitis: 1, encephalitis: 1, hypohysitis: 1). There were no responders by response evaluation criteria in solid tumors criteria but a subject experienced a delayed response after initial progressive disease. In this subject, new metastases after 2 doses of Ipilimumab established progressive disease. But continued administration of the agent per protocol resulted in significant delayed regression of the primary lesion and 20 hepatic metastases. This was reflected in tumor markers normalization, and clinically significant improvement of performance status. Single agent Ipilimumab at 3.0 mg/kg/dose is ineffective for the treatment of advanced pancreas cancer. However, a significant delayed response in one subject of this trial suggests that immunotherapeutic approaches to pancreas cancer deserve further exploration.
C1 [Royal, Richard E.; Levy, Catherine; Turner, Keli; Mathur, Aarti; Hughes, Marybeth; Kammula, Udai S.; Sherry, Richard M.; Topalian, Suzanne L.; Yang, James C.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Turner, Keli] NCI, Clin Res Training Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lowy, Israel] Medarex Inc, Princeton, NJ USA.
RP Royal, RE (reprint author), 1515 Holcombe Blvd,Unit 444, Houston, TX 77098 USA.
EM rroyal@mdanderson.org
FU National Cancer Institute, National Institutes of Health
FX Supported by the Intramural Research Program of the National Cancer
Institute, National Institutes of Health.
NR 46
TC 184
Z9 187
U1 5
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2010
VL 33
IS 8
BP 828
EP 833
DI 10.1097/CJI.0b013e3181eec14c
PG 6
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 653XQ
UT WOS:000282131800009
PM 20842054
ER
PT J
AU Goff, SL
Smith, FO
Klapper, JA
Sherry, R
Wunderlich, JR
Steinberg, SM
White, D
Rosenberg, SA
Dudley, ME
Yang, JC
AF Goff, Stephanie L.
Smith, Franz O.
Klapper, Jacob A.
Sherry, Richard
Wunderlich, John R.
Steinberg, Seth M.
White, Donald
Rosenberg, Steven A.
Dudley, Mark E.
Yang, James C.
TI Tumor Infiltrating Lymphocyte Therapy for Metastatic Melanoma: Analysis
of Tumors Resected for TIL
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE metastatic melanoma; tumor-infiltrating lymphocytes; adoptive cell
transfer
ID ADOPTIVE CELL THERAPY; TCR; INTERLEUKIN-2
AB Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) can mediate objective tumor regression in 49% to 72% of patients with many long-term durable responses. To undergo treatment a patient must have (1) a resectable tumor from which (2) TIL can be generated that (3) exhibit tumor-specific reactivity. From July 2002 to July 2007, 787 tumors from 402 patients were processed for possible use in the generation of TIL, leading to the eventual treatment of 107 patients (27%). Viable TILs were generated in 376 patients (94%), and active, specific TILs were identified in 269 patients (67%). Patient demographics and tumor characteristics were analyzed for possible prognostic factors for growth and activity. Gastrointestinal-derived TIL grew less frequently, whereas lymph node and lung-derived TIL exhibited specific activity more often. TIL that grew and exhibited specific reactivity were from tumors that were larger in diameter and digests that had a higher percentage of lymphocytes. Despite these considerations, active, specific TIL could be generated from almost any site of metastasis. As more centers begin exploring the use of adoptive transfer with TIL, this compendium may provide a framework for therapeutic decision making and future investigation.
C1 [Goff, Stephanie L.; Smith, Franz O.; Klapper, Jacob A.; Sherry, Richard; Wunderlich, John R.; White, Donald; Rosenberg, Steven A.; Dudley, Mark E.; Yang, James C.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Goff, SL (reprint author), NCI, Surg Branch, NIH, CRC 3W-3940,10 Ctr Dr, Bethesda, MD 20892 USA.
EM slgoffmd@gmail.com
FU NIH Intramural Research
FX Funded by NIH Intramural Research.
NR 15
TC 43
Z9 46
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2010
VL 33
IS 8
BP 840
EP 847
DI 10.1097/CJI.0b013e3181f05b91
PG 8
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 653XQ
UT WOS:000282131800011
PM 20842052
ER
PT J
AU Abate-Daga, D
Park, TS
Palmer, DC
Restifo, NP
Rosenberg, SA
Morgan, RA
AF Abate-Daga, Daniel
Park, Tristen S.
Palmer, Douglas C.
Restifo, Nicholas P.
Rosenberg, Steven A.
Morgan, Richard A.
TI Development of a gamma-Retroviral Vector for the Expression of
Artificial miRNAs in Human T Lymphocytes
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
C1 [Abate-Daga, Daniel; Park, Tristen S.; Palmer, Douglas C.; Restifo, Nicholas P.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RI Restifo, Nicholas/A-5713-2008
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 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2010
VL 33
IS 8
BP 859
EP 859
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 653XQ
UT WOS:000282131800014
ER
PT J
AU Bedognetti, D
Uccellini, L
Wang, E
Dudley, ME
Pos, Z
Ascierto, ML
De Giorgi, V
Liu, H
Chen, J
Sertoli, MR
Marincola, FM
Rosenberg, SA
AF Bedognetti, Davide
Uccellini, Lorenzo
Wang, Ena
Dudley, Mark E.
Pos, Zoltan
Ascierto, Maria Libera
De Giorgi, Valeria
Liu, Hui
Chen, Jingou
Sertoli, Mario Roberto
Marincola, Francesco M.
Rosenberg, Steven A.
TI Evaluation of CXCR3 and CCR5 Polymorphisms and Gene-Expression as
Predictive Biomarkers of Clinical Response to Adoptive Therapy in
Melanoma Patients
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
C1 [Bedognetti, Davide; Uccellini, Lorenzo; Wang, Ena; Pos, Zoltan; Ascierto, Maria Libera; De Giorgi, Valeria; Liu, Hui; Chen, Jingou; Marincola, Francesco M.] NIH, Dept Transfus Med, CC, Bethesda, MD USA.
[Dudley, Mark E.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Bedognetti, Davide; Sertoli, Mario Roberto] Univ Genoa, Dept Oncol Biol Genet, Genoa, Italy.
RI Bedognetti, Davide/A-9090-2012; Ascierto, Maria Libera/A-9239-2012
NR 0
TC 2
Z9 2
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2010
VL 33
IS 8
BP 860
EP 860
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 653XQ
UT WOS:000282131800016
ER
PT J
AU Kerkar, SP
Reger, R
Muranski, P
Yu, ZY
Palmer, D
Chinnasamy, D
Klebanoff, CA
Ji, Y
Gattinoni, L
Rosenberg, SA
Trinchieri, G
Restifo, NP
AF Kerkar, Sid P.
Reger, Robert
Muranski, Pawel
Yu, Zhiya
Palmer, Douglas
Chinnasamy, Dhanalakshmi
Klebanoff, Christopher A.
Ji, Yun
Gattinoni, Luca
Rosenberg, Steven A.
Trinchieri, Giorgio
Restifo, Nicholas P.
TI Functional Reprogramming of the Tumor Stroma by IL-12 Engineered T Cells
is Required for Anti-tumor Immunity
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
C1 [Kerkar, Sid P.; Reger, Robert; Muranski, Pawel; Yu, Zhiya; Palmer, Douglas; Chinnasamy, Dhanalakshmi; Klebanoff, Christopher A.; Ji, Yun; Gattinoni, Luca; Rosenberg, Steven A.; Restifo, Nicholas P.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Bethesda, MD 20892 USA.
RI Restifo, Nicholas/A-5713-2008
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 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2010
VL 33
IS 8
BP 861
EP 861
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 653XQ
UT WOS:000282131800020
ER
PT J
AU Muranski, PJ
Borman, Z
Kerkar, S
Ji, Y
Gattinoni, L
Reger, R
Klebanoff, C
Yu, ZY
Ferreyra, G
Kern, S
Danner, RL
Restifo, NP
AF Muranski, Pawel J.
Borman, Zachary
Kerkar, Sid
Ji, Yun
Gattinoni, Luca
Reger, Robert
Klebanoff, Christopher
Yu, Zhiya
Ferreyra, Gabriela
Kern, Steven
Danner, Robert L.
Restifo, Nicholas P.
TI Adoptively Transferred Anti-Tumor Th17 Cells are Long-Lived and Evolve
Into a Highly Active Memory Population with a Unique Molecular Signature
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
C1 [Muranski, Pawel J.; Borman, Zachary; Kerkar, Sid; Ji, Yun; Gattinoni, Luca; Reger, Robert; Klebanoff, Christopher; Yu, Zhiya; Restifo, Nicholas P.] NCI, Bethesda, MD 20892 USA.
[Ferreyra, Gabriela; Kern, Steven; Danner, Robert L.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
RI Restifo, Nicholas/A-5713-2008
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 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2010
VL 33
IS 8
BP 862
EP 863
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 653XQ
UT WOS:000282131800024
ER
PT J
AU Park, TS
Inozume, T
Ahmadzadeh, M
Hanada, KI
Yang, J
Rosenberg, SA
Morgan, RA
AF Park, Tristen S.
Inozume, Takashi
Ahmadzadeh, Mojgan
Hanada, Ken-ichi
Yang, James
Rosenberg, Steven A.
Morgan, Richard A.
TI Artifical MicroRNA Targeting Programmed Death Receptor-1 to Enhance
Adoptive Cell Transfer Therapy for Cancer
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
C1 [Park, Tristen S.; Inozume, Takashi; Ahmadzadeh, Mojgan; Hanada, Ken-ichi; Yang, James; Rosenberg, Steven A.; Morgan, Richard A.] NIH, Surg Branch, Bethesda, MD 20892 USA.
RI Hanada, Ken-ichi/L-2481-2013
OI Hanada, Ken-ichi/0000-0003-2959-1257
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2010
VL 33
IS 8
BP 863
EP 863
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 653XQ
UT WOS:000282131800025
ER
PT J
AU Ascierto, ML
Kmieciak, M
Idowu, M
Grimes, M
Dumur, C
Wang, E
Marincola, FM
Bear, HD
Manjili, MH
AF Ascierto, Maria-Libera
Kmieciak, Maciej
Idowu, Michael
Grimes, Margaret
Dumur, Catherine
Wang, Ena
Marincola, Francesco M.
Bear, Harry D.
Manjili, Masoud H.
TI Signatures of Immune Function Genes Associated with Recurrence-Free
Survival in Breast Cancer Patients
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
C1 [Ascierto, Maria-Libera; Wang, Ena; Marincola, Francesco M.] NIH, Bethesda, MD 20892 USA.
[Kmieciak, Maciej; Idowu, Michael; Grimes, Margaret; Dumur, Catherine; Bear, Harry D.; Manjili, Masoud H.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA.
RI Ascierto, Maria Libera/A-9239-2012
NR 0
TC 1
Z9 1
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2010
VL 33
IS 8
BP 881
EP 881
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 653XQ
UT WOS:000282131800081
ER
PT J
AU De Giorgi, V
Ascierto, ML
Pos, Z
Buonaguro, L
Buonaguro, FM
Wang, E
Marincola, FM
AF De Giorgi, Valeria
Ascierto, Maria Libera
Pos, Zoltan
Buonaguro, Luigi
Buonaguro, Franco M.
Wang, Ena
Marincola, Francesco M.
TI Melanoma and IRFs: A New Classification of Melanoma
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
C1 [De Giorgi, Valeria; Ascierto, Maria Libera; Pos, Zoltan; Wang, Ena; Marincola, Francesco M.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Buonaguro, Luigi; Buonaguro, Franco M.] Fdn G Pascale, Lab Mol Biol & Viral Oncogenesis, Naples, Italy.
[Buonaguro, Luigi; Buonaguro, Franco M.] Fdn G Pascale, AIDS Reference Ctr, Ist Nazl Tumori, Naples, Italy.
RI Ascierto, Maria Libera/A-9239-2012; De Giorgi, Valeria/D-4582-2017
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2010
VL 33
IS 8
BP 885
EP 886
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 653XQ
UT WOS:000282131800095
ER
PT J
AU Ascierto, ML
Worschech, A
Castiello, L
Wang, R
Pos, Z
Uccellini, L
Bedognetti, D
De Giorgi, V
Thomas, J
Yu, ZY
Balachandran, S
Rossano, F
Restifo, N
Szalay, A
Ascierto, P
Wang, E
Marincola, FM
AF Ascierto, Maria L.
Worschech, Andrea
Castiello, Luciano
Wang, Richard
Pos, Zoltan
Uccellini, Lorenzo
Bedognetti, Davide
De Giorgi, Valeria
Thomas, Jaime
Yu, Zhiya
Balachandran, Siddharth
Rossano, Fabio
Restifo, Nicholas
Szalay, A.
Ascierto, Paolo
Wang, Ena
Marincola, Francesco M.
TI IKK Complex and NF-kappa B: Linkage Between Innate Immune Response and
Oncolytic Based Viral Therapy
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
C1 [Ascierto, Maria L.; Castiello, Luciano; Wang, Richard; Pos, Zoltan; Uccellini, Lorenzo; Bedognetti, Davide; De Giorgi, Valeria; Thomas, Jaime; Wang, Ena; Marincola, Francesco M.] Natl Inst Hlth, Dept Transfus Med, Bethesda, MD USA.
[Yu, Zhiya; Restifo, Nicholas] Natl Canc Inst, Bethesda, MD USA.
[Worschech, Andrea; Szalay, A.] Genelux Corp, San Diego, CA USA.
[Balachandran, Siddharth] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Rossano, Fabio; Ascierto, Paolo] Dept Gen Pathol, Naples, Italy.
RI Restifo, Nicholas/A-5713-2008; Bedognetti, Davide/A-9090-2012; Ascierto,
Maria Libera/A-9239-2012; Worschech, Andrea/I-3919-2012; De Giorgi,
Valeria/D-4582-2017
OI Worschech, Andrea/0000-0002-4303-8653;
NR 0
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2010
VL 33
IS 8
BP 891
EP 892
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 653XQ
UT WOS:000282131800114
ER
PT J
AU Gore, A
Muralidhar, M
Espey, MG
Degenhardt, K
Mantell, LL
AF Gore, Ashwini
Muralidhar, Maitreyi
Espey, Michael Graham
Degenhardt, Kurt
Mantell, Lin L.
TI Hyperoxia sensing: From molecular mechanisms to significance in disease
SO JOURNAL OF IMMUNOTOXICOLOGY
LA English
DT Review
DE Hyperoxia; inflammation; sensing; apoptosis; cell death; signaling;
acute lung injury; ROS
ID NF-KAPPA-B; ACUTE LUNG INJURY; GLYCATION END-PRODUCTS;
TUMOR-NECROSIS-FACTOR; PULMONARY OXYGEN-TOXICITY; ACTIVATED
PROTEIN-KINASE; RESPIRATORY-DISTRESS-SYNDROME; SIGNAL-TRANSDUCTION
PATHWAYS; VASCULAR ENDOTHELIAL-CELLS; TRANSCRIPTION FACTOR NRF2
AB Oxygen therapy using mechanical ventilation with hyperoxia is necessary to treat patients with respiratory failure and distress. However, prolonged exposure to hyperoxia leads to the generation of excessive reactive oxygen species (ROS), causing cellular damage and multiple organ dysfunctions. As the lungs are directly exposed, hyperoxia can cause both acute and chronic inflammatory lung injury and compromise innate immunity. ROS may contribute to pulmonary oxygen toxicity by overwhelming redox homeostasis, altering signaling cascades that affect cell fate, ultimately leading to hyperoxia-induced acute lung injury (HALI). HALI is characterized by pronounced inflammatory responses with leukocyte infiltration, injury, and death of pulmonary cells, including epithelia, endothelia, and macrophages. Under hyperoxic conditions, ROS mediate both direct and indirect modulation of signaling molecules such as protein kinases, transcription factors, receptors, and pro-and anti-apoptotic factors. The focus of this review is to elaborate on hyperoxia-activated key sensing molecules and current understanding of their signaling mechanisms in HALI. A better understanding of the signaling pathways leading to HALI may provide valuable insights on its pathogenesis and may help in designing more effective therapeutic approaches.
C1 [Gore, Ashwini; Muralidhar, Maitreyi; Degenhardt, Kurt; Mantell, Lin L.] St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Allied Hlth Profess, Queens, NY 11439 USA.
[Espey, Michael Graham] NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD USA.
[Mantell, Lin L.] N Shore LIJ Hlth Syst, Feinstein Inst Med Res, Ctr Lung & Heart Res, Manhasset, NY USA.
[Mantell, Lin L.] N Shore LIJ Hlth Syst, Feinstein Inst Med Res, Ctr Inflammat & Immunol, Manhasset, NY USA.
RP Mantell, LL (reprint author), St Johns Univ, Dept Pharmaceut Sci, Coll Pharm, 128-SB28 St Albert Hall,8000 Utopia Pkwy, Queens, NY 11439 USA.
EM mantelll@stjohns.edu
FU National Heart and Blood Institute [HL093708]; St. John's University;
Feinstein Institute for Medical Research at the North Shore-Long Island
Jewish Health System
FX This work was supported by grants from the National Heart and Blood
Institute (HL093708, LLM), St. John's University and the Feinstein
Institute for Medical Research at the North Shore-Long Island Jewish
Health System. The authors are alone responsible for the content and
writing of the paper.
NR 192
TC 43
Z9 56
U1 1
U2 9
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 1547-691X
J9 J IMMUNOTOXICOL
JI J. Immunotoxicol.
PD OCT-DEC
PY 2010
VL 7
IS 4
BP 239
EP 254
DI 10.3109/1547691X.2010.492254
PG 16
WC Toxicology
SC Toxicology
GA 681LJ
UT WOS:000284316600001
PM 20586583
ER
PT J
AU Guo, TL
Germolec, DR
Roesh, DM
White, KL
AF Guo, Tai L.
Germolec, Dori R.
Roesh, Denise M.
White, Kimber L., Jr.
TI Immunomodulation in female B6C3F1 mice following treatment with the HIV
protease inhibitor saquinavir for 28 days by gavage
SO JOURNAL OF IMMUNOTOXICOLOGY
LA English
DT Article
DE Saquinavir; immunomodulation; antibody-forming cell response
ID ANTIRETROVIRAL THERAPY; IN-VITRO; IMMUNE FUNCTION; TUMOR-CELLS;
RITONAVIR; INFECTION; VIVO; COMBINATION; LYMPHOCYTES; FORMULATION
AB Saquinavir (SQV) is a protease inhibitor that binds to the protease active site of the human immunodeficiency virus and prevents the cleavage of viral polyproteins resulting in the formation of non-infectious virus particles. The purpose of these studies was to determine the potential effects of SQV on the immune system in female B6C3F1 mice. SQV was administered by gavage twice daily for 28 days at total doses of 300, 600, and 1200 mg/kg/day. No significant differences were observed in body weight, or the weights of spleen, thymus, liver, kidneys, or lungs. Exposure to SQV produced no biologically meaningful changes in hematological parameters. However, a statistically significant increase in the number of T-cells (23%) was observed at the high dose level of SQV. The number of splenic immature T-cells (CD4(+)CD8(+) cells) also showed increases of 46% and 92% at the 600 and 1200 mg/kg dose levels, respectively. The immunoglobulin M antibody-forming cell (AFC) response was significantly increased by 41% when the data were expressed as AFC/10(6) spleen cells at the 1200 mg/kg dose level. Treatment with SQV had no effects on the mixed leukocyte response. Overall, the activities of natural killer cells and cytotoxic T-cells were not altered in SQV-treated animals when compared to vehicle controls. In addition, exposure to SQV did not affect host resistance in the B16F10 melanoma model. In conclusion, SQV produced an enhancement of the humoral immune response, possibly through modulating T-cell function in female B6C3F1 mice.
C1 [Guo, Tai L.; Roesh, Denise M.; White, Kimber L., Jr.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA.
[Germolec, Dori R.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP White, KL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, POB 980613, Richmond, VA 23298 USA.
EM klwhite@vcu.edu
FU NIEHS [NO1-ES-05454]
FX This study was supported by the NIEHS contract NO1-ES-05454. Dr. Kimber
L. White, Jr. is the owner of a company, ImmunoTox (R), Inc., that
conducts immunotoxicological studies under Good Laboratory Practices
(GLP); however, none of the work presented here involved his company.
NR 40
TC 1
Z9 1
U1 0
U2 1
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 1547-691X
J9 J IMMUNOTOXICOL
JI J. Immunotoxicol.
PD OCT-DEC
PY 2010
VL 7
IS 4
BP 289
EP 297
DI 10.3109/1547691X.2010.495097
PG 9
WC Toxicology
SC Toxicology
GA 681LJ
UT WOS:000284316600005
PM 20560775
ER
PT J
AU Smith, MJ
Germolec, DR
Luebke, RW
Sheth, CM
Auttachoat, W
Guo, TL
White, KL
AF Smith, Matthew J.
Germolec, Dori R.
Luebke, Robert W.
Sheth, Christopher M.
Auttachoat, Wimolnut
Guo, Tai L.
White, Kimber L., Jr.
TI Immunotoxicity of dibromoacetic acid administered via drinking water to
female B6C3F1 mice
SO JOURNAL OF IMMUNOTOXICOLOGY
LA English
DT Article
DE Dibromoacetic acid; immunotoxicity; drinking water; disinfection
by-products; haloacetic acids
ID DISINFECTION BY-PRODUCTS; HOST-RESISTANCE; IMMUNE-RESPONSE; EXPOSURE;
RATS; MODULATION; TOXICITY; CARCINOGENICITY; GENOTOXICITY; ANTIBODY
AB Dibromoacetic acid (DBA) is a disinfection by-product commonly found in drinking water as a result of chlorination/ozonation processes. The Environmental Protection Agency estimates that more than 200 million people consume disinfected water in the United States. This study was conducted to evaluate the potential immunotoxicological effects of DBA exposure when administered for 28 days via drinking water to B6C3F1 mice, at concentrations of 125, 500, and 1000 mg/L. Multiple endpoints were evaluated to assess innate, humoral, and cell-mediated immune components, as well as host resistance. Standard toxicological parameters were unaffected, with the exception of a dose-responsive increase in liver weight and a decrease in thymus weight at the two highest exposure levels. Splenocyte differentials were affected, although the effects were not dose-responsive. Exposure to DBA did not significantly affect humoral immunity (immunoglobulin M [IgM] plaque assay and serum IgM anti-sheep erythrocyte titers) or cell-mediated immunity (mixed-leukocyte response). No effects were observed on innate immune function in either interferon-gamma-induced in vitro macrophage cytotoxic activity or basal natural killer (NK)-cell activity. Augmented NK-cell activity (following exposure to polyinosinic-polycytidylic acid) was decreased at the low dose, however the effect was not dose-responsive. Finally, DBA exposure had no effect on resistance to infection with either Streptococcus pneumoniae or Plasmodium yoelii, or challenge with B16F10 melanoma cells. With the exception of changes in thymus weight, these results indicate that DBA exposure resulted in no immunotoxic effects at concentrations much larger than those considered acceptable in human drinking water.
C1 [Smith, Matthew J.; Sheth, Christopher M.; Auttachoat, Wimolnut; Guo, Tai L.; White, Kimber L., Jr.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA.
[Germolec, Dori R.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Luebke, Robert W.] US EPA, Immunotoxicol Branch, Expt Toxicol Div, NHEERL, Res Triangle Pk, NC USA.
RP White, KL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Med Coll Virginia Campus,Strauss Bldg,Room 2-011,, Richmond, VA 23298 USA.
EM kwhite@vcu.edu
FU NIEHS [ES 05454]; U.S. Environmental Protection Agency [DW75937992]
FX This article may, in part, be the work product of an employee or group
of employees of the National Institute of Environmental Health Sciences
(NIEHS), National Institutes of Health (NIH), however, the statements,
opinions or conclusions contained therein do not necessarily represent
the statements, opinions or conclusions of NIEHS, NIH or the United
States government. This report has been reviewed by the U. S.
Environmental Protection Agency's Office of Research and Development,
and approved for publication. Approval does not signify that the
contents necessarily reflect the views and policies of the agency nor
does mention of trade names or commercial products constitute
endorsement or recommendation for use. This work was supported in part
by NIEHS Contract ES 05454 and by the U.S. Environmental Protection
Agency under interagency agreement DW75937992.
NR 25
TC 3
Z9 3
U1 1
U2 8
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 1547-691X
J9 J IMMUNOTOXICOL
JI J. Immunotoxicol.
PD OCT-DEC
PY 2010
VL 7
IS 4
BP 333
EP 343
DI 10.3109/1547691X.2010.519744
PG 11
WC Toxicology
SC Toxicology
GA 681LJ
UT WOS:000284316600010
PM 20958156
ER
PT J
AU Kennedy, AD
Wardenburg, JB
Gardner, DJ
Long, D
Whitney, AR
Braughton, KR
Schneewind, O
DeLeo, FR
AF Kennedy, Adam D.
Wardenburg, Juliane Bubeck
Gardner, Donald J.
Long, Daniel
Whitney, Adeline R.
Braughton, Kevin R.
Schneewind, Olaf
DeLeo, Frank R.
TI Targeting of Alpha-Hemolysin by Active or Passive Immunization Decreases
Severity of USA300 Skin Infection in a Mouse Model
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID RESISTANT STAPHYLOCOCCUS-AUREUS; PANTON-VALENTINE LEUKOCIDIN;
SITE-DIRECTED MUTAGENESIS; MURINE MODEL; IN-VITRO; VIRULENCE
DETERMINANT; HUMAN KERATINOCYTES; TOXIN GENE; PNEUMONIA; PATHOGENESIS
AB Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are predominantly those affecting skin and soft tissues. Although progress has been made, our knowledge of the molecules that contribute to the pathogenesis of CA-MRSA skin infections is incomplete. We tested the hypothesis that alpha-hemolysin (Hla) contributes to the severity of USA300 skin infections in mice and determined whether vaccination against Hla reduces disease severity. Isogenic hla-negative (Delta hla) strains caused skin lesions in a mouse infection model that were significantly smaller than those caused by wild-type USA300 and Newman strains. Moreover, infection due to wild-type strains produced dermonecrotic skin lesions, whereas there was little or no dermonecrosis in mice infected with Delta hla strains. Passive immunization with Hla-specific antisera or active immunization with a nontoxigenic form of Hla significantly reduced the size of skin lesions caused by USA300 and prevented dermonecrosis. We conclude that Hla is a potential target for therapeutics or vaccines designed to moderate severe S. aureus skin infections.
C1 [Kennedy, Adam D.; Whitney, Adeline R.; Braughton, Kevin R.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Gardner, Donald J.; Long, Daniel] NIAID, Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Wardenburg, Juliane Bubeck; Schneewind, Olaf] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA.
[Wardenburg, Juliane Bubeck] Univ Chicago, Dept Pediat, Chicago, IL 60637 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 (NIH); Region V "Great Lakes" Regional Center of
Excellence in Biodefense and Emerging Infectious Diseases Consortium
(NIH) [1-U54-AI-057153]
FX Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health (NIH), and Region V
"Great Lakes" Regional Center of Excellence in Biodefense and Emerging
Infectious Diseases Consortium (NIH Award 1-U54-AI-057153 to J.B.W. and
O.S.).
NR 38
TC 166
Z9 170
U1 2
U2 15
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 OCT 1
PY 2010
VL 202
IS 7
BP 1050
EP 1058
DI 10.1086/656043
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 651FR
UT WOS:000281912100009
PM 20726702
ER
PT J
AU Marshall, V
Martro, E
Labo, N
Ray, A
Wang, DA
Mbisa, G
Bagni, RK
Volfovsky, N
Casabona, J
Whitby, D
AF Marshall, Vickie
Martro, Elisa
Labo, Nazzarena
Ray, Alex
Wang, Dian
Mbisa, Georginia
Bagni, Rachel K.
Volfovsky, Natalia
Casabona, Jordi
Whitby, Denise
CA EURO-SHAKS Study Grp
TI Kaposi Sarcoma (KS)-Associated Herpesvirus MicroRNA Sequence Analysis
and KS Risk in a European AIDS-KS Case Control Study
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; SINGLE NUCLEOTIDE POLYMORPHISM;
HUMAN-HERPESVIRUS-8 INFECTION; ENCODED MICRORNAS; UNITED-STATES;
CANCER-RISK; IDENTIFICATION; RESPONSES; CELLS; IMMUNODEFICIENCY
AB Background. We recently identified polymorphisms in Kaposi sarcoma-associated herpesvirus (KSHV)-encoded microRNA (miRNA) sequences from clinical subjects. Here, we examine whether any of these may contribute to KS risk in a European AIDS-KS case-control study.
Methods. KSHV load in peripheral blood was determined by real-time quantitative polymerase chain reaction. Samples that had detectable viral loads were used to amplify the 2.8-kb miRNA encoding region plus a 646-bp fragment of the K12/T0.7 gene. Additionally, we characterized an 840-bp fragment of the K1 gene to determine KSHV subtypes.
Results. KSHV DNA was detected in peripheral blood mononuclear cells of 49.6% of case patients and 6.8% of controls, and viral loads tended to be higher in case patients. Sequences from the miRNA-encoding regions were conserved overall, but distinct polymorphisms were detected, some of which occurred in primary miRNAs, pre-miRNAs, or mature miRNAs.
Conclusions. Patients with KS were more likely to have detectable viral loads than were controls without disease. Despite high conservation in KSHV miRNA-encoded sequences, polymorphisms were observed, including some that have been reported elsewhere. Some polymorphisms could affect mature miRNA processing and appear to be associated with KS risk.
C1 [Marshall, Vickie; Labo, Nazzarena; Ray, Alex; Wang, Dian; Mbisa, Georginia; Whitby, Denise] NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21702 USA.
[Bagni, Rachel K.] NCI, Mol Detect Grp, Prot Express Lab, Adv Technol Program,SAIC Frederick, Frederick, MD 21702 USA.
[Volfovsky, Natalia] NCI, Adv Biomed Comp Ctr, Informat Syst Program, SAIC Frederick, Frederick, MD 21702 USA.
[Martro, Elisa] Hosp Badalona Germans Trias & Pujol, Microbiol Serv, Badalona, Spain.
[Casabona, Jordi] Hosp Badalona Germans Trias & Pujol, Dept Salut, Ctr Estudis Epidemiol HIV SIDS Catalunya, Badalona, Spain.
[Martro, Elisa] CIBER Epidemiol & Salud Publ, Madrid, Spain.
RP Whitby, D (reprint author), NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, POB B, Frederick, MD 21702 USA.
EM whitbyd@mail.nih.gov
RI Labo, Nazzarena/H-8655-2012; Gaya, Antonio/G-1726-2010; Martro,
Elisa/K-9688-2015;
OI Labo, Nazzarena/0000-0001-5953-4064; Gaya, Antonio/0000-0002-2200-5801;
Martro, Elisa/0000-0002-2867-6649; Ocana, Inma/0000-0003-3699-0790;
Casabona-Barbara, Jordi/0000-0003-4816-5536
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; DG XII of the European Commission (EURO-SHAKS)
FX National Cancer Institute, National Institutes of Health (contract no.
HHSN261200800001E), and DG XII of the European Commission (EURO-SHAKS).
NR 29
TC 14
Z9 14
U1 0
U2 3
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD OCT 1
PY 2010
VL 202
IS 7
BP 1126
EP 1135
DI 10.1086/656045
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 651FR
UT WOS:000281912100017
PM 20715927
ER
PT J
AU Kaler, SG
Liew, CJ
Donsante, A
Hicks, JD
Sato, S
Greenfield, JC
AF Kaler, Stephen G.
Liew, Clarissa J.
Donsante, Anthony
Hicks, Julia D.
Sato, Susumu
Greenfield, Jacquelyn C.
TI Molecular correlates of epilepsy in early diagnosed and treated Menkes
disease
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Article
ID EARLY COPPER THERAPY; HIPPOCAMPAL-NEURONS; HORN SYNDROME; MUTATION;
PLASMA
AB Epilepsy is a major feature of Menkes disease, an X-linked recessive infantile neurodegenerative disorder caused by mutations in ATP7A, which produces a copper-transporting ATPase. Three prior surveys indicated clinical seizures and electroencephalographic (EEG) abnormalities in a combined 27 of 29 (93%) symptomatic Menkes disease patients diagnosed at 2 months of age or older. To assess the influence of earlier, presymptomatic diagnosis and treatment on seizure semiology and brain electrical activity, we evaluated 71 EEGs in 24 Menkes disease patients who were diagnosed and treated with copper injections in early infancy (a parts per thousand currency sign6 weeks of age), and whose ATP7A mutations we determined. Clinical seizures were observed in only 12.5% (3/24) of these patients, although 46% (11/24) had at least one abnormal EEG tracing, including 50% of patients with large deletions in ATP7A, 50% of those with small deletions, 60% of those with nonsense mutations, and 57% of those with canonical splice junction mutations. In contrast, five patients with mutations shown to retain partial function, either via some correct RNA splicing or residual copper transport capacity, had neither clinical seizures nor EEG abnormalities. Our findings suggest that early diagnosis and treatment improve brain electrical activity and decrease seizure occurrence in classical Menkes disease irrespective of the precise molecular defect. Subjects with ATP7A mutations that retain some function seem particularly well protected by early intervention against the possibility of epilepsy.
C1 [Kaler, Stephen G.; Donsante, Anthony; Hicks, Julia D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD 20892 USA.
[Liew, Clarissa J.; Sato, Susumu; Greenfield, Jacquelyn C.] NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA.
RP Kaler, SG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bldg 10,Room 10N-313,10 Ctr Dr,MSC 1853, Bethesda, MD 20892 USA.
EM kalers@mail.nih.gov
FU NIH
FX This study was supported by the NIH intramural research program. We
thank the participating subjects and their parents, and gratefully
acknowledge Maryellen Rechen and the nursing staffs of the Pediatric
Inpatient, Day Hospital, and Outpatient units at the NIH Clinical Center
for their expert patient care.
NR 25
TC 25
Z9 27
U1 0
U2 0
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 OCT
PY 2010
VL 33
IS 5
BP 583
EP 589
DI 10.1007/s10545-010-9118-2
PG 7
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 655SP
UT WOS:000282270100016
PM 20652413
ER
PT J
AU Quevedo-Diaz, MA
Song, C
Xiong, YB
Chen, HY
Wahl, LM
Radulovic, S
Medvedev, AE
AF Quevedo-Diaz, Marco A.
Song, Chang
Xiong, Yanbao
Chen, Haiyan
Wahl, Larry M.
Radulovic, Suzana
Medvedev, Andrei E.
TI Involvement of TLR2 and TLR4 in cell responses to Rickettsia akari
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE innate immunity; Toll-like receptors; signal transduction; cell
activation; monocytes/ macrophages
ID TOLL-LIKE RECEPTOR; NF-KAPPA-B; RESPIRATORY SYNCYTIAL VIRUS;
PATTERN-RECOGNITION RECEPTOR; ENDOTOXIN TOLERANCE; SIGNAL-TRANSDUCTION;
GENE-EXPRESSION; CUTTING EDGE; ALVEOLAR MACROPHAGES; ENDOTHELIAL-CELLS
AB A better understanding of the pathogenesis of rickettsial disease requires elucidation of mechanisms governing host defense during infection. TLRs are primary sensors of microbial pathogens that activate innate immune cells, as well as initiate and orchestrate adaptive immune responses. However, the role of TLRs in rickettsia recognition and cell activation remains poorly understood. In this study, we examined the involvement of TLR2 and TLR4 in recognition of Rickettsia akari, a causative agent of rickettsialpox. Transfection-based complementation of TLR2/4-negative HEK293T cells with human TLR2 or TLR4 coexpressed with CD14 and MD-2 enabled I kappa B-alpha degradation, NF-kappa B reporter activation, and IL-8 expression in response to heat-killed (HK) R. akari. The presence of the R753Q TLR2 or D299G TLR4 polymorphisms significantly impaired the capacities of the respective TLRs to signal HK R. akari-mediated NF-kappa B reporter activation in HEK293T transfectants. Blocking Ab against TLR2 or TLR4 markedly inhibited TNF-alpha release from human monocytes stimulated with HK R. akari, and TNF-alpha secretion elicited by infection with live R. akari was reduced significantly only upon blocking of TLR2 and TLR4. Live and HK R. akari exerted phosphorylation of IRAK1 and p38 MAPK in 293/TLR4/MD-2 or 293/TLR2 stable cell lines, whereas only live bacteria elicited responses in TLR2/4-negative HEK293T cells. These data demonstrate that HK R. akari triggers cell activation via TLR2 or TLR4 and suggest use of additional TLRs and/or NLRs by live R. akari. J. Leukoc. Biol. 88: 675-685; 2010.
C1 [Quevedo-Diaz, Marco A.; Song, Chang; Xiong, Yanbao; Chen, Haiyan; Radulovic, Suzana; Medvedev, Andrei E.] Univ Maryland, Dept Microbiol & Immunol, Sch Med, Baltimore, MD 21201 USA.
[Wahl, Larry M.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Medvedev, AE (reprint author), Univ Maryland, Dept Microbiol & Immunol, Sch Med, 685 W Baltimore St,HSF I Bldg,Rm 380, Baltimore, MD 21201 USA.
EM amedvedev@som.umaryland.edu
FU NIH [R21 AI067468]; University of Maryland, Baltimore (UMB)-University
of Maryland College Park (UMCP) Intramural NIH
FX This work was supported by NIH grant R21 AI067468 and University of
Maryland, Baltimore (UMB)-University of Maryland College Park (UMCP)
Intramural NIH seed grant (to A. E. M.). We are thankful to Dr. Douglas
T. Golenbock and Katherine Fitzgerald (University of Massachusetts
School of Medicine) for providing us with expression vectors and cell
lines.
NR 73
TC 13
Z9 13
U1 0
U2 5
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD OCT
PY 2010
VL 88
IS 4
BP 675
EP 685
DI 10.1189/jlb.1009674
PG 11
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 692ZW
UT WOS:000285195400009
PM 20616112
ER
PT J
AU Rodriguez, IR
Larrayoz, IM
AF Rodriguez, Ignacio R.
Larrayoz, Ignacio M.
TI Cholesterol oxidation in the retina: implications of 7KCh formation in
chronic inflammation and age-related macular degeneration
SO JOURNAL OF LIPID RESEARCH
LA English
DT Review
DE 7-ketocholesterol; cytokines; oxysterols
ID LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE-CELLS; OXYSTEROL-BINDING-PROTEIN;
ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; LIVER-X-RECEPTORS;
HUMAN ATHEROSCLEROTIC LESIONS; SINGLET OXYGEN INTERMEDIACY; OXIDIZED
LDL; STEROL 27-HYDROXYLASE
AB This review will discuss the formation and potential implications of 7-ketocholesterol (7KCh) in the retina. 7KCh is a proinflammatory oxysterol known to be present in high amounts in oxidized LDL deposits associated with atheromatous plaques. 7KCh is generated in situ in these lipoprotein deposits where it can accumulate and reach very high concentrations. In normal primate retina, 7KCh has been found associated with lipoprotein deposits in the choriocapillaris, Bruch's membrane, and the retinal pigment epithelium (RPE). In photodamaged rats, 7KCh has been found in the neural retina in areas of high mitochondrial content, ganglion cells, photoreceptor inner segments and synapses, and the RPE. Intermediates found by LCMS indicate 7KCh is formed via a free radical-mediated mechanism catalyzed by iron. 7KCh seems to activate several kinase signaling pathways that work via nuclear factor kappa B and cause the induction of vascular endothelial growth factor, interleukin (IL)-6, and IL-8. There seems to be little evidence of 7KCh metabolism in the retina, although some form of efflux mechanism may be active. The chronic mode of formation and the potent inflammatory properties of 7KCh indicate it may be an "age-related" risk factor in aging diseases such as atherosclerosis, Alzheimer's, and age-related macular degeneration.-Rodriguez, I. R., and I. M. Larrayoz. Cholesterol oxidation in the retina: implications of 7-KCh formation in chronic inflammation and age-related macular degeneration. J. Lipid Res. 2010. 51:2847-2862.
C1 [Rodriguez, Ignacio R.; Larrayoz, Ignacio M.] NEI, Mech Retinal Dis Sect, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA.
RP Rodriguez, IR (reprint author), NEI, Mech Retinal Dis Sect, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA.
EM rodriguezi@nei.nih.gov
RI Larrayoz, Ignacio/I-5613-2012
OI Larrayoz, Ignacio/0000-0003-1629-152X
NR 147
TC 56
Z9 56
U1 2
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
J9 J LIPID RES
JI J. Lipid Res.
PD OCT
PY 2010
VL 51
IS 10
BP 2847
EP 2862
DI 10.1194/jlr.R004820
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 649GS
UT WOS:000281756800001
PM 20567027
ER
PT J
AU Gao, F
Kiesewetter, D
Chang, L
Rapoport, SI
Igarashi, M
AF Gao, Fei
Kiesewetter, Dale
Chang, Lisa
Rapoport, Stanley I.
Igarashi, Miki
TI Quantifying conversion of linoleic to arachidonic and other n-6
polyunsaturated fatty acids in unanesthetized rats
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE liver; diet; modeling; kinetics
ID LOW-DENSITY LIPOPROTEIN; DOCOSAHEXAENOIC ACID; BRAIN PHOSPHOLIPIDS;
GENE-TRANSCRIPTION; HALF-LIVES; ADULT RATS; METABOLISM; ALPHA; DIET;
BIOSYNTHESIS
AB Isotope feeding studies report a wide range of conversion fractions of dietary shorter-chain polyunsaturated fatty acids (PUFAs) to long-chain PUFAs, which limits assessing nutritional requirements and organ effects of arachidonic (AA, 20:4n-6) and docosahexaenoic (DHA, 22:6n-3) acids. In this study, whole-body (largely liver) steady-state conversion coefficients and rates of circulating unesterified linoleic acid (LA, 18:2n-6) to esterified AA and other elongated n-6 PUFAs were quantified directly using operational equations, in unanesthetized adult rats on a high-DHA but AA-free diet, using 2 h of intravenous [U-(13)C] LA infusion. Unesterified LA was converted to esterified LA in plasma at a greater rate than to esterified gamma-linolenic (gamma-LNA, 18:3n-6), eicosatrienoic acid (ETA, 20:3n-6), or AA. The steady-state whole-body synthesis-secretion (conversion) coefficient k(i)(*) to AA equaled 5.4 x 10(-3) min(-1), while the conversion rate (coefficient x concentration) equaled 16.1 mu mol/day. This rate exceeds the reported brain AA consumption rate by 27-fold. As brain and heart cannot synthesize significant AA from circulating LA, liver synthesis is necessary to maintain their homeostatic AA concentrations in the absence of dietary AA. The heavy-isotope intravenous infusion method could be used to quantify steady-state liver synthesis-secretion of AA from LA under different conditions in rodents and in humans.-Gao, F., D. Kiesewetter, L. Chang, S. I. Rapoport, and M. Igarashi. Quantifying conversion of linoleic to arachidonic and other n-6 polyunsaturated fatty acids in unanesthetized rats. J Lipid Res. 2010. 51:2940-2946.
C1 [Gao, Fei; Chang, Lisa; Rapoport, Stanley I.; Igarashi, Miki] Natl Inst Biomed Imaging & Bioengn, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Kiesewetter, Dale] Natl Inst Biomed Imaging & Bioengn, NIA, NIH, Bethesda, MD USA.
[Kiesewetter, Dale] Natl Inst Biomed Imaging & Bioengn, Positron Emiss Tomog Radiochem Grp, NIH, Bethesda, MD USA.
RP Gao, F (reprint author), Natl Inst Biomed Imaging & Bioengn, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
EM gaof@mail.nih.gov
FU National Institute on Aging; National Institute of Biomedical Imaging
and Bioengineering of the National Institutes of Health
FX This work was supported entirely by the Intramural Research Programs of
the National Institute on Aging and the National Institute of Biomedical
Imaging and Bioengineering of the National Institutes of Health. Its
contents are solely the responsibility of the authors and do not
necessarily represent the official views of the National Institutes of
Health. The authors have no conflict of interest with regard to this
work.
NR 48
TC 9
Z9 9
U1 1
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
J9 J LIPID RES
JI J. Lipid Res.
PD OCT
PY 2010
VL 51
IS 10
BP 2940
EP 2946
DI 10.1194/jlr.M005595
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 649GS
UT WOS:000281756800007
PM 20622136
ER
PT J
AU Bronte-Tinkew, J
Scott, ME
Lilja, E
AF Bronte-Tinkew, Jacinta
Scott, Mindy E.
Lilja, Emily
TI Single Custodial Fathers' Involvement and Parenting: Implications for
Outcomes in Emerging Adulthood
SO JOURNAL OF MARRIAGE AND FAMILY
LA English
DT Article
DE adolescents; emerging adults; parental involvement; parenting styles;
single-parent families
ID ADOLESCENT RISK BEHAVIORS; FAMILY-STRUCTURE; LIFE-COURSE; YOUNG-ADULT;
PATERNAL INVOLVEMENT; ACADEMIC-ACHIEVEMENT; INTACT FAMILIES;
SELF-ESTEEM; CHILD; COHABITATION
AB Using a sample of 3,977 youths from the National Longitudinal Survey of Youth (NLSY97), this study examines the unique characteristics of single-custodial-father families with adolescents and the effects of single fathers' involvement and parenting on outcomes in emerging adulthood. Findings suggest that single-custodial-father families are distinct from single-mother and 2-biological-parent families in terms of sociodemographic characteristics, parenting styles, and involvement. Parenting styles and involvement mediate the differences between single-father families and 2-parent families in terms of high school completion and disconnectedness and partially mediate differences for single-custodial-father families with a partner. Family and sociodemographic characteristics are also associated with being disconnected for adolescents residing with a cohabiting custodial father.
C1 [Bronte-Tinkew, Jacinta] NIH, Ctr Sci Review, Bethesda, MD 20892 USA.
[Scott, Mindy E.; Lilja, Emily] Child Trends, Washington, DC 20008 USA.
RP Bronte-Tinkew, J (reprint author), NIH, Ctr Sci Review, 6701 Rockledge Dr,Room 3164,MSC 7770, Bethesda, MD 20892 USA.
EM jacinta.bronte-tinkew@nih.gov; mscott@childtrends.org;
elilja@childtrends.org
NR 62
TC 12
Z9 12
U1 1
U2 24
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-2445
J9 J MARRIAGE FAM
JI J. Marriage Fam.
PD OCT
PY 2010
VL 72
IS 5
BP 1107
EP 1127
DI 10.1111/j.1741-3737.2010.00753.x
PG 21
WC Family Studies; Sociology
SC Family Studies; Sociology
GA 656YD
UT WOS:000282376100005
ER
PT J
AU Jahouh, F
Saksena, R
Aiello, D
Napoli, A
Sindona, G
Kovac, P
Banoub, JH
AF Jahouh, Farid
Saksena, Rina
Aiello, Donatella
Napoli, Anna
Sindona, Giovanni
Kovac, Pavol
Banoub, Joseph H.
TI Glycation sites in neoglycoglycoconjugates from the terminal
monosaccharide antigen of the O-PS of Vibrio cholerae O1, serotype
Ogawa, and BSA revealed by matrix-assisted laser desorption-ionization
tandem mass spectrometry
SO JOURNAL OF MASS SPECTROMETRY
LA English
DT Article
DE MALDI-TOF/TOF-MS; MALDI-CID-TOF-TOF-MS/MS; neoglycoconjugate vaccine;
hapten; BSA; protein carrier
ID BOVINE SERUM-ALBUMIN; CONJUGATE VACCINES; LIPOPOLYSACCHARIDE; PROTEINS;
INABA; POLYSACCHARIDE; NOMENCLATURE; SACCHARIDE; FRAGMENTS; CARRIER
AB We present the MALDI-TOF/TOF-MS analyses of various hapten - bovine serum albumin (BSA) neoglycoconjugates obtained by squaric acid chemistry coupling of the spacer-equipped, terminal monosaccharide of the O-specific polysaccharide of Vibrio cholerae O1, serotype Ogawa, to BSA. These analyses allowed not only to calculate the molecular masses of the hapten-BSA neoglycoconjugates with different hapten-BSA ratios (4.3, 6.6 and 13.2) but, more importantly, also to localize the covalent linkages (conjugation sites) between the hapten and the carrier protein. Determination of the site of glycation was based on comparison of the MALDI-TOF/TOF-MS analysis of the peptides resulting from the digestion of BSA with similar data resulting from the digestion of BSA glycoconjugates, followed by sequencing by MALDI-TOF/TOF-MS/MS of the glycated peptides. The product-ion scans of the protonated molecules were carried out with a MALDI-TOF/TOF-MS/MS tandem mass spectrometer equipped with a high-collision energy cell. The high-energy collision-induced dissociation (CID) spectra afforded product ions formed by fragmentation of the carbohydrate hapten and amino acid sequences conjugated with fragments of the carbohydrate hapten. We were able to identify three conjugation sites on lysine residues (Lys235, Lys437 and Lys455). It was shown that these lysine residues are very reactive and bind lysine specific reagents. We presume that these Lys residues belong to those that are considered to be sterically more accessible on the surface of the tridimensional structure. The identification of the y-series product ions was very useful for the sequencing of various peptides. The series of a- and b-product ions confirmed the sequence of the conjugated peptides. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Banoub, Joseph H.] Dept Fisheries & Oceans Canada, Sci Branch, Special Projects, St John, NF A1C 5X1, Canada.
[Jahouh, Farid; Banoub, Joseph H.] Mem Univ Newfoundland, Dept Chem, St John, NF A1B 3X7, Canada.
[Saksena, Rina; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
[Aiello, Donatella; Napoli, Anna; Sindona, Giovanni] Univ Calabria, Dept Chem, Arcavacata Di Rende, CS, Italy.
RP Banoub, JH (reprint author), Dept Fisheries & Oceans Canada, Sci Branch, Special Projects, St John, NF A1C 5X1, Canada.
EM banoubjo@dfo-mpo.gc.ca
RI NAPOLI, ANNA/B-5250-2011;
OI NAPOLI, ANNA/0000-0002-7004-7643; sindona, giovanni/0000-0002-5623-5795
NR 34
TC 10
Z9 10
U1 2
U2 9
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1076-5174
J9 J MASS SPECTROM
JI J. Mass Spectrom.
PD OCT
PY 2010
VL 45
IS 10
BP 1148
EP 1159
DI 10.1002/jms.1796
PG 12
WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA 672TQ
UT WOS:000283610200008
PM 20860010
ER
PT J
AU Soto, E
Romero, R
Vaisbuch, E
Erez, O
Mazaki-Tovi, S
Kusanovic, JP
Dong, Z
Chaiworapongsa, T
Yeo, L
Mittal, P
Hassan, SS
AF Soto, Eleazar
Romero, Roberto
Vaisbuch, Edi
Erez, Offer
Mazaki-Tovi, Shali
Kusanovic, Juan Pedro
Dong, Zhong
Chaiworapongsa, Tinnakorn
Yeo, Lami
Mittal, Pooja
Hassan, Sonia S.
TI Fragment Bb: evidence for activation of the alternative pathway of the
complement system in pregnant women with acute pyelonephritis
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Acute respiratory distress syndrome; asymptomatic bacteriuria;
inflammation; innate immunity; pregnancy; Th1/Th2; urinary tract
infection
ID INFLAMMATORY RESPONSE SYNDROME; FACTOR-H POLYMORPHISM; INNATE
IMMUNE-SYSTEM; MACULAR DEGENERATION; COMPLICATING PREGNANCY; ARTHRITIS;
C5A; LEUKOCYTES; MONOCYTES; SEPSIS
AB Objective. Pyelonephritis during pregnancy is associated with a more severe course than in the non-pregnant state. This has been attributed to an increased susceptibility of pregnant women to microbial products. The complement system is part of innate immunity and its alternative pathway is activated mainly by microorganisms. The purpose of this study was to determine if activation of the alternative pathway of the complement system (determined by maternal fragment Bb concentrations) occurs in pregnant women with acute pyelonephritis.
Methods. This cross-sectional study included the following groups: (1) normal pregnant women (n = 62) and (2) pregnant women with pyelonephritis (n-38). Maternal plasma fragment Bb concentrations were determined by ELISA. Nonparametric statistics were used for analyses.
Results. (1) Pregnant women with pyelonephritis had a higher median plasma concentration of fragment Bb than those with a normal pregnancy (1.3 mu g/ml, IQR: 1.1-1.9 vs. 0.8 mu g/ml, IQR: 0.7-0.9; p<50.001); (2) No significant differences were observed in the median maternal plasma concentration of fragment Bb between pregnant women with pyelonephritis who had a positive blood culture and those with a negative blood culture (1.4 mu g/ml, IQR: 1.1-3.5 vs. 1.3 mu g/ml, IQR: 1.1-1.9; p = 0.2).
Conclusions. Pregnant women with acute pyelonephritis have evidence of activation of the alternative pathway of the complement system, regardless of the presence or absence of a positive blood culture.
C1 [Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA.
[Soto, Eleazar; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Yeo, Lami; Mittal, Pooja; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI 48201 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Soto, Eleazar; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Dong, Zhong; Chaiworapongsa, Tinnakorn; Yeo, Lami; Mittal, Pooja; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
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 by the Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.
NR 69
TC 8
Z9 8
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 OCT
PY 2010
VL 23
IS 10
BP 1085
EP 1090
DI 10.3109/14767051003649870
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 653HW
UT WOS:000282081100002
PM 20218820
ER
PT J
AU Cruciani, L
Romero, R
Vaisbuch, E
Kusanovic, JP
Chaiworapongsa, T
Mazaki-Tovi, S
Dong, Z
Kim, SK
Ogge, G
Yeo, L
Mittal, P
Hassan, SS
AF Cruciani, Laura
Romero, Roberto
Vaisbuch, Edi
Kusanovic, Juan Pedro
Chaiworapongsa, Tinnakorn
Mazaki-Tovi, Shali
Dong, Zhong
Kim, Sun Kwon
Ogge, Giovanna
Yeo, Lami
Mittal, Pooja
Hassan, Sonia S.
TI Pentraxin 3 in maternal circulation: An association with preterm labor
and preterm PROM, but not with intra-amniotic infection/inflammation
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Amniocentesis; cytokines; MIAC; microbial invasion of the amniotic
cavity; pattern recognition receptors; preterm delivery; preterm
prelabor rupture of membranes; PPROM; pregnancy
ID C-REACTIVE PROTEIN; AMYLOID-P COMPONENT; TUMOR-NECROSIS-FACTOR;
ACUTE-PHASE PROTEINS; RECOGNITION RECEPTOR PTX3; HUMORAL INNATE
IMMUNITY; NORMAL HUMAN-PREGNANCY; LONG PENTRAXIN; DENDRITIC CELLS;
METABOLIC CHARACTERISTICS
AB Objective. Pentraxin 3 (PTX3) is an acute-phase protein that has an important role in the regulation of the innate immune response. The aim of this study was to determine if maternal plasma PTX3 concentration changes in the presence of intra-amniotic infection and/or inflammation (IAI) in women with preterm labor (PTL) and intact membranes, as well as those with preterm prelabor rupture of membranes (preterm PROM).
Study design. This cross-sectional study included women in the following groups: (1) nonpregnant (n = 40); (2) uncomplicated pregnancies in the first (n 22), second (n 22) or third trimester (n 71, including 50 women at term not in labor); (3) uncomplicated pregnancies at term with spontaneous labor (n 49); (4) PTL and intact membranes who delivered at term (n 49); (5) PTL without IAI who delivered preterm (n 26); (6) PTL with IAI (n 65); (7) preterm PROM without IAI (n 25); and (8) preterm PROM with IAI (n 77). Maternal plasma PTX3 concentrations were determined by ELISA.
Results. (1) Maternal plasma PTX3 concentrations increased with advancing gestational age (r = 0.62, p < 50.001); (2) women at term with spontaneous labor had a higher median plasma PTX3 concentration than those at term not in labor (8.29 ng/ml vs. 5.98 ng/ml, p = 0.013); (3) patients with an episode of PTL, regardless of the presence or absence of IAI and whether these patients delivered preterm or at term had a higher median plasma PTX3 concentration than normal pregnant women (p<0.001 for all comparisons); (4) similarly, patients with preterm PROM, with or without IAI had a higher median plasma PTX3 concentration than normal pregnant women (p<0.001 for both comparisons); and (5) among patients with PTL and those with preterm PROM, IAI was not associated with significant changes in the median maternal plasma PTX3 concentrations.
Conclusions. The maternal plasma PTX3 concentration increases with advancing gestational age and is significantly elevated during labor at term and in the presence of spontaneous preterm labor or preterm PROM. These findings could not be explained by the presence of IAI, suggesting that the increased PTX3 concentration is part of the physiologic or pathologic activation of the pro-inflammatory response in the maternal circulation during the process of labor at term or preterm.
C1 [Romero, Roberto] Wayne State Univ, Perinatol Res Branch, Hutzel Womens Hosp, NICHD,NIH,DHHS, Detroit, MI 48201 USA.
[Cruciani, Laura; Romero, Roberto; Vaisbuch, Edi; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Mazaki-Tovi, Shali; Dong, Zhong; Kim, Sun Kwon; Ogge, Giovanna; Yeo, Lami; Mittal, Pooja; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Romero, Roberto; Vaisbuch, Edi; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Mazaki-Tovi, Shali; Yeo, Lami; Mittal, Pooja; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, Hutzel Womens Hosp, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
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 by the Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.
NR 79
TC 12
Z9 12
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 OCT
PY 2010
VL 23
IS 10
BP 1097
EP 1105
DI 10.3109/14767050903551509
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 653HW
UT WOS:000282081100004
PM 20121391
ER
PT J
AU Mazaki-Tovi, S
Vaisbuch, E
Romero, R
Kusanovic, JP
Chaiworapongsa, T
Kim, SK
Nhan-Chang, CL
Gomez, R
Savasan, ZA
Madan, I
Yoon, BH
Yeo, L
Mittal, P
Ogge, G
Gonzalez, JM
Hassan, SS
AF Mazaki-Tovi, Shali
Vaisbuch, Edi
Romero, Roberto
Kusanovic, Juan Pedro
Chaiworapongsa, Tinnakorn
Kim, Sun Kwon
Nhan-Chang, Chia-Ling
Gomez, Ricardo
Savasan, Zeynep Alpay
Madan, Ichchha
Yoon, Bo Hyun
Yeo, Lami
Mittal, Pooja
Ogge, Giovanna
Gonzalez, Juan M.
Hassan, Sonia S.
TI Maternal and neonatal circulating visfatin concentrations in patients
with pre-eclampsia and a small-for-gestational age neonate
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Visfatin; adipokines; cytokine; pregnancy; foetal growth restriction;
appropriate-for-gestational age; umbilical cord blood
ID COLONY-ENHANCING FACTOR; SERUM ADIPONECTIN MULTIMERS; HUMAN FETAL
MEMBRANES; INTRAUTERINE GROWTH RESTRICTION; FACTOR RECEPTOR-1
CONCENTRATION; TYPE-2 DIABETES-MELLITUS; NORMAL-PREGNANCY; SOLUBLE
ENDOGLIN; PRETERM LABOR; BIRTH-WEIGHT
AB Objective. Maternal circulating visfatin concentrations are higher in patients with a small-for-gestational-age (SGA) neonate than in those who delivered an appropriate-for-gestational age (AGA) neonate or in those with pre-eclampsia. It has been proposed that enhanced transfer of visfatin from the foetal to maternal circulation may account for the high concentrations of maternal visfatin observed in patients with an SGA neonate. The aims of this study were: (1) to determine whether cord blood visfatin concentrations differ between normal neonates, SGA neonates and newborns of pre-eclamptic mothers; and (2) to assess the relationship between maternal and foetal circulating visfatin concentrations in patients with an SGA neonate and those with pre-eclampsia.
Study design. This cross-sectional study included 88 pregnant women and their neonates, as well as 22 preterm neonates in the following groups: (1) 44 normal pregnant women at term and their AGA neonates; (2) 22 normotensive pregnant women and their SGA neonates; (3) 22 women with pre-eclampsia and their neonates; and (4) 22 preterm neonates delivered following spontaneous preterm labour without funisitis or histologic chorioamnionitis, matched for gestational age with infants of pre-eclamptic mothers. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Nonparametric statistics were used for analyses.
Results. (1) The median visfatin concentration was lower in umbilical cord blood than in maternal circulation, in normal pregnancy, SGA and pre-eclampsia groups (p<0.001 for all comparisons); (2) the median cord blood visfatin concentrations did not differ significantly between term AGA or SGA neonates, infants of mothers with pre-eclampsia and their gestational-age-matched preterm AGA neonates; (3) maternal and cord blood visfatin concentrations correlated only in the normal term group (r=0.48, p=0.04).
Conclusion. Circulating visfatin concentrations are lower in the foetal than in the maternal circulation and did not significantly differ between the study groups. Thus, it is unlikely that the foetal circulation is the source of the high maternal visfatin concentrations reported in patients with an SGA neonate.
C1 [Mazaki-Tovi, Shali; Vaisbuch, Edi; Romero, Roberto; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Nhan-Chang, Chia-Ling; Savasan, Zeynep Alpay; Madan, Ichchha; Yeo, Lami; Mittal, Pooja; Ogge, Giovanna; Gonzalez, Juan M.; Hassan, Sonia S.] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Detroit, MI 48201 USA.
[Mazaki-Tovi, Shali; Vaisbuch, Edi; Romero, Roberto; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Nhan-Chang, Chia-Ling; Savasan, Zeynep Alpay; Madan, Ichchha; Yeo, Lami; Mittal, Pooja; Ogge, Giovanna; Gonzalez, Juan M.; Hassan, Sonia S.] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Bethesda, MD USA.
[Mazaki-Tovi, Shali; Vaisbuch, Edi; Romero, Roberto; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Nhan-Chang, Chia-Ling; Savasan, Zeynep Alpay; Madan, Ichchha; Yeo, Lami; Mittal, Pooja; Gonzalez, Juan M.; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Gomez, Ricardo] Pontificia Univ Catolica Chile, Sotero Rio Hosp, Dept Obstet & Gynecol, CEDIP Ctr Perinatal Diag & Res, Santiago, Chile.
[Yoon, Bo Hyun] Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea.
RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Box 4,3990 John R, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
RI Ogge, Giovanna/G-6109-2011; Yoon, Bo Hyun/H-6344-2011;
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Perinatology Research Branch, Division of Intramural Research Program of
the 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 Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, NIH, DHHS.
NR 108
TC 17
Z9 17
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 OCT
PY 2010
VL 23
IS 10
BP 1119
EP 1128
DI 10.3109/14767050903572190
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 653HW
UT WOS:000282081100007
PM 20121389
ER
PT J
AU Jones, NL
Peiffer, AM
Lambros, A
Guthold, M
Johnson, AD
Tytell, M
Ronca, AE
Eldridge, JC
AF Jones, Nancy L.
Peiffer, Ann M.
Lambros, Ann
Guthold, Martin
Johnson, A. Daniel
Tytell, Michael
Ronca, April E.
Eldridge, J. Charles
TI Developing a problem-based learning (PBL) curriculum for professionalism
and scientific integrity training for biomedical graduate students
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
ID RESPONSIBLE CONDUCT; EDUCATION; ETHICS
AB A multidisciplinary faculty committee designed a curriculum to shape biomedical graduate students into researchers with a high commitment to professionalism and social responsibility and to provide students with tools to navigate complex, rapidly evolving academic and societal environments with a strong ethical commitment. The curriculum used problem-based learning (PBL), because it is active and learner-centred and focuses on skill and process development. Two courses were developed: Scientific Professionalism: Scientific Integrity addressed discipline-specific and broad professional norms and obligations for the ethical practice of science and responsible conduct of research (RCR). Scientific Professionalism: Bioethics and Social Responsibility focused on current ethical and bioethical issues within the scientific profession, and implications of research for society. Each small-group session examined case scenarios that included: (1) learning objectives for professional norms and obligations; (2) key ethical issues and philosophies within each topic area; (3) one or more of the RCR instructional areas; and (4) at least one type of moral reflection. Cases emphasised professional standards, obligations and underlying philosophies for the ethical practice of science, competing interests of stakeholders and oversight of science (internal and external). To our knowledge, this is the first use of a longitudinal, multi-semester PBL course to teach scientific integrity and professionalism. Both faculty and students endorsed the active learning approach for these topics, in contrast to a compliance-based approach that emphasises learning rules and regulations.
C1 [Jones, Nancy L.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC 27106 USA.
[Peiffer, Ann M.] Wake Forest Univ Hlth Sci, Dept Radiol, Winston Salem, NC USA.
[Lambros, Ann] Wake Forest Univ Hlth Sci, Ctr Excellence Res Teaching & Learning, Winston Salem, NC USA.
[Lambros, Ann] Wake Forest Univ Hlth Sci, Dept Social Sci & Hlth Policy, Winston Salem, NC USA.
[Guthold, Martin] Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA.
Wake Forest Univ, Dept Biol, Winston Salem, NC 27109 USA.
[Tytell, Michael] Wake Forest Univ Hlth Sci, Dept Neurobiol & Anat, Winston Salem, NC USA.
[Ronca, April E.] Wake Forest Univ Hlth Sci, Dept Obstet & Gynecol, Winston Salem, NC USA.
[Eldridge, J. Charles] Wake Forest Univ Hlth Sci, Dept Physiol & Pharmacol, Winston Salem, NC USA.
RP Jones, NL (reprint author), NIAID, SPEB, OSPFM, NIH,DHHS, Bldg 31,7A46F,MSC 2520, Bethesda, MD 20892 USA.
EM jonesna@niaid.nih.gov
FU National Science Foundation [NSF 0530023]
FX This project was supported by NSF 0530023 from the National Science
Foundation (JCE, principal investigator).
NR 29
TC 11
Z9 11
U1 4
U2 24
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
J9 J MED ETHICS
JI J. Med. Ethics
PD OCT
PY 2010
VL 36
IS 10
BP 614
EP 619
DI 10.1136/jme.2009.035220
PG 6
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 655VI
UT WOS:000282282400008
PM 20797979
ER
PT J
AU Jones, NL
Peiffer, AM
Lambros, A
Eldridge, JC
AF Jones, Nancy L.
Peiffer, Ann M.
Lambros, Ann
Eldridge, J. Charles
TI Problem-based learning for professionalism and scientific integrity
training of biomedical graduate students: process evaluation
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
ID RESPONSIBLE CONDUCT; ETHICS; PERCEPTIONS; INSTRUCTION; EDUCATION
AB Objective We conducted a process evaluation to (a) assess the effectiveness of a new problem-based learning curriculum designed to teach professionalism and scientific integrity to biomedical graduate students and (b) modify the course to enhance its relevance and effectiveness. The content presented realistic cases and issues in the practice of science, to promote skill development and to acculturate students to professional norms of science.
Method We used 5-step Likert-scaled questions, open-ended questions, and interviews of students and facilitators to assess curricular effectiveness.
Results Both facilitators and students perceived course objectives were achieved. For example, respondents preferred active learning over lectures; both faculty and students perceived that the curriculum increased their understanding of norms, role obligations and responsibilities of professional scientists. They also reported an increased ability to identify ethical situations and felt that they had developed skills in moral reasoning and effective group work.
Conclusions These data helped to improve course implementation and instructional material. For example, to correct a negative perception that this was an 'ethics' course, we redesigned case debriefing activities to reinforce learning objectives and important skills. We refined cases to be more engaging and relevant for students, and gave facilitators more specific training and resources for each case. The problem-based learning small group strategy can stimulate an environment whereby participants are more aware of ethical implications of science, and increase their socialisation and open communication about professional behaviour.
C1 [Jones, Nancy L.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC USA.
[Jones, Nancy L.] Trinity Int Univ, Dept Bioeth, Deerfield, IL USA.
[Peiffer, Ann M.] Wake Forest Univ Hlth Sci, Dept Radiol, Winston Salem, NC USA.
[Lambros, Ann] Wake Forest Univ Hlth Sci, Ctr Excellence Res Teaching & Learning Social Sci, Winston Salem, NC USA.
[Eldridge, J. Charles] Wake Forest Univ Hlth Sci, Dept Physiol & Pharmacol, Winston Salem, NC USA.
RP Jones, NL (reprint author), NIAID, SPEB, OSPFM, NIH,DHHS, Bldg 31,7A46F,MSC 2520, Bethesda, MD 20892 USA.
EM jonesna@niaid.nih.gov
FU National Science Foundation,Wilson Boulevard, Arlington, Virginia, USA;
NSF [0530023]
FX This project was supported by NSF 0530023 (JCE, principal investigator),
The National Science Foundation, 4201 Wilson Boulevard, Arlington,
Virginia 22230, USA
NR 19
TC 7
Z9 8
U1 2
U2 14
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
J9 J MED ETHICS
JI J. Med. Ethics
PD OCT
PY 2010
VL 36
IS 10
BP 620
EP 626
DI 10.1136/jme.2009.035238
PG 7
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 655VI
UT WOS:000282282400009
PM 20663754
ER
PT J
AU Miller, FG
Truog, RD
AF Miller, Franklin G.
Truog, Robert D.
TI Decapitation and the definition of death
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
ID BRAIN-DEATH
AB Although established in the law and current practice, the determination of death according to neurological criteria continues to be controversial. Some scholars have advocated return to the traditional circulatory and respiratory criteria for determining death because individuals diagnosed as 'brain dead' display an extensive range of integrated biological functioning with the aid of mechanical ventilation. Others have attempted to refute this stance by appealing to the analogy between decapitation and brain death. Since a decapitated animal is obviously dead, and 'brain death' represents physiological decapitation, brain dead individuals must be dead. In this article we refute this 'decapitation gambit.' We argue that decapitated animals are not necessarily dead, and that, moreover, the analogy between decapitation and the clinical syndrome of brain death is flawed.
C1 [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
[Truog, Robert D.] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
FU Clinical Center, NIH
FX This research was supported in part by the Intramural Research Program
of the Clinical Center, NIH.
NR 15
TC 8
Z9 8
U1 0
U2 6
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
J9 J MED ETHICS
JI J. Med. Ethics
PD OCT
PY 2010
VL 36
IS 10
BP 632
EP 634
DI 10.1136/jme.2009.035196
PG 3
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 655VI
UT WOS:000282282400011
PM 20650913
ER
PT J
AU Pangilinan, F
Mitchell, A
VanderMeer, J
Molloy, AM
Troendle, J
Conley, M
Kirke, PN
Sutton, M
Sequeira, JM
Quadros, EV
Scott, JM
Mills, JL
Brody, LC
AF Pangilinan, F.
Mitchell, A.
VanderMeer, J.
Molloy, A. M.
Troendle, J.
Conley, M.
Kirke, P. N.
Sutton, M.
Sequeira, J. M.
Quadros, E. V.
Scott, J. M.
Mills, J. L.
Brody, L. C.
TI Transcobalamin II receptor polymorphisms are associated with increased
risk for neural tube defects
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID MATERNAL VITAMIN-B-12 STATUS; AMNIOTIC-FLUID; SPINA-BIFIDA; HOMOCYSTEINE
REMETHYLATION; HAPLOTYPE RECONSTRUCTION; IRISH POPULATION;
BIRTH-DEFECTS; GENETIC RISK; FOLATE; REDUCTASE
AB Objective Women who have low cobalamin (vitamin B(12)) levels are at increased risk for having children with neural tube defects (NTDs). The transcobalamin II receptor (TCbIR) mediates uptake of cobalamin into cells. Inherited variants in the TCbIR gene as NTD risk factors were evaluated.
Methods Case-control and family-based tests of association were used to screen common variation in TCbIR as genetic risk factors for NTDs in a large Irish group. A confirmatory group of NTD triads was used to test positive findings.
Results 2 tightly linked variants associated with NTDs in a recessive model were found: TCbIR rs2336573 (G220R; p(corr)=0.0080, corrected for multiple hypothesis testing) and TCbIR rs9426 (p(corr)=0.0279). These variants were also associated with NTDs in a family-based test before multiple test correction (log-linear analysis of a recessive model: rs2336573 (G220R; RR=6.59, p=0.0037) and rs9426 (RR=6.71, p=0.0035)). A copy number variant distal to TCbIR and two previously unreported exonic insertion-deletion polymorphisms were described.
Conclusions TCbIR rs2336573 (G220R) and TCbIR rs9426 represent a significant risk factor in NTD cases in the Irish population. The homozygous risk genotype was not detected in nearly 1000 controls, indicating that this NTD risk factor may be of low frequency and high penetrance. 9 other variants are in perfect linkage disequilibrium with the associated single nucleotide polymorphisms. Additional work is required to identify the disease-causing variant. Our data suggest that variation in TCbIR plays a role in NTD risk and that these variants may modulate cobalamin metabolism.
C1 [Pangilinan, F.; Mitchell, A.; VanderMeer, J.; Brody, L. C.] NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, Bethesda, MD 20892 USA.
[Molloy, A. M.] Trinity Coll Dublin, Dept Clin Med, Dublin, Ireland.
[Troendle, J.; Conley, M.; Mills, J. L.] Eunice Kennedy Shriver NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Kirke, P. N.; Sutton, M.] Hlth Res Board, Child Hlth Epidemiol Unit, Dublin, Ireland.
[Sequeira, J. M.; Quadros, E. V.] SUNY Downstate Med Ctr, Dept Med, Brooklyn, NY USA.
[Sequeira, J. M.; Quadros, E. V.] SUNY Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY USA.
[Scott, J. M.] Trinity Coll Dublin, Dept Biochem, Dublin, Ireland.
RP Brody, LC (reprint author), NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, Room 5306,Bldg 50,50 S Dr,MSC 8004, Bethesda, MD 20892 USA.
EM lbrody@helix.nih.gov
OI Molloy, Anne/0000-0002-1688-9049
FU National Human Genome Research Institute; Eunice Kennedy Shriver
National Institute of Child Health and Human Development; National
Institutes of Health [DK064732]; Department of Health and Human
Services; Health Research Board, Ireland
FX The authors acknowledge the research support from the intramural
research programmes of the National Human Genome Research Institute, the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, the National Institutes of Health, the Department of Health
and Human Services and the Health Research Board, Ireland. EVQ and JMS
are supported by the National Institutes of Health grant DK064732.
NR 52
TC 20
Z9 20
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
J9 J MED GENET
JI J. Med. Genet.
PD OCT
PY 2010
VL 47
IS 10
BP 677
EP 685
DI 10.1136/jmg.2009.073775
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 671TI
UT WOS:000283533500005
PM 20577008
ER
PT J
AU Yao, K
Crawford, JR
Komaroff, AL
Ablashi, DV
Jacobson, S
AF Yao, Karen
Crawford, John R.
Komaroff, Anthony L.
Ablashi, Dharam V.
Jacobson, Steven
TI Review Part 2: Human Herpesvirus-6 in Central Nervous System Diseases
SO JOURNAL OF MEDICAL VIROLOGY
LA English
DT Article
DE HHV-6; central nervous system
ID CHRONIC-FATIGUE-SYNDROME; STEM-CELL TRANSPLANTATION;
POLYMERASE-CHAIN-REACTION; MULTIPLE-SCLEROSIS PATIENTS; CONTROL
BRAIN-TISSUE; SERUM HHV-6 DNA; CEREBROSPINAL-FLUID; HUMAN-HERPESVIRUS-6
INFECTION; LIMBIC ENCEPHALITIS; FATAL ENCEPHALITIS
C1 [Yao, Karen; Jacobson, Steven] NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA.
[Crawford, John R.] Univ Calif San Diego, Dept Neurosci & Pediat, San Diego, CA 92103 USA.
[Komaroff, Anthony L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Komaroff, Anthony L.] Harvard Univ, Sch Med, Boston, MA USA.
[Ablashi, Dharam V.] HHV 6 Fdn, Santa Barbara, CA USA.
RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, NIH, Bldg 10,Room 5C-103, Bethesda, MD 20892 USA.
EM jacobsons@ninds.nih.gov
FU Intramural NIH HHS [Z01 NS002817-18, Z01 NS003040-01, Z01 NS002817-19]
NR 110
TC 39
Z9 40
U1 2
U2 3
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 OCT
PY 2010
VL 82
IS 10
BP 1669
EP 1678
DI 10.1002/jmv.21861
PG 10
WC Virology
SC Virology
GA 640VE
UT WOS:000281081000007
PM 20827763
ER
PT J
AU Lynn, EG
Stevens, MV
Wong, RP
Carabenciov, D
Jacobson, J
Murphy, E
Sack, MN
AF Lynn, Edward G.
Stevens, Mark V.
Wong, Renee P.
Carabenciov, Darin
Jacobson, Jeremy
Murphy, Elizabeth
Sack, Michael N.
TI Transient upregulation of PGC-1 alpha diminishes cardiac ischemia
tolerance via upregulation of ANT1
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Article
DE PGC-1 alpha; Cardiac ischemia-reperfusion; ANTI
ID THERMOGENIC COACTIVATOR PGC-1; MITOCHONDRIAL BIOGENESIS;
SKELETAL-MUSCLE; GENE-EXPRESSION; MECHANISMS; CARDIOMYOPATHY;
CARDIOPROTECTION; OVEREXPRESSION; PROTECTION; PROTEIN-3
AB Prolonged cardiac overexpression of the mitochondrial biogenesis regulatory transcriptional coactivator PGC-1 alpha disrupts cardiac contractile function and its genetic ablation limits cardiac capacity to enhance workload. In contrast, transient induction of PGC-1 alpha alleviates neuronal cell oxidative stress and enhances skeletal myotube anti-oxidant defenses. We explored whether transient upregulation of PGC-1 alpha in the heart protects against ischemia-reperfusion injury. The transient induction of PGC-1 alpha in the cardiac-restricted inducible PGC-1 alpha transgenic mouse, increased PGC-1 alpha protein levels 5-fold. Following 25 min of ischemia and 2 h of reperfusion on a Langendorff perfusion apparatus, contractile recovery and the rate pressure product was significantly blunted in mice overexpressing PGC-1 alpha vs. controls. Affymetrix gene array analysis showed a 3-fold PGC-1 alpha-mediated upregulation of adenine nucleotide translocase 1 (ANT1). As ANT1 upregulation induces cardiomyocyte cell death we investigated whether the induction of ANT1 by PGC-1 alpha contributes to this enhanced ischemia-stress susceptibility. Infection with adenovirus harboring PGC-1 alpha into cardiac-derived H9c2 cells significantly upregulates ANT1 without changing basal cell viability. In response to anoxia-reoxygenation injury cell death is significantly increased following PGC-1 alpha overexpression. This detrimental effect is abolished following siRNA knockdown of ANT1. Similarly, the attenuation of ANT-1 in the presence of PGC-1 alpha overexpression preserves the mitochondrial membrane potential in response to hydrogen-peroxide stress. Interestingly, the isolated knockdown of ANT1 also protects H9c2 cells from anoxia-reoxygenation injury. Taken together these data suggest that transient induction of PGC-1 alpha in the murine heart decreases ischemia-reperfusion contractile recovery and diminishes anoxia-reoxygenation tolerance in H9c2 cells. These adverse phenotypes appear to be mediated, in part, by PGC-1 alpha induced upregulation of ANT1. Published by Elsevier Ltd.
C1 [Lynn, Edward G.; Stevens, Mark V.; Wong, Renee P.; Carabenciov, Darin; Jacobson, Jeremy; Murphy, Elizabeth; Sack, Michael N.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Sack, MN (reprint author), NHLBI, Translat Med Branch, NIH, Bld 10-CRC,Room 5-3150,10 Ctr Dr, Bethesda, MD 20892 USA.
EM sackm@nhlbi.nih.gov
OI Lynn, Edward/0000-0002-8011-5558
FU NHLBI Division of Intramural Research
FX We would like to thank the members of the NHLBI Genotyping Core,
including Nalini Raghavachari and Xiuli Xu for their assistance with the
gene array expression analysis. We would also like to thank Ann Williams
from the NHLBI Flow Cytometry core for assistance. This work is funded
by NHLBI Division of Intramural Research Funds. We thank Daniel P. Kelly
and Maria L Valencik for the gift of the cardiac inducible PGC-1 alpha
transgenic mouse.
NR 34
TC 15
Z9 17
U1 0
U2 3
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 OCT
PY 2010
VL 49
IS 4
BP 693
EP 698
DI 10.1016/j.yjmcc.2010.06.008
PG 6
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 650TR
UT WOS:000281875900017
PM 20600099
ER
PT J
AU Pagan, I
Firth, C
Holmes, EC
AF Pagan, Israel
Firth, Cadhla
Holmes, Edward C.
TI Phylogenetic Analysis Reveals Rapid Evolutionary Dynamics in the Plant
RNA Virus Genus Tobamovirus
SO JOURNAL OF MOLECULAR EVOLUTION
LA English
DT Article
DE Tobamoviruses; Evolutionary dynamics; Virus-host codivergence
ID TOBACCO-MOSAIC-VIRUS; SPONTANEOUS MUTATION; NICOTIANA-GLAUCA;
POPULATION; RECOMBINATION; SUBSTITUTION; BOTTLENECKS; RESISTANCE; RATES;
MODEL
AB Early studies on the evolutionary dynamics of plant RNA viruses suggested that they may evolve more slowly than their animal counterparts, sometimes dramatically so. However, these estimates were often based on an assumption of virus host codivergence over time-scales of many millions of years that is difficult to verify. An important example are viruses of the genus Tobamovirus, where the assumption of host virus codivergence over 100 million years has led to rate estimates in the range of similar to 1 x 10-8 nucleotide substitutions per site, per year. Such a low evolutionary rate is in apparent contradiction with the ability of some tobamoviruses to quickly overcome inbred genetic resistance. To resolve how rapidly molecular evolution proceeds in the tobomaviruses, we estimated rates of nucleotide substitution, times to common ancestry, and the extent of congruence between virus and host phylogenies. Using Bayesian coalescent methods applied to time-stamped sequences, we estimated mean evolutionary rates at the nucleotide and amino acid levels of between 1 x 10(-5) and 1.3 x 10(-3) substitutions per site, per year, and hence similar to those seen in a broad range of animal and plant RNA viruses. Under these rates, a conservative estimate for the time of origin of the sampled tobamoviruses is within the last 100,000 years, and hence a far more recently than proposed assuming codivergence. This is supported by our cophylogeny analysis which revealed significantly discordant evolutionary histories between the tobamoviruses and the plant families they infect.
C1 [Pagan, Israel; Firth, Cadhla; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Pagan, I (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM jip3@psu.edu
RI Pagan, Israel/H-1843-2015;
OI Pagan, Israel/0000-0001-8876-1194; Holmes, Edward/0000-0001-9596-3552
FU Marie Curie Fellowship [PIOF-GA-2009-236470]; NSERC Canada; NIH
[R01-GM080533]
FX This work was supported by Marie Curie Fellowship PIOF-GA-2009-236470 to
IF, NSERC Canada to CF, and NIH grant R01-GM080533 to ECH. We thank Dr.
Andrew Kitchen for valuable comments, and all the authors who kindly
provided collection information for their sequence data.
NR 47
TC 20
Z9 21
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0022-2844
J9 J MOL EVOL
JI J. Mol. Evol.
PD OCT
PY 2010
VL 71
IS 4
BP 298
EP 307
DI 10.1007/s00239-010-9385-4
PG 10
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA 658FK
UT WOS:000282475700005
PM 20838783
ER
PT J
AU Kane, LA
Youle, RJ
AF Kane, Lesley A.
Youle, Richard J.
TI Mitochondrial fission and fusion and their roles in the heart
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Review
DE Mitochondria; Fission; Fusion; Heart
ID DYNAMIN-RELATED GTPASE; DOMINANT OPTIC ATROPHY; INNER-MEMBRANE-FUSION;
WD REPEAT PROTEIN; OUTER-MEMBRANE; SACCHAROMYCES-CEREVISIAE; GIANT
MITOCHONDRIA; MAMMALIAN-CELLS; S-NITROSYLATION; SKELETAL-MUSCLE
AB Mitochondria are dynamic organelles that usually exist in extensive and interconnected networks that undergo constant remodeling through fission and fusion. These processes are governed by distinct sets of proteins whose mechanism and regulation we are only beginning to fully understand. Early studies on mitochondrial dynamics were performed in yeast and simple mammalian cell culture models that allowed easy visualization of these intricate networks. Equipped with this core understanding, the field is now expanding into more complex systems. Cardiac cells are a particularly interesting example because they have unique energetic and spatial demands that make the study of their mitochondria both challenging and potentially very fruitful. This review will provide an overview of mitochondrial fission and fusion as well as recent developments in the understanding of these processes in the heart.
C1 [Youle, Richard J.] NINDS, Surg Neurol Branch, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
[Kane, Lesley A.; Youle, Richard J.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Youle, RJ (reprint author), NINDS, Surg Neurol Branch, Porter Neurosci Res Ctr, Bldg 35,Room 2C-917,35 Convent Dr,MSC 3704, Bethesda, MD 20892 USA.
EM youle@helix.nih.gov
FU National Institutes of Health
FX The authors' would like to thank Geoffrey Hesketh for the images used in
Fig. 2. Work in the authors' laboratory is funded by the Intramural
Research Program of the National Institute of Neurological Disorders and
Stroke, National Institutes of Health.
NR 95
TC 22
Z9 22
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
J9 J MOL MED
JI J. Mol. Med.
PD OCT
PY 2010
VL 88
IS 10
BP 971
EP 979
DI 10.1007/s00109-010-0674-6
PG 9
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 652ZT
UT WOS:000282052100003
PM 20835916
ER
PT J
AU Chen, J
Aguilera, G
AF Chen, J.
Aguilera, G.
TI Vasopressin Protects Hippocampal Neurones in Culture Against Nutrient
Deprivation or Glutamate-Induced Apoptosis
SO JOURNAL OF NEUROENDOCRINOLOGY
LA English
DT Article
DE vasopressin; V1 receptor; apoptosis; MAPK; ERK; PI3; Akt; hippocampus
ID METHYL-D-ASPARTATE; EPIDERMAL GROWTH-FACTOR; MAP KINASE CASCADE;
SIGNAL-TRANSDUCTION; RAT HIPPOCAMPUS; AMINO-ACIDS; CELL-LINE; RECEPTOR;
BRAIN; PATHWAY
AB Vasopressin (VP) secreted within the brain modulates neuronal function by acting as a neurotransmitter. Recent studies show that VP prevents serum deprivation-induced apoptosis in the neuronal cell line, H32. To determine whether VP is anti-apoptotic in hippocampal neurones, primary cultures of these neurones were used to examine the effect of VP on neuronal culture supplement (B27) deprivation-, or glutamate-induced apoptosis, and the signalling pathways mediating the effects. Removal of B27 supplement from the culture medium for 24 h or the addition of glutamate (3-10 mu m) decreased neuronal viability (P < 0.05) and increased Tdt-mediated dUTP nick-end labelling (TUNEL) staining and caspase-3 activity (P < 0.05), which is consistent with apoptotic cell death. VP (10 nm) reduced B27 deprivation- or glutamate-induced cell death (P < 0.05). These anti-apoptotic effects of VP were completely blocked by a V1 but not a V2 receptor antagonist, indicating that they are mediated via V1 VP receptors. The anti-apoptotic effect of VP in neurones involves activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and inositol trisphosphate/protein kinase B (Akt) signalling pathways. This was shown by the transient increases in phospho-ERK and phospho-Akt after incubation with VP revealed by western blot analyses, and the ability of specific inhibitors to reduce the inhibitory effect of VP on caspase-3 activity and TUNEL staining by 70% and 35%, respectively (P < 0.05). These studies demonstrate that VP has anti-apoptotic actions in hippocampal neurones, an effect that is mediated by the MAPK/ERK and phosphatidylinositol-3 kinase/Akt signalling pathways. The ability of VP to reduce nutrient deprivation or glutamate overstimulation-induced neuronal death suggests that VP acts as a neuroprotective agent within the brain.
C1 [Chen, J.; Aguilera, G.] NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
RP Aguilera, G (reprint author), NICHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH,CRC, Room 1E-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA.
EM greti_aguilera@nih.gov
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 64
TC 9
Z9 10
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0953-8194
J9 J NEUROENDOCRINOL
JI J. Neuroendocrinol.
PD OCT
PY 2010
VL 22
IS 10
BP 1072
EP 1081
DI 10.1111/j.1365-2826.2010.02054.x
PG 10
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 650DH
UT WOS:000281828400004
PM 20673301
ER
PT J
AU Benninger, DH
Lomarev, M
Lopez, G
Wassermann, EM
Li, XB
Considine, E
Hallett, M
AF Benninger, David H.
Lomarev, Mikhail
Lopez, Grisel
Wassermann, Eric M.
Li, Xiaobai
Considine, Elaine
Hallett, Mark
TI Transcranial direct current stimulation for the treatment of Parkinson's
disease
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Article
ID HUMAN MOTOR CORTEX; NONINVASIVE CORTICAL STIMULATION; GLOBUS-PALLIDUS
STIMULATION; DEEP BRAIN-STIMULATION; MAGNETIC STIMULATION;
DC-STIMULATION; EXCITABILITY CHANGES; SUBTHALAMIC NUCLEUS; DOPAMINE
RELEASE; MODULATION
AB Background Progression of Parkinson's disease (PD) is characterised by motor deficits which eventually respond less to dopaminergic therapy and thus pose a therapeutic challenge. Deep brain stimulation has proven efficacy but carries risks and is not possible in all patients. Non-invasive brain stimulation has shown promising results and may provide a therapeutic alternative.
Objective To investigate the efficacy of transcranial direct current stimulation (tDCS) in the treatment of PD.
Design Randomised, double blind, sham controlled study.
Setting Research institution.
Methods The efficacy of anodal tDCS applied to the motor and prefrontal cortices was investigated in eight sessions over 2.5 weeks. Assessment over a 3 month period included timed tests of gait (primary outcome measure) and bradykinesia in the upper extremities, Unified Parkinson's Disease Rating Scale (UPDRS), Serial Reaction Time Task, Beck Depression Inventory, Health Survey and self-assessment of mobility.
Results Twenty-five PD patients were investigated, 13 receiving tDCS and 12 sham stimulation. tDCS improved gait by some measures for a short time and improved bradykinesia in both the on and off states for longer than 3 months. Changes in UPDRS, reaction time, physical and mental well being, and self-assessed mobility did not differ between the tDCS and sham interventions.
Conclusion tDCS of the motor and prefrontal cortices may have therapeutic potential in PD but better stimulation parameters need to be established to make the technique clinically viable.
C1 [Benninger, David H.] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Lomarev, Mikhail] St Petersburg VM Bekhterev Psychoneurol Res Inst, St Petersburg, Russia.
[Wassermann, Eric M.] NINDS, Brain Stimulat Unit, NIH, Bethesda, MD 20892 USA.
RP Benninger, DH (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 7D37 MSC1428,Ctr Dr, Bethesda, MD 20892 USA.
EM benningerd@ninds.nih.gov
RI Benninger, David/A-8157-2015
OI Benninger, David/0000-0002-1049-9533
FU NINDS, NIH; USAMRMC [W81XWH-06-1-0534]; National Institutes of Health
FX This research was supported by the Intramural Research Program of the
NINDS, NIH and in part by a grant from the USAMRMC (W81XWH-06-1-0534).;
MH has received personal compensation or travel expenses for activities
with Neurotoxin Institute, John Templeton Foundation, Parkinson's and
Ageing Research Foundation, University of Pennsylvania, Thomas Jefferson
University, Baylor College of Medicine, American Academy of Neurology,
Medical University of South Carolina, Northshore-Long Island Jewish
Hospital, American Clinical Neurophysiology Society, Columbia
University, University of Alabama, Blackwell Publisher, Cambridge
University Press, Springer Verlag, Taylor and Francis Group, Oxford
University Press, John Wiley and Sons and Elsevier as an advisory board
member, an editor, a writer or a speaker. MH has received licence fee
payments from the National Institutes of Health for the H-coil, a type
of coil for magnetic stimulation. MH and his wife held stock in Agilent
Technologies, Amgen, Amylin Pharmaceuticals, Merck and Co, Monsanto Co
New Del, Sanofi Aventis Adr, Coventry Health Care Inc, Sigma Aldrich
Corp, Warner Chilcott Ltd, Pfizer Inc, Genentech, Inc, United Health
Group, St Jude Medical and Eli Lilly and Company.
NR 40
TC 88
Z9 92
U1 2
U2 26
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD OCT
PY 2010
VL 81
IS 10
BP 1105
EP 1111
DI 10.1136/jnnp.2009.202556
PG 7
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 654OD
UT WOS:000282176900053
PM 20870863
ER
PT J
AU Akahata, Y
Abrams, A
Oh, U
Maloney, E
Jacobson, S
AF Akahata, Yoshimi
Abrams, Anna
Oh, Unsong
Maloney, Elizabeth
Jacobson, Steven
TI The use of a luciferase immunoprecipitation systems (LIPS) assay in the
detection of anti-HTLV-I antibody responses in HAM/TSP, ATL, and
asymptomatic HTLV-I carriers
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on NeuroVirology
CY OCT 12-16, 2010
CL Milan, ITALY
C1 [Akahata, Yoshimi; Abrams, Anna; Oh, Unsong; Jacobson, Steven] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Maloney, Elizabeth] US FDA, Div Epidemiol, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD OCT
PY 2010
VL 16
SU 1
BP 3
EP 4
PG 2
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 670GS
UT WOS:000283409800008
ER
PT J
AU Boasso, A
Royle, CM
Doumazos, S
Aquino, VN
Biasin, M
Piacentini, L
Fuchs, D
Lo Caputo, S
Shearer, GM
Clerici, M
Graham, DR
AF Boasso, Adriano
Royle, Caroline M.
Doumazos, Spyridon
Aquino, Veronica N.
Biasin, Mara
Piacentini, Luca
Fuchs, Dietmar
Lo Caputo, Sergio
Shearer, Gene M.
Clerici, Mario
Graham, David R.
TI Chronic innate immune activation in the immunopathogenesis of HIV
infection
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on NeuroVirology
CY OCT 12-16, 2010
CL Milan, ITALY
C1 [Boasso, Adriano; Royle, Caroline M.; Doumazos, Spyridon] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Med,Immunol Sect, Chelsea & Westminster Hosp,Div Infect Dis, London, England.
[Aquino, Veronica N.; Graham, David R.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Retrovirus Lab, Baltimore, MD USA.
[Biasin, Mara; Piacentini, Luca; Clerici, Mario] Univ Milan, Cattedra Immunol, Milan, Italy.
[Fuchs, Dietmar] Innsbruck Med Univ, Bioctr, Div Biol Chem, Innsbruck, Austria.
[Lo Caputo, Sergio] Osped SM Annunziata, Div Malattie Infett, Florence, Italy.
[Shearer, Gene M.] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Clerici, Mario] Fdn Don Gnocchi IRCCS, Milan, Italy.
[Graham, David R.] Johns Hopkins Sch Med, Dept Med, Johns Hopkins Bayview Prote Ctr, Baltimore, MD USA.
RI biasin, mara/G-7426-2012; Piacentini, Luca/K-8908-2016
OI Piacentini, Luca/0000-0003-1022-4481
NR 0
TC 0
Z9 0
U1 0
U2 4
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD OCT
PY 2010
VL 16
SU 1
BP 11
EP 12
PG 2
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 670GS
UT WOS:000283409800024
ER
PT J
AU Marshall, LJ
Dunham, LD
Major, EO
AF Marshall, Leslie J.
Dunham, Lisa D.
Major, Eugene O.
TI The Transcription Factor Spi-B Binds Unique Sequences Present in the
Tandem Repeat Promoter/Enhancer of JC Virus and Supports Viral Activity
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on NeuroVirology
CY OCT 12-16, 2010
CL Milan, ITALY
C1 [Marshall, Leslie J.; Dunham, Lisa D.; Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD OCT
PY 2010
VL 16
SU 1
BP 54
EP 54
PG 1
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 670GS
UT WOS:000283409800117
ER
PT J
AU Oh, U
McCormick, M
Datta, D
Turner, R
Bobb, K
Monie, D
Sliskovic, DR
Zhang, J
Meshulam, J
Jacobson, S
AF Oh, Unsong
McCormick, Matthew
Datta, Dibyadeep
Turner, Richard
Bobb, Kathryn
Monie, Dileep
Sliskovic, D. Robert
Zhang, Jie
Meshulam, Jeffrey
Jacobson, Steven
TI NFkB activation promotes immune activation in HTLV-I-associated
myelopathy/tropical spastic paraparesis
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on NeuroVirology
CY OCT 12-16, 2010
CL Milan, ITALY
C1 [Oh, Unsong; McCormick, Matthew; Datta, Dibyadeep; Turner, Richard; Jacobson, Steven] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Bobb, Kathryn; Monie, Dileep; Zhang, Jie; Meshulam, Jeffrey] Profectus Biosci Inc, Baltimore, MD USA.
[Sliskovic, D. Robert] IDSC, Chelsea, MI USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD OCT
PY 2010
VL 16
SU 1
BP 63
EP 64
PG 2
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 670GS
UT WOS:000283409800139
ER
PT J
AU Wohler, JE
Gaitan, MI
Harberts, E
Huebner, A
Silva, AC
Reich, DS
AF Wohler, Jillian E.
Gaitan, Maria I.
Harberts, Erin
Huebner, Alyssa
Silva, Afonso C.
Reich, Daniel S.
TI Effects of HHV-6A Infection in the Common Marmoset
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on NeuroVirology
CY OCT 12-16, 2010
CL Milan, ITALY
C1 [Wohler, Jillian E.; Harberts, Erin; Huebner, Alyssa] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Gaitan, Maria I.; Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Silva, Afonso C.] NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RI Silva, Afonso/A-7129-2009; Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD OCT
PY 2010
VL 16
SU 1
BP 90
EP 91
PG 2
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 670GS
UT WOS:000283409800197
ER
PT J
AU Krebs-Smith, SM
Guenther, PM
Subar, AF
Kirkpatrick, SI
Dodd, KW
AF Krebs-Smith, Susan M.
Guenther, Patricia M.
Subar, Amy F.
Kirkpatrick, Sharon I.
Dodd, Kevin W.
TI Americans Do Not Meet Federal Dietary Recommendations
SO JOURNAL OF NUTRITION
LA English
DT Article
ID INTAKE DISTRIBUTIONS; FOOD GUIDANCE; POPULATION; NUTRIENTS; PATTERNS;
SYSTEM
AB A longstanding goal of dietary surveillance has been to estimate the proportion of the population with intakes above or below a target, such as a recommended level of intake. However, until now, statistical methods for assessing the alignment of food intakes with recommendations have been lacking. The purposes of this study were to demonstrate the National Cancer Institute's method of estimating the distribution of usual intake of foods and determine the proportion of the U.S. population who does not meet federal dietary recommendations. Data were obtained from the 2001-2004 NHANES for 16,338 persons, aged 2 y and older. Quantities of foods reported on 24-h recalls were translated into amounts of various food groups using the MyPyramid Equivalents Database. Usual dietary intake distributions were modeled, accounting for sequence effect; weekend/weekday effect, sex, age, poverty income ratio, and race/ethnicity. The majority of the population did not meet recommendations for all of the nutrient-rich food groups, except total grains and meat and beans. Concomitantly, overconsumption of energy from solid fats, added sugars, and alcoholic beverages ("empty calories") was ubiquitous. Over 80% of persons age >= 71 y and over 90% of all other sex-age groups had intakes of empty calories that exceeded the discretionary calorie allowances. In conclusion, nearly the entire U.S. population consumes a diet that is not on par with recommendations. These findings add another piece to the rather disturbing picture that is emerging of a nation's diet in crisis. J. Nutr. 140: 1832-1838, 2010.
C1 [Krebs-Smith, Susan M.; Subar, Amy F.; Kirkpatrick, Sharon I.; Dodd, Kevin W.] NCI, Bethesda, MD 20892 USA.
[Guenther, Patricia M.] USDA, Ctr Nutr Policy & Promot, Alexandria, VA 22302 USA.
RP Krebs-Smith, SM (reprint author), NCI, Bethesda, MD 20892 USA.
EM krebssms@mail.nih.gov
OI Kirkpatrick, Sharon/0000-0001-9896-5975
NR 30
TC 250
Z9 251
U1 1
U2 18
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD OCT
PY 2010
VL 140
IS 10
BP 1832
EP 1838
DI 10.3945/jn.110.124826
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 704WM
UT WOS:000286086300019
PM 20702750
ER
PT J
AU Mehr, S
Jones, KJ
Singh-Grewal, D
Aksentijevich, I
Kakakios, A
AF Mehr, Sam
Jones, Kristi J.
Singh-Grewal, Davinder
Aksentijevich, Ivona
Kakakios, Alyson
TI Chronic urticaria of neonatal onset: A potential sign of
autoinflammation
SO JOURNAL OF PAEDIATRICS AND CHILD HEALTH
LA English
DT Article
DE anakinra; chronic infantile neurological; cutaneous and articular
syndrome; NOMID
ID CIAS1 MUTATIONS; CRYOPYRINOPATHIES
AB We present a 6 year old boy with chronic urticaria of neonatal onset associated in childhood with features of neurological and joint inflammation. Genetic analysis confirmed the diagnosis of neonatal onset multi-inflammatory disorder (NOMID). Daily subcutaneous anti-IL-1 receptor antagonist therapy resulted in a dramatic and sustained amelioration of systemic inflammation. NOMID must be considered in any child with chronic urticaria of neonatal/infantile onset, particularly if associated with joint and/or neurological inflammation.
C1 [Mehr, Sam; Kakakios, Alyson] Childrens Hosp Westmead, Dept Allergy & Immunol, Sydney, NSW 2145, Australia.
[Singh-Grewal, Davinder] Childrens Hosp Westmead, Dept Rheumatol, Sydney, NSW 2145, Australia.
[Jones, Kristi J.] Childrens Hosp Westmead, Western Sydney Genet Program, Sydney, NSW 2145, Australia.
[Mehr, Sam; Singh-Grewal, Davinder] Univ Sydney, Childrens Hosp Westmead, Sch Clin, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia.
[Aksentijevich, Ivona] Natl Inst Arthrit & Musculoskeletal & Skin Dis, Genet & Genom Branch, Bethesda, MD USA.
RP Kakakios, A (reprint author), Childrens Hosp Westmead, Dept Allergy Immunol & Infect Dis, Locked Bag 4001, Sydney, NSW 2145, Australia.
EM alysonk@chw.edu.au
FU Australian Allergy Foundation
FX SM was partly supported by funds received from the Australian Allergy
Foundation.
NR 5
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1034-4810
J9 J PAEDIATR CHILD H
JI J. Paediatr. Child Health
PD OCT
PY 2010
VL 46
IS 10
BP 608
EP 610
DI 10.1111/j.1440-1754.2009.01688.x
PG 3
WC Pediatrics
SC Pediatrics
GA 667BR
UT WOS:000283168100015
PM 20163528
ER
PT J
AU Raetz, EA
Salzer, WL
AF Raetz, Elizabeth A.
Salzer, Wanda L.
TI Tolerability and Efficacy of L-Asparaginase Therapy in Pediatric
Patients With Acute Lymphoblastic Leukemia
SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
LA English
DT Article
DE L-asparaginase; pegaspargase; acute lymphoblastic leukemia; toxicity;
hypersensitivity
ID ACUTE LYMPHOCYTIC-LEUKEMIA; ESCHERICHIA-COLI-ASPARAGINASE; CHILDRENS
ONCOLOGY GROUP; RECEIVING L-ASPARAGINASE; ERWINIA L-ASPARAGINASE; DOSE
L-ASPARAGINASE; CANCER-STUDY-GROUP; PEG-ASPARAGINASE; SYNTHETASE
EXPRESSION; E. COLI
AB L-asparaginase (L-ASNase) has been an essential component of multiagent chemotherapy for acute lymphoblastic leukemia in childhood for over 3 decades. There are currently 2 Food and Drug Administration (FDA)-approved formulations of L-ASNase derived from Escherichia coli and 1 non-FDA approved formulation derived from Erwinia chrysanthemi. Modifications in L-ASNase have included pegylation, which decreases drug immunogenicity and increases the half-life, allowing less frequent administration. Although L-ASNase is well-tolerated in most patients and causes little myelosuppression, significant toxicities occur in up to 30% of patients. Hypersensitivity is the most common toxicity of L-ASNase therapy and limits the further use of the drug. Other significant toxicities relate to a reduction in protein synthesis and include pancreatitis, thrombosis, central nervous system complications, and liver dysfunction. The spectrum of common toxicities and the efficacy of different formulations of L-ASNase are presented in this review.
C1 [Raetz, Elizabeth A.] NYU, Inst Canc, Dept Pediat, Div Pediat Hematol Oncol,Sch Med, New York, NY 10016 USA.
[Salzer, Wanda L.] NCI, Bethesda, MD 20892 USA.
RP Raetz, EA (reprint author), NYU, Inst Canc, Dept Pediat, Div Pediat Hematol Oncol,Sch Med, 160 E 32nd St,2nd Floor, New York, NY 10016 USA.
EM elizabeth.raetz@nyumc.org
NR 104
TC 37
Z9 39
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1077-4114
J9 J PEDIAT HEMATOL ONC
JI J. Pediatr. Hematol. Oncol.
PD OCT
PY 2010
VL 32
IS 7
BP 554
EP 563
DI 10.1097/MPH.0b013e3181e6f003
PG 10
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 664TC
UT WOS:000282984400007
PM 20724951
ER
PT J
AU Choi, MR
Jiles, C
Seibel, NL
AF Choi, Mi Rim
Jiles, Cynthia
Seibel, Nita L.
TI Aprepitant Use in Children, Adolescents, and Young Adults for the
Control of Chemotherapy-Induced Nausea and Vomiting (CINV)
SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
LA English
DT Article
DE aprepitant; chemotherapy induced nausea and vomiting; antiemetics;
pediatric
ID RECEPTOR ANTAGONIST APREPITANT; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND;
RECEIVING CHEMOTHERAPY; CANCER-PATIENTS; DEXAMETHASONE; ANTIEMETICS;
PROPHYLAXIS; PREVENTION; EFFICACY
AB Background: One of the most common and distressing side effects for cancer patients is chemotherapy-induced nausea and vomiting (CINV). New antiemetics, such as the NK-1 receptor inhibitor aprepitant, have been reported to improve control of this side effect in adults. However, little is known about its effect in the pediatric oncology population, with only a few reported cases in the literature.
Methods: This was a retrospective chart review on the use of aprepitant in the pediatric oncology population in our institution.
Results: Thirty-two charts and a total of 146 cycles of chemotherapy were reviewed. Mean age was 10 years. Highly emetogenic chemotherapy was used in 23/32 patients and moderately emetogenic chemotherapy in 9/32. Antiemetic regimens consisted of aprepitant + 5-HT3 RA + dexamethasone (Regimen 1, 20/32 patients) or aprepitant + 5-HT3 RA (Regimen 2, in 12/32). Eight out of thirty-two patients were chemotherapy-naive and received aprepitant on their first cycle. In 24/32 patients, aprepitant was added later in their treatment, with 12/24 reporting resolution of CINV after its addition.
Conclusions: Aprepitant when combined with standard antiemetics, was well tolerated in the pediatric oncology population studied. However, there is still a need to conduct prospective studies to determine the optimal efficacy of aprepitant in the pediatric oncology population.
C1 [Choi, Mi Rim; Jiles, Cynthia; Seibel, Nita L.] Childrens Natl Med Ctr, Div Hematol & Oncol, Washington, DC 20010 USA.
[Seibel, Nita L.] George Washington Univ, Sch Med & Publ Hlth, Washington, DC USA.
RP Seibel, NL (reprint author), NCI, Canc Therapy Evaluat Program, 6130 Execut Blvd,Room 7025, Bethesda, MD 20892 USA.
EM seibelnl@mail.nih.gov
NR 22
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Z9 14
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1077-4114
J9 J PEDIAT HEMATOL ONC
JI J. Pediatr. Hematol. Oncol.
PD OCT
PY 2010
VL 32
IS 7
BP E268
EP E271
DI 10.1097/MPH.0b013e3181e5e1af
PG 4
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 664TC
UT WOS:000282984400017
PM 20736848
ER
PT J
AU Bolton, JM
Pagura, J
Enns, MW
Grant, B
Sareen, J
AF Bolton, James M.
Pagura, Jina
Enns, Murray W.
Grant, Bridget
Sareen, Jitender
TI A population-based longitudinal study of risk factors for suicide
attempts in major depressive disorder
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Major depressive disorder; Suicide attempt; Epidemiology; Anxiety
disorder; Personality disorder
ID NATIONAL EPIDEMIOLOGIC SURVEY; ALCOHOL-USE-DISORDER; PSYCHIATRIC
DIAGNOSTIC MODULES; POSTTRAUMATIC-STRESS-DISORDER; INTERVIEW SCHEDULE
AUDADIS; 10-YEAR FOLLOW-UP; PERSONALITY-DISORDERS; ANXIETY DISORDERS;
CLINICAL PREDICTORS; MENTAL-DISORDERS
AB No longitudinal study has examined risk factors for future suicide attempts in major depressive disorder in a nationally representative sample. The objective of this study was to investigate baseline sociodemographic characteristics, comorbid mental disorders, specific depressive symptoms, and previous suicidal behavior as potential risk factors for suicide attempts at 3 years follow-up. Data came from the national epidemiologic survey on alcohol and related conditions (NESARC), a large nationally representative longitudinal survey of mental illness in adults (Wave 1 (2001-2002); Wave 2 (2004-2005) n = 34,653]. Logistic regression examined associations between risk factors present at Wave 1 and suicide attempts at Wave 2 (n = 169) among individuals with major depressive disorder at baseline assessment (n = 6004). Risk factors for incident suicide attempts at Wave 2 (n = 63) were identified among those with major depressive disorder at Wave 1 and no lifetime history of suicide attempts (n = 5170). Results revealed specific comorbid anxiety, personality, and substance use disorders to be associated with incident suicide attempts at Wave 2. Comorbid borderline personality disorder was strongly associated with suicide attempts in all models. Several comorbid disorders were strongly associated with suicide attempts at Wave 2 even after adjusting for previous suicidal behavior, notably posttraumatic stress disorder (adjusted odds ratio (AOR) = 2.20; 95% confidence interval (95% CI) 1.27-3.83) and dependent personality disorder (AOR = 4.43; 95% CI 1.93-10.18). These findings suggest that mental illness comorbidity confers an increased risk of future suicide attempts in major depressive disorder that is not solely accounted for by past suicidal behavior. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Bolton, James M.; Enns, Murray W.; Sareen, Jitender] Univ Manitoba, Dept Psychiat, Winnipeg, MB R3T 2N2, Canada.
[Pagura, Jina] Univ Manitoba, Dept Clin Psychol, Winnipeg, MB, Canada.
[Enns, Murray W.; Sareen, Jitender] Univ Manitoba, Dept Community Hlth Sci, Winnipeg, MB R3T 2N2, Canada.
[Grant, Bridget] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIA, Bethesda, MD USA.
RP Bolton, JM (reprint author), PZ430-771 Bannatyne Ave, Winnipeg, MB R3E 3N4, Canada.
EM jbolton@hsc.mb.ca
FU Manitoba Health Research Council; Canadian Institutes of Health Research
(CIHR) [152348]
FX Preparation of this article was supported by:; (1) Manitoba Health
Research Council operating grant awarded to Dr. Bolton.; (2) Canadian
Institutes of Health Research (CIHR) New Investigator Award (#152348) to
Dr. Sareen.
NR 58
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U1 3
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD OCT
PY 2010
VL 44
IS 13
BP 817
EP 826
DI 10.1016/j.jpsychires.2010.01.003
PG 10
WC Psychiatry
SC Psychiatry
GA 657FO
UT WOS:000282398800003
PM 20122697
ER
PT J
AU Kenakin, T
Agnati, LF
Caron, M
Fredholm, B
Guidoli, D
Kobilka, B
Lefkowitz, RW
Lohse, M
Woods, A
Fuxe, K
AF Kenakin, Terry
Agnati, Luigi F.
Caron, Marc
Fredholm, Bertil
Guidoli, Diego
Kobilka, Brian
Lefkowitz, Robert W.
Lohse, Martin
Woods, Amina
Fuxe, Kjell
TI International Workshop at the Nobel Forum, Karolinska Institutet on G
protein-coupled receptors: finding the words to describe monomers,
oligomers, and their molecular mechanisms and defining their meaning.
Can a consensus be reached?
SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
LA English
DT Article
ID LIGANDS; ACTIVATION; REVEALS
AB A meeting was held May 1 9, 2010 at the Karolinski Institute on Nomenclature in Pharmacology. This meeting occurred in conjunction with the Symposium The Changing World of G Protein Coupled Receptors: From Monomers to Dimers and Receptor Mosaics (Higher-order Oligomers) held the previous day at the Royal Swedish Academy of Science. Two broad topics of nomenclature were discussed; ligand nomenclature and the definition of 'receptor-receptor' interactions. This paper summarizes discussions on these topics along with a consensus definition of the term 'receptor-receptor' interaction.
C1 [Kenakin, Terry] GlaxoSmithKline Res & Dev Ltd, Res Triangle Pk, NC 27709 USA.
[Agnati, Luigi F.] IRCCS, San Camillo, Lido Venezia, Italy.
[Lefkowitz, Robert W.] Duke Univ, Howard Hughes Med Inst, Durham, NC USA.
[Fredholm, Bertil; Fuxe, Kjell] Karolinska Inst, Stockholm, Sweden.
[Guidoli, Diego] Univ Padua, Padua, Italy.
[Kobilka, Brian] Stanford Univ, Stanford, CA 94305 USA.
[Lohse, Martin] Univ Wurzburg, Wurzburg, GA USA.
[Woods, Amina] NIDA IRP, Baltimore, MD USA.
RP Kenakin, T (reprint author), GlaxoSmithKline Res & Dev Ltd, POB 13398, Res Triangle Pk, NC 27709 USA.
EM terry.p.kenakin@gsk.com
RI Lohse, Martin/A-7160-2012;
OI Lohse, Martin/0000-0002-0599-3510; Fuxe, Kjell/0000-0001-8491-4288
NR 7
TC 16
Z9 16
U1 0
U2 8
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1079-9893
J9 J RECEPT SIG TRANSD
JI J. Recept. Signal Transduct.
PD OCT
PY 2010
VL 30
IS 5
SI SI
BP 284
EP 286
DI 10.3109/10799893.2010.512438
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 671CD
UT WOS:000283476500003
PM 20858022
ER
PT J
AU Woods, AS
AF Woods, Amina S.
TI The dopamine D-4 receptor, the ultimate disordered protein
SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
LA English
DT Article
DE Dopamine D4 Receptor; Disordered proteins; AKAP; Heteromers; Adenosine
A2A Receptor
ID ELECTROSTATIC INTERACTION; ADENOSINE A(2A); SH3 DOMAINS;
HETEROMERIZATION; PREDICTION; COMPLEXITY; SEQUENCE; MOSAICS; NEURONS
AB The human D4 dopamine receptor is a synaptic neurotransmitter receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its structure makes it a very unusual and interesting G protein-coupled receptor (GPCR) as it has several polymorphic variants of its gene in the region encoding the third intracellular loop (IL3). This region contains from two to seven or more similar 48 base pair repeats. These repeats cause this protein to have a very high disorder index and this, in turn, makes it very interactive with other proteins. Among GPCRs in general, the unusually proline-rich IL3 is unique to the D4 receptor (D4R). We believe that, as in the D2R, this region of the receptor plays a role in it's interaction with other receptors.
C1 NIDA IRP, NIH, Struct Biol Unit, Cellular Neurobiol Branch, Baltimore, MD 21224 USA.
RP Woods, AS (reprint author), NIDA IRP, NIH, Struct Biol Unit, Cellular Neurobiol Branch, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM awoods@intra.nida.nih.gov
FU National Institute on Drug Abuse, NIH; Office of National Drug Control
Policy (ONDCP)
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse, NIH. The authors thank the Office of
National Drug Control Policy (ONDCP) for instrumentation funding,
with-out which this and other projects could not have been accomplished.
NR 28
TC 12
Z9 14
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1079-9893
J9 J RECEPT SIG TRANSD
JI J. Recept. Signal Transduct.
PD OCT
PY 2010
VL 30
IS 5
SI SI
BP 331
EP 336
DI 10.3109/10799893.2010.513842
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 671CD
UT WOS:000283476500008
PM 20836733
ER
PT J
AU Silverman, MN
Sternberg, EM
AF Silverman, Marni N.
Sternberg, Esther M.
TI Matching Therapy to Body Rhythms: An Endocrine Approach to Treating
Rheumatoid Arthritis
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Editorial Material
ID PREDNISONE; EFFICACY
C1 [Silverman, Marni N.; Sternberg, Esther M.] NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Rockville, MD 20852 USA.
RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, NIH, 5625 Fishers Lane,Room 4N-13,MSC 9401, Rockville, MD 20852 USA.
EM sternbee@mail.nih.gov
FU Intramural NIH HHS [ZIA MH002585-20]
NR 8
TC 6
Z9 7
U1 0
U2 0
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA
SN 0315-162X
J9 J RHEUMATOL
JI J. Rheumatol.
PD OCT
PY 2010
VL 37
IS 10
BP 1981
EP 1982
DI 10.3899/jrheum.100688
PG 2
WC Rheumatology
SC Rheumatology
GA 663DY
UT WOS:000282864400001
PM 20889607
ER
PT J
AU Strohsnitter, WC
Noller, KL
Troisi, R
Robboy, SJ
Hatch, EE
Titus-Ernstoff, L
Kaufman, RH
Palmer, JR
Anderson, D
Hoover, RN
AF Strohsnitter, William C.
Noller, Kenneth L.
Troisi, Rebecca
Robboy, Stanley J.
Hatch, Elizabeth E.
Titus-Ernstoff, Linda
Kaufman, Raymond H.
Palmer, Julie R.
Anderson, Diane
Hoover, Robert N.
TI Autoimmune Disease Incidence Among Women Prenatally Exposed to
Diethylstilbestrol
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Article
DE DIETHYLSTILBESTROL; PRENATAL EXPOSURE; AUTOIMMUNE DISEASE; PROSPECTIVE
STUDY
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; IN-UTERO; REVISED
CRITERIA; RISK; PREGNANCY; CLASSIFICATION; EPIDEMIOLOGY; HEALTH; CANCER
AB Objective. Animal studies have suggested that prenatal diethylstilbestrol (DES) exposure may alter immune system development and function including antigen self-recognition. A cohort study was conducted to investigate whether prenatal DES exposure might influence the incidence of at least some specific autoimmune diseases in women.
Methods. A group of women who were and were not prenatally exposed to DES have been followed for more than 25 years for numerous health outcomes including autoimmune disease. To verify diagnoses, medical records or physician abstracts were requested for all women who reported a diagnosis of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), optic neuritis (ON), and idiopathic thrombocytopenic purpura (ITP). Incidence rates of these autoimmune diseases were compared between women who were and who were not prenatally DES-exposed.
Results. Overall, there was no increase in verified autoimmune disease among DES-exposed women relative to those who were not exposed (RR 1.2; 95% CI 0.7, 2.1). There was, however, a positive association between prenatal DES exposure and RA among women younger than 45 years (RR 4.9; 95% CI 1.1, 21.6) and an inverse association among women who were 45 years and older (RR 0.1; 95% CI 0.01, 0.7).
Conclusion. Overall, these data provide little support for an association between prenatal DES exposure and development of autoimmune disease. The implication that such exposure may be related to RA in an unusual age-related manner is based on small numbers of cases and warrants further study. (First Release July 15 2010; J Rheumatol 2010;37:2167-73; doi:10.3899/jrheum.091092)
C1 [Strohsnitter, William C.] Tufts Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA.
[Palmer, Julie R.] Boston Univ, Sch Publ Hlth, Slone Epidemiol Ctr, Boston, MA USA.
[Noller, Kenneth L.] Amer Board Obstet & Gynecol, Dallas, TX USA.
[Troisi, Rebecca; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Robboy, Stanley J.] Duke Univ, Dept Pathol, Durham, NC 27706 USA.
[Titus-Ernstoff, Linda] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA.
[Kaufman, Raymond H.] Methodist Hosp, Houston, TX 77030 USA.
[Anderson, Diane] Univ Chicago, Chicago, IL 60637 USA.
RP Strohsnitter, WC (reprint author), Tufts Med Ctr, Dept Obstet & Gynecol, 800 Washington St, Boston, MA 02111 USA.
EM wstrohsnitter@tuftsmedicalcenter.org
OI Palmer, Julie/0000-0002-6534-335X; Hatch, Elizabeth/0000-0001-7901-3928
FU NIH [N01-CP-55507, N01-CP-55508, N01-CP-55509, N01-CP-55510,
N01-CP-51010-66]
FX Supported by NIH contracts N01-CP-55507, N01-CP-55508, N01-CP-55509,
N01-CP-55510, and N01-CP-51010-66.
NR 28
TC 7
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U1 1
U2 3
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA
SN 0315-162X
J9 J RHEUMATOL
JI J. Rheumatol.
PD OCT
PY 2010
VL 37
IS 10
BP 2167
EP 2173
DI 10.3899/jrheum.091092
PG 7
WC Rheumatology
SC Rheumatology
GA 663DY
UT WOS:000282864400029
PM 20634240
ER
PT J
AU Catherino, WH
Malik, M
Driggers, P
Chappel, S
Segars, J
Davis, J
AF Catherino, William H.
Malik, Minnie
Driggers, Paul
Chappel, Scott
Segars, James
Davis, Joseph
TI Novel, orally active selective progesterone receptor modulator CP8947
inhibits leiomyoma cell proliferation without adversely affecting
endometrium or myometrium
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE Selective progesterone receptor modulator; Apoptosis; Endometrium;
Leiomyoma; Myometrium; Extracellular matrix
ID UTERINE LEIOMYOMATA; PENICILLIUM-OBLATUM; MIFEPRISTONE; CDB-2914;
FIBROIDS; WOMEN; ELUCIDATION; ASOPRISNIL; MANAGEMENT; CDB-4124
AB Uterine leiomyomas are highly prevalent and often symptomatic, but current medical therapies are limited. A novel, potent, selective, orally active therapy is needed. The goal of these studies was to determine the progesterone receptor (PR) specificity and activation, endometrial response, and impact on leiomyoma cell proliferation and extracellular matrix (ECM) production of the novel non-steroidal selective progesterone receptor modulators (SPRMs) CP8863 and CP8947. In vitro progestational activity was assessed by alkaline phosphatase assay and ER-a expression. In vivo progestational activity was assayed by the McPhail assay. Proliferation and gene expression studies were performed in immortalized human leiomyoma and myometrial cells. Both CP8863 and CP8947 were highly selective for progesterone receptor (PR) but not for ER-alpha, AR, and GR. Both compounds induced alkaline phosphatase comparably to progesterone, while CP8947 induced ER-alpha in leiomyoma cells but not myometrial cells. CP8947 was progestational in rabbit endometrium Nanomolar CP8947 treatment inhibited human leiomyoma but not myometrial cell proliferation. Extracellular matrix components were decreased in leiomyoma cells, including COL1A1 and COL7A1 at nanomolar concentrations. CP8947 was a potent novel non-steroidal SPRM that was selective for PR, demonstrated progestational activity in enclometrium, inhibited leiomyoma cell proliferation and decreased ECM component production, without disrupting myometrial cell proliferation. Published by Elsevier Ltd.
C1 [Catherino, William H.; Malik, Minnie; Segars, James] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
[Catherino, William H.; Driggers, Paul; Segars, James; Davis, Joseph] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Chappel, Scott] Tokai Pharmaceut Inc, Cambridge, MA USA.
RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM wcatherino@usuhs.mil
OI Malik, Minnie/0000-0003-1129-6575
FU Tokai Pharmaceuticals, Inc.; PRAE, NICHD, NIH
FX This work was supported by a research grant from Tokai Pharmaceuticals,
Inc. and by the intramural research program of the PRAE, NICHD, NIH
NR 42
TC 17
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U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid Biochem. Mol. Biol.
PD OCT
PY 2010
VL 122
IS 4
BP 279
EP 286
DI 10.1016/j.jsbmb.2010.05.005
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 673TW
UT WOS:000283687100020
PM 20493256
ER
PT J
AU Hopkins, R
Esposito, D
Gillette, W
AF Hopkins, Ralph
Esposito, Dominic
Gillette, William
TI Widening the bottleneck: Increasing success in protein expression and
purification
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE Protein purification; Baculovirus; High throughput
ID ENABLING TECHNOLOGIES; STRUCTURAL GENOMICS; CLONING; DNA
AB The number of variables at play in the expression and purification of a single protein dwarf those involved in sequencing a genome. Although certain trends are apparent, there is no one-size-fits-all approach to the process of purifying proteins. Thus, whereas numerous genome sequencing projects are providing an overwhelming number of interesting open reading frames for structural biologists to study, fully realizing the potential of this resource is still only a distant hope. We will discuss several current approaches to high throughput expression and purification as well as strategies that have served us well to quickly identify lead protein expression constructs in the context of a core service protein expression and purification laboratory. The use of the baculovirus expression vector system and implementation of a purification screening method will be emphasized. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Hopkins, Ralph; Esposito, Dominic; Gillette, William] NCI, Prot Express Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Gillette, W (reprint author), NCI, Prot Express Lab, SAIC Frederick Inc, Bldg 327,Room 6, Frederick, MD 21702 USA.
EM gillettew@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government.
NR 13
TC 5
Z9 5
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD OCT
PY 2010
VL 172
IS 1
SI SI
BP 14
EP 20
DI 10.1016/j.jsb.2010.07.005
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 650YA
UT WOS:000281889200003
PM 20650317
ER
PT J
AU Merikangas, KR
He, JP
Burstein, M
Swanson, SA
Avenevoli, S
Cui, LH
Benjet, C
Georgiades, K
Swendsen, J
AF Merikangas, Kathleen Ries
He, Jian-ping
Burstein, Marcy
Swanson, Sonja A.
Avenevoli, Shelli
Cui, Lihong
Benjet, Corina
Georgiades, Katholiki
Swendsen, Joel
TI Lifetime Prevalence of Mental Disorders in U.S. Adolescents: Results
from the National Comorbidity Survey Replication-Adolescent Supplement
(NCS-A)
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE epidemiology; adolescents; mental disorders; National Comorbidity
Survey; correlates
ID HIGH-SCHOOL-STUDENTS; III-R DISORDERS; PSYCHIATRIC-DISORDERS;
RISK-FACTORS; CHILD; HEALTH; EPIDEMIOLOGY; RATES; PSYCHOPATHOLOGY;
ANXIETY
AB Objective: To present estimates of the lifetime prevalence of DSM-IV mental disorders with and without severe impairment, their comorbidity across broad classes of disorder, and their sociodemographic correlates. Method: The National Comorbidity Survey Adolescent Supplement NCS-A is a nationally representative face-to-face survey of 10,123 adolescents aged 13 to 18 years in the continental United States. DSM-IV mental disorders were assessed using a modified version of the fully structured World Health Organization Composite International Diagnostic Interview. Results: Anxiety disorders were the most common condition (31.9%), followed by behavior disorders (19.1%), mood disorders (14.3%), and substance use disorders (11.4%), with approximately 40% of participants with one class of disorder also meeting criteria for another class of lifetime disorder. The overall prevalence of disorders with severe impairment and/or distress was 22.2% (11.2% with mood disorders, 8.3% with anxiety disorders, and 9.6% behavior disorders). The median age of onset for disorder classes was earliest for anxiety (6 years), followed by 11 years for behavior, 13 years for mood, and 15 years for substance use disorders. Conclusions: These findings provide the first prevalence data on a broad range of mental disorders in a nationally representative sample of U.S. adolescents. Approximately one in every four to five youth in the U.S. meets criteria for a mental disorder with severe impairment across their lifetime. The likelihood that common mental disorders in adults first emerge in childhood and adolescence highlights the need for a transition from the common focus on treatment of U.S. youth to that of prevention and early intervention. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(10):980-989.
C1 [Merikangas, Kathleen Ries; He, Jian-ping; Burstein, Marcy; Swanson, Sonja A.; Cui, Lihong] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA.
[Avenevoli, Shelli] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA.
[Georgiades, Katholiki] McMaster Univ, Hamilton, ON L8S 4L8, Canada.
[Swendsen, Joel] CNRS, Natl Ctr Sci Res, Bordeaux, France.
RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bldg 35,Room 1A201,35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
EM kathleen.merikangas@nih.gov
RI Benjet, Corina/D-7363-2012;
OI Benjet, Corina/0000-0002-4569-6094
FU National Institute of Mental Health [U01-MH60220]; National Institute of
Drug Abuse [R01 DA016558]; Robert Wood Johnson Foundation [044708]; John
W. Alden Trust
FX The National Comorbidity Survey Adolescent Supplement (NCS-A) and the
larger program of related NCS surveys ore supported by the National
Institute of Mental Health (U01-MH60220) and the National Institute of
Drug Abuse (R01 DA016558) with supplemental support from Substance Abuse
and Mental Health Services Administration, the Robert Wood Johnson
Foundation (Grant 044708), and the John W. Alden Trust. The NCS-A was
carried out in conjunction with the World Health Organization World
Mental Health Survey Initiative.; This work was supported by the
Intramural Research Program of the Notional Institute of Mental Health.
The views and opinions expressed in this article are those of the
authors and should not be construed to represent the views of any of the
sponsoring organizations, agencies, or U.S. Government.
NR 44
TC 974
Z9 984
U1 30
U2 180
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD OCT
PY 2010
VL 49
IS 10
BP 980
EP 989
DI 10.1016/j.jaac.2010.05.017
PG 10
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 655ZQ
UT WOS:000282295600002
PM 20855043
ER
PT J
AU Oji, V
Tadini, G
Akiyama, M
Bardon, CB
Bodemer, C
Bourrat, E
Coudiere, P
DiGiovanna, JJ
Elias, P
Fischer, J
Fleckman, P
Gina, M
Harper, J
Hashimoto, T
Hausser, I
Hennies, HC
Hohl, D
Hovnanian, A
Ishida-Yamamoto, A
Jacyk, WK
Leachman, S
Leigh, I
Mazereeuw-Hautier, J
Milstone, L
Morice-Picard, F
Paller, AS
Richard, G
Schmuth, M
Shimizu, H
Sprecher, E
Van Steensel, M
Taieb, A
Toro, JR
Vabres, P
Vahlquist, A
Williams, M
Traupe, H
AF Oji, Vinzenz
Tadini, Gianluca
Akiyama, Masashi
Bardon, Claudine Blanchet
Bodemer, Christine
Bourrat, Emmanuelle
Coudiere, Philippe
DiGiovanna, John J.
Elias, Peter
Fischer, Judith
Fleckman, Philip
Gina, Michal
Harper, John
Hashimoto, Takashi
Hausser, Ingrid
Hennies, Hans Christian
Hohl, Daniel
Hovnanian, Alain
Ishida-Yamamoto, Akemi
Jacyk, Witold K.
Leachman, Sancy
Leigh, Irene
Mazereeuw-Hautier, Juliette
Milstone, Leonard
Morice-Picard, Fanny
Paller, Amy S.
Richard, Gabriele
Schmuth, Matthias
Shimizu, Hiroshi
Sprecher, Eli
Van Steensel, Maurice
Taieb, Alain
Toro, Jorge R.
Vabres, Pierre
Vahlquist, Anders
Williams, Mary
Traupe, Heiko
TI Revised nomenclature and classification of inherited ichthyoses: Results
of the First Ichthyosis Consensus Conference in Soreze 2009
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
DE autosomal recessive congenital ichthyosis; epidermolytic ichthyosis;
genetics; histology; keratinopathic ichthyosis; mendelian disorders of
cornification; superficial epidermolytic ichthyosis; ultrastructure
ID RECESSIVE CONGENITAL ICHTHYOSIS; BATHING-SUIT ICHTHYOSIS; EPIDERMAL
PERMEABILITY BARRIER; HEALING COLLODION BABY; CHANARIN-DORFMAN-SYNDROME;
SJOGREN-LARSSON-SYNDROME; LIPID STORAGE DISEASE; OF-FUNCTION MUTATIONS;
PEELING-SKIN-SYNDROME; EPIDERMOLYTIC HYPERKERATOSIS
AB Background: Inherited ichthyoses belong to a large, clinically and etiologically heterogeneous group of mendelian disorders of cornification; typically involving the entire integument. Over the recent years, much progress has been made defining their molecular causes. However, there is no internationally accepted classification and terminology.
Objective: We sought to establish a consensus for the nomenclature and classification of inherited ichthyoses.
Methods: The classification project started at the First World Conference on Ichthyosis in 2007. A large international network of expert clinicians, skin pathologists, and geneticists entertained an interactive dialogue over 2 years, eventually leading to the First Ichthyosis Consensus Conference held in Soreze, France, on January 23 and 24, 2009, where subcommittees on different issues proposed terminology that was debated until consensus was reached.
Results: It was agreed that currently the nosology should remain clinically based. "Syndromic" versus "nonsyndromic" forms provide a useful major subdivision. Several clinical terms and controversial disease names have been redefined: eg, the group caused by keratin mutations is referred to by the umbrella term, "keratinopathic ichthyosis"-under which are included epidermolytic ichthyosis, superficial epidermolytic ichthyosis, and ichthyosis Curth-Macklin. "Autosomal recessive congenital ichthyosis" is proposed as an umbrella term for the harlequin ichthyosis, lamellar ichthyosis, and the congenital ichthyosiform erythroderma group.
Limitations: As more becomes known about these diseases in the future, modifications will be needed.
Conclusion: We have achieved an international consensus for the classification of inherited ichthyosis that should be useful for all clinicians and can serve as reference point for future research. (I Am Acad Dermatol 2010;63:607-41.)
C1 [Oji, Vinzenz; Traupe, Heiko] Univ Hosp Munster, Dept Dermatol, D-48149 Munster, Germany.
[Tadini, Gianluca] Osped Maggiore, Ist Ricovero & Cura Carattere Sci, Ist Sci Dermatol, Ctr Malattie Cutanee Ereditarie, Milan, Italy.
[Akiyama, Masashi; Shimizu, Hiroshi] Hokkaido Univ, Grad Sch Med, Dept Dermatol, Sapporo, Hokkaido, Japan.
[Bardon, Claudine Blanchet; Bourrat, Emmanuelle] Hop St Louis, Dept Dermatol, Paris, France.
[Bodemer, Christine] Univ Paris 05, Hop Necker Enfants Malad, APHP,Dept Dermatol, Natl Reference Ctr Genodermatoseis,Ctr Reference, F-75270 Paris 06, France.
[Coudiere, Philippe] Pierre Fabre Dermatol, Lavaur, France.
[DiGiovanna, John J.] Brown Univ, Warren Alpert Sch Med, Dept Dermatol, Div Dermatopharmacol, Providence, RI 02912 USA.
[Elias, Peter] Dept Vet Affairs Med Ctr, San Francisco, CA USA.
[Fischer, Judith] Ctr Natl Genotypage, Evry, France.
[Fleckman, Philip] Univ Washington, Div Dermatol, Seattle, WA 98195 USA.
[Gina, Michal; Hohl, Daniel] CHU Vaudois, Serv Dermatol Hosp, Hosp Cantonaux, CH-1011 Lausanne, Switzerland.
[Harper, John] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
[Hashimoto, Takashi] Kurume Univ, Sch Med, Dept Dermatol, Fukuoka, Japan.
[Hausser, Ingrid] Univ Hosp Heidelberg, Dept Dermatol, Heidelberg, Germany.
[Hennies, Hans Christian] Univ Cologne, Cologne Ctr Genom, Div Dermatogenet, Cologne, Germany.
[Hovnanian, Alain] Univ Paris 05, Hop Necker Enfants Malad, APHP, Dept Genet, F-75270 Paris 06, France.
[Hovnanian, Alain] Univ Paris 05, Hop Necker Enfants Malad, APHP, Dept Dermatol, F-75270 Paris 06, France.
[Ishida-Yamamoto, Akemi] Asahikawa Med Coll, Dept Dermatol, Asahikawa, Hokkaido 078, Japan.
[Hovnanian, Alain] Fac Med Toulouse, INSERM, U781, F-31073 Toulouse, France.
[Jacyk, Witold K.] Univ Pretoria, Dept Dermatol, ZA-0002 Pretoria, South Africa.
[Leachman, Sancy] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
[Leigh, Irene] Barts & London Med Sch Queen Mary, Inst Cell & Mol Sci, Ctr Cutaneous Res, London, England.
[Mazereeuw-Hautier, Juliette] Purpan Hosp, Dept Dermatol, Reference Ctr Rare Skin Dis, Toulouse, France.
[Milstone, Leonard] Yale Univ, New Haven, CT USA.
[Morice-Picard, Fanny; Taieb, Alain] Hop St Andre, Natl Reference Ctr Rare Skin Dis, Dept Dermatol & Pediat Dermatol, Bordeaux, France.
[Paller, Amy S.] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA.
[Paller, Amy S.] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA.
[Richard, Gabriele] GeneDx, Gaithersburg, MD USA.
[Schmuth, Matthias; Williams, Mary] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Schmuth, Matthias] Innsbruck Med Univ, Dept Dermatol, Innsbruck, Austria.
[Sprecher, Eli] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Dermatol, IL-69978 Tel Aviv, Israel.
[Van Steensel, Maurice] Maastricht Univ, Med Ctr, Dept Dermatol, Maastricht, Netherlands.
[Van Steensel, Maurice] GROW Res Sch Oncol & Dev Biol, Maastricht, Netherlands.
[Toro, Jorge R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Vabres, Pierre] Univ Bourgogne, Dept Dermatol, Hop Bocage, Dijon, France.
[Vahlquist, Anders] Uppsala Univ, Dept Med Sci Dermatol & Venereol, Uppsala, Sweden.
RP Oji, V (reprint author), Univ Hosp Munster, Dept Dermatol, Von Esmarch Str 58, D-48149 Munster, Germany.
EM ojiv@uni-muenster.de
RI MORICE-PICARD, Fanny/M-5125-2014; Fischer, Judith/E-6327-2016;
OI Oji, Vinzenz/0000-0003-1380-4828
FU Network for lchthyoses and Related Keratinization Disorders
(Bundesministerium fur Bildung und Forschung) [GFGM01143901]; Foundation
for lchthyosis and Related Skin Types (United States); Ichthyosis
Patient Organization of Germany
FX The accommodation and travel costs of the participants and the
conference rooms of the Ichthyosis Consensus Conference were sponsored
by the Laboratories Pierre Fabre, Castres, France. Moreover, our work is
supported by the Network for lchthyoses and Related Keratinization
Disorders (Bundesministerium fur Bildung und Forschung, GFGM01143901),
the Foundation for lchthyosis and Related Skin Types (United States),
and the Ichthyosis Patient Organization of Germany (Selbsthilfe
Ichthyose e. V.).
NR 235
TC 184
Z9 192
U1 3
U2 14
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD OCT
PY 2010
VL 63
IS 4
BP 607
EP 641
DI 10.1016/j.jaad.2009.11.020
PG 35
WC Dermatology
SC Dermatology
GA 653DZ
UT WOS:000282069400008
PM 20643494
ER
PT J
AU Zhu, BP
Han, JX
Shi, J
Shung, KK
Wei, Q
Huang, YH
Kosec, M
Zhou, QF
AF Zhu, Benpeng
Han, Jiangxue
Shi, Jing
Shung, Koping Krik
Wei, Qing
Huang, Yuhong
Kosec, Marija
Zhou, Qifa
TI Lift-Off PMN-PT Thick Film for High-Frequency Ultrasonic Biomicroscopy
SO JOURNAL OF THE AMERICAN CERAMIC SOCIETY
LA English
DT Article
ID TRANSDUCERS
AB Piezoelectric 0.65Pb(Mg(1/3)Nb(2/3))O(3)-0.35PbTiO(3) (PMN-35PT) thick film with a thickness of approximately 12 mu m has been deposited on the platinum-buffered Si substrate using a sol-gel composite method. The separation of the film from the substrate was achieved using a wet chemical method. The lifted-off PMN-35PT thick film exhibited good dielectric and ferroelectric properties. At 1 kHz, the dielectric constant and the dielectric loss were 3326 and 0.037, respectively, while the remnant polarization was 30.0 mu C/cm2. A high-frequency single-element acoustic transducer fabricated with this film showed a bandwidth at -6 dB of 63.6% at 110 MHz.
C1 [Zhu, Benpeng; Han, Jiangxue; Shung, Koping Krik; Zhou, Qifa] Univ So Calif, Dept Biomed Engn, NIH, Transducer Resource Ctr, Los Angeles, CA 90089 USA.
[Zhu, Benpeng] Huazhong Univ Sci & Technol, Dept Elect Sci & Technol, Wuhan 430074, Peoples R China.
[Shi, Jing] Wuhan Univ, Dept Phys, Minist Educ, Key Lab Acoust & Photon Mat & Devices, Wuhan 430072, Peoples R China.
[Wei, Qing; Huang, Yuhong] Chemat Technol Inc, Northridge, CA 91324 USA.
[Kosec, Marija] Jozef Stefan Inst, SI-1000 Ljubljana, Slovenia.
RP Zhou, QF (reprint author), Univ So Calif, Dept Biomed Engn, NIH, Transducer Resource Ctr, Los Angeles, CA 90089 USA.
EM qifazhou@usc.edu
FU NIH [P41-EB2182]; NSF SBIR [IIP-0838881]
FX This work was supported by the NIH grant P41-EB2182 and NSF SBIR Phase I
IIP-0838881.
NR 12
TC 13
Z9 13
U1 2
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-7820
J9 J AM CERAM SOC
JI J. Am. Ceram. Soc.
PD OCT
PY 2010
VL 93
IS 10
BP 2929
EP 2931
DI 10.1111/j.1551-2916.2010.03873.x
PG 3
WC Materials Science, Ceramics
SC Materials Science
GA 660JN
UT WOS:000282637200002
PM 21170158
ER
PT J
AU Saldanha, LG
Dwyer, JT
Andrews, KW
Bailey, RL
Gahche, JJ
Hardy, CJ
Holden, JM
Picciano, MF
Roseland, JM
Thomas, PR
Wolf, WR
AF Saldanha, Leila G.
Dwyer, Johanna T.
Andrews, Karen W.
Bailey, Regan L.
Gahche, Jaime J.
Hardy, Constance J.
Holden, Joanne M.
Picciano, Mary Frances
Roseland, Janet M.
Thomas, Paul R.
Wolf, Wayne R.
TI Online Dietary Supplement Resources
SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION
LA English
DT Article
C1 [Saldanha, Leila G.] NIH, Off Dietary Supplements, Alexandria, VA USA.
[Dwyer, Johanna T.; Bailey, Regan L.; Picciano, Mary Frances; Thomas, Paul R.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Andrews, Karen W.; Holden, Joanne M.; Roseland, Janet M.] ARS, USDA, Nutrient Data Lab, Beltsville, MD USA.
[Gahche, Jaime J.] CDC, Natl Hlth & Nutr Examinat Survey Planning Branch, Natl Ctr Hlth Stat, Hyattsville, MD USA.
[Hardy, Constance J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Wolf, Wayne R.] Food Composit & Methods Dev Lab, Beltsville, MD USA.
RP Saldanha, LG (reprint author), NIH, Off Dietary Supplements, Alexandria, VA USA.
OI Dwyer, Johanna/0000-0002-0783-1769
FU Office of Dietary Supplements, National Institutes of Health; ODS
FX Funds for the preparation of this article were provided by the Office of
Dietary Supplements, National Institutes of Health.; Describes the ODS
programs and offers links to research resources and research sponsored
by ODS.
NR 2
TC 7
Z9 8
U1 0
U2 1
PU AMER DIETETIC ASSOC
PI CHICAGO
PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA
SN 0002-8223
J9 J AM DIET ASSOC
JI J. Am. Diet. Assoc.
PD OCT
PY 2010
VL 110
IS 10
BP 1426
EP +
DI 10.1016/j.jada.2010.08.013
PG 4
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 657DJ
UT WOS:000282392600003
PM 20869478
ER
PT J
AU Reedy, J
Krebs-Smith, SM
AF Reedy, Jill
Krebs-Smith, Susan M.
TI Dietary Sources of Energy, Solid Fats, and Added Sugars among Children
and Adolescents in the United States
SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION
LA English
DT Article
ID BODY-MASS INDEX; US CHILDREN; NUTRIENTS; HEALTH; ADULTS; TRENDS; AGE
AB Objective The objective of this research was to identify top dietary sources of energy, solid fats, and added sugars among 2- to 18-year-olds in the United States.
Methods Data from the National Health and Nutrition Examination Survey, a cross-sectional study, were used to examine food sources (percentage contribution and mean intake with standard errors) of total energy (data from 2005-2006) and energy from solid fats and added sugars (data from 2003-2004). Differences were investigated by age, sex, race/ethnicity, and family income, and the consumption of empty calories defined as the sum of energy from solid fats and added sugars was compared with the corresponding discretionary calorie allowance.
Results The top sources of energy for 2- to 18-year-olds were grain desserts (138 kcal/day), pizza (136 kcal/day), and soda (118 kcal/day). Sugar-sweetened beverages (soda and fruit drinks combined) provided 173 kcal/day. Major contributors varied by age, sex, race/ethnicity, and income. Nearly 40% of total energy consumed (798 of 2,027 kcal/day) by 2- to 18-year-olds were in the form of empty calories (433 kcal from solid fat and 365 kcal from added sugars). Consumption of empty calories far exceeded the corresponding discretionary calorie allowance for all sex age groups (which range from 8% to 20%). Half of empty calories came from six foods: soda, fruit drinks, dairy desserts, grain desserts, pizza, and whole milk.
Conclusions There is an overlap between the major sources of energy and empty calories: soda, grain desserts, pizza, and whole milk. The landscape of choices available to children and adolescents must change to provide fewer unhealthy foods and more healthy foods with less energy. Identifying top sources of energy and empty calories can provide targets for changes in the marketplace and food environment. However, product reformulation alone is not sufficient the flow of empty calories into the food supply must be reduced. J Am Diet Assoc. 2010;110:1477-1484.
C1 [Reedy, Jill; Krebs-Smith, Susan M.] NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Reedy, J (reprint author), NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA.
EM reedyj@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 27
TC 251
Z9 256
U1 3
U2 51
PU AMER DIETETIC ASSOC
PI CHICAGO
PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA
SN 0002-8223
J9 J AM DIET ASSOC
JI J. Am. Diet. Assoc.
PD OCT
PY 2010
VL 110
IS 10
BP 1477
EP 1484
DI 10.1016/j.jada.2010.07.010
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 657DJ
UT WOS:000282392600012
PM 20869486
ER
PT J
AU Toner, CD
Davis, CD
Milner, JA
AF Toner, Cheryl D.
Davis, Cindy D.
Milner, John A.
TI The Vitamin D and Cancer Conundrum: Aiming at a Moving Target
SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION
LA English
DT Review
ID SERUM 25-HYDROXYVITAMIN D; D-RECEPTOR POLYMORPHISMS; PROSTATE-CANCER;
BREAST-CANCER; D DEFICIENCY; MULTIPLE-SCLEROSIS; COLORECTAL-CANCER; D
SUPPLEMENTATION; BLOOD-PRESSURE; BODY-FAT
AB The case for the influence of vitamin D on health, including cancer prevention, is increasingly compelling. While some are calling for increases in the Tolerable Upper Intake Level, fortification, and dietary supplementation, questions regarding dose and individual response variability continue to merit attention. Colorectal cancer risk reduction with adequate vitamin D status is well documented. Protection has also been observed for cancer at all sites, skin, prostate, and breast. At the same time, some individuals may be adversely affected by elevated 25(OH)D concentrations with respect to risk of cancers of the prostate, breast, pancreas, and esophagus, and in some cases a U- or J-shaped association has been suggested. Future research should seek to clarify if and for whom there may be an increased risk for cancer at particular sites with high 25(OH)D concentrations, and the concentrations at which risk increases. Fundamentally, prospective longitudinal studies of these relationships are warranted. The health status, life stage, adiposity, estrogen exposure, and nutritional status of study participants should be taken into account. Continued investigation is necessary to ensure that vitamin D recommendations are appropriately targeted to individuals who stand to benefit most, while protecting vulnerable subgroups from risk of overexposure. J Am Diet Assoc. 2010;110:1492-1500.
C1 [Toner, Cheryl D.; Davis, Cindy D.; Milner, John A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Toner, Cheryl D.] CDT Consulting LLC, Fairfax, VA USA.
RP Milner, JA (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH,Dept Hlth & Human Serv, 6130 Execut Blvd,Execut Plaza N Suite 3164, Bethesda, MD 20892 USA.
EM milnerj@mail.nih.gov
NR 106
TC 39
Z9 43
U1 0
U2 11
PU AMER DIETETIC ASSOC
PI CHICAGO
PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA
SN 0002-8223
J9 J AM DIET ASSOC
JI J. Am. Diet. Assoc.
PD OCT
PY 2010
VL 110
IS 10
BP 1492
EP 1500
DI 10.1016/j.jada.2010.07.007
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 657DJ
UT WOS:000282392600014
PM 20869488
ER
PT J
AU Chale-Rush, A
Guralnik, JM
Walkup, MP
Miller, ME
Rejeski, WJ
Katula, JA
King, AC
Glynn, NW
Manini, TM
Blair, SN
Fielding, RA
AF Chale-Rush, Angela
Guralnik, Jack M.
Walkup, Michael P.
Miller, Michael E.
Rejeski, W. Jack
Katula, Jeffrey A.
King, Abby C.
Glynn, Nancy W.
Manini, Todd M.
Blair, Steven N.
Fielding, Roger A.
TI Relationship Between Physical Functioning and Physical Activity in the
Lifestyle Interventions and Independence for Elders Pilot
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE older adults; mobility disability; physical function performance
ID PERIPHERAL ARTERIAL-DISEASE; LOWER-EXTREMITY FUNCTION; WALK 400 METERS;
OLDER-ADULTS; ACTIVITY QUESTIONNAIRE; DEPRESSIVE SYMPTOMS; MOBILITY
LIMITATION; BODY-COMPOSITION; MUSCLE STRENGTH; PERFORMANCE
AB OBJECTIVES
To determine whether participation in usual moderate-intensity or more-vigorous physical activity (MVPA) is associated with physical function performance and to identify sociodemographic, psychosocial, and disease-related covariates that may also compromise physical function performance.
DESIGN
Cross-sectional analysis of baseline variables of a randomized controlled intervention trial.
SETTING
Four academic research centers.
PARTICIPANTS
Four hundred twenty-four older adults aged 70 to 89 at risk for mobility disability (scoring < 10 on the Short Physical Performance Battery (SPPB)) and able to complete the 400-m walk test within 15 minutes.
MEASUREMENTS
Minutes of MVPA (dichotomized according to above or below 150 min/wk of MVPA) assessed according to the Community Healthy Activities Model Program for Seniors questionnaire, SPPB score, 400-m walk test, sex, body mass index (BMI), depressive symptoms, age, and number of medications.
RESULTS
The SPPB summary score was associated with minutes of MVPA (=0.16, P=.001). In multiple regression analyses, age, minutes of MVPA, number of medications, and depressive symptoms were associated with performance on the composite SPPB (P <.05). There was an association between 400-m walk time and minutes of MVPA (=-0.18; P <.001). In multiple regression analyses, age, sex, minutes of MVPA, BMI, and number of medications were associated with performance on the 400-m walk test (P <.05).
CONCLUSION
Minutes of MVPA, sex, BMI, depressive symptoms, age, and number of medications are associated with physical function performance and should all be taken into consideration in the prevention of mobility disability.
C1 [Chale-Rush, Angela; Fielding, Roger A.] Tufts Univ, Nutr Exercise Physiol & Sarcopenia Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Walkup, Michael P.; Miller, Michael E.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat, Winston Salem, NC USA.
[Rejeski, W. Jack; Katula, Jeffrey A.] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27109 USA.
[King, Abby C.] Stanford Univ, Dept Med, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA.
[Glynn, Nancy W.] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA.
[Manini, Todd M.] Univ Florida, Coll Med, Dept Aging & Geriatr Res, Inst Aging, Gainesville, FL USA.
[Blair, Steven N.] Univ S Carolina, Dept Exercise Sci & Epidemiol Biostat, Arnold Sch Publ Hlth, Columbia, SC 29208 USA.
RP Fielding, RA (reprint author), Tufts Univ, Nutr Exercise Physiol & Sarcopenia Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
EM roger.fielding@tufts.edu
RI Katula, Jeffrey/K-5905-2013;
OI Glynn, Nancy/0000-0003-2265-0162
FU U.S. Department of Agriculture [58-1950-7-707, DK007651]; Boston Claude
D. Pepper Older Americans Independence Center [1P30AG031679]; National
Institutes on Health (NIH), National Institute on Aging Cooperative
Agreement [UO1 AG22376]; National Institute on Aging, NIH; Pittsburgh
Claude D. Pepper Center [P30 AG024827]; National Institute on Aging
[K24AG021507]
FX Drs. Chale-Rush's and Fielding's contribution are supported by U.S.
Department of Agriculture Grants 58-1950-7-707 and DK007651 and the
Boston Claude D. Pepper Older Americans Independence Center
(1P30AG031679). Any opinions, findings, conclusions, or recommendations
expressed in this publication are those of the authors and do not
necessarily reflect the view of the U.S. Department of Agriculture.; The
LIFE-P Study is funded by National Institutes on Health (NIH), National
Institute on Aging Cooperative Agreement; UO1 AG22376 and sponsored in
part by the Intramural Research Program, National Institute on Aging,
NIH.; The Pittsburgh Field Center was partially supported by the
Pittsburgh Claude D. Pepper Center P30 AG024827.; Dr. Gill is the
recipient of a Midcareer Investigator Award in Patient-Oriented Research
(K24AG021507) from the National Institute on Aging.
NR 29
TC 22
Z9 22
U1 4
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD OCT
PY 2010
VL 58
IS 10
BP 1918
EP 1924
DI 10.1111/j.1532-5415.2010.03008.x
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 660ZP
UT WOS:000282690900012
PM 20738437
ER
PT J
AU Guralnik, JM
Kritchevsky, SB
AF Guralnik, Jack M.
Kritchevsky, Stephen B.
TI Translating Research to Promote Healthy Aging: The Complementary Role of
Longitudinal Studies and Clinical Trials
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE longitudinal studies; observational studies; clinical trials
ID PROSTATE-CANCER; BLOOD-PRESSURE; OLDER PERSONS; MORTALITY; RISK;
DISABILITY; DISEASE; ANEMIA; STROKE; HYPERTENSION
AB An important challenge in epidemiology is the difficulty in inferring causality from observational studies. Even the best longitudinal studies have limitations in this regard, and when clinical trials are feasible, they will provide more-definite evidence of causality, but even when clinical trials are feasible, a large amount can be learned about the disease process, assessment techniques, subject selection criteria, and the effect of potential interventions from longitudinal studies. This review covers the theoretical issues supporting the value and limitations of longitudinal studies, the practical utilization in clinical trials of different aspects of knowledge that can be gained from longitudinal studies, critical issues in the translation of longitudinal observational studies into clinical trials, and the value of observational studies in broadening the applicability of specific trials. Relevant issues are illustrated with examples of unsuccessful and successful trials, with a major emphasis on clinical trials of physical activity in older persons. J Am Geriatr Soc 58:S337-S342, 2010.
C1 [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
RP Guralnik, JM (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Room 3-C309, Bethesda, MD 20892 USA.
EM jack.guralnik@nih.gov
OI Kritchevsky, Stephen/0000-0003-3336-6781
FU Robert Wood Johnson Foundation; National Institute on Aging, National
Institutes of Heatlh, Wake Forest University Claude D. Pepper Older
Americans Independence Center [P30 AG21332]
FX The article is based on a January 2009, conference on Longitudinal
Studies in Aging supported by a grant from the Robert Wood Johnson
Foundation.; Supported in part by the Intramural Research Program,
National Institute on Aging, National Institutes of Heatlh, Wake Forest
University Claude D. Pepper Older Americans Independence Center (P30
AG21332).
NR 22
TC 14
Z9 14
U1 1
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD OCT
PY 2010
VL 58
SU 2
BP S337
EP S342
DI 10.1111/j.1532-5415.2010.02938.x
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 656YJ
UT WOS:000282376700013
PM 21029064
ER
PT J
AU Kelly-Hayes, M
AF Kelly-Hayes, Margaret
TI Influence of Age and Health Behaviors on Stroke Risk: Lessons from
Longitudinal Studies
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE stroke; prevention; risk factors; disability
ID CORONARY-HEART-DISEASE; LARGE SOCIAL NETWORK; ISCHEMIC-STROKE;
PHYSICAL-ACTIVITY; CIGARETTE-SMOKING; LIFETIME RISK; CARDIOVASCULAR
HEALTH; DEPRESSIVE SYMPTOMS; NORTHERN MANHATTAN; BLOOD-PRESSURE
AB Stroke is a major cause of death and serious neurological disability in older adults in the United States today. The most effective means available for reducing the burden of stroke involves risk factor modification. Given the growing number of older adults at risk for stroke, it is increasingly important to identify health behaviors that can produce significant change. Ongoing longitudinal studies have identified several behavioral factors that have been shown to improve overall health and reduce the risk of stroke, including effective management of hypertension, cessation of cigarette smoking for those who smoke, and maintaining a healthy diet and active physical lifestyle. Because modification of risk factors remains a primary intervention for effective prevention of stroke, community-based studies that address and institute stroke prevention strategies have the best opportunity to reduce or postpone the devastating effect of stroke. J Am Geriatr Soc 58:S325-S328, 2010.
C1 [Kelly-Hayes, Margaret] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Kelly-Hayes, Margaret] NHLBI, Framingham Heart Study, Boston, MA USA.
RP Kelly-Hayes, M (reprint author), Boston Univ, Sch Med, Dept Neurol, 72 E Concord St,B 610, Boston, MA 02118 USA.
EM mkhayes@bu.edu
FU Robert Wood Johnson Foundation; Framingham Heart Study National Heart,
Lung, and Blood Institute [N01-HC-25195]; National Institute of
Neurological Disorders and Stroke [5 R01 NS17950]
FX The article is based on a conference on longitudinal studies in aging
held in January 2009 and sponsored by a grant from the Robert Wood
Johnson Foundation.; Supported by Framingham Heart Study National Heart,
Lung, and Blood Institute Contract N01-HC-25195 and Grant 5 R01 NS17950
from the National Institute of Neurological Disorders and Stroke.
NR 39
TC 12
Z9 12
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD OCT
PY 2010
VL 58
SU 2
BP S325
EP S328
DI 10.1111/j.1532-5415.2010.02915.x
PG 4
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 656YJ
UT WOS:000282376700011
PM 21029062
ER
PT J
AU Schrack, JA
Simonsick, EM
Ferrucci, L
AF Schrack, Jennifer A.
Simonsick, Eleanor M.
Ferrucci, Luigi
TI The Energetic Pathway to Mobility Loss: An Emerging New Framework for
Longitudinal Studies on Aging
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE energy; aging; physical function; gait speed; fatigue
ID LOWER-EXTREMITY FUNCTION; HEALTHY OLDER-ADULTS; PHYSICAL PERFORMANCE
BATTERY; DISTANCE CORRIDOR WALK; FUNCTIONAL PERFORMANCE; SUBSEQUENT
DISABILITY; OVERGROUND WALKING; AEROBIC CAPACITY; ACTIVITY LEVEL;
OXYGEN-UPTAKE
AB The capacity to walk independently is a central component of independent living. Numerous large and well-designed longitudinal studies have shown that gait speed, a reliable marker of mobility, tends to decline with age and as a consequence of chronic disease. This decline in performance is of utmost importance because slow walking speed is a strong, independent predictor of disability, healthcare utilization, nursing home admission, and mortality. Based on these robust findings, it has been postulated that age-associated decline in walking speed is a reliable barometer of the effect of biological aging on health and functional status. Despite the extraordinary prognostic information that walking speed provides, which is often superior to traditional medical information, there is a limited understanding of the mechanisms that underlie age-and disease-related gait speed decline. Identifying the mechanisms that underlie the prognostic value of walking speed should be a central theme in the design of the next generation of longitudinal studies of aging, with appropriate measures introduced and analytical approaches incorporated.
This study hypothesized that a scarcity of available energy induces the decline in customary walking speed with aging and disease. Based on work in the Baltimore Longitudinal Study of Aging, examples of measures, operationalized dimensions, and analytical models that may be implemented to address this are provided. The main premise is simple: the biochemical processes that maintain life, secure homeostatic equilibrium, and prevent the collapse of health require energy. If energy becomes deficient, adaptive behaviors develop to conserve energy. J Am Geriatr Soc 58:S329-S336, 2010.
C1 [Schrack, Jennifer A.] Johns Hopkins Univ, Ctr Aging & Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Schrack, Jennifer A.; Simonsick, Eleanor M.; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
RP Schrack, JA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, 2024 E Monument St,Suite 2-700, Baltimore, MD 21205 USA.
EM jschrack@jhsph.edu
FU Robert Wood Johnson Foundation; National Institutes of Health, National
Institute on Aging (NIA)
FX This paper is based on a conference on Longitudinal Studies in Aging
held in January 2008 supported by a grant from the Robert Wood Johnson
Foundation.; This research was supported by the Intramural Research
Program of the National Institutes of Health, National Institute on
Aging (NIA).
NR 47
TC 50
Z9 52
U1 0
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD OCT
PY 2010
VL 58
SU 2
BP S329
EP S336
DI 10.1111/j.1532-5415.2010.02913.x
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 656YJ
UT WOS:000282376700012
PM 21029063
ER
PT J
AU Gates, MB
Tomer, KB
Deterding, LJ
AF Gates, Matthew B.
Tomer, Kenneth B.
Deterding, Leesa J.
TI Comparison of Metal and Metal Oxide Media for Phosphopeptide Enrichment
Prior to Mass Spectrometric Analyses
SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
LA English
DT Article
ID HIGHLY SELECTIVE ENRICHMENT; TITANIUM-DIOXIDE; PHOSPHORYLATED PEPTIDES;
AFFINITY-CHROMATOGRAPHY; PROTEIN-PHOSPHORYLATION; PROTEOLYTIC DIGESTS;
HISTONE-H5; SITES; TIO2; H1
AB Several affinity resins consisting of ionic metals or metal oxides were investigated for their phosphopeptide enrichment capabilities with subsequent mass spectrometric analyses. Commercially-available enrichment metal oxide affinity chromatography (MOAC) resins using manufacturer's and/or published protocols were compared and evaluated for the most efficient and selective method that could be implemented as a standard enrichment procedure. From these comparative analyses, using a tryptic digest of casein proteins, it was determined that in our hands, two of the resins out-performed the others based on a variety of criteria, including the number of phosphorylation sites identified during MS analyses, the lower numbers of nonspecifically bound peptides observed, and the limits of detection. Applicability of these enrichment resins to a complex biological mixture was investigated. For this work, a mixture of avian histones was digested, subjected to titanium dioxide phosphopeptide enrichment, and analyzed by mass spectrometry. Eight phosphorylated tryptic peptides were observed following enrichment and subsequent LC/MS/MS analyses. Of note, seven of the eight phosphopeptides were not observed without titanium dioxide enrichment. From these analyses, four sites of phosphorylation were unequivocally determined, two of which have not been reported previously. Four additional phosphopeptides were observed; however, the site of phosphorylation could not be distinguished but was localized to one of two possible amino acids. These methods should aid in the investigation of proteins post-translationally modified with phosphate, especially those present at low concentrations as was demonstrated by successful enrichment at the femtomole level. (J Am Soc Mass Spectrom 2010, 21, 1649-1659) Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry
C1 [Gates, Matthew B.; Tomer, Kenneth B.; Deterding, Leesa J.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Deterding, LJ (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233,MD F0-03, Res Triangle Pk, NC 27709 USA.
EM deterdi2@niehs.nih.gov
RI Tomer, Kenneth/E-8018-2013
FU H, National Institute of Environmental Health Sciences [ES050171]
FX The authors acknowledge support for this research by the Intra-mural
Research Program of the NIH, National Institute of Environmental Health
Sciences (ES050171). The authors thank Dr. Roxana Iacob and Dr. Jeffrey
Kuhn for their assistance and thoughtful input, and Dr. Allison
Schorzman and Dr. Jason Williams for critical review of this manuscript.
NIEHS does not endorse or recommend any commercial products, processes,
or services. The views and opinions expressed by authors affiliated with
NIEHS do not necessarily state or reflect those of the U.S. Government,
and they may not be used for advertising or product endorsement
purposes.
NR 33
TC 24
Z9 25
U1 1
U2 21
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1044-0305
J9 J AM SOC MASS SPECTR
JI J. Am. Soc. Mass Spectrom.
PD OCT
PY 2010
VL 21
IS 10
BP 1649
EP 1659
DI 10.1016/j.jasms.2010.06.005
PG 11
WC Biochemical Research Methods; Chemistry, Analytical; Chemistry,
Physical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA 659EC
UT WOS:000282548800003
PM 20634090
ER
PT J
AU Hager-Braun, C
Hochleitner, EO
Gorny, MK
Zolla-Pazner, S
Bienstock, RJ
Tomer, KB
AF Hager-Braun, Christine
Hochleitner, Elisabeth O.
Gorny, Miroslaw K.
Zolla-Pazner, Susan
Bienstock, Rachelle J.
Tomer, Kenneth B.
TI Characterization of a Discontinuous Epitope of the HIV Envelope Protein
gp120 Recognized by a Human Monoclonal Antibody Using Chemical
Modification and Mass Spectrometric Analysis
SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; IMMUNOGLOBULIN G1 B12; GLYCOPROTEIN
GP120; NEUTRALIZING ANTIBODIES; ARGININE RESIDUES; SURFACE-TOPOLOGY;
BINDING-SITE; RECEPTOR; RETROVIRUS; CORE
AB A subset of the neutralizing anti-HIV antibodies recognize epitopes on the envelope protein gp120 of the human immunodeficiency virus. These epitopes are exposed during conformational changes when gp120 binds to its primary receptor CD4. Based on chemical modification of lysine and arginine residues followed by mass spectrometric analysis, we determined the epitope on gp120 recognized by the human monoclonal antibody 559/64-D, which was previously found to be specific for the CD4 binding domain. Twenty-four lysine and arginine residues in recombinant full-length glycosylated gp120 were characterized; the relative reactivities of two lysine residues and five arginine residues were affected by the binding of 559/64-D. The data show that the epitope is discontinuous and is located in the proximity of the CD4-binding site. Additionally, the reactivities of a residue that is located in the secondary receptor binding region and several residues distant from the CD4 binding site were also altered by Ab binding. These data suggest that binding of 559/64-D induced conformational changes which result in altered surface exposure of specific amino acids distant from the CD4-binding site. Consequently, binding of 559/64-D to gp120 affects not only the CD4-binding site, which is recognized as the epitope, but appears to have a global effect on surface exposed residues of the full-length glycosylated gp120. (J Am Soc Mass Spectrom 2010, 21, 1687-1698) (C) 2010 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry
C1 [Hager-Braun, Christine; Hochleitner, Elisabeth O.; Bienstock, Rachelle J.; Tomer, Kenneth B.] Natl Inst Environm Hlth Sci, NIH, DHHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
[Gorny, Miroslaw K.; Zolla-Pazner, Susan] NYU, Sch Med, New York, NY USA.
[Gorny, Miroslaw K.; Zolla-Pazner, Susan] Vet Affairs New York Harbor Healthcare Syst, New York, NY USA.
RP Tomer, KB (reprint author), Natl Inst Environm Hlth Sci, NIH, DHHS, Struct Biol Lab, Bldg 101,MD F0-03,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM tomer@niehs.nih.gov
RI Tomer, Kenneth/E-8018-2013;
OI Bienstock, Rachelle/0000-0001-5228-3610; Gorny,
Miroslaw/0000-0002-2714-8780
FU National Institute of Environmental Health Sciences/National Institutes
of Health [z050150]; NIH/NHLBI [HL59725]
FX The authors acknowledge support in part for this research by the
Intramural Research Program of the National Institute of Environmental
Health Sciences/National Institutes of Health (z050150) and the
NIH/NHLBI (grant HL59725 to S.Z.-P).
NR 54
TC 7
Z9 7
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1044-0305
J9 J AM SOC MASS SPECTR
JI J. Am. Soc. Mass Spectrom.
PD OCT
PY 2010
VL 21
IS 10
BP 1687
EP 1698
DI 10.1016/j.jasms.2010.03.031
PG 12
WC Biochemical Research Methods; Chemistry, Analytical; Chemistry,
Physical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA 659EC
UT WOS:000282548800007
PM 20434359
ER
PT J
AU Jeang, KT
AF Jeang, Kuan-Teh
TI HTLV-1 and Adult T-Cell Leukemia: Insights into Viral Transformation of
Cells 30 Years After Virus Discovery
SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
LA English
DT Review
DE adult T cell leukemia; aneuploidy; HTLV; p53; spindle assembly
checkpoint
ID NF-KAPPA-B; I TAX ONCOPROTEIN; INTERLEUKIN-2 RECEPTOR GENE; 1ST HUMAN
RETROVIRUS; TYPE-1 TAX; RETINOBLASTOMA PROTEIN; CYCLE PROGRESSION; P53
INHIBITION; DNA-DAMAGE; G(1) PHASE
AB Human T-cell leukemia virus type 1 (HTLV-1), the etiological agent of adult T-cell leukemia, was the first human retrovirus to be isolated It is now the 30(th) anniversary of the initial discovery of HTLV-1 This review discusses recent insights into the role of the HTLV-1 Tax oncoprotein in cellular proliferation and the abrogation of cellular checkpoints that lead to disease progression
C1 NIH, Bethesda, MD 20892 USA.
RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
RI Jeang, Kuan-Teh/A-2424-2008
FU National Institute of Allergy and Infectious Diseases
FX The views expressed in this review are the personal opinions of the
author and do not reflect the views of his employer, the US National
Institutes of Health. Work in KTJ's laboratory is supported by
intramural funds from the National Institute of Allergy and Infectious
Diseases.
NR 82
TC 15
Z9 15
U1 0
U2 3
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 0929-6646
J9 J FORMOS MED ASSOC
JI J. Formos. Med. Assoc.
PD OCT
PY 2010
VL 109
IS 10
BP 688
EP 693
DI 10.1016/S0929-6646(10)60112-X
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 673AQ
UT WOS:000283630900002
PM 20970064
ER
PT J
AU Boyle, EW
AF Boyle, Eric W.
TI The History of American Homeopathy: From Rational Medicine to Holistic
Care
SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES
LA English
DT Book Review
C1 NIH, Off Hist, Bethesda, MD 20892 USA.
RP Boyle, EW (reprint author), NIH, Off Hist, Bldg 45,Room 3,An 38,45 Ctr Dr,MSC 6330, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-5045
J9 J HIST MED ALL SCI
JI J. Hist. Med. Allied Sci.
PD OCT
PY 2010
VL 65
IS 4
BP 589
EP 591
DI 10.1093/jhmas/jrq030
PG 3
WC Health Care Sciences & Services; History & Philosophy Of Science
SC Health Care Sciences & Services; History & Philosophy of Science
GA 669JW
UT WOS:000283344700011
ER
PT J
AU Workman, TE
Fiszman, M
Hurdle, JF
Rindflesch, TC
AF Workman, T. Elizabeth
Fiszman, Marcelo
Hurdle, John F.
Rindflesch, Thomas C.
TI Biomedical text summarization to support genetic database curation:
using Semantic MEDLINE to create a secondary database of genetic
information
SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION
LA English
DT Article
ID TRANSCRIPTION FACTORS; SYSTEMS BIOLOGY; LIBRARY
AB Objective: This paper examines the development and evaluation of an automatic summarization system in the domain of molecular genetics. The system is a potential component of an advanced biomedical information management application called Semantic MEDLINE and could assist librarians in developing secondary databases of genetic information extracted from the primary literature.
Methods: An existing summarization system was modified for identifying biomedical text relevant to the genetic etiology of disease. The summarization system was evaluated on the task of identifying data describing genes associated with bladder cancer in MEDLINE citations. A gold standard was produced using records from Genetics Home Reference and Online Mendelian Inheritance in Man. Genes in text found by the system were compared to the gold standard. Recall, precision, and F-measure were calculated.
Results: The system achieved recall of 46%, and precision of 88% (F-measure=0.61) by taking Gene References into Function (GeneRIFs) into account.
Conclusion: The new summarization schema for genetic etiology has potential as a component in Semantic MEDLINE to support the work of data curators.
C1 [Workman, T. Elizabeth; Hurdle, John F.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT 84112 USA.
[Rindflesch, Thomas C.] Natl Lib Med, Semant Knowledge Representat Project, Bethesda, MD 20894 USA.
RP Workman, TE (reprint author), Univ Utah, Dept Biomed Informat, 26 S 2000 E,HSEB 5700, Salt Lake City, UT 84112 USA.
EM liz.workman@utah.edu; fiszmanm@mail.nih.gov; john.hurdle@utah.edu;
tcr@nlm.nih.gov
FU NLM NIH HHS [T15 LM007124, T15LM007123]
NR 35
TC 6
Z9 6
U1 0
U2 4
PU MEDICAL LIBRARY ASSOC
PI CHICAGO
PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA
SN 1536-5050
J9 J MED LIBR ASSOC
JI J. Med. Libr. Assoc.
PD OCT
PY 2010
VL 98
IS 4
BP 273
EP 281
DI 10.3163/1536-5050.98.4.003
PG 9
WC Information Science & Library Science
SC Information Science & Library Science
GA 661VY
UT WOS:000282761900003
PM 20936065
ER
PT J
AU Hauptmann, M
Stewart, PA
Lubin, JH
Freeman, LEB
Hornung, RW
Herrick, RF
Hoover, RN
Fraumeni, JF
Blair, A
Hayes, RB
AF Hauptmann, M.
Stewart, P. A.
Lubin, J. H.
Freeman, L. E. Beane
Hornung, R. W.
Herrick, R. F.
Hoover, R. N.
Fraumeni, J. F., Jr.
Blair, A.
Hayes, R. B.
TI Re: Mortality From Lymphohematopoietic Malignancies and Brain Cancer
Among Embalmers Exposed to Formaldehyde Response
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
C1 [Hauptmann, M.; Stewart, P. A.; Lubin, J. H.; Freeman, L. E. Beane; Hoover, R. N.; Hayes, R. B.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Hauptmann, M.] Netherlands Canc Inst, Dept Bioinformat & Stat, Amsterdam, Netherlands.
[Stewart, P. A.] Stewart Exposure Assessments LLC, Arlington, VA USA.
[Hornung, R. W.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Herrick, R. F.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Hayes, R. B.] NYU Med Ctr, Dept Environm Med, New York, NY 10016 USA.
RP Freeman, LEB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM freemala@mail.nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD OCT
PY 2010
VL 102
IS 19
BP 1519
EP 1520
DI 10.1093/jnci/djq333
PG 2
WC Oncology
SC Oncology
GA 661TQ
UT WOS:000282751400015
ER
PT J
AU Gage, JC
Castle, PE
AF Gage, Julia C.
Castle, Philip E.
TI Preventing Cervical Cancer Globally by Acting Locally: If Not Now, When?
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID HUMAN-PAPILLOMAVIRUS INFECTION; HIV ACQUISITION; QUADRIVALENT VACCINE;
NEOPLASIA; DNA; WOMEN; RISK; REGRESSION; LESIONS; TESTS
C1 [Gage, Julia C.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Castle, Philip E.] NCI, Hormone & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
RP Castle, PE (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Executive Blvd,Rm 5026,MSC 7234, Bethesda, MD 20892 USA.
EM castlep@mail.nih.gov
FU Intramural NIH HHS
NR 30
TC 13
Z9 13
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD OCT
PY 2010
VL 102
IS 20
BP 1524
EP 1527
DI 10.1093/jnci/djq382
PG 4
WC Oncology
SC Oncology
GA 673PS
UT WOS:000283676000002
PM 20884892
ER
PT J
AU Demenais, F
Mohamdi, H
Chaudru, V
Goldstein, AM
Bishop, JAN
Bishop, DT
Kanetsky, PA
Hayward, NK
Gillanders, E
Elder, DE
Avril, MF
Azizi, E
van Belle, P
Bergman, W
Bianchi-Scarra, G
Bressac-de Paillerets, B
Calista, D
Carrera, C
Hansson, J
Harland, M
Hogg, D
Hoiom, V
Holland, EA
Ingvar, C
Landi, MT
Lang, JM
Mackie, RM
Mann, GJ
Ming, ME
Njauw, CJ
Olsson, H
Palmer, J
Pastorino, L
Puig, S
Randerson-Moor, J
Stark, M
Tsao, H
Tucker, MA
van der Velden, P
Yang, XR
Gruis, N
AF Demenais, F.
Mohamdi, H.
Chaudru, V.
Goldstein, A. M.
Bishop, J. A. Newton
Bishop, D. T.
Kanetsky, P. A.
Hayward, N. K.
Gillanders, E.
Elder, D. E.
Avril, M. F.
Azizi, E.
van Belle, P.
Bergman, W.
Bianchi-Scarra, G.
Bressac-de Paillerets, B.
Calista, D.
Carrera, C.
Hansson, J.
Harland, M.
Hogg, D.
Hoiom, V.
Holland, E. A.
Ingvar, C.
Landi, M. T.
Lang, J. M.
Mackie, R. M.
Mann, G. J.
Ming, M. E.
Njauw, C. J.
Olsson, H.
Palmer, J.
Pastorino, L.
Puig, S.
Randerson-Moor, J.
Stark, M.
Tsao, H.
Tucker, M. A.
van der Velden, P.
Yang, X. R.
Gruis, N.
CA Melanoma Genetics Consortium
TI Association of MC1R Variants and Host Phenotypes With Melanoma Risk in
CDKN2A Mutation Carriers: A GenoMEL Study
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID HUMAN MELANOCORTIN-1 RECEPTOR; MULTIPLE PRIMARY MELANOMAS; STIMULATING
HORMONE; CUTANEOUS MELANOMA; PRONE FAMILIES; GENE VARIANTS; RED HAIR;
SKIN PIGMENTATION; HUMAN MELANOCYTES; WIDE ASSOCIATION
AB Background Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.
Methods We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, >= 2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.
Results Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 x 10(-6) < P < .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; P(trend) = 1.86 x 10(-8)). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 <= P <= .04), hair color (.006 <= P <= .06), and number of nevi (6.9 x 10(-6) <= P <= .02).
Conclusion Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.
C1 [Demenais, F.; Mohamdi, H.; Chaudru, V.; Bressac-de Paillerets, B.] Fdn Jean Dausset CEPH, INSERM, U946, F-75010 Paris, France.
[Demenais, F.; Mohamdi, H.] Univ Paris Diderot, Inst Univ Hematol, Paris, France.
[Chaudru, V.] Univ Evry Val Essonne, Evry, France.
[Goldstein, A. M.; Landi, M. T.; Tucker, M. A.; Yang, X. R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Bishop, J. A. Newton; Bishop, D. T.; Harland, M.; Randerson-Moor, J.] St James Univ Hosp, Epidemiol & Biostat Sect, Leeds Inst Mol Med, Canc Res UK Clin Ctr, Leeds LS9 7TF, W Yorkshire, England.
[Kanetsky, P. A.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Kanetsky, P. A.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Hayward, N. K.; Palmer, J.; Stark, M.] Queensland Inst Med Res, Oncogen Lab, Brisbane, Qld 4006, Australia.
[Gillanders, E.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
[Elder, D. E.; van Belle, P.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Avril, M. F.] Univ Paris 05, Serv Dermatol, Hop Cochin, AP HP, Paris, France.
[Azizi, E.] Tel Aviv Univ, Dept Dermatol, Sheba Med Ctr, Sackler Fac Med, Tel Aviv, Israel.
[Bergman, W.; van der Velden, P.; Gruis, N.] Leiden Univ Med Ctr, Dept Dermatol, Leiden, Netherlands.
[Bianchi-Scarra, G.; Pastorino, L.] Univ Genoa, Dept Oncol Biol & Genet, I-16126 Genoa, Italy.
[Bianchi-Scarra, G.] San Martino Hosp, Lab Genet Rare Hereditary Canc, Genoa, Italy.
[Bressac-de Paillerets, B.] Inst Canc Gustave Roussy, Dept Mol Genet, Villejuif, France.
[Calista, D.] Maurizio Bufalini Hosp, Dermatol Unit, Cesena, Italy.
[Gillanders, E.] Hosp Clin Barcelona, Dept Dermatol, Melanoma Unit, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.
[Carrera, C.; Puig, S.] Ctr Invest Biomed Red CIBER Enfermedades Rares, Barcelona, Spain.
[Hansson, J.; Hoiom, V.] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
[Hogg, D.] Univ Toronto, Dept Med, Toronto, ON, Canada.
[Hogg, D.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada.
[Holland, E. A.; Mann, G. J.] Univ Sydney, Westmead Inst Canc Res, Westmead Millennium Inst, Westmead, NSW 2145, Australia.
[Holland, E. A.; Mann, G. J.] Melanoma Inst Australia, Westmead, NSW, Australia.
[Ingvar, C.] Univ Lund Hosp, Dept Surg, S-22185 Lund, Sweden.
[Lang, J. M.; Mackie, R. M.] Univ Glasgow, Dept Med Genet, Glasgow, Lanark, Scotland.
[Lang, J. M.; Mackie, R. M.] Univ Glasgow, Dept Publ Hlth, Glasgow, Lanark, Scotland.
[Ming, M. E.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA.
[Ming, M. E.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Njauw, C. J.; Tsao, H.] Massachusetts Gen Hosp, Wellman Ctr Photomed, MGH Melanoma & Pigmented Les Ctr, Boston, MA 02114 USA.
[Njauw, C. J.; Tsao, H.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Olsson, H.] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden.
RP Demenais, F (reprint author), Fdn Jean Dausset CEPH, INSERM, U946, 27 Rue Juliette Dodu, F-75010 Paris, France.
EM florence.demenais@inserm.fr
RI Stark, Mitchell/E-3542-2010; Mann, Graham/G-4758-2014; Bianchi Scarra,
Giovanna/G-8933-2014; Demenais, Florence/G-3298-2013; Tucker,
Margaret/B-4297-2015; hayward, nicholas/C-1367-2015; Duffy,
David/B-7392-2013; Marti, Rosa/A-2256-2010; Bruno, William/N-7477-2013;
Hoiom, Veronica/F-4153-2012; bertazzi, pietro alberto/D-5039-2017
OI Bishop, Tim/0000-0002-8752-8785; Newton Bishop,
Julia/0000-0001-9147-6802; Puig, Susana/0000-0003-1337-9745; CARRERA,
CRISTINA/0000-0003-1608-8820; Badenas, Celia/0000-0002-0621-0477; Gruis,
Nelleke/0000-0002-5210-9150; Stark, Mitchell/0000-0002-4510-2161; Mann,
Graham/0000-0003-1301-405X; Bianchi Scarra,
Giovanna/0000-0002-6127-1192; Demenais, Florence/0000-0001-8361-0936;
hayward, nicholas/0000-0003-4760-1033; Duffy, David/0000-0001-7227-632X;
Marti, Rosa/0000-0001-6866-6114; Bruno, William/0000-0002-0337-0168;
bertazzi, pietro alberto/0000-0003-3475-2449
FU European Community [LSH-CT-2006-018702]; National Institutes of Health
[RO1 CA83115, RO1 CA88363, RO1 CA5558-01A2]; Ligue Nationale contre le
Cancer [PRE05/FD, PRE09/FD]; Programme Hospitalier de Recherche Clinique
[PHRC 2007-AOM-07-195]; French Institut National du Cancer [13];
National Cancer Institute, Division of Cancer Epidemiology and Genetics,
National Institutes of Health; Cancer Research UK Programme
[C588/A4994]; Australian National Health and Medical Research Council;
Cancer Councils of New South Wales, Victoria and Queensland; Cancer
Institute NSW; Italian Ministry of Health [DGRST. 4/4235-P1.9. A. B];
Swedish Cancer Society; Radiumhemmet Research Funds; Swedish Research
Council; Swedish Cancer foundation; Regional funds in Skane; University
Hospital in Lund; Fondo de Investigaciones Sanitarias, Spain [03/0019,
05/0302, 06/0265]
FX European Community FP6 Network of Excellence Award (LSH-CT-2006-018702
to J.A.N.B. and N.G.); the National Institutes of Health (RO1 CA83115 to
D. E. E., RO1 CA88363 to N.K.H., RO1 CA5558-01A2 to M. T. L.); the Ligue
Nationale contre le Cancer (PRE05/FD and PRE09/FD to F. D.); the
Programme Hospitalier de Recherche Clinique (PHRC 2007-AOM-07-195 to F.
D. and M. F. A.); the French Institut National du Cancer (Melanoma
Network RS Number 13 to BB-dP); the Intramural Research Program of the
National Cancer Institute, Division of Cancer Epidemiology and Genetics,
National Institutes of Health to A. M. G, M. T. L., M. A. T and X.R.Y.;
the Cancer Research UK Programme Award (C588/A4994 to J.A.N.B. and D. T.
B.); the Australian National Health and Medical Research Council (to
N.K.H. and to G.J.M.); the Cancer Councils of New South Wales, Victoria
and Queensland to N.K.H. and G.J.M.; the Cancer Institute NSW to N.K.H.
and G.J.M.; the Italian Ministry of Health (DGRST. 4/4235-P1.9. A. B to
G. B-S.); the Swedish Cancer Society to J.H.: the Radiumhemmet Research
Funds to J.H.; the Swedish Research Council to J.H; the Swedish Cancer
foundation to C. I and H.O.; the Regional funds in Skane to C. I and
H.O.; the funds at the University Hospital in Lund to C. I and H.O.; and
Fondo de Investigaciones Sanitarias, Spain (03/0019, 05/0302, 06/0265 to
S.P.).
NR 59
TC 38
Z9 40
U1 0
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD OCT
PY 2010
VL 102
IS 20
BP 1568
EP 1583
DI 10.1093/jnci/djq363
PG 16
WC Oncology
SC Oncology
GA 673PS
UT WOS:000283676000010
PM 20876876
ER
PT J
AU Howlader, N
Ries, LAG
Mariotto, AB
Reichman, ME
Ruhl, J
Cronin, KA
AF Howlader, Nadia
Ries, Lynn A. G.
Mariotto, Angela B.
Reichman, Marsha E.
Ruhl, Jennifer
Cronin, Kathleen A.
TI Improved Estimates of Cancer-Specific Survival Rates From
Population-Based Data
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID DEATH CERTIFICATES; RELATIVE SURVIVAL; MORTALITY; US
AB Background Accurate estimates of cancer survival are important for assessing optimal patient care and prognosis. Evaluation of these estimates via relative survival (a ratio of observed and expected survival rates) requires a population life table that is matched to the cancer population by age, sex, race and/or ethnicity, socioeconomic status, and ideally risk factors for the cancer under examination. Because life tables for all subgroups in a study may be unavailable, we investigated whether cause-specific survival could be used as an alternative for relative survival.
Methods We used data from the Surveillance, Epidemiology, and End Results Program for 2 330 905 cancer patients from January 1, 1992, through December 31, 2004. We defined cancer-specific deaths according to the following variables: cause of death, only one tumor or the first of multiple tumors, site of the original cancer diagnosis, and comorbidities. Estimates of relative survival and cause-specific survival that were derived by use of an actuarial method were compared.
Results Among breast cancer patients who were white, black, or of Asian or Pacific Islander descent and who were older than 65 years, estimates of 5-year relative survival (107.5%, 106.6%, and 103.0%, respectively) were higher than estimates of 5-year cause-specific survival (98.6%, 95% confidence interval [CI] = 98.4% to 98.8%; 97.4%, 95% CI = 96.2% to 98.2%; and 99.2%, 95% CI = 98.4%, 99.6%, respectively). Relative survival methods likely underestimated rates for cancers of the oral cavity and pharynx (eg, for white cancer patients aged >= 65 years, relative survival = 54.2%, 95% CI = 53.1% to 55.3%, and cause-specific survival = 60.1%, 95% CI = 59.1% to 60.9%) and the lung and bronchus (eg, for black cancer patients aged >65 years, relative survival = 10.5%, 95% CI = 9.9% to 11.2%, and cause-specific survival = 11.9%, 95% CI = 11.2 % to 12.6%), largely because of mismatches between the population with these diseases and the population used to derive the life table. Socioeconomic differences between groups with low and high status in relative survival estimates appeared to be inflated (eg, corpus and uterus socioeconomic status gradient was 13.3% by relative survival methods and 8.8% by cause-specific survival methods).
Conclusion Although accuracy of the cause of death on a death certificate can be problematic for cause-specific survival estimates, cause-specific survival methods may be an alternative to relative survival methods when suitable life tables are not available.
C1 [Howlader, Nadia] NCI, Data Anal & Interpretat Branch, Surveillance Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA.
RP Howlader, N (reprint author), NCI, Data Anal & Interpretat Branch, Surveillance Res Program, Div Canc Control & Populat Sci,NIH, 6116 Executive Blvd,Ste 504, Bethesda, MD 20892 USA.
EM howladern@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
FX Division of Cancer Control and Population Sciences, Surveillance
Research Program, National Cancer Institute, National Institutes of
Health.
NR 28
TC 121
Z9 128
U1 0
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD OCT
PY 2010
VL 102
IS 20
BP 1584
EP 1598
DI 10.1093/jnci/djq366
PG 15
WC Oncology
SC Oncology
GA 673PS
UT WOS:000283676000011
PM 20937991
ER
PT J
AU Raffensperger, S
Kuczmarski, MF
Hotchkiss, L
Cotugna, N
Evans, MK
Zonderman, AB
AF Raffensperger, Sarah
Kuczmarski, Marie Fanelli
Hotchkiss, Lawrence
Cotugna, Nancy
Evans, Michele K.
Zonderman, Alan B.
TI Effect of Race and Predictors of Socioeconomic Status on Diet Quality in
the HANDLS Study Sample
SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
LA English
DT Article
DE race/ethnicity; socioeconomic status; antioxidants; free radicals;
superoxides
ID FOOD STORE AVAILABILITY; MISSISSIPPI-DELTA; NATIONAL-HEALTH;
UNITED-STATES; US ADULTS; NUTRITION; PREVENTION; PATTERNS; NEIGHBORHOOD;
POPULATION
AB Purpose: To examine effects of race and predictors of socioeconomic status (SES) on nutrient-based diet quality and their contribution to health disparities in an urban population of low SES.
Design: Data were analyzed from a sample of the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) Study participants examining effects of age, sex, race, income, poverty income ratio, education, employment, and smoking status on nutrient-based diet quality as measured by a micronutrient composite index of nutrient adequacy ratios and a mean adequacy ratio. Regression models were used to examine associations and t tests were used to look at racial differences.
Subjects: African American and white adults ages 30 to 64 years residing in 12 predefined census tracts in Baltimore, Maryland.
Results: Sex, age, education, poverty income ratio, and income were statistically significant predictors of diet quality for African Americans, while sex, education, and smoking status were statistically significant for whites. African Americans had lower mean adequacy ratio scores than whites (76.4 vs 79.1). Whites had significantly higher nutrient adequacy ratios scores for thiamin, riboflavin, folate, B(12), vitamins A and E, magnesium, copper, zinc, and calcium, while African Americans had higher vitamin C scores.
Conclusion: Education significantly impacted diet quality in the HANDLS sample, but race cannot be discounted. Whether the racial differences in diet quality are indicative of cultural differences in food preferences, selection, preparation, and availability, or disparities in socioeconomic status remains unclear.
C1 [Raffensperger, Sarah; Kuczmarski, Marie Fanelli; Cotugna, Nancy] Univ Delaware, Dept Hlth Nutr & Exercise Sci, Newark, DE 19716 USA.
[Hotchkiss, Lawrence] Univ Delaware, Dept Informat Technol, Newark, DE 19716 USA.
[Evans, Michele K.; Zonderman, Alan B.] NIA, Biomed Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA.
RP Cotugna, N (reprint author), Univ Delaware, Dept Hlth Nutr & Exercise Sci, Newark, DE 19716 USA.
EM ncotugna@udel.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institute of Aging, National Institutes of Health
FX This research was funded by the Intramural Research Program of the
National Institute of Aging, National Institutes of Health.
NR 40
TC 20
Z9 20
U1 0
U2 12
PU NATL MED ASSOC
PI WASHINGON
PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA
SN 0027-9684
J9 J NATL MED ASSOC
JI J. Natl. Med. Assoc.
PD OCT
PY 2010
VL 102
IS 10
BP 923
EP 930
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 672VN
UT WOS:000283615100009
PM 21053707
ER
PT J
AU Patz, EF
Caporaso, NE
Dubinett, SM
Massion, PP
Hirsch, FR
Minna, JD
Gatsonis, C
Duan, FH
Adams, A
Apgar, C
Medina, RM
Aberle, DR
AF Patz, Edward F., Jr.
Caporaso, Neil E.
Dubinett, Steven M.
Massion, Pierre P.
Hirsch, Fred R.
Minna, John D.
Gatsonis, Constantine
Duan, Fenghai
Adams, Amanda
Apgar, Charles
Medina, Rosa M.
Aberle, Denise R.
TI National Lung Cancer Screening Trial American College of Radiology
Imaging Network Specimen Biorepository Originating from the Contemporary
Screening for the Detection of Lung Cancer Trial (NLST, ACRIN 6654)
Design, Intent, and Availability of Specimens for Validation of Lung
Cancer Biomarkers
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Editorial Material
ID OVERDIAGNOSIS BIAS; PROJECT; DIAGNOSIS; NODULES
C1 [Patz, Edward F., Jr.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA.
[Patz, Edward F., Jr.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
[Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA.
Vanderbilt Univ, Med Ctr, Div Pulm & Crit Care Med, Thorac Oncol Ctr, Nashville, TN USA.
[Hirsch, Fred R.] Univ Colorado, Ctr Canc, Aurora, CO USA.
[Minna, John D.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA.
[Gatsonis, Constantine; Duan, Fenghai; Adams, Amanda] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA.
[Apgar, Charles; Medina, Rosa M.] Amer Coll Radiol, ACRIN Adm, Philadelphia, PA USA.
[Aberle, Denise R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci Thorac Imaging & Bioengn, Los Angeles, CA 90095 USA.
RP Patz, EF (reprint author), Duke Univ, Med Ctr, Dept Radiol, Box 3808, Durham, NC 27710 USA.
EM patz0002@mc.duke.edu
RI Duan, Fenghai/J-3709-2014
OI Duan, Fenghai/0000-0002-5084-0070
FU NCI NIH HHS [P50 CA070907, U01 CA079778, U01 CA080098]
NR 14
TC 14
Z9 14
U1 0
U2 1
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 OCT
PY 2010
VL 5
IS 10
BP 1502
EP 1506
DI 10.1097/JTO.0b013e3181f1c634
PG 5
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 653UI
UT WOS:000282122000004
PM 20871260
ER
PT J
AU Engels, EA
AF Engels, Eric A.
TI Epidemiology of Thymoma and Associated Malignancies
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 1st International Conference Thymic Malignancies
CY AUG 20-21, 2009
CL Bethesda, MD
DE Thymoma; Epidemiology; Secondary malignancies; Sarcomas; Cancer
registries; Non-Hodgkin's lymphoma
ID EPSTEIN-BARR-VIRUS; THYMIC EPITHELIAL TUMORS; IN-SITU HYBRIDIZATION;
HUMAN FOAMY VIRUS; MYASTHENIA-GRAVIS; UNITED-STATES; CANCERS; RISK;
NEOPLASMS; INFECTION
AB Background: Thymoma is a rare malignancy of unknown etiology.
Methods: The author examined patterns in thymoma incidence in the US general population using data from Surveillance, Epidemiology, and End Results (SEER) cancer registries. Prior studies concerning the risk of additional malignancies in thymoma patients were reviewed.
Results: Based on cancer registry data, the overall incidence of thymoma in the US is 0.13 per 100,000 person-years. Thymoma is exceedingly uncommon in children and young adults, rises in incidence in middle age, and peaks in the seventh decade of life. Thymoma incidence is especially high among Asians and Pacific Islanders in the US. While several studies based at single treatment centers have suggested that thymoma patients have a broadly increased risk for other malignancies, follow up data from US cancer registries support a more limited spectrum of cancer risk. In particular, thymoma patients have a subsequently elevated risk for developing B-cell non-Hodgkin's lymphoma. Based on limited data, thymoma patients may also have an elevated risk for developing soft tissue sarcomas.
Discussion: Thymoma is a rare malignancy. The excess risk for non-Hodgkin's lymphoma is consistent with an effect of immune disturbance arising from the thymoma or its treatment. While descriptive epidemiologic data may yield clues to the etiology of thymoma, large multi-center case-control studies will be required to formally evaluate environmental and genetic risk factors.
C1 [Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Engels, EA (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Executive Blvd,EPS 7076, Bethesda, MD 20892 USA.
EM engelse@exchange.nih.gov
NR 34
TC 83
Z9 94
U1 3
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD OCT
PY 2010
VL 5
SU 4
BP S260
EP S265
DI 10.1097/JTO.0b013e3181f1f62d
PG 6
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 658PV
UT WOS:000282502800002
PM 20859116
ER
PT J
AU Giaccone, G
AF Giaccone, Giuseppe
TI Foreword
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Editorial Material
C1 [Giaccone, Giuseppe] NCI, Med Oncol & Affiliated Branches, NIH, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
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 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD OCT
PY 2010
VL 5
SU 4
BP S259
EP S259
DI 10.1097/JTO.0b013e3181f1f61c
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 658PV
UT WOS:000282502800001
PM 20859115
ER
PT J
AU Lee, DK
Hakim, FT
Gress, RE
AF Lee, Diana K.
Hakim, Frances T.
Gress, Ronald E.
TI The Thymus and the Immune System Layered Levels of Control
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 1st International Conference Thymic Malignancies
CY AUG 20-21, 2009
CL Bethesda, MD
DE Thymopoiesis; Thymic epithelial cells; Thymocytes; IGF-1; KGF; Androgen
withdrawal
ID KERATINOCYTE GROWTH-FACTOR; T-CELL DEVELOPMENT; EPITHELIAL-CELLS;
IN-VIVO; THYMOPOIESIS; INCREASES; EXPANSION; CONSEQUENCES; RECEPTOR;
SUBSETS
AB Control points of normal thymopoiesis may provide insights into strategies for interrupting cell interactions in thymomas which appear to maintain active T cell production. Thymus production of T cells represents one of two pathways by which peripheral T cell populations are maintained or, if lost, regenerated. The production of T cells by the thymus results from a series of thymus epithelial cell (TEC) - thymocyte interactions from entry of thymocyte precursors into the thymus to release of mature naive single positive T cells into the periphery. Within this series of interactions, certain control points have been identified, all of which act through TEC to modulate thymopoiesis.
C1 [Gress, Ronald E.] NCI, NIH, Ctr Canc Res, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Gress, RE (reprint author), NCI, NIH, Ctr Canc Res, Expt Transplantat & Immunol Branch, 10 Ctr Dr,Bldg 10,Room CRC3-3350, Bethesda, MD 20892 USA.
EM gressr@mail.nih.gov
NR 25
TC 5
Z9 7
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD OCT
PY 2010
VL 5
SU 4
BP S273
EP S276
DI 10.1097/JTO.0b013e3181f20474
PG 4
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 658PV
UT WOS:000282502800004
PM 20859118
ER
PT J
AU Rajan, A
Giaccone, G
AF Rajan, Arun
Giaccone, Giuseppe
TI Targeted Therapy for Advanced Thymic Tumors
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 1st International Conference Thymic Malignancies
CY AUG 20-21, 2009
CL Bethesda, MD
DE Thymoma; Thymic carcinoma; Targeted therapy; Gefitinib; Imatinib;
Belinostat; Sorafenib; Cixutumumab; Octreotide
ID SOLID TUMORS; THYMOMA; CARCINOMA; KIT; CETUXIMAB; IMATINIB
AB The use of targeted therapies for the treatment of thymic malignancies is documented in the literature. However, only a few drugs have undergone evaluation in phase II trials. Most of the evidence for the benefit of biologic therapies for thymic malignancies is in the form of case reports and small case series. No major activity has been observed with any agent so far, likely due to the lack of selection of patients for targeted therapies and the small numbers studied. A better understanding of the biology of these tumors will be essential in furthering the field.
C1 [Giaccone, Giuseppe] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 12N226, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
FU Intramural NIH HHS [ZID BC010951-02]
NR 26
TC 10
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 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD OCT
PY 2010
VL 5
SU 4
BP S361
EP S364
PG 4
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 658PV
UT WOS:000282502800020
PM 20859134
ER
PT J
AU Wright, CD
AF Wright, Cameron D.
TI Extended Resections for Thymic Malignancies
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 1st International Conference Thymic Malignancies
CY AUG 20-21, 2009
CL Bethesda, MD
DE Thymic malignancy; Superior vena cava resection; Pleuropneumonectomy
ID SUPERIOR VENA-CAVA; STAGE IVA THYMOMA; MEDIASTINAL MALIGNANCIES;
MULTIMODALITY THERAPY; TUMORS; MANAGEMENT; RECURRENCE; REPLACEMENT;
PREDICTORS; INVASION
AB Almost all series reporting on the results of resection in thymic tumors indicate that the performance of a complete resection is probably the most important prognostic factor. This issue is not a factor in Masaoka stage I and II tumors that are almost always easily completely resected and have an excellent prognosis. Masaoka stage III tumors that invade the pericardium, lungs, or great vessels have relatively higher incomplete resection rates, significantly higher recurrence rates, and thus a worse prognosis. There are several small reports on the efficacy of resection of the great veins when involved by a thymic malignancy with low morbidity and meaningful long-term survival. Superior vena cava reconstruction is commonly performed by a polytetrafluroethylene, venous, or pericardial graft. These cases can usually be identified preoperatively and, thus, considered for induction therapy. Because these types of cases are almost always of marginal respectability in terms of obtaining a true en bloc resection, there is an increasing enthusiasm for offering induction therapy in an effort to enhance resectability. Preliminary results suggest increased R0 resection rates and improved survival with induction therapy for locally advanced tumors. The optimal induction treatment is unknown. The ultimate extended surgery for advanced thymic tumors is an extrapleural pneumonectomy performed for extensive pleural disease (Masaoka stage IVA). These rarely performed operations are done for IVA disease found at initial presentation and for recurrent disease as a salvage procedure. Again these advanced patients are probably best managed by induction chemotherapy followed by resection.
C1 [Wright, Cameron D.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA.
[Wright, Cameron D.] NCI, Dept Med Oncol, Bethesda, MD 20892 USA.
RP Wright, CD (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,32 Fruit St, Boston, MA 02114 USA.
EM cdwright@partners.org
NR 22
TC 7
Z9 7
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD OCT
PY 2010
VL 5
SU 4
BP S344
EP S347
PG 4
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 658PV
UT WOS:000282502800016
PM 20859130
ER
PT J
AU Crane, NJ
Gillern, SM
Tajkarimi, K
Levin, IW
Pinto, PA
Elster, EA
AF Crane, Nicole J.
Gillern, Suzanne M.
Tajkarimi, Kambiz
Levin, Ira W.
Pinto, Peter A.
Elster, Eric A.
TI Visual Enhancement of Laparoscopic Partial Nephrectomy With 3-Charge
Coupled Device Camera: Assessing Intraoperative Tissue Perfusion and
Vascular Anatomy by Visible Hemoglobin Spectral Response
SO JOURNAL OF UROLOGY
LA English
DT Article
DE kidney; nephrectomy; video-assisted surgery; laparoscopy; ischemia
ID NEPHRON SPARING SURGERY; PATHOLOGICAL OUTCOMES; RENAL ISCHEMIA; WARM
ISCHEMIA; HILAR TUMORS; SHORT-TERM; FEASIBILITY; TECHNOLOGY; IMPACT
AB Purpose: We report the novel use of 3-charge coupled device camera technology to infer tissue oxygenation. The technique can aid surgeons to reliably differentiate vascular structures and noninvasively assess laparoscopic intraoperative changes in renal tissue perfusion during and after warm ischemia.
Materials and Methods: We analyzed select digital video images from 10 laparoscopic partial nephrectomies for their individual 3-charge coupled device response. We enhanced surgical images by subtracting the red charge coupled device response from the blue response and overlaying the calculated image on the original image. Mean intensity values for regions of interest were compared and used to differentiate arterial and venous vasculature, and ischemic and nonischemic renal parenchyma.
Results: The 3-charge coupled device enhanced images clearly delineated the vessels in all cases. Arteries were indicated by an intense red color while veins were shown in blue. Differences in mean region of interest intensity values for arteries and veins were statistically significant (p > 0.0001). Three-charge coupled device analysis of pre-clamp and post-clamp renal images revealed visible, dramatic color enhancement for ischemic vs nonischemic kidneys. Differences in the mean region of interest intensity values were also significant (p < 0.05).
Conclusions: We present a simple use of conventional 3-charge coupled device camera technology in a way that may provide urological surgeons with the ability to reliably distinguish vascular structures during hilar dissection, and detect and monitor changes in renal tissue perfusion during and after warm ischemia.
C1 [Crane, Nicole J.; Gillern, Suzanne M.; Elster, Eric A.] Uniformed Serv Univ Hlth Sci, Naval Med Res Ctr, Dept Regenerat Med, Silver Spring, MD 20910 USA.
[Tajkarimi, Kambiz; Pinto, Peter A.] NCI, NIH, Bethesda, MD 20892 USA.
[Levin, Ira W.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Elster, Eric A.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA.
[Gillern, Suzanne M.] Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA.
[Tajkarimi, Kambiz] George Washington Univ, Dept Urol, Washington, DC USA.
RP Elster, EA (reprint author), Uniformed Serv Univ Hlth Sci, Naval Med Res Ctr, Dept Regenerat Med, 503 Robert Grant Ave,Suite 2W123, Silver Spring, MD 20910 USA.
EM eric.elster@med.navy.mil
FU United States Navy Bureau of Medicine and Surgery [PE 0604771N]; Office
of Naval Research work unit [604771N.0933. 001.A0812]; Vibernet
FX Supported by the United States Navy Bureau of Medicine and Surgery under
the Medical Development Program (PE 0604771N), Office of Naval Research
work unit No. 604771N.0933. 001.A0812, Combat Wound Initiative Program
and intramural program of National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health.; Financial interest
and/or other relationship with Vibernet.
NR 29
TC 18
Z9 18
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD OCT
PY 2010
VL 184
IS 4
BP 1279
EP 1285
DI 10.1016/j.juro.2010.06.010
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 660CB
UT WOS:000282615400010
PM 20723937
ER
PT J
AU Rockx, B
Bossart, KN
Feldmann, F
Geisbert, JB
Hickey, AC
Brining, D
Callison, J
Safronetz, D
Marzi, A
Kercher, L
Long, D
Broder, CC
Feldmann, H
Geisbert, TW
AF Rockx, Barry
Bossart, Katharine N.
Feldmann, Friederike
Geisbert, Joan B.
Hickey, Andrew C.
Brining, Douglas
Callison, Julie
Safronetz, David
Marzi, Andrea
Kercher, Lisa
Long, Dan
Broder, Christopher C.
Feldmann, Heinz
Geisbert, Thomas W.
TI A Novel Model of Lethal Hendra Virus Infection in African Green Monkeys
and the Effectiveness of Ribavirin Treatment
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID NIPAH VIRUS; HAMSTER MODEL; FATAL ENCEPHALITIS; SUBUNIT VACCINE;
PARAMYXOVIRUS; PATHOGENESIS; PROTECTION; ANTIBODY; HORSES; DEATH
AB The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are emerging zoonotic paramyxoviruses that can cause severe and often lethal neurologic and/or respiratory disease in a wide variety of mammalian hosts, including humans. There are presently no licensed vaccines or treatment options approved for human or veterinarian use. Guinea pigs, hamsters, cats, and ferrets, have been evaluated as animal models of human HeV infection, but studies in nonhuman primates (NHP) have not been reported, and the development and approval of any vaccine or antiviral for human use will likely require efficacy studies in an NHP model. Here, we examined the pathogenesis of HeV in the African green monkey (AGM) following intratracheal inoculation. Exposure of AGMs to HeV produced a uniformly lethal infection, and the observed clinical signs and pathology were highly consistent with HeV-mediated disease seen in humans. Ribavirin has been used to treat patients infected with either HeV or NiV; however, its utility in improving outcome remains, at best, uncertain. We examined the antiviral effect of ribavirin in a cohort of nine AGMs before or after exposure to HeV. Ribavirin treatment delayed disease onset by 1 to 2 days, with no significant benefit for disease progression and outcome. Together our findings introduce a new disease model of acute HeV infection suitable for testing antiviral strategies and also demonstrate that, while ribavirin may have some antiviral activity against the henipaviruses, its use as an effective standalone therapy for HeV infection is questionable.
C1 [Geisbert, Joan B.; Geisbert, Thomas W.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA.
[Geisbert, Joan B.; Geisbert, Thomas W.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
[Rockx, Barry; Feldmann, Friederike; Callison, Julie; Safronetz, David; Marzi, Andrea; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
[Brining, Douglas; Kercher, Lisa; Long, Dan] NIAID, Rocky Mt Vet Branch, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
[Bossart, Katharine N.; Geisbert, Joan B.; Geisbert, Thomas W.] Boston Univ, Sch Med, Natl Emerging Infect Dis Labs Inst, Boston, MA 02118 USA.
[Bossart, Katharine N.; Geisbert, Thomas W.] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
[Hickey, Andrew C.; Broder, Christopher C.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
RP Geisbert, TW (reprint author), Univ Texas Med Branch, Galveston Natl Lab, 301 Univ Blvd, Galveston, TX 77555 USA.
EM feldmannh@niaid.nih.gov; tom.geisbert@utmb.edu
OI Bossart, Katharine/0000-0001-6886-6896
FU Department of Health and Human Services, NIH [AI082121, AI057159]; DIR,
NIAID, NIH
FX This study was supported in part by the Department of Health and Human
Services, NIH, grants AI082121 and AI057159 to Thomas W. Geisbert and
funding from DIR, NIAID, NIH, to the Laboratory of Virology.
NR 30
TC 47
Z9 47
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2010
VL 84
IS 19
BP 9831
EP 9839
DI 10.1128/JVI.01163-10
PG 9
WC Virology
SC Virology
GA 660KQ
UT WOS:000282641800017
PM 20660198
ER
PT J
AU Abram, ME
Ferris, AL
Shao, W
Alvord, WG
Hughes, SH
AF Abram, Michael E.
Ferris, Andrea L.
Shao, Wei
Alvord, W. Gregory
Hughes, Stephen H.
TI Nature, Position, and Frequency of Mutations Made in a Single Cycle of
HIV-1 Replication
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RESISTANT REVERSE-TRANSCRIPTASE;
RETROVIRAL SHUTTLE VECTOR; DEPENDENT DNA-SYNTHESIS; BOVINE
LEUKEMIA-VIRUS; RNA-POLYMERASE-II; IN-VITRO; MUTANT FREQUENCIES;
GENETIC-VARIATION; BROAD-SPECTRUM
AB There is considerable HIV-1 variation in patients. The extent of the variation is due to the high rate of viral replication, the high viral load, and the errors made during viral replication. Mutations can arise from errors made either by host DNA-dependent RNA polymerase II or by HIV-1 reverse transcriptase (RT), but the relative contributions of these two enzymes to the mutation rate are unknown. In addition, mutations in RT can affect its fidelity, but the effect of mutations in RT on the nature of the mutations that arise in vivo is poorly understood. We have developed an efficient system, based on existing technology, to analyze the mutations that arise in an HIV-1 vector in a single cycle of replication. A lacZ alpha reporter gene is used to identify viral DNAs that contain mutations which are analyzed by DNA sequencing. The forward mutation rate in this system is 1.4 x 10(-5) mutations/bp/cycle, equivalent to the retroviral average. This rate is about 3-fold lower than previously reported for HIV-1 in vivo and is much lower than what has been reported for purified HIV-1 RT in vitro. Although the mutation rate was not affected by the orientation of lacZ alpha, the sites favored for mutations (hot spots) in lacZ alpha depended on which strand of lacZ alpha was present in the viral RNA. The pattern of hot spots seen in lacZ alpha in vivo did not match any of the published data obtained when purified RT was used to copy lacZ alpha in vitro.
C1 [Abram, Michael E.; Ferris, Andrea L.; Hughes, Stephen H.] NCI Frederick, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Shao, Wei] SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD USA.
[Alvord, W. Gregory] NCI Frederick, Data Management Serv, Frederick, MD 21702 USA.
RP Hughes, SH (reprint author), NCI Frederick, HIV Drug Resistance Program, POB B,Bldg 539,Rm 130A, Frederick, MD 21702 USA.
EM hughesst@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 78
TC 82
Z9 85
U1 1
U2 21
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2010
VL 84
IS 19
BP 9864
EP 9878
DI 10.1128/JVI.00915-10
PG 15
WC Virology
SC Virology
GA 660KQ
UT WOS:000282641800020
PM 20660205
ER
PT J
AU Burdick, R
Smith, JL
Chaipan, C
Friew, Y
Chen, JB
Venkatachari, NJ
Delviks-Frankenberry, KA
Hu, WS
Pathak, VK
AF Burdick, Ryan
Smith, Jessica L.
Chaipan, Chawaree
Friew, Yeshitila
Chen, Jianbo
Venkatachari, Narasimhan J.
Delviks-Frankenberry, Krista A.
Hu, Wei-Shau
Pathak, Vinay K.
TI P Body-Associated Protein Mov10 Inhibits HIV-1 Replication at Multiple
Stages
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; STRESS GRANULES; GENOMIC RNA; VIF
PROTEIN; 7SL RNA; APOBEC3G; BODIES; GENE; INFECTION; MICRORNA
AB Recent studies have shown that APOBEC3G (A3G), a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) replication, is localized to cytoplasmic mRNA-processing bodies (P bodies). However, the functional relevance of A3G colocalization with P body marker proteins has not been established. To explore the relationship between HIV-1, A3G, and P bodies, we analyzed the effects of overexpression of P body marker proteins Mov10, DCP1a, and DCP2 on HIV-1 replication. Our results show that overexpression of Mov10, a putative RNA helicase that was previously reported to belong to the DExD superfamily and was recently reported to belong to the Upf1-like group of helicases, but not the decapping enzymes DCP1a and DCP2, leads to potent inhibition of HIV-1 replication at multiple stages. Mov10 overexpression in the virus producer cells resulted in reductions in the steady-state levels of the HIV-1 Gag protein and virus production; Mov10 was efficiently incorporated into virions and reduced virus infectivity, in part by inhibiting reverse transcription. In addition, A3G and Mov10 overexpression reduced proteolytic processing of HIV-1 Gag. The inhibitory effects of A3G and Mov10 were additive, implying a lack of functional interaction between the two inhibitors. Small interfering RNA (siRNA)-mediated knockdown of endogenous Mov10 by 80% resulted in a 2-fold reduction in virus production but no discernible impact on the infectivity of the viruses after normalization for the p24 input, suggesting that endogenous Mov10 was not required for viral infectivity. Overall, these results show that Mov10 can potently inhibit HIV-1 replication at multiple stages.
C1 [Burdick, Ryan; Smith, Jessica L.; Chaipan, Chawaree; Friew, Yeshitila; Venkatachari, Narasimhan J.; Delviks-Frankenberry, Krista A.; Pathak, Vinay K.] NCI, HIV Drug Resistance Program, Viral Mutat Sect, Frederick, MD 21702 USA.
[Chen, Jianbo; Hu, Wei-Shau] NCI, HIV Drug Resistance Program, Viral Recombinat Sect, Frederick, MD 21702 USA.
RP Pathak, VK (reprint author), NCI, HIV Drug Resistance Program, Viral Mutat Sect, POB B,Bldg 535,Room 334, Frederick, MD 21702 USA.
EM vinay.pathak@nih.gov
RI Delviks-Frankenberry, Krista/M-4822-2013; Chen, Jianbo/N-3737-2014
OI Chen, Jianbo/0000-0001-6491-6577
FU NIH, Center for Cancer Research, National Cancer Institute
FX This research was supported in part by the Intramural Research Program
of the NIH, Center for Cancer Research, National Cancer Institute.
NR 50
TC 69
Z9 73
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2010
VL 84
IS 19
BP 10241
EP 10253
DI 10.1128/JVI.00585-10
PG 13
WC Virology
SC Virology
GA 660KQ
UT WOS:000282641800055
PM 20668078
ER
PT J
AU Kong, L
Huang, CC
Coales, SJ
Molnar, KS
Skinner, J
Hamuro, Y
Kwong, PD
AF Kong, Leopold
Huang, Chih-chin
Coales, Stephen J.
Molnar, Kathleen S.
Skinner, Jeff
Hamuro, Yoshitomo
Kwong, Peter D.
TI Local Conformational Stability of HIV-1 gp120 in Unliganded and
CD4-Bound States as Defined by Amide Hydrogen/Deuterium Exchange
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HYDROGEN-DEUTERIUM EXCHANGE;
CORECEPTOR-BINDING-SITE; MASS-SPECTROMETRY; ENVELOPE GLYCOPROTEIN;
PROTEIN-STRUCTURE; ATOMIC-STRUCTURE; STRUCTURAL BASIS; HUMAN CD4;
RECEPTOR
AB The binding reaction of the HIV-1 gp120 envelope glycoprotein to the CD4 receptor involves exceptional changes in enthalpy and entropy. Crystal structures of gp120 in unliganded and various ligand-bound states, meanwhile, reveal an inner domain able to fold into diverse conformations, a structurally invariant outer domain, and, in the CD4-bound state, a bridging sheet minidomain. These studies, however, provide only hints as to the flexibility of each state. Here we use amide hydrogen/deuterium exchange coupled to mass spectrometry to provide quantifications of local conformational stability for HIV-1 gp120 in unliganded and CD4-bound states. On average, unliganded core gp120 displayed >10,000-fold slower exchange of backbone-amide hydrogens than a theoretically unstructured protein of the same composition, with binding by CD4 reducing the rate of gp120 amide exchange a further 10-fold. For the structurally constant CD4, alterations in exchange correlated well with alterations in binding surface (P value = 0.0004). For the structurally variable gp120, however, reductions in flexibility extended outside the binding surface, and regions of expected high structural diversity (inner domain/bridging sheet) displayed roughly 20-fold more rapid exchange in the unliganded state than regions of low diversity (outer domain). Thus, despite an extraordinary reduction in entropy, neither unliganded gp120 nor free CD4 was substantially unstructured, suggesting that most of the diverse conformations that make up the gp120 unliganded state are reasonably ordered. The results provide a framework for understanding how local conformational stability influences entropic change, conformational diversity, and structural rearrangements in the gp120-CD4 binding reaction.
C1 [Kong, Leopold; Huang, Chih-chin; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Kong, Leopold] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
[Coales, Stephen J.; Molnar, Kathleen S.; Hamuro, Yoshitomo] ExSAR Corp, Monmouth Jct 08852, NJ USA.
[Skinner, Jeff] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Bldg 40,Room 4508, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov
OI Skinner, Jeff/0000-0001-5697-0442
FU NIH; Bill and Melinda Gates Foundation Grand Challenges in Global Heath
Initiative; NIH/Oxford/Cambridge
FX Support for this work was provided by the NIH Intramural Research
Program, a grant from the Bill and Melinda Gates Foundation Grand
Challenges in Global Heath Initiative, and the NIH/Oxford/Cambridge
Graduate Partnerships Program.
NR 49
TC 27
Z9 27
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2010
VL 84
IS 19
BP 10311
EP 10321
DI 10.1128/JVI.00688-10
PG 11
WC Virology
SC Virology
GA 660KQ
UT WOS:000282641800061
PM 20660185
ER
PT J
AU Geisbert, TW
Bailey, M
Geisbert, JB
Asiedu, C
Roederer, M
Grazia-Pau, M
Custers, J
Jahrling, P
Goudsmit, J
Koup, R
Sullivan, NJ
AF Geisbert, Thomas W.
Bailey, Michael
Geisbert, Joan B.
Asiedu, Clement
Roederer, Mario
Grazia-Pau, Maria
Custers, Jerome
Jahrling, Peter
Goudsmit, Jaap
Koup, Richard
Sullivan, Nancy J.
TI Vector Choice Determines Immunogenicity and Potency of Genetic Vaccines
against Angola Marburg Virus in Nonhuman Primates
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID T-CELL RESPONSES; DNA VACCINES; EBOLA-VIRUS; HEMORRHAGIC-FEVER;
GUINEA-PIGS; INFECTION; PROTECTION; PATHOGENESIS; VACCINATION; HUMANS
AB The immunogenicity and durability of genetic vaccines are influenced by the composition of gene inserts and choice of delivery vector. DNA vectors are a promising vaccine approach showing efficacy when combined in prime-boost regimens with recombinant protein or viral vectors, but they have shown limited comparative efficacy as a stand-alone platform in primates, due possibly to suboptimal gene expression or cell targeting. Here, regimens using DNA plasmids modified for optimal antigen expression and recombinant adenovirus (rAd) vectors, all encoding the glycoprotein (GP) gene from Angola Marburg virus (MARV), were compared for their ability to provide immune protection against lethal MARV Angola infection. Heterologous DNA-GP/rAd5-GP prime-boost and single-modality rAd5-GP, as well as the DNA-GP-only vaccine, prevented death in all vaccinated subjects after challenge with a lethal dose of MARV Angola. The DNA/DNA vaccine induced humoral responses comparable to those induced by a single inoculation with rAd5-GP, as well as CD4(+) and CD8(+) cellular immune responses, with skewing toward CD4(+) T-cell activity against MARV GP. Vaccine regimens containing rAd-GP, alone or as a boost, exhibited cellular responses with CD8(+) T-cell dominance. Across vaccine groups, CD8(+) T-cell subset dominance comprising cells exhibiting a tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) double-positive functional phenotype was associated with an absence or low frequency of clinical symptoms, suggesting that both the magnitude and functional phenotype of CD8(+) T cells may determine vaccine efficacy against infection by MARV Angola.
C1 [Bailey, Michael; Asiedu, Clement; Sullivan, Nancy J.] NIAID, Biodef Res Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Roederer, Mario; Koup, Richard] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Geisbert, Thomas W.; Geisbert, Joan B.] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.
[Jahrling, Peter] NIAID, Integrated Res Facil, NIH, Bethesda, MD 20817 USA.
[Grazia-Pau, Maria; Custers, Jerome; Goudsmit, Jaap] Crucell, NL-2333 CN Leiden, Netherlands.
RP Sullivan, NJ (reprint author), NIAID, Biodef Res Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM nsullivan@nih.gov
NR 28
TC 33
Z9 33
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2010
VL 84
IS 19
BP 10386
EP 10394
DI 10.1128/JVI.00594-10
PG 9
WC Virology
SC Virology
GA 660KQ
UT WOS:000282641800068
PM 20660192
ER
PT J
AU Liu, JY
Keele, BF
Li, H
Keating, S
Norris, PJ
Carville, A
Mansfield, KG
Tomaras, GD
Haynes, BF
Kolodkin-Gal, D
Letvin, NL
Hahn, BH
Shaw, GM
Barouch, DH
AF Liu, Jinyan
Keele, Brandon F.
Li, Hui
Keating, Sheila
Norris, Philip J.
Carville, Angela
Mansfield, Keith G.
Tomaras, Georgia D.
Haynes, Barton F.
Kolodkin-Gal, Dror
Letvin, Norman L.
Hahn, Beatrice H.
Shaw, George M.
Barouch, Dan H.
TI Low-Dose Mucosal Simian Immunodeficiency Virus Infection Restricts Early
Replication Kinetics and Transmitted Virus Variants in Rhesus Monkeys
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HIV-1 INFECTION; DOUBLE-BLIND; VACCINE; RESPONSES; CHALLENGE; TRIAL;
METAANALYSIS; SIVMAC251; MACAQUES; THAILAND
AB Defining the earliest virologic events following human immunodeficiency virus type 1 (HIV-1) transmission may be critical for the design of vaccine strategies aimed at blocking acquisition of HIV-1 infection. In particular, the length of the eclipse phase and the number of transmitted virus variants may define the window in which a prophylactic vaccine must act. Here we show that the dose of the virus inoculum affects these key virologic parameters following intrarectal simian immunodeficiency virus (SIV) infection of rhesus monkeys. Low-dose SIV infection resulted in a lengthened eclipse phase, fewer transmitted virus variants, and decreased innate immune activation compared with these parameters in high-dose SIV infection. These data suggest a mechanism by which it may be considerably easier for a vaccine to protect against low-risk HIV-1 transmission than against high-risk HIV-1 transmission. These findings have implications for the design and interpretation of HIV-1 vaccine efficacy studies.
C1 [Liu, Jinyan; Barouch, Dan H.] Beth Israel Deaconess Med Ctr, Div Vaccine Res, Boston, MA 02215 USA.
[Kolodkin-Gal, Dror; Letvin, Norman L.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA.
[Keele, Brandon F.] NCI, SAIC Frederick, Frederick, MD 21702 USA.
[Li, Hui; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Birmingham, AL 35294 USA.
[Keating, Sheila; Norris, Philip J.] Univ Calif San Francisco, San Francisco, CA 94118 USA.
[Keating, Sheila; Norris, Philip J.] Blood Syst Res Inst, San Francisco, CA 94118 USA.
[Carville, Angela; Mansfield, Keith G.] Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA.
[Tomaras, Georgia D.; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA.
[Barouch, Dan H.] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA.
RP Barouch, DH (reprint author), Beth Israel Deaconess Med Ctr, Div Vaccine Res, E CLS 1047,330 Brookline Ave, Boston, MA 02215 USA.
EM dbarouch@bidmc.harvard.edu
RI Keating, Sheila/B-1652-2013; Tomaras, Georgia/J-5041-2016
FU National Institutes of Health Center for HIV/AIDS Vaccine Immunology
[AI067854]; National Institutes of Health [AI066305, AI066924, AI078526,
AI084794, AI087383, RR000168, HHSN266200400088C]
FX We acknowledge support from the National Institutes of Health Center for
HIV/AIDS Vaccine Immunology (AI067854), as well as from the National
Institutes of Health (AI066305, AI066924, AI078526, AI084794, AI087383,
RR000168, and HHSN266200400088C). The authors declare no competing
financial interests.
NR 21
TC 75
Z9 76
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2010
VL 84
IS 19
BP 10406
EP 10412
DI 10.1128/JVI.01155-10
PG 7
WC Virology
SC Virology
GA 660KQ
UT WOS:000282641800071
PM 20686016
ER
PT J
AU Gosert, R
Kardas, P
Major, EO
Hirsch, HH
AF Gosert, Rainer
Kardas, Piotr
Major, Eugene O.
Hirsch, Hans H.
TI Rearranged JC Virus Noncoding Control Regions Found in Progressive
Multifocal Leukoencephalopathy Patient Samples Increase Virus Early Gene
Expression and Replication Rate
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN POLYOMAVIRUS JC; ACTIVE
ANTIRETROVIRAL THERAPY; CEREBROSPINAL-FLUID; REGULATORY REGION; IMMUNE
RECONSTITUTION; TAT PROTEIN; HUMAN BRAIN; IN-VIVO; SEQUENCES
AB Polyomavirus JC (JCV) infects similar to 60% of the general population, followed by asymptomatic urinary shedding in similar to 20%. In patients with pronounced immunodeficiency, including HIV/AIDS, JCV can cause progressive multifocal leukoencephalopathy (PML), a devastating brain disease of high mortality. While JCV in the urine of healthy people has a linear noncoding control region called the archetype NCCR (at-NCCR), JCV in brain and cerebrospinal fluid (CSF) of PML patients bear rearranged NCCRs (rr-NCCRs). Although JCV NCCR rearrangements are deemed pathognomonic for PML, their role as a viral determinant is unclear. We sequenced JCV NCCRs found in CSF of eight HIV/AIDS patients newly diagnosed with PML and analyzed their effect on early and late gene expression using a bidirectional reporter vector recapitulating the circular polyomavirus early and late gene organization. The rr-NCCR sequences were highly diverse, but all increased viral early reporter gene expression in progenitor-derived astrocytes, glia-derived cells, and human kidney compared to the expression levels with the at-NCCR. The expression of simian virus 40 (SV40) large T antigen or HIV Tat expression in trans was associated with a strong increase of at-NCCR-controlled early gene expression, while rr-NCCRs were less responsive. The insertion of rr-NCCRs into the JCV genome backbone revealed higher viral replication rates for rr-NCCR compared to those of the at-NCCR JCV in human progenitor-derived astrocytes or glia cells, which was abrogated in SV40 large T-expressing COS-7 cells. We conclude that naturally occurring JCV rr-NCCR variants from PML patients confer increased early gene expression and higher replication rates compared to those of at-NCCR JCV and thereby increase cytopathology.
C1 [Gosert, Rainer; Kardas, Piotr; Hirsch, Hans H.] Univ Basel, Dept Biomed, Inst Med Microbiol, CH-4003 Basel, Switzerland.
[Major, Eugene O.] NINDS, NIH, Bethesda, MD 20892 USA.
[Hirsch, Hans H.] Univ Basel Hosp, Infect Dis & Hosp Epidemiol, CH-4031 Basel, Switzerland.
RP Hirsch, HH (reprint author), Univ Basel, Dept Biomed, Inst Med Microbiol, CH-4003 Basel, Switzerland.
EM hans.hirsch@unibas.ch
NR 60
TC 54
Z9 54
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2010
VL 84
IS 20
BP 10448
EP 10456
DI 10.1128/JVI.00614-10
PG 9
WC Virology
SC Virology
GA 660KW
UT WOS:000282642600002
PM 20686041
ER
PT J
AU Liu, J
Ruckwardt, TJ
Chen, M
Nicewonger, JD
Johnson, TR
Graham, BS
AF Liu, Jie
Ruckwardt, Tracy J.
Chen, Man
Nicewonger, John D.
Johnson, Teresa R.
Graham, Barney S.
TI Epitope-Specific Regulatory CD4 T Cells Reduce Virus-Induced Illness
while Preserving CD8 T-Cell Effector Function at the Site of Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; TRANSCRIPTION FACTOR FOXP3;
VIRAL-INFECTION; IMMUNODOMINANCE DISPARITIES; MICE; RESPONSES; DISEASE;
SUBSETS; ANTIGEN; MODEL
AB The role of epitope-specific regulatory CD4 T cells in modulating CD8 T-cell-mediated immunopathology during acute viral infection has not been well defined. In the murine model of respiratory syncytial virus (RSV) infection, CD8 T cells play an important role in both viral clearance and immunopathology. We have previously characterized two RSV epitope-specific CD4 T-cell responses with distinct phenotypic properties. One of them, the IA(b)M(209)-specific subset, constitutively expresses FoxP3 and modulates CD8 T-cell function in vitro. We show here that the IA(b)M(209)-specific CD4 T-cell response regulates CD8 T-cell function in vivo and is associated with diminished RSV-induced illness without affecting viral clearance at the site of infection. Achieving the optimal balance of regulatory and effector T-cell function is an important consideration for designing future vaccines.
C1 [Liu, Jie; Ruckwardt, Tracy J.; Chen, Man; Nicewonger, John D.; Johnson, Teresa R.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA.
EM bgraham@nih.gov
FU NIAID
FX We thank the NIAID-sponsored tetramer core facility at Emory University
(Atlanta, GA) for assisting in the construction of the class II
tetramers and Mythreyi Shastri for her editorial work.
NR 50
TC 12
Z9 12
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2010
VL 84
IS 20
BP 10501
EP 10509
DI 10.1128/JVI.00963-10
PG 9
WC Virology
SC Virology
GA 660KW
UT WOS:000282642600007
PM 20686045
ER
PT J
AU Radoshitzky, SR
Dong, LA
Chi, XO
Clester, JC
Retterer, C
Spurgers, K
Kuhn, JH
Sandwick, S
Ruthel, G
Kota, K
Boltz, D
Warren, T
Kranzusch, PJ
Whelan, SPJ
Bavari, S
AF Radoshitzky, Sheli R.
Dong, Lian
Chi, Xiaoli
Clester, Jeremiah C.
Retterer, Cary
Spurgers, Kevin
Kuhn, Jens H.
Sandwick, Sarah
Ruthel, Gordon
Kota, Krishna
Boltz, Dutch
Warren, Travis
Kranzusch, Philip J.
Whelan, Sean P. J.
Bavari, Sina
TI Infectious Lassa Virus, but Not Filoviruses, Is Restricted by
BST-2/Tetherin
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PROTEIN SORTING PATHWAY; HUMAN DENDRITIC CELLS; VALLEY FEVER VIRUS;
EBOLA-VIRUS; MATRIX PROTEIN; NIPAH-VIRUS; SIGNAL PEPTIDE; INTERFERON
RESPONSE; ZAIRE EBOLAVIRUS; IN-VITRO
AB Bone marrow stromal antigen 2 (BST-2/tetherin) is a cellular membrane protein that inhibits the release of HIV-1. We show for the first time, using infectious viruses, that BST-2 also inhibits egress of arenaviruses but has no effect on filovirus replication and spread. Specifically, infectious Lassa virus (LASV) release significantly decreased or increased in human cells in which BST-2 was either stably expressed or knocked down, respectively. In contrast, replication and spread of infectious Zaire ebolavirus (ZEBOV) and Lake Victoria marburgvirus (MARV) were not affected by these conditions. Replication of infectious Rift Valley fever virus (RVFV) and cowpox virus (CPXV) was also not affected by BST-2 expression. Elevated cellular levels of human or murine BST-2 inhibited the release of virus-like particles (VLPs) consisting of the matrix proteins of multiple highly virulent NIAID Priority Pathogens, including arenaviruses (LASV and Machupo virus [MACV]), filoviruses (ZEBOV and MARV), and paramyxoviruses (Nipah virus). Although the glycoproteins of filoviruses counteracted the antiviral activity of BST-2 in the context of VLPs, they could not rescue arenaviral (LASV and MACV) VLP release upon BST-2 overexpression. Furthermore, we did not observe colocalization of filoviral glycoproteins with BST-2 during infection with authentic viruses. None of the arenavirus-encoded proteins rescued budding of VLPs in the presence of BST-2. Our results demonstrate that BST-2 might be a broad antiviral factor with the ability to restrict release of a wide variety of human pathogens. However, at least filoviruses, RVFV, and CPXV are immune to its inhibitory effect.
C1 [Radoshitzky, Sheli R.; Dong, Lian; Chi, Xiaoli; Clester, Jeremiah C.; Retterer, Cary; Spurgers, Kevin; Sandwick, Sarah; Ruthel, Gordon; Kota, Krishna; Boltz, Dutch; Warren, Travis; Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
[Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD 21702 USA.
[Kuhn, Jens H.] Tunnell Consulting, King Of Prussia, PA 19406 USA.
[Kranzusch, Philip J.; Whelan, Sean P. J.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
RP Bavari, S (reprint author), USA, Med Res Inst Infect Dis, 1425 Porter St,Natl Interagency Biodef Campus, Frederick, MD 21702 USA.
EM sina.bavari@amedd.army.mil
RI Kuhn, Jens H./B-7615-2011
OI Kuhn, Jens H./0000-0002-7800-6045
FU Joint Science and Technology Office for Chemical and Biological Defense
[4.10022_08_RD_B]
FX Work performed at the U.S. Army Medical Research Institute of Infectious
Diseases (USAMRIID) was supported by grant 4.10022_08_RD_B from the
Joint Science and Technology Office for Chemical and Biological Defense.
NR 66
TC 74
Z9 78
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2010
VL 84
IS 20
BP 10569
EP 10580
DI 10.1128/JVI.00103-10
PG 12
WC Virology
SC Virology
GA 660KW
UT WOS:000282642600013
PM 20686043
ER
PT J
AU Karanam, B
Peng, SW
Li, T
Buck, C
Day, PM
Roden, RBS
AF Karanam, Balasubramanyam
Peng, Shiwen
Li, Tong
Buck, Christopher
Day, Patricia M.
Roden, Richard B. S.
TI Papillomavirus Infection Requires gamma Secretase
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MINOR CAPSID PROTEIN; POSITIVELY CHARGED TERMINI; AMYLOID PRECURSOR
PROTEIN; VIRUS-LIKE PARTICLES; HUMAN KERATINOCYTES; HEPARAN-SULFATE;
EXTRACELLULAR-MATRIX; L2; MEMBRANE; PATHWAY
AB The mechanism by which papillomaviruses breach cellular membranes to deliver their genomic cargo to the nucleus is poorly understood. Here, we show that infection by a broad range of papillomavirus types requires the intramembrane protease gamma secretase. The gamma-secretase inhibitor (S, S)-2-[2-(3,5-difluorophenyl)-acetylamino]- N-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4] diazepin-3-yl)-propionamide (compound XXI) inhibits infection in vitro by all types of papillomavirus pseudovirions tested, with a 50% inhibitory concentration (IC(50)) of 130 to 1,000 pM, regardless of reporter construct and without impacting cellular viability. Conversely, XXI does not inhibit in vitro infection by adenovirus or pseudovirions derived from the BK or Merkel cell polyomaviruses. Vaginal application of XXI prevents infection of the mouse genital tract by human papillomavirus type 16 (HPV16) pseudovirions. Nicastrin and presenilin-1 are essential components of the gamma-secretase complex, and mouse embryo fibroblasts deficient in any one of these components were not infected by HPV16, whereas wild-type and beta-secretase (BACE1)-deficient cells were susceptible. Neither the uptake of HPV16 into Lamp-1-positive perinuclear vesicles nor the disassembly of capsid to reveal both internal L1 and L2 epitopes and bromodeoxyuridine (BrdU)-labeled encapsidated DNA is dependent upon gamma-secretase activity. However, blockade of gamma-secretase activity by XXI prevents the BrdU-labeled DNA encapsidated by HPV16 from reaching the ND10 subnuclear domains. Since prior studies indicate that L2 is critical for endosomal escape and targeting of the viral DNA to ND10 and that gamma secretase is located in endosomal membranes, our findings suggest that either L2 or an intracellular receptor are cleaved by gamma secretase as papillomavirus escapes the endosome.
C1 [Karanam, Balasubramanyam; Peng, Shiwen; Li, Tong; Roden, Richard B. S.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA.
[Roden, Richard B. S.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21231 USA.
[Roden, Richard B. S.] Johns Hopkins Univ, Dept Gynecol & Obstet, Baltimore, MD 21231 USA.
[Buck, Christopher; Day, Patricia M.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA.
RP Roden, RBS (reprint author), Johns Hopkins Univ, Dept Pathol, Room 308,Canc Res Bldg 2,1550 Orleans St, Baltimore, MD 21231 USA.
EM roden@jhmi.edu
FU National Institutes of Health, National Cancer Institute [R01CA118790,
R01 CA133749]; SPORE in Cervical Cancer [P50 CA098252]; GlaxoSmithKline
FX Funding for this study was provided by the National Institutes of
Health, National Cancer Institute (grants R01CA118790 and R01 CA133749)
and SPORE in Cervical Cancer (grant P50 CA098252 to R. B. S. R.).; R. B.
S. R. has served as a paid consultant of Merck & Co, Inc., and Knobbe
Martens Olson & Bear LLC. R. B. S. R. has received unrestricted
educational grant funding from GlaxoSmithKline. R. B. S. R. is a
coinventor on L2 patents licensed to Shantha Biotechnics, Ltd., PaxVax,
Inc., and Acambis, Inc., and to GlaxoSmithKline. The terms of these
arrangements are being managed by Johns Hopkins University in accordance
with its conflict of interest policies.
NR 53
TC 30
Z9 30
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2010
VL 84
IS 20
BP 10661
EP 10670
DI 10.1128/JVI.01081-10
PG 10
WC Virology
SC Virology
GA 660KW
UT WOS:000282642600021
PM 20702627
ER
PT J
AU Schmeisser, H
Mejido, J
Balinsky, CA
Morrow, AN
Clark, CR
Zhao, T
Zoon, KC
AF Schmeisser, H.
Mejido, J.
Balinsky, C. A.
Morrow, A. N.
Clark, C. R.
Zhao, T.
Zoon, K. C.
TI Identification of Alpha Interferon-Induced Genes Associated with
Antiviral Activity in Daudi Cells and Characterization of IFIT3 as a
Novel Antiviral Gene
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID INDUCED NUCLEAR FACTORS; STIMULATED GENES; IFN-ALPHA; IN-VITRO;
ANTIPROLIFERATIVE ACTIVITY; PERIPHERAL-BLOOD; PROMOTER ELEMENT; MXA
PROTEIN; FOAMY VIRUS; RIG-G
AB A novel assay was developed for Daudi cells in which the antiviral (AV) and antiproliferative (AP) activities of interferon (IFN) can be measured simultaneously. Using this novel assay, conditions allowing IFN AV protection but no growth inhibition were identified and selected. Daudi cells were treated under these conditions, and gene expression microarray analyses were performed. The results of the analysis identified 25 genes associated with IFN-alpha AV activity. Upregulation of 23 IFN-induced genes was confirmed by using reverse transcription-PCR. Of 25 gene products, 17 were detected by Western blotting at 24 h. Of the 25 genes, 10 have not been previously linked to AV activity of IFN-alpha. The most upregulated gene was IFIT3 (for IFN-induced protein with tetratricopeptide repeats 3). The results from antibody neutralizing experiments suggested an association of the identified genes with IFN-alpha AV activity. This association was strengthened by results from IFIT3-small interfering RNA transfection experiments showing decreased expression of IFIT3 and a reduction in the AV activity induced by IFN-alpha. Overexpression of IFIT3 resulted in a decrease of virus titer. Transcription of AV genes after the treatment of cells with higher concentrations of IFN having an AP effect on Daudi cells suggested pleiotropic functions of identified gene products.
C1 [Zoon, K. C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA.
RP Zoon, KC (reprint author), NIAID, Cytokine Biol Sect, NIH, MSC 8001,50 Ctr Dr,Bldg 50,Rm 5515, Bethesda, MD 20892 USA.
EM kzoon@niaid.nih.gov
FU NIH (NIAID)
FX This research was supported by the Intramural Research Program of the
NIH (NIAID).
NR 41
TC 33
Z9 35
U1 1
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2010
VL 84
IS 20
BP 10671
EP 10680
DI 10.1128/JVI.00818-10
PG 10
WC Virology
SC Virology
GA 660KW
UT WOS:000282642600022
PM 20686046
ER
PT J
AU Alpert, MD
Rahmberg, AR
Neidermyer, W
Ng, SK
Carville, A
Camp, JV
Wilson, RL
Piatak, M
Mansfield, KG
Li, WJ
Miller, CJ
Lifson, JD
Kozlowski, PA
Evans, DT
AF Alpert, Michael D.
Rahmberg, Andrew R.
Neidermyer, William
Ng, Sharon K.
Carville, Angela
Camp, Jeremy V.
Wilson, Robert L.
Piatak, Michael, Jr.
Mansfield, Keith G.
Li, Wenjun
Miller, Christopher J.
Lifson, Jeffrey D.
Kozlowski, Pamela A.
Evans, David T.
TI Envelope-Modified Single-Cycle Simian Immunodeficiency Virus Selectively
Enhances Antibody Responses and Partially Protects against Repeated,
Low-Dose Vaginal Challenge
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CYTOTOXIC T-LYMPHOCYTES; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSES;
RHESUS MACAQUES; ATTENUATED SIV; IN-VIVO; MEDIATED NEUTRALIZATION;
MONOCLONAL-ANTIBODIES; REPLICATION-COMPETENT; GLYCOSYLATION SITES
AB Immunization of rhesus macaques with strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection elicits T-cell responses to multiple viral gene products and antibodies capable of neutralizing lab-adapted SIV, but not neutralization-resistant primary isolates of SIV. In an effort to improve upon the antibody responses, we immunized rhesus macaques with three strains of single-cycle SIV (scSIV) that express envelope glycoproteins modified to lack structural features thought to interfere with the development of neutralizing antibodies. These envelope-modified strains of scSIV lacked either five potential N-linked glycosylation sites in gp120, three potential N-linked glycosylation sites in gp41, or 100 amino acids in the V1V2 region of gp120. Three doses consisting of a mixture of the three envelope-modified strains of scSIV were administered on weeks 0, 6, and 12, followed by two booster inoculations with vesicular stomatitis virus (VSV) G trans-complemented scSIV on weeks 18 and 24. Although this immunization regimen did not elicit antibodies capable of detectably neutralizing SIV(mac)239 or SIV(mac)251(UCD), neutralizing antibody titers to the envelope-modified strains were selectively enhanced. Virus-specific antibodies and T cells were observed in the vaginal mucosa. After 20 weeks of repeated, low-dose vaginal challenge with SIV(mac)251(UCD), six of eight immunized animals versus six of six naive controls became infected. Although immunization did not significantly reduce the likelihood of acquiring immunodeficiency virus infection, statistically significant reductions in peak and set point viral loads were observed in the immunized animals relative to the naive control animals.
C1 [Alpert, Michael D.; Rahmberg, Andrew R.; Neidermyer, William; Ng, Sharon K.; Evans, David T.] Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA.
[Carville, Angela; Mansfield, Keith G.] Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Dept Pathol, Southborough, MA 01772 USA.
[Camp, Jeremy V.; Wilson, Robert L.; Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, New Orleans, LA 70112 USA.
[Camp, Jeremy V.; Wilson, Robert L.; Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA 70112 USA.
[Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, SAIC Frederick, Frederick, MD 21702 USA.
[Li, Wenjun] Univ Massachusetts, Worcester, MA 01655 USA.
[Miller, Christopher J.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA.
RP Evans, DT (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Dept Microbiol & Mol Genet, 1 Pine Hill Dr, Southborough, MA 01772 USA.
EM david_evans@hms.harvard.edu
RI Li, Wenjun/F-5634-2015
OI Li, Wenjun/0000-0001-5335-7386
FU National Institutes of Health [AI063993, AI071306, RR000168]; National
Cancer Institute, National Institutes of Health [HHSN261200800001E];
Elizabeth Glaser Pediatric AIDS Foundation
FX This work was supported by grants AI063993, AI071306, and RR000168 from
the National Institutes of Health and by federal funds from the National
Cancer Institute, National Institutes of Health, under contract no.
HHSN261200800001E. D.T.E. is an Elizabeth Glaser Scientist supported by
the Elizabeth Glaser Pediatric AIDS Foundation.
NR 88
TC 8
Z9 8
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2010
VL 84
IS 20
BP 10748
EP 10764
DI 10.1128/JVI.00945-10
PG 17
WC Virology
SC Virology
GA 660KW
UT WOS:000282642600029
PM 20702641
ER
PT J
AU Kolokithas, A
Rosenke, K
Malik, F
Hendrick, D
Swanson, L
Santiago, ML
Portis, JL
Hasenkrug, KJ
Evans, LH
AF Kolokithas, Angelo
Rosenke, Kyle
Malik, Frank
Hendrick, Duncan
Swanson, Lukas
Santiago, Mario L.
Portis, John L.
Hasenkrug, Kim J.
Evans, Leonard H.
TI The Glycosylated Gag Protein of a Murine Leukemia Virus Inhibits the
Antiretroviral Function of APOBEC3
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IN-VIVO; IDENTIFICATION; RETROVIRUS; CELLS; GENE; PATHOGENESIS;
RESTRICTION; INFECTION; STRAINS; XMRV
AB APOBEC proteins have evolved as innate defenses against retroviral infections. Human immunodeficiency virus (HIV) encodes the Vif protein to evade human APOBEC3G; however, mouse retroviruses do not encode a Vif homologue, and it has not been understood how they evade mouse APOBEC3. We report here a murine leukemia virus (MuLV) that utilizes its glycosylated Gag protein (gGag) to evade APOBEC3. gGag is critical for infection of in vitro cell lines in the presence of APOBEC3. Furthermore, a gGag-deficient virus restricted for replication in wild-type mice replicates efficiently in APOBEC3 knockout mice, implying a novel role of gGag in circumventing the action of APOBEC3 in vivo.
C1 [Kolokithas, Angelo; Rosenke, Kyle; Malik, Frank; Hendrick, Duncan; Swanson, Lukas; Santiago, Mario L.; Portis, John L.; Hasenkrug, Kim J.; Evans, Leonard H.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Evans, LH (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA.
EM levans@niaid.nih.gov
OI Santiago, Mario L./0000-0001-7792-2706
FU NIH, NIAID
FX This research was supported by the Intramural Research Program of the
NIH, NIAID.
NR 35
TC 33
Z9 33
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD OCT
PY 2010
VL 84
IS 20
BP 10933
EP 10936
DI 10.1128/JVI.01023-10
PG 4
WC Virology
SC Virology
GA 660KW
UT WOS:000282642600048
PM 20702647
ER
PT J
AU Pinn, VW
AF Pinn, Vivian W.
TI Seventh Annual NIH Interdisciplinary Women's Health Research Symposium
November 9, 2010
SO JOURNAL OF WOMENS HEALTH
LA English
DT Editorial Material
C1 NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA.
RP Pinn, VW (reprint author), NIH, Off Res Womens Hlth, 6707 Democracy Blvd,Suite 400, Bethesda, MD 20892 USA.
EM orwh-research@od.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD OCT
PY 2010
VL 19
IS 10
BP 1777
EP 1778
PG 2
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 660WF
UT WOS:000282676500001
ER
PT J
AU Kelly, TN
Gu, DF
Jaquish, CE
Rao, DC
Chen, J
Cao, J
Chen, JC
Li, JX
Lu, FH
Ma, JX
Mu, JJ
Whelton, PK
He, JA
AF Kelly, Tanika N.
Gu, Dongfeng
Jaquish, Cashell E.
Rao, D. C.
Chen, Jing
Cao, Jie
Chen, Jichun
Li, Jianxin
Lu, Fanghong
Ma, Jixiang
Mu, Jianjun
Whelton, Paul K.
He, Jiang
TI Maternal History of Hypertension Predicts Blood Pressure Response to
Potassium in a Han Chinese Population: The GenSalt Study
SO JOURNAL OF WOMENS HEALTH
LA English
DT Meeting Abstract
C1 [Kelly, Tanika N.; He, Jiang] Tulane Univ, Dept Epidemiol, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA.
[Gu, Dongfeng; Cao, Jie; Chen, Jichun; Li, Jianxin] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100037, Peoples R China.
[Gu, Dongfeng; Cao, Jie; Chen, Jichun; Li, Jianxin] Chinese Acad Med Sci, Fuwai Hosp, Beijing 100037, Peoples R China.
[Gu, Dongfeng; Cao, Jie; Chen, Jichun; Li, Jianxin] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Gu, Dongfeng; Cao, Jie; Chen, Jichun; Li, Jianxin] Chinese Natl Ctr Cardiovasc Dis Control & Res, Beijing, Peoples R China.
[Jaquish, Cashell E.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD USA.
[Rao, D. C.] Washington Univ, Div Biostat, Sch Med, St Louis, MO 63130 USA.
[Chen, Jing] Tulane Univ, Dept Med, Sch Med, New Orleans, LA 70118 USA.
[Mu, Jianjun] Xi An Jiao Tong Univ, Dept Med, Xian, Shanxi, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD OCT
PY 2010
VL 19
IS 10
BP 1787
EP 1787
PG 1
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 660WF
UT WOS:000282676500033
ER
PT J
AU Madkour, AS
Farhat, T
Halpern, CT
Godeau, E
Gabhainn, SN
AF Madkour, Aubrey Spriggs
Farhat, Tilda
Halpern, Carolyn Tucker
Godeau, Emmanuelle
Gabhainn, Saoirse Nic
TI Early Adolescent Sexual Initiation and Physical/Psychological Symptoms:
A Comparative Analysis of Five Nations
SO JOURNAL OF YOUTH AND ADOLESCENCE
LA English
DT Article
DE Sexual behavior; Adolescent; Gender differences; Depressive symptoms;
Cross-national
ID SCHOOL-AGED CHILDREN; DEPRESSIVE SYMPTOMS; NEIGHBORHOOD CONTEXT;
DEVELOPED-COUNTRIES; HEALTH COMPLAINTS; FAMILY-STRUCTURE;
DOUBLE-STANDARD; UNITED-STATES; BEHAVIOR; YOUTH
AB Although most people in developed countries experience sexual initiation during adolescence, little is known about inter-country variability in the psychosocial correlates of early initiation. Population-based samples of 15-year-olds (n = 6,111, 52% female) who participated in the Health Behaviors in School-Aged Children Study (Finland, Scotland, France and Poland, 1997/1998) or the National Longitudinal Study of Adolescent Health (United States, 1996) self-reported sexual intercourse experience and physical (headaches, trouble sleeping) or psychological (unhappiness, loneliness, sadness, moodiness) symptoms. Analyses were conducted stratified by gender. Sexual initiation prevalence and symptoms scores varied significantly across nations. In adjusted models, sexual initiation was not related to symptoms among boys in any nation, but significantly positively related to symptoms among girls in Poland and the US. Results support variability by gender and nation in the relationship between adolescents' sexual initiation and physical/psychological symptoms. Empirically investigating specific features of national contexts that generate these differences should be explored further.
C1 [Madkour, Aubrey Spriggs] Tulane Univ, Dept Community Hlth Sci, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA.
[Farhat, Tilda] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Halpern, Carolyn Tucker] Univ N Carolina, Dept Maternal & Child Hlth, Chapel Hill, NC USA.
[Halpern, Carolyn Tucker] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[Godeau, Emmanuelle] Univ Toulouse 3, INSERM, UMR U558, F-31062 Toulouse, France.
[Godeau, Emmanuelle] Acad Toulouse, Serv Med Rectorat, Toulouse, France.
[Gabhainn, Saoirse Nic] Natl Univ Ireland Galway, Hlth Promot Res Ctr, Sch Hlth Sci, Galway, Ireland.
RP Madkour, AS (reprint author), Tulane Univ, Dept Community Hlth Sci, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA.
EM aspriggs@tulane.edu
FU NICHD NIH HHS [P01 HD031921, T32 HD007168, T32-HD07168, R24 HD050924,
L40 HD066680]
NR 66
TC 17
Z9 17
U1 0
U2 13
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0047-2891
J9 J YOUTH ADOLESCENCE
JI J. Youth Adolesc.
PD OCT
PY 2010
VL 39
IS 10
BP 1211
EP 1225
DI 10.1007/s10964-010-9521-x
PG 15
WC Psychology, Developmental
SC Psychology
GA 635UG
UT WOS:000280681600008
PM 20333456
ER
PT J
AU Le Couteur, DG
Lakatta, EG
AF Le Couteur, David G.
Lakatta, Edward G.
TI A Vascular Theory of Aging
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Editorial Material
ID CARDIOVASCULAR-DISEASE ENTERPRISES; SUBCLINICAL ARTERIAL-DISEASE; MAJOR
SHAREHOLDERS; HEART-DISEASE; LIFE-SPAN; HEALTH; ATHEROSCLEROSIS;
RESTRICTION; RAT
C1 [Le Couteur, David G.] Univ Sydney, ANZAC Res Inst, Concord RG Hosp, Sydney, NSW 2139, Australia.
[Le Couteur, David G.] Univ Sydney, Ctr Educ & Res Ageing, Concord RG Hosp, Sydney, NSW 2139, Australia.
[Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
RP Le Couteur, DG (reprint author), Univ Sydney, ANZAC Res Inst, Concord RG Hosp, Sydney, NSW 2139, Australia.
EM david.lecouteur@sydney.edu.au
NR 29
TC 11
Z9 11
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD OCT
PY 2010
VL 65
IS 10
BP 1025
EP 1027
DI 10.1093/gerona/glq135
PG 3
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 651WK
UT WOS:000281957800001
PM 20650862
ER
PT J
AU Ungvari, Z
Kaley, G
de Cabo, R
Sonntag, WE
Csiszar, A
AF Ungvari, Zoltan
Kaley, Gabor
de Cabo, Rafael
Sonntag, William E.
Csiszar, Anna
TI Mechanisms of Vascular Aging: New Perspectives
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Review
DE Vascular aging; Oxidative stress; Endothelial dysfunction;
Atherosclerosis; Stroke; Myocardial infarction
ID GROWTH-FACTOR-I; NF-KAPPA-B; ENDOTHELIAL PROGENITOR CELLS; TERM CALORIC
RESTRICTION; NECROSIS-FACTOR-ALPHA; ACTIVATED PROTEIN-KINASE;
AGE-DEPENDENT IMPAIRMENT; GLYCATION END-PRODUCT; NITRIC-OXIDE SYNTHASE;
MUSCLE FEED ARTERIES
AB This review focuses on molecular, cellular, and functional changes that occur in the vasculature during aging; explores the links between mitochondrial oxidative stress, inflammation, and development of vascular disease in the elderly patients; and provides a landscape of molecular mechanisms involved in cellular oxidative stress resistance, which could be targeted for the prevention or amelioration of unsuccessful vascular aging. Practical interventions for prevention of age-associated vascular dysfunction and disease in old age are considered here based on emerging knowledge of the effects of anti-inflammatory treatments, regular exercise, dietary interventions, and caloric restriction mimetics.
C1 [Ungvari, Zoltan; Sonntag, William E.; Csiszar, Anna] Univ Oklahoma, Reynolds Oklahoma Ctr Aging, Dept Geriatr Med, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
[Kaley, Gabor] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA.
[de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
RP Ungvari, Z (reprint author), Univ Oklahoma, Reynolds Oklahoma Ctr Aging, Dept Geriatr Med, Hlth Sci Ctr, 975 NE 10th St,BRC 1303, Oklahoma City, OK 73104 USA.
EM zoltan-ungvari@ouhsc.edu
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU American Diabetes Association; American Federation for Aging Research;
National Institutes of Health (NIH) [HL077256, HL43023, AG11370]
FX This work was supported by grants from the American Diabetes
Association, the American Federation for Aging Research, and the
National Institutes of Health (NIH) (HL077256, HL43023, AG11370) and the
Intramural Research Program of NIH (to R.d.C.).
NR 188
TC 210
Z9 221
U1 4
U2 26
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD OCT
PY 2010
VL 65
IS 10
BP 1028
EP 1041
DI 10.1093/gerona/glq113
PG 14
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 651WK
UT WOS:000281957800002
PM 20576649
ER
PT J
AU Lewis, TT
Sutton-Tyrrell, K
Penninx, BW
Vogelzangs, N
Harris, TB
Vaidean, GD
Ayonayon, HN
Kim, L
Lakatta, EG
Newman, AB
AF Lewis, Tene T.
Sutton-Tyrrell, Kim
Penninx, Brenda W.
Vogelzangs, Nicole
Harris, Tamara B.
Vaidean, Georgeta D.
Ayonayon, Hilsa N.
Kim, Lauren
Lakatta, Edward G.
Newman, Anne B.
TI Race, Psychosocial Factors, and Aortic Pulse Wave Velocity: The Health,
Aging, and Body Composition Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Psychosocial; Social support; Arterial stiffness; Cardiovascular
disease; African-Americans
ID ARTERIAL STIFFNESS; DEPRESSIVE SYMPTOMS; EMOTIONAL SUPPORT;
CARDIOVASCULAR REACTIVITY; MYOCARDIAL-INFARCTION; RACIAL-DIFFERENCES;
AFRICAN-AMERICAN; SOCIAL NETWORKS; BLOOD-PRESSURE; OLDER-ADULTS
AB Background. Increasingly, researchers have begun to explore pathways through which psychosocial factors might influence cardiovascular disease, with some emphasis on early markers. The current study examined the cross-sectional association between psychosocial factors and aortic pulse wave velocity (an early marker of cardiovascular disease) in a biracial cohort of older adults. We were particularly interested in determining whether the association between psychosocial factors and aortic pulse wave velocity differed for older blacks compared with whites.
Methods. Participants were 2,488 (40% black and 52% female) older adults from the Health, Aging, and Body Composition Study. Carotid-femoral aortic pulse wave velocity was assessed using standard methodologies. Depressive symptoms, anxiety symptoms, negative life events, and inadequate emotional support were assessed, and a summary psychosocial risk index was created.
Results. In multivariable linear regression models, psychosocial risk was not associated with aortic pulse wave velocity (Estimate [Est] = .00, p = .83), but there was a significant Race x Psychosocial risk interaction (Est = .07, p = .01), after adjusting for age, race, sex, and education. Further analyses revealed that this association was driven by the inadequate emotional support component of psychosocial risk (Race x Inadequate emotional support, p = .005). In race-stratified analyses, inadequate emotional support was associated with higher levels of arterial stiffness in older blacks (Est = .05, p = .04) but not whites (Est = -.04, p = .13). This association persisted after adjusting for demographics, cardiovascular risk factors, and social network characteristics.
Conclusions. Findings suggest that older blacks may be particularly vulnerable to the effects of inadequate emotional support on vascular health. Interventions aimed at increasing social support among this population might be beneficial in reducing cardiovascular disease risk.
C1 [Lewis, Tene T.] Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA.
[Sutton-Tyrrell, Kim; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA.
[Penninx, Brenda W.; Vogelzangs, Nicole] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Penninx, Brenda W.; Vogelzangs, Nicole] Vrije Univ Amsterdam, Med Ctr, Inst Res Extramural Med, Amsterdam, Netherlands.
[Harris, Tamara B.; Kim, Lauren] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Vaidean, Georgeta D.] Univ Memphis, Dept Prevent Med, Memphis, TN 38152 USA.
[Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, Bethesda, MD 20892 USA.
RP Lewis, TT (reprint author), 60 Coll St,4th Floor, New Haven, CT 06520 USA.
EM tene.lewis@yale.edu
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; National Center for Minority Health and Health
Disparities; National Heart, Lung, and Blood Institute [HL092591];
National Institutes of Health
FX The Health, Aging, and Body Composition Study was funded by the National
Institute on Aging (N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106).
T.T.L. received additional support from a Visiting Scholar Award funded
by the National Center for Minority Health and Health Disparities and a
Career Development Award funded by the National Heart, Lung, and Blood
Institute (HL092591). This research was supported in part by the
Intramural Research Program of the National Institutes of Health,
National Institute on Aging.
NR 42
TC 7
Z9 7
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD OCT
PY 2010
VL 65
IS 10
BP 1079
EP 1085
DI 10.1093/gerona/glq089
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 651WK
UT WOS:000281957800007
PM 20522528
ER
PT J
AU Watson, NL
Rosano, C
Boudreau, RM
Simonsick, EM
Ferrucci, L
Sutton-Tyrrell, K
Hardy, SE
Atkinson, HH
Yaffe, K
Satterfield, S
Harris, TB
Newman, AB
AF Watson, N. L.
Rosano, C.
Boudreau, R. M.
Simonsick, E. M.
Ferrucci, L.
Sutton-Tyrrell, K.
Hardy, S. E.
Atkinson, H. H.
Yaffe, K.
Satterfield, S.
Harris, T. B.
Newman, A. B.
CA Health ABC Study
TI Executive Function, Memory, and Gait Speed Decline in Well-Functioning
Older Adults
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Aging; Cognitive function; Gait speed
ID WHITE-MATTER HYPERINTENSITIES; DWELLING ELDERLY-PEOPLE;
BODY-COMPOSITION; COGNITIVE FUNCTION; PHYSICAL PERFORMANCE; WOMENS
HEALTH; WALKING SPEED; ASSOCIATION; DISEASE; DISABILITY
AB Background. In community-dwelling older adults, global cognitive function predicts longitudinal gait speed decline. Few prospective studies have evaluated whether specific executive cognitive deficits in aging may account for gait slowing over time.
Methods. Multiple cognitive tasks were administered at baseline in 909 participants in the Health, Aging, and Body Composition Study Cognitive Vitality Substudy (mean age 75.2 +/- 2.8 years, 50.6% women, 48.4% black). Usual gait speed (m/s) over 20 minutes was assessed at baseline and over a 5-year follow-up.
Results. Poorer performance in each cognitive task was cross-sectionally associated with slower gait independent of demographic and health characteristics. In longitudinal analyses, each 1 SD poorer performance in global function, verbal memory, and executive function was associated with 0.003-0.004 m/s greater gait speed decline per year (p=.03-.05) after adjustment for baseline gait speed, demographic, and health characteristics.
Conclusions. In this well-functioning cohort, several cognitive tasks were associated with gait speed cross-sectionally and predicted longitudinal gait speed decline. These data are consistent with a shared pathology underlying cognitive and motor declines but do not suggest that specific executive cognitive deficits account for slowing of usual gait in aging.
C1 [Watson, N. L.; Rosano, C.; Boudreau, R. M.; Sutton-Tyrrell, K.; Newman, A. B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Simonsick, E. M.; Ferrucci, L.] NIA, Clin Res Branch, Intramural Res Program, Baltimore, MD 21224 USA.
[Hardy, S. E.; Newman, A. B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA.
[Atkinson, H. H.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA.
[Yaffe, K.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Yaffe, K.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Satterfield, S.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
RP Watson, NL (reprint author), Univ Pittsburgh, Dept Epidemiol, 130 N Bellefield Ave,4th Floor, Pittsburgh, PA 15213 USA.
EM watsonn@edc.pitt.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506;
Rosano, Caterina/0000-0002-4271-6010; Boudreau,
Robert/0000-0003-0162-5187
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; National Institutes of Health, NIA
FX This work was supported by National Institute on Aging (NIA) contract
numbers N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 and in part by
the Intramural Research Program of the National Institutes of Health,
NIA.
NR 52
TC 88
Z9 88
U1 3
U2 13
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD OCT
PY 2010
VL 65
IS 10
BP 1093
EP 1100
DI 10.1093/gerona/glq111
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 651WK
UT WOS:000281957800009
PM 20581339
ER
PT J
AU Brown, P
Gipson, C
AF Brown, Patricia
Gipson, Chester
TI A word from OLAW and USDA
SO LAB ANIMAL
LA English
DT Editorial Material
C1 [Brown, Patricia] NIH, OLAW, OD, HHS, Bethesda, MD 20892 USA.
[Gipson, Chester] USDA, APHIS, AC, Washington, DC USA.
RP Brown, P (reprint author), NIH, OLAW, OD, HHS, Bethesda, MD 20892 USA.
NR 1
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
J9 LAB ANIMAL
JI Lab Anim.
PD OCT
PY 2010
VL 39
IS 10
BP 299
EP 299
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA 660TP
UT WOS:000282668300005
PM 20859274
ER
PT J
AU Pogribny, IP
Starlard-Davenport, A
Tryndyak, VP
Han, T
Ross, SA
Rusyn, I
Beland, FA
AF Pogribny, Igor P.
Starlard-Davenport, Athena
Tryndyak, Volodymyr P.
Han, Tao
Ross, Sharon A.
Rusyn, Ivan
Beland, Frederick A.
TI Difference in expression of hepatic microRNAs miR-29c, miR-34a, miR-155,
and miR-200b is associated with strain-specific susceptibility to
dietary nonalcoholic steatohepatitis in mice
SO LABORATORY INVESTIGATION
LA English
DT Article
DE methyl-deficient diet; mice; microRNA; nonalcoholic steatohepatitis;
strain difference.
ID FATTY LIVER-DISEASE; BINDING-PROTEIN-BETA; HUMAN
HEPATOCELLULAR-CARCINOMA; MITOCHONDRIAL-DNA DAMAGE; INDUCED OXIDATIVE
STRESS; HUMAN BREAST-CANCER; GENE-EXPRESSION; DOWN-REGULATION;
E-CADHERIN; C/EBP-BETA
AB The importance of dysregulation of microRNA (miRNA) expression in nonalcoholic steatohepatitis (NASH) has been increasingly recognized; however, the association between altered expression of miRNAs and pathophysiological features of NASH and whether there is a connection between susceptibility to NASH and altered expression of miRNAs are largely unknown. In this study, male inbred C57BL/6J and DBA/2J mice were fed a lipogenic methyl-deficient diet that causes liver injury similar to human NASH, and the expression of miRNAs and the level of proteins targeted by these miRNAs in the livers were determined. Administration of the methyl-deficient diet triggered NASH-specific changes in the livers of C57BL/6J and DBA/2J mice, with the magnitude being more severe in DBA/2J mice. This was evidenced by a greater extent of expression of fibrosis-related genes in the livers of methyl-deficient DBA/2J mice. The development of NASH was accompanied by prominent changes in the expression of miRNAs, including miR-29c, miR-34a, miR-155, and miR-200b. Interestingly, changes in the expression of these miRNAs and protein levels of their targets, including Cebp-b, Socs 1, Zeb-1, and E-cadherin, in the livers of DBA/2J mice fed a methyl-deficient diet were more pronounced as compared with those in C57BL/6J mice. These results show that alterations in the expression of miRNAs are a prominent event during development of NASH induced by methyl deficiency and strongly suggest that severity of NASH and susceptibility to NASH may be determined by variations in miRNA expression response. More important, our data provide a mechanistic link between alterations in miRNA expression and pathophysiological and pathomorphological features of NASH. Laboratory Investigation (2010) 90, 1437-1446; doi: 10.1038/labinvest.2010.113; published online 14 June 2010
C1 [Pogribny, Igor P.; Starlard-Davenport, Athena; Tryndyak, Volodymyr P.; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
[Han, Tao] Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA.
[Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA.
RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3990 NCTR Rd,HFT-140, Jefferson, AR 72079 USA.
EM igor.pogribny@fda.hhs.gov
RI Rusyn, Ivan/S-2426-2016
FU NIEHS NIH HHS [R01 ES015241]
NR 50
TC 87
Z9 95
U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD OCT
PY 2010
VL 90
IS 10
BP 1437
EP 1446
DI 10.1038/labinvest.2010.113
PG 10
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 655TY
UT WOS:000282273900004
PM 20548288
ER
PT J
AU Stroeve, JHM
Brufau, G
Stellaard, F
Gonzalez, FJ
Staels, B
Kuipers, F
AF Stroeve, Johanna H. M.
Brufau, Gemma
Stellaard, Frans
Gonzalez, Frank J.
Staels, Bart
Kuipers, Folkert
TI Intestinal FXR-mediated FGF15 production contributes to diurnal control
of hepatic bile acid synthesis in mice
SO LABORATORY INVESTIGATION
LA English
DT Article
DE bile acids; circadian rhythm; Cyp7A1; enterohepatic circulation; Fgf15;
Fxr
ID FARNESOID-X-RECEPTOR; NUCLEAR RECEPTOR; DEFICIENT MICE; CHOLESTEROL;
METABOLISM; HOMEOSTASIS; LIVER; GENE; FIBROBLAST-GROWTH-FACTOR-19;
TRANSCRIPTION
AB Hepatic bile acid synthesis is subject to complex modes of transcriptional control, in which the bile acid-activated nuclear receptor farnesoid X receptor (FXR) in liver and intestine-derived, FXR-controlled fibroblast growth factor 15 (Fgf15) are involved. The Fgf15 pathway is assumed to contribute significantly to control of hepatic bile acid synthesis. However, scientific evidence supporting this assumption is primarily based on gene expression data. Using intestine-selective FXR knockout mice (iFXR-KO), we show that contribution of intestinal FXR-Fgf15 signalling in regulation of hepatic cholesterol 7a-hydroxylase (Cyp7A1) expression depends on time of the day with increased hepatic Cyp7A1 expression in iFXR-KO mice compared with controls exclusively during the dark phase. To assess the physiological relevance hereof, we determined effects of intestine-selective deletion of FXR on physiological parameters such as bile formation and kinetics of the enterohepatic circulation of bile acids. It appeared that intestinal FXR deficiency leads to a modest but significant increase in cholic acid pool size, without changes in fractional turnover rate. As a consequence, bile flow and biliary bile acid secretion rates were increased in iFXR-KO mice compared with controls. Feeding a bile acid-containing diet or treatment with a bile acid sequestrant similarly affected bile formation in iFXR-KO and control mice and induced similar changes in Cyp7A1 and Cyp8B1 expression patterns. In conclusion, this study is the first to demonstrate the physiological relevance of the contribution of the intestinal FXR-Fgf15 signalling pathway in control of hepatic bile acid synthesis. Fgf15 contributes to the regulation of hepatic bile acid synthesis in mice mainly during the dark phase. Expansion of the circulating bile acid pool as well as bile acid sequestration diminishes the contribution of intestinal FXR-Fgf15 signalling in control of hepatic bile acid synthesis and bile formation. Laboratory Investigation (2010) 90, 1457-1467; doi: 10.1038/labinvest.2010.107; published online 7 June 2010
C1 [Stroeve, Johanna H. M.] Univ Groningen, Univ Med Ctr Groningen, CMC V, Ctr Liver Digest & Metab Dis,Dept Pediat, NL-9700 RB Groningen, Netherlands.
[Stellaard, Frans; Kuipers, Folkert] Univ Groningen, Univ Med Ctr Groningen, Ctr Liver Digest & Metab Dis, Dept Lab Med, NL-9700 RB Groningen, Netherlands.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Staels, Bart] Inst Pasteur, Dept Atherosclerose, Lille, France.
[Staels, Bart] INSERM, UMR 545, F-59045 Lille, France.
[Staels, Bart] Univ Lille 2, Fac Sci Pharmaceut & Biol, Lille, France.
[Staels, Bart] Univ Lille 2, Fac Med, Lille, France.
RP Stroeve, JHM (reprint author), Univ Groningen, Univ Med Ctr Groningen, CMC V, Ctr Liver Digest & Metab Dis,Dept Pediat, Hanzepl 1,POB 30-001, NL-9700 RB Groningen, Netherlands.
EM J.H.M.Stroeve@med.umcg.nl
OI Staels, Bart/0000-0002-3784-1503
FU European Commission [LSHM-CT-2005-018734]; Agence Nationale pour la
Recherche (ANR) [LSHM-CT-2005-018734]
FX We thank our colleagues for stimulating scientific discussions and
advice. Our work is part of the project 'Hepatic and adipose tissue and
functions in the metabolic syndrome' (HEPADIP, see
http://www.hepadip.org/), which is supported by the European Commission
as an Integrated Project under the 6th Framework Programme (Contract
LSHM-CT-2005-018734). In addition, B.S. is recipient of a grant from
'Agence Nationale pour la Recherche' (ANR). Grant number: 'HEPADIP'
(Contract LSHM-CT-2005-018734) and 'Agence Nationale pour la Recerche'
(ANR).
NR 26
TC 31
Z9 33
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD OCT
PY 2010
VL 90
IS 10
BP 1457
EP 1467
DI 10.1038/labinvest.2010.107
PG 11
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 655TY
UT WOS:000282273900006
PM 20531290
ER
PT J
AU Laaksovirta, H
Peuralinna, T
Schymick, JC
Scholz, SW
Lai, SL
Myllykangas, L
Sulkava, R
Jansson, L
Hernandez, DG
Gibbs, JR
Nalls, MA
Heckerman, D
Tienari, PJ
Traynor, BJ
AF Laaksovirta, Hannu
Peuralinna, Terhi
Schymick, Jennifer C.
Scholz, Sonja W.
Lai, Shaoi-Lin
Myllykangas, Liisa
Sulkava, Raimo
Jansson, Lilja
Hernandez, Dena G.
Gibbs, J. Raphael
Nalls, Michael A.
Heckerman, David
Tienari, Pentti J.
Traynor, Bryan J.
TI Chromosome 9p21 in amyotrophic lateral sclerosis in Finland: a
genome-wide association study
SO LANCET NEUROLOGY
LA English
DT Article
ID FRONTOTEMPORAL LOBAR DEGENERATION; MOTOR-NEURON DISEASE; DEMENTIA;
POPULATION; ALS; SUSCEPTIBILITY; LINKAGE; PREVALENCE; VARIANTS; FAMILIES
AB Background The genetic cause of amyotrophic lateral sclerosis (ALS) is not well understood. Finland is a well suited location for a genome-wide association study of ALS because the incidence of the disease is one of the highest in the world, and because the genetic homogeneity of the Finnish population enhances the ability to detect risk loci. We aimed to identify genetic risk factors for ALS in the Finnish population.
Methods We did a genome-wide association study of Finnish patients with ALS and control individuals by use of Illumina genome-wide genotyping arrays. DNA was collected from patients who attended an ALS specialty clinic that receives referrals from neurologists throughout Finland. Control samples were from a population-based study of elderly Finnish individuals. Patients known to carry D90A alleles of the SOD1 gene (n=40) were included in the final analysis as positive controls to assess whether our genome-wide association study was able to detect an association signal at this locus.
Findings We obtained samples from 442 patients with ALS and 521 control individuals. After quality control filters were applied, 318167 single nucleotide polymorphisms (SNPs) from 405 people with ALS and 497 control individuals were available for analysis. We identified two association peaks that exceeded genome-wide significance. One was located on chromosome 21q22 (rs13048019, p=2. 58x10(-8)), which corresponds to the autosomal recessive D90A allele of the SOD1 gene. The other was detected in a 232 kb block of linkage disequilibrium (rs3849942, p=9. 11x10(-11)) in a region of chromosome 9p that was previously identified in linkage studies of families with ALS. Within this region, we defined a 42-SNP haplotype that was associated with significantly increased risk of ALS (p=7.47x10(-33) when people with familial ALS were compared with controls, odds ratio 21.0,95% CI 11.2-39.1) and which overlapped with an association locus recently reported for frontotemporal dementia. For the 93 patients with familial ALS, the population attributable risk for the chromosome 9p21 locus was 37-9% (95% CI 27.7-48.1) and that for D90A homozygosity was 25.5% (16.9-34.1).
Interpretation The chromosome 9p21 locus is a major cause of familial ALS in the Finnish population. Our data suggest the presence of a founder mutation for chromosome 9p21-linked ALS. Furthermore, the overlap with the risk haplotype recently reported for frontotemporal dementia provides further evidence of a shared genetic cause for these two neurodegenerative diseases.
Funding National Institutes of Health and National Institute on Aging, Microsoft Research, ALS Association, Helsinki University Central Hospital, Finnish Academy, Finnish Medical Society Duodecim, and Kuopio University.
C1 [Schymick, Jennifer C.; Lai, Shaoi-Lin; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Scholz, Sonja W.; Hernandez, Dena G.; Nalls, Michael A.] NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Laaksovirta, Hannu; Peuralinna, Terhi; Jansson, Lilja; Tienari, Pentti J.] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland.
[Laaksovirta, Hannu; Peuralinna, Terhi; Jansson, Lilja; Tienari, Pentti J.] Univ Helsinki, Mol Neurol Programme, Biomedicum, Helsinki, Finland.
[Scholz, Sonja W.] Georgetown Univ, Dept Neurosci, Washington, DC USA.
[Lai, Shaoi-Lin] Chang Gung Univ Hosp, Chiayi, Taiwan.
[Lai, Shaoi-Lin] Coll Med, Chiayi, Taiwan.
[Myllykangas, Liisa] Univ Helsinki, Dept Pathol, Haartman Inst, Helsinki, Finland.
[Myllykangas, Liisa] Folkhalsan Res Ctr, Helsinki, Finland.
[Sulkava, Raimo] Univ Eastern Finland, Sect Geriatr, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
[Heckerman, David] Microsoft Res, Los Angeles, CA USA.
[Traynor, Bryan J.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA.
RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, 35 Convent Dr,Room 1A-1000, Bethesda, MD 20892 USA.
EM traynorb@mail.nih.gov
RI Tienari, Pentti/A-4893-2012; Traynor, Bryan/G-5690-2010;
OI Scholz, Sonja/0000-0002-6623-0429
FU Sanofi-Aventis; Rhone-Poulenc Rorer; National Institutes of Health;
National Institute on Aging [Z01-AG000949-02]; Microsoft Research; ALS
Association; Helsinki University Central Hospital; Finnish Academy;
Finnish Medical Society Duodecim; Kuopio University
FX HL has received payment from Sanofi-Aventis and Rhone-Poulenc Rorer for
development of educational presentations including services on speakers'
bureaus, as well as travel and accommodation expenses from
Rhone-Poulenc-Rorer. DH is senior director of the eScience Research
Group at Microsoft Research. None of the other authors has any conflicts
of interest.; This work was supported in part by the Intramural Research
Program of the National Institutes of Health, and the National Institute
on Aging (Z01-AG000949-02) and was also funded by Microsoft Research,
the ALS Association, the Helsinki University Central Hospital, the
Finnish Academy, the Finnish Medical Society Duodecim, and Kuopio
University. We thank the DNA extraction and storage facility of the
National Institute for Health and Welfare and Institute for Molecular
Medicine in Finland (FIMM), Helsinki, Finland, and Tuomo Polvikoski,
Institute for Ageing and Health, Campus for Ageing and Vitality,
Newcastle University, UK, for their help with DNA extraction from the
patients diagnosed with ALS.
NR 32
TC 129
Z9 130
U1 0
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
J9 LANCET NEUROL
JI Lancet Neurol.
PD OCT
PY 2010
VL 9
IS 10
BP 978
EP 985
DI 10.1016/S1474-4422(10)70184-8
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 672WC
UT WOS:000283616700012
PM 20801718
ER
PT J
AU Shatunov, A
Mok, K
Newhouse, S
Weale, ME
Smith, B
Vance, C
Johnson, L
Veldink, JH
van Es, MA
van den Berg, LH
Robberecht, W
Van Damme, P
Hardiman, O
Farmer, AE
Lewis, CM
Butler, AW
Abel, O
Andersen, PM
Fogh, I
Silani, V
Chio, A
Traynor, BJ
Melki, J
Meininger, V
Landers, JE
McGuffin, P
Glass, JD
Pall, H
Leigh, PN
Hardy, J
Brown, RH
Powell, JF
Orrell, RW
Morrison, KE
Shaw, PJ
Shaw, CE
Al-Chalabi, A
AF Shatunov, Aleksey
Mok, Kin
Newhouse, Stephen
Weale, Michael E.
Smith, Bradley
Vance, Caroline
Johnson, Lauren
Veldink, Jan H.
van Es, Michael A.
van den Berg, Leonard H.
Robberecht, Wim
Van Damme, Philip
Hardiman, Orla
Farmer, Anne E.
Lewis, Cathryn M.
Butler, Amy W.
Abel, Olubunmi
Andersen, Peter M.
Fogh, Isabella
Silani, Vincenzo
Chio, Adriano
Traynor, Bryan J.
Melki, Judith
Meininger, Vincent
Landers, John E.
McGuffin, Peter
Glass, Jonathan D.
Pall, Hardev
Leigh, P. Nigel
Hardy, John
Brown, Robert H., Jr.
Powell, John F.
Orrell, Richard W.
Morrison, Karen E.
Shaw, Pamela J.
Shaw, Christopher E.
Al-Chalabi, Ammar
TI Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and
seven other countries: a genome-wide association study
SO LANCET NEUROLOGY
LA English
DT Article
ID FRONTOTEMPORAL LOBAR DEGENERATION; COPY NUMBER VARIATION;
SUSCEPTIBILITY; POPULATION; DEMENTIA; GENE; ALS; LINKAGE; LOCI; IRISH
AB Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons that results in progressive weakness and death from respiratory failure, commonly within about 3 years. Previous studies have shown association of a locus on chromosome 9p with ALS and linkage with ALS-frontotemporal dementia. We aimed to test whether this genomic region is also associated with ALS in an independent set of UK samples, and to identify risk factors associated with ALS in a further genome-wide association study that combined data from the independent analysis with those from other countries.
Methods We collected samples from patients with sporadic ALS from 20 UK hospitals and obtained UK control samples from the control groups of the Depression Case Control study, the Bipolar Affective Case Control Study, and the British 1958 birth cohort DNA collection. Genotyping of DNA in this independent analysis was done with Illumina HumanHap550 BeadChips. We then undertook a joint genome-wide analysis that combined data from the independent set with published data from the UK, USA, Netherlands, Ireland, Italy, France, Sweden, and Belgium. The threshold for significance was p=0.05 in the independent analysis, because we were interested in replicating a small number of previously reported associations, whereas the Bonferroni-corrected threshold for significance in the joint analysis was p=2.20x10(-7).
Findings After quality control, samples were available from 599 patients and 4144 control individuals in the independent set. In this analysis, two single nucleotide polymorphisms in a locus on chromosome 9p21.2 were associated with ALS: rs3849942 (p=2.22x10(-6); odds ratio [OR] 1.39, 95% CI 1.21-1.59) and rs2814707 (p=3.32x10(-6); 1.38, 1.20-1.58). In the joint analysis, which included samples from 4312 patients with ALS and 8425 control individuals, rs3849942 (p=4. 64x10(-10); OR 1.22, 95% CI 1.15-1.30) and rs2814707 (p=4.72x10(-10); 1.22, 1.15-1.30) were associated with ALS.
Interpretation We have found strong evidence of a genetic association of two single nucleotide polymorphisms on chromosome 9 with sporadic ALS, in line with findings from previous independent GWAS of ALS and linkage studies of ALS frontotemporal dementia. Our findings together with these earlier findings suggest that genetic variation at this locus on chromosome 9 causes sporadic ALS and familial ALS frontotemporal dementia. Resequencing studies and then functional analysis should be done to identify the defective gene.
Funding ALS Therapy Alliance, the Angel Fund, the Medical Research Council, the Motor Neurone Disease Association of Great Britain and Northern Ireland, the Wellcome Trust, and the National Institute for Health Research Dementias and Neurodegenerative Diseases Research Network (DeNDRoN).
C1 [Al-Chalabi, Ammar] Kings Coll London, Med Res Council Ctr Neurodegenerat Res, Inst Psychiat, Dept Clin Neurosci, London SE5 8AF, England.
[Weale, Michael E.; Lewis, Cathryn M.] Guys Hosp, Dept Med & Mol Genet, London SE1 9RT, England.
[Farmer, Anne E.; Lewis, Cathryn M.; Butler, Amy W.; McGuffin, Peter] Inst Psychiat, Med Res Council Ctr Social Genet & Dev Psychiat, London, England.
[Powell, John F.] Inst Psychiat, Dept Neurosci, London SE5 8AF, England.
[Mok, Kin; Hardy, John; Orrell, Richard W.] UCL, Inst Neurol, London, England.
[Veldink, Jan H.; van Es, Michael A.; van den Berg, Leonard H.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands.
[Robberecht, Wim; Van Damme, Philip] Katholieke Univ Leuven Hosp, Dept Neurol, Louvain, Belgium.
[Robberecht, Wim; Van Damme, Philip] Univ Louvain, Neurobiol Lab, Vesalius Res Ctr, VIB, Louvain, Belgium.
[Hardiman, Orla] Beaumont Hosp, Dept Neurol, Dublin, Ireland.
[Hardiman, Orla] Trinity Coll Dublin, Dublin, Ireland.
[Andersen, Peter M.] Umea Univ, Dept Clin Neurosci, S-90187 Umea, Sweden.
[Silani, Vincenzo] Univ Milan, Dept Neurol, Dino Ferrari Ctr, IRCCS,Ist Auxol Italiano, Milan, Italy.
[Silani, Vincenzo] Univ Milan, Neurosci Lab, Dino Ferrari Ctr, IRCCS,Ist Auxol Italiano, Milan, Italy.
[Chio, Adriano] Univ Turin, Dept Neurosci, Turin, Italy.
[Chio, Adriano] Azienda Osped Univ San Giovanni Battista, Turin, Italy.
[Traynor, Bryan J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Melki, Judith] INSERM, UMR 788, Paris, France.
[Melki, Judith] Univ Paris 11, Bicetre Hosp, Paris, France.
[Meininger, Vincent] Univ Paris 06, Hop La Pitie Salpetriere, Assistance Publ Hop Paris, Paris, France.
[Landers, John E.; Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA.
[Glass, Jonathan D.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA.
[Pall, Hardev; Morrison, Karen E.] Univ Birmingham, Coll Med & Dent, Sch Clin & Expt Med, Birmingham, W Midlands, England.
[Pall, Hardev; Morrison, Karen E.] Univ Hosp Birmingham NHS Fdn Trust, Div Neurosci, Birmingham, W Midlands, England.
[Shaw, Pamela J.] Univ Sheffield, Acad Neurol Unit, Dept Neurosci, Fac Med Dent & Hlth, Sheffield, S Yorkshire, England.
RP Al-Chalabi, A (reprint author), Kings Coll London, Med Res Council Ctr Neurodegenerat Res, Inst Psychiat, Dept Clin Neurosci, PO41, London SE5 8AF, England.
EM ammar.al-chalabi@kcl.ac.uk
RI Vance, Caroline/C-3047-2012; McGuffin, Peter/A-1565-2012; Orrell,
Richard/L-2123-2013; Smith, Bradley/H-6107-2013; Lewis,
Cathryn/A-5225-2010; Al-Chalabi, Ammar/E-5361-2010; Shatunov,
Aleksey/E-6946-2011; Powell, John/G-4412-2011; Van Damme,
Philip/A-6464-2009; Hardy, John/C-2451-2009; Weale, Michael/F-2587-2010;
Mok, Kin/F-5860-2012; Traynor, Bryan/G-5690-2010; Newhouse,
Stephen/C-9330-2011;
OI Vance, Caroline/0000-0001-5780-6951; McGuffin,
Peter/0000-0002-9888-2907; Lewis, Cathryn/0000-0002-8249-8476;
Al-Chalabi, Ammar/0000-0002-4924-7712; Powell, John/0000-0001-6124-439X;
Van Damme, Philip/0000-0001-6384-0611; Weale,
Michael/0000-0003-4593-1186; Newhouse, Stephen/0000-0002-1843-9842;
Chio, Adriano/0000-0001-9579-5341; Silani, Vincenzo/0000-0002-7698-3854;
Hardiman, Orla/0000-0003-2610-1291
FU Motor Neurone Disease Association [3/3]; Wellcome Trust [070122/A/02/Z,
068545/Z/02]; Angel Fund; ALS Therapy Alliance; Motor Neurone Disease
Association for genotyping [10/57]; Medical Research Council [G0000934,
G0701420]; Prinses Beatrix Fonds; VSB Fonda; Kersten Foundation;
Netherlands ALS Foundation; Adessium Foundation (LHvdB); Brain
Foundation of the Netherlands; University of Leuven (Methusalem);
Belgian Federal Science Policy Office [P6/43]; Italian Ministry of
Health [31]; National Institutes of Health; National Institute on Aging
[Z01-AG000949-02]; Fondazione Vialli e Mauro per la SLA [3/2008];
Federazione Italians Giuoco Calcio [2/2008]; ALS Association; ALS
Society of Canada; MNDA Iceland; National Institute for Health Research
Biomedical Research Centre for Mental Health
FX The independent study case samples were obtained from the UK DNA bank
for Motor Neuron Disease Research, which was funded by the Motor Neurone
Disease Association grant 3/3 and the Wellcome Trust grant
070122/A/02/Z, with additional support from the National Institute for
Health Research Dementias and Neurodegenerative Diseases Research
Network (DeNDRoN). Genotyping of the independent study case samples was
funded by grants from the Angel Fund and ALS Therapy Alliance, with
additional funding to RO and JH from the Motor Neurone Disease
Association for genotyping (grant 10/57). We acknowledge use of genotype
data from the British 1958 birth cohort DNA collection, which was funded
by the Medical Research Council grant G0000934 and the Wellcome Trust
grant 068545/Z/02. Controls for the DeCC study and BACCS were genotyped
under the Medical Research Council grant G0701420. This project has been
supported by the Prinses Beatrix Fonds, VSB Fonda, The Kersten
Foundation, The Netherlands ALS Foundation, and The Adessium Foundation
(LHvdB). JHV is supported by grants from The Brain Foundation of the
Netherlands. WR is supported by grants from the University of Leuven
(Methusalem) and the Interuniversity Attraction Poles (IUAP) program
P6/43 of the Belgian Federal Science Policy Office. VS is supported by
the Italian Ministry of Health (Ricerca Finalizzata 2007 number 31).
This work was supported in part by the Intramural Research Program of
the National Institutes of Health, and the National Institute on Aging
(Z01-AG000949-02). AC is supported by the Italian Ministry of Health
(Ricerca Sanitaria Finalizzata, 2007, number 30), the Fondazione Vialli
e Mauro per la SLA (grant 3/2008), and the Federazione Italians Giuoco
Calcio (Grant 2/2008). We thank the ALS Association, the ALS Society of
Canada, MNDA Iceland, and the National Institute for Health Research
Biomedical Research Centre for Mental Health for support, and Kuang Lin
for programming advice.
NR 35
TC 117
Z9 118
U1 2
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
EI 1474-4465
J9 LANCET NEUROL
JI Lancet Neurol.
PD OCT
PY 2010
VL 9
IS 10
BP 986
EP 994
DI 10.1016/S1474-4422(10)70197-6
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 672WC
UT WOS:000283616700013
PM 20801717
ER
PT J
AU Bible, KC
Suman, VJ
Molina, JR
Smallridge, RC
Maples, WJ
Menefee, ME
Rubin, J
Sideras, K
Morris, JC
McIver, B
Burton, JK
Webster, KP
Bieber, C
Traynor, AM
Flynn, PJ
Goh, BC
Tang, H
Ivy, SP
Erlichman, C
AF Bible, Keith C.
Suman, Vera J.
Molina, Julian R.
Smallridge, Robert C.
Maples, William J.
Menefee, Michael E.
Rubin, Joseph
Sideras, Kostandinos
Morris, John C., III
McIver, Bryan
Burton, Jill K.
Webster, Kevin P.
Bieber, Carolyn
Traynor, Anne M.
Flynn, Patrick J.
Goh, Boon Cher
Tang, Hui
Ivy, Susan Percy
Erlichman, Charles
CA Mayo Clinic Canc Ctr
Mayo Phase 2 Consortium
TI Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic
differentiated thyroid cancers: results of a phase 2 consortium study
SO LANCET ONCOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; II TRIAL; INCREASED EXPRESSION;
UNITED-STATES; CARCINOMA; SORAFENIB; STATISTICS; INHIBITOR; SURVIVAL
AB Background Chemotherapy has historically proven ineffective in advanced differentiated thyroid cancers, but the realisation that various tyrosine kinases are activated in the disease suggested a potential therapeutic role for tyrosine-kinase inhibitors. We investigated the safety and efficacy of pazopanib.
Methods This phase 2 trial was done from Feb 22, 2008, to Jan 31, 2009, in patients with metastatic, rapidly progressive, radioiodine-refractory differentiated thyroid cancers. Each patient received 800 mg continuous pazopanib daily in 4-week cycles until disease progression, drug intolerance, or both occurred. Up to two previous therapies were allowed, and measurable disease with radiographic progression in the 6-month period before enrolment was a requirement for inclusion. The primary endpoint was any tumour response, according to the Response Evaluation Criteria in Solid Tumors 1.0. This study is registered with ClinicalTrials.gov, number NCT00625846.
Findings 39 patients were enrolled. One patient had received no previous radioiodine therapy and another withdrew consent before treatment. Clinical outcomes could, therefore, be assessed in 37 patients (19 [51%] men, median age 63 years). The study is closed to accrual of new patients, but several enrolled patients are still being treated. Patients received a median of 12 cycles (range 1 to >23, total >383). Confirmed partial responses were recorded in 18 patients (response rate 49%, 95% CI 35-68), with likelihood of response lasting longer than 1 year calculated to be 66%. Maximum concentration of pazopanib in plasma during cycle one was significantly correlated with radiographic response (r=-0.40, p=0.021). 16 (43%) patients required dose reductions owing to adverse events, the most frequent of which (any grade) were fatigue (29 patients), skin and hair hypopigmentation (28), diarrhoea (27), and nausea (27). Two patients who died during treatment had pre-existing contributory disorders.
Interpretation Pazopanib seems to represent a promising therapeutic option for patients with advanced differentiated thyroid cancers. The correlation of the patient's response and pazopanib concentration during the first cycle might indicate that treatment can be individualised to achieve optimum outcomes. Assessment of pazopanib in an expanded cohort of patients with differentiated thyroid cancer, as well as in cohorts of patients with medullary and anaplastic thyroid cancers, is presently being done.
C1 [Bible, Keith C.; Molina, Julian R.; Rubin, Joseph; Sideras, Kostandinos; Burton, Jill K.; Webster, Kevin P.; Erlichman, Charles] Mayo Clin, Div Med Oncol, Rochester, MN 55901 USA.
[Suman, Vera J.; Tang, Hui] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55901 USA.
[Morris, John C., III; McIver, Bryan] Mayo Clin, Div Endocrinol, Rochester, MN 55901 USA.
[Smallridge, Robert C.] Mayo Clin Florida, Div Endocrinol, Jacksonville, FL USA.
[Maples, William J.; Menefee, Michael E.; Bieber, Carolyn] Mayo Clin Florida, Div Med Oncol, Jacksonville, FL USA.
[Traynor, Anne M.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
[Goh, Boon Cher] Natl Univ Singapore Hosp, Singapore, Singapore.
[Ivy, Susan Percy] NCI, Ctr Translat Expt Therapeut, Bethesda, MD 20892 USA.
RP Bible, KC (reprint author), Mayo Clin, Div Med Oncol, 200 First St SW, Rochester, MN 55901 USA.
EM bible.keith@mayo.edu
RI Tang, Hui/B-3643-2010;
OI Sideras, Kostandinos/0000-0002-4698-2105
FU National Cancer Institute [NCI CA15083, CM62205]
FX KCB, JAM. and CE were supported in part by the National Cancer Institute
(grants CA15083 and CM62205).; National Cancer Institute, supported in
part by NCI CA15083 and CM62205.
NR 29
TC 203
Z9 207
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD OCT
PY 2010
VL 11
IS 10
BP 962
EP 972
DI 10.1016/S1470-2045(10)70203-5
PG 11
WC Oncology
SC Oncology
GA 667RE
UT WOS:000283210600022
PM 20851682
ER
PT J
AU Litzinger, MT
Foon, KA
Tsang, KY
Schlom, J
Palena, C
AF Litzinger, Mary T.
Foon, Kenneth A.
Tsang, Kwong-Yok
Schlom, Jeffrey
Palena, Claudia
TI Comparative analysis of MVA-CD40L and MVA-TRICOM vectors for enhancing
the immunogenicity of chronic lymphocytic leukemia (CLL) cells
SO LEUKEMIA RESEARCH
LA English
DT Article
DE Immunotherapy; CLL; TRICOM; CD40L; Vaccine
ID MODIFIED VACCINIA VIRUS; ANTIGEN-PRESENTING CELLS; HUMAN B-CELLS;
COSTIMULATORY MOLECULES; RECOMBINANT VECTOR; THERAPEUTIC VACCINATION;
INDUCE EXPRESSION; IMMUNE-RESPONSES; DENDRITIC CELLS; T-LYMPHOCYTES
AB Adenoviral transduction with CD40L and poxviral transduction with B7-1, ICAM-1, and LFA-3 (TRICOM) have been used to enhance the antigen-presenting capacity of chronic lymphocytic leukemia (CLL) cells. This study compares the same vector (modified vaccinia virus strain Ankara (MVA)) encoding CD40L or TRICOM for its ability to enhance the immunogenicity of CLL cells. CLL cells from some patients showed differential responses to each vector in terms of induction of autologous T-cell responses. This study supports the rationale for the use of CLL cells modified ex vivo with pre-specified recombinant MVA vectors as a whole tumor-cell vaccine for immunotherapy in CLL patients. Published by Elsevier Ltd.
C1 [Litzinger, Mary T.; Tsang, Kwong-Yok; Schlom, Jeffrey; Palena, Claudia] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Foon, Kenneth A.] Univ Pittsburgh, Div Hematol & Oncol, Inst Canc, Pittsburgh, PA USA.
RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA.
FU NIH; Center for Cancer Research; National Cancer Institute
FX We acknowledge the technical assistance of Margie Duberstein and the
editorial assistance of Debra Weingarten in the preparation of this
manuscript. We thank Dr. James Hodge and Dr. Ravi Madan for critical
reading of the manuscript. This research was supported by the NIH
Intramural Research Program, Center for Cancer Research, National Cancer
Institute.
NR 37
TC 4
Z9 5
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2126
J9 LEUKEMIA RES
JI Leuk. Res.
PD OCT
PY 2010
VL 34
IS 10
BP 1351
EP 1357
DI 10.1016/j.leukres.2009.12.013
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA 642LI
UT WOS:000281214700017
PM 20122733
ER
PT J
AU Reddy, P
Naidoo, RN
Robins, TG
Mentz, G
London, SJ
Li, HL
Naidoo, R
AF Reddy, Poovendhree
Naidoo, Rajen N.
Robins, Thomas G.
Mentz, Graciela
London, Stephanie J.
Li, Huiling
Naidoo, Richard
TI GSTM1, GSTP1, and NQO1 Polymorphisms and Susceptibility to Atopy and
Airway Hyperresponsiveness among South African Schoolchildren
SO LUNG
LA English
DT Article
DE Genetic polymorphism; Glutathione-S-transferases; Nicotinamide quinone
oxidoreductase; Oxidative stress; Atopy; AHR
ID GLUTATHIONE-S-TRANSFERASE; BRONCHIAL HYPERRESPONSIVENESS; RISK-FACTORS;
ASTHMA; GENE; INFLAMMATION; LOCUS; ASSOCIATION; PREVALENCE; CHILDREN
AB Glutathione-S-transferases (GSTM1 and GSTP1) and nicotinamide quinone oxidoreductase (NQO1) genes play an important role in cellular protection against oxidative stress which has been linked to asthma pathogenesis. We investigated whether common, functional polymorphisms in GSTM1, GSTP1 and NQO1 influence airway hyperreactivity (AHR) and atopy among schoolchildren in South Africa. Genomic DNA was extracted from 317 primary schoolchildren, aged 9-11 years, from urban, low socioeconomic communities of Durban, South Africa. GSTM1 (null vs. present genotype), GSTP1 (Ile105Val; AA -> AG + GG), and NQO1 (Pro/187Ser; CC -> CT/TT) genotypes were determined using polymerase chain reaction (PCR) methods. Atopy was defined as a positive skin-prick test to any of several common allergens. Airway hyperreactivity (AHR) was evaluated by pulmonary function testing before and after methacholine challenge. Among the children, 30% were GSTM1 null, 65% carried the G allele for GSTP1, and 36% carried the C allele for NQO1. The frequency of GSTM1, GSTP1, and NQO1 variants among our South African sample was similar to frequencies found in similar ethnic groups worldwide. Marked airway reactivity (PC(20) a parts per thousand currency sign 2 mg/ml) was found in 10.3% of children and approximately 40% of them were atopic. No significant associations for GSTM1 and NQO1 with either AHR or atopy were identified. A significant protective effect against atopy was found among children with one or two copies of the GSTP1 G allele.
C1 [Naidoo, Rajen N.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Occupat & Environm Hlth, ZA-4013 Durban, South Africa.
[Reddy, Poovendhree] Durban Univ Technol, Dept Community Hlth Studies, Durban, South Africa.
[Robins, Thomas G.; Mentz, Graciela] Univ Michigan, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[London, Stephanie J.; Li, Huiling] NIEHS, Div Intramural Res, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Naidoo, Richard] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Pfizer Mol Biol Unit, ZA-4013 Durban, South Africa.
RP Naidoo, RN (reprint author), Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Occupat & Environm Hlth, Private Bag 7, ZA-4013 Durban, South Africa.
EM naidoon@ukzn.ac.za
RI Naidoo, Rajen/N-4712-2013;
OI London, Stephanie/0000-0003-4911-5290
FU eThekwini Municipality; Durban University of Technology; National
Research Foundation (NRF), South Africa; National Institute of
Environmental Health Sciences, National Institutes of Health, Department
of Health and Human Services, USA [Z01 49019]
FX We thank the participants of the South Durban Health Study, both the
children and parents, for their dedicated cooperation and commitment.
Members of the study team, in particular Caron Jack, Joy Kistnasamy, and
Pamela Nasirumbi, are gratefully acknowledged. We also thank Prof. Mary
Lou Thompson for statistical advice and Zakeer Gafoor for assistance
with geno-typing. This study was supported by the eThekwini
Municipality, Durban University of Technology, and the National Research
Foundation (NRF), South Africa. This work was supported in part by the
Intramural Research Program of the National Institute of Environmental
Health Sciences, National Institutes of Health, Department of Health and
Human Services, USA (Z01 49019).
NR 22
TC 9
Z9 13
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0341-2040
J9 LUNG
JI Lung
PD OCT
PY 2010
VL 188
IS 5
BP 409
EP 414
DI 10.1007/s00408-010-9246-3
PG 6
WC Respiratory System
SC Respiratory System
GA 650OU
UT WOS:000281859800008
PM 20526719
ER
PT J
AU Sultan, F
Hamodeh, S
Murayama, Y
Saleem, KS
Logothetis, N
AF Sultan, Fahad
Hamodeh, Salah
Murayama, Yusuke
Saleem, Kadharbatcha S.
Logothetis, Nikos
TI Flat map areal topography in Macaca mulatta based on combined MRI and
histology
SO MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE Primate; Visual cortex; Maps; Neocortex
ID SUPERIOR TEMPORAL SULCUS; MEDIAL PREFRONTAL NETWORKS; CEREBRAL-CORTEX;
MACAQUE MONKEYS; RHESUS-MONKEY; VISUAL AREAS; DIFFERENTIAL CONNECTIONS;
CORTICAL CONNECTIONS; THALAMIC AFFERENTS; COORDINATE SYSTEM
AB Flattened representations are a useful approach to represent the convoluted complex surface of the neocortex of primates and other large-brained mammals. In this study, we compared the flattened representation of neocortical areas obtained from the recently published MRI and histology atlas of the rhesus monkey brain (Saleem KS, Logothetis NK. A combined MRI and histology atlas of the rhesus monkey brain in stereotaxic coordinates. London: Academic; 2007) with other previously published maps. Our results confirm that flat map representations are advantageous due to their ease of use and that current flat maps are well comparable to each other. Some differences arise due to different distinguishing criteria and here too flat maps can help to reveal them. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Sultan, Fahad; Hamodeh, Salah] HIH Clin Brain Res, Dept Cognit Neurol, D-72076 Tubingen, Germany.
[Murayama, Yusuke; Logothetis, Nikos] Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany.
[Saleem, Kadharbatcha S.] NIMH, NIH, Neuropsychol Lab, Bethesda, MD 20892 USA.
RP Sultan, F (reprint author), HIH Clin Brain Res, Dept Cognit Neurol, D-72076 Tubingen, Germany.
EM fahad.sultan@uni-tuebingen.de
OI Saleem, Kadharbatcha S/0000-0002-4450-9234
NR 48
TC 5
Z9 5
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0730-725X
J9 MAGN RESON IMAGING
JI Magn. Reson. Imaging
PD OCT
PY 2010
VL 28
IS 8
SI SI
BP 1159
EP 1164
DI 10.1016/j.mri.2010.03.023
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 658NZ
UT WOS:000282498000015
PM 20471190
ER
PT J
AU Goense, J
Logothetis, NK
Merkle, H
AF Goense, Jozien
Logothetis, Nikos K.
Merkle, Hellmut
TI Flexible, phase-matched, linear receive arrays for high-field MRI in
monkeys
SO MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE Monkey; Phased array; fMRI; Physiological noise
ID OCULAR DOMINANCE COLUMNS; HIGH-RESOLUTION FMRI; FUNCTIONAL MRI; LAMINAR
SPECIFICITY; SPIN-ECHO; PHYSIOLOGICAL NOISE; HEAD COIL; 1.5 T; DESIGN;
SIGNAL
AB High signal-to-noise ratios (SNR) are essential for high-resolution anatomical and functional MRI. Phased arrays are advantageous for this but have the drawback that they often have inflexible and bulky configurations. Particularly in experiments where functional MRI is combined with simultaneous electrophysiology, space constraints can be prohibitive. To this end we developed a highly flexible multiple receive element phased array for use on anesthetized monkeys. The elements are interchangeable and different sizes and combinations of coil elements can be used, for instance, combinations of single and overlapped elements. The preamplifiers including control electronics are detachable and can serve a variety of prefabricated and phase matched arrays of different configurations, allowing the elements to always be placed in close proximity to the area of interest. Optimizing performance of the individual elements ensured high SNR at the cortical surface as well as in deeper laying structures. Performance of a variety of arrangements of gapped linear arrays was evaluated at 4.7 and 7T in high-resolution anatomical and functional MRI. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Goense, Jozien; Logothetis, Nikos K.] Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, D-72076 Tubingen, Germany.
[Logothetis, Nikos K.] Univ Manchester, Div Imaging Sci & Biomed Engn, Manchester M13 9PT, Lancs, England.
[Merkle, Hellmut] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Goense, J (reprint author), Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, Spemannstr 38, D-72076 Tubingen, Germany.
EM jozien.goense@tuebingen.mpg.de
FU Max-Planck Society; National Institutes of Health, National Institute
Neurological Disorders and Stroke, Bethesda, MD, USA
FX This work was supported by the Max-Planck Society and in part by the
Intramural Program of the National Institutes of Health, National
Institute Neurological Disorders and Stroke, Bethesda, MD, USA. We thank
Mark Augath for technical support and Alexander Rauch for comments on an
earlier version of the manuscript.
NR 36
TC 15
Z9 15
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0730-725X
J9 MAGN RESON IMAGING
JI Magn. Reson. Imaging
PD OCT
PY 2010
VL 28
IS 8
SI SI
BP 1183
EP 1191
DI 10.1016/j.mri.2010.03.026
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 658NZ
UT WOS:000282498000018
PM 20456890
ER
PT J
AU Duyn, JH
AF Duyn, Jozef H.
TI Study of brain anatomy with high-field MRI: recent progress
SO MAGNETIC RESONANCE IMAGING
LA English
DT Review
DE High field MRI; Magnetic susceptibility; Brain; Contrast; Iron
ID WHITE-MATTER CONTRAST; ARRAY HEAD COIL; IRON CONTENT; IN-VIVO;
PHASED-ARRAY; 8 TESLA; 7.0 T; SUSCEPTIBILITY; IMAGES; MICROSCOPY
AB Recent developments in high-field magnetic resonance imaging technology have led to improved contrast and resolution and are opening up new possibilities for the study of human brain anatomy. In particular, techniques sensitized to magnetic susceptibility contrast provide particular advantages at high field that have allowed visualization of brain structures that have been difficult to detect with conventional technology. In this review, some of these developments and techniques will be discussed, and an attempt will be made to interpret magnetic susceptibility contrast based on recent studies. Published by Elsevier Inc.
C1 NINDS, Lab Adv MRI, LFMI, NIH, Bethesda, MD 20892 USA.
RP Duyn, JH (reprint author), NINDS, Lab Adv MRI, LFMI, NIH, Bethesda, MD 20892 USA.
EM jhd@helix.nih.gov
NR 50
TC 24
Z9 24
U1 1
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0730-725X
J9 MAGN RESON IMAGING
JI Magn. Reson. Imaging
PD OCT
PY 2010
VL 28
IS 8
SI SI
BP 1210
EP 1215
DI 10.1016/j.mri.2010.02.007
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 658NZ
UT WOS:000282498000021
PM 20392587
ER
PT J
AU Tyler, DJ
Lopez, O
Cole, MA
Carr, CA
Stuckey, DJ
Lakatta, E
Clarke, K
Spencer, RG
AF Tyler, Damian J.
Lopez, Orlando
Cole, Mark A.
Carr, Carolyn A.
Stuckey, Daniel J.
Lakatta, Edward
Clarke, Kieran
Spencer, Richard G.
TI Ongoing Dual-Angle Measurements for the Correction of Partial Saturation
in (31)P MR Spectroscopy
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE cardiovascular; biochemistry; heart
ID MAGNETIC-RESONANCE-SPECTROSCOPY; NEGLECTING CHEMICAL-EXCHANGE; GRAPHICAL
USER-INTERFACE; LATTICE-RELAXATION TIMES; CREATINE-KINASE REACTION;
ONE-PULSE EXPERIMENT; IN-VIVO NMR; METABOLITE CONCENTRATIONS;
QUANTITATION ERRORS; MUSCLE
AB Use of a repetition time similar to, or shorter than, metabolite T(1)s is common in NMR spectroscopy of biological samples to improve the signal-to-noise ratio. Conventionally, the partial saturation that results from this is corrected using saturation factors. However, this can lead to erroneous results in the presence of chemical exchange or nonconstant T(1)s. We describe an alternative approach to correction for saturation, based on ongoing dual-angle T(1) measurement. Using (31)P magnetic resonance spectroscopy of the perfused rat heart undergoing ischemia-reperfusion, we demonstrate that signal alternations in the data acquired by the dual-angle approach are eliminated by the ongoing dual-angle T(1) measurement correction scheme, meaning that metabolite concentration and T(1) measurement can be made throughout the course of the ischemia-reperfusion protocol. Simulations, based on parameters pertinent to the perfused rat heart, demonstrate that accurate saturation correction is possible with this method except at times of rapid concentration change. Additionally, compared to the conventional saturation factor correction method, the ongoing dual-angle T(1) measurement correction scheme results in improved accuracy in determining the [phosphocreatine] recovery time constant. Thus, the ongoing dual-angle T(1) measurements procedure permits accurate monitoring of metabolite concentrations even in the setting of chemical exchange and T(1) changes and allows more accurate analysis of bioenergetic status. Magn Reson Med 64:957-966, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Tyler, Damian J.; Cole, Mark A.; Carr, Carolyn A.; Stuckey, Daniel J.; Clarke, Kieran] Univ Oxford, Dept Physiol Anat & Genet, CMRG, Oxford OX1 3PT, England.
[Lopez, Orlando; Spencer, Richard G.] NIA, Magnet Resonance Imaging & Spect Sect, NIH, Baltimore, MD 21224 USA.
[Lakatta, Edward] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
RP Tyler, DJ (reprint author), Univ Oxford, Dept Physiol Anat & Genet, CMRG, Sherrington Bldg,Parks Rd, Oxford OX1 3PT, England.
EM damian.tyler@dpag.ox.ac.uk
RI Tyler, Damian/E-6296-2011;
OI Tyler, Damian/0000-0002-0780-8905; stuckey, daniel/0000-0001-8888-627X
FU Medical Research Council (MRC) [G0601490]; British Heart Foundation
(BHF) [PG/07/070/23365, RG/07/004/22659, RG/07/059/23259]; National
Institute on Aging
FX Grant sponsor: Medical Research Council (MRC); Grant number: G0601490;
Grant sponsor: British Heart Foundation (BHF); Grant numbers:
PG/07/070/23365, RG/07/004/22659, RG/07/059/23259; Grant sponsor:
National Institute on Aging (Intramural Research Program of the NIH).
NR 25
TC 4
Z9 4
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD OCT
PY 2010
VL 64
IS 4
BP 957
EP 966
DI 10.1002/mrm.22511
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 658FY
UT WOS:000282477100004
PM 20740663
ER
PT J
AU Lui, JC
Chen, WP
Barnes, KM
Baron, J
AF Lui, Julian C.
Chen, Weiping
Barnes, Kevin M.
Baron, Jeffrey
TI Changes in gene expression associated with aging commonly originate
during juvenile growth
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Article
DE Aging; Postnatal growth; Microarray; Genetic program; Proliferation
ID UBIQUITIN-CONJUGATING ENZYME; LIFE-SPAN EXTENSION; CALORIC RESTRICTION;
STEM-CELL; IMPRINTED GENE; SOMATIC GROWTH; MICE; AGE; INFILTRATION;
METABOLISM
AB In mammals proliferation is rapid in many tissues during early postnatal life causing rapid somatic growth This robust proliferation is then suppressed as the animal approaches adult size bringing many tissues to a quiescent state where proliferation occurs only as needed to replace dying cells Recent evidence suggests that the mechanism responsible for this decline in proliferation involves a multi-organ genetic program We hypothesized that this genetic program continues to progress into later adult life eventually suppressing proliferation to levels below those needed for tissue renewal thus contributing to aging We therefore used expression microarray to compare the temporal changes in gene expression that occur in adult mouse organs during aging to those occurring as juvenile proliferation slows We found that many of the changes in gene expression that occur during the aging process originate during the period of juvenile growth deceleration Bioinformatic analyses of the genes that show persistent decline in expression throughout postnatal life indicated that cell-cycle-related genes are strongly over-represented Thus the findings support the hypothesis that the genetic program that slows juvenile growth to limit body size persists into adulthood and thus may eventually hamper tissue maintenance and repair contributing to the aging process (C) 2010 Elsevier Ireland Ltd All rights reserved
C1 [Lui, Julian C.; Barnes, Kevin M.; Baron, Jeffrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hu, Dev Endocrinol Branch, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Chen, Weiping] NIDDKD, Microarray Core Facil, NIH, Bethesda, MD 20892 USA.
RP Lui, JC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hu, Dev Endocrinol Branch, Program Dev Endocrinol & Genet, NIH, CRC Room 1,3330 10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA.
RI Lui, Chun Kin Julian/E-2253-2012
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development NIH
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development NIH
NR 63
TC 11
Z9 11
U1 2
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD OCT
PY 2010
VL 131
IS 10
BP 641
EP 649
DI 10.1016/j.mad.2010.08.010
PG 9
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 686FD
UT WOS:000284681300005
PM 20816690
ER
PT J
AU Jumpertz, R
Thearle, MS
Bunt, JC
Krakoff, J
AF Jumpertz, Reiner
Thearle, Marie S.
Bunt, Joy C.
Krakoff, Jonathan
TI Assessment of non insulin-mediated glucose uptake: association with body
fat and glycemic status
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
ID DIABETES-MELLITUS; PIMA-INDIANS; MODEL; TOLERANCE; SENSITIVITY;
RESISTANCE; DISPOSAL; NIDDM; RATES
AB In the fasting state, approximately 83% of glucose uptake occurs via non-insulin-mediated mechanisms. A widely accepted static rate for NIMGU is 1.62 mg kg(-1).min(-1). To investigate the variability of NIMGU, we examined differences by glucose tolerance, sex, age, race (American Indian/African American/Caucasian), and adiposity in 616 volunteers (including individuals with normal glucose regulation [NGR] and impaired glucose regulation [IGR] and diabetes mellitus [DM]) using data from euglycemic-hyperinsulinemic clamp experiments. NIMGU was determined by plotting basal glucose output and insulin action against fasting and steady-state clamp insulin. The intercept with the y-axis after extrapolation was interpreted as NIMGU at zero insulin. Body composition was determined by dual-energy x-ray absorptiometry; and glucose regulation, by a 75-g oral glucose tolerance test. Energy expenditure was measured by indirect calorimetry in a metabolic chamber. In individuals with NGR (n = 385), NIMGU was 1.63 mg kg(estimated metabolic body size (fat free mass + 17.7 kg))(-1) min(-1) (95% confidence interval, 1.59-1.66). NIMGU increased with 1GR and DM (IGR: n = 189, 1.67 [1.62-1.72]; DM: n = 42, 2.39 [2.29-2.49]; P < .0001 across groups). NIMGU did not differ by sex (P = .13), age (P = .22), or race (P = .06); however, NIMGU was associated with percentage body fat (r(2) = 0.04, P < .0001). Furthermore, NIMGU was positively associated with 24-hour and sleep energy expenditure (r(2) = 0.002, P = .03; r(2) = 0.01, P < .01). Extrapolated NIMGU in individuals with NGR is remarkably consistent with previously published data. Our results indicate that NIMGU is associated with adiposity. NIMGU increases with declining glucose tolerance perhaps to preserve glucose uptake during increased insulin resistance. Published by Elsevier Inc.
C1 [Jumpertz, Reiner; Thearle, Marie S.; Bunt, Joy C.; Krakoff, Jonathan] NIDDKD, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ 85016 USA.
RP Jumpertz, R (reprint author), NIDDKD, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ 85016 USA.
EM jumpertzr@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank all study volunteers for their contribution to this study. We
also thank the staff of the Clinical Research Unit on the fifth floor of
the Phoenix Indian Medical Center. This study was supported by the
intramural research program of the National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 25
TC 4
Z9 4
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 0026-0495
J9 METABOLISM
JI Metab.-Clin. Exp.
PD OCT
PY 2010
VL 59
IS 10
BP 1396
EP 1401
DI 10.1016/j.metabol.2010.01.006
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 656YG
UT WOS:000282376400003
PM 20153490
ER
PT J
AU Lenfant, C
AF Lenfant, Claude
TI Chest pain of cardiac and noncardiac origin
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; EMERGENCY-DEPARTMENT; PRIMARY-CARE;
MYOCARDIAL-INFARCTION; STABLE ANGINA; HEART-DISEASE; WOMEN; COHORT;
PREVALENCE; PROGNOSIS
AB Chest pain is one of the most common symptoms driving patients to a physician's office or the hospital's emergency department. In approximately half of the cases, chest pain is of cardiac origin, either ischemic cardiac or nonischemic cardiac disease. The other half is due to noncardiac causes, primarily esophageal disorder. Pain from either origin may occur in the same patient. In addition, psychological and psychiatric factors play a significant role in the perception and severity of the chest pain, irrespective of its cause. Chest pain of ischemic cardiac disease is called angina pectoris. Stable angina may be the prelude of ischemic cardiac disease; and for this reason, it is essential to ensure a correct diagnosis. In most cases, further testing, such as exercise testing and angiography, should be considered. The more severe form of chest pain, unstable angina, also requires a firm diagnosis because it indicates severe coronary disease and is the earliest manifestation of acute myocardial infarction. Once a diagnosis of stable or unstable angina is established, and if a decision is made not to use invasive therapy, such as coronary bypass, percutaneous transluminal coronary angioplasty, or stent insertion, effective medical treatment of associated cardiac risk factors is a must. Acute myocardial infarction occurring after a diagnosis of angina greatly increases the risk of subsequent death. Chest pain in women warrants added attention because women underestimate their likelihood to have coronary heart disease. A factor that complicates the clinical assessment of patients with chest pain (both cardiac and noncardiac in origin) is the relatively common presence of psychological and psychiatric conditions such as depression or panic disorder. These factors have been found to cause or worsen chest pain; but unfortunately, they may not be easily detected. Noncardiac chest pain represents the remaining half of all cases of chest pain. Although there are a number of causes, gastroesophageal disorders are by far the most prevalent, especially gastroesophageal reflux disease. Fortunately, this disease can be diagnosed and treated effectively by proton-pump inhibitors. The other types of non-gastroesophageal reflux disease related noncardiac chest pain are more difficult to diagnose and treat. In conclusion, the cause of chest pain must be accurately diagnosed; and treatment must be pursued according to the cause, especially if the cause is of cardiac origin. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Lenfant, Claude] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Lenfant, C (reprint author), POB 65278, Vancouver, WA 98665 USA.
EM lenfantc@prodigy.net
NR 49
TC 15
Z9 17
U1 1
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
J9 METABOLISM
JI Metab.-Clin. Exp.
PD OCT
PY 2010
VL 59
IS 10
SU 1
BP S41
EP S46
DI 10.1016/j.metabol.2010.07.014
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 656YI
UT WOS:000282376600010
PM 20837193
ER
PT J
AU Wang, YX
Zuo, XB
Wang, JB
Yu, P
Butcher, SE
AF Wang, Yun-Xing
Zuo, Xiaobing
Wang, Jinbu
Yu, Ping
Butcher, Samuel E.
TI Rapid global structure determination of large RNA and RNA complexes
using NMR and small-angle X-ray scattering
SO METHODS
LA English
DT Review
DE RNA global structure in solution; SAXS; NMR; New methods
ID RESIDUAL DIPOLAR COUPLINGS; TURNIP CRINKLE VIRUS; TETRALOOP-RECEPTOR
COMPLEX; TRANSLATIONAL ENHANCER; RELATIVE ORIENTATION; SPIN SYSTEMS;
BASE-PAIRS; SAXS DATA; RESOLUTION; DYNAMICS
AB Among the greatest advances in biology today are the discoveries of various roles played by RNA in biological processes. However, despite significant advances in RNA structure determination using X-ray crystallography [1] and solution NMR [2-4], the number of bona fide RNA structures is very limited, in comparison with the growing number of known functional RNAs. This is because of great difficulty in growing crystals or/and obtaining phase information, and severe size constraints on structure determination by solution NMR spectroscopy. Clearly, there is an acute need for new methodologies for RNA structure determination. The prevailing approach for structure determination of RNA in solution is a "bottom-up" approach that was basically transplanted from the approach used for determining protein structures, despite vast differences in both structural features and chemical compositions between these two types of biomacromolecules. In this chapter, we describe a new method, which has been reported recently, for rapid global structure determination of RNAs using solution-based NMR spectroscopy and small-angle X-ray scattering. The method treats duplexes as major building blocks of RNA structures. By determining the global orientations of the duplexes and the overall shape, the global structure of an RNA can be constructed and further regularized using Xplor-NIH. The utility of the method was demonstrated in global structure determination of two RNAs, a 71-nt and 102-nt RNAs with an estimated backbone RMSD similar to 3.0 angstrom. The global structure opens door to high-resolution structure determination in solution. Published by Elsevier Inc.
C1 [Wang, Yun-Xing; Zuo, Xiaobing; Wang, Jinbu; Yu, Ping] NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Butcher, Samuel E.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA.
RP Wang, YX (reprint author), NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
EM wangyu@ncifcrf.gov
RI Zuo, Xiaobing/F-1469-2010;
OI Zuo, Xiaobing/0000-0002-0134-4804
FU NIGMS NIH HHS [R01 GM065166]
NR 65
TC 28
Z9 28
U1 0
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
J9 METHODS
JI Methods
PD OCT
PY 2010
VL 52
IS 2
BP 180
EP 191
DI 10.1016/j.ymeth.2010.06.009
PG 12
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 663RV
UT WOS:000282907000009
PM 20554045
ER
PT J
AU Yahiro, K
Morinaga, N
Moss, J
Noda, M
AF Yahiro, Kinnosuke
Morinaga, Naoko
Moss, Joel
Noda, Masatoshi
TI Subtilase cytotoxin induces apoptosis in HeLa cells by mitochondrial
permeabilization via activation of Bax/Bak, independent of
C/EBF-homologue protein (CHOP), Ire1 alpha or JNK signaling
SO MICROBIAL PATHOGENESIS
LA English
DT Article
DE Subtilase cytotoxin; ER stress; Apoptosis; Bax; Bak
ID ENDOPLASMIC-RETICULUM STRESS; TOXIGENIC ESCHERICHIA-COLI; CHAPERONE BIP;
VERO CELLS; BAX; BCL-2; DEATH; FAMILY; MEMBRANE; POTENT
AB Subtilase cytotoxin (SubAB) is an AB(5) cytotoxin produced by some strains of Shiga-toxigenic Escherichia colt The A subunit is a subtilase-like serine protease and cleaves an endoplasmic reticulum (ER) chaperone, BiP, leading to transient inhibition of protein synthesis and cell cycle arrest at G(1) phase, and inducing caspase-dependent apoptosis via mitochondrial membrane damage in Vero cells. Here we investigated the mechanism of mitochondrial permeabilization in HeLa cells SubAB-induced cytochrome c release into cytosol did not depend on mitochondrial permeability transition pore (PTP), since cyclosporine A did not suppress cytochrome c release SubAB did not change the expression of anti-apoptotic Bcl-2 or Bcl-XL and pro-apoptotic Box or Bak, but triggered Box and Bak conformational changes and association of Bax with Bak Silencing using siRNA of both bax and bak genes, but not bax, bak, or bun alone, resulted in reduction of cytochrome c release, caspase-3 activation. DNA ladder formation and cytotoxicity, indicating that Box and Bak were involved in apoptosis SubAB activated ER transmembrane transducers, Ire1 alpha, and cJun N-terminal kinase (JNK), and induced C/EBF-homologue protein (CHOP) To investigate whether these signals were involved in cytochrome c release by Bax activation, we silenced ire la, ink or chop. however, silencing did not decrease SubAB-induced cytochrome c release, suggesting that these signals were not necessary for SubAB-induced mitochondrial permeabilization by Bax activation (C) 2010 Elsevier Ltd All rights reserved
C1 [Yahiro, Kinnosuke; Morinaga, Naoko; Noda, Masatoshi] Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, Chiba 2608670, Japan.
[Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Yahiro, K (reprint author), Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan.
FU Japan Society for the Promotion of Science; Japan Science and Technology
Agency; National Institute of Health, National Heart, Lung and Blood
Institute
FX This work was supported by Grants-in Aid for Scientific Research from
Japan Society for the Promotion of Science and for Improvement of
Research Environment for Young Researchers from Japan Science and
Technology Agency Joel Moss was supported by the Intramural Research
Program, National Institute of Health, National Heart, Lung and Blood
Institute. We thank Dr. Iwao Kato, the former professor of Chiba
University, for useful discussions and critical review of the
manuscript. We thank Dr. Eisuke Nishida and Dr. Hiroyuki Seimia for
providing JNK expression vector.
NR 40
TC 13
Z9 14
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0882-4010
J9 MICROB PATHOGENESIS
JI Microb. Pathog.
PD OCT
PY 2010
VL 49
IS 4
BP 153
EP 163
DI 10.1016/j.micpath.2010.05.007
PG 11
WC Immunology; Microbiology
SC Immunology; Microbiology
GA 639AY
UT WOS:000280944400003
PM 20561923
ER
PT J
AU Sastalla, I
Maltese, LM
Pomerantseva, OM
Pomerantsev, AP
Keane-Myers, A
Leppla, SH
AF Sastalla, Inka
Maltese, Lauren M.
Pomerantseva, Olga M.
Pomerantsev, Andrei P.
Keane-Myers, Andrea
Leppla, Stephen H.
TI Activation of the latent PlcR regulon in Bacillus anthracis
SO MICROBIOLOGY-SGM
LA English
DT Article
ID CHOLESTEROL-DEPENDENT CYTOLYSIN; PHOSPHOLIPASE-C; ANTHROLYSIN-O; CEREUS
GROUP; NONHEMOLYTIC ENTEROTOXIN; GENOME SEQUENCE; THURINGIENSIS;
VIRULENCE; IDENTIFICATION; EXPRESSION
AB Many genes in Bacillus cereus and Bacillus thuringiensis are under the control of the transcriptional regulator PlcR and its regulatory peptide, PapR. In Bacillus anthracis, the causative agent of anthrax, PlcR is inactivated by truncation, and consequently genes having PlcR binding sites are expressed at very low levels when compared with B. cereus. We found that activation of the PlcR regulon in B. anthracis by expression of a PlcR-PapR fusion protein does not alter sporulation in strains containing the virulence plasmid pXO1 and thereby the global regulator AtxA. Using comparative 2D gel electrophoresis, we showed that activation of the PlcR regulon in B. anthracis leads to upregulation of many proteins found in the secretome of B. cereus, including phospholipases and proteases, such as the putative protease BA1995. Transcriptional analysis demonstrated expression of BA1995 to be dependent on PlcR-PapR, even though the putative PlcR recognition site of the BA1995 gene does not exactly match the PlcR consensus sequence, explaining why this protein had escaped recognition as belonging to the PlcR regulon. Additionally, while transcription of major PlcR-dependent haemolysins, sphingomyelinase and anthrolysin O is enhanced in response to PlcR activation in B. anthracis, only anthrolysin O contributes significantly to lysis of human erythrocytes. In contrast, the toxicity of bacterial culture supernatants from a PlcR-positive strain towards murine macrophages occurred independently of anthrolysin O expression in vitro and in vivo.
C1 [Sastalla, Inka; Maltese, Lauren M.; Pomerantsev, Andrei P.; Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA.
[Pomerantseva, Olga M.; Keane-Myers, Andrea] USN, Biol Def Res Directorate, Res Ctr, Rockville, MD USA.
RP Leppla, SH (reprint author), NIAID, Lab Bacterial Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sleppla@niaid.nih.gov
FU National Institutes of Health (NIH), National Institute of Allergy and
Infectious Diseases (NIAID), Bethesda, MD, USA
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Institute of Allergy and
Infectious Diseases (NIAID), Bethesda, MD, USA. We thank Zachary Newman
for supplying BMDM cells, Devorah Crown for assistance with animal
experiments, the NIAID RTB for performing 2D SDS-PAGE and MS, and Dr
Clinton Leysath for assistance with flow cytometry. The views expressed
in this article are those of the authors and do not necessarily reflect
the official policy or position of the Department of the Navy,
Department of Defense, nor the US Government.
NR 46
TC 8
Z9 12
U1 0
U2 4
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 1350-0872
J9 MICROBIOL-SGM
JI Microbiology-(UK)
PD OCT
PY 2010
VL 156
BP 2982
EP 2993
DI 10.1099/mic.0.041418-0
PN 10
PG 12
WC Microbiology
SC Microbiology
GA 670UZ
UT WOS:000283454100010
PM 20688829
ER
PT J
AU Wang, SM
Duyn, JH
AF Wang, Shumin
Duyn, Jeff H.
TI A TOPOLOGY-BASED MULTILEVEL SCHEME FOR FAST INTEGRAL-EQUATION METHODS
SO MICROWAVE AND OPTICAL TECHNOLOGY LETTERS
LA English
DT Article
DE method of moments; fast integral methods; multilevel scheme
ID ELECTROMAGNETIC SCATTERING; ALGORITHM; APPROXIMATION; MATRICES; MOMENTS
AB A topology-based multilevel scheme is proposed for fast integral-equation simulations. Low-level subdomains are formed at first by exploring topological connectivity between basis functions: Profile reduction and quad-tree image compression are then applied to construct a heuristic multilevel scheme from a symbolic rank map. Numerical results verified this approach and demonstrated its computational efficiency. (C) 2010 Wiley Periodicals, Inc. Microwave Opt Technol Lett 52:2195-2198,2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.25468
C1 [Wang, Shumin; Duyn, Jeff H.] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA.
RP Wang, SM (reprint author), Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA.
EM wangshu@ninds.nih.gov
RI Duyn, Jozef/F-2483-2010
NR 13
TC 2
Z9 2
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0895-2477
J9 MICROW OPT TECHN LET
JI Microw. Opt. Technol. Lett.
PD OCT
PY 2010
VL 52
IS 10
BP 2195
EP 2198
DI 10.1002/mop.25468
PG 4
WC Engineering, Electrical & Electronic; Optics
SC Engineering; Optics
GA 636NN
UT WOS:000280744100010
ER
PT J
AU Cuchalova, L
Kouba, T
Herrmannova, A
Danyi, I
Chiu, WL
Valasek, L
AF Cuchalova, Lucie
Kouba, Tomas
Herrmannova, Anna
Danyi, Istvan
Chiu, Wen-ling
Valasek, Leos
TI The RNA Recognition Motif of Eukaryotic Translation Initiation Factor 3g
(eIF3g) Is Required for Resumption of Scanning of Posttermination
Ribosomes for Reinitiation on GCN4 and Together with eIF3i Stimulates
Linear Scanning
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID OPEN READING FRAMES; START CODON SELECTION; MESSENGER-RNA;
SACCHAROMYCES-CEREVISIAE; IN-VIVO; 40S RIBOSOME; ESCHERICHIA-COLI;
GENE-EXPRESSION; STOP CODONS; YEAST
AB Recent reports have begun unraveling the details of various roles of individual eukaryotic translation initiation factor 3 (eIF3) subunits in translation initiation. Here we describe functional characterization of two essential Saccharomyces cerevisiae eIF3 subunits, g/Tif35 and i/Tif34, previously suggested to be dispensable for formation of the 48S preinitiation complexes (PICs) in vitro. A triple-Ala substitution of conserved residues in the RRM of g/Tif35 (g/tif35-KLF) or a single-point mutation in the WD40 repeat 6 of i/Tif34 (i/tif34-Q258R) produces severe growth defects and decreases the rate of translation initiation in vivo without affecting the integrity of eIF3 and formation of the 43S PICs in vivo. Both mutations also diminish induction of GCN4 expression, which occurs upon starvation via reinitiation. Whereas g/tif35-KLF impedes resumption of scanning for downstream reinitiation by 40S ribosomes terminating at upstream open reading frame 1 (uORF1) in the GCN4 mRNA leader, i/tif34-Q258R prevents full GCN4 derepression by impairing the rate of scanning of posttermination 40S ribosomes moving downstream from uORF1. In addition, g/tif35-KLF reduces processivity of scanning through stable secondary structures, and g/Tif35 specifically interacts with Rps3 and Rps20 located near the ribosomal mRNA entry channel. Together these results implicate g/Tif35 and i/Tif34 in stimulation of linear scanning and, specifically in the case of g/Tif35, also in proper regulation of the GCN4 reinitiation mechanism.
C1 [Cuchalova, Lucie; Kouba, Tomas; Herrmannova, Anna; Danyi, Istvan; Valasek, Leos] Inst Microbiol AVCR, Lab Regulat Gene Express, Vvi, Prague, Czech Republic.
[Chiu, Wen-ling] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Valasek, L (reprint author), Inst Microbiol AVCR, Lab Regulat Gene Express, Vvi, Videnska 1083, Prague, Czech Republic.
EM valasekl@biomed.cas.cz
RI Herrmannova, Anna/I-1745-2014; Valasek, Leos/I-5743-2014; Cuchalova,
Lucie/H-4650-2014
FU Howard Hughes Medical Institute; Wellcome Trust [076456/Z/05/Z]; Academy
of Sciences of the Czech Republic [AV0Z50200510]
FX This research was supported by the Howard Hughes Medical Institute, The
Wellcome Trust grant 076456/Z/05/Z, a Fellowship of Jan E. Purkyne from
the Academy of Sciences of the Czech Republic, and Institutional
Research Concept AV0Z50200510.
NR 62
TC 40
Z9 41
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD OCT
PY 2010
VL 30
IS 19
BP 4671
EP 4686
DI 10.1128/MCB.00430-10
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 648VB
UT WOS:000281721400010
PM 20679478
ER
PT J
AU Schug, TT
Xu, Q
Gao, HM
Peres-da-Silva, A
Draper, DW
Fessler, MB
Purushotham, A
Li, XL
AF Schug, Thaddeus T.
Xu, Qing
Gao, Huiming
Peres-da-Silva, Ashwin
Draper, David W.
Fessler, Michael B.
Purushotham, Aparna
Li, Xiaoling
TI Myeloid Deletion of SIRT1 Induces Inflammatory Signaling in Response to
Environmental Stress
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID NF-KAPPA-B; INDUCED INSULIN-RESISTANCE; CALORIE RESTRICTION; DEPENDENT
TRANSCRIPTION; ALTERNATIVE ACTIVATION; PULMONARY INFLAMMATION;
GENE-EXPRESSION; CELL-SURVIVAL; PROTEIN SIR2; LIFE-SPAN
AB Macrophage activation and infiltration into resident tissues is known to mediate local inflammation and is a hallmark feature of metabolic syndrome. Members of the sirtuin family of proteins regulate numerous physiological processes, including those involved in nutrient regulation and the promotion of longevity. However, the important role that SIRT1, the leading sirtuin family member, plays in immune response remains unclear. In this study, we demonstrate that SIRT1 modulates the acetylation status of the RelA/p65 subunit of NF-kappa B and thus plays a pivotal role in regulating the inflammatory, immune, and apoptotic responses in mammals. Using a myeloid cell-specific SIRT1 knockout (Mac-SIRT1 KO) mouse model, we show that ablation of SIRT1 in macrophages renders NF-kappa B hyperacetylated, resulting in increased transcriptional activation of proinflammatory target genes. Consistent with increased proinflammatory gene expression, Mac-SIRT1 KO mice challenged with a high-fat diet display high levels of activated macrophages in liver and adipose tissue, predisposing the animals to development of systemic insulin resistance and metabolic derangement. In summary, we report that SIRT1, in macrophages, functions to inhibit NF-kappa B-mediated transcription, implying that myeloid cell-specific modulation of this sirtuin may be beneficial in the treatment of inflammation and its associated diseases.
C1 [Schug, Thaddeus T.; Xu, Qing; Peres-da-Silva, Ashwin; Purushotham, Aparna; Li, Xiaoling] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Gao, Huiming] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Draper, David W.; Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
RP Li, XL (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM lix3@niehs.nih.gov
RI gao, huiming/C-8454-2012
FU NIH, National Institute of Environmental Health Sciences [Z01 ES102205]
FX This research was supported by a grant from the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences,
to X. L. (Z01 ES102205).
NR 44
TC 126
Z9 135
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD OCT
PY 2010
VL 30
IS 19
BP 4712
EP 4721
DI 10.1128/MCB.00657-10
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 648VB
UT WOS:000281721400013
PM 20647536
ER
PT J
AU Arevalo, JC
Wu, SH
Takahashi, T
Zhang, H
Yu, T
Yano, H
Milner, TA
Tessarollo, L
Ninan, I
Arancio, O
Chao, MV
AF Carlos Arevalo, Juan
Wu, Synphen H.
Takahashi, Takuya
Zhang, Hong
Yu, Tao
Yano, Hiroko
Milner, Teresa A.
Tessarollo, Lino
Ninan, Ipe
Arancio, Ottavio
Chao, Moses V.
TI The ARMS/Kidins220 scaffold protein modulates synaptic transmission
SO MOLECULAR AND CELLULAR NEUROSCIENCE
LA English
DT Article
DE ARMS-Kidins220; Scaffold; Synaptic transmission
ID AMPA RECEPTOR TRAFFICKING; LONG-TERM POTENTIATION; GLUTAMATE RECEPTORS;
MOLECULAR-MECHANISMS; PKA PHOSPHORYLATION; HIPPOCAMPAL-NEURONS; GLUR1
SUBUNIT; PLASTICITY; NEUROTROPHIN; RECTIFICATION
AB Activity-dependent changes of synaptic connections are facilitated by a variety of scaffold proteins, including PSD-95, Shank, SAP97 and GRIP, which serve to organize ion channels, receptors and enzymatic activities and to coordinate the actin cytoskeleton. The abundance of these scaffold proteins raises questions about the functional specificity of action of each protein. Here we report that basal synaptic transmission is regulated in an unexpected manner by the ankyrin repeat-rich membrane-spanning (ARMS/Kidins220) scaffold protein. In particular, decreases in the levels of ARMS/Kidins220 in vivo led to an increase in basal synaptic transmission in the hippocampus, without affecting paired pulse facilitation. One explanation to account for the effects of ARMS/Kidins220 is an interaction with the AMPA receptor subunit. GluA1, which could be observed after immunoprecipitation. Importantly, shRNA and cell surface biotinylation experiments indicate that ARMS/Kidins220 levels have an impact on GluA1 phosphorylation and localization. Moreover, ARMS/Kidins220 is a negative regulator of AMPAR function, which was confirmed by inward rectification assays. These results provide evidence that modulation of ARMS/Kidins220 levels can regulate basal synaptic strength in a specific manner in hippocampal neurons. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Carlos Arevalo, Juan; Wu, Synphen H.; Yano, Hiroko; Ninan, Ipe; Chao, Moses V.] NYU, Sch Med, Skirball Inst Biomol Med, Mol Neurobiol Program,Dept Cell Biol, New York, NY 10016 USA.
[Carlos Arevalo, Juan; Wu, Synphen H.; Yano, Hiroko; Ninan, Ipe; Chao, Moses V.] NYU, Sch Med, Skirball Inst Biomol Med, Mol Neurobiol Program,Dept Physiol & Neurosci, New York, NY 10016 USA.
[Carlos Arevalo, Juan; Wu, Synphen H.; Yano, Hiroko; Ninan, Ipe; Chao, Moses V.] NYU, Sch Med, Skirball Inst Biomol Med, Mol Neurobiol Program,Dept Psychiat & Neural Sci, New York, NY 10016 USA.
[Carlos Arevalo, Juan; Yu, Tao] Univ Salamanca, Inst Neurociencias Castilla & Leon INCyL, Salamanca 37007, Spain.
[Takahashi, Takuya] Yokohama City Univ, Dept Physiol, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan.
[Zhang, Hong; Arancio, Ottavio] Columbia Univ, Dept Pathol, Taub Inst, New York, NY 10032 USA.
[Milner, Teresa A.] Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10065 USA.
[Milner, Teresa A.] Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10065 USA.
[Tessarollo, Lino] NCI, Neural Dev Grp, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Arevalo, JC (reprint author), NYU, Sch Med, Skirball Inst Biomol Med, Mol Neurobiol Program,Dept Cell Biol, New York, NY 10016 USA.
EM arevalojc@usal.es; Moses.Chao@med.nyu.edu
RI IBSAL, Secretaria/H-3719-2011; ArAvalo, Juan Carlos/J-8154-2014;
OI ArAvalo, Juan Carlos/0000-0003-1994-3095; Ninan,
Ipe/0000-0001-9774-6455; Chao, Moses/0000-0002-6969-3744
FU NIH [HL18974, DA08259, NS049442, NS21072, HD23315]; Medical Scientist
Training Program; Ministerio de Ciencia e Innovacion [BFU2008-00162];
Junta Castilla y Leon [SA074A08]; Alzheimer's Association
FX We thank G. Schiavo for the ARMS/Kidins220 monoclonal antibody; E. Ziff
for the GluA1 construct; D. Trono for the lentiviral plasmids; members
of the Moses V. Chao, Barbara L. Hempstead, and Francis S. Lee
laboratories for the helpful discussions; Enrique Lopez-Poveda for his
help writing the MatLab custom-program to quantify immunofluorescence
images and Belen Dominguez for continuous support. This work was
supported by NIH grants (HL18974 and DA08259) to T.A.M., NIH grant
(NS049442) to O.A., NIH grants (NS21072 and HD23315) to M.V.C., the
Intramural Research Program of the NIH (LT.), the Medical Scientist
Training Program (S.H.W.), and by a Marie Curie International
Reintegration Grant within the 7th European Community
Framework Programme, by Ministerio de Ciencia e Innovacion Grant
BFU2008-00162, and by Junta Castilla y Leon Grant SA074A08 to J.C.A.
J.C.A. is a "Ramon y Cajal" Investigator from the University of
Salamanca and a NARSAD 2007 Young Investigator Awardee. I.N. is a NARSAD
2008 Young Investigator and a recipient of Alzheimer's Association New
Investigator Award.
NR 42
TC 17
Z9 17
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 1044-7431
J9 MOL CELL NEUROSCI
JI Mol. Cell. Neurosci.
PD OCT
PY 2010
VL 45
IS 2
BP 92
EP 100
DI 10.1016/j.mcn.2010.06.002
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 644CF
UT WOS:000281347300002
PM 20547223
ER
PT J
AU Franchini, G
AF Franchini, Genoveffa
TI HTLV-1 and HIV-1 "Accessory" proteins: A Misleading Misnomer
SO MOLECULAR ASPECTS OF MEDICINE
LA English
DT Editorial Material
C1 NCI, Anim Models Retroviral Vaccine Sect, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
RP Franchini, G (reprint author), NCI, Anim Models Retroviral Vaccine Sect, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
EM franchig@mail.nih.gov
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 0098-2997
J9 MOL ASPECTS MED
JI Mol. Asp. Med.
PD OCT
PY 2010
VL 31
IS 5
SI SI
BP 331
EP 332
DI 10.1016/j.mam.2010.08.001
PG 2
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 694GV
UT WOS:000285283900001
PM 20708638
ER
PT J
AU Van Prooyen, N
Andresen, V
Gold, H
Bialuk, I
Pise-Masison, C
Franchini, G
AF Van Prooyen, Nancy
Andresen, Vibeke
Gold, Heather
Bialuk, Izabela
Pise-Masison, Cynthia
Franchini, Genoveffa
TI Hijacking the T-cell communication network by the human T-cell
leukemia/lymphoma virus type 1 (HTLV-1) p12 and p8 proteins
SO MOLECULAR ASPECTS OF MEDICINE
LA English
DT Review
DE HTLV-1; p12; p8; T-cells; orf-I; Virus transmission; Immunological
synapse
ID I-ASSOCIATED MYELOPATHY; OPEN READING FRAMES; VACUOLAR H+-ATPASE;
LEUKEMIA-VIRUS; MESSENGER-RNA; NUCLEAR FACTOR; SIGNAL-TRANSDUCTION;
MONONUCLEAR-CELLS; SJOGRENS-SYNDROME; HAM/TSP PATIENTS
AB The non-structural proteins encoded by the orf-I, II, III, and IV genes of the human T-cell leukemia/lymphoma virus type 1 (HTLV-1) genome, are critical for the modulation of cellular gene expression and T-cell proliferation, the escape from cytotoxic T-cells and natural killer cells, and virus expression. In here, we review the main functions of the HTLV-1 orf-I products. The 12 kDa product from orf-I (p12) is proteolytically cleaved within the endoplasmic reticulum (ER) to generate the 8 kDa protein (p8). At the steady state, both proteins are expressed at similar levels in transfected T-cells. The p12 protein remains in the ER and cis-Golgi, whereas the p8 protein traffics to the cell surface and is recruited to the immunological synapse. The p12 and the p8 proteins have seemingly opposite effects on T-cells; the ER resident p12, modulates T-cell activation and proliferation, whereas p8 induces T-cell anergy. The p8 protein also increases the formation of cellular conduits, is transferred to neighboring T-cells, and increases virus transmission. The requirement for HTLV-1 infectivity of orf-I is demonstrated by the loss of virus infectivity in macaques exposed to an engineered virus, whereby expression of orf-I was ablated. Altogether the current knowledge demonstrates that the concerted activity of p8 and p12 is essential for the persistence of virus infected cells in the host. Published by Elsevier Ltd.
C1 [Van Prooyen, Nancy; Andresen, Vibeke; Gold, Heather; Bialuk, Izabela; Pise-Masison, Cynthia; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, Vaccine Branch, NIH, Bldg 41 Room D-804, Bethesda, MD 20892 USA.
EM franchig@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 thank
Teresa Habina for editorial assistance. We are very grateful to Dustin
Edwards and Shari Gordon for critical reading of the manuscript.
NR 90
TC 23
Z9 23
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0098-2997
J9 MOL ASPECTS MED
JI Mol. Asp. Med.
PD OCT
PY 2010
VL 31
IS 5
SI SI
BP 333
EP 343
DI 10.1016/j.mam.2010.07.001
PG 11
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 694GV
UT WOS:000285283900002
PM 20673780
ER
PT J
AU Silic-Benussi, M
Biasiotto, R
Andresen, V
Franchini, G
D'Agostino, DM
Ciminale, V
AF Silic-Benussi, Micol
Biasiotto, Roberta
Andresen, Vibeke
Franchini, Genoveffa
D'Agostino, Donna M.
Ciminale, Vincenzo
TI HTLV-1 p13, a small protein with a busy agenda
SO MOLECULAR ASPECTS OF MEDICINE
LA English
DT Review
DE Mitochondria; K plus channel; HTLV-1; Apoptosis; Leukemia
ID LEUKEMIA-VIRUS TYPE-1; ACTIVATED T-CELLS; THIOREDOXIN-BINDING PROTEIN-2;
P13(II) PROTEIN; MEDIATED APOPTOSIS; ACCESSORY PROTEINS;
GENE-EXPRESSION; NUCLEAR FACTOR; I TAX; DEATH
AB Human T-cell leukemia virus type 1 (HTLV-1) infection is characterized by life-long persistence of the virus in the host. While most infected individuals remain asymptomatic, 3-5% will eventually develop adult T-cell leukemia/lymphoma (ATLL) or tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM) after a clinical latency that can span years (TSP/HAM) to decades (ATLL). The major oncogenic determinant among HTLV-1 proteins is the Tax transactivator, which influences the expression and function of a great number of cellular proteins, drives cell proliferation, reduces cell death, and induces genetic instability.
The present review is focused on the current knowledge of p13, an HTLV-1 accessory protein targeted to the inner mitochondrial membrane and, under certain conditions, to the nucleus. In mitochondria, p13 produces an inward K+ current that results in an increased production of ROS by mitochondria. These effects are linked to the protein's effects on cell turnover which include activation of primary T-cells and reduced proliferation/sensitization to death of tumor cells. Recent findings suggest that in the presence of Tax, p13 is subjected to ubiquitylation and partly targeted to the nucleus. Nuclear p13 binds Tax and inhibits its transcriptional activity. These findings suggest that the protein might exert distinct functions depending on its intracellular localization and influence both the turnover of infected cells and the balance between viral latency and productive infection. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Silic-Benussi, Micol; Biasiotto, Roberta; D'Agostino, Donna M.; Ciminale, Vincenzo] Univ Padua, Dipartimento Sci Oncol & Chirurg, I-35128 Padua, Italy.
[Andresen, Vibeke; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.
[D'Agostino, Donna M.; Ciminale, Vincenzo] IRCCS, Ist Oncol Veneto, I-35128 Padua, Italy.
RP Ciminale, V (reprint author), Univ Padua, Dipartimento Sci Oncol & Chirurg, Via Gattamelata 64, I-35128 Padua, Italy.
EM v.ciminale@unipd.it
RI Biasiotto, Roberta/G-2903-2012
FU Associazione Italiana per la Ricerca sul Cancro; European Union
[2005-018704]; Ministero per l'Universita e la Ricerca Scientifica, e
Tecnologica - Progetti di Ricerca di Interesse Nazionale; Ministero
della Salute [RFPS-2006-2-342-010]; University of Padova; National
Cancer Institute National Institutes of Health
FX We thank Luigi Chieco-Bianchi, Paolo Bernardi, Fabio di Lisa and Ilaria
Cavallari for valuable discussions. This work was supported by grants
from the Associazione Italiana per la Ricerca sul Cancro (V.C.), the
European Union ('The role of chronic infections in the development of
cancer': Contract No. 2005-018704, to V.C.), the Ministero per
l'Universita e la Ricerca Scientifica, e Tecnologica - Progetti di
Ricerca di Interesse Nazionale (V.C.), the Ministero della Salute
(progetto RFPS-2006-2-342-010), the University of Padova (D.M.D., V.C.),
and National Cancer Institute National Institutes of Health intramural
grants (V.A., G.F.).
NR 47
TC 15
Z9 16
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0098-2997
J9 MOL ASPECTS MED
JI Mol. Asp. Med.
PD OCT
PY 2010
VL 31
IS 5
SI SI
BP 350
EP 358
DI 10.1016/j.mam.2010.03.001
PG 9
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 694GV
UT WOS:000285283900004
PM 20332002
ER
PT J
AU Andrew, A
Strebel, K
AF Andrew, Amy
Strebel, Klaus
TI HIV-1 Vpu targets cell surface markers CD4 and BST-2 through distinct
mechanisms
SO MOLECULAR ASPECTS OF MEDICINE
LA English
DT Review
DE Vpu; Degradation of CD4; HIV-1 release; BST-2; beta-TrCP
ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-U VPU; CLATHRIN-MEDIATED
ENDOCYTOSIS; VIRAL PARTICLE RELEASE; FULL-LENGTH VPU; CYTOPLASMIC
DOMAIN; ENDOPLASMIC-RETICULUM; ENVELOPE GLYCOPROTEIN; TRANSMEMBRANE
DOMAIN; DOWN-MODULATION
AB Vpu is a small integral membrane protein encoded by HIV-1 and some SIV isolates. The protein is known to induce degradation of the viral receptor molecule CD4 and to enhance the release of newly formed virions from the cell surface. Vpu accomplishes these two functions through two distinct mechanisms. In the case of CD4, Vpu acts as a molecular adaptor to connect CD4 to an E3 ubiquitin ligase complex resulting in CD4 degradation by cellular proteasomes. This requires signals located in Vpu's cytoplasmic domain. Enhancement of virus release on the other hand involves the neutralization of a cellular host factor, BST-2 (also known as CD317, HM1.24, or tetherin) and requires Vpu's TM domain. The current review discusses recent advances on the role of Vpu in controlling degradation of CD4 and in regulating virus release. Published by Elsevier Ltd.
C1 [Andrew, Amy; Strebel, Klaus] NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Strebel, K (reprint author), NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, Bldg 4,Room 310,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA.
EM kstrebel@nih.gov
FU NIH; NIH, NIAID
FX This work was supported in part by a Grant from the NIH Intramural AIDS
Targeted Antiviral Program to K.S. and by the Intramural Research
Program of the NIH, NIAID.
NR 121
TC 25
Z9 25
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0098-2997
J9 MOL ASPECTS MED
JI Mol. Asp. Med.
PD OCT
PY 2010
VL 31
IS 5
SI SI
BP 407
EP 417
DI 10.1016/j.mam.2010.08.002
PG 11
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 694GV
UT WOS:000285283900009
PM 20858517
ER
PT J
AU Renvoise, B
Parker, RL
Yang, D
Bakowska, JC
Hurley, JH
Blackstone, C
AF Renvoise, Benoit
Parker, Rell L.
Yang, Dong
Bakowska, Joanna C.
Hurley, James H.
Blackstone, Craig
TI SPG20 Protein Spartin Is Recruited to Midbodies by ESCRT-III Protein
Ist1 and Participates in Cytokinesis
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID HEREDITARY SPASTIC PARAPLEGIA; TROYER-SYNDROME; STRUCTURAL BASIS;
COMPLEX; VPS4; LOCALIZATION; RECOGNITION; MACHINERY; INTERACTS; FEATURES
AB Hereditary spastic paraplegias (HSPs, SPG1-46) are inherited neurological disorders characterized by lower extremity spastic weakness. Loss-of-function SPG20 gene mutations cause an autosomal recessive HSP known as Troyer syndrome. The SPG20 protein spartin localizes to lipid droplets and endosomes, and it interacts with tail interacting protein 47 (TIP47) as well as the ubiquitin E3 ligases atrophin-1-interacting protein (AIP)4 and AIP5. Spartin harbors a domain contained within microtubule-interacting and trafficking molecules (MIT) at its N-terminus, and most proteins with MIT domains interact with specific ESCRT-III proteins. Using yeast two-hybrid and in vitro surface plasmon resonance assays, we demonstrate that the spartin MIT domain binds with micromolar affinity to the endosomal sorting complex required for transport (ESCRT)-III protein increased sodium tolerance (Ist)1 but not to ESCRT-III proteins charged multivesicular body proteins 1-7. Spartin colocalizes with Ist1 at the midbody, and depletion of Ist1 in cells by small interfering RNA significantly decreases the number of cells where spartin is present at midbodies. Depletion of spartin does not affect Ist1 localization to midbodies but markedly impairs cytokinesis. A structure-based amino acid substitution in the spartin MIT domain (F24D) blocks the spartin-Ist1 interaction. Spartin F24D does not localize to the midbody and acts in a dominant-negative manner to impair cytokinesis. These data suggest that Ist1 interaction is important for spartin recruitment to the midbody and that spartin participates in cytokinesis.
C1 [Renvoise, Benoit; Parker, Rell L.; Blackstone, Craig] NINDS, Cellular Neurol Unit, Neurogenet Branch, Bethesda, MD 20892 USA.
[Yang, Dong; Hurley, James H.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Parker, Rell L.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA.
[Bakowska, Joanna C.] Loyola Univ, Dept Pharmacol & Expt Therapeut, Chicago Stritch Sch Med, Maywood, IL 60153 USA.
RP Blackstone, C (reprint author), NINDS, Cellular Neurol Unit, Neurogenet Branch, Bethesda, MD 20892 USA.
EM blackstc@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke; National
Institute of Diabetes and Digestive Diseases, National Institutes of
Health; National Institutes of Health [NS-050137]; Howard Hughes Medical
Institute-National Institutes of Health
FX We thank J. Nagle and D. Kauffman (DNA Sequencing Facility, National
Institute of Neurological Disorders and Stroke, National Institutes of
Health, Bethesda, MD) for DNA sequencing. This research was supported by
the Intramural Research programs of the National Institute of
Neurological Disorders and Stroke (B. R., C. B.) and the National
Institute of Diabetes and Digestive Diseases (D.Y., J. H. H.), National
Institutes of Health; the National Institutes of Health Bench-to-Bedside
Program (J. H. H., C. B.); the Howard Hughes Medical Institute-National
Institutes of Health Research Scholars Program (R. P.); and National
Institutes of Health K22 training grant NS-050137 (to J. C. B.).
NR 40
TC 34
Z9 38
U1 0
U2 5
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD OCT 1
PY 2010
VL 21
IS 19
BP 3293
EP 3303
DI 10.1091/mbc.E09-10-0879
PG 11
WC Cell Biology
SC Cell Biology
GA 655UJ
UT WOS:000282275600002
PM 20719964
ER
PT J
AU Perez-Victoria, FJ
Schindler, C
Magadan, JG
Mardones, GA
Delevoye, C
Romao, M
Raposo, G
Bonifacino, JS
AF Perez-Victoria, F. Javier
Schindler, Christina
Magadan, Javier G.
Mardones, Gonzalo A.
Delevoye, Cedric
Romao, Maryse
Raposo, Graca
Bonifacino, Juan S.
TI Ang2/Fat-Free Is a Conserved Subunit of the Golgi-associated Retrograde
Protein Complex
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID MOTOR-NEURON DISEASE; SNARE TLG1P; WOBBLER MOUSE; GARP COMPLEX;
VFT-COMPLEX; ESCRT-I; MICE; AUTOPHAGY; NEURODEGENERATION; IDENTIFICATION
AB The Golgi-associated retrograde protein (GARP) complex mediates tethering and fusion of endosome-derived transport carriers to the trans-Golgi network (TGN). In the yeast Saccharomyces cerevisiae, GARP comprises four subunits named Vps51p, Vps52p, Vps53p, and Vps54p. Orthologues of the GARP subunits, except for Vps51p, have been identified in all other eukaryotes. A yeast two-hybrid screen of a human cDNA library yielded a phylogenetically conserved protein, Ang2/Fat-free, which interacts with human Vps52, Vps53 and Vps54. Human Ang2 is larger than yeast Vps51p, but exhibits significant homology in an N-terminal coiled-coil region that mediates assembly with other GARP subunits. Biochemical analyses show that human Ang2, Vps52, Vps53 and Vps54 form an obligatory 1: 1: 1: 1 complex that strongly interacts with the regulatory Habc domain of the TGN SNARE, Syntaxin 6. Depletion of Ang2 or the GARP subunits similarly impairs protein retrieval to the TGN, lysosomal enzyme sorting, endosomal cholesterol traffico and autophagy. These findings indicate that Ang2 is the missing component of the GARP complex in most eukaryotes.
C1 [Perez-Victoria, F. Javier; Schindler, Christina; Magadan, Javier G.; Mardones, Gonzalo A.; Bonifacino, Juan S.] NIH, Cell Biol & Metab Program, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Delevoye, Cedric; Romao, Maryse; Raposo, Graca] CNRS, UMR 144, Inst Curie, F-75248 Paris, France.
RP Bonifacino, JS (reprint author), NIH, Cell Biol & Metab Program, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
EM juan@helix.nih.gov
OI Bonifacino, Juan S./0000-0002-5673-6370
FU National Institute of Child Health and Human Development, NIH; Centre
National de la Recherche Scientifique and Institut Curie; Deutsche
Forschungsgemeinschaft
FX We thank X. Zhu and N. Tsai for technical assistance, M. Krieger for
antibody to Cog8, and J. Dacks for discussion. This work was funded by
the National Institutes of Health (NIH) Intramural Program of National
Institute of Child Health and Human Development, NIH (J. S. B), and the
Centre National de la Recherche Scientifique and Institut Curie (G. R.).
C. S. was supported by a fellowship from the Deutsche
Forschungsgemeinschaft.
NR 40
TC 32
Z9 37
U1 0
U2 9
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD OCT 1
PY 2010
VL 21
IS 19
BP 3386
EP 3395
DI 10.1091/mbc.E10-05-0392
PG 10
WC Cell Biology
SC Cell Biology
GA 655UJ
UT WOS:000282275600010
PM 20685960
ER
PT J
AU Afkarian, M
Bhasin, M
Dillon, ST
Guerrero, MC
Nelson, RG
Knowler, WC
Thadhani, R
Libermann, TA
AF Afkarian, Maryam
Bhasin, Manoj
Dillon, Simon T.
Guerrero, Manuel C.
Nelson, Robert G.
Knowler, William C.
Thadhani, Ravi
Libermann, Towia A.
TI Optimizing a Proteomics Platform for Urine Biomarker Discovery
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID SAMPLE PREPARATION; DIABETIC-NEPHROPATHY; 2-DIMENSIONAL ELECTROPHORESIS;
GEL-ELECTROPHORESIS; PROTEINS; QUANTITATION; COLLECTION; PREDICT
AB Biomarker discovery approaches in urine have been hindered by concerns for reproducibility and inadequate standardization of proteomics protocols. In this study, we describe an optimized quantitative proteomics strategy for urine biomarker discovery, which is applicable to fresh or long frozen samples. We used urine from healthy controls to standardize iTRAQ (isobaric tags for relative and absolute quantitation) for variation induced by protease inhibitors, starting protein and iTRAQ label quantities, protein extraction methods, and depletion of albumin and immunoglobulin G (IgG). We observed the following: (a) Absence of protease inhibitors did not affect the number or identity of the high confidence proteins. (b) Use of less than 20 mu g of protein per sample led to a significant drop in the number of identified proteins. (c) Use of as little as a quarter unit of an iTRAQ label did not affect the number or identity of the identified proteins. (d) Protein extraction by methanol precipitation led to the highest protein yields and the most reproducible spectra. (e) Depletion of albumin and IgG did not increase the number of identified proteins or deepen the proteome coverage. Applying this optimized protocol to four pairs of long frozen urine samples from diabetic Pima Indians with or without nephropathy, we observed patterns suggesting segregation of cases and controls by iTRAQ spectra. We also identified several previously reported candidate biomarkers that showed trends toward differential expression, albeit not reaching statistical significance in this small sample set. Molecular & Cellular Proteomics 9:2195-2204, 2010.
C1 [Bhasin, Manoj; Dillon, Simon T.; Guerrero, Manuel C.; Libermann, Towia A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Genom & Prote Ctr, Sch Med, Boston, MA 02215 USA.
[Bhasin, Manoj; Dillon, Simon T.; Guerrero, Manuel C.; Libermann, Towia A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dana Farber Harvard Canc Ctr Canc Prote Core, Sch Med, Boston, MA 02215 USA.
[Afkarian, Maryam; Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Nelson, Robert G.; Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85014 USA.
RP Libermann, TA (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Genom & Prote Ctr, Sch Med, Res N Bldg,Rm 380C,99 Brookline Ave, Boston, MA 02215 USA.
EM tliberma@bidmc.harvard.edu
RI Libermann, Towia/F-9866-2010; Nelson, Robert/B-1470-2012;
OI Libermann, Towia/0000-0002-4006-8179
FU National Institutes of Health through NIDDK; Juvenile Diabetes Research
Foundation
FX This work was supported, in whole or in part, by the National Institutes
of Health through the Intramural Research Program of the NIDDK. This
work was also supported by a research grant from the Juvenile Diabetes
Research Foundation (to R. T.).
NR 25
TC 39
Z9 41
U1 0
U2 9
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 1535-9476
EI 1535-9484
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD OCT
PY 2010
VL 9
IS 10
BP 2195
EP 2204
DI 10.1074/mcp.M110.000992
PG 10
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 656VJ
UT WOS:000282368900010
PM 20511394
ER
PT J
AU Fernandez-Irigoyen, J
Santamaria, E
Chien, YH
Hwu, WL
Korman, SH
Faghfoury, H
Schulze, A
Hoganson, GE
Stabler, SP
Allen, RH
Wagner, C
Mudd, SH
Corrales, FJ
AF Fernandez-Irigoyen, Joaquin
Santamaria, Enrique
Chien, Yin-Hsiu
Hwu, Wuh-Liang
Korman, Stanley H.
Faghfoury, Hanna
Schulze, Andreas
Hoganson, George E.
Stabler, Sally P.
Allen, Robert H.
Wagner, Conrad
Mudd, S. Harvey
Corrales, Fernando J.
TI Enzymatic activity of methionine adenosyltransferase variants identified
in patients with persistent hypermethioninemia
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Methionine adenosyltransferase; Hypermethioninemia;
S-adenosylmethionine; Tripolyphosphate
ID S-ADENOSYLMETHIONINE SYNTHETASE; I/III DEFICIENCY;
HEPATOCELLULAR-CARCINOMA; MOLECULAR-MECHANISMS; TOTAL HOMOCYSTEINE;
LIVER; MUTATION; ADENOSYLHOMOCYSTEINE; METABOLISM; EXPRESSION
AB Methionine adenosyltransferases (MAT's) are central enzymes in living organisms that have been conserved with a high degree of homology among species. In the liver, MAT I and III, tetrameric and dimeric isoforms of the same catalytic subunit encoded by the gene MAT1A, account for the predominant portion of total body synthesis of S-adenosylmethionine (SAM), a versatile sulfonium ion-containing molecule involved in a variety of vital metabolic reactions and in the control of hepatocyte proliferation and differentiation. During the past 15 years 28 MAT1A mutations have been described in patients with elevated plasma methionines, total homocysteines at most only moderately elevated, and normal levels of tyrosine and other aminoacids. In this study we describe functional analyses that determine the MAT and tripolyphosphatase (PPPase) activities of 18 MAT1A variants, six of them novel, and none of them previously assayed for activity. With the exception of G69S and Y92H, all recombinant proteins showed impairment (usually severe) of MAT activity. Tripolyphosphate (PPPi) hydrolysis was decreased only in some mutant proteins but, when it was decreased MAT activity was always also impaired. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Fernandez-Irigoyen, Joaquin; Santamaria, Enrique; Corrales, Fernando J.] Univ Navarra, Ctr Appl Med Res CIMA, Prote Unit, Div Hepatol & Gene Therapy, Pamplona 31008, Spain.
[Chien, Yin-Hsiu; Hwu, Wuh-Liang] Natl Taiwan Univ Hosp, Dept Med Genet, Taipei, Taiwan.
[Korman, Stanley H.] Hadassah Hebrew Univ Med Ctr, Dept Human Genet & Metab Dis, Jerusalem, Israel.
[Faghfoury, Hanna; Schulze, Andreas] Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada.
[Hoganson, George E.] Univ Illinois, Coll Med, Dept Pediat, Chicago, IL USA.
[Faghfoury, Hanna; Schulze, Andreas] Univ Toronto, Toronto, ON, Canada.
[Stabler, Sally P.; Allen, Robert H.] Univ Colorado, Hlth Sci Ctr, Div Hematol, Aurora, CO USA.
[Wagner, Conrad] Vanderbilt Univ, Med Ctr, Dept Biochem, Nashville, TN USA.
[Mudd, S. Harvey] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Corrales, FJ (reprint author), Univ Navarra, Ctr Appl Med Res CIMA, Prote Unit, Div Hepatol & Gene Therapy, Pamplona 31008, Spain.
EM fjcorrales@unav.es
OI HWU, WUH-LIANG/0000-0001-6690-4879; CHIEN, YIN-HSIU/0000-0001-8802-5728
FU Ministerio de Ciencia e Innovacion [ISCIII-RETIC RD06/0020]
FX The technical assistance of Manuela Molina and Maria I. Mora is
acknowledged. This work was supported by: the agreement between FIMA and
the "UTE project CIMA"; grants Plan Nacional I+D+I SAF2008-0154 from
Ministerio de Ciencia e Innovacion to FJC; ISCIII-RETIC RD06/0020 to MAA
and FJC.
NR 52
TC 15
Z9 15
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD OCT-NOV
PY 2010
VL 101
IS 2-3
BP 172
EP 177
DI 10.1016/j.ymgme.2010.07.009
PG 6
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 672TK
UT WOS:000283609600014
PM 20675163
ER
PT J
AU Fu, R
Yanjanin, NM
Bianconi, S
Pavan, WJ
Porter, FD
AF Fu, Rao
Yanjanin, Nicole M.
Bianconi, Simona
Pavan, William J.
Porter, Forbes D.
TI Oxidative stress in Niemann-Pick disease, type C
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Neurodegenerative disease; Lysosomal storage disease; Oxidative stress;
Coenzyme Q10; Trolox equivalent antioxidant capacity
ID LOW-DENSITY-LIPOPROTEIN; COENZYME Q(10); CHOLESTEROL HOMEOSTASIS;
MITOCHONDRIAL-FUNCTION; ALZHEIMERS-DISEASE; ALPHA-TOCOPHEROL; BINDING
PROTEIN; METABOLISM; GENE; ACCUMULATION
AB Niemann-Pick disease, type C (NPC) is a neurodegenerative lysosomal storage disorder due to impaired intracellular cholesterol and lipid transport. Increased oxidative stress has been reported in human NPC1 mutant fibroblasts and in tissues from Npc1 mutant mice. However, oxidative stress in NPC patients has not been established. In this study, we demonstrated increased oxidative stress in NPC patients. Evaluation of serum from 37 NPC patients, compared to control values, showed significant decreases (p<.01) in both the fraction of reduced coenzyme Q10 (CoQ10) and trolox equivalent antioxidant capacity (TEAC). Both findings are consistent with increased oxidative stress in NPC. Supplementation with CoQ10 was not effective in correcting the decreased fraction of reduced CoQ10. Increased oxidative stress may be a contributing factor to the pathology of NPC, and demonstration of increased oxidative stress in NPC patients provides both a rationale and the biomarkers necessary to test the efficacy of antioxidant therapy in NPC. Published by Elsevier Inc.
C1 [Fu, Rao; Yanjanin, Nicole M.; Bianconi, Simona; Porter, Forbes D.] NICHD, Program Dev Endocrinol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Fu, Rao] Peking Univ, Hlth Sci Ctr, Beijing 100191, Peoples R China.
[Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, DHHS, Bethesda, MD 20892 USA.
RP Porter, FD (reprint author), Bld 10,Rm 9D42,10 Ctr Dr, Bethesda, MD 20892 USA.
EM fdporter@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Human Genome Research Institute; Office of Rare
Diseases; Ara Parseghian Medical Research Foundation; Dana's Angels
Research Trust; Hadley Hope Foundation; Ed Cutler (Phlebotomy Services
International)
FX This work was supported by the intramural programs of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, the
National Human Genome Research Institute, and a Bench-to-Bedside grant
from the Office of Rare Diseases. NY was supported by funding from the
Ara Parseghian Medical Research Foundation and Dana's Angels Research
Trust. Collection of control blood samples was organized and supported
by Hadley Hope Foundation and Ed Cutler (Phlebotomy Services
International). RF is a Ph.D. candidate of Health Science Center of
Peking University. We would also like to acknowledge the contribution of
the caretakers and patients who have participated in this study.
NR 45
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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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD OCT-NOV
PY 2010
VL 101
IS 2-3
BP 214
EP 218
DI 10.1016/j.ymgme.2010.06.018
PG 5
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 672TK
UT WOS:000283609600021
PM 20667755
ER
PT J
AU Puri, A
AF Puri, Anu
TI Nanoparticles: Crossing barriers and membrane interactions FOREWORD
SO MOLECULAR MEMBRANE BIOLOGY
LA English
DT Editorial Material
C1 NCI, NIH, Frederick, MD 21701 USA.
RP Puri, A (reprint author), NCI, NIH, Frederick, MD 21701 USA.
EM apuri@helix.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0968-7688
J9 MOL MEMBR BIOL
JI Mol. Membr. Biol.
PD OCT
PY 2010
VL 27
IS 7
BP 213
EP 214
DI 10.3109/09687688.2010.509115
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 672NE
UT WOS:000283591200001
PM 20929338
ER
PT J
AU Rosenblum, LT
Kosaka, N
Mitsunaga, M
Choyke, PL
Kobayashi, H
AF Rosenblum, Lauren T.
Kosaka, Nobuyuki
Mitsunaga, Makoto
Choyke, Peter L.
Kobayashi, Hisataka
TI In vivo molecular imaging using nanomaterials: General in vivo
characteristics of nano-sized reagents and applications for cancer
diagnosis (Review)
SO MOLECULAR MEMBRANE BIOLOGY
LA English
DT Review
DE Molecular imaging; nanomaterial; quantum dot; dendrimer; iron oxide
particle
ID SENTINEL LYMPH-NODE; MRI CONTRAST AGENTS; MAGNETIC RESONANCE
LYMPHANGIOGRAPHY; II QUANTUM DOTS; POLYAMIDOAMINE DENDRIMERS; REAL-TIME;
CELL; NANOPARTICLES; MULTICOLOR; BIOCOMPATIBILITY
AB Nanoparticles present a new collection of contrast agents for the field of in vivo molecular imaging. This review focuses on promising molecular imaging probes for optical and magnetic resonance imaging based on four representative nanomaterial(s) platforms: quantum dots, upconversion phosphors, superparamagnetic iron oxides, and dendrimer-based agents. Quantum dots are extremely efficient fluorescent nanoparticles with size-tunable emission properties, enabling high sensitivity and greater depth penetration. Their heavy metal composition and long retention in the body, however, pose concerns for clinical translational applications. Upconversion phosphors generate excellent signal-to-background contrast because they emit light with higher energy than the excitation photons and autofluorescence signals. For MRI, iron oxide particles also generate excellent signal and have been used in liver imaging and for cell tracking studies. As they are metabolized through endogenous iron salvage pathways, they have already been introduced as clinical contrast agents. Lastly, dendrimers, a 'soft' nanoparticle, can be used as a structural basis for the attachment of small molecule imaging agents and/or targeting groups. This array of nanoparticles should offer insights into the uses and potentials of nanoparticles for the molecular imaging.
C1 [Rosenblum, Lauren T.; Kosaka, Nobuyuki; Mitsunaga, Makoto; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B69,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kobayash@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.
NR 62
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U1 6
U2 61
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0968-7688
J9 MOL MEMBR BIOL
JI Mol. Membr. Biol.
PD OCT
PY 2010
VL 27
IS 7
BP 274
EP 285
DI 10.3109/09687688.2010.481640
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 672NE
UT WOS:000283591200006
PM 20455640
ER
PT J
AU Yavlovich, A
Smith, B
Gupta, K
Blumenthal, R
Puri, A
AF Yavlovich, Amichai
Smith, Brandon
Gupta, Kshitij
Blumenthal, Robert
Puri, Anu
TI Light-sensitive lipid-based nanoparticles for drug delivery: design
principles and future considerations for biological applications
SO MOLECULAR MEMBRANE BIOLOGY
LA English
DT Article
DE Lipid-based nanoparticles; drug delivery; laser; cancer therapy;
photodynamic therapy; liposomes; photo-triggering
ID STERICALLY STABILIZED LIPOSOMES; BIOADHESIVE PATCH SYSTEMS; GOLD
NANOPARTICLES; PHOTODYNAMIC THERAPY; PHOTOSENSITIVE LIPOSOMES; SOLUTE
RELEASE; PHOTOINDUCED DESTABILIZATION; MULTILAMELLAR VESICLES;
NUCLEAR-LOCALIZATION; METAL NANOPARTICLES
AB Radiation-based therapies aided by nanoparticles have been developed for decades, and can be primarily categorized into two main platforms. First, delivery of payload of photo-reactive drugs (photosensitizers) using the conventional nanoparticles, and second, design and development of photo-triggerable nanoparticles (primarily liposomes) to attain light-assisted on-demand drug delivery. The main focus of this review is to provide an update of the history, current status and future applications of photo-triggerable lipid-based nanoparticles (light-sensitive liposomes). We will begin with a brief overview on the applications of liposomes for delivery of photosensitizers, including the choice of photosensitizers for photodynamic therapy, as well as the currently available light sources (lasers) used for these applications. The main segment of this review will encompass the details of strategies used to develop photo-triggerable liposomes for their drug delivery function. The principles underlying the assembly of photoreactive lipids into nanoparticles (liposomes) and photo-triggering mechanisms will be presented. We will also discuss factors that limit the applications of these liposomes for in vivo triggered drug delivery and emerging concepts that may lead to the biologically viable photo-activation strategies. We will conclude with our view point on the future perspectives of light-sensitive liposomes in the clinic.
C1 [Yavlovich, Amichai; Smith, Brandon; Gupta, Kshitij; Blumenthal, Robert; Puri, Anu] NCI, CCR Nanobiol Program, NIH, Frederick, MD 21702 USA.
RP Puri, A (reprint author), NCI, CCR Nanobiol Program, NIH, Bldg 469,Rm 216A,POB B,Miller Dr, Frederick, MD 21702 USA.
EM apuri@helix.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.
NR 127
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U1 4
U2 38
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0968-7688
J9 MOL MEMBR BIOL
JI Mol. Membr. Biol.
PD OCT
PY 2010
VL 27
IS 7
BP 364
EP 381
DI 10.3109/09687688.2010.507788
PG 18
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 672NE
UT WOS:000283591200013
PM 20939770
ER
PT J
AU Vecchiarelli, AG
Han, YW
Tan, X
Mizuuchi, M
Ghirlando, R
Biertumpfel, C
Funnell, BE
Mizuuchi, K
AF Vecchiarelli, Anthony G.
Han, Yong-Woon
Tan, Xin
Mizuuchi, Michiyo
Ghirlando, Rodolfo
Biertuempfel, Christian
Funnell, Barbara E.
Mizuuchi, Kiyoshi
TI ATP control of dynamic P1 ParA-DNA interactions: a key role for the
nucleoid in plasmid partition
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID BACTERIAL CHROMOSOME SEGREGATION; ESCHERICHIA-COLI; PROTEIN PARA;
F-PLASMID; BACILLUS-SUBTILIS; PATTERN-FORMATION; DIVISION SITE; BINDING;
SOPA; POLYMERIZATION
AB P>P1 ParA is a member of the Walker-type family of partition ATPases involved in the segregation of plasmids and bacterial chromosomes. ATPases of this class interact with DNA non-specifically in vitro and colocalize with the bacterial nucleoid to generate a variety of reported patterns in vivo. Here, we directly visualize ParA binding to DNA using total internal reflection fluorescence microscopy. This activity depends on, and is highly specific for ATP. DNA-binding activity is not coupled to ATP hydrolysis. Rather, ParA undergoes a slow multi-step conformational transition upon ATP binding, which licenses ParA to bind non-specific DNA. The kinetics provide a time-delay switch to allow slow cycling between the DNA binding and non-binding forms of ParA. We propose that this time delay, combined with stimulation of ParA's ATPase activity by ParB bound to the plasmid DNA, generates an uneven distribution of the nucleoid-associated ParA, and provides the motive force for plasmid segregation prior to cell division.
C1 Kyoto Univ, Present addresses Inst Integrated Cell Mat Sci, Sakyo Ku, Kyoto 6068501, Japan.
[Vecchiarelli, Anthony G.; Funnell, Barbara E.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
[Han, Yong-Woon; Tan, Xin; Mizuuchi, Michiyo; Ghirlando, Rodolfo; Biertuempfel, Christian; Mizuuchi, Kiyoshi] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Funnell, BE (reprint author), Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada.
EM b.funnell@utoronto.ca; Kmizu@helix.nih.gov
RI Ghirlando, Rodolfo/A-8880-2009;
OI Biertumpfel, Christian/0000-0002-7528-6547; Vecchiarelli,
Anna/0000-0002-3185-6720
FU University of Toronto; Eric Hani Fellowship; Canadian Institutes of
Health Research [37997]
FX We are grateful to Vassili Ivanov for his help with the microscope
system, to Wei Yang for the use of instruments for stopped-flow and
SEC/MALS experiments, and to Natalie Erdmann for construction of the
parA-gfp fusion. This work was supported by the University of Toronto
Open Fellowship and an Eric Hani Fellowship (to A.G.V.), by Grant 37997
from the Canadian Institutes of Health Research (to B.E.F.), and by
intramural research fund for NIDDK, NIH, HHS, US Government (to K.M.).
NR 46
TC 70
Z9 70
U1 2
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0950-382X
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD OCT
PY 2010
VL 78
IS 1
BP 78
EP 91
DI 10.1111/j.1365-2958.2010.07314.x
PG 14
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 654MR
UT WOS:000282172900008
PM 20659294
ER
PT J
AU Peterson, JH
Woolhead, CA
Bernstein, HD
AF Peterson, Janine H.
Woolhead, Cheryl A.
Bernstein, Harris D.
TI The conformation of a nascent polypeptide inside the ribosome tunnel
affects protein targeting and protein folding
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID SIGNAL RECOGNITION PARTICLE; ESCHERICHIA-COLI RIBOSOME; EXIT TUNNEL;
TRIGGER FACTOR; MEMBRANE-PROTEINS; CONDUCTING CHANNEL; PEPTIDE; CHAINS;
SEQUENCE; L23
AB In this report, we describe insights into the function of the ribosome tunnel that were obtained through an analysis of an unusual 25 residue N-terminal motif (EspP(1-25)) associated with the signal peptide of the Escherichia coli EspP protein. It was previously shown that EspP(1-25) inhibits signal peptide recognition by the signal recognition particle, and we now show that fusion of EspP(1-25) to a cytoplasmic protein causes it to aggregate. We obtained two lines of evidence that both of these effects are attributable to the conformation of EspP(1-25) inside the ribosome tunnel. First, we found that mutations in EspP(1-25) that abolished its effects on protein targeting and protein folding altered the cross-linking of short nascent chains to ribosomal components. Second, we found that a mutation in L22 that distorts the tunnel mimicked the effects of the EspP(1-25) mutations on protein biogenesis. Our results provide evidence that the conformation of a polypeptide inside the ribosome tunnel can influence protein folding under physiological conditions and suggest that ribosomal mutations might increase the solubility of at least some aggregation-prone proteins produced in E. coli.
C1 [Peterson, Janine H.; Bernstein, Harris D.] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
[Woolhead, Cheryl A.] Univ Glasgow, Fac Biomed & Life Sci, Div Biochem & Mol Biol, Glasgow G12 8QQ, Lanark, Scotland.
RP Bernstein, HD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
EM harris_bernstein@nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases; BBSRC
[BB/G011281]
FX We thank Jim Bardwell, Bernd Bukau, Isabelle Iost, Rowena Matthews,
Matthias Muller and Knud Nierhaus for gifts of strains and antisera. We
also thank Manu Hegde and Frances Yap for helpful comments on the
manuscript. This work was supported by the Intramural Research Program
of the National Institute of Diabetes and Digestive and Kidney Diseases
and by BBSRC Grant BB/G011281 to C.A.W.
NR 55
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U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0950-382X
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD OCT
PY 2010
VL 78
IS 1
BP 203
EP 217
DI 10.1111/j.1365-2958.2010.07325.x
PG 15
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 654MR
UT WOS:000282172900016
PM 20804452
ER
PT J
AU Oquendo, MA
Canino, G
Lehner, T
Licinio, J
AF Oquendo, M. A.
Canino, G.
Lehner, T.
Licinio, J.
TI Genetic repositories for the study of major psychiatric conditions: what
do we know about ethnic minorities' genetic vulnerability?
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE diversity; race; DNA
ID BIPOLAR AFFECTIVE-DISORDER; STORED BIOLOGICAL SAMPLES; UNITED-STATES;
SEQUENCE VARIATIONS; MEXICAN-AMERICANS; AFRICAN-AMERICAN;
ETHICAL-ISSUES; SCHIZOPHRENIA; ASSOCIATION; POPULATIONS
AB In spite of considerable efforts, no genes of major effect have been found across an entire diagnostic category in psychiatry. Possible reasons for this may include difficulties in defining the phenotype, the complex relationship between genotype and gene expression and population stratification. This last problem has often been managed by restricting genetic sampling to only one ethnic group. An unintended consequence of using this strategy is that the major repositories of genetic material for the study of psychiatric conditions in the United States suffer from a paucity of genetic samples from non-Caucasian groups. Thus, these groups are being relatively understudied in terms of the genetic antecedents to psychiatric disease. The authors provide solutions including the need to augment the representation of African-American, Latino and Asian-Americans among research participants; a more nuanced approach to identify ancestry; and the development of analytic and genetic strategies to handle the issue of ethnic heterogeneity in samples. Molecular Psychiatry (2010) 15, 970-975; doi:10.1038/mp.2010.11; published online 23 February 2010
C1 [Oquendo, M. A.] New York State Psychiat Inst & Hosp, Dept Psychiat, New York, NY 10032 USA.
[Oquendo, M. A.] Columbia Univ, New York, NY USA.
[Canino, G.] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA.
[Lehner, T.] NIMH, Bethesda, MD 20892 USA.
[Licinio, J.] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia.
RP Oquendo, MA (reprint author), New York State Psychiat Inst & Hosp, Dept Psychiat, 1051 Riverside Dr,Unit 42, New York, NY 10032 USA.
EM mao4@columbia.edu
RI Licinio, Julio/L-4244-2013
OI Licinio, Julio/0000-0001-6905-5884
FU NIMH NIH HHS [R01 MH048514]
NR 41
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U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD OCT
PY 2010
VL 15
IS 10
BP 970
EP 975
DI 10.1038/mp.2010.11
PG 6
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 653MS
UT WOS:000282096200001
PM 20177407
ER
PT J
AU Rosenberg, SA
AF Rosenberg, Steven A.
TI Of Mice, Not Men: No Evidence for Graft-versus-Host Disease in Humans
Receiving T-Cell Receptor-Transduced Autologous T Cells
SO MOLECULAR THERAPY
LA English
DT Editorial Material
ID CANCER REGRESSION; GENE-THERAPY
C1 NCI, Surg Branch, NIH, CRC, Bethesda, MD 20892 USA.
RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, CRC, 10 Ctr Dr,Room 3-3940, Bethesda, MD 20892 USA.
EM sar@nih.gov
NR 6
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U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD OCT
PY 2010
VL 18
IS 10
BP 1744
EP 1745
DI 10.1038/mt.2010.195
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 659BE
UT WOS:000282541200003
PM 20885433
ER
PT J
AU Huang, X
Guo, HF
Tammana, S
Jung, YC
Mellgren, E
Bassi, P
Cao, Q
Tu, ZJ
Kim, YC
Ekker, SC
Wu, XL
Wang, SM
Zhou, XZ
AF Huang, Xin
Guo, Hongfeng
Tammana, Syam
Jung, Yong-Chul
Mellgren, Emil
Bassi, Preetinder
Cao, Qing
Tu, Zheng Jin
Kim, Yeong C.
Ekker, Stephen C.
Wu, Xiaolin
Wang, San Ming
Zhou, Xianzheng
TI Gene Transfer Efficiency and Genome-Wide Integration Profiling of
Sleeping Beauty, Tol2, and PiggyBac Transposons in Human Primary T Cells
SO MOLECULAR THERAPY
LA English
DT Article
ID MAMMALIAN-CELLS; STEM-CELLS; EXPRESSION; THERAPY; SYSTEM;
TRANSFORMATION; LYMPHOCYTES; EVOLUTION; MAP4K4; FISH
AB In this study, we compared the genomic integration efficiencies and transposition site preferences of Sleeping Beauty (SB or SB11), Tol2, and piggyBac (PB) transposon systems in primary T cells derived from peripheral blood lymphocytes (PBL) and umbilical cord blood (UCB). We found that PB demonstrated the highest efficiency of stable gene transfer in PBL-derived T cells, whereas SB11 and Tol2 mediated intermediate and lowest efficiencies, respectively. Southern hybridization analysis demonstrated that PB generated the highest number of integrants when compared to SB and Tol2 in both PBL and UCB T cells. Tol2 and PB appeared more likely to promote clonal expansion than SB, which may be in part due to the dysregulated expression of cancer-related genes near the insertion sites. Genome-wide integration analysis demonstrated that SB, Tol2, and PB integrations occurred in all the chromosomes without preference. Additionally, Tol2 and PB integration sites were mainly localized near transcriptional start sites (TSSs), CpG islands and DNasel hypersensitive sites, whereas SB integrations were randomly distributed. These results suggest that SB may be a preferential choice of the delivery vector in T cells due to its random integration site preference and relatively high efficiency, and support continuing development of SB-mediated T-cell phase I trials.
C1 [Huang, Xin; Guo, Hongfeng; Zhou, Xianzheng] Univ Minnesota, Sch Med, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
[Huang, Xin; Guo, Hongfeng; Zhou, Xianzheng] Univ Minnesota, Sch Med, Div Pediat Blood & Marrow Transplantat, Minneapolis, MN 55455 USA.
[Huang, Xin; Guo, Hongfeng; Zhou, Xianzheng] Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA.
[Huang, Xin; Guo, Hongfeng; Zhou, Xianzheng] Univ Minnesota, Sch Med, Ctr Genome Engn, Minneapolis, MN 55455 USA.
[Tammana, Syam; Zhou, Xianzheng] Univ Minnesota, Grad Sch, Grad Program Microbial Engn, Minneapolis, MN 55455 USA.
[Jung, Yong-Chul; Kim, Yeong C.; Wang, San Ming] Northwestern Univ, Evanston NW Healthcare Res Inst, Ctr Funct Genom, Evanston, IL USA.
[Mellgren, Emil] Macalester Coll, St Paul, MN 55105 USA.
[Bassi, Preetinder] Univ Minnesota, Coll Biol Sci, Minneapolis, MN 55455 USA.
[Cao, Qing] Univ Minnesota, Sch Med, Biostat & Informat Core Masonic Canc Ctr, Minneapolis, MN 55455 USA.
[Tu, Zheng Jin] Univ Minnesota, Inst Supercomp, Minneapolis, MN 55455 USA.
[Ekker, Stephen C.] Mayo Clin, Rochester, MN USA.
[Wu, Xiaolin] Natl Canc Inst Frederick, Lab Mol Technol, SAIC Frederick Inc, Frederick, MD USA.
RP Zhou, XZ (reprint author), Univ Minnesota, Sch Med, Masonic Canc Ctr, MMC 366,420 Delaware St, Minneapolis, MN 55455 USA.
EM zhoux058@umn.edu
FU Children's Cancer Research Fund in Minneapolis, Alliance for Cancer Gene
Therapy; Gabrielle's Angel (formerly G&P) Foundation for Cancer
Research; Sidney Kimmel Foundation for Cancer Research; University of
Minnesota; University Minnesota Medical School Dean's Commitment;
Leukemia Research Fund; American Society of Hematology; Undergraduate
Research Opportunity Program Award; Multicultural Summer Research
Opportunities Award; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]
FX We thank Sonja Nodland (University of Minnesota Masonic Cancer Center)
for major editing, R. Scott McIvor, David Largaespada, and Perry Hackett
(University of Minnesota Center for Genome Engineering, Minneapolis, MN)
for critical review of the manuscript. We also thank John E. Wagner for
providing cord blood, Malcolm J. Fraser (University of Notre Dame, Notre
Dame, IN) for providing piggyBac vectors, Andrew C. Wilber (Southern
Illinois University, Springfield, IL) for providing Sleeping Beauty
transposon recoverable vector, Kevin A.T. Silverstein (Bioinformatics
Core Facility at Masonic Cancer Center, University of Minnesota) for the
independent evaluation on the data, and Linan Ma (Biostatistics and
Informatics Core at the Masonic Cancer Center, University of Minnesota)
for initial statistical analysis. This work was supported by grants from
the Children's Cancer Research Fund in Minneapolis, Alliance for Cancer
Gene Therapy, the Gabrielle's Angel (formerly G&P) Foundation for Cancer
Research, the Sidney Kimmel Foundation for Cancer Research Kimmel
Scholar Program, the University of Minnesota Translational Research
Grant, the University Minnesota Medical School Dean's Commitment (X.Z.),
and Leukemia Research Fund. E.M. was a recipient of American Society of
Hematology Research Trainee Award. P.B. was a recipient of the
Undergraduate Research Opportunity Program Award and the Multicultural
Summer Research Opportunities Award. This project was funded in whole or
in part with federal funds from the National Cancer Institute, National
Institutes of Health, under Contract No. HHSN261200800001E (X.W.). 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. Contribution statement: X.H. designed
and performed the research, analyzed the data, and wrote the paper;
H.G., S.T., E.M., and P.B. performed the research. Y.-C.J. performed DNA
sequencing and analyzed the data; Q.C. performed the statistical
analyses; Z.J.T. and Y.C.K. performed integration site analysis; S.C.E.
provided miniTol2 construct and discussed the research; X.W. preformed
integration bioinformatic analyses and wrote the paper; S.M.W. analyzed
the data and wrote the paper; X.Z. oversaw the research and wrote the
paper. The authors declare no competitive financial interests.
NR 45
TC 72
Z9 75
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD OCT
PY 2010
VL 18
IS 10
BP 1803
EP 1813
DI 10.1038/mt.2010.141
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 659BE
UT WOS:000282541200011
PM 20606646
ER
PT J
AU Bagnato, F
Salman, Z
Kane, R
Auh, S
Cantor, FK
Ehrmantraut, M
Gallo, A
Ikonomidou, VN
Ohayon, J
Pellicano, C
Stern, SK
McFarland, HF
AF Bagnato, Francesca
Salman, Zeena
Kane, Robert
Auh, Sungyoung
Cantor, Fredric K.
Ehrmantraut, Mary
Gallo, Antonio
Ikonomidou, Vasiliki N.
Ohayon, Joan
Pellicano, Clelia
Stern, Susan K.
McFarland, Henry F.
TI T(1) cortical hypointensities and their association with cognitive
disability in multiple sclerosis
SO MULTIPLE SCLEROSIS
LA English
DT Article
DE MRI; multiple sclerosis; T2 lesions
ID INVERSION-RECOVERY; INTRACORTICAL LESIONS; FUNCTIONAL COMPOSITE;
IMPAIRMENT; PATHOLOGY; ATROPHY
AB Objective: To assess the incidence of T(1) hypointense NLs by 3.0-Tesla magnetic resonance imaging (MRI) in patients with MS and examine neocortical lesion association with cognitive impairment.
Methods: In this case-control study, 21 MS patients and 21 age-, sex- and years of education-matched healthy volunteers underwent: (i) a neuropsychological examination rating cognitive impairment (Minimal Assessment of Cognitive Function in MS); (ii) a 3.0-Tesla MRI inclusive of an isotropic 1.0 mm(3) three-dimensional inversion prepared spoiled gradient-recalled-echo (3D-IRSPGR) image and T(1)- and T(2)-weighted images. Hypointensities on 3D-IRSPGR lying in the cortex, either entirely or partially were counted and association between NLs and cognitive impairment investigated.
Results: A total of 95 NLs were observed in 14 (66.7%) patients. NL+ patients performed poorer (p = 0.020) than NLpatients only on the delayed recall component of the California Verbal Learning Test. This difference lost statistical significance when a correction for white matter lesion volume was employed.
Conclusions: Although T(1) hypointense NLs may be present in a relatively high proportion of multiple sclerosis patients, the impact that they have in cognitive impairment is not independent from white matter disease.
C1 [Bagnato, Francesca; Salman, Zeena; Cantor, Fredric K.; Ehrmantraut, Mary; Gallo, Antonio; Ikonomidou, Vasiliki N.; Ohayon, Joan; Pellicano, Clelia; Stern, Susan K.; McFarland, Henry F.] NINDS, NIB, NIH, Bethesda, MD 20892 USA.
[Kane, Robert] Vet Affairs Med Ctr, MS Ctr Excellence, Baltimore, MD 21201 USA.
[Auh, Sungyoung] NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA.
RP Bagnato, F (reprint author), NINDS, NIB, NIH, Bldg 10,Room 5C103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bagnatof@ninds.nih.gov
RI Pellicano, Clelia/K-1062-2016
OI Pellicano, Clelia/0000-0002-3272-1094
NR 35
TC 14
Z9 14
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
J9 MULT SCLER
JI Mult. Scler.
PD OCT
PY 2010
VL 16
IS 10
BP 1203
EP 1212
DI 10.1177/1352458510377223
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 656KG
UT WOS:000282332100007
PM 20699284
ER
PT J
AU Jacobson, S
AF Jacobson, S.
TI Role of human herpesviruses in multiple sclerosis
SO MULTIPLE SCLEROSIS
LA English
DT Meeting Abstract
CT Conference on Pan-Asian Committee for Treatment and Research in Multiple
Sclerosis (PACTRIMS)
CY AUG 26-28, 2010
CL Bali, INDONESIA
C1 [Jacobson, S.] NIH, Viral Immunol Sect, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
J9 MULT SCLER
JI Mult. Scler.
PD OCT
PY 2010
VL 16
IS 10
BP 1268
EP 1268
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 656KG
UT WOS:000282332100018
ER
PT J
AU Sena, LM
Fishman, SJ
Jenkins, KJ
Xu, H
Brechbiel, MW
Regino, CAS
Kosaka, N
Bernardo, M
Choyke, PL
Kobayashi, H
AF Sena, Laureen M.
Fishman, Steven J.
Jenkins, Kathy J.
Xu, Heng
Brechbiel, Martin W.
Regino, Celeste A. S.
Kosaka, Nobuyuki
Bernardo, Marcelino
Choyke, Peter L.
Kobayashi, Hisataka
TI Magnetic resonance lymphangiography with a nano-sized gadolinium-labeled
dendrimer in small and large animal models
SO NANOMEDICINE
LA English
DT Article
DE dendrimer; magnetic resonance lymphangiography; nanomaterials; pig;
thoracic duct
ID IMAGING CONTRAST AGENTS; PERCUTANEOUS SCLEROTHERAPY; LYMPHATIC
MALFORMATIONS; BREAST-CANCER; CELLS; VISUALIZATION; HORIZONS; DELIVERY;
NODES; MICE
AB Aim: Imaging of the lymphatic system is critical in preoperative planning of resections of complex lymphatic malformations. However, safe, effective imaging methods with sufficient resolution to identify the lymphatics have been lacking. In this study, we demonstrate the use of gadolinium-labeled dendrimers to image the lymphatics in small and large animal models during magnetic resonance lymphangiography. Methods: Polyamidoamine G6-Gd_1B4M_N-hydroxysuccinimide was synthesized and administered intradermally in the extremities of normal mice and pigs at several doses. Results: The lymphatics were well demonstrated in both animal models and there was rapid uptake in the deep lymphatic system, including the thoracic duct. A significant dose reduction was achieved (1 mu mol Gd/kg) in the 35-kg pig compared with mice, while still producing excellent results. No toxicity was observed and only minor inflammatory changes were observed at the injection site 30 days later. Conclusion: We demonstrate that a low dose of a macromolecular magnetic resonance contrast agent can provide rapid imaging of the deep lymphatic system in both small and large animals. This data provides a basis to consider a similar agent in clinical trials.
C1 [Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Sena, Laureen M.; Fishman, Steven J.; Jenkins, Kathy J.] Boston Childrens Hosp, Boston, MA USA.
RP Choyke, PL (reprint author), NCI, Mol Imaging Program, NIH, Bldg 10,Room B9B69, Bethesda, MD 20892 USA.
EM pchoyke@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. 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 24
TC 18
Z9 19
U1 0
U2 4
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1743-5889
J9 NANOMEDICINE-UK
JI Nanomedicine
PD OCT
PY 2010
VL 5
IS 8
BP 1183
EP 1191
DI 10.2217/NNM.10.70
PG 9
WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology
SC Biotechnology & Applied Microbiology; Science & Technology - Other
Topics
GA 679YM
UT WOS:000284196700010
PM 21039196
ER
PT J
AU Satterlee, JS
Schubeler, D
Ng, HH
AF Satterlee, John S.
Schuebeler, Dirk
Ng, Huck-Hui
TI Tackling the epigenome: challenges and opportunities for collaboration
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID EMBRYONIC STEM-CELLS; DNA METHYLATION; HUMAN GENOME; DIFFERENTIATED
CELLS; CHROMATIN; CANCER; EPIGENETICS; REVEALS; PLURIPOTENT; THERAPY
C1 [Satterlee, John S.] US Natl Inst Drug Abuse, Bethesda, MD USA.
[Schuebeler, Dirk] Friedrich Miescher Inst, CH-4002 Basel, Switzerland.
[Ng, Huck-Hui] Genome Inst Singapore, Singapore, Singapore.
RP Satterlee, JS (reprint author), US Natl Inst Drug Abuse, Bethesda, MD USA.
EM satterleej@nida.nih.gov
RI Ng, Huck Hui/A-1135-2009
NR 63
TC 49
Z9 51
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD OCT
PY 2010
VL 28
IS 10
BP 1039
EP 1044
DI 10.1038/nbt1010-1039
PG 6
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 663GF
UT WOS:000282870500024
PM 20944594
ER
PT J
AU Lippincott-Schwartz, J
AF Lippincott-Schwartz, Jennifer
TI The long road: peering into live cells
SO NATURE CELL BIOLOGY
LA English
DT Editorial Material
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
RP Lippincott-Schwartz, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
EM lippincj@mail.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD OCT
PY 2010
VL 12
IS 10
BP 918
EP 918
DI 10.1038/ncb1010-918
PG 1
WC Cell Biology
SC Cell Biology
GA 656UJ
UT WOS:000282363500002
PM 20885416
ER
PT J
AU McElhinny, SAN
Kumar, D
Clark, AB
Watt, DL
Watts, BE
Lundstrom, EB
Johansson, E
Chabes, A
Kunkel, TA
AF McElhinny, Stephanie A. Nick
Kumar, Dinesh
Clark, Alan B.
Watt, Danielle L.
Watts, Brian E.
Lundstrom, Else-Britt
Johansson, Erik
Chabes, Andrei
Kunkel, Thomas A.
TI Genome instability due to ribonucleotide incorporation into DNA
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; POLYMERASE-EPSILON; ESCHERICHIA-COLI;
SUBSTRATE-SPECIFICITY; REPLICATION FORK; YEAST; PURIFICATION; MUTATIONS;
RESIDUE; SUGAR
AB Maintaining the chemical identity of DNA depends on ribonucleotide exclusion by DNA polymerases. However, ribonucleotide exclusion during DNA synthesis in vitro is imperfect. To determine whether ribonucleotides are incorporated during DNA replication in vivo, we substituted leucine or glycine for an active-site methionine in yeast DNA polymerase epsilon ( Pol epsilon). Ribonucleotide incorporation in vitro was three-fold lower for M644L and 11-fold higher for M644G Pol epsilon compared to wildtype Pol epsilon. This hierarchy was recapitulated in vivo in yeast strains lacking RNase H2. Moreover, the pol2-M644G rnh201 Delta strain progressed more slowly through S phase, had elevated dNTP pools and generated 2-5-base-pair deletions in repetitive sequences at a high rate and in a gene orientation-dependent manner. The data indicate that ribonucleotides are incorporated during replication in vivo, that they are removed by RNase H2-dependent repair and that defective repair results in replicative stress and genome instability via DNA strand misalignment.
C1 [McElhinny, Stephanie A. Nick; Clark, Alan B.; Watt, Danielle L.; Watts, Brian E.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[McElhinny, Stephanie A. Nick; Clark, Alan B.; Watt, Danielle L.; Watts, Brian E.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Kumar, Dinesh; Lundstrom, Else-Britt; Johansson, Erik; Chabes, Andrei] Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden.
[Chabes, Andrei] Umea Univ, Lab Mol Infect Med Sweden, Umea, Sweden.
RP McElhinny, SAN (reprint author), NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
OI Chabes, Andrei/0000-0003-1708-8259
FU Division of Intramural Research of the US National Institutes of Health,
National Institute of Environmental Health Sciences; Swedish Foundation
for Strategic Research; Swedish Research Council; Swedish Cancer
Society; Umea University
FX We thank K. Bebenek and J. Williams for thoughtful comments on the
manuscript and the National Institute of Environmental Health Sciences
Molecular Genetics Core for technical support in DNA sequence analysis
of ura3 mutants. This work was supported in part by Project Z01 ES065070
(to T. A. K.) from the Division of Intramural Research of the US
National Institutes of Health, National Institute of Environmental
Health Sciences, in part by the Swedish Foundation for Strategic
Research, the Swedish Research Council and the Swedish Cancer Society
(to A. C.) and in part by the Swedish Research Council, the Swedish
Cancer Society, Smartafonden and the fund for Basic Science-oriented
Biotechnology, Medical Faculty of Umea University (to E. J.).
NR 37
TC 152
Z9 153
U1 1
U2 21
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
EI 1552-4469
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD OCT
PY 2010
VL 6
IS 10
BP 774
EP 781
DI 10.1038/NCHEMBIO.424
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 651YM
UT WOS:000281964100015
ER
PT J
AU Church, DM
Lappalainen, I
Sneddon, TP
Hinton, J
Maguire, M
Lopez, J
Garner, J
Paschall, J
DiCuccio, M
Yaschenko, E
Scherer, SW
Feuk, L
Flicek, P
AF Church, Deanna M.
Lappalainen, Ilkka
Sneddon, Tam P.
Hinton, Jonathan
Maguire, Michael
Lopez, John
Garner, John
Paschall, Justin
DiCuccio, Michael
Yaschenko, Eugene
Scherer, Stephen W.
Feuk, Lars
Flicek, Paul
TI Public data archives for genomic structural variation
SO NATURE GENETICS
LA English
DT Letter
ID COPY-NUMBER; SEGMENTAL DUPLICATION
C1 [Church, Deanna M.; Sneddon, Tam P.; Lopez, John; Garner, John; Paschall, Justin; DiCuccio, Michael; Yaschenko, Eugene] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Lappalainen, Ilkka; Hinton, Jonathan; Maguire, Michael; Flicek, Paul] European Bioinformat Inst, Cambridge, England.
[Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada.
[Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada.
[Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Feuk, Lars] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden.
RP Church, DM (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM church@ncbi.nlm.nih.gov; flicek@ebi.ac.uk
RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013;
OI Scherer, Stephen /0000-0002-8326-1999; Sneddon, Tam
Paterson/0000-0003-1137-8992; Lappalainen, Ilkka/0000-0001-5762-893X;
Flicek, Paul/0000-0002-3897-7955
FU Intramural NIH HHS [Z99 LM999999]
NR 15
TC 47
Z9 47
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD OCT
PY 2010
VL 42
IS 10
BP 813
EP 814
DI 10.1038/ng1010-813
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA 655UO
UT WOS:000282276600002
PM 20877315
ER
PT J
AU Goode, LL
Chenevix-Trench, G
Song, H
Ramus, SJ
Notaridou, M
Lawrenson, K
Widschwendter, M
Vierkant, RA
Larson, MC
Kjaer, SK
Birrer, MJ
Berchuck, A
Schildkraut, J
Tomlinson, I
Kiemeney, LA
Cook, LS
Gronwald, J
Garcia-Closas, M
Gore, ME
Campbell, I
Whittemore, AS
Sutphen, R
Phelan, C
Anton-Culver, H
Pearce, CL
Lambrechts, D
Rossing, MA
Chang-Claude, J
Moysich, KB
Goodman, MT
Dork, T
Nevanlinna, H
Ness, RB
Rafnar, T
Hogdall, C
Hogdall, E
Fridley, BL
Cunningham, JM
Sieh, W
McGuire, V
Godwin, AK
Cramer, DW
Hernandez, D
Levine, D
Lu, K
Iversen, ES
Palmieri, RT
Houlston, R
van Altena, AM
Aben, KKH
Massuger, LFAG
Brooks-Wilson, A
Kelemen, LE
Le, ND
Jakubowska, A
Lubinski, J
Medrek, K
Stafford, A
Easton, DF
Tyrer, J
Bolton, KL
Harrington, P
Eccles, D
Chen, A
Molina, AN
Davila, BN
Arango, H
Tsai, Y
Chen, ZH
Risch, HA
McLaughlin, J
Narod, SA
Ziogas, A
Brewster, W
Gentry-Maharaj, A
Menon, U
Wu, AH
Stram, DO
Pike, MC
Beesley, J
Webb, PM
Chen, XQ
Ekici, AB
Thiel, FC
Beckmann, MW
Yang, H
Wentzensen, N
Lissowska, J
Fasching, PA
Despierre, E
Amant, F
Vergote, I
Doherty, J
Hein, R
Wang-Gohrke, S
Lurie, G
Carney, ME
Thompson, PJ
Runnebaum, I
Hillemanns, P
Durst, M
Antonenkova, N
Bogdanova, N
Leminen, A
Butzow, R
Heikkinen, T
Stefansson, K
Sulem, P
Besenbacher, S
Sellers, TA
Gayther, SA
Pharoah, PDP
AF Goode, Llen L.
Chenevix-Trench, Georgia
Song, Honglin
Ramus, Susan J.
Notaridou, Maria
Lawrenson, Kate
Widschwendter, Martin
Vierkant, Robert A.
Larson, Melissa C.
Kjaer, Susanne K.
Birrer, Michael J.
Berchuck, Andrew
Schildkraut, Joellen
Tomlinson, Ian
Kiemeney, Lambertus A.
Cook, Linda S.
Gronwald, Jacek
Garcia-Closas, Montserrat
Gore, Martin E.
Campbell, Ian
Whittemore, Alice S.
Sutphen, Rebecca
Phelan, Catherine
Anton-Culver, Hoda
Pearce, Celeste Leigh
Lambrechts, Diether
Rossing, Mary Anne
Chang-Claude, Jenny
Moysich, Kirsten B.
Goodman, Marc T.
Doerk, Thilo
Nevanlinna, Heli
Ness, Roberta B.
Rafnar, Thorunn
Hogdall, Claus
Hogdall, Estrid
Fridley, Brooke L.
Cunningham, Julie M.
Sieh, Weiva
McGuire, Valerie
Godwin, Andrew K.
Cramer, Daniel W.
Hernandez, Dena
Levine, Douglas
Lu, Karen
Iversen, Edwin S.
Palmieri, Rachel T.
Houlston, Richard
van Altena, Anne M.
Aben, Katja K. H.
Massuger, Leon F. A. G.
Brooks-Wilson, Angela
Kelemen, Linda E.
Le, Nhu D.
Jakubowska, Anna
Lubinski, Jan
Medrek, Krzysztof
Stafford, Anne
Easton, Douglas F.
Tyrer, Jonathan
Bolton, Kelly L.
Harrington, Patricia
Eccles, Diana
Chen, Ann
Molina, Ashley N.
Davila, Barbara N.
Arango, Hector
Tsai, Yu
Chen, Zhihua
Risch, Harvey A.
McLaughlin, John
Narod, Steven A.
Ziogas, Argyrios
Brewster, Wendy
Gentry-Maharaj, Aleksandra
Menon, Usha
Wu, Anna H.
Stram, Daniel O.
Pike, Malcolm C.
Beesley, Jonathan
Webb, Penelope M.
Chen, Xiaoqing
Ekici, Arif B.
Thiel, Falk C.
Beckmann, Matthias W.
Yang, Hannah
Wentzensen, Nicolas
Lissowska, Jolanta
Fasching, Peter A.
Despierre, Evelyn
Amant, Frederic
Vergote, Ignace
Doherty, Jennifer
Hein, Rebecca
Wang-Gohrke, Shan
Lurie, Galina
Carney, Michael E.
Thompson, Pamela J.
Runnebaum, Ingo
Hillemanns, Peter
Duerst, Matthias
Antonenkova, Natalia
Bogdanova, Natalia
Leminen, Arto
Butzow, Ralf
Heikkinen, Tuomas
Stefansson, Kari
Sulem, Patrick
Besenbacher, Soeren
Sellers, Thomas A.
Gayther, Simon A.
Pharoah, Paul D. P.
CA Wellcome Trust Case-Control Conso
Australian Canc Study Ovarian Canc
Australian Ovarian Canc Study Grp
OCAC
TI A genome-wide association study identifies susceptibility loci for
ovarian cancer at 2q31 and 8q24
SO NATURE GENETICS
LA English
DT Article
ID COLORECTAL-CANCER; POLY(ADP-RIBOSE) POLYMERASE; EPITHELIAL-CELLS;
MULTIPLE LOCI; IN-VITRO; GENE; METAANALYSIS; VARIANTS; CARRIERS
AB Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2)(1). Here, we report on nine additional candidate loci (defined as having P <= 10(-4)) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P <= 5 x 10(-8) (8q24, P = 8.0 x 10(-15) and 2q31, P = 3.8 x 10(-14)) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 x 10(-8) and 17q21, P = 1.4 x 10(-7)). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development.
C1 [Goode, Llen L.; Vierkant, Robert A.; Larson, Melissa C.; Fridley, Brooke L.] Mayo Clin Coll Med, Dept Hlth Sci Res, Rochester, MN USA.
[Chenevix-Trench, Georgia; Beesley, Jonathan; Webb, Penelope M.; Chen, Xiaoqing; Australian Canc Study Ovarian Canc] Post Off Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld, Australia.
[Song, Honglin; Stafford, Anne; Tyrer, Jonathan; Harrington, Patricia] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cancer Res United Kingdom, Cambridge, England.
[Notaridou, Maria; Lawrenson, Kate; Widschwendter, Martin; Menon, Usha; Gayther, Simon A.] UCL, Dept Gynecol Oncol, Elizabeth Garrett Anderson EGA Inst Womens Hlt, London, England.
[Kjaer, Susanne K.; Runnebaum, Ingo] Juliane Marie Ctr, Dept Gynecol & Obstet, Copenhagen, Denmark.
[Kjaer, Susanne K.; Runnebaum, Ingo] Inst Canc Epidemiol, Dept Virus, Hormones & Canc, Danish Canc Soc, Copenhagen, Denmark.
[Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Berchuck, Andrew; Schildkraut, Joellen] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC USA.
[Tomlinson, Ian] London Sch Med & Dent, Inst Canc, Ctr Mol Oncol & Imaging, London, England.
[Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol, Biostatist & Hlth Technol Assessment HTA, NL-6525 ED Nijmegen, Netherlands.
[Lubinski, Jan] Univ New Mexico, Div Epidemiol & Biostatist, Albuquerque, NM 87131 USA.
[Cook, Linda S.] Alberta Hlth Services Canc Care, Calgary, AB, Canada.
[Gronwald, Jacek; Medrek, Krzysztof] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland.
[Garcia-Closas, Montserrat; Wentzensen, Nicolas] Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Gore, Martin E.] Royal Marsden Hosp, Gynecol Oncol Unit, London, England.
[Campbell, Ian] Peter MacCallum Canc Inst, Ctr Canc Genom & Predict Med, Melbourne, Australia.
[Campbell, Ian] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia.
[Whittemore, Alice S.; Molina, Ashley N.; Davila, Barbara N.] Stanford Univ, Sch Med, Div Epidemiol & Biostatist, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Sutphen, Rebecca; Sieh, Weiva; McGuire, Valerie] Univ S Florida, Coll Med, Pediat Epidemiol Ctr, Tampa, FL USA.
[Phelan, Catherine] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Anton-Culver, Hoda] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA.
[Pearce, Celeste Leigh; Wu, Anna H.; Stram, Daniel O.; Pike, Malcolm C.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA.
[Lambrechts, Diether] VIB, Vesalius Res Ctr, Brussels, Belgium.
[Lambrechts, Diether] LU Leuven, Louvain, Belgium.
[Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
[Chang-Claude, Jenny; Hein, Rebecca] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA.
[Goodman, Marc T.; Carney, Michael E.; Thompson, Pamela J.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA.
[Doerk, Thilo] Hannover Med Sch, Clin Obstet & Gynaecol, Hannover, Germany.
[Nevanlinna, Heli; Leminen, Arto; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki, Finland.
[Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Rafnar, Thorunn; Stefansson, Kari; Sulem, Patrick; Besenbacher, Soeren] DeCODE Genet, Reykjavik, Iceland.
[Hogdall, Claus] Juliane Marie Ctr, Dept Gynecol & Obstet, Copenhagen, Denmark.
[Hogdall, Estrid] Hormones & Canc Inst Canc Epidemiol, Danish Canc Soc, Dept Virus, Copenhagen, Denmark.
[Cunningham, Julie M.] Mayo Clin Coll Med, Dept Lab Med & Pathol, Rochester, MN USA.
[Godwin, Andrew K.] Fox Chase Canc Ctr, Dept Med Oncol, Womens Canc Program, Philadelphia, PA 19111 USA.
[Cramer, Daniel W.] Brigham & Womens Hosp, Obstetr & Gynecol Epidemiol Ctr, Boston, MA 02115 USA.
[Hernandez, Dena] Natl Inst Hlth, NIA, Bethesda, MD USA.
[Levine, Douglas] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Lu, Karen] MD Anderson Canc Ctr, Houston, TX USA.
[Iversen, Edwin S.] Duke Univ, Dept Stat, Durham, NC USA.
[Palmieri, Rachel T.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Houlston, Richard] Inst Canc Res, Royal Canc Hosp, Mol & Populat Genet Team, London, England.
[van Altena, Anne M.; Massuger, Leon F. A. G.] Radboud Univ Nijmegen, Med Ctr, Dept Gynaecol, NL-6525 ED Nijmegen, Netherlands.
[Aben, Katja K. H.] Comprehens Canc Ctr E, Nijmegen, Netherlands.
[Brooks-Wilson, Angela] Genome Sci Ctr, British Columbia Canc Agcy, Vancouver, BC, Canada.
[Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC, Canada.
[Kelemen, Linda E.] Alberta Hlth Serv Canc Care, Calgary, AB, Canada.
[Le, Nhu D.] British Columbia Canc Agcy, Cancer Control Res, Vancouver, BC V5Z 4E6, Canada.
[Easton, Douglas F.] Univ Cambridge, Strangeways Res Lab, Canc Res United Kingdom Genet Epidemiol Unit, Cambridge, England.
[Bolton, Kelly L.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England.
[Eccles, Diana] Univ Southampton, Sch Med, Wessex Clin Genet Serv Princess Anne Hosp, Southampton, Hants, England.
[Arango, Hector] W Coast Gynecol Oncol, Clearwater, FL USA.
[Risch, Harvey A.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA.
[McLaughlin, John] Canc Care Ontario, Toronto, ON, Canada.
[Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada.
[Brewster, Wendy] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA.
[Australian Ovarian Canc Study Grp] Peter MacCallum Canc Inst, Melbourne, Australia.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, D-8520 Erlangen, Germany.
[Thiel, Falk C.] Univ Breast Ctr Franconia, Univ Hosp Erlangen, Dept Gynecol & Obstet, Erlangen, Germany.
[Beckmann, Matthias W.; Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Beckmann, Matthias W.; Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Fasching, Peter A.] Univ Calif Los Angeles, Dept Med, Div Hematol & Oncol, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Despierre, Evelyn; Amant, Frederic; Vergote, Ignace] Univ Hosp Leuven, Dept Gynecol Oncol, Leuven, Belgium.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynaecol, Ulm, Germany.
[Duerst, Matthias] Friedrich Schiller Univ, Clin Obstet & Gynaecol, Jena, Germany.
[Antonenkova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandro N, Minsk, Byelarus.
[Bogdanova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandro N, Minsk, Byelarus.
[Bogdanova, Natalia] Hannover Med Sch, Clin Obstet & Gynaecol, D-3000 Hannover, Germany.
[Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki, Finland.
[Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland.
[Pharoah, Paul D. P.] Univ Cambridge, Strangeways Res Lab, Canc Res United Kingdom Dept Oncol, Cambridge, England.
[Pharoah, Paul D. P.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England.
RP Gayther, SA (reprint author), Mayo Clin Coll Med, Dept Hlth Sci Res, Rochester, MN USA.
EM gayther@usc.edu
RI Menon, Usha/C-4716-2008; Verdrengh, Evelien/H-4571-2012; Webb,
Penelope/D-5736-2013; Ekici, Arif/C-3971-2013; Fridley,
Brooke/D-8315-2015; Garcia-Closas, Montserrat /F-3871-2015; van Altena,
Anne/B-9824-2016; McLaughlin, John/E-4577-2013; Kiemeney,
Lambertus/D-3357-2009; Tang, Macy/B-9798-2014; Brooks-Wilson,
Angela/E-9399-2012; Massuger, Leon/H-8072-2014; Jakubowska,
Anna/O-8050-2014; Dork, Thilo/J-8620-2012; Aben, Katja/G-9686-2016;
Gronwald, Jacek/A-4576-2017;
OI Webb, Penelope/0000-0003-0733-5930; Fridley, Brooke/0000-0001-7739-7956;
Garcia-Closas, Montserrat /0000-0003-1033-2650; Kiemeney,
Lambertus/0000-0002-2368-1326; Brooks-Wilson,
Angela/0000-0003-1009-6408; Aben, Katja/0000-0002-0214-2147; Gronwald,
Jacek/0000-0002-3643-2871; Vierkant, Robert/0000-0001-6242-5221; Kjaer,
Susanne/0000-0002-8347-1398; Ramus, Susan/0000-0003-0005-7798;
Lissowska, Jolanta/0000-0003-2695-5799; Nevanlinna,
Heli/0000-0002-0916-2976; Besenbacher, Soren/0000-0003-1455-1738;
Houlston, Richard/0000-0002-5268-0242
FU Ovarian Cancer Research Fund; Mermaid 1; Danish Cancer Society; National
Cancer Institute, Bethesda, Maryland, USA [R01-CA61107]; US National
Institutes of Health; National Cancer Institute [R01CA- 122443,
CA-58860, CA-92044, R01-CA58598, N01-CN-55424, N01-PC-67001,
N01-PC-35137]; Mayo Foundation; US National Cancer Institute; Department
of Health and Human Services; Ovarian Cancer Specialized Program of
Research Excellence (SPORE) [P50 CA083638]; Cancer Research UK; Eastern
Cancer Registration and Information Centre for subject recruitment; US
National Institutes of Health [R01-CA106414, R01-CA-63682, R01CA- 63678,
R01-CA112523, R01-CA-87538]; American Cancer Society
[CRTG-00-196-01-CCE]; Advanced Cancer Detection Center; Department of
Defense [DAMD17-98-1-8659]; Canadian Institutes for Health Research;
Canadian Cancer Society; University of California, Irvine
[R01-CA-114343]; Lon V Smith Foundation [LVS-39420]; OAK Foundation;
National Health and Medical Research Council of Australia [199600]; US
Army Medical Research and Materiel Command [DAMD17-01-1-0729,
W81XWH-06-1-0220]; Cancer Council Tasmania; Cancer Foundation of Western
Australia; ELAN Foundation; Erlangen University Hospital; German Federal
Ministry of Education and Research of Germany; Programme of Clinical
Biomedical Research [01 GB 9401]; University of Ulm; German Cancer
Research Center; California Cancer Research Program [00-01389V-20170,
2110200]; Helsinki University Central Hospital; Academy of Finland;
Finnish Cancer Society
FX This study made use of data generated by the Wellcome Trust Case Control
consortium. A full list of the investigators who contributed to the
generation of the data is available from http://www. wtccc. org.
uk/.Funding for the project was provided by the Wellcome Trust under
award 076113. The Ovarian Cancer Association Consortium is supported by
a grant from the Ovarian Cancer Research Fund thanks to donations by the
family and friends of Kathryn Sladek Smith.; The MAL study is supported
by grants from Mermaid 1, the Danish Cancer Society and the National
Cancer Institute, Bethesda, Maryland, USA (R01-CA61107). The MAY study
and the phase 3 and combined analyses were supported by the US National
Institutes of Health, National Cancer Institute grants R01CA- 122443 and
funding from the Mayo Foundation. The PBCS was funded by Intramural
Research Funds of the US National Cancer Institute, Department of Health
and Human Services. The Fox Chase Cancer Center ovarian cancer study,
part of the National Cancer Institute collaboration, is supported by an
Ovarian Cancer Specialized Program of Research Excellence (SPORE) (P50
CA083638). The NCO study is supported by the US National Institutes of
Health, National Cancer Institute grant R01-CA-76016. The SEA study is
funded by a programme grant from Cancer Research UK. We thank the SEARCH
team and the Eastern Cancer Registration and Information Centre for
subject recruitment. The TBO study was supported by the US National
Institutes of Health (R01-CA106414); the American Cancer Society
(CRTG-00-196-01-CCE); and the Advanced Cancer Detection Center Grant,
Department of Defense (DAMD17-98-1-8659). The TOR study was supported by
grants from the Canadian Institutes for Health Research, the National
Cancer Institute of Canada with funds provided by the Canadian Cancer
Society and the US National Institutes of Health (R01-CA-63682 and
R01CA- 63678). Additional support for the TOR, NCO, MAY, TBO and NCI
studies was provided by the University of California, Irvine grant
R01-CA-114343. The UCI study is supported by the US National Institutes
of Health, National Cancer Institute grants CA-58860, CA-92044 and the
Lon V Smith Foundation grant LVS-39420. The UKO study is supported by
funding from Cancer Research UK, the Eve Appeal and the OAK Foundation.
Some of this work was undertaken at University College London
Hospital/University College London, who received a proportion of funding
from the Department of Health's National Institutes for Health Research
Biomedical Research Centre funding scheme. We particularly thank I.
Jacobs, E. Wozniak, A. Ryan, J. Ford and N. Balogun for their
contribution to the study. The AUS study is supported by the National
Health and Medical Research Council of Australia (199600), US Army
Medical Research and Materiel Command under DAMD17-01-1-0729 (award no.
W81XWH-06-1-0220) and the Cancer Council Tasmania and Cancer Foundation
of Western Australia. G. C.-M. T. and P. M. W. are Research Fellows of
the National Health and Medical Research Council. The Australian Ovarian
Cancer Study (AOCS) Management Group (D. Bowtell, A. deFazio, G. C.-T.,
D. G., A. K. G. and P. M. W.) gratefully acknowledges the contribution
of all the clinical and scientific collaborators (see http://www.
aocstudy. org/). The Australian Cancer Study (ACS) Management Group
comprises P. D. P. P., P. M. W., A. Green, N. Hayward and D. Whiteman.
The BAV study is supported by the ELAN Foundation and Erlangen
University Hospital. The BEL study is supported by the National Cancer
Plan-Action 29 for the support of Translational Research. The DOV study
(Seattle Diseases of the Ovary) was supported by the US National
Institutes of Health grants R01-CA112523 and R01-CA-87538. The GER study
was supported by the German Federal Ministry of Education and Research
of Germany, the Programme of Clinical Biomedical Research (01 GB 9401),
and the genotyping was supported in part by the state of
Baden-Wrttemberg through the Medical Faculty, University of Ulm (P.
685).; Data management wassupported by the German Cancer Research
Center. The HAW study was supported by the US Public Health Service
grant R01-CA58598 and contracts N01-CN-55424, N01-PC-67001 and
N01-PC-35137 from the National Cancer Institute, US National Institutes
of Health, Department of Health and Human Services. Funding for the USC
study was received from the California Cancer Research Program grants
00-01389V-20170 and 2110200, US Public Health Service grants CA14089,
CA17054, CA61132, CA63464, N01-PC-67010 and R03CA113148 and the
California Department of Health Services sub-contract 050E8709 as part
of its statewide cancer reporting program (University of Southern
California). The HJO study gratefully acknowledges the contribution of
F. Kramer and W. Zheng to the recruitment of subjects at Hannover
Medical School. The HMO study gratefully acknowledges the help of L.
Gacucova in sample preparation. The HOC study was financially supported
by the Helsinki University Central Hospital Research Fund, Academy of
Finland and the Finnish Cancer Society.
NR 30
TC 131
Z9 132
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD OCT
PY 2010
VL 42
IS 10
BP 874
EP +
DI 10.1038/ng.668
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 655UO
UT WOS:000282276600018
ER
PT J
AU Bolton, KL
Tyrer, J
Song, H
Ramus, SJ
Notaridou, M
Jones, C
Sher, T
Gentry-Maharaj, A
Wozniak, E
Tsai, YY
Weidhaas, J
Paik, D
Van den Berg, DJ
Stram, DO
Pearce, CL
Wu, AH
Brewster, W
Anton-Culver, H
Ziogas, A
Narod, SA
Levine, DA
Kaye, SB
Brown, R
Paul, J
Flanagan, J
Sieh, W
McGuire, V
Whittemore, AS
Campbell, I
Gore, ME
Lissowska, J
Yang, HP
Medrek, K
Gronwald, J
Lubinski, J
Jakubowska, A
Le, ND
Cook, LS
Kelemen, LE
Brook-Wilson, A
Massuger, LFAG
Kiemeney, LA
Aben, KKH
van Altena, AM
Houlston, R
Tomlinson, I
Palmieri, RT
Moorman, PG
Schildkraut, J
Iversen, ES
Phelan, C
Vierkant, RA
Cunningham, JM
Goode, EL
Fridley, BL
Kruger-Kjaer, S
Blaeker, J
Hogdall, E
Hogdall, C
Gross, J
Karlan, BY
Ness, RB
Edwards, RP
Odunsi, K
Moyisch, KB
Baker, JA
Modugno, F
Heikkinenen, T
Butzow, R
Nevanlinna, H
Leminen, A
Bogdanova, N
Antonenkova, N
Doerk, T
Hillemanns, P
Duurst, M
Runnebaum, I
Thompson, PJ
Carney, ME
Goodman, MT
Lurie, G
Wang-Gohrke, S
Hein, R
Chang-Claude, J
Rossing, MA
Cushing-Haugen, KL
Doherty, J
Chen, C
Rafnar, T
Besenbacher, S
Sulem, P
Stefansson, K
Birrer, MJ
Terry, KL
Hernandez, D
Cramer, DW
Vergote, I
Amant, F
Lambrechts, D
Despierre, E
Fasching, PA
Beckmann, MW
Thiel, FC
Ekici, AB
Chen, XQ
Johnatty, SE
Webb, PM
Beesley, J
Chanock, S
Garcia-Closas, M
Sellers, T
Easton, DF
Berchuck, A
Chenevix-Trench, G
Pharoah, PDP
Gayther, SA
AF Bolton, Kelly L.
Tyrer, Jonathan
Song, Honglin
Ramus, Susan J.
Notaridou, Maria
Jones, Chris
Sher, Tanya 3
Gentry-Maharaj, Aleksandra
Wozniak, Eva
Tsai, Ya-Yu
Weidhaas, Joanne
Paik, Daniel
Van den Berg, David J.
Stram, Daniel O.
Pearce, Celeste Leigh
Wu, Anna H.
Brewster, Wendy
Anton-Culver, Hoda
Ziogas, Argyrios
Narod, Steven A.
Levine, Douglas A.
Kaye, Stanley B.
Brown, Robert
Paul, Jim
Flanagan, James
Sieh, Weiva
McGuire, Valerie
Whittemore, Alice S.
Campbell, Ian
Gore, Martin E.
Lissowska, Jolanta
Yang, Hanna P.
Medrek, Krzysztof
Gronwald, Jacek
Lubinski, Jan
Jakubowska, Anna
Le, Nhu D.
Cook, Linda S.
Kelemen, Linda E.
Brook-Wilson, Angela
Massuger, Leon F. A. G.
Kiemeney, Lambertus A.
Aben, Katja K. H.
van Altena, Anne M.
Houlston, Richard
Tomlinson, Ian
Palmieri, Rachel T.
Moorman, Patricia G.
Schildkraut, Joellen
Iversen, Edwin S.
Phelan, Catherine
Vierkant, Robert A.
Cunningham, Julie M.
Goode, Ellen L.
Fridley, Brooke L.
Kruger-Kjaer, Susan
Blaeker, Jan
Hogdall, Estrid
Hogdall, Claus
Gross, Jenny
Karlan, Beth Y.
Ness, Roberta B.
Edwards, Robert P.
Odunsi, Kunle
Moyisch, Kirsten B.
Baker, Julie A.
Modugno, Francesmary
Heikkinenen, Tuomas
Butzow, Ralf
Nevanlinna, Heli
Leminen, Arto
Bogdanova, Natalia
Antonenkova, Natalia
Doerk, Thilo
Hillemanns, Peter
Duerst, Matthias
Runnebaum, Ingo
Thompson, Pamela J.
Carney, Michael E.
Goodman, Marc T.
Lurie, Galina
Wang-Gohrke, Shan
Hein, Rebecca
Chang-Claude, Jenny
Rossing, Mary Anne
Cushing-Haugen, Kara L.
Doherty, Jennifer
Chen, Chu
Rafnar, Thorunn
Besenbacher, Soren
Sulem, Patrick
Stefansson, Kari
Birrer, Michael J.
Terry, Kathryn L.
Hernandez, Dena
Cramer, Daniel W.
Vergote, Ignace
Amant, Frederic
Lambrechts, Diether
Despierre, Evelyn
Fasching, Peter A.
Beckmann, Matthias W.
Thiel, Falk C.
Ekici, Arif B.
Chen, Xiaoqing
Johnatty, Sharon E.
Webb, Penelope M.
Beesley, Jonathan
Chanock, Stephen
Garcia-Closas, Montserrat
Sellers, Tom
Easton, Douglas F.
Berchuck, Andrew
Chenevix-Trench, Georgia
Pharoah, Paul D. P.
Gayther, Simon A.
CA Australian Ovarian Canc Study Grp
Australian Canc Study Ovarian Canc
Ovarian Canc Assoc Consortium
TI Common variants at 19p13 are associated with susceptibility to ovarian
cancer
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BRCA1; GENOTYPES; COMPLEX; BREAST; CELLS
AB Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women(1). We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5 x 10(-4) and P = 6 x 10(-4), respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3 x 10(-9) and P = 4 x 10(-11), respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.
C1 [Bolton, Kelly L.; Tyrer, Jonathan; Song, Honglin; Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Bolton, Kelly L.; Yang, Hanna P.; Kiemeney, Lambertus A.; Chanock, Stephen; Garcia-Closas, Montserrat] Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Ramus, Susan J.; Notaridou, Maria; Jones, Chris; Sher, Tanya 3; Gentry-Maharaj, Aleksandra; Gayther, Simon A.] UCL, Inst Womens Hlth, Dept Gynecol Oncol, EGA, London, England.
[Tsai, Ya-Yu] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Weidhaas, Joanne] Yale Univ, Dept Therapeut Radiol, New Haven, CT 06510 USA.
[Paik, Daniel] Yale Univ, Dept Obstet & Gynecol, New Haven, CT USA.
[Van den Berg, David J.; Stram, Daniel O.; Pearce, Celeste Leigh; Wu, Anna H.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Brewster, Wendy; Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA.
[Narod, Steven A.] Ctr Res Womens Hlth, Toronto, ON, Canada.
[Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA.
[Kaye, Stanley B.] Inst Canc Res, Med Sect, Sutton, Surrey, England.
[Brown, Robert; Flanagan, James] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London, England.
[Paul, Jim] Univ Glasgow, Canc Res UK Clin Trials Unit, Glasgow, Lanark, Scotland.
[Sieh, Weiva; McGuire, Valerie; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Australian Ovarian Canc Study Grp] Peter MacCallum Canc Inst, Melbourne, Australia.
[Campbell, Ian; Gore, Martin E.] Royal Marsden Hosp, Gynecol Oncol Unit, London SW3 6JJ, England.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Medrek, Krzysztof; Gronwald, Jacek; Lubinski, Jan; Jakubowska, Anna] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
[Le, Nhu D.] British Columbia Canc Agcy, Canc Control Res, Vancouver, BC V5Z 4E6, Canada.
[Cook, Linda S.] Univ New Mexico, Div Epidemiol & Biostatist, Albuquerque, NM 87131 USA.
[Cook, Linda S.; Kelemen, Linda E.] Alberta Hlth Serv Canc Care, Calgary, AB, Canada.
[Brook-Wilson, Angela] British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Brook-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
[Massuger, Leon F. A. G.; van Altena, Anne M.] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Gynaecol, Nijmegen, Netherlands.
[Aben, Katja K. H.] Comprehens Canc Ctr E, Nijmegen, Netherlands.
[Houlston, Richard] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England.
[Tomlinson, Ian] Wellcome Trust Ctr Human Genet, Populat & Funct Genet Lab, Oxford, England.
[Palmieri, Rachel T.; Moorman, Patricia G.; Schildkraut, Joellen; Berchuck, Andrew] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC USA.
[Iversen, Edwin S.] Duke Univ, Dept Stat, Durham, NC USA.
[Vierkant, Robert A.; Goode, Ellen L.; Fridley, Brooke L.] Mayo Clin Coll Med, Dept Hlth Sci Res, Rochester, MN USA.
[Cunningham, Julie M.] Mayo Clin Coll Med, Dept Lab Med & Pathol, Rochester, MN USA.
[Kruger-Kjaer, Susan; Hogdall, Estrid] Danish Canc Soc, Dept Virus, Copenhagen, Denmark.
[Kruger-Kjaer, Susan; Hogdall, Estrid] Danish Canc Soc, Canc Inst Canc Epidemiol, Canc Inst Canc Epidemiol, Copenhagen, Denmark.
[Blaeker, Jan] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark.
[Hogdall, Claus] Juliane Marie Ctr, Gynaecol Clin, Copenhagen, Denmark.
[Gross, Jenny; Karlan, Beth Y.] Cedars Sinai Med Ctr, Womens Canc Res Inst, Samuel Oschin Comprehens Canc Ctr, Los Angeles, CA 90048 USA.
[Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Edwards, Robert P.] Magee Womens Hosp, Pittsburgh, PA USA.
[Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA.
[Moyisch, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA.
[Baker, Julie A.] Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA.
[Modugno, Francesmary] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Heikkinenen, Tuomas; Butzow, Ralf; Nevanlinna, Heli; Leminen, Arto] Univ Helsinki, Cent Hosp, Dept Obstet & Gynaecol, Helsinki, Finland.
[Bogdanova, Natalia; Antonenkova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandro, Minsk, Byelarus.
[Doerk, Thilo; Hillemanns, Peter] Hannover Med Sch, Clin Obstet & Gynaecol, D-3000 Hannover, Germany.
[Duerst, Matthias; Runnebaum, Ingo] Friedrich Schiller Univ, Clin Obstet & Gynaecol, Jena, Germany.
[Thompson, Pamela J.; Carney, Michael E.; Goodman, Marc T.; Lurie, Galina] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany.
[Hein, Rebecca; Chang-Claude, Jenny] Deutsch Krebsforschungszentrum, Div Canc Epidemiol, Unit Genet Epidemiol, D-6900 Heidelberg, Germany.
[Rossing, Mary Anne; Cushing-Haugen, Kara L.; Doherty, Jennifer; Chen, Chu] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
[Rafnar, Thorunn; Besenbacher, Soren; Sulem, Patrick; Stefansson, Kari] DeCODE Genet, Reykjavik, Iceland.
[Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Terry, Kathryn L.; Cramer, Daniel W.] Brigham & Womens Hosp, Obstetr & Gynecol Epidemiol Ctr, Boston, MA 02115 USA.
[Hernandez, Dena] Natl Inst Hlth, NIA, Bethesda, MD USA.
[Vergote, Ignace; Amant, Frederic; Despierre, Evelyn] Univ Hosp Leuven, Dept Gynecol Oncol, Louvain, Belgium.
[Lambrechts, Diether] Vesalius Res Ctr VIB & KU Leuven, Louvain, Belgium.
[Fasching, Peter A.] David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA USA.
[Beckmann, Matthias W.] Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Beckmann, Matthias W.] Inst Oncol, M Sklodowska Curie Canc Ctr, Warsaw, Poland.
[Thiel, Falk C.] Univ Hosp Erlangen, Dept Obstet & Gynaecol, Erlangen, Germany.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany.
[Chen, Xiaoqing; Johnatty, Sharon E.; Webb, Penelope M.; Beesley, Jonathan; Chenevix-Trench, Georgia; Australian Canc Study Ovarian Canc] Post Off Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld, Australia.
RP Pharoah, PDP (reprint author), Univ Cambridge, Dept Oncol, Cambridge, England.
EM paul1@srl.cam.ac.uk
RI Bowtell, David/H-1007-2016; Johnatty, Sharon/R-8890-2016; Gronwald,
Jacek/A-4576-2017; Brooks-Wilson, Angela/E-9399-2012; Verdrengh,
Evelien/H-4571-2012; Lester, Jenny/B-5933-2012; Webb,
Penelope/D-5736-2013; Ekici, Arif/C-3971-2013; Kiemeney,
Lambertus/D-3357-2009; Tang, Macy/B-9798-2014; Massuger,
Leon/H-8072-2014; Jakubowska, Anna/O-8050-2014; Fridley,
Brooke/D-8315-2015; Garcia-Closas, Montserrat /F-3871-2015; campbell,
Ian/F-6006-2011; van Altena, Anne/B-9824-2016; Aben, Katja/G-9686-2016
OI Bowtell, David/0000-0001-9089-7525; Johnatty,
Sharon/0000-0002-7888-1966; Gronwald, Jacek/0000-0002-3643-2871;
Brooks-Wilson, Angela/0000-0003-1009-6408; Vierkant,
Robert/0000-0001-6242-5221; Weidhaas, Joanne/0000-0002-5096-3281; Ramus,
Susan/0000-0003-0005-7798; Lissowska, Jolanta/0000-0003-2695-5799;
Nevanlinna, Heli/0000-0002-0916-2976; Besenbacher,
Soren/0000-0003-1455-1738; Houlston, Richard/0000-0002-5268-0242; Webb,
Penelope/0000-0003-0733-5930; Kiemeney, Lambertus/0000-0002-2368-1326;
Fridley, Brooke/0000-0001-7739-7956; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Aben, Katja/0000-0002-0214-2147
FU Cancer Research UK; Wellcome Trust [076113]; Ovarian Cancer Research
Fund; Mermaid/Eve Appeal; National Health and Medical Research Council;
Deutsche Krebshilfe; National Health Service; Danish Cancer Society;
Ovarian Cancer Research Fund [PPD/RPCI.07]; Roswell Park Cancer
Institute Alliance Foundation; US National Cancer Institute [CA58860,
CA92044, P50CA105009, R01CA122443, R01CA126841-01, R01CA16056,
R01CA61107, R01CA71766, R01CA054419, R01CA114343, R01CA87538,
R01CA112523, R01CA58598, N01CN55424, N01PC35137]; US Army Medical
Research and Material Command [DAMD17-01-1-0729]; Cancer Council
Victoria; Cancer Council Queensland; Cancer Council New South Wales;
Cancer Council South Australia; Cancer Council Tasmania; Cancer
Foundation of Western Australia; National Health and Medical Research
Council of Australia [199600, 400281]; German Federal Ministry of
Education and Research of Germany Programme of Clinical Biomedical
Research [01 GB 9401]; University of Ulm [P. 685]; Mayo Foundation; Lon
V. Smith Foundation [LVS-39420]; Oak Foundation; University College
Hospital National Institute for Health Research Biomedical Research
Centre; Royal Marsden Hospital Biomedical Research Centre
FX The genotyping and data analysis for this study was supported by a
project grant from Cancer Research UK. We acknowledge the computational
resources provided by the University of Cambridge (CamGrid). This study
makes use of data generated by the Wellcome Trust Case-Control
consortium. A full list of the investigators who contributed to the
generation of the data is available from http://www. wtccc. org. uk/.
Funding for the project was provided by the Wellcome Trust under award
076113. The Ovarian Cancer Association Consortium is supported by a
grant from the Ovarian Cancer Research Fund thanks to donations by the
family and friends of K. Sladek Smith. The results published here are in
part based upon data generated by The Cancer Genome Atlas Pilot Project
established by the National Cancer Institute and National Human Genome
Research Institute. Information about TCGA and the investigators and
institutions who constitute the TCGA research network can be found at
http://cancergenome. nih. gov/. S.J.R. is supported by the Mermaid/Eve
Appeal. G. C.-T. and P. M. W. are supported by the National Health and
Medical Research Council. P. A. F. is supported by the Deutsche
Krebshilfe. M. E. G. acknowledges National Health Service funding to the
National Institutes of Health Research Centre at the Royal Marsden
Hospital, and D. F. E. is a Principal Research Fellow of Cancer Research
UK. Funding of the constituent studies was provided by the Danish Cancer
Society, the Ovarian Cancer Research Fund (PPD/RPCI.07), the Roswell
Park Cancer Institute Alliance Foundation, the US National Cancer
Institute (CA58860, CA92044, P50CA105009, R01CA122443, R01CA126841-01,
R01CA16056, R01CA61107, R01CA71766, R01CA054419, R01CA114343,
R01CA87538, R01CA112523, R01CA58598, N01CN55424, N01PC35137 and
Intramural research funds), the US Army Medical Research and Material
Command (DAMD17-01-1-0729), Cancer Council Victoria, Cancer Council
Queensland, Cancer Council New South Wales, Cancer Council South
Australia, Cancer Council Tasmania and Cancer Foundation of Western
Australia, the National Health and Medical Research Council of Australia
(199600 and 400281), the German Federal Ministry of Education and
Research of Germany Programme of Clinical Biomedical Research (01 GB
9401), the state of Baden-Wurttemberg through Medical Faculty of the
University of Ulm (P. 685), the Mayo Foundation, the Lon V. Smith
Foundation (LVS-39420), the Oak Foundation, the University College
Hospital National Institute for Health Research Biomedical Research
Centre and the Royal Marsden Hospital Biomedical Research Centre.
NR 24
TC 144
Z9 148
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD OCT
PY 2010
VL 42
IS 10
BP 880
EP +
DI 10.1038/ng.666
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 655UO
UT WOS:000282276600019
PM 20852633
ER
PT J
AU Antoniou, AC
Wang, XS
Fredericksen, ZS
McGuffog, L
Tarrell, R
Sinilnikova, OM
Healey, S
Morrison, J
Kartsonaki, C
Lesnick, T
Ghoussaini, M
Barrowdale, D
Peock, S
Cook, M
Oliver, C
Frost, D
Eccles, D
Evans, DG
Eeles, R
Izatt, L
Chu, C
Douglas, F
Paterson, J
Stoppa-Lyonnet, D
Houdayer, C
Mazoyer, S
Giraud, S
Lasset, C
Remenieras, A
Caron, O
Hardouin, A
Berthet, P
Hogervorst, FBL
Rookus, MA
Jager, A
van den Ouweland, A
Hoogerbrugge, N
van der Luijt, RB
Meijers-Heijboer, H
Garcia, EBG
Devilee, P
Vreeswijk, MPG
Lubinski, J
Jakubowska, A
Gronwald, J
Huzarski, T
Byrski, T
Gorski, B
Cybulski, C
Spurdle, AB
Holland, H
Goldgar, DE
John, EM
Hopper, JL
Southey, M
Buys, SS
Daly, MB
Terry, MB
Schmutzler, RK
Wappenschmidt, B
Engel, C
Meindl, A
Preisler-Adams, S
Arnold, N
Niederacher, D
Sutter, C
Domchek, SM
Nathanson, KL
Rebbeck, T
Blum, JL
Piedmonte, M
Rodriguez, GC
Wakeley, K
Boggess, JF
Basil, J
Blank, SV
Friedman, E
Kaufman, B
Laitman, Y
Milgrom, R
Andrulis, IL
Glendon, G
Ozcelik, H
Kirchhoff, T
Vijai, J
Gaudet, MM
Altshuler, D
Guiducci, C
Loman, N
Harbst, K
Rantala, J
Ehrencrona, H
Gerdes, AM
Thomassen, M
Sunde, L
Peterlongo, P
Manoukian, S
Bonanni, B
Viel, A
Radice, P
Caldes, T
de la Hoya, M
Singer, CF
Fink-Retter, A
Greene, MH
Mai, PL
Loud, JT
Guidugli, L
Lindor, NM
Hansen, TVO
Nielsen, FC
Blanco, I
Lazaro, C
Garber, J
Ramus, SJ
Gayther, SA
Phelan, C
Narod, S
Szabo, CI
Benitez, J
Osorio, A
Nevanlinna, H
Heikkinen, T
Caligo, MA
Beattie, MS
Hamann, U
Godwin, AK
Montagna, M
Casella, C
Neuhausen, SL
Karlan, BY
Tung, N
Toland, AE
Weitzel, J
Olopade, O
Simard, J
Soucy, P
Rubinstein, WS
Arason, A
Rennert, G
Martin, NG
Montgomery, GW
Chang-Claude, J
Flesch-Janys, D
Brauch, H
Severi, G
Baglietto, L
Cox, A
Cross, SS
Miron, P
Gerty, SM
Tapper, W
Yannoukakos, D
Fountzilas, G
Fasching, PA
Beckmann, MW
Silva, IDS
Peto, J
Lambrechts, D
Paridaens, R
Rudiger, T
Forsti, A
Winqvist, R
Pylkaas, K
Diasio, RB
Lee, AM
Eckel-Passow, J
Vachon, C
Blows, F
Driver, K
Dunning, A
Pharoah, PPD
Offit, K
Pankratz, VS
Hakonarson, H
Chenevix-Trench, G
Easton, DF
Couch, FJ
AF Antoniou, Antonis C.
Wang, Xianshu
Fredericksen, Zachary S.
McGuffog, Lesley
Tarrell, Robert
Sinilnikova, Olga M.
Healey, Sue
Morrison, Jonathan
Kartsonaki, Christiana
Lesnick, Timothy
Ghoussaini, Maya
Barrowdale, Daniel
Peock, Susan
Cook, Margaret
Oliver, Clare
Frost, Debra
Eccles, Diana
Evans, D. Gareth
Eeles, Ros
Izatt, Louise
Chu, Carol
Douglas, Fiona
Paterson, Joan
Stoppa-Lyonnet, Dominique
Houdayer, Claude
Mazoyer, Sylvie
Giraud, Sophie
Lasset, Christine
Remenieras, Audrey
Caron, Olivier
Hardouin, Agnes
Berthet, Pascaline
Hogervorst, Frans B. L.
Rookus, Matti A.
Jager, Agnes
van den Ouweland, Ans
Hoogerbrugge, Nicoline
van der Luijt, Rob B.
Meijers-Heijboer, Hanne
Garcia, Encarna B. Gomez
Devilee, Peter
Vreeswijk, Maaike P. G.
Lubinski, Jan
Jakubowska, Anna
Gronwald, Jacek
Huzarski, Tomasz
Byrski, Tomasz
Gorski, Bohdan
Cybulski, Cezary
Spurdle, Amanda B.
Holland, Helene
Goldgar, David E.
John, Esther M.
Hopper, John L.
Southey, Melissa
Buys, Saundra S.
Daly, Mary B.
Terry, Mary-Beth
Schmutzler, Rita K.
Wappenschmidt, Barbara
Engel, Christoph
Meindl, Alfons
Preisler-Adams, Sabine
Arnold, Norbert
Niederacher, Dieter
Sutter, Christian
Domchek, Susan M.
Nathanson, Katherine L.
Rebbeck, Timothy
Blum, Joanne L.
Piedmonte, Marion
Rodriguez, Gustavo C.
Wakeley, Katie
Boggess, John F.
Basil, Jack
Blank, Stephanie V.
Friedman, Eitan
Kaufman, Bella
Laitman, Yael
Milgrom, Roni
Andrulis, Irene L.
Glendon, Gord
Ozcelik, Hilmi
Kirchhoff, Tomas
Vijai, Joseph
Gaudet, Mia M.
Altshuler, David
Guiducci, Candace
Loman, Niklas
Harbst, Katja
Rantala, Johanna
Ehrencrona, Hans
Gerdes, Anne-Marie
Thomassen, Mads
Sunde, Lone
Peterlongo, Paolo
Manoukian, Siranoush
Bonanni, Bernardo
Viel, Alessandra
Radice, Paolo
Caldes, Trinidad
de la Hoya, Miguel
Singer, Christian F.
Fink-Retter, Anneliese
Greene, Mark H.
Mai, Phuong L.
Loud, Jennifer T.
Guidugli, Lucia
Lindor, Noralane M.
Hansen, Thomas V. O.
Nielsen, Finn C.
Blanco, Ignacio
Lazaro, Conxi
Garber, Judy
Ramus, Susan J.
Gayther, Simon A.
Phelan, Catherine
Narod, Stephen
Szabo, Csilla I.
Benitez, Javier
Osorio, Ana
Nevanlinna, Heli
Heikkinen, Tuomas
Caligo, Maria A.
Beattie, Mary S.
Hamann, Ute
Godwin, Andrew K.
Montagna, Marco
Casella, Cinzia
Neuhausen, Susan L.
Karlan, Beth Y.
Tung, Nadine
Toland, Amanda E.
Weitzel, Jeffrey
Olopade, Olofunmilayo
Simard, Jacques
Soucy, Penny
Rubinstein, Wendy S.
Arason, Adalgeir
Rennert, Gad
Martin, Nicholas G.
Montgomery, Grant W.
Chang-Claude, Jenny
Flesch-Janys, Dieter
Brauch, Hiltrud
Severi, Gianluca
Baglietto, Laura
Cox, Angela
Cross, Simon S.
Miron, Penelope
Gerty, Sue M.
Tapper, William
Yannoukakos, Drakoulis
Fountzilas, George
Fasching, Peter A.
Beckmann, Matthias W.
Silva, Isabel dos Santos
Peto, Julian
Lambrechts, Diether
Paridaens, Robert
Ruediger, Thomas
Foersti, Asta
Winqvist, Robert
Pylkaes, Katri
Diasio, Robert B.
Lee, Adam M.
Eckel-Passow, Jeanette
Vachon, Celine
Blows, Fiona
Driver, Kristy
Dunning, Alison
Pharoah, Paul P. D.
Offit, Kenneth
Pankratz, V. Shane
Hakonarson, Hakon
Chenevix-Trench, Georgia
Easton, Douglas F.
Couch, Fergus J.
CA EMBRACE
GEMO Study Collaborators
HEBON
KConFab
SWE-BRCA
MOD SQUAD
GENICA
TI A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation
carriers and is associated with hormone receptor-negative breast cancer
in the general population
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ESTROGEN-RECEPTOR; COMMON VARIANTS; CONFER
SUSCEPTIBILITY; OVARIAN-CANCER; NONSENSE; ALLELES; COMPLEX; 2Q35
AB Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P(trend) = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P(trend) = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P(trend) = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P(trend) = 1.1 x 10(-7)).
C1 [Antoniou, Antonis C.; McGuffog, Lesley; Morrison, Jonathan; Kartsonaki, Christiana; Barrowdale, Daniel; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Tung, Nadine; Blows, Fiona; Driver, Kristy; Dunning, Alison; Pharoah, Paul P. D.; Easton, Douglas F.; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Wang, Xianshu; Guidugli, Lucia; Szabo, Csilla I.; Toland, Amanda E.; Couch, Fergus J.] Dept Lab Med & Pathol, Mayo Clin, Rochester, MN USA.
[Fredericksen, Zachary S.; Tarrell, Robert; Lesnick, Timothy; Weitzel, Jeffrey; Eckel-Passow, Jeanette; Vachon, Celine; Pankratz, V. Shane] Dept Hlth Sci Res, Mayo Clin, Rochester, MN USA.
[Sinilnikova, Olga M.; Giraud, Sophie; Olopade, Olofunmilayo] Univ Lyon Ctr Leon Berard, Ctr Hosp, Unit Mixte Genet Constitutionnelle Canc Frequents, Lyon, France.
[Sinilnikova, Olga M.; Mazoyer, Sylvie; Simard, Jacques] Univ Lyon, Ctr Leon Berard, CNRS, Equipe Labellisee LIGUE 2008, Lyon, France.
[Healey, Sue; Ghoussaini, Maya; Spurdle, Amanda B.; Holland, Helene; Simard, Jacques; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Eccles, Diana; Gerty, Sue M.; Tapper, William] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England.
[Evans, D. Gareth] Cent Manchester Univ Hosp, Manchester Acad Hlth Sci Ctr, NHSFT, Manchester, Lancs, England.
[Eeles, Ros] Inst Canc Res & Royal Marsden NHS Fdn, Oncogenet Team, Sutton, Surrey, England.
[Izatt, Louise; Soucy, Penny] Guys & St Thomas NHS Fdn Trust, Clin Genet, London, England.
[Chu, Carol] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England.
[Douglas, Fiona] Newcastle Tyne Hosp NHS Trust, Ctr Life, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England.
Addenbrookes Hosp, Dept Clin Genet, E Anglian Reg Genet Serv, Cambridge, England.
[Stoppa-Lyonnet, Dominique; Houdayer, Claude] Univ Paris 05, Inst Curie, INSERM U509, Serv Genet Oncolog, Paris, France.
[Lasset, Christine] Univ Lyon 1, CNRS, UMR5558, F-69365 Lyon, France.
[Lasset, Christine] Ctr Leon Berard, Unit Prevent & Epidemiol Genet, Lyon, France.
[Remenieras, Audrey] Inst Cancerol Gustave Roussy, Dept Genet, Villejuif, France.
[Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Consultat Genet, Villejuif, France.
[Hardouin, Agnes; Berthet, Pascaline; Miron, Penelope] Ctr Francois Baclesse, F-14021 Caen, France.
[GEMO Study Collaborators] Federat Natl Ctr Lutte Contre Canc, Grp Genet & Canc, Canc Genet Network, GEMO Study, Paris, France.
[Hogervorst, Frans B. L.] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands.
[Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands.
[Jager, Agnes] Erasmus Univ, Med Ctr, Rotterdam Family Canc Clin, Dept Clin Genet, Rotterdam, Netherlands.
[van den Ouweland, Ans] Rotterdam Family Canc Clin, Erasmus Univ Med Ctr, Dept Clin Genet, Rotterdam, Netherlands.
Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[van der Luijt, Rob B.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[Meijers-Heijboer, Hanne] Vrije Univ Amsterdam, Dept Clin Genet, Amsterdam, Netherlands.
[Garcia, Encarna B. Gomez] Maastricht Univ, Med Ctr, Dept Clin Genet, Sch Oncol & Dev Biol, Maastricht, Netherlands.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
[Vreeswijk, Maaike P. G.] Leiden Univ, Med Ctr, Dept Toxicogenet, Leiden, Netherlands.
[Lubinski, Jan; Jakubowska, Anna; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Gorski, Bohdan; Cybulski, Cezary] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
[KConFab] Peter MacCallum Canc Inst, Kathleen Cuningham Fdn Consortium Res Familial Br, kConFab, Melbourne, Vic 3000, Australia.
[Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA.
[John, Esther M.] Stanford Univ, Sch Med, Canc Prevent Inst Calif, Stanford, CA USA.
[Hopper, John L.; Southey, Melissa] Univ Melbourne, Melbourne, Vic, Australia.
[Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA.
[Daly, Mary B.; Godwin, Andrew K.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Terry, Mary-Beth] Columbia Univ, New York, NY USA.
[Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, Cologne, Germany.
[Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Cologne, CIO, Cologne, Germany.
[Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany.
[Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, Div Tumor Genet, Klinikum Rechts Isar, Munich, Germany.
[Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, Munster, Germany.
[Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, Kiel, Germany.
[Niederacher, Dieter] Univ Dusseldorf, Univ Hosp Dusseldorf, Div Mol Genet, Dept Obstet & Gynaecol, Dusseldorf, Germany.
[Sutter, Christian] Univ Heidelberg, Div Mol Diagnost, Inst Human Genet, Heidelberg, Germany.
[Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy] Univ Penn, Philadelphia, PA 19104 USA.
[Blum, Joanne L.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA.
[Piedmonte, Marion] Roswell Pk Canc Inst, Gynecol Oncol Grp 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.
[Basil, Jack] St Elizabeth Hosp, Edgewood, KY USA.
[Blank, Stephanie V.] NYU, Sch Med, New York, NY USA.
[Friedman, Eitan; Laitman, Yael; Milgrom, Roni] Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, Tel Hashomer, Israel.
[Kaufman, Bella] Inst Oncol, Sheba Med Ctr, Tel Hashomer, Israel.
[Andrulis, Irene L.; Glendon, Gord] Ontario Canc Inst, Ontario Canc Genet Network, Toronto, ON M4X 1K9, Canada.
[Ozcelik, Hilmi] Samuel Lunenfeld Res Inst, Fred Litwin Ctr Canc Genet, Toronto, ON, Canada.
[Andrulis, Irene L.; Offit, Kenneth] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Kirchhoff, Tomas; Vijai, Joseph] Mem Hosp, Clin Genet Serv, New York, NY USA.
[Kirchhoff, Tomas; Vijai, Joseph] Sloan Kettering Inst, Canc Biol & Genet Program, Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Gaudet, Mia M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
[Gaudet, Mia M.] Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, New York, NY USA.
[Altshuler, David; Guiducci, Candace] Broad Inst Harvard, Cambridge, MA USA.
[Altshuler, David; Guiducci, Candace] MIT, Cambridge, MA 02139 USA.
[Loman, Niklas; Harbst, Katja] Lund Univ, Dept Oncol, Lund, Sweden.
[Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.
[Ehrencrona, Hans] Uppsala Univ, Dept Genet & Pathol Rudbeck Lab, Uppsala, Sweden.
[Gerdes, Anne-Marie] Dept Clin Genet, Copenhagen, Denmark.
[Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark.
[Sunde, Lone] Aalborg & Aarhus Univ, Dept Clin Genet, Aalborg, Denmark.
[Peterlongo, Paolo; Radice, Paolo] Fdn Inst Ricovero Cura Carattere Sci, Unit Genet Susceptibil Canc, Dept Expt Oncol & Mol Med, Ist Nazl Tumori, Milan, Italy.
[Peterlongo, Paolo; Radice, Paolo] Fdn Ist Fdn Italiana Ricera Cancro FIRC Oncol Mol, IFOM, Milan, Italy.
[Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predict Med, Milan, Italy.
[Bonanni, Bernardo; de la Hoya, Miguel] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy.
[Viel, Alessandra] Ctr Riferimento Oncol, Div Expt Oncol, IRCCS, I-33081 Aviano, PN, Italy.
[Caldes, Trinidad] Hosp Clin San Carlos, Madrid, Spain.
[Singer, Christian F.; Fink-Retter, Anneliese] Med Univ Vienna, Dept Obstet Gynecol, Vienna, Austria.
[Greene, Mark H.; Mai, Phuong L.; Loud, Jennifer T.] Natl Canc Inst, Div Canc Epidemiol & Genet, Clin Genet Branch, Bethesda, MD USA.
[Lindor, Noralane M.] Mayo Clin Rochester, Rochester, MN USA.
[Hansen, Thomas V. O.; Nielsen, Finn C.] Copenhagen Univ Hosp, Dept Clin Biochem, Copenhagen, Denmark.
[Blanco, Ignacio; Lazaro, Conxi] Gran Via Hosp, Catalan Inst Oncol, Hereditary Canc Program, Barcelona, Spain.
[Garber, Judy] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ramus, Susan J.; Gayther, Simon A.] UCL, Dept Gynecol Oncol, EGA, London, England.
[Phelan, Catherine] Res Inst, Womens Coll, Toronto, ON, Canada.
[Narod, Stephen] H Lee Moffitt Canc Ctr & Res Inst, Dept Epidemiol & Genet, Tampa, FL USA.
[Benitez, Javier; Osorio, Ana] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Madrid, Spain.
[Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Ctr Hosp, Dept Obstet & Gynecol, Helsinki, Finland.
[Caligo, Maria A.] Univ Pisa, Dept Oncol, Div Surg Mol & Ultrastructural Pathol, Pisa, Italy.
[Beattie, Mary S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Beattie, Mary S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Beattie, Mary S.] Univ Calif San Francisco, Canc Risk Program, Helen Diller Family Canc Ctr, San Francisco, CA 94143 USA.
[Hamann, Ute; Foersti, Asta] German Canc Res Ctr, Heidelberg, Germany.
[Montagna, Marco; Casella, Cinzia] Ist Oncol Veneto IRCCS, Immunol & Mol Oncol Unit, Padua, Italy.
[Neuhausen, Susan L.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA.
[Karlan, Beth Y.] Canc Res Inst, Samuel Oschin Canc Inst, Div Gynecol Oncol, Cedars Sinai Med Ctr, Los Angeles, CA USA.
[Karlan, Beth Y.] Univ Calif Los Angeles, Dept Obstet & Gynecol, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Toland, Amanda E.] Ohio State Univ, Coll Med, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Weitzel, Jeffrey] City Hope Canc Ctr, Div Clin Canc Genet, Duarte, CA USA.
[Olopade, Olofunmilayo] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Simard, Jacques] Univ Quebec, Ctr Hosp, Canc Genom Lab, Quebec City, PQ, Canada.
[Simard, Jacques] Univ Laval, Ctr Rech Ctr Hosp Univ Quebec CHUQ, Quebec City, PQ G1K 7P4, Canada.
[Rubinstein, Wendy S.] Northshore Univ Hlth Syst, Evanston, IL USA.
[Arason, Adalgeir] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland.
[Rennert, Gad] Queensland Inst Med Res, QIMR GWAS Collect, Brisbane, Qld 4006, Australia.
[Martin, Nicholas G.; Montgomery, Grant W.] B Rappaport Fac Med Techn, Haifa, Israel.
[Martin, Nicholas G.; Montgomery, Grant W.] Carmel Hosp, Dept Commun Med & Epidemiol, Clalit Hlth Serv Natl Canc Control Ctr, Haifa, Israel.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany.
[Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
[Severi, Gianluca; Baglietto, Laura] Canc Epidemiol Ctr, MCCS, Melbourne, Australia.
[Cox, Angela] Univ Sheffield, Dept Oncol, Fac Med Dent & Hlth, Inst Canc Studies, Sheffield, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Fac Med Dent & Hlth, Sheffield, S Yorkshire, England.
[Miron, Penelope] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab Inst Radioisotopes & Radiodiagno, Athens, Greece.
[Fountzilas, George] Aristotle Univ Thessaloniki, Papageorgiou Hosp, Dept Med Oncol, Thessaloniki, Greece.
[Fountzilas, George] Aristotle Univ Thessaloniki, Papageorgiou Hosp, Dept Med Oncol, Thessaloniki, Greece.
[Fasching, Peter A.] Calif State Univ Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90032 USA.
[Beckmann, Matthias W.] Univers Hosp Erlangen, Dept Gynecol & Obstet, Erlangen, Germany.
[Silva, Isabel dos Santos; Peto, Julian] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, Cancer Res UK Epidemiol & Genet Grp, London WC1, England.
[Lambrechts, Diether] VRC, VIB, Leuven, Belgium.
[Paridaens, Robert] Univ Hosp Leuven, Multidisciplinary Breast Ctr, Leuven, Belgium.
[Ruediger, Thomas] Inst Pathol, Stadt Klinikum Karlsruhe, Karlsruhe, Germany.
[Foersti, Asta] Lund Univ, Ctr Primary Hlth Care Res, Lund, Sweden.
[Winqvist, Robert; Pylkaes, Katri] Univ Oulu, Dept Clin Genet & Biocenter Oulu, Canc Genet Lab, Oulu Univ Hosp, Oulu, Finland.
[Diasio, Robert B.; Lee, Adam M.] Mayo Clin, Dept Pharmacol, Rochester, MN USA.
[Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Gen, Philadelphia, PA 19104 USA.
RP Couch, FJ (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
EM couch.fergus@mayo.edu
RI Spurdle, Amanda/A-4978-2011; BYRSKI, Tomasz/I-2844-2014; Ehrencrona,
Hans/M-5619-2014; Jakubowska, Anna/O-8050-2014; Montgomery,
Grant/B-7148-2008; Gronwald, Jacek/A-4576-2017; manoukian,
siranoush/E-7132-2017; Osorio, Ana/I-4324-2014; Altshuler,
David/A-4476-2009; Arnold, Norbert/E-3012-2010; Toland,
Amanda/E-4202-2011; montagna, marco/E-2225-2012; Verdrengh,
Evelien/H-4571-2012; Fink, Rainer/C-5333-2008; Andrulis,
Irene/E-7267-2013; Sunde, Lone/H-7402-2013; Joseph, Vijai/J-9158-2013;
Hoogerbrugge, Nicoline/O-1016-2013; Radice, Paolo/O-3119-2013; Blanco,
Ignacio/D-2565-2013
OI Kirchhoff, Tomas/0000-0002-9055-2364; Yannoukakos,
Drakoulis/0000-0001-7509-3510; Dunning, Alison
Margaret/0000-0001-6651-7166; Martin, Nicholas/0000-0003-4069-8020;
Evans, Gareth/0000-0002-8482-5784; Ramus, Susan/0000-0003-0005-7798;
Spurdle, Amanda/0000-0003-1337-7897; Barrowdale,
Daniel/0000-0003-1661-3939; Cross, Simon/0000-0003-2044-1754; Sunde,
Lone/0000-0002-8479-165X; Nevanlinna, Heli/0000-0002-0916-2976; dos
Santos Silva, Isabel/0000-0002-6596-8798; Cox,
Angela/0000-0002-5138-1099; Ehrencrona, Hans/0000-0002-5589-3622;
Montgomery, Grant/0000-0002-4140-8139; Gronwald,
Jacek/0000-0002-3643-2871; manoukian, siranoush/0000-0002-6034-7562;
Eeles, Rosalind/0000-0002-3698-6241; Nathanson,
Katherine/0000-0002-6740-0901; Osorio, Ana/0000-0001-8124-3984;
Altshuler, David/0000-0002-7250-4107; Arnold,
Norbert/0000-0003-4523-8808; montagna, marco/0000-0002-4929-2150; Fink,
Rainer/0000-0002-6896-4266; Joseph, Vijai/0000-0002-7933-151X; Blanco,
Ignacio/0000-0002-7414-7481
FU Breast Cancer Research Foundation (BCRF); US National Institutes of
Health [CA128978]; Cancer Research UK
FX Financial support for this study was provided by the Breast Cancer
Research Foundation (BCRF), Susan G. Komen for the Cure and US National
Institutes of Health grant CA128978 to F. J. C. and by Cancer Research
UK to D. F. E. and A. C. A. A. C. A. is a Cancer Research UK Senior
Cancer Research Fellow and D. F. E. is a Cancer Research UK Principal
Research Fellow. The authors thank Cancer Genetic Markers of
Susceptability (CGEMS) and Wellcome Trust Case Control Consortium
(WTCCC) for provision of genotype data from controls. Study specific
acknowledgments listed in Supplementary Note.
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PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD OCT
PY 2010
VL 42
IS 10
BP 885
EP +
DI 10.1038/ng.669
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 655UO
UT WOS:000282276600020
PM 20852631
ER
PT J
AU Jacobelli, J
Friedman, RS
Conti, MA
Lennon-Dumenil, AM
Piel, M
Sorensen, CM
Adelstein, RS
Krummel, MF
AF Jacobelli, Jordan
Friedman, Rachel S.
Conti, Mary Anne
Lennon-Dumenil, Ana-Maria
Piel, Matthieu
Sorensen, Caitlin M.
Adelstein, Robert S.
Krummel, Matthew F.
TI Confinement-optimized three-dimensional T cell amoeboid motility is
modulated via myosin IIA-regulated adhesions
SO NATURE IMMUNOLOGY
LA English
DT Article
ID FIBROBLASTIC RETICULAR CELLS; LYMPH-NODE; LEUKOCYTE MIGRATION; CHAIN;
SPEED; ADHESIVENESS; LYMPHOCYTES; CHEMOTAXIS; MICROSCOPY; LOCOMOTION
AB During trafficking through tissues, T cells fine-tune their motility to balance the extent and duration of cell-surface contacts versus the need to traverse an entire organ. Here we show that in vivo, myosin IIA-deficient T cells had a triad of defects, including overadherence to high-endothelial venules, less interstitial migration and inefficient completion of recirculation through lymph nodes. Spatiotemporal analysis of three-dimensional motility in microchannels showed that the degree of confinement and myosin IIA function, rather than integrin adhesion (as proposed by the haptokinetic model), optimized motility rate. This motility occurred via a myosin IIA-dependent rapid 'walking' mode with multiple small and simultaneous adhesions to the substrate, which prevented spurious and prolonged adhesions. Adhesion discrimination provided by myosin IIA is thus necessary for the optimization of motility through complex tissues.
C1 [Jacobelli, Jordan; Friedman, Rachel S.; Sorensen, Caitlin M.; Krummel, Matthew F.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
[Conti, Mary Anne; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
[Lennon-Dumenil, Ana-Maria; Piel, Matthieu] Inst Curie, Inst Natl Sante Rech Med, U653, Paris, France.
RP Krummel, MF (reprint author), Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
EM matthew.krummel@ucsf.edu
RI piel, matthieu/A-2956-2010; Lennon-Dumenil, Ana-Maria/I-6716-2016;
OI Adelstein, Robert/0000-0002-8683-2144
FU National Institutes of Health [AI52116]; Larry L. Hillblom Foundation
FX We thank P. Beemiller for help with two-photon data analysis with Imaris
and Matlab software; S. Peck for assistance in maintenance of
microscopes; M. Tang (Stanford Microfabrication Center) for Silicon
Masters; S. Jiang for technical assistance with cell sorting; O. Khan
and M. Werner for help with mouse genotyping; M. Heuze for assistance in
setting up the microchannel system; and B. Sauer (Stowers Institute for
Medical Research) for the pBS479 vector. Supported by the National
Institutes of Health (AI52116 to M.F.K.) and the Larry L. Hillblom
Foundation (R.S.F.).
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD OCT
PY 2010
VL 11
IS 10
BP 953
EP U110
DI 10.1038/ni.1936
PG 12
WC Immunology
SC Immunology
GA 651KP
UT WOS:000281926900015
PM 20835229
ER
PT J
AU Lovinger, DM
AF Lovinger, David M.
TI Endocannabinoids rein in pain outside the brain
SO NATURE NEUROSCIENCE
LA English
DT Editorial Material
ID CANNABINOID RECEPTORS; EFFICACY; BLOCKADE; OBESITY
C1 NIAAA, Lab Integrat Neurosci, Bethesda, MD USA.
RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, Bethesda, MD USA.
EM lovindav@mail.nih.gov
NR 12
TC 1
Z9 1
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD OCT
PY 2010
VL 13
IS 10
BP 1155
EP 1156
DI 10.1038/nn1010-1155
PG 2
WC Neurosciences
SC Neurosciences & Neurology
GA 654MB
UT WOS:000282171300003
PM 20877276
ER
PT J
AU Evers, DM
Matta, JA
Hoe, HS
Zarkowsky, D
Lee, SH
Isaac, JT
Pak, DTS
AF Evers, Danielle M.
Matta, Jose A.
Hoe, Hyang-Sook
Zarkowsky, Devin
Lee, Sang Hyoung
Isaac, John T.
Pak, Daniel T. S.
TI Plk2 attachment to NSF induces homeostatic removal of GluA2 during
chronic overexcitation
SO NATURE NEUROSCIENCE
LA English
DT Article
ID AMPA RECEPTOR TRAFFICKING; ETHYLMALEIMIDE-SENSITIVE FACTOR;
DOMAIN-CONTAINING PROTEINS; LONG-TERM POTENTIATION; POLO-LIKE KINASE;
HIPPOCAMPAL-NEURONS; SYNAPTIC-TRANSMISSION; SURFACE EXPRESSION; SUBUNIT
COMPOSITION; BINDING PROTEIN
AB Trafficking of AMPA receptors (AMPARs) is important for many forms of synaptic plasticity. However, the link between activity and resulting synaptic alterations is not fully understood. We identified a direct interaction between N-ethylmaleimide-sensitive fusion protein (NSF), an ATPase involved in membrane fusion events and stabilization of surface AMPARs, and Polo-like kinase-2 (Plk2), an activity-inducible kinase that homeostatically decreases excitatory synapse number and strength. Plk2 disrupted the interaction of NSF with the GluA2 subunit of AMPARs, promoting extensive loss of surface GluA2 in rat hippocampal neurons, greater association of GluA2 with adaptor proteins PICK1 and GRIP1, and decreased synaptic AMPAR current. Plk2 engagement of NSF, but not Plk2 kinase activity, was required for this mechanism and occurred through a motif in the Plk2 protein that was independent of the canonical polo box interaction sites. These data reveal that heightened synaptic activity, acting through Plk2, leads to homeostatic decreases in surface AMPAR expression via the direct dissociation of NSF from GluA2.
C1 [Evers, Danielle M.; Matta, Jose A.; Zarkowsky, Devin; Pak, Daniel T. S.] Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA.
[Matta, Jose A.; Isaac, John T.] NIGMS, NIH, Bethesda, MD USA.
[Hoe, Hyang-Sook] Georgetown Univ, Dept Neurosci, Washington, DC 20007 USA.
[Lee, Sang Hyoung] Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA.
RP Pak, DTS (reprint author), Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA.
EM dtp6@georgetown.edu
FU US National Institutes of Health; National Institute of Neurological
Disorders and Stroke (Biacore Molecular Interactions Shared Resource of
Lombardi Comprehensive Cancer Center) [NS048085, F31NS061467,
P30CA051008]
FX We thank L. Bilello for technical assistance. This work was supported by
US National Institutes of Health and National Institute of Neurological
Disorders and Stroke grants NS048085 (D.T.S.P.), F31NS061467 (D.M.E.)
and P30CA051008 (Biacore Molecular Interactions Shared Resource of
Lombardi Comprehensive Cancer Center).
NR 50
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U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD OCT
PY 2010
VL 13
IS 10
BP 1199
EP 1207
DI 10.1038/nn.2624
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 654MB
UT WOS:000282171300011
PM 20802490
ER
PT J
AU Chittajallu, R
Isaac, JTR
AF Chittajallu, Ramesh
Isaac, John T. R.
TI Emergence of cortical inhibition by coordinated sensory-driven
plasticity at distinct synaptic loci
SO NATURE NEUROSCIENCE
LA English
DT Article
ID RAT BARREL CORTEX; THALAMOCORTICAL FEEDFORWARD INHIBITION; EXCITATORY
NEURONAL NETWORK; FAST-SPIKING INTERNEURONS; RECEPTOR SUBUNIT NR3A;
SPINY STELLATE CELLS; NMDA RECEPTORS; LAYER-IV; SOMATOSENSORY CORTEX;
REGIONAL EXPRESSION
AB Feedforward GABAergic inhibition sets the dendritic integration window, thereby controlling timing and output in cortical circuits. However, the manner in which feedforward inhibitory circuits emerge is unclear, despite this being a critical step for neocortical development and function. We found that sensory experience drove plasticity of the feedforward inhibitory circuit in mouse layer 4 somatosensory barrel cortex in the second postnatal week via two distinct mechanisms. First, sensory experience selectively strengthened thalamocortical-to-feedforward interneuron inputs via a presynaptic mechanism but did not regulate other inhibitory circuit components. Second, experience drove a postsynaptic mechanism in which a downregulation of a prominent thalamocortical NMDA excitatory postsynaptic potential in stellate cells regulated the final expression of functional feedforward inhibitory input. Thus, experience is required for specific, coordinated changes at thalamocortical synapses onto both inhibitory and excitatory neurons, producing a circuit plasticity that results in maturation of functional feedforward inhibition in layer 4.
C1 [Chittajallu, Ramesh; Isaac, John T. R.] NINDS, Dev Synapt Plast Sect, NIH, Bethesda, MD 20892 USA.
RP Chittajallu, R (reprint author), NINDS, Dev Synapt Plast Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM chittajallur@ninds.nih.gov; isaacj@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke
FX We thank C. McBain for discussions and Y. Yanagawa (Gunma University)
for providing GAD67-GFP knockin mouse. This work was supported by the
National Institute of Neurological Disorders and Stroke Intramural
Program.
NR 42
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U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD OCT
PY 2010
VL 13
IS 10
BP 1240
EP 1248
DI 10.1038/nn.2639
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 654MB
UT WOS:000282171300016
PM 20871602
ER
PT J
AU Logothetis, NK
Augath, M
Murayama, Y
Rauch, A
Sultan, F
Goense, J
Oeltermann, A
Merkle, H
AF Logothetis, Nikos K.
Augath, Mark
Murayama, Yusuke
Rauch, Alexander
Sultan, Fahad
Goense, Jozien
Oeltermann, Axel
Merkle, Hellmut
TI The effects of electrical microstimulation on cortical signal
propagation
SO NATURE NEUROSCIENCE
LA English
DT Article
ID TRANSCRANIAL MAGNETIC STIMULATION; CAT VISUAL-CORTEX; FRONTAL EYE FIELD;
STRIATE CORTEX; INTRACORTICAL MICROSTIMULATION; FUNCTIONAL MRI; RAT
NEOCORTEX; MOTOR CORTEX; FMRI SIGNAL; AREA MT
AB Electrical stimulation has been used in animals and humans to study potential causal links between neural activity and specific cognitive functions. Recently, it has found increasing use in electrotherapy and neural prostheses. However, the manner in which electrical stimulation-elicited signals propagate in brain tissues remains unclear. We used combined electrostimulation, neurophysiology, microinjection and functional magnetic resonance imaging (fMRI) to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We found that stimulation of a site in the lateral geniculate nucleus (LGN) increased the fMRI signal in the regions of primary visual cortex (V1) that received input from that site, but suppressed it in the retinotopically matched regions of extrastriate cortex. Consistent with previous observations, intracranial recordings indicated that a short excitatory response occurring immediately after a stimulation pulse was followed by a long-lasting inhibition. Following microinjections of GABA antagonists in V1, LGN stimulation induced positive fMRI signals in all of the cortical areas. Taken together, our findings suggest that electrical stimulation disrupts cortico-cortical signal propagation by silencing the output of any neocortical area whose afferents are electrically stimulated.
C1 [Logothetis, Nikos K.; Augath, Mark; Murayama, Yusuke; Rauch, Alexander; Goense, Jozien; Oeltermann, Axel] Max Planck Inst Biol Cybernet, Tubingen, Germany.
[Logothetis, Nikos K.] Univ Manchester, Manchester, Lancs, England.
[Sultan, Fahad] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Cognit Neurol, Tubingen, Germany.
[Merkle, Hellmut] NINDS, Lab Funct & Mol Imaging, US NIH, Bethesda, MD 20892 USA.
RP Logothetis, NK (reprint author), Max Planck Inst Biol Cybernet, Tubingen, Germany.
EM nikos.logothetis@tuebingen.mpg.de
FU Max Planck Society; German Research Foundation [DFG SFB-A9]; US National
Institutes of Health (National Institute Neurological Disorders and
Stroke)
FX We thank C. Kayser, O. Eschenko and M. Munk for reading the manuscript
and for useful suggestions. Many thanks also go to D. Blaurock for
editing, S. Weber for fine-mechanic work and T. Steudel and P. Douay for
help with the alert monkey experiments. This research was supported by
the Max Planck Society, the German Research Foundation (DFG SFB-A9) and
by the intramural research program of the US National Institutes of
Health (National Institute Neurological Disorders and Stroke, H.M.).
NR 50
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PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD OCT
PY 2010
VL 13
IS 10
BP 1283
EP 1291
DI 10.1038/nn.2631
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 654MB
UT WOS:000282171300022
PM 20818384
ER
PT J
AU Makarova, KS
Yutin, N
Bell, SD
Koonin, EV
AF Makarova, Kira S.
Yutin, Natalya
Bell, Stephen D.
Koonin, Eugene V.
TI Evolution of diverse cell division and vesicle formation systems in
Archaea
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Article
ID SULFOLOBUS-SOLFATARICUS; BACILLUS-SUBTILIS; ESCRT; FTSZ; EUKARYOTES;
ORIGIN; CYTOSKELETON; GENOMICS; PROSTHECOBACTER; CRENARCHAEOTA
AB Recently a novel cell division system comprised of homologues of eukaryotic ESCRT-III (endosomal sorting complex required for transport III) proteins was discovered in the hyperthermophilic crenarchaeote Sulfolobus acidocaldarius. On the basis of this discovery, we undertook a comparative genomic analysis of the machineries for cell division and vesicle formation in Archaea. Archaea possess at least three distinct membrane remodelling systems: the FtsZ-based bacterial-type system, the ESCRT-III-based eukaryote-like system and a putative novel system that uses an archaeal actin-related protein. Many archaeal genomes encode assortments of components from different systems. Evolutionary reconstruction from these findings suggests that the last common ancestor of the extant Archaea possessed a complex membrane remodelling apparatus, different components of which were lost during subsequent evolution of archaeal lineages. By contrast, eukaryotes seem to have inherited all three ancestral systems.
C1 [Makarova, Kira S.; Yutin, Natalya; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Bell, Stephen D.] Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM stephen.bell@path.ox.ac.uk
FU US National Institutes of Health; National Library of Medicine; Edward
Penley Abraham Trust
FX The authors thank Y. Wolf for useful discussions and help with the
preparation of figure 3. The authors' research is supported by the
Intramural Research Program of the US National Institutes of Health,
National Library of Medicine (K.S.M., N.Y. and E.V.K.) and by the Edward
Penley Abraham Trust (S.D.B.).
NR 57
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U1 5
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1740-1526
J9 NAT REV MICROBIOL
JI Nat. Rev. Microbiol.
PD OCT
PY 2010
VL 8
IS 10
BP 731
EP 741
DI 10.1038/nrmicro2406
PG 11
WC Microbiology
SC Microbiology
GA 651EU
UT WOS:000281908700012
PM 20818414
ER
PT J
AU Merino, JG
Warach, S
AF Merino, Jose G.
Warach, Steven
TI Imaging of acute stroke
SO NATURE REVIEWS NEUROLOGY
LA English
DT Review
ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; MIDDLE
CEREBRAL-ARTERY; DIGITAL-SUBTRACTION-ANGIOGRAPHY; NEPHROGENIC SYSTEMIC
FIBROSIS; PERFUSION COMPUTED-TOMOGRAPHY; CONTRAST-INDUCED NEPHROPATHY;
BRAIN-BARRIER DISRUPTION; TRANSCRANIAL DOPPLER ULTRASONOGRAPHY;
PERIPHERAL VASCULAR-DISEASE
AB Brain imaging provides an objective basis for the clinical inferences that direct individual patient management in the acute stroke setting. A brain CT or MRI scan is required for all patients with suspected stroke or transient ischemic attack. Thrombolytic therapy is arguably the most important aspect of acute stroke management; however, most decisions in acute stroke do not relate to this treatment. Stroke imaging must, therefore, provide information beyond the presence or absence of intracranial hemorrhage (ICH) and early evidence of a large infarct. Noncontrast CT and gradient-recalled echo MRI show comparable accuracy in the diagnosis of acute ICH. Diffusion-weighted MRI is more sensitive than noncontrast CT for differentiation of acute ischemic stroke from nonstroke conditions. Combined multimodal parenchymal, perfusion and vascular imaging with CT or MRI has the potential to identify patients with an ischemic penumbra that might be appropriate for acute reperfusion therapies. MRI identifies a broader range of acute and chronic cerebrovascular pathologies than does CT and, hence, could aid decisions about acute intervention, in-hospital management, and secondary prevention. Here, we present an overview of the diagnostic information that clinicians might gain from CT and MRI in the setting of acute stroke, along with the advantages and disadvantages of these techniques.
C1 [Warach, Steven] Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA.
[Merino, Jose G.] Suburban Hosp Stroke Program, Bethesda, MD 20007 USA.
RP Warach, S (reprint author), Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, NIH, Room B1D-733,MSC 1063, Bethesda, MD 20892 USA.
EM warachs@ninds.nih.gov
OI Merino, Jose/0000-0002-6676-0008
FU Division of Intramural Research of the National Institute of
Neurological Disorders and Stroke, NIH
FX This work was supported by the Division of Intramural Research of the
National Institute of Neurological Disorders and Stroke, NIH.
NR 155
TC 38
Z9 40
U1 2
U2 16
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4758
J9 NAT REV NEUROL
JI Nat. Rev. Neurol.
PD OCT
PY 2010
VL 6
IS 10
BP 560
EP 571
DI 10.1038/nrneurol.2010.129
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA 660LB
UT WOS:000282643100008
PM 20842186
ER
PT J
AU Luo, LQ
Rodriguez, E
Jerbi, K
Lachaux, JP
Martinerie, J
Corbetta, M
Shulman, GL
Piomelli, D
Turrigiano, GG
Nelson, SB
Joels, M
de Kloet, ER
Holsboer, F
Amodio, DM
Frith, CD
Block, ML
Zecca, L
Hong, JS
Dantzer, R
Kelley, KW
Craig, AD
AF Luo, Liqun
Rodriguez, Eugenio
Jerbi, Karim
Lachaux, Jean-Philippe
Martinerie, Jacques
Corbetta, Maurizio
Shulman, Gordon L.
Piomelli, Daniele
Turrigiano, Gina G.
Nelson, Sacha B.
Joels, Marian
de Kloet, E. Ronald
Holsboer, Florian
Amodio, David M.
Frith, Chris D.
Block, Michelle L.
Zecca, Luigi
Hong, Jau-Shyong
Dantzer, Robert
Kelley, Keith W.
Craig, A. D. (Bud)
TI Ten years of Nature Reviews Neuroscience: insights from the highly cited
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Article
ID HOMEOSTATIC SYNAPTIC PLASTICITY; GLUCOCORTICOID-RECEPTOR GENE;
STIMULUS-DRIVEN ATTENTION; VISUAL-CORTEX; SPATIAL ATTENTION;
RHO-GTPASES; CANNABINOID RECEPTOR; HUMAN BRAIN; NEURODEGENERATIVE
DISEASE; NEUROLOGICAL DISORDERS
AB To celebrate the first 10 years of Nature Reviews Neuroscience, we invited the authors of the most cited article of each year to look back on the state of their field of research at the time of publication and the impact their article has had, and to discuss the questions that might be answered in the next 10 years. This selection of highly cited articles provides interesting snapshots of the progress that has been made in diverse areas of neuroscience. They show the enormous influence of neuroimaging techniques and highlight concepts that have generated substantial interest in the past decade, such as neuroimmunology, social neuroscience and the 'network approach' to brain function. These advancements will pave the way for further exciting discoveries that lie ahead.
C1 [Luo, Liqun] Stanford Univ, Dept Biol, Howard Hughes Med Inst, Stanford, CA 94305 USA.
[Rodriguez, Eugenio] Pontificia Univ Catolica Chile, Santiago 8940000, Chile.
[Rodriguez, Eugenio] Max Planck Inst Brain Res, D-60528 Frankfurt, Germany.
[Jerbi, Karim; Lachaux, Jean-Philippe] Univ Lyon 1, INSERM, U821, F-69365 Lyon, France.
[Martinerie, Jacques] Univ Paris 06, Hop La Pitie Salpetriere, Ctr Rech Inst Cerveau & Moelle Epiniere, COGIMAGE,CNRS,INSERM,U975, F-75651 Paris, France.
[Corbetta, Maurizio; Shulman, Gordon L.] Washington Univ, Sch Med, St Louis, MO 63110 USA.
[Piomelli, Daniele] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA.
[Piomelli, Daniele] Italian Inst Technol, Unit Drug Discovery & Dev, I-16163 Genoa, Italy.
[Turrigiano, Gina G.; Nelson, Sacha B.] Brandeis Univ, Dept Biol, Waltham, MA 02454 USA.
[Turrigiano, Gina G.; Nelson, Sacha B.] Brandeis Univ, Natl Ctr Behav Genom, Waltham, MA 02454 USA.
[Joels, Marian] UMC Utrecht, Div Neurosci, Rudolf Magnus Inst, Dept Neurosci & Pharmacol, NL-3584 CG Utrecht, Netherlands.
[de Kloet, E. Ronald] LUMC, Leiden Amsterdam Ctr Drug Res, Dept Med Pharmacol, NL-2300 RA Leiden, Netherlands.
[Holsboer, Florian] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Amodio, David M.] New York Univ, Dept Psychol, New York, NY 10003 USA.
[Amodio, David M.] New York Univ, Ctr Neural Sci, New York, NY 10003 USA.
[Frith, Chris D.] Aarhus Univ, Aarhus Univ Hosp, Ctr Functionally Integrat Neurosci, DK-8000 Aarhus C, Denmark.
[Frith, Chris D.] UCL, Wellcome Trust Ctr Neuroimaging, London WC1N 3BG, England.
[Block, Michelle L.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA.
[Zecca, Luigi] Italian Natl Res Council, Inst Biomed Technol, I-20090 Milan, Italy.
[Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, NIH Res Triangle Pk, Res Triangle Pk, NC 27709 USA.
[Dantzer, Robert; Kelley, Keith W.] Univ Illinois, Integrat Immunol & Behav Program, Dept Anim Sci, Coll Agr Consumer & Environm Sci, Urbana, IL 61801 USA.
[Dantzer, Robert; Kelley, Keith W.] Univ Illinois, Coll Med, Dept Pathol, Urbana, IL 61801 USA.
[Craig, A. D. (Bud)] Barrow Neurol Inst, Atkinson Res Lab, Phoenix, AZ 85013 USA.
RP Luo, LQ (reprint author), Stanford Univ, Dept Biol, Howard Hughes Med Inst, Stanford, CA 94305 USA.
RI Frith, Chris/A-2171-2009; Frank, David/E-8213-2012; Joels,
Marian/P-6415-2016;
OI Frith, Chris/0000-0002-8665-0690; Nelson, Sacha/0000-0002-0108-8599;
Kelley, Keith W./0000-0002-6837-8793; Dantzer,
Robert/0000-0001-9399-6107
FU National Institutes of Health (NIH); Howard Hughes Medical Institute;
Comision Nacional de Investigacion Cientifica y Tecnologica; Deutscher
Akademischer Austauschdienst; Fondation pour la Recherche Medicale;
European Project [HEALTH-F2-2008-200728]; National Institute on Drug
Abuse; National Alliance for Research on Schizophrenia and Depression;
Royal Academy of Arts and Sciences (KNAW); American National Science
Foundation [BCS 0847350]; Danish National Research Foundation; National
Institute of Environmental Health Sciences (NIEHS)/NIH [R01ES016951];
Lombardia Region Department of Industry; NIEHS; NIH [R01 AG 029573, R01
MH 079829]
FX L. L. thanks support from the National Institutes of Health (NIH) and
the Howard Hughes Medical Institute. E. R. was partly supported by the
Comision Nacional de Investigacion Cientifica y Tecnologica and the
Deutscher Akademischer Austauschdienst. K.J. and J.P.L. were partly
supported by the Fondation pour la Recherche Medicale and by the
BrainSync FP7 European Project (grant HEALTH-F2-2008-200728). M. C. and
G. L. S. thank S. Astafiev for assistance with figure 1. D. P.
gratefully acknowledges support from the National Institute on Drug
Abuse and the National Alliance for Research on Schizophrenia and
Depression. G. G. T. and S.B.N. thank all members of their laboratories,
past and present, as well as the many colleagues and collaborators who
have contributed to the genesis of their ideas. E.R.d.K. gratefully
acknowledges the support of the Royal Academy of Arts and Sciences
(KNAW). D. M. A. is supported by grant BCS 0847350 from the American
National Science Foundation and C. D. F. is supported by the Danish
National Research Foundation. M. L. B. was supported by the National
Institute of Environmental Health Sciences (NIEHS)/NIH Outstanding New
Environmental Scientist Award (grant R01ES016951). L.Z. was supported by
the Lombardia Region Department of Industry, Project Metadistretti.
J.-S. H was partly funded by the Intramural Research Program of the
NIEHS (part of the NIH). K. W. K. is supported by the NIH (grant R01 AG
029573) and R. D. is supported by the NIH (grant R01 MH 079829). A. D.
C. is grateful to the James S. McDonnell Foundation and to the Barrow
Neurological Foundation.
NR 116
TC 16
Z9 16
U1 1
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-003X
J9 NAT REV NEUROSCI
JI Nat. Rev. Neurosci.
PD OCT
PY 2010
VL 11
IS 10
BP 718
EP +
DI 10.1038/nrn2912
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 651LF
UT WOS:000281928500005
PM 20852655
ER
PT J
AU Tu, XY
Das, K
Han, QW
Bauman, JD
Clark, AD
Hou, XR
Frenkel, YV
Gaffney, BL
Jones, RA
Boyer, PL
Hughes, SH
Sarafianos, SG
Arnold, E
AF Tu, Xiongying
Das, Kalyan
Han, Qianwei
Bauman, Joseph D.
Clark, Arthur D., Jr.
Hou, Xiaorong
Frenkel, Yulia V.
Gaffney, Barbara L.
Jones, Roger A.
Boyer, Paul L.
Hughes, Stephen H.
Sarafianos, Stefan G.
Arnold, Eddy
TI Structural basis of HIV-1 resistance to AZT by excision
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 REVERSE-TRANSCRIPTASE; HIGH-LEVEL
RESISTANCE; ATP-MEDIATED EXCISION; IN-VIVO MUTATION; PRIMER-UNBLOCKING;
3'-AZIDO-3'-DEOXYTHYMIDINE AZT; MOLECULAR-MECHANISMS; ANGSTROM
RESOLUTION; CRYSTAL-STRUCTURE
AB Human immunodeficiency virus (HIV-1) develops resistance to 3'-azido-2',3'-deoxythymidine (AZT, zidovudine) by acquiring mutations in reverse transcriptase that enhance the ATP-mediated excision of AZT monophosphate from the 3' end of the primer. The excision reaction occurs at the dNTP-binding site, uses ATP as a pyrophosphate donor, unblocks the primer terminus and allows reverse transcriptase to continue viral DNA synthesis. The excision product is AZT adenosine dinucleoside tetraphosphate ( AZTppppA). We determined five crystal structures: wild-type reverse transcriptase-double-stranded DNA (RT-dsDNA)-AZTppppA; AZT-resistant (AZTr; M41L D67N K70R T215Y K219Q) RT-dsDNA-AZTppppA; AZTr RT-dsDNA terminated with AZT at dNTP-and primer-binding sites; and AZTr apo reverse transcriptase. The AMP part of AZTppppA bound differently to wild-type and AZTr reverse transcriptases, whereas the AZT triphosphate part bound the two enzymes similarly. Thus, the resistance mutations create a high-affinity ATP-binding site. The structure of the site provides an opportunity to design inhibitors of AZT-monophosphate excision.
C1 [Tu, Xiongying; Das, Kalyan; Bauman, Joseph D.; Clark, Arthur D., Jr.; Frenkel, Yulia V.; Sarafianos, Stefan G.; Arnold, Eddy] Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
[Tu, Xiongying; Das, Kalyan; Han, Qianwei; Bauman, Joseph D.; Clark, Arthur D., Jr.; Hou, Xiaorong; Frenkel, Yulia V.; Gaffney, Barbara L.; Jones, Roger A.; Sarafianos, Stefan G.; Arnold, Eddy] Rutgers State Univ, Dept Chem & Biol, Piscataway, NJ 08854 USA.
[Boyer, Paul L.; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
RP Arnold, E (reprint author), Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
EM arnold@cabm.rutgers.edu
RI Tu, Xiongying/H-7983-2012;
OI Sarafianos, Stefan G/0000-0002-5840-154X
FU US National Institutes of Health (NIH) [AI 27690, P01 GM 066671]; US
National Cancer Institute (NCI); Center for Cancer Research; US National
Institute of General Medical Sciences
FX We acknowledge personnel at the Cornell High Energy Synchrotron Source
and the Advanced Photon Source for support of data collection, the
members of our laboratories, including R. Bandwar and S. Martinez, for
valuable conversations and assistance, and P. Clark for assistance with
protein preparation. We are grateful to the US National Institutes of
Health (NIH; grants R37 MERIT Award AI 27690 to E.A. and P01 GM 066671
to E.A. and R.A.J.) for support of reverse transcriptase structural
studies. S. H. H. was supported by the Intramural Research Program of
NIH, US National Cancer Institute (NCI), Center for Cancer Research and
US National Institute of General Medical Sciences. This research was
supported, in part, by the Intramural Research Program of the NIH, NCI,
Center for Cancer Research.
NR 60
TC 59
Z9 60
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD OCT
PY 2010
VL 17
IS 10
BP 1202
EP +
DI 10.1038/nsmb.1908
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 659JU
UT WOS:000282563600009
PM 20852643
ER
PT J
AU Soderblom, C
Stadler, J
Jupille, H
Blackstone, C
Shupliakov, O
Hanna, MC
AF Soderblom, Cynthia
Stadler, Julia
Jupille, Henri
Blackstone, Craig
Shupliakov, Oleg
Hanna, Michael C.
TI Targeted disruption of the Mast syndrome gene SPG21 in mice impairs hind
limb function and alters axon branching in cultured cortical neurons
SO NEUROGENETICS
LA English
DT Article
DE Maspardin; ACP33; CD4; Hereditary spastic paraplegia; Rab7
ID HEREDITARY SPASTIC PARAPLEGIA; MUTATIONS; DISEASE; ELONGATION;
NEUROPATHY; DEMENTIA; ATLASTIN; FORM
AB Mast syndrome (SPG21) is a childhood-onset, autosomal recessive, complicated form of hereditary spastic paraplegia (HSP) characterized by dementia, thin corpus callosum, white matter abnormalities, and cerebellar and extrapyramidal signs in addition to spastic paraparesis. A nucleotide insertion resulting in premature truncation of the SPG21 gene product maspardin underlies this disorder, likely leading to loss of protein function. In this study, we generated SPG21-/- knockout mice by homologous recombination as a possible animal model for SPG21. Though SPG21-/- mice appeared normal at birth, within several months they developed gradually progressive hind limb dysfunction. Cerebral cortical neurons cultured from SPG21-/- mice exhibited significantly more axonal branching than neurons from wild-type animals, while comprehensive neuropathological analysis of SPG21-/- mice did not reveal definitive abnormalities. Since alterations in axon branching have been seen in neurons derived from animal models of other forms of HSP as well as motor neuron diseases, this may represent a common cellular pathogenic theme.
C1 [Hanna, Michael C.] Texas A&M Univ, Dept Biol & Environm Sci, Commerce, TX 75428 USA.
[Soderblom, Cynthia] Karolinska Inst, Natl Inst Hlth, Grad Partnerships Program, S-17177 Stockholm, Sweden.
[Soderblom, Cynthia; Shupliakov, Oleg] Karolinska Inst, DBRM, Dept Neurosci, S-17177 Stockholm, Sweden.
[Soderblom, Cynthia; Stadler, Julia; Jupille, Henri; Blackstone, Craig; Hanna, Michael C.] NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
RP Hanna, MC (reprint author), Texas A&M Univ, Dept Biol & Environm Sci, Commerce, TX 75428 USA.
EM michael_hanna@tamu-commerce.edu
OI Shupliakov, Oleg/0000-0001-5352-6848
FU National Institute of Neurological Disorders and Stroke, National
Institutes of Health; National Institute of General Medical Sciences;
Swedish Research Council [13473, 20587]
FX The authors wish to thank James Nagle and Debbie Kauffman (NINDS DNA
Sequencing Facility) for DNA sequencing and Dr. Peng-Peng Zhu for
generation of the phylogenetic tree. This work was supported by the
Intramural Research Program of the National Institute of Neurological
Disorders and Stroke, National Institutes of Health [to C. S., J.S.,
H.J., C. B, and M. C. H.], the National Institute of General Medical
Sciences Pharmacology Research Associate (PRAT) Program and the Swedish
Research Council [grant numbers 13473, 20587 to O.S.].
NR 30
TC 11
Z9 13
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1364-6745
J9 NEUROGENETICS
JI Neurogenetics
PD OCT
PY 2010
VL 11
IS 4
BP 369
EP 378
DI 10.1007/s10048-010-0252-7
PG 10
WC Genetics & Heredity; Clinical Neurology
SC Genetics & Heredity; Neurosciences & Neurology
GA 654QN
UT WOS:000282183200001
PM 20661613
ER
PT J
AU Thambisetty, M
Wan, J
Carass, A
An, Y
Prince, JL
Resnick, SM
AF Thambisetty, Madhav
Wan, Jing
Carass, Aaron
An, Yang
Prince, Jerry L.
Resnick, Susan M.
TI Longitudinal changes in cortical thickness associated with normal aging
SO NEUROIMAGE
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; IMPLICIT SURFACE EVOLUTION; BRAIN VOLUME
CHANGES; ALZHEIMERS-DISEASE; ENTORHINAL CORTEX; CEREBRAL-CORTEX;
OLDER-ADULTS; IN-VIVO; PATTERN-CLASSIFICATION; SEX-DIFFERENCES
AB Imaging studies of anatomic changes in regional gray matter volumes and cortical thickness have documented age effects in many brain regions, but the majority of such studies have been cross-sectional investigations of individuals studied at a single point in time. In this study, using serial imaging assessments of participants in the Baltimore Longitudinal Study of Aging (BLSA), we investigate longitudinal changes in cortical thickness during aging in a cohort of 66 older adults (mean age 68.78; sd. 6.6; range 60-84 at baseline) without dementia. We used the Cortical Reconstruction Using Implicit Surface Evolution CRUISE suite of algorithms to automatically generate a reconstruction of the cortical surface and identified twenty gyral based regions of interest per hemisphere. Using mixed effects regression, we investigated longitudinal changes in these regions over a mean follow-up interval of 8 years. The main finding in this study is that age-related decline in cortical thickness is widespread, but shows an anterior posterior gradient with frontal and parietal regions, in general, exhibiting greater rates of decline than temporal and occipital. There were fewer regions in the right hemisphere showing statistically significant age-associated longitudinal decreases in mean cortical thickness. Males showed greater rates of decline in the middle frontal, inferior parietal, parahippocampal, postcentral, and superior temporal gyri in the left hemisphere, right precuneus and bilaterally in the superior parietal and cingulate regions. Significant nonlinear changes over time were observed in the postcentral, precentral, and orbitofrontal gyri on the left and inferior parietal, cingulate, and orbitofrontal gyri on the right. Published by Elsevier Inc.
C1 [Thambisetty, Madhav] NIA, Biomed Res Ctr, Lab Personal & Cognit, Baltimore, MD 21224 USA.
[Wan, Jing; Carass, Aaron; Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA.
RP Thambisetty, M (reprint author), NIA, Biomed Res Ctr, Lab Personal & Cognit, 04B311,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM thambisettym@mail.nih.gov
RI Prince, Jerry/A-3281-2010;
OI Prince, Jerry/0000-0002-6553-0876; Carass, Aaron/0000-0003-4939-5085
FU NIH, National Institute on Aging; National Institute of Neurological
Disorders and Stroke (NINDS), National Institute of Health (NIH)
[R01-NS37747, RO1-AG016324, R01-NS054255, R01 NS052585-01]; NCRR
[P41-RR14075, R01 RR16594-01A1]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging. Partial support was provided by
the National Institute of Neurological Disorders and Stroke (NINDS), a
part of the National Institute of Health (NIH), through grants
R01-NS37747, RO1-AG016324 and R01-NS054255. The authors have no known
conflicts of interest. The atlas data was provided by Dr. Bruce Fischl,
Martinos Center for Biomedical Imaging, and supported by the NCRR
through grants P41-RR14075 and R01 RR16594-01A1 and by the NIH/NINDS
through grant R01 NS052585-01. We are grateful to the BLSA participants
and neuroimaging staff
NR 66
TC 88
Z9 88
U1 1
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD OCT 1
PY 2010
VL 52
IS 4
BP 1215
EP 1223
DI 10.1016/j.neuroimage.2010.04.258
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 635YY
UT WOS:000280695200009
PM 20441796
ER
PT J
AU Shin, WY
Geng, XJ
Gu, H
Zhan, W
Zou, QH
Yang, YH
AF Shin, Wanyong
Geng, Xiujuan
Gu, Hong
Zhan, Wang
Zou, Qihong
Yang, Yihong
TI Automated brain tissue segmentation based on fractional signal mapping
from inversion recovery Look-Locker acquisition
SO NEUROIMAGE
LA English
DT Article
DE Magnetic resonance imaging; Automated segmentation; Brain tissue;
Partial volume effect; Fractional volume; Fast T1 mapping
ID MAGNETIC-RESONANCE IMAGES; WHITE-MATTER; MR-IMAGES; CEREBROSPINAL-FLUID;
FUZZY CLASSIFIERS; RELAXATION-TIMES; GRAY-MATTER; VOLUME;
CLASSIFICATION; QUANTIFICATION
AB Most current automated segmentation methods are performed on T(1)- or T(2)-weighted MR images, relying on relative image intensity that is dependent on other MR parameters and sensitive to B(1) magnetic field inhomogeneity. Here, we propose an image segmentation method based on quantitative longitudinal magnetization relaxation time (T(1)) of brain tissues. Considering the partial volume effect, fractional volume maps of brain tissues (white matter, gray matter, and cerebrospinal fluid) were obtained by fitting the observed signal in an inversion recovery procedure to a linear combination of three exponential functions, which represents the relaxations of each of the tissue types. A Look-Locker acquisition was employed to accelerate the acquisition process. The feasibility and efficacy of this proposed method were evaluated using simulations and experiments. The potential applications of this method in the study of neurological disease as well as normal brain development and aging are discussed. Published by Elsevier Inc.
C1 [Shin, Wanyong; Geng, Xiujuan; Gu, Hong; Zou, Qihong; Yang, Yihong] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA.
[Zhan, Wang] Univ Calif San Francisco, Dept Radiol, VA Med Ctr, San Francisco, CA 94121 USA.
RP Shin, WY (reprint author), NIDA, Neuroimaging Res Branch, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM shinwa@nida.nih.gov; yihongyang@intra.nida.nih.gov
RI Geng, Xiujuan/I-3852-2012
FU National Institute on Drug Abuse (NIDA), National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute on Drug Abuse (NIDA), National Institutes of Health.
The authors would like to thank Dr. Thomas Ross and Dr. Annabelle
Belcher of the NIDA for his helpful discussions and suggestions, and Dr.
Leon Axel for suggesting the validation of FRASIER using the
down-sampling approach.
NR 35
TC 7
Z9 7
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 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD OCT 1
PY 2010
VL 52
IS 4
BP 1347
EP 1354
DI 10.1016/j.neuroimage.2010.05.001
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 635YY
UT WOS:000280695200023
PM 20452444
ER
PT J
AU Green, S
Ralph, MAL
Moll, J
Stamatakis, EA
Grafman, J
Zahn, R
AF Green, Sophie
Ralph, Matthew A. Lambon
Moll, Jorge
Stamatakis, Emmanuel A.
Grafman, Jordan
Zahn, Roland
TI Selective functional integration between anterior temporal and distinct
fronto-mesolimbic regions during guilt and indignation
SO NEUROIMAGE
LA English
DT Article
DE Moral emotions; fMRI; Psychophysiological interaction; Anterior temporal
lobe; Subgenual cingulate cortex; Septal region; Orbitofrontal cortex;
Semantics; Guilt; Indignation; Anger; Major depression
ID FRONTOTEMPORAL LOBAR DEGENERATION; SEMANTIC DEMENTIA; HUMAN BRAIN;
CINGULATE CORTEX; NEURAL BASIS; ORBITOFRONTAL CORTEX; MORAL COGNITION;
FMRI; MEMORY; MRI
AB It has been hypothesized that the experience of different moral sentiments such as guilt and indignation is underpinned by activation in temporal and fronto-mesolimbic regions and that functional integration between these regions is necessary for the differentiated experience of these moral sentiments. A recent fMRI study revealed that the right superior anterior temporal lobe (ATL) was activated irrespective of the context of moral feelings (guilt or indignation). This region has been associated with context-independent conceptual social knowledge which allows us to make fine-grained differentiations between qualities of social behaviours (e.g. "critical" and "faultfinding"). This knowledge is required to make emotional evaluations of social behaviour. In contrast to the context-independent activation of the ATL, there were context-dependent activations within different fronto-mesolimbic regions for guilt and indignation. However, it is unknown whether functional integration occurs between these regions and whether regional patterns of integration are distinctive for the experience of different moral sentiments. Here, we used fMRI and psychophysiological interaction analysis, an established measure of functional integration to investigate this issue. We found selective functional integration between the right superior ATL and a subgenual cingulate region during the experience of guilt and between the right superior ATL and the lateral orbitofrontal cortex for indignation. Our data provide the first evidence for functional integration of conceptual social knowledge representations in the right superior ATL with representations of different feeling contexts in fronto-mesolimbic regions. We speculate that this functional architecture allows for the conceptually differentiated experience of moral sentiments in healthy individuals. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Green, Sophie; Ralph, Matthew A. Lambon; Zahn, Roland] Univ Manchester, Sch Psychol Sci, Neurosci & Aphasia Res Unit, Manchester M13 9PL, Lancs, England.
[Moll, Jorge] DOr Inst Res & Educ IDOR, Cognit & Behav Neurosci Unit, BR-22280080 Rio De Janeiro, Brazil.
[Grafman, Jordan; Zahn, Roland] NINDS, NIH, Cognit Neurosci Sect, Bethesda, MD 20892 USA.
[Stamatakis, Emmanuel A.] Univ Cambridge, Sch Clin Med, Div Anaesthesia, Cambridge, England.
RP Zahn, R (reprint author), Univ Manchester, Sch Psychol Sci, Neurosci & Aphasia Res Unit, Manchester M13 9PL, Lancs, England.
EM roland.zahn@manchester.ac.uk
RI Zahn, Roland/C-4665-2008; Moll, Jorge/B-2654-2013; Neurociencia,
Inct/I-1011-2013; Lambon Ralph, Matthew/A-1695-2009;
OI Zahn, Roland/0000-0002-8447-1453; Lambon Ralph,
Matthew/0000-0001-5907-2488; Moll, Jorge/0000-0002-4297-591X; Grafman,
Jordan H./0000-0001-8645-4457
FU NINDS (USA); Federal Ministry of Education and Research [BMBF-LPD
9901/8-122]; MRC; Faculty of Medical and Human Sciences, The University
of Manchester, UK; LABS-D'Or Hospital Network, Rio de Janeiro, Brazil;
Queens' College, Cambridge, UK
FX This study was supported by NINDS (USA) intramural funding to J.G. and a
German National Academy of Sciences Leopoldina Fellowship funded by the
Federal Ministry of Education and Research (BMBF-LPD 9901/8-122) to R.Z.
S.G. was funded by an MRC PhD studentship. R.Z. was supported by a
Stepping Stones Fellowship from the Faculty of Medical and Human
Sciences, The University of Manchester, UK. J.M. was supported by the
LABS-D'Or Hospital Network, Rio de Janeiro, Brazil. E.A.S. was funded by
a Stephen Erskine Fellowship, Queens' College, Cambridge, UK.
NR 71
TC 23
Z9 23
U1 2
U2 16
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD OCT 1
PY 2010
VL 52
IS 4
BP 1720
EP 1726
DI 10.1016/j.neuroimage.2010.05.038
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 635YY
UT WOS:000280695200060
PM 20493953
ER
PT J
AU Cheng, J
Zhou, XB
Miller, EL
Alvarez, VA
Sabatini, BL
Wong, STC
AF Cheng, Jie
Zhou, Xiaobo
Miller, Eric L.
Alvarez, Veronica A.
Sabatini, Bernardo L.
Wong, Stephen T. C.
TI Oriented Markov Random Field Based Dendritic Spine Segmentation for
Fluorescence Microscopy Images
SO NEUROINFORMATICS
LA English
DT Article
DE Dendritic spine; Segmentation; Automatic detection; Microscopy image
ID FUNCTIONAL MRI DATA; DISORDERS; ALGORITHM
AB Dendritic spines have been shown to be closely related to various functional properties of the neuron. Usually dendritic spines are manually labeled to analyze their morphological changes, which is very time-consuming and susceptible to operator bias, even with the assistance of computers. To deal with these issues, several methods have been recently proposed to automatically detect and measure the dendritic spines with little human interaction. However, problems such as degraded detection performance for images with larger pixel size (e.g. 0.125 mu m/pixel instead of 0.08 mu m/pixel) still exist in these methods. Moreover, the shapes of detected spines are also distorted. For example, the "necks" of some spines are missed. Here we present an oriented Markov random field (OMRF) based algorithm which improves spine detection as well as their geometric characterization. We begin with the identification of a region of interest (ROI) containing all the dendrites and spines to be analyzed. For this purpose, we introduce an adaptive procedure for identifying the image background. Next, the OMRF model is discussed within a statistical framework and the segmentation is solved as a maximum a posteriori estimation (MAP) problem, whose optimal solution is found by a knowledge-guided iterative conditional mode (KICM) algorithm. Compared with the existing algorithms, the proposed algorithm not only provides a more accurate representation of the spine shape, but also improves the detection performance by more than 50% with regard to reducing both the misses and false detection.
C1 [Cheng, Jie; Zhou, Xiaobo; Wong, Stephen T. C.] Methodist Hosp, Res Inst, Ctr Bioengn & Informat, Houston, TX 77030 USA.
[Cheng, Jie; Zhou, Xiaobo; Wong, Stephen T. C.] Methodist Hosp, Dept Radiol, Weill Cornell Med Coll, Houston, TX 77030 USA.
[Alvarez, Veronica A.] NIAAA, SNS, LIN, NIH, Bethesda, MD 20892 USA.
[Sabatini, Bernardo L.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Miller, Eric L.] Tufts Univ, Dept Elect & Comp Engn, Medford, MA 02155 USA.
RP Wong, STC (reprint author), Methodist Hosp, Res Inst, Ctr Bioengn & Informat, Houston, TX 77030 USA.
EM stwong@tmhs.org
RI Miller, Eric/B-2546-2008; Cheng, Jie/F-6855-2013; Alvarez, Veronica
/E-9745-2015
OI Miller, Eric/0000-0002-3156-6002; Cheng, Jie/0000-0003-4471-9087;
Alvarez, Veronica /0000-0003-2611-8675
FU NIH [R01 LM008696]
FX The testing images and manual results are provided by Bernardo L.
Sabatini's lab. Thanks Dr. Fuhai Li for help testing the codes. This
research is funded by a NIH R01 LM008696 Grant to STCW. Finally, the
authors want to thank the reviewers for their many helpful comments.
NR 31
TC 1
Z9 1
U1 0
U2 4
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1539-2791
EI 1559-0089
J9 NEUROINFORMATICS
JI Neuroinformatics
PD OCT
PY 2010
VL 8
IS 3
BP 157
EP 170
DI 10.1007/s12021-010-9073-y
PG 14
WC Computer Science, Interdisciplinary Applications; Neurosciences
SC Computer Science; Neurosciences & Neurology
GA 655AH
UT WOS:000282212500003
PM 20585900
ER
PT J
AU Bonnemann, CG
AF Bonnemann, C. G.
TI Molecular therapeutic approaches to the extracellular matrix-related
congenital muscular dystrophies
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 15th International Congress of the World-Muscle-Society
CY OCT 12-16, 2010
CL Kumamoto, JAPAN
SP World Muscle Soc
C1 [Bonnemann, C. G.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
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 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2010
VL 20
IS 9-10
BP 597
EP 597
DI 10.1016/j.nmd.2010.07.009
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 659JO
UT WOS:000282563000005
ER
PT J
AU Yardeni, T
Manoli, I
Ciccone, C
Hoogstraten-Miller, S
Darvish, D
Anikster, Y
Maples, P
Jay, CM
Gahl, WA
Nemunaitis, J
Huizing, M
AF Yardeni, T.
Manoli, I.
Ciccone, C.
Hoogstraten-Miller, S.
Darvish, D.
Anikster, Y.
Maples, P.
Jay, C. M.
Gahl, W. A.
Nemunaitis, J.
Huizing, M.
TI A non-viral, GNE-lipoplex treatment to correct sialylation defects in
hereditary inclusion body myopathy (HIBM)
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 15th International Congress of the World-Muscle-Society
CY OCT 12-16, 2010
CL Kumamoto, JAPAN
SP World Muscle Soc
C1 [Hoogstraten-Miller, S.] NHGRI, NIH, OLAM, Bethesda, MD 20892 USA.
[Darvish, D.] HIBM Res Grp, Encino, NM USA.
[Anikster, Y.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Maples, P.; Jay, C. M.; Nemunaitis, J.] Gradalis Inc, Dallas, TX USA.
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 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2010
VL 20
IS 9-10
BP 620
EP 621
DI 10.1016/j.nmd.2010.07.081
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 659JO
UT WOS:000282563000077
ER
PT J
AU Olive, M
Odgerel, Z
Martinez, A
Poza, JJ
Garcia-Bragado, F
Jerico, I
Maravi, E
Ramos-Arroyo, M
Gonzalez-Mera, L
Goldfarb, LG
AF Olive, M.
Odgerel, Z.
Martinez, A.
Poza, J. J.
Garcia-Bragado, F.
Jerico, I.
Maravi, E.
Ramos-Arroyo, M.
Gonzalez-Mera, L.
Goldfarb, L. G.
TI Intranuclear rods in three Spanish families with ZASPopathy
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 15th International Congress of the World-Muscle-Society
CY OCT 12-16, 2010
CL Kumamoto, JAPAN
SP World Muscle Soc
C1 [Olive, M.; Martinez, A.; Gonzalez-Mera, L.] IDIBELL Bellvitge Hosp, Inst Neuropathol, Barcelona, Spain.
[Olive, M.] Hosp Llobregat, Neuromuscular Unit, Barcelona, Spain.
[Odgerel, Z.; Goldfarb, L. G.] NINDS, NIH, Bethesda, MD 20892 USA.
[Martinez, A.; Gonzalez-Mera, L.] IDIBELL Hosp Bellvitge, Neuromuscular Unit, Barcelona, Spain.
[Poza, J. J.] Hosp Donostia, San Sebastian, Spain.
[Garcia-Bragado, F.; Jerico, I.; Maravi, E.; Ramos-Arroyo, M.] Hosp Virgen Camino, Pamplona, Spain.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2010
VL 20
IS 9-10
BP 623
EP 623
DI 10.1016/j.nmd.2010.07.089
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 659JO
UT WOS:000282563000085
ER
PT J
AU Sambuughin, N
Kyle, SY
Olive, M
Duff, RM
Bayarsaikhan, M
Sivadorai, P
Nowak, KJ
Mastaglia, FL
North, K
Ilkovski, B
van Engelen, B
Lamont, P
Davis, MR
Laing, NG
Goldfarb, LG
AF Sambuughin, N.
Kyle, S. Y.
Olive, M.
Duff, R. M.
Bayarsaikhan, M.
Sivadorai, P.
Nowak, K. J.
Mastaglia, F. L.
North, K.
Ilkovski, B.
van Engelen, B.
Lamont, P.
Davis, M. R.
Laing, N. G.
Goldfarb, L. G.
TI A new member of the BTB/Kelch family of proteins is mutated in nemaline
myopathy type 6 (NEM6)
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 15th International Congress of the World-Muscle-Society
CY OCT 12-16, 2010
CL Kumamoto, JAPAN
SP World Muscle Soc
C1 [Sambuughin, N.; Bayarsaikhan, M.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Kyle, S. Y.; Duff, R. M.; Nowak, K. J.; Mastaglia, F. L.; Laing, N. G.] Univ Western Australia, Perth, WA 6009, Australia.
[Olive, M.] Inst Neuropatol, Barcelona, Spain.
[Sivadorai, P.; Lamont, P.; Davis, M. R.] Royal Perth Hosp, Perth, WA, Australia.
[North, K.; Ilkovski, B.] Childrens Hosp Westmead, Sydney, NSW, Australia.
[van Engelen, B.] Radboud Univ Nijmegen, Nijmegen Med Ctr, Nijmegen, Netherlands.
[Goldfarb, L. G.] NIH, Bethesda, MD 20892 USA.
RI van Engelen, Baziel/D-3475-2009; Engelen, B.G.M./H-8027-2014
NR 0
TC 1
Z9 1
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2010
VL 20
IS 9-10
BP 638
EP 638
DI 10.1016/j.nmd.2010.07.134
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 659JO
UT WOS:000282563000130
ER
PT J
AU Guglieri, M
Herr, B
McColl, E
Eagle, M
Pandya, S
McDermott, M
Tawil, R
Martens, W
Annis, C
Hirtz, D
Kirschner, J
Korinthenberg, R
Hart, K
Brown, M
Rafferty, K
Griggs, R
Bushby, K
AF Guglieri, M.
Herr, B.
McColl, E.
Eagle, M.
Pandya, S.
McDermott, M.
Tawil, R.
Martens, W.
Annis, C.
Hirtz, D.
Kirschner, J.
Korinthenberg, R.
Hart, K.
Brown, M.
Rafferty, K.
Griggs, R.
Bushby, K.
TI FOR-DMD: double-blind randomized trial to optimize steroid regime in
Duchenne Muscular Dystrophy (DMD)
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 15th International Congress of the World-Muscle-Society
CY OCT 12-16, 2010
CL Kumamoto, JAPAN
SP World Muscle Soc
C1 [Guglieri, M.] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Herr, B.; Pandya, S.; McDermott, M.; Tawil, R.; Martens, W.; Annis, C.; Hart, K.; Brown, M.; Griggs, R.] Univ Rochester, Sch Med & Dent, Rochester, NY 14627 USA.
[Hirtz, D.] Natl Inst Neurol Disorders & Storke, NIH, Bethesda, MD 20892 USA.
[Kirschner, J.; Korinthenberg, R.] Univ Freiburg, Freiburg, Germany.
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 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2010
VL 20
IS 9-10
BP 657
EP 657
DI 10.1016/j.nmd.2010.07.194
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 659JO
UT WOS:000282563000190
ER
PT J
AU Keil, A
Bradley, MM
Ihssen, N
Heim, S
Vila, J
Guerra, P
Lang, PJ
AF Keil, Andreas
Bradley, Margaret M.
Ihssen, Niklas
Heim, Sabine
Vila, Jaime
Guerra, Pedro
Lang, Peter J.
TI Defensive engagement and perceptual enhancement
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Human; Dense array EEG; Cardiac defense; Emotion; Steady state potential
ID MOTIVATED ATTENTION; CARDIAC DEFENSE; VISUAL-CORTEX; HEART-RATE;
EMOTION; BRAIN; FEAR
AB We tested whether visual cortical sensitivity to external cues in the context of an acute defensive reaction is heightened or attenuated A strong cardiac defense (fear) response was elicited by presenting an abrupt loud acoustic stimulus following a 10-min period of quiescence Electrocortical responses to aversive and neutral pictures following defensive stimulus onset were measured using dense-array EEG Pictures were flickered at 12 5 Hz to evoke steady-state visual evoked potentials (ssVEP) which can be reliably extracted on the basis of single trials Visual cortical activity indexing perceptual processing was substantially heightened when pictures were shown in temporal proximity to (i e 5s after) the defense stimulus Replicating previous studies aversive visual stimuli were associated with enhanced ssVEP amplitude compared to neutral stimuli Acute defense facilitates visual perception of external cues and preserves accurate discrimination between threatening and safe cues (C) 2010 Elsevier Ltd All rights reserved
C1 [Keil, Andreas] Univ Florida, Dept Psychol, NIMH Ctr Study Emot & Attent, Gainesville, FL 32608 USA.
[Ihssen, Niklas] Bangor Univ, Bangor, Gwynedd, Wales.
[Heim, Sabine] Deutsch Inst Int Padag Forsch, Frankfurt, Germany.
[Vila, Jaime; Guerra, Pedro] Univ Granada, Granada, Spain.
RP Keil, A (reprint author), Univ Florida, Dept Psychol, NIMH Ctr Study Emot & Attent, POB 112766, Gainesville, FL 32608 USA.
RI Keil, Andreas/F-9427-2011; Vila, Jaime/F-9719-2010; Ihssen,
Niklas/B-6324-2012; Frank, David/E-8213-2012
OI Keil, Andreas/0000-0002-4064-1924; Vila, Jaime/0000-0002-1767-8606;
Ihssen, Niklas/0000-0001-8386-1524;
FU NIMH [P50-MH072850, R21 MH082702, R01 MH084392]; Deutsche
Forschungsgememschaft
FX This research was supported in part by NIMH grants P50-MH072850 and R21
MH082702 to P J Lang by NIMH grant R01 MH084392 to A Keil and by grants
from the Deutsche Forschungsgememschaft The authors would like to thank
Felix Bartsch for assistance in data reduction
NR 28
TC 10
Z9 11
U1 2
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD OCT
PY 2010
VL 48
IS 12
BP 3580
EP 3584
DI 10.1016/j.neuropsychologia.2010.08.007
PG 5
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 677UM
UT WOS:000284017300023
PM 20713075
ER
PT J
AU Tsai, LK
Leng, Y
Wang, ZF
Leeds, P
Chuang, DM
AF Tsai, Li-Kai
Leng, Yan
Wang, Zhifei
Leeds, Peter
Chuang, De-Maw
TI The Mood Stabilizers Valproic Acid and Lithium Enhance Mesenchymal Stem
Cell Migration via Distinct Mechanisms
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE CXCR4; lithium; mesenchymal stem cells; migration; MMP-9; valproic acid
ID HISTONE DEACETYLASE INHIBITORS; AMYOTROPHIC-LATERAL-SCLEROSIS;
GLYCOGEN-SYNTHASE KINASE-3; MARROW STROMAL CELLS; HUMAN BONE-MARROW;
NF-KAPPA-B; MOUSE MODEL; NEURODEGENERATIVE DISORDERS;
MYOCARDIAL-INFARCTION; ISCHEMIC BRAIN
AB Mesenchymal stem cells (MSCs) show high potential for the therapy of several human diseases; however, the effectiveness of MSC transplantation has been hampered by the relatively poor migratory capacity of these cells toward disease target sites. This study investigated whether treatment of MSCs with two mood stabilizers-valproic acid (VPA) and lithium-would enhance cell migration and, if so, to explore the mechanisms underlying their effects. Short-term (3h) exposure of MSCs to a relatively high concentration (2.5 mM) of VPA markedly increased the transcript and protein levels of CXC chemokine receptor 4 (CXCR4). VPA-induced CXCR4 expression required inhibition of histone deacetylases (HDACs), including the HDACI isoform, and involved histone hyperacetylation at the promoter region of the CXCR4 gene. Notably, VPA treatment enhanced stromal cell-derived factor-1 alpha (SDF-1 alpha)-mediated MSC migration, which was completely blocked by AMD3100, a CXCR4 antagonist. Treatment of MSCs with lithium (2.5mM for 1 day) selectively elevated the transcript and protein levels of matrix metalloproteinase-9 (MMP-9) and its enzymatic activity; these effects were mimicked by inhibition or gene silencing of glycogen synthase kinase-3 beta (GSK-3 beta). Lithium treatment also potentiated SDF-1 alpha-dependent MSC migration across the extracellular matrix, which was suppressed by two MMP-9 inhibitors, doxycycline and GM6001. Combining VPA and lithium treatment further increased MSC migration. Overall, VPA and lithium stimulated MSC migration through distinct targets and mediators: HDAC-CXCR4 and GSK-3 beta-MMP-9, respectively. Neuropsychopharmacology (2010) 35, 2225-2237; doi:10.1038/npp.2010.97; published online 7 July 2010
C1 [Tsai, Li-Kai; Leng, Yan; Wang, Zhifei; Leeds, Peter; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Tsai, Li-Kai] Natl Taiwan Univ Hosp, Dept Neurol, Taipei, Taiwan.
[Tsai, Li-Kai] Natl Taiwan Univ Hosp, Stroke Ctr, Taipei, Taiwan.
[Tsai, Li-Kai] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan.
RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, 10 Ctr Dr,MSC1363, Bethesda, MD 20892 USA.
EM chuang@mail.nih.gov
RI Wang, Zhifei/I-2787-2013;
OI Tsai, Li-Kai/0000-0001-8420-6951
FU National Institute of Mental Health, National Institutes of Health,
Department of Health and Human Services (IRP-NIMH-NIH-DHHS); National
Taiwan University Hospital; HSU
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health,
Department of Health and Human Services (IRP-NIMH-NIH-DHHS), by National
Taiwan University Hospital, and by the HSU family gift fund. We thank Dr
Chen-Hung Ting of Academia Sinica, Taiwan, for primer design in the ChIP
assay, Mr Dave Luckenbaugh of the National Institute of Mental Health
for assistance in statistical analysis, and Ms Ioline Henter and Dr
Joshua Hunsberger of the National Institute of Mental Health for
assistance in the preparation of the paper.
NR 52
TC 34
Z9 42
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD OCT
PY 2010
VL 35
IS 11
BP 2225
EP 2237
DI 10.1038/npp.2010.97
PG 13
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 650BB
UT WOS:000281821200008
PM 20613717
ER
PT J
AU Senegas, J
Liu, W
Dahnke, H
Song, H
Jordan, EK
Frank, JA
AF Senegas, Julien
Liu, Wei
Dahnke, Hannes
Song, Hotaek
Jordan, E. Kay
Frank, Joseph A.
TI Fast T-2 Relaxometry with an Accelerated Multi-echo Spin-echo Sequence
SO NMR IN BIOMEDICINE
LA English
DT Article
DE T-2 relaxometry; undersampling; k-t BLAST; k-t GRAPPA; SPIO labeled
cells
ID IN-VIVO; ARTICULAR-CARTILAGE; R2 RELAXOMETRY; DYNAMIC MRI; T2;
RELAXATION; GRAPPA; QUANTIFICATION; RECONSTRUCTION; FRACTION
AB A new method has been developed to reduce the number of phase-encoding steps in a multi-echo spin-echo imaging sequence allowing fast 12 mapping without loss of spatial resolution. In the proposed approach, the k-space data at each echo time were undersampled and a reconstruction algorithm that exploited the temporal correlation of the MR signal in k-space was used to reconstruct alias-free images. A specific application of this algorithm with multiple-receiver acquisition, offering an alternative to existing parallel imaging methods, has also been introduced. The fast T-2 mapping method has been validated in human brain T-2 measurements in a group of nine volunteers with acceleration factors up to 3.4. The results demonstrated that the proposed method exhibited excellent linear correlation with the regular T-2 mapping with full sampling and achieved better image reconstruction and T-2 mapping with respect to SNR and reconstruction artifacts than the selected reference acceleration techniques. The new method has also been applied for quantitative tracking of injected magnetically labeled breast cancer cells in the rat brain with acceleration factors of 1.8 and 3.0. The proposed technique can provide an effective approach for accelerated T-2 quantification, especially for experiments with single-channel coil when parallel imaging is not applicable. Copyright (c) 2010 John Wiley & Sons, Ltd.
C1 [Liu, Wei] Philips Res N Amer, Briarcliff Manor, NY 10510 USA.
[Senegas, Julien; Dahnke, Hannes] Philips Res Europe, Hamburg, Germany.
[Liu, Wei; Song, Hotaek; Jordan, E. Kay; Frank, Joseph A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Song, Hotaek] Yonsei Univ, Coll Med, Dept Radiol, Seoul 120749, South Korea.
[Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
RP Liu, W (reprint author), Philips Res N Amer, 345 Scarborough Rd, Briarcliff Manor, NY 10510 USA.
EM wei.liu_1@philips.com
FU Clinical Center at the National Institutes of Health; Philips Research
North America
FX The authors would like to acknowledge Dr Diane Palmieri for the generous
donation and creation of the MDA-MB-231BRL-Luc breast cancer cell line
and Dr Stefanie Remmele for valuable discussion. This work was sponsored
in part by the Intramural Research Program at the Clinical Center at the
National Institutes of Health and a cooperative research and development
agreement with Philips Research North America.
NR 33
TC 4
Z9 4
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD OCT
PY 2010
VL 23
IS 8
BP 958
EP 967
DI 10.1002/nbm.1521
PG 10
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 666GP
UT WOS:000283102800007
PM 20878973
ER
PT J
AU Li, SZ
Zhang, Y
Wang, SM
Araneta, MF
Johnson, CS
Xiang, Y
Innis, RB
Shen, J
AF Li, Shizhe
Zhang, Yan
Wang, Shumin
Araneta, Maria Ferraris
Johnson, Christopher S.
Xiang, Yun
Innis, Robert B.
Shen, Jun
TI C-13 MRS of occipital and frontal lobes at 3 T using a volume coil for
stochastic proton decoupling
SO NMR IN BIOMEDICINE
LA English
DT Article
DE MRS; carbon-13; human brain; stochastic decoupling
ID MAGNETIC-RESONANCE-SPECTROSCOPY; TRICARBOXYLIC-ACID CYCLE; HUMAN BRAIN;
IN-VIVO; HUMAN HEAD; 4 TESLA; DIELECTRIC-PROPERTIES; GLUTAMATE
METABOLISM; BIOLOGICAL TISSUES; DECONVOLUTION
AB Previously, we devised a novel strategy for in vivo C-13 MRS using (2-C-13)glucose infusion and low-power proton decoupling, and proposed that this strategy could be used to acquire C-13 MR spectra from the frontal lobe of the human brain. Here, we demonstrate, for the first time, in vivo C-13 MRS of human frontal lobe acquired at 3 T. Because the primary metabolites of [2-C-13]glucose can be decoupled using very-low-radiofrequency power, we used a volume coil for proton decoupling in this study. The homogeneous B-1 field of the volume coil was found to significantly enhance the decoupling efficiency of the stochastic decoupling sequence. Detailed specific absorption rates inside the human head were analyzed using the finite difference time domain method to ensure experimental safety. In vivo C-13 spectra from the occipital and frontal lobes of the human brain were obtained. At a decoupling power of 30W (time-averaged power, 2.45W), the spectra from the occipital lobe showed well-resolved spectral resolution and excellent signal-to-noise ratio. Although frontal lobe C-13 spectra were affected by local B-0 field inhomogeneity, we demonstrated that the spectral quality could be improved using post-acquisition data processing. In particular, we showed that the frontal lobe glutamine C5 at 178.5 ppm and aspartate C4 at 178.3 ppm could be spectrally resolved with effective proton decoupling and B-0 field correction. Because of its large spatial coverage, volume coil decoupling provides the potential to acquire C-13 MRS from more than one brain region simultaneously. Copyright (c) 2010 John Wiley & Sons, Ltd.
C1 [Araneta, Maria Ferraris; Johnson, Christopher S.; Xiang, Yun; Innis, Robert B.; Shen, Jun] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Li, Shizhe; Zhang, Yan; Shen, Jun] NIMH, Magnet Resonance Spect Core Fac, NIH, Bethesda, MD 20892 USA.
[Wang, Shumin] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Shen, J (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM shenj@mail.nih.gov
FU National Institute of Mental Health, National Institutes of Health
(NIMH-NIH)
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
(NIMH-NIH). The authors have no conflict of interest to disclose,
financial or otherwise.
NR 42
TC 11
Z9 11
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
EI 1099-1492
J9 NMR BIOMED
JI NMR Biomed.
PD OCT
PY 2010
VL 23
IS 8
BP 977
EP 985
DI 10.1002/nbm.1524
PG 9
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 666GP
UT WOS:000283102800009
PM 20878974
ER
PT J
AU Schneider, TD
AF Schneider, Thomas D.
TI 70% efficiency of bistate molecular machines explained by information
theory, high dimensional geometry and evolutionary convergence
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ECORI RESTRICTION ENDONUCLEASE; REPLICATION INITIATOR REPA; DNA-BINDING
SITES; SEQUENCE LOGOS; CHANNEL CAPACITY; QUANTUM YIELD; PROTEIN;
RECOGNITION; P1; BASE
AB The relationship between information and energy is key to understanding biological systems. We can display the information in DNA sequences specifically bound by proteins by using sequence logos, and we can measure the corresponding binding energy. These can be compared by noting that one of the forms of the second law of thermodynamics defines the minimum energy dissipation required to gain one bit of information. Under the isothermal conditions that molecular machines function this is epsilon(min) = k(B)T in 2 joules per bit (k(B) is Boltzmann's constant and T is the absolute temperature). Then an efficiency of binding can be computed by dividing the information in a logo by the free energy of binding after it has been converted to bits. The isothermal efficiencies of not only genetic control systems, but also visual pigments are near 70%. From information and coding theory, the theoretical efficiency limit for bistate molecular machines is ln 2 = 0.6931. Evolutionary convergence to maximum efficiency is limited by the constraint that molecular states must be distinct from each other. The result indicates that natural molecular machines operate close to their information processing maximum (the channel capacity), and implies that nanotechnology can attain this goal.
C1 NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
RP Schneider, TD (reprint author), NCI, Ctr Canc Res, Nanobiol Program, Bldg 469,Room 215,POB B, Frederick, MD 21702 USA.
EM toms@alum.mit.edu
OI Schneider, Thomas/0000-0002-9841-1531
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research
FX Intramural Research Program of the National Institutes of Health;
National Cancer Institute; Center for Cancer Research. Funding for open
acess charge: National Cancer Institute.
NR 70
TC 13
Z9 13
U1 1
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD OCT
PY 2010
VL 38
IS 18
BP 5995
EP 6006
DI 10.1093/nar/gkq389
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 666LL
UT WOS:000283116600011
PM 20562221
ER
PT J
AU Aniba, MR
Poch, O
Marchler-Bauer, A
Thompson, JD
AF Aniba, Mohamed Radhouene
Poch, Olivier
Marchler-Bauer, Aron
Thompson, Julie Dawn
TI AlexSys: a knowledge-based expert system for multiple sequence alignment
construction and analysis
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DATABASE SEARCHES; PROTEIN SEQUENCES; T-COFFEE; ACCURACY;
BIOINFORMATICS; DISCOVERY; BENCHMARK
AB Multiple sequence alignment (MSA) is a cornerstone of modern molecular biology and represents a unique means of investigating the patterns of conservation and diversity in complex biological systems. Many different algorithms have been developed to construct MSAs, but previous studies have shown that no single aligner consistently outperforms the rest. This has led to the development of a number of 'meta-methods' that systematically run several aligners and merge the output into one single solution. Although these methods generally produce more accurate alignments, they are inefficient because all the aligners need to be run first and the choice of the best solution is made a posteriori. Here, we describe the development of a new expert system, AlexSys, for the multiple alignment of protein sequences. AlexSys incorporates an intelligent inference engine to automatically select an appropriate aligner a priori, depending only on the nature of the input sequences. The inference engine was trained on a large set of reference multiple alignments, using a novel machine learning approach. Applying AlexSys to a test set of 178 alignments, we show that the expert system represents a good compromise between alignment quality and running time, making it suitable for high throughput projects. AlexSys is freely available from http://www.w3.org/1999/xlink">http://alnitak.u-strasbg.fr/similar to aniba/alexsys.
C1 [Aniba, Mohamed Radhouene; Poch, Olivier; Thompson, Julie Dawn] IGBMC, Dept Struct Biol & Genom, F-67400 Illkirch Graffenstaden, France.
[Aniba, Mohamed Radhouene; Poch, Olivier; Thompson, Julie Dawn] INSERM, F-67400 Illkirch Graffenstaden, France.
[Aniba, Mohamed Radhouene; Poch, Olivier; Thompson, Julie Dawn] CNRS, UMR7104, F-67400 Illkirch Graffenstaden, France.
[Aniba, Mohamed Radhouene; Poch, Olivier; Thompson, Julie Dawn] Univ Strasbourg, F-67000 Strasbourg, France.
[Marchler-Bauer, Aron] NCBI NLM NIH, Bethesda, MD 20894 USA.
RP Thompson, JD (reprint author), IGBMC, Dept Struct Biol & Genom, F-67400 Illkirch Graffenstaden, France.
EM julie.thompson@igbmc.fr
RI Marchler-Bauer, Aron/A-9681-2009; Thompson, Julie/F-3208-2010;
OI Marchler-Bauer, Aron/0000-0003-1516-0712
FU Centre National de la Recherche Scientifique (CNRS); Institut National
de la Sante et de la Recherche Medicale (INSERM); Universite de
Strasbourg
FX Institute funds from the Centre National de la Recherche Scientifique
(CNRS); Institut National de la Sante et de la Recherche Medicale
(INSERM); Universite de Strasbourg. Funding for open access charge: CNRS
(Centre National de la Recherche Scientifique).
NR 54
TC 9
Z9 9
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD OCT
PY 2010
VL 38
IS 19
BP 6338
EP 6349
DI 10.1093/nar/gkq526
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 673SA
UT WOS:000283682100010
PM 20530533
ER
PT J
AU Ming, X
Alam, MR
Fisher, M
Yan, YJ
Chen, XY
Juliano, RL
AF Ming, Xin
Alam, Md Rowshon
Fisher, Michael
Yan, Yongjun
Chen, Xiaoyuan
Juliano, Rudolph L.
TI Intracellular delivery of an antisense oligonucleotide via endocytosis
of a G protein-coupled receptor
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID HUMAN PROSTATE ADENOCARCINOMA; PEPTIDE-RECEPTOR; SIRNA OLIGONUCLEOTIDES;
NONHUMAN-PRIMATES; RNA-INTERFERENCE; BOMBESIN ANALOGS; GENE DELIVERY;
CANCER-CELLS; TRAFFICKING; THERAPY
AB Gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor superfamily, has been utilized for receptor-mediated targeting of imaging and therapeutic agents; here we extend its use to oligonucleotide delivery. A splice-shifting antisense oligonucleotide was conjugated to a bombesin (BBN) peptide, and its intracellular delivery was tested in GRPR expressing PC3 cells stably transfected with a luciferase gene interrupted by an abnormally spliced intron. The BBN-conjugate produced significantly higher luciferase expression compared to unmodified oligonucleotide, and this increase was reversed by excess BBN peptide. Kinetic studies revealed a combination of saturable, receptor-mediated endocytosis and non-saturable pinocytosis for uptake of the conjugate. The K(m) value for saturable uptake was similar to the EC(50) value for the pharmacological response, indicating that receptor-mediated endocytosis was a primary contributor to the response. Use of pharmacological and molecular inhibitors of endocytosis showed that the conjugate utilized a clathrin-, actin- and dynamin-dependent pathway to enter PC3 cells. The BBN-conjugate partially localized in endomembrane vesicles that were associated with Rab7 or Rab9, demonstrating that it was transported to late endosomes and the trans-golgi network. These observations suggest that the BBN-oligonucleotide conjugate enters cells via a process of GRPR mediated endocytosis followed by trafficking to deep endomembrane compartments.
C1 [Ming, Xin; Alam, Md Rowshon; Fisher, Michael; Juliano, Rudolph L.] Univ N Carolina, Div Mol Pharmaceut, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
[Yan, Yongjun; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20810 USA.
RP Juliano, RL (reprint author), Univ N Carolina, Div Mol Pharmaceut, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
EM arjay@med.unc.edu
RI Ming, Xin/M-6691-2013
OI Ming, Xin/0000-0001-8368-250X
FU National Institutes of Health [P01GM059299]
FX Grant P01GM059299 to R.L.J. Funding for open access charge: National
Institutes of Health (grant P01GM059299).
NR 45
TC 39
Z9 40
U1 2
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD OCT
PY 2010
VL 38
IS 19
BP 6567
EP 6576
DI 10.1093/nar/gkq534
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 673SA
UT WOS:000283682100029
PM 20551131
ER
PT J
AU Massad, LS
Evans, CT
Weber, KM
Goderre, JL
Hessol, NA
Henry, D
Colie, C
Strickler, HD
Watts, DH
Wilson, TE
AF Massad, L. Stewart
Evans, Charlesnika T.
Weber, Kathleen M.
Goderre, Johanna L.
Hessol, Nancy A.
Henry, Donna
Colie, Christine
Strickler, Howard D.
Watts, D. Heather
Wilson, Tracey E.
TI Changes in Knowledge of Cervical Cancer Prevention and Human
Papillomavirus Among Women With Human Immunodeficiency Virus
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID INTERAGENCY HIV; PAPANICOLAOU SMEARS; HPV VACCINE; ABNORMALITIES;
PREVALENCE; COLPOSCOPY
AB OBJECTIVE: To estimate changes in high-risk women's knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination since introduction and marketing of HPV vaccines.
METHODS: At study visits in 2007 and 2008-2009, women with the human immunodeficiency virus (HIV) and at-risk comparison women in a multicenter U.S. cohort study completed 44-item self-report questionnaires exploring their knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results from 2007 were compared with those obtained in 2008-2009. Knowledge scores were correlated with demographic variables, measures of education and attention, and medical factors. Significant associations were assessed in multivariable models.
RESULTS: HIV-seropositive women had higher knowledge scores than seronegative women at baseline (13.2 +/- 5.7 compared with 11.8 +/- 6.0, P<.001) and follow-up (14.1 +/- 5.3 compared with 13.2 +/- 5.5, P=.01), but the change in scores was similar (0.9 +/- 5.3 compared with 1.5 +/- 5.5, P=.13). Knowledge that cervical cancer is caused by a virus rose significantly (P=.005), but only to 24%. Belief that cervical cancer is preventable only rose from 52% to 55% (P=.04), but more than 90% of women in both periods believed regular Pap testing was important. In analysis of covariance models, higher baseline score, younger age, higher education level, higher income, and former-as opposed to never-drug users, but not HIV status, were associated with improved knowledge.
CONCLUSION: High-risk women's understanding of cervical cancer and HPV has improved, but gaps remain. Improvement has been weakest for less educated and lower-income women. (Obstet Gynecol 2010;116:941-7)
C1 Washington Univ, Sch Med, St Louis, MO USA.
Hines VA Med Ctr, Dept Vet Affairs, Chicago, IL USA.
Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
John H Stroger Jr Hosp Cook Cty, CORE Ctr, Chicago, IL USA.
Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
Montefiore Med Ctr, Bronx, NY 10467 USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Georgetown Univ, Sch Med, Washington, DC USA.
Albert Einstein Coll Med, Bronx, NY 10467 USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
RP Massad, LS (reprint author), Div Gynecol Oncol, 4911 Barnes Jewish Hosp Plaza, St Louis, MO 63110 USA.
EM massadl@wudosis.wustl.edu
FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004,
UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590];
Eunice Kennedy Shriver National Institute of Child Health and Human
Development [UO1-HD-32632]; National Cancer Institute; National
Institute on Drug Abuse; National Institute on Deafness and Other
Communication Disorders; National Center for Research Resources [UL1
RR024131]; NCI [R01 CA85178-01]
FX The Women's Interagency HIV Study (WIHS) is funded by the National
Institute of Allergy and Infectious Diseases (UO1-AI-35004,
UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and
UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (UO1-HD-32632). The study is cofunded
by the National Cancer Institute, the National Institute on Drug Abuse,
and the National Institute on Deafness and Other Communication
Disorders. Funding is also provided by the National Center for Research
Resources (UCSF-CTSI Grant Number UL1 RR024131). H.D.S. was supported by
NCI R01 CA85178-01.
NR 23
TC 8
Z9 9
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD OCT
PY 2010
VL 116
IS 4
BP 941
EP 947
DI 10.1097/AOG.0b013e3181f2dbae
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 653DO
UT WOS:000282067700020
PM 20859159
ER
PT J
AU Huff, J
AF Huff, James
TI Predicting chemicals causing cancer in animals as human carcinogens
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Letter
ID RISKS
C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA.
RP Huff, J (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA.
EM huff1@niehs.nih.gov
NR 7
TC 8
Z9 8
U1 0
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD OCT
PY 2010
VL 67
IS 10
BP 720
EP 720
DI 10.1136/oem.2009.054569
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 827ZJ
UT WOS:000295469100012
PM 20837652
ER
PT J
AU Davies, MA
Samuels, Y
AF Davies, M. A.
Samuels, Y.
TI Analysis of the genome to personalize therapy for melanoma
SO ONCOGENE
LA English
DT Review
DE BRAF; NRAS; C-KIT; ERBB4; GN alpha Q
ID MULTIKINASE INHIBITOR SORAFENIB; PHASE-II TRIAL; RECOMBINANT
INTERLEUKIN-2 THERAPY; COOPERATIVE-ONCOLOGY-GROUP; KIT PROTEIN
EXPRESSION; ACUTE MYELOID-LEUKEMIA; PRIMARY UVEAL MELANOMA; METASTATIC
MELANOMA; CUTANEOUS MELANOMA; BRAF MUTATIONS
AB The treatment of cancer is being revolutionized by an improved understanding of the genetic events that occur in tumors. Advances in the understanding of the prevalence and patterns of mutations in melanoma have recently led to impressive results in trials of personalized, targeted therapies for this disease. In this review, we will discuss the molecular targets that have been validated clinically, additional genetic events that are candidates for future trials, and the challenges that remain to improve outcomes further in this aggressive disease. Oncogene (2010) 29, 5545-5555; doi:10.1038/onc.2010.323; published online 9 August 2010
C1 [Samuels, Y.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Davies, M. A.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA.
[Davies, M. A.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
RP Samuels, Y (reprint author), NHGRI, Canc Genet Branch, NIH, 50 South Dr,MSC 8000,Bldg 50,Room 5140, Bethesda, MD 20892 USA.
EM samuelsy@mail.nih.gov
FU ASCO; M D Anderson Cancer Center SPORE in Melanoma [5 P50 CA093459 03
PP-DRP3]; National Human Genome Research Institute, National Institutes
of Health, USA
FX We thank Darryl Leja for graphical expertize and Nature Genetics for
permission to use figures from paper doi:10.1038/ng.438. This work was
supported by grants from ASCO (Young Investigator Award) and M D
Anderson Cancer Center SPORE in Melanoma (Developmental Research Grant;
5 P50 CA093459 03 PP-DRP3; to MAD) and the Intramural Research Programs
of the National Human Genome Research Institute, National Institutes of
Health, USA (to YS).
NR 119
TC 55
Z9 59
U1 6
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT
PY 2010
VL 29
IS 41
BP 5545
EP 5555
DI 10.1038/onc.2010.323
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 664FX
UT WOS:000282946900001
PM 20697348
ER
PT J
AU Lu, C
Everhart, L
Tilan, J
Kuo, L
Sun, CCJ
Munivenkatappa, RB
Jonsson-Rylander, AC
Sun, J
Kuan-Celarier, A
Li, L
Abe, K
Zukowska, Z
Toretsky, JA
Kitlinska, J
AF Lu, C.
Everhart, L.
Tilan, J.
Kuo, L.
Sun, C-C J.
Munivenkatappa, R. B.
Jonsson-Rylander, A.-C.
Sun, J.
Kuan-Celarier, A.
Li, L.
Abe, K.
Zukowska, Z.
Toretsky, J. A.
Kitlinska, J.
TI Neuropeptide Y and its Y2 receptor: potential targets in neuroblastoma
therapy
SO ONCOGENE
LA English
DT Article
DE neuropeptide Y; neuroblastoma; angiogenesis
ID BAX-DEPENDENT APOPTOSIS; SMOOTH-MUSCLE-CELLS; INDUCED ANGIOGENESIS;
NEURO-BLASTOMA; ADRENAL-GLAND; YY2 RECEPTOR; EXPRESSION; BIM; TUMORS;
PHOSPHORYLATION
AB Neuroblastomas are pediatric tumors that develop from sympathetic precursors and express neuronal proteins, such as neuropeptide Y (NPY). NPY is a sympathetic neurotransmitter acting via multiple receptors (Y1-Y5R). Both NPY and Y2Rs are commonly expressed in neuroblastoma cell lines and tissues. The peptide secreted from neuroblastomas stimulates tumor cell proliferation and angiogenesis. As both processes are Y2R-mediated, the aim of this study was to assess Y2R as a potential therapeutic target for neuroblastoma. In vitro, Y2R antagonist (BIIE0246) prevented activation of p44/42 mitogen-activated protein kinase (MAPK) induced by endogenous NPY, which resulted in decreased proliferation and induction of Bim-mediated apoptosis. Similar growth-inhibitory effects were achieved with NPY small interfering RNA (siRNA) and Y2R siRNA. In vivo, Y2R antagonist significantly inhibited growth of SK-N-BE(2) and SK-N-AS xenografts, which was associated with decreased activation of p44/42 MAPK, as well as reduced proliferation (Ki67) and increased apoptosis (TdT-mediated dUTP nick end labeling; TUNEL). The Y2R antagonist also exerted an antiangiogenic effect. In vitro, it reduced the proliferation of endothelial cells induced by neuroblastoma-conditioned media. Consequently, the Y2R antagonist-treated xenografts had decreased vascularization and a high degree of focal fibrosis. In human neuroblastoma tissues, the expression of Y2R was observed in both tumor and endothelial cells, while NPY was predominantly expressed in neuroblastoma cells. In summary, Y2R is a promising new target for neuroblastoma therapy affecting both cancer cells and tumor vasculature. Oncogene (2010) 29, 5630-5642; doi:10.1038/onc.2010.301; published online 2 August 2010
C1 [Lu, C.; Everhart, L.; Tilan, J.; Kuo, L.; Kuan-Celarier, A.; Li, L.; Zukowska, Z.; Kitlinska, J.] Georgetown Univ, Dept Physiol & Biophys, Washington, DC 20057 USA.
[Sun, C-C J.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Munivenkatappa, R. B.] Univ Maryland, Sch Med, Dept Surg, Div Transplantat, Baltimore, MD 21201 USA.
[Jonsson-Rylander, A.-C.] AstraZeneca, Dept Biosci, Molndal, Sweden.
[Sun, J.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Abe, K.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Toretsky, J. A.] Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
RP Kitlinska, J (reprint author), Georgetown Univ, Dept Physiol & Biophys, BSB 231A,3900 Reservoir Rd NW, Washington, DC 20057 USA.
EM jbk4@georgetown.edu
RI Lu, Congyi/G-3984-2013
FU NIH [1R01CA123211-01]; Children's Cancer Foundation (Baltimore, MD, USA)
FX This work was supported by NIH Grant 1R01CA123211-01 and funding from
Children's Cancer Foundation (Baltimore, MD, USA) to Joanna Kitlinska.
The authors would like to thank John Styliaris and David Hur for help in
performing experiments. We also thank the Flow Cytometry/Cell Sorting
Shared Resources of Lombardi Comprehensive Cancer Center for technical
assistance and Children's Oncology Group for providing human samples.
NR 42
TC 25
Z9 25
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT
PY 2010
VL 29
IS 41
BP 5630
EP 5642
DI 10.1038/onc.2010.301
PG 13
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 664FX
UT WOS:000282946900009
PM 20676138
ER
PT J
AU Cheng, L
Zhou, Z
Flesken-Nikitin, A
Toshkov, IA
Wang, W
Camps, J
Ried, T
Nikitin, AY
AF Cheng, L.
Zhou, Z.
Flesken-Nikitin, A.
Toshkov, I. A.
Wang, W.
Camps, J.
Ried, T.
Nikitin, A. Y.
TI Rb inactivation accelerates neoplastic growth and substitutes for
recurrent amplification of cIAP1, cIAP2 and Yap1 in sporadic mammary
carcinoma associated with p53 deficiency
SO ONCOGENE
LA English
DT Article
DE breast cancer; genomic maintenance; mouse; models of cancer;
oncogenomics; tumor suppressor
ID CONDITIONAL MOUSE MODEL; HUMAN BREAST-CANCER; TUMOR SUPPRESSION; SOMATIC
INACTIVATION; LIVER TUMORIGENESIS; GENOME INTEGRITY; PROSTATE-CANCER;
TRANSGENIC MICE; HIGH-FREQUENCY; NEURAL CREST
AB Genetically defined mouse models offer an important tool to identify critical secondary genetic alterations with relevance to human cancer pathogenesis. We used newly generated MMTV-Cre105Ayn mice to inactivate p53 and/or Rb strictly in the mammary epithelium, and to determine recurrent genomic changes associated with deficiencies of these genes. p53 inactivation led to formation of estrogen receptor-positive raloxifene-responsive mammary carcinomas with features of luminal subtype B. Rb deficiency was insufficient to initiate carcinogenesis but promoted genomic instability and growth rate of neoplasms associated with p53 inactivation. Genome-wide analysis of mammary carcinomas identified a recurrent amplification at chromosome band 9A1, a locus orthologous to human 11q22, which contains protooncogenes cIAP1 (Birc2), cIAP2 (Birc3) and Yap1. It is interesting that this amplicon was preferentially detected in carcinomas carrying wild-type Rb. However, all three genes were overexpressed in carcinomas with p53 and Rb inactivation, likely due to E2F-mediated transactivation, and cooperated in carcinogenesis according to gene knockdown experiments. These findings establish a model of luminal subtype B mammary carcinoma, identify critical role of cIAP1, cIAP2 and Yap1 co-expression in mammary carcinogenesis and provide an explanation for the lack of recurrent amplifications of cIAP1, cIAP2 and Yap1 in some tumors with frequent Rb deficiency, such as mammary carcinoma. Oncogene (2010) 29, 5700-5711; doi:10.1038/onc.2010.300; published online 2 August 2010
C1 [Cheng, L.; Zhou, Z.; Flesken-Nikitin, A.; Toshkov, I. A.; Nikitin, A. Y.] Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA.
[Wang, W.] Cornell Univ, Microarray Core Facil, Ithaca, NY 14853 USA.
[Camps, J.; Ried, T.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Nikitin, AY (reprint author), Cornell Univ, Dept Biomed Sci, T2 014A VRT Campus Rd, Ithaca, NY 14853 USA.
EM an58@cornell.edu
FU NIH/NCI [R01 CA96823]; NYSTEM [C023050]
FX We thank David C Corney for critical reading of this paper and Dr Anton
Berns (Netherlands Cancer Institute, Amsterdam, The Netherlands) for the
generous gift of the p53floxP/floxP and
RbfloxP/floxP mice. This work was supported by grants R01
CA96823 (NIH/NCI) and C023050 (NYSTEM) to AYN.
NR 50
TC 16
Z9 16
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT
PY 2010
VL 29
IS 42
BP 5700
EP 5711
DI 10.1038/onc.2010.300
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 668IT
UT WOS:000283262500006
PM 20676140
ER
PT J
AU Herbert, BS
Chanoux, RA
Liu, YL
Baenziger, PH
Goswami, CP
McClintick, JN
Edenberg, HJ
Pennington, RE
Lipkin, SM
Kopelovich, L
AF Herbert, Brittney-Shea
Chanoux, Rebecca A.
Liu, Yunlong
Baenziger, Peter H.
Goswami, Chirayu P.
McClintick, Jeanette N.
Edenberg, Howard J.
Pennington, Robert E.
Lipkin, Steven M.
Kopelovich, Levy
TI A molecular signature of normal breast epithelial and stromal cells from
Li-Fraumeni syndrome mutation carriers
SO ONCOTARGET
LA English
DT Article
DE one-hit effects; gene expression profiling; Li-Fraumeni Syndrome;
chemoprevention; breast cancer
ID TUMOR-SUPPRESSOR GENE; FALSE DISCOVERY RATE; ONE-HIT; PROMOTER
HYPERMETHYLATION; P53 RESTORATION; CANCER FAMILY; MUTANT P53; CYCLIN D2;
EXPRESSION; MICE
AB Specific changes in gene expression during cancer initiation should enable discovery of biomarkers for risk assessment, early detection and targets for chemoprevention. It has been previously demonstrated that altered mRNA and proteome signatures of morphologically normal cells bearing a single inherited "hit" in a tumor suppressor gene parallel many changes observed in the corresponding sporadic cancer. Here, we report on the global gene expression profile of morphologically normal, cultured primary breast epithelial and stromal cells from Li-Fraumeni syndrome (LFS) TP53 mutation carriers. Our analyses identified multiple changes in gene expression in both morphologically normal breast epithelial and stromal cells associated with TP53 haploinsufficiency, as well as interlocking pathways. Notably, a dysregulated p53 signaling pathway was readily detectable. Pharmacological intervention with the p53 rescue compounds CP-31398 and PRIMA-1 provided further evidence in support of the central role of p53 in affecting these changes in LFS cells and treatment for this cancer. Because loss of signaling mediated by TP53 is associated with the development and survival of many human tumors, identification of gene expression profiles in morphologically normal cells that carry "one-hit" p53 mutations may reveal novel biomarkers, enabling the discovery of potential targets for chemoprevention of sporadic tumors as well.
C1 [Herbert, Brittney-Shea; Chanoux, Rebecca A.; Liu, Yunlong; Edenberg, Howard J.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[Herbert, Brittney-Shea] Indiana Univ Sch Med, Melvin & Bren Simon Canc Ctr, Indianapolis, IN USA.
[Liu, Yunlong; Baenziger, Peter H.; Goswami, Chirayu P.] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA.
[Liu, Yunlong] Indiana Univ Sch Med, Dept Med, Div Biostat, Indianapolis, IN USA.
[Liu, Yunlong; McClintick, Jeanette N.; Edenberg, Howard J.] Indiana Univ Sch Med, Ctr Med Genom, Indianapolis, IN USA.
[McClintick, Jeanette N.; Edenberg, Howard J.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA.
[Pennington, Robert E.] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN USA.
[Lipkin, Steven M.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Lipkin, Steven M.] Weill Cornell Med Coll, Dept Med Genet, New York, NY USA.
[Kopelovich, Levy] Natl Canc Inst, Canc Prevent Div, Bethesda, MD USA.
RP Herbert, BS (reprint author), Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
EM brherber@iupui.edu; kopelovl@mail.nih.gov
RI Baenziger, Peter/C-6490-2014;
OI Baenziger, Peter/0000-0002-9109-6954; Edenberg,
Howard/0000-0003-0344-9690
FU Indiana Genomics Initiative at Indiana University (INGEN Registered
Trademark); Lilly Endowment, Inc.; National Cancer Institute [N01
CN-43300]; IU Simon Cancer Center; INGEN
FX We thank M. Fox, E. Gentry, A. Hochreiter-Hufford, and C.B. Smith for
technical assistance, and J.W. Shay for LFS-50 and WT cell lines. The
microarray studies were carried out using the facilities of the Center
for Medical Genomics at Indiana University School of Medicine. The
Center for Medical Genomics is supported in part by the Indiana Genomics
Initiative at Indiana University (INGEN (R), which is supported in part
by the Lilly Endowment, Inc.). This work was supported by National
Cancer Institute N01 CN-43300, IU Simon Cancer Center, and INGEN.
NR 57
TC 21
Z9 21
U1 0
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD OCT
PY 2010
VL 1
IS 6
BP 405
EP 422
PG 18
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 802JC
UT WOS:000293504900004
PM 21311097
ER
PT J
AU Jeang, KT
AF Jeang, Kuan-Teh
TI Human T cell leukemia virus type 1 (HTLV-1) and oncogene or oncomiR
addiction?
SO ONCOTARGET
LA English
DT Article
DE HTLV; ATL; MicroRNAs; Leukemia; oncogene
ID 1ST HUMAN RETROVIRUS; TAX GENE; I PX; LYMPHOCYTES; MECHANISMS;
EXPRESSION; MICRORNAS; DISCOVERY; DISEASE; PROTEIN
AB The mechanism of HTLV-1 transformation of cells to Adult T cell leukemia (ATL) remains not fully understood. Currently, the viral Tax oncoprotein is known to be required to initiate transformation. Emerging evidence suggests that Tax is not needed to maintain the transformed ATL phenotype. Recent studies have shown that HTLV-1 transformed cells show deregulated expression of cellular microRNAs (miRNAs). Here we discuss the possibility that early ATL cells are Tax-oncogene-addicted while late ATL cells are oncogenic microRNA (oncomiR) - addicted. The potential utility of interrupting oncomiR addiction as a cancer treatment is broached.
C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM kjeang@nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU National Institute of Allergy and Infectious Diseases
FX The views expressed here are the personal opinions of the author and do
not reflect the views of his employer, the US National Institutes of
Health. Work in KTJ's laboratory is supported by intramural funds from
the National Institute of Allergy and Infectious Diseases. The author
thanks Daniel Schmidt and Lauren Lee for help with manuscript and figure
preparations.
NR 33
TC 15
Z9 16
U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD OCT
PY 2010
VL 1
IS 6
BP 453
EP 456
PG 4
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 802JC
UT WOS:000293504900008
PM 21311101
ER
PT J
AU Heimpel, H
Kratz, CP
Flotho, C
Brittinger, G
Konig, E
Lauenstein, T
Duhrsen, U
AF Heimpel, H.
Kratz, C. P.
Flotho, C.
Brittinger, G.
Koenig, E.
Lauenstein, T.
Duehrsen, U.
TI Congenital dyserythropoietic anemia with thrombocytopenia and
extramedullary erythropoiesis due to a germline GATA-1 mutation
SO ONKOLOGIE
LA English
DT Meeting Abstract
C1 [Heimpel, H.] Univ Ulm, Zentrum Innere Med, Innere Med Klin 3, Ulm, Germany.
[Kratz, C. P.] NCI, Clin Genet Branch, Rockville, MD USA.
[Flotho, C.] Univ Freiburg, Zentrum Kinderheilkunde & Jugendmed, Klin Hamatol & Onkol 4, Freiburg, Germany.
[Brittinger, G.; Koenig, E.; Duehrsen, U.] Univ Klinikum Essen, Klin Hamatol, Essen, Germany.
[Lauenstein, T.] Univ Klinikum Essen, Inst Diagnost & Intervent Radiol & Neuroradiol, Essen, Germany.
RI Lauenstein, Thomas/H-4239-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0378-584X
J9 ONKOLOGIE
JI Onkologie
PD OCT
PY 2010
VL 33
SU 6
BP 112
EP 112
PG 1
GA 664UN
UT WOS:000282988400309
ER
PT J
AU Gerbitz, A
Sukumar, M
Helm, F
Wilke, A
Friese, C
Fahrenwaldt, C
Lehmann, F
Loddenkemper, C
Kammertons, T
Mautner, J
Blankenstein, T
Bornkamm, G
AF Gerbitz, A.
Sukumar, M.
Helm, F.
Wilke, A.
Friese, C.
Fahrenwaldt, C.
Lehmann, F.
Loddenkemper, C.
Kammertoens, T.
Mautner, J.
Blankenstein, T.
Bornkamm, G.
TI Host interferon-gamma signaling and cross-presentation is required for
elimination of antigen-loss variants of high-grade B cell lymphomas:
Implications for adoptive T-cell therapy
SO ONKOLOGIE
LA English
DT Meeting Abstract
C1 [Gerbitz, A.] Univ Erlangen Nurnberg, Erlangen, Germany.
[Sukumar, M.] NIH, Surg Branch, Bethesda, MD 20892 USA.
[Helm, F.; Wilke, A.; Friese, C.; Fahrenwaldt, C.; Kammertoens, T.; Blankenstein, T.] Charite CBF, Inst Immunol, Berlin, Germany.
[Lehmann, F.; Bornkamm, G.] Helmholtz Zentrum Munchen, Inst Klin Mol Biol & Tumorgenet, Munich, Germany.
[Loddenkemper, C.] Tech Univ Munich, Inst Pathol, Munich, Germany.
[Mautner, J.] Tech Univ Munich, Kinderklin, Klin Kooperat Grp, Munich, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0378-584X
J9 ONKOLOGIE
JI Onkologie
PD OCT
PY 2010
VL 33
SU 6
BP 288
EP 288
PG 1
GA 664UN
UT WOS:000282988401367
ER
PT J
AU Young, N
AF Young, N.
TI Human bone marrow failure and the role of telomere biology in human
disease
SO ONKOLOGIE
LA English
DT Meeting Abstract
C1 [Young, N.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0378-584X
J9 ONKOLOGIE
JI Onkologie
PD OCT
PY 2010
VL 33
SU 6
BP 294
EP 294
PG 1
GA 664UN
UT WOS:000282988401387
ER
PT J
AU Barnett, ML
Pihlstrom, BL
AF Barnett, M. L.
Pihlstrom, B. L.
TI Considerations in establishing an oral disease clinical research center
SO ORAL DISEASES
LA English
DT Review
DE clinical research; research center; human subject protections; research
training; industry-sponsored research
AB High quality clinical research is necessary to improve oral health and translate research findings to the practice of dentistry. This has led many academic institutions to consider establishing a formal clinical research center. This is not a trivial undertaking and requires that the center have an appropriate physical infrastructure, trained investigators with recognized expertise in the planning and conduct of high quality clinical research, and very importantly, a financial plan to assure its long-term sustainability. The purpose of this paper is to provide some guidance and practical advice with respect to factors that should be considered in developing and maintaining a successful oral disease clinical research center.
C1 [Barnett, M. L.] SUNY Buffalo, Sch Dent Med, Buffalo, NY 14260 USA.
[Pihlstrom, B. L.] Univ Minnesota, Sch Dent, Bethesda, MD USA.
[Pihlstrom, B. L.] Natl Inst Dent & Craniofacial Res, Div Clin Res & Hlth Promot, NIH, Bethesda, MD USA.
RP Barnett, ML (reprint author), 289 Sayre Dr, Princeton, NJ 08540 USA.
EM mlbgums@aol.com
FU United States National Institutes of Health (NIH)
FX The main source of government funding for oral health research worldwide
is the United States National Institutes of Health (NIH), specifically
the National Institute of Dental and Craniofacial Research (NIDCR). All
applications for U.S. government funding must be submitted in response
to a Funding Opportunity Announcement (FOA) posted on the Grants.gov
website (http://www.grants.gov/applicants/ find_grant_opportunities.jsp)
or the websites of specific granting agencies. Oral health FOAs can be
found at three locations: (1) the Grants.gov website, (2) the NIH Guide
for Grants and Contracts (http://grants.nih.gov/grants/guide/) and, (3)
the NIDCR website (http://www.nidcr.nih.gov/). Most NIH funding is
awarded to U.S. investigators, but the NIH supports research in other
countries if resources such as investigator expertise, instrumentation,
or patient populations are not available in the U.S and if the findings
are applicable to people living in the U.S. Investigators who are
interested in obtaining government funding from other countries should
consult public health agencies in those countries for funding
opportunities.
NR 5
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1354-523X
EI 1601-0825
J9 ORAL DIS
JI Oral Dis.
PD OCT
PY 2010
VL 16
IS 7
BP 586
EP 591
DI 10.1111/j.1601-0825.2010.01673.x
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 650EI
UT WOS:000281831600002
PM 20846148
ER
PT J
AU Oladeinde, OA
Hong, SY
Holland, RJ
Maciag, AE
Keefer, LK
Saavedra, JE
Nandurdikar, RS
AF Oladeinde, Oyebola A.
Hong, Sam Y.
Holland, Ryan J.
Maciag, Anna E.
Keefer, Larry K.
Saavedra, Joseph E.
Nandurdikar, Rahul S.
TI "Click" Reaction in Conjunction with Diazeniumdiolate Chemistry:
Developing High-Load Nitric Oxide Donors
SO ORGANIC LETTERS
LA English
DT Article
ID AZIDE-ALKYNE CYCLOADDITION; 1,3-DIPOLAR CYCLOADDITIONS; NOBEL LECTURE;
DISCOVERY; PRODRUG; ANALOGS; TRENDS; DRUGS
AB The use of Cu(I)-catalyzed "click" reactions of alkyne-substituted diazeniumdiolate prodrugs with bis- and tetrakis-azido compounds is described. The "click" reaction for the bis-azide using CuSO(4)/Na-ascorbate predominantly gave the expected bis-triazole. However, CuI/diisopropylethylamine predominantly gave uncommon triazolo-triazole products as a result of oxidative coupling. Neither set of "click" conditions showed evidence of compromising the integrity of the diazeniumdiolate groups. The chemistry developed has applications in the synthesis of polyvalent and dendritic nitric oxide donors.
C1 [Maciag, Anna E.; Saavedra, Joseph E.] NCI, Basic Sci Program, SAIC Frederick, Frederick, MD 21702 USA.
[Oladeinde, Oyebola A.; Hong, Sam Y.; Holland, Ryan J.; Keefer, Larry K.; Nandurdikar, Rahul S.] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.
RP Saavedra, JE (reprint author), NCI, Basic Sci Program, SAIC Frederick, Frederick, MD 21702 USA.
EM saavedjo@mail.nih.gov; nandurdikarr@mail.nih.gov
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX This project has been funded with Federal funds from the National Cancer
Institute, National Institutes of Health, under contract
HHSN261200800001E and by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. We thank Dr.
Sergey Tarasov and Ms. Marzena A. Dyba of the Biophysics Resource in the
Structural Biophysics Laboratory, NCI-Frederick, for assistance with the
high-resolution mass spectrometry studies.
NR 25
TC 13
Z9 13
U1 0
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1523-7060
J9 ORG LETT
JI Org. Lett.
PD OCT 1
PY 2010
VL 12
IS 19
BP 4256
EP 4259
DI 10.1021/ol101645k
PG 4
WC Chemistry, Organic
SC Chemistry
GA 652WP
UT WOS:000282041900011
PM 20812718
ER
PT J
AU Berger, VW
AF Berger, V. W.
TI Assessing the quality of randomization and allocation concealment
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Letter
C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA.
EM vb78c@nih.gov
NR 4
TC 2
Z9 2
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1063-4584
J9 OSTEOARTHR CARTILAGE
JI Osteoarthritis Cartilage
PD OCT
PY 2010
VL 18
IS 10
BP 1361
EP 1361
DI 10.1016/j.joca.2010.05.022
PG 1
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 670UK
UT WOS:000283452600019
PM 20650327
ER
PT J
AU Gabay, OH
Lee, E
Booth, R
Gagarina, V
Dvir-Ginzberg, M
Hall, DJ
AF Gabay, O. H.
Lee, E.
Booth, R.
Gagarina, V.
Dvir-Ginzberg, M.
Hall, D. J.
TI INCREASED EXPRESSION OF ARTHRITIC MARKER GENES IN THE CARTILAGE OF SIRT1
NULL MICE
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Meeting Abstract
CT World Congress of the OsteoArthritis-Research-Society-International
CY SEP 23-26, 2010
CL Brussels, BELGIUM
SP OsteoArthritis Res Soc Int
C1 [Gabay, O. H.; Lee, E.; Booth, R.; Gagarina, V.; Hall, D. J.] NIH, Bethesda, MD 20892 USA.
[Dvir-Ginzberg, M.] Hebrew Univ Hadassah Ein Kerem, Fac Med Dent, Lab Cartilage Biol, Inst Dent Sci, Jerusalem, Israel.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 1063-4584
J9 OSTEOARTHR CARTILAGE
JI Osteoarthritis Cartilage
PD OCT
PY 2010
VL 18
SU 2
BP S49
EP S49
PG 1
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 670UN
UT WOS:000283452900117
ER
PT J
AU Gabay, OH
Lee, E
Booth, R
Gagarina, V
Dvir-Ginzberg, M
Hall, DJ
AF Gabay, O. H.
Lee, E.
Booth, R.
Gagarina, V.
Dvir-Ginzberg, M.
Hall, D. J.
TI A POSITIVE ROLE OF DBC1, A SIRT1 REPRESSOR, IN THE ARTHRITIC RESPONSE IN
HUMAN CHONDROCYTES
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Meeting Abstract
CT World Congress of the OsteoArthritis-Research-Society-International
CY SEP 23-26, 2010
CL Brussels, BELGIUM
SP OsteoArthritis Res Soc Int
C1 [Gabay, O. H.; Lee, E.; Booth, R.; Gagarina, V.; Hall, D. J.] NIH, Bethesda, MD 20892 USA.
[Dvir-Ginzberg, M.] Hebrew Univ Hadassah Ein Kerem, Lab Cartilage Biol, Inst Dent Sci, Fac Med Dent, Jerusalem, Israel.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 1063-4584
J9 OSTEOARTHR CARTILAGE
JI Osteoarthritis Cartilage
PD OCT
PY 2010
VL 18
SU 2
BP S17
EP S17
PG 1
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 670UN
UT WOS:000283452900042
ER
PT J
AU Jonsson, H
Helgadottir, GP
Aspelund, T
Eiriksdottir, G
Sigurdsson, S
Siggeirsdottir, K
Ingvarsson, T
Harris, TB
Launer, L
Gudnason, V
AF Jonsson, H.
Helgadottir, G. P.
Aspelund, T.
Eiriksdottir, G.
Sigurdsson, S.
Siggeirsdottir, K.
Ingvarsson, T.
Harris, T. B.
Launer, L.
Gudnason, V.
TI THE PRESENCE OF TOTAL KNEE OR HIP REPLACEMENTS DUE TO OA STRENGTHENS THE
POSITIVE ASSOCIATION BETWEEN HAND OA AND ATHEROSCLEROSIS IN FEMALES: THE
AGES-REYKJAVIK STUDY
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Meeting Abstract
CT World Congress of the OsteoArthritis-Research-Society-International
CY SEP 23-26, 2010
CL Brussels, BELGIUM
SP OsteoArthritis Res Soc Int
C1 [Jonsson, H.; Helgadottir, G. P.; Aspelund, T.; Gudnason, V.] Univ Iceland, Reykjavik, Iceland.
[Aspelund, T.; Eiriksdottir, G.; Sigurdsson, S.; Siggeirsdottir, K.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland.
[Ingvarsson, T.] Cent Hosp, Akureyri, Iceland.
[Harris, T. B.; Launer, L.] Inst Aging, Bethesda, MD USA.
RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason,
Vilmundur/K-6885-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084
NR 0
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 1063-4584
J9 OSTEOARTHR CARTILAGE
JI Osteoarthritis Cartilage
PD OCT
PY 2010
VL 18
SU 2
BP S127
EP S127
PG 1
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 670UN
UT WOS:000283452900306
ER
PT J
AU Sigurjonsdottir, K
Bjorgulfsson, TM
Aspelund, T
Eiriksdottir, G
Sigurdsson, S
Ingvarsson, T
Harris, TB
Launer, L
Gudnason, V
Jonsson, H
AF Sigurjonsdottir, K.
Bjorgulfsson, T. M.
Aspelund, T.
Eiriksdottir, G.
Sigurdsson, S.
Ingvarsson, T.
Harris, T. B.
Launer, L.
Gudnason, V.
Jonsson, H.
TI TYPE 3 FINGER LENGTH PATTERN IS ASSOCIATED WITH TOTAL KNEE (TKR) BUT NOT
WITH HIP REPLACEMENTS (THR) IN THE ELDERLY: THE AGES-REYKJAVIK STUDY
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Meeting Abstract
CT World Congress of the OsteoArthritis-Research-Society-International
CY SEP 23-26, 2010
CL Brussels, BELGIUM
SP OsteoArthritis Res Soc Int
C1 [Sigurjonsdottir, K.; Bjorgulfsson, T. M.; Aspelund, T.; Gudnason, V.; Jonsson, H.] Univ Iceland, Reykjavik, Iceland.
[Aspelund, T.; Eiriksdottir, G.; Sigurdsson, S.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland.
[Ingvarsson, T.] Ctr Hosp, Akureyri, Iceland.
[Harris, T. B.; Launer, L.] NIA, Bethesda, MD 20892 USA.
RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason,
Vilmundur/K-6885-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084
NR 0
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 1063-4584
J9 OSTEOARTHR CARTILAGE
JI Osteoarthritis Cartilage
PD OCT
PY 2010
VL 18
SU 2
BP S33
EP S33
PG 1
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 670UN
UT WOS:000283452900079
ER
PT J
AU Portnoy, DB
Roter, D
Erby, LH
AF Portnoy, David B.
Roter, Debra
Erby, Lori H.
TI The role of numeracy on client knowledge in BRCA genetic counseling
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Numeracy; Patient-provider interaction; Genetic counseling; Patient
learning
ID DECISIONAL CONFLICT SCALE; ORAL LITERACY DEMAND; BREAST-CANCER; HEALTH
LITERACY; RISK; COMMUNICATION; INFORMATION; EDUCATION; DIALOGUE;
OUTCOMES
AB Objective: To assess the impact of numeracy and health literacy on client's ability to learn information orally communicated during a BRCA 1/2 genetic counseling session.
Methods: Fifty-nine videotaped simulated genetic counseling sessions were shown to 246 analogue clients (AC) recruited to imagine themselves as the client in the genetic counseling session. AC numeracy, genetic literacy, state and trait anxiety, and decisional conflict were assessed. The primary outcome was AC learning about BRCA 1/2.
Results: Health literacy and numeracy were moderately correlated, and each independently predicted learning. Higher numeracy was associated with higher knowledge scores only among ACs with adequate literacy. Decisional conflict was not related to literacy, numeracy, or knowledge acquisition. It was, however, inversely related to state anxiety so that the higher post-session state anxiety, the lower the AC's decisional conflict.
Conclusion: Numeracy and health literacy are associated with learning of orally communicated information during genetic counseling. It appears that numeracy can facilitate learning for literate subjects: it does not, however, make any difference in learning ability of clients with significant literacy deficits.
Practice implications: Numeracy plays an important role in client's ability to learn information communicated during medical sessions, especially among clients who are otherwise regarded as literate. Published by Elsevier Ireland Ltd.
C1 [Portnoy, David B.] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA.
[Roter, Debra; Erby, Lori H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA.
RP Portnoy, DB (reprint author), NCI, Canc Prevent Fellowship Program, NIH, Execut Plaza N,6130 Execut Blvd,Room 4051, Bethesda, MD 20892 USA.
EM portnoydb@mail.nih.gov
RI Roter, Debra/N-8830-2014;
OI Portnoy, David/0000-0003-2175-9457
FU National Human Genome Research Institute of the NIH [1R01HG002688-01A1]
FX This research was supported by grant 1R01HG002688-01A1 (PI D.Roter),
Genetic Counseling Processes and Analogue Client Outcome, funded by the
National Human Genome Research Institute of the NIH.
NR 30
TC 17
Z9 17
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD OCT
PY 2010
VL 81
IS 1
BP 131
EP 136
DI 10.1016/j.pec.2010.09.036
PG 6
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA 653EL
UT WOS:000282070900022
PM 19854023
ER
PT J
AU Kolb, EA
Gorlick, R
Houghton, PJ
Morton, CL
Neale, G
Keir, ST
Carol, H
Lock, R
Phelps, D
Kang, MH
Reynolds, CP
Maris, JM
Billups, C
Smith, MA
AF Kolb, E. Anders
Gorlick, Richard
Houghton, Peter J.
Morton, Christopher L.
Neale, Geoffrey
Keir, Stephen T.
Carol, Hernan
Lock, Richard
Phelps, Doris
Kang, Min H.
Reynolds, C. Patrick
Maris, John M.
Billups, Catherine
Smith, Malcolm A.
TI Initial Testing (Stage 1) of AZD6244 (ARRY-142886) by the Pediatric
Preclinical Testing Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE AZD6244; developmental therapeutics; preclinical testing
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; KINASE KINASE-1/2 INHIBITOR; PATHWAY
ACTIVATION; BRAF GENE; IN-VIVO; B-RAF; PILOCYTIC ASTROCYTOMAS; MAMMALIAN
TARGET; CANCER MODELS; MAPK PATHWAY
AB Background. AZD6244 (ARRY-142886) is a potent small molecule inhibitor of MEK1/2 that is in phase 2 clinical development Procedures. AZD6244 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro panel (1 nM-10 mu M) In vivo AZD6244 was tested at a close of 100 mg/kg administered orally twice daily 5 days per week for 6 weeks Subsequently, AZD6244 was evaluated against two juvenile pilocytic astrocytoma (JPA) xenografts using once and twice daily dosing schedules Phosphorylation of ERK1/2 was used as a surrogate for in vivo inhibition of MEK1/2 was determined by immunoblotting Results. At the highest concentration used in vitro (10 mu M) AZD6244 only inhibited growth by 50% in 5 of the 23 cell lines Against the in vivo tumor panels, AZD6244 induced significant differences in FFS distribution in 10 of 37 (27%) solid tumor models and 0 of 6 acute lymphoblastic leukemia (ALL) models There were no objective responses Pharmacodynamic studies indicated at this close and schedule AZD6244 completely inhibited ERK1/2 phosphorylation AZD6244 was evaluated against two IPA xenografts, BT-35 (wild-type BRAF) and BT 40 (mutant [V600E] BRAF) BT-40 xenografts were highly sensitive to AZD6244, whereas BT-35 xenografts progressed on AZD6244 treatment Conclusions. At the close and schedule of administration used, AZD6244 as a single agent had limited in vitro and in vivo activity against the PPTP tumor panels despite inhibition of MEK1/2 activity However, AZD6244 was highly active against BT-40 JPA xenografts that harbor constitutively activated BRAF, causing complete regressions Pediatr Blood Cancer 2010,55 668-677 (C) 2010 Wiley-Liss, Inc
C1 [Kolb, E. Anders] AI duPont Hosp tor Children, Nemours Ctr Childhood Canc Res, Wilmington, DE 19803 USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Houghton, Peter J.; Morton, Christopher L.; Neale, Geoffrey; Phelps, Doris; Billups, Catherine] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Carol, Hernan; Lock, Richard] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
[Kang, Min H.; Reynolds, C. Patrick] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Smith, Malcolm A.] NCI, Cancer Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Kolb, EA (reprint author), AI duPont Hosp tor Children, Nemours Ctr Childhood Canc Res, 1600 Rockland Rd, Wilmington, DE 19803 USA.
RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock,
Richard/G-4253-2013;
OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C.
Patrick/0000-0002-2827-8536
FU National Cancer Institute [NOI-CM-42216, CA21765, CA108786]
FX Grant sponsor National Cancer Institute, Grant numbers NOI-CM-42216,
CA21765, CA108786
NR 33
TC 30
Z9 30
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD OCT
PY 2010
VL 55
IS 4
BP 668
EP 677
DI 10.1002/pbc.22576
PG 10
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 646LU
UT WOS:000281542900016
PM 20806365
ER
PT J
AU Chao, MM
Todd, MA
Kontny, U
Neas, K
Sullivan, MJ
Hunter, AG
Picketts, DJ
Kratz, CP
AF Chao, Mwe Mwe
Todd, Matthew A.
Kontny, Udo
Neas, Katherine
Sullivan, Michael J.
Hunter, Alasdair G.
Picketts, David J.
Kratz, Christian P.
TI T-Cell Acute Lymphoblastic Leukemia in Association With
Borjeson-Forssman-Lehmann Syndrome Due To a Mutation in PHF6
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE Borjeson-Forssman-Lehmann syndrome; PHF6; T-cell ALL/lymphoma
ID GERMLINE MUTATIONS; GENE; THROMBOCYTOPENIA; PROTEIN
AB Borjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked mental retardation syndrome that is caused by germline mutations in PHF6 We describe a 9-year-old male with BFLS, who developed T-cell acute lymphoblastic leukemia (T-ALL) The PHF6 gene is located on the X chromosome and encodes a protein with two PHD-type zinc finger domains and four nuclear localization sequences Previously, overexpression of Phf6 was observed in murine T-cell lymphomas Our observation indicates that BEES may represent a cancer predisposition syndrome and that mutations of PHF6 contribute to T-ALL Pediatr Blood Cancer 2010,55 722-724 (C) 2010 Wiley-Liss, Inc
C1 [Kratz, Christian P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Chao, Mwe Mwe] Childrens Natl Med Ctr, Div Pediat Hematol Oncol, Washington, DC 20010 USA.
[Todd, Matthew A.; Picketts, David J.] Univ Ottawa, Ottawa Hlth Res Inst, Ottawa, ON, Canada.
[Kontny, Udo] Univ Freiburg, Div Pediat Hematol Oncol, Dept Pediat & Adolescent Med, Freiburg, Germany.
[Neas, Katherine] Capital & Coast Dist Hlth Board, Cent & So Reg Genet Serv, Wellington, New Zealand.
[Sullivan, Michael J.] Univ Otago, Dept Paediat, Childrens Canc Res Grp, Childrens Haematol Oncol Ctr,Chrsitchurch Sch Med, Christchurch, New Zealand.
[Hunter, Alasdair G.] Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada.
RP Kratz, CP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room EPS 7030, Rockville, MD 20852 USA.
RI Sullivan, Michael/B-5459-2012
FU National Cancer Institute, National Institutes of Health; Canadian
Institutes of Health Research
FX C P K 's work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health. D J P's work
is funded by grants from the Canadian Institutes of Health Research We
thank Lemuel Racacho for technical assistance
NR 13
TC 18
Z9 18
U1 3
U2 7
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD OCT
PY 2010
VL 55
IS 4
BP 722
EP 724
DI 10.1002/pbc.22574
PG 3
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 646LU
UT WOS:000281542900023
PM 20806366
ER
PT J
AU Moon, SS
Wang, YH
Shane, AL
Trang, N
Ray, P
Dennehy, P
Baek, LJ
Parashar, U
Glass, RI
Jiang, BM
AF Moon, Sung-Sil
Wang, Yuhuan
Shane, Andi L.
Trang Nguyen
Ray, Pratima
Dennehy, Penelope
Baek, Luck Ju
Parashar, Umesh
Glass, Roger I.
Jiang, Baoming
TI Inhibitory Effect of Breast Milk on Infectivity of Live Oral Rotavirus
Vaccines
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE rotavirus; RV1; RV5; neutralizing activity; breast milk
ID INFANTS; DIARRHEA; EFFICACY; SAFETY; IMMUNOGENICITY; CHILDREN; RIX4414;
PROTECTION; SEROTYPES; RIT-4237
AB Background: Live oral rotavirus vaccines have been less immunogenic and efficacious among children in poor developing countries compared with middle income and industrialized countries for reasons that are not yet completely understood. We assessed whether the neutralizing activity of breast milk could lower the titer of vaccine virus and explain this difference in vitro.
Methods: Breast milk samples were collected from mothers who were breast-feeding infants 4 to 29 weeks of age (ie, vaccine eligible age) in India (N = 40), Vietnam (N = 77), South Korea (N = 34), and the United States (N = 51). We examined breast milk for rotavirus-specific IgA and neutralizing activity against 3 rotavirus vaccine strains-RV1, RV5 G1, and 116E using enzyme immunoassays. The inhibitory effect of breast milk on RV1 was further examined by a plaque reduction assay.
Findings: Breast milk from Indian women had the highest IgA and neutralizing titers against all 3 vaccine strains, while lower but comparable median IgA and neutralizing titers were detected in breast milk from Korean and Vietnamese women, and the lowest titers were seen in American women. Neutralizing activity was greatest against the 2 vaccine strains of human origin, RV1 and 116E. This neutralizing activity in one half of the breast milk specimens from Indian women could reduce the effective titer of RV1 by similar to 2 logs, of 116E by 1.5 logs, and RV5 G1 strain by similar to 1 log more than that of breast milk from American women.
Interpretation: The lower immunogenicity and efficacy of rotavirus vaccines in poor developing countries could be explained, in part, by higher titers of IgA and neutralizing activity in breast milk consumed by their infants at the time of immunization that could effectively reduce the potency of the vaccine. Strategies to overcome this negative effect, such as delaying breast-feeding at the time of immunization, should be evaluated.
C1 [Jiang, Baoming] Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA.
[Shane, Andi L.] Emory Univ, Div Pediat Infect Dis, Atlanta, GA 30322 USA.
[Trang Nguyen] Natl Inst Hyg & Epidemiol, Hanoi, Vietnam.
[Ray, Pratima] All India Inst Med Sci, Dept Pediat, Delhi, India.
[Dennehy, Penelope] Rhode Isl Hosp, Dept Pediat, Providence, RI USA.
[Baek, Luck Ju] Korea Univ, Coll Med, Dept Microbiol, Seoul 136705, South Korea.
[Glass, Roger I.] NIH, Fogarty Int Ctr, Rockville, MD USA.
RP Jiang, BM (reprint author), Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, Natl Ctr Immunizat & Resp Dis, MS G04,1600 Clifton Rd NE, Atlanta, GA 30333 USA.
EM bxj4@cdc.gov
OI Dennehy, Penelope/0000-0002-2259-5370; Ray, Pratima/0000-0002-2182-2279
FU CDC; NIH National Center for Research Resources [K12RR017643,
1KL2RR025009]
FX Supported (in part) by CDC program funds. Also supported (in part) by
the NIH National Center for Research Resources, grants K12RR017643 and
1KL2RR025009 (to S.A.L.).
NR 25
TC 57
Z9 57
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD OCT
PY 2010
VL 29
IS 10
BP 919
EP 923
DI 10.1097/INF.0b013e3181e232ea
PG 5
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 653EC
UT WOS:000282069700005
PM 20442687
ER
PT J
AU Vanprapar, N
Cressey, TR
Chokephaibulkit, K
Muresan, P
Plipat, N
Sirisanthana, V
Prasitsuebsai, W
Hongsiriwan, S
Chotpitayasunondh, T
Eksaengsri, A
Toye, M
Smith, ME
McIntosh, K
Capparelli, E
Yogev, R
AF Vanprapar, Nirun
Cressey, Tim R.
Chokephaibulkit, Kulkanya
Muresan, Petronella
Plipat, Nottasorn
Sirisanthana, Virat
Prasitsuebsai, Wasana
Hongsiriwan, Suchat
Chotpitayasunondh, Tawee
Eksaengsri, Achara
Toye, MariPat
Smith, Mary Elizabeth
McIntosh, Kenneth
Capparelli, Edmund
Yogev, Ram
CA IMPAACT P1056 Team
TI A Chewable Pediatric Fixed-dose Combination Tablet of Stavudine,
Lamivudine, and Nevirapine Pharmacokinetics and Safety Compared With the
Individual Liquid Formulations in Human Immunodeficiency Virus-infected
Children in Thailand
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article; Proceedings Paper
CT 16th Conference on Retroviruses and Opportunistic Infections (CROI)
CY FEB 08-11, 2009
CL Montreal, CANADA
DE pharmacokinetics; antiretrovirals; fixed-dose combinations; children;
Thailand
ID HIV-INFECTED CHILDREN; ACTIVE ANTIRETROVIRAL THERAPY;
PLASMA-CONCENTRATIONS; EFFICACY; 2',3'-DIDEHYDRO-3'-DEOXYTHYMIDINE;
THAILAND; PROGRAM
AB Background: Pediatric fixed-dose combinations (FDCs) are needed to facilitate antiretroviral therapy in children. We evaluated the relative bioavailability, safety, and therapeutic adequacy of a novel chewable pediatric FDC tablet of stavudine (7 mg), lamivudine (30 mg), and nevirapine (50 mg), referred to as GPO-VIR S7, and compared it with the individual original brand-name liquid formulations in human immunodeficiency virus-infected Thai children.
Methods: The International Maternal Pediatric Adolescent AIDS Clinical Trials group (IMPAACT) P1056 study was a phase I/II, 2-arm, randomized, open-label, multidose pharmacokinetic cross-over study. Children >= 6 to <= 30 kg receiving nevirapine-based HAART for at least 4 weeks were randomized to receive GPO-VIR S7 chewable tablets or the equivalent liquid formulations. Children were stratified by weight and dosing was weight-based. Intensive 12-hour blood sampling was performed on day 28, and subjects then crossed-over to the alternate formulation at equal doses with identical 12-hour sampling on day 56. Pharmacokinetic indices were determined by noncompartmental analysis.
Results: Thirty-four children completed the study. While taking Government Pharmaceutical Organization (GPO)-VIR S7 the geometric mean (90% CI) area under the curve was 1.54 mu g.hr/mL (1.42-1.67) for stavudine, 6.39 (5.82-7.00) for lamivudine, and 74.06 (65.62-83.60) for nevirapine. Nevirapine drug exposure for GPO-VIR S7 was therapeutically adequate. Geometric mean area under the curve ratios (90% CI) of GPO-VIR S7/liquid formulation for stavudine, lamivudine, and nevirapine were 0.97 (0.92-1.02), 1.41 (1.30-1.53), and 1.08 (1.04-1.13), respectively. No serious drug-related toxicity was reported.
Conclusions: The chewable FDC was safe and provided therapeutically adequate plasma drug exposures in human immunodeficiency virus-infected children. Substituting the FDC for liquid formulations can simplify antiretroviral therapy.
C1 [Vanprapar, Nirun; Chokephaibulkit, Kulkanya; Prasitsuebsai, Wasana] Mahidol Univ, Dept Pediat, Fac Med, Siriraj Hosp, Bangkok 10700, Thailand.
[Cressey, Tim R.] Chiang Mai Univ, Dept Med Technol, Program HIV Prevent & Treatment IRD, Fac Associated Med Sci, Chiang Mai 50000, Thailand.
[Cressey, Tim R.; Muresan, Petronella; McIntosh, Kenneth] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Plipat, Nottasorn] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Sirisanthana, Virat; McIntosh, Kenneth] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand.
[Hongsiriwan, Suchat] Chonburi Reg Hosp, Dept Pediat, Chon Buri, Thailand.
[Chotpitayasunondh, Tawee] QSNICH, Bangkok, Thailand.
[Eksaengsri, Achara] GPO, Bangkok, Thailand.
[Toye, MariPat] Baystate Med Ctr, Dept Pediat, Springfield, MA 01199 USA.
[Smith, Mary Elizabeth] NIAID, NIH, Bethesda, MD 20892 USA.
Childrens Hosp, Pediat Pharmacol Res Unit, Boston, MA 02115 USA.
[Capparelli, Edmund] Univ Calif San Diego, San Diego, CA 92103 USA.
[Yogev, Ram] Chicago Childrens Mem Hosp, Chicago, IL USA.
RP Chokephaibulkit, K (reprint author), Mahidol Univ, Dept Pediat, Fac Med, Siriraj Hosp, 2 Prannok Rd, Bangkok 10700, Thailand.
EM sikch@mahidol.ac.th
FU NIAID NIH HHS [U01 AI068632-03, 1 U01 AI068616, 5 U01 AI41110, AI068632,
U01 AI041110, U01 AI068616, U01 AI068632, U01 AI069429, U01AI069429, UM1
AI068632]; NICHD NIH HHS [HHSN267200800001C]; NIDDK NIH HHS
[HHSN267200800001G]
NR 31
TC 18
Z9 18
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD OCT
PY 2010
VL 29
IS 10
BP 940
EP 944
DI 10.1097/INF.0b013e3181e2189d
PG 5
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 653EC
UT WOS:000282069700009
PM 20453709
ER
PT J
AU Walsh, TJ
Maertens, JA
Madero, L
Reilly, AF
Lehrnbecher, T
Groll, AH
Jafri, HS
Green, M
Nania, JJ
Bourque, MR
Wise, BA
Strohmaier, KM
Taylor, AF
Kartsonis, NA
Chow, JW
Arndt, CAS
dePauw, B
AF Walsh, Thomas J.
Maertens, Johan A.
Madero, Luis
Reilly, Anne F.
Lehrnbecher, Thomas
Groll, Andreas H.
Jafri, Hasan S.
Green, Michael
Nania, Joseph J.
Bourque, Michael R.
Wise, Beth Ann
Strohmaier, Kim M.
Taylor, Arlene F.
Kartsonis, Nicholas A.
Chow, Joseph W.
Arndt, Carola A. S.
dePauw, Ben E.
TI Caspofungin Versus Liposomal Amphotericin B Are They Really Comparable?
Reply
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Letter
ID PEDIATRIC-PATIENTS; ANTIFUNGAL THERAPY; PERSISTENT FEVER; MULTICENTER;
NEUTROPENIA; INFECTIONS; CHILDREN
C1 [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Walsh, Thomas J.] Cornell Univ, Transplantat Oncol Infect Dis Program, Weill Cornell Med Coll, New York, NY 10021 USA.
[Maertens, Johan A.] Katholieke Univ Leuven Hosp, Acute Leukemia & Stem Cell Transplantat Unit, Dept Hematol, Leuven, Belgium.
[Madero, Luis] Hosp Univ Nino Jesus, Madrid, Spain.
[Reilly, Anne F.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA USA.
[Lehrnbecher, Thomas] Goethe Univ Frankfurt, Frankfurt, Germany.
[Groll, Andreas H.] Univ Childrens Hosp Munster, Infect Dis Res Program, Dept Pediat Hematol Oncol, Munster, Germany.
[Jafri, Hasan S.] Univ Texas SW Med Ctr Dallas, Div Pediat Infect Dis, Dept Pediat, Dallas, TX 75390 USA.
[Jafri, Hasan S.] MedImmune, Clin Dev, Gaithersburg, MD USA.
[Green, Michael] Childrens Hosp Pittsburgh, Dept Pediat Surg & Clin, Div Infect Dis, Pittsburgh, PA 15213 USA.
[Green, Michael] Childrens Hosp Pittsburgh, Dept Translat Sci, Div Infect Dis, Pittsburgh, PA 15213 USA.
[Nania, Joseph J.] Vanderbilt Univ, Dept Pediat, Div Pediat Infect Dis, Nashville, TN USA.
[Bourque, Michael R.; Wise, Beth Ann; Strohmaier, Kim M.; Taylor, Arlene F.; Kartsonis, Nicholas A.; Chow, Joseph W.] Merck Res Labs, N Wales, PA USA.
[Arndt, Carola A. S.] Mayo Clin, Rochester, MN USA.
[dePauw, Ben E.] Radboud Univ Nijmegen, Nijmegen Med Ctr, NL-6525 ED Nijmegen, Netherlands.
RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
NR 6
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD OCT
PY 2010
VL 29
IS 10
BP 986
EP 987
DI 10.1097/INF.0b013e3181f2d88c
PG 2
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 653EC
UT WOS:000282069700025
ER
PT J
AU Staber, J
Burnightt, E
Korsakov, P
Sarvida, ME
McCaffrey, A
Kaminski, J
McCray, P
AF Staber, Janice
Burnightt, Erin
Korsakov, Pasha
Sarvida, Marie-Ellen
McCaffrey, Anton
Kaminski, Joseph
McCray, Paul
TI A GENE TRANSFER APPROACH TOWARDS HEMOPHILIA A CORRECTION USING THE
PIGGYBAC TRANSPOSON VECTOR
SO PEDIATRIC RESEARCH
LA English
DT Meeting Abstract
CT 51st Scientific Meeting on Annual Midwest Society-for-Pediatric-Research
CY OCT 21-22, 2010
CL Iowa City, IA
SP Midwest Soc Pediat Res
C1 [Staber, Janice; Burnightt, Erin; Korsakov, Pasha] UIHC, Dept Pediat, Iowa City, IA USA.
[Sarvida, Marie-Ellen] Loyola Univ Hlth Syst, Maywood, IL USA.
[McCaffrey, Anton] UIHC, Iowa City, IA USA.
[Kaminski, Joseph] Natl Inst Hlth, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU INT PEDIATRIC RESEARCH FOUNDATION, INC
PI BALTIMORE
PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA
SN 0031-3998
J9 PEDIATR RES
JI Pediatr. Res.
PD OCT
PY 2010
VL 68
IS 4
MA 10
BP 356
EP 356
PG 1
WC Pediatrics
SC Pediatrics
GA 653FO
UT WOS:000282074100026
ER
PT J
AU Benjamin, DK
Stoll, BJ
Gantz, MG
Walsh, MC
Sanchez, PJ
Das, A
Shankaran, S
Higgins, RD
Auten, KJ
Miller, NA
Walsh, TJ
Laptook, AR
Carlo, WA
Kennedy, KA
Finer, NN
Duara, S
Schibler, K
Chapman, RL
Van Meurs, KP
Frantz, ID
Phelps, DL
Poindexter, BB
Bell, EF
O'Shea, TM
Watterberg, KL
Goldberg, RN
AF Benjamin, Daniel K., Jr.
Stoll, Barbara J.
Gantz, Marie G.
Walsh, Michele C.
Sanchez, Pablo J.
Das, Abhik
Shankaran, Seetha
Higgins, Rosemary D.
Auten, Kathy J.
Miller, Nancy A.
Walsh, Thomas J.
Laptook, Abbot R.
Carlo, Waldemar A.
Kennedy, Kathleen A.
Finer, Neil N.
Duara, Shahnaz
Schibler, Kurt
Chapman, Rachel L.
Van Meurs, Krisa P.
Frantz, Ivan D., III
Phelps, Dale L.
Poindexter, Brenda B.
Bell, Edward F.
O'Shea, T. Michael
Watterberg, Kristi L.
Goldberg, Ronald N.
CA Eunice Kennedy Shriver Natl Inst
TI Neonatal Candidiasis: Epidemiology, Risk Factors, and Clinical Judgment
SO PEDIATRICS
LA English
DT Article
DE candidiasis; premature infant; risk factors
ID BIRTH-WEIGHT INFANTS; FLUCONAZOLE PROPHYLAXIS; INVASIVE CANDIDIASIS;
FUNGAL COLONIZATION; CANDIDEMIA; INFECTION; SUSCEPTIBILITY; MULTICENTER;
THERAPY
AB OBJECTIVE: Invasive candidiasis is a leading cause of infection-related morbidity and mortality in extremely low birth weight (< 1000-g) infants. We quantified risk factors that predict infection in premature infants at high risk and compared clinical judgment with a prediction model of invasive candidiasis.
METHODS: The study involved a prospective observational cohort of infants < 1000 g birth weight at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. At each sepsis evaluation, clinical information was recorded, cultures were obtained, and clinicians prospectively recorded their estimate of the probability of invasive candidiasis. Two models were generated with invasive candidiasis as their outcome: (1) potentially modifiable risk factors; and (2) a clinical model at time of blood culture to predict candidiasis.
RESULTS: Invasive candidiasis occurred in 137 of 1515 (9.0%) infants and was documented by positive culture from >= 1 of these sources: blood (n = 96); cerebrospinal fluid (n = 9); urine obtained by catheterization (n = 52); or other sterile body fluid (n = 10). Mortality rate was not different for infants who had positive blood culture compared with those with isolated positive urine culture. Incidence of candida varied from 2% to 28% at the 13 centers that enrolled >= 50 infants. Potentially modifiable risk factors included central catheter, broad-spectrum antibiotics (eg, third-generation cephalosporins), intravenous lipid emulsion, endotracheal tube, and antenatal antibiotics. The clinical prediction model had an area under the receiver operating characteristic curve of 0.79 and was superior to clinician judgment (0.70) in predicting subsequent invasive candidiasis.
CONCLUSION: Previous antibiotics, presence of a central catheter or endotracheal tube, and center were strongly associated with invasive candidiasis. Modeling was more accurate in predicting invasive candidiasis than clinical judgment. Pediatrics 2010;126:e865-e873
C1 [Stoll, Barbara J.] Emory Univ & Childrens Healthcare Atlanta, Dept Pediat, Atlanta, GA USA.
[Gantz, Marie G.] RTI Int, Statist Epidemiol Unit, Res Triangle Pk, NC USA.
[Walsh, Michele C.] Case Western Reserve Univ, Dept Pediat, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA.
[Sanchez, Pablo J.; Miller, Nancy A.] Univ Texas Dallas, Dept Pediat, SW Med Ctr, Dallas, TX 75230 USA.
[Das, Abhik] RTI Int, Statist & Epidemiol Unit, Rockville, MD USA.
[Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Walsh, Thomas J.] Human Dev & Natl Canc Inst, Natl Inst Hlth, Bethesda, MD USA.
[Laptook, Abbot R.] Brown Univ, Dept Pediat, Women & Infants Hosp, Providence, RI 02912 USA.
[Carlo, Waldemar A.] Univ Alabama, Dept Pediat, Birmingham, AL USA.
[Kennedy, Kathleen A.] Univ Texas Houston, Sch Med, Dept Pediat, Houston, TX USA.
[Finer, Neil N.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA.
[Duara, Shahnaz] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Schibler, Kurt] Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH USA.
[Chapman, Rachel L.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Frantz, Ivan D., III] Tufts Med Ctr, Boston, MA USA.
[Phelps, Dale L.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Poindexter, Brenda B.] Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
[Bell, Edward F.] Univ Iowa, Iowa City, IA USA.
[O'Shea, T. Michael] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Watterberg, Kristi L.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Auten, Kathy J.; Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
RP Benjamin, DK (reprint author), Duke Clin, Res Inst, 2400 Pratt St, Durham, NC 27705 USA.
EM danny.benjamin@duke.edu
FU Thrasher Research Fund; NICHD [HD044799]; National Institutes of Health
FX Dr Benjamin received support from the Thrasher Research Fund and the
NICHD (grant HD044799). The National Institutes of Health and NICHD
provided grant support for the Neonatal Research Network's candidiasis
study (recruitment 2004-2007). Data collected at participating sites of
the NICHD NRN were transmitted to RTI International, the
data-coordinating center (DCC) for the network, which stored, managed,
and analyzed the data for this study. On behalf of the NRN, Drs Das (DCC
principal investigator) and Gantz (DCC Statistician) had full access to
all the data in the study and take responsibility for the integrity of
the data and accuracy of the data analysis. Dr Benjamin also had full
access to all of the data in the study through RTI International and had
final responsibility for the decision to submit for publication.; The
NRN steering committee chairs were Alan H. Jobe, MD, PhD (University of
Cincinnati) (2001-2006) and Michael S. Caplan, MD (University of Chicago
Pritzker School of Medicine) (2006-2011). The following investigators
(and NIH/NICHD grant numbers), in addition to those listed as authors,
participated in this study: William Oh, MD, and Angelita Hensman, BSN,
RNC (Brown University, Women & Infants Hospital of Rhode Island) (U10
HD27904); Nancy S. Newman, BA, RN (Case Western Reserve University and
Rainbow Babies & Children's Hospital) (CCTS UL1 RR24989, GCRC M01 RR80,
and U10 HD21364); C. Michael Cotten, MD, and Katherine A. Foy, RN (Duke
University Hospital, Alamance Regional Medical Center, and Durham
Regional Hospital) (CCTS UL1 RR24128, GCRC M01 RR30, and U10 HD40492);
Ellen C. Hale, RN, BS, CCRC, Ann M. Blackwelder, RNC, MS, and Michelle
Tidwell, BSN (Emory University, Children's Healthcare of Atlanta, Grady
Memorial Hospital, and Emory Hospital Midtown) (CCTS UL1 RR25008, GCRC
M01 RR39, and U10 HD27851); Stephanie Wilson Archer, MA (NICHD); Brenda
L. MacKinnon, RNC, Ellen Nylen, RN, and Anne Furey, MPH (Floating
Hospital for Children at Tufts Medical Center) (GCRC M01 RR54 and U10
HD53119); James A. Lemons, MD, Dianne Herron, RN, Lucy Miller, RN, BSN,
CCRC, and Leslie D. Wilson, RN, BSN (Indiana University Hospital,
Methodist Hospital, Riley Hospital for Children, and Wishard Health
Services) (GCRC M01 RR750 and U10 HD27856); W. Kenneth Poole, PhD, Betty
Hastings, Carolyn Petrie Huitema, MS, Kristin M. Zaterka-Baxter, RN,
Scott E. Schaefer, MS, and Jeanette O'Donnell Auman, BS (RTI
International) (U10 HD36790); David K. Stevenson, MD, M. Bethany Ball,
BS, CCRC, and Melinda S. Proud, RCP (Lucile Packard Children's Hospital)
(GCRC M01 RR70 and U10 HD27880); Monica V. Collins, RN, BSN, MaEd, and
Shirley S. Cosby, RN, BSN (University of Alabama at Birmingham Health
System and Children's Hospital of Alabama) (GCRC M01 RR32 and U10
HD34216); Maynard R. Rasmussen, MD, David Kaegi, MD, Kathy Arnell, RNC,
Clarence Demetrio, RN, Chris Henderson, RCP, CRTT, and Wade Rich, BSHS,
RRT (University of California-San Diego Medical Center and Sharp Mary
Birch Hospital for Women) (U10 HD40461); Kurt Schibler, MD, Edward F.
Donovan, MD, Kathleen Bridges, MD, Barbara Alexander, RN, Cathy Grisby,
BSN, CCRC, Holly L. Mincey, RN, BSN, and Jody Hessing, RN (Cincinnati
Children's Hospital Medical Center, University of Cincinnati Hospital,
and Good Samaritan Hospital) (GCRC M01 RR8084 and U10 HD27853); Karen J.
Johnson, RN, BSN (University of Iowa Children's Hospital) (CTSA UL1
RR24979, GCRC M01 RR59, and U10 HD53109); Ruth Everett-Thomas, RN, MSN
(University of Miami Holtz Children's Hospital) (GCRC M01 RR16587 and
U10 HD21397); Conra Backstrom Lacy, RN (University of New Mexico Health
Sciences Center) (GCRC M01 RR997 and U10 HD53089); Linda J. Reubens, RN,
CCRC, Erica Burnell, RN, Cassandra A. Horihan, MS, and Rosemary L.
Jensen (University of Rochester Golisano Children's Hospital) (GCRC M01
RR44 and U10 HD40521); Walid A. Salhab, MD, Charles R. Rosenfeld, MD,
Gaynelle Hensley, RN, and Melissa H. Leps, RN, and Alicia Guzman
(University of Texas Southwestern Medical Center at Dallas Parkland
Health & Hospital System and Children's Medical Center Dallas) (CCTS UL1
RR24982, GCRC M01 RR633, and U10 HD40689); Jon E. Tyson, MD, MPH, Esther
G. Akpa, RN, BSN, Beverly Harris, RN, BSN, Anna E. Lis, RN, BSN, Georgia
E. McDavid, RN, Sarah Martin, RN, BSN, and Patti L.; Pierce Tate, RCP
(University of Texas Health Science Center at Houston Medical School and
Childrens Memorial Hermann Hospital) (U10 HD21373); Roger G. Faix, MD,
Bradley A. Yoder, MD, Karen A. Osborne, RN, BSN, Jennifer J. Jensen, RN,
BSN, Cynthia Spencer, RNC, R. Edison Steele, RN, Karena Strong, RN, BSN,
and Kimberlee Weaver-Lewis, RN, BSN (University of Utah University
Hospital, LDS Hospital, and Primary Children's Medical Center) (CTSA UL1
RR25764, GCRC M01 RR64, and U10 HD53124); Nancy J. Peters, RN, CCRP
(Wake Forest University Baptist Medical Center, Forsyth Medical Center,
and Brenner Children's Hospital) (GCRC M01 RR7122 and U10 HD40498);
Rebecca Bara, RN, BSN (Wayne State University, Hutzel Women's Hospital
and Children's Hospital of Michigan) (U10 HD21385); and Richard A.
Ehrenkranz, MD, Rachel L. Chapman, MD, Patricia Gettner, RN, and Monica
Konstantino, RN, BSN (Yale University and Yale-New Haven Children's
Hospital) (CCTS UL1 RR24139, GCRC M01 RR6022, and U10 HD27871).
NR 24
TC 90
Z9 92
U1 0
U2 4
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD OCT
PY 2010
VL 126
IS 4
BP E865
EP E873
DI 10.1542/peds.2009-3412
PG 9
WC Pediatrics
SC Pediatrics
GA 658WW
UT WOS:000282526100014
PM 20876174
ER
PT J
AU Choi, SH
Aid, S
Choi, U
Bosetti, F
AF Choi, S-H
Aid, S.
Choi, U.
Bosetti, F.
TI Cyclooxygenases-1 and-2 differentially modulate leukocyte recruitment
into the inflamed brain
SO PHARMACOGENOMICS JOURNAL
LA English
DT Article
DE LPS; cyclooxygenase; neuroinflammation; leukocyte
ID CENTRAL-NERVOUS-SYSTEM; NONSTEROIDAL ANTIINFLAMMATORY AGENTS;
EXPERIMENTAL PNEUMOCOCCAL MENINGITIS; DENDRITIC CELL-MIGRATION;
NECROSIS-FACTOR-ALPHA; PROSTAGLANDIN E-2; INFLAMMATORY RESPONSE; BARRIER
PERMEABILITY; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE
AB Peripheral leukocyte recruitment in neuroinflammatory conditions can exacerbate brain tissue damage by releasing cytotoxic mediators and by increasing vascular permeability. Cyclooxygenase (COX)-derived prostaglandins promote the migration of several immune cells in vitro, however, the specific roles of COX-1 and -2 on leukocyte recruitment in vivo have not been investigated. To examine the specific effects of COX-1 or COX-2 deficiency on neuroinflammation-induced leukocyte infiltration, we used a model of intracerebroventricular lipopolysaccharide (LPS)-induced neuroinflammation in COX-1(-/-), COX-2(-/-), and their respective wild-type (WT) ((+/+)) mice. After LPS, leukocyte infiltration and inflammatory response were attenuated in COX-1(-/-) and increased in COX-2(-/-) mice, compared with their respective WT controls. This influx of leukocytes was accompanied by a marked disruption of blood-brain barrier and differential expression of chemokines. These results indicate that COX-1 and COX-2 deletion differentially modulate leukocyte recruitment during neuroinflammation, and suggest that inhibition of COX-1 activity is beneficial, whereas COX-2 inhibition is detrimental, during a primary neuroinflammatory response. The Pharmacogenomics Journal (2010) 10, 448-457; doi:10.1038/tpj.2009.68; published online 29 December 2009
C1 [Choi, S-H; Aid, S.; Bosetti, F.] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Choi, U.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
RP Bosetti, F (reprint author), NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, 9 Mem Dr,Bldg 9,Rm 1S126, Bethesda, MD 20892 USA.
EM frances@mail.nih.gov
FU National Institute on Aging, National Institutes of Health
FX We thank Dr Robert Langenbach (Laboratory of Molecular Carcinogenesis,
National Institute of Environmental Health Sciences, National Institutes
of Health) for providing COX-1 / , COX-2 / , and
their WT mice. This work was supported by the Intramural Research
Program of the National Institute on Aging, National Institutes of
Health.
NR 70
TC 25
Z9 27
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1470-269X
J9 PHARMACOGENOMICS J
JI Pharmacogenomics J.
PD OCT
PY 2010
VL 10
IS 5
BP 448
EP 457
DI 10.1038/tpj.2009.68
PG 10
WC Genetics & Heredity; Pharmacology & Pharmacy
SC Genetics & Heredity; Pharmacology & Pharmacy
GA 660DM
UT WOS:000282619700008
PM 20038958
ER
PT J
AU Ohlmann, P
de Castro, S
Brown, GG
Gachet, C
Jacobson, KA
Harden, TK
AF Ohlmann, Philippe
de Castro, Sonia
Brown, Garth G., Jr.
Gachet, Christian
Jacobson, Kenneth A.
Harden, T. Kendall
TI Quantification of recombinant and platelet P2Y(1) receptors utilizing a
[I-125]-labeled high-affinity antagonist
2-iodo-N-6-methyl-(N)-methanocarba-2 '-deoxyadenosine-3 ',5
'-bisphosphate ([I-126]MRS2500)
SO PHARMACOLOGICAL RESEARCH
LA English
DT Article
DE P2Y1 receptor; Competitive antagonist; Radioligand; MRS2500; Platelet
ID GENETIC POLYMORPHISMS; P2Y1 RECEPTOR; ACTIVATION; ADP; AGGREGATION;
AGONIST; PATHOPHYSIOLOGY; DESENSITIZATION; CLOPIDOGREL; DIMORPHISM
AB The ADP-activated P2Y(1) receptor is broadly expressed and plays a crucial role in ADP-promoted platelet aggregation. We previously synthesized 2-iodo-N6-methy1-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate (MR52500), as a selective, high-affinity, competitive antagonist of this receptor. Here we report utilization of a trimethylstannyl precursor molecule for the multi-step radiochemical synthesis of a [I-125]-labeled form of MRS2500. [I-125]MRS2500 bound selectively to Sf9 insect cell membranes expressing the human P2Y(1) receptor but did not specifically bind to membranes isolated from empty vector-infected cells. Binding of [I-125]MRS2500 to P2Y(1) receptors was saturable with a Kd of 1.2 nM. Known agonists and antagonists of the P2Y(1) receptor inhibited [I-125]MRS2500 binding to P2Y(1) receptor-expressing membranes with potencies in agreement with those previously observed in functional assays of this receptor. A high-affinity binding site for [I-125]MRS2500 also was observed on intact human platelets (Kd = 0.61 nM) and mouse platelets (Kd =1.20 nM) that exhibited the pharmacological selectivity of the P2Y(1) receptor. The densities of sites observed were 151 sites/platelet and 229 sites/platelet in human and mouse platelets, respectively. In contrast, specific binding was not observed in platelets isolated from P2Y(1) receptor(-/-) mice. Taken together, these data illustrate the synthesis and characterization of a novel P2Y(1) receptor radioligand and its utility for examining P2Y(1) receptors natively expressed on human and mouse platelets. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Ohlmann, Philippe; Gachet, Christian] INSERM, UMR S949, F-67087 Strasbourg, France.
[Ohlmann, Philippe; Gachet, Christian] Univ Strasbourg, F-67087 Strasbourg, France.
[de Castro, Sonia; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA.
[Brown, Garth G., Jr.] PerkinElmer Inc, Waltham, MA 02451 USA.
RP Harden, TK (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, CB 7365, Chapel Hill, NC 27599 USA.
EM tkh@med.unc.edu
RI de castro, sonia/E-7303-2012; Jacobson, Kenneth/A-1530-2009; Gachet,
Christian/H-9156-2016
OI de castro, sonia/0000-0002-3838-6856; Jacobson,
Kenneth/0000-0001-8104-1493;
FU National Institutes of Health [GM38213]; NIDDK; Ministerio de Educacion
y Ciencia, Spain
FX We thank Anthony Joseph (PerkinElmer) for technical assistance. This
work was supported by National Institutes of Health grant GM38213 and by
the NIDDK Intramural Research Program. S. de Castro thanks Ministerio de
Educacion y Ciencia, Spain for financial support.
NR 27
TC 13
Z9 13
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-6618
J9 PHARMACOL RES
JI Pharmacol. Res.
PD OCT
PY 2010
VL 62
IS 4
BP 344
EP 351
DI 10.1016/j.phrs.2010.05.007
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 644IN
UT WOS:000281368600008
PM 20594939
ER
PT J
AU Arko, L
Katsyv, I
Park, GE
Luan, WP
Park, JK
AF Arko, Leopold
Katsyv, Igor
Park, Grace E.
Luan, William Patrick
Park, John K.
TI Experimental approaches for the treatment of malignant gliomas
SO PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
DE Malignant glioma; Glioblastoma; Anaplastic astrocytoma; Chemotherapy;
Biologic therapy; Immunotherapy; Clinical trial
ID GROWTH-FACTOR RECEPTOR; PHASE-II TRIAL; RECURRENT
GLIOBLASTOMA-MULTIFORME; TYROSINE KINASE INHIBITOR; HIGH-GRADE GLIOMA;
NEWLY-DIAGNOSED GLIOBLASTOMA; BRAIN-TUMOR CONSORTIUM; ACTIVATED
KILLER-CELLS; CENTRAL-NERVOUS-SYSTEM; LONG-TERM SURVIVAL
AB Malignant gliomas, which include glioblastomas and anaplastic astrocytomas, are the most common primary tumors of the brain. Over the past 30 years, the standard treatment for these tumors has evolved to include maximal safe surgical resection, radiation therapy and temozolomide chemotherapy. While the median survival of patients with glioblastomas has improved from 6 months to 14.6 months, these tumors continue to be lethal for the vast majority of patients. There has, however, been recent substantial progress in our mechanistic understanding of tumor development and growth. The translation of these genetic, epigenetic and biochemical findings into therapies that have been tested in clinical trials is the subject of this review. Published by Elsevier Inc.
C1 [Arko, Leopold; Katsyv, Igor; Luan, William Patrick; Park, John K.] NINDS, Surg & Mol Neurooncol Unit, NIH, Bethesda, MD 20892 USA.
[Arko, Leopold] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA.
[Arko, Leopold] Univ New Mexico Sch Med, Albuquerque, NM USA.
[Park, Grace E.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Park, JK (reprint author), 35 Convent Dr,Rm 2B-1002, Bethesda, MD 20892 USA.
EM parkjk@ninds.nih.gov
OI Arko, Leopold/0000-0003-1052-5671; Luan, William
Patrick/0000-0003-4731-937X
FU National Institute of Neurological Disorders and Stroke, NIH; National
Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH;
Howard Hughes Medical Institute-National Institutes of Health
FX This work was supported by the intramural research programs of the
National Institute of Neurological Disorders and Stroke and the National
Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, and
the Howard Hughes Medical Institute-National Institutes of Health
Research Scholars Program.
NR 446
TC 46
Z9 46
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0163-7258
J9 PHARMACOL THERAPEUT
JI Pharmacol. Ther.
PD OCT
PY 2010
VL 128
IS 1
BP 1
EP 36
DI 10.1016/j.pharmthera.2010.04.015
PG 36
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 662XE
UT WOS:000282846800001
PM 20546782
ER
PT J
AU Lopez-Novoa, JM
Martinez-Salgado, C
Rodriguez-Pena, AB
Hernandez, FJL
AF Lopez-Novoa, Jose M.
Martinez-Salgado, Carlos
Rodriguez-Pena, Ana B.
Lopez Hernandez, Francisco J.
TI Common pathophysiological mechanisms of chronic kidney disease:
Therapeutic perspectives
SO PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
DE Chronic renal disease; Animal models; Hypertension; Diabetes; Ureteral
obstruction; Renal mass reduction; Therapy
ID ANGIOTENSIN-CONVERTING-ENZYME; RENAL INTERSTITIAL FIBROSIS;
PLATELET-ACTIVATING-FACTOR; SPONTANEOUSLY HYPERTENSIVE-RATS;
GROWTH-FACTOR-BETA; UNILATERAL URETERAL OBSTRUCTION; II RECEPTOR
BLOCKERS; SMOOTH-MUSCLE-CELLS; FACTOR-KAPPA-B; GLOMERULAR MESANGIAL
CELLS
AB It is estimated that over 10% of the adult population in developed countries have some degree of chronic kidney disease (CKD). CKD is a progressive and irreversible deterioration of the renal excretory function that results in implementation of renal replacement therapy in the form of dialysis or renal transplant, which may also lead to death. CKD poses a growing problem to society as the incidence of the disease increases at an annual rate of 8%, and consumes up to 2% of the global health expenditure. CKD is caused by a variety of factors including diabetes, hypertension, infection, reduced blood supply to the kidneys, obstruction of the urinary tract and genetic alterations. The nephropathies associated with some of these conditions have been modeled in animals, this being crucial to understanding their pathophysiological mechanism and assessing prospective treatments at the preclinical level. This article reviews and updates the pathophysiological knowledge acquired primarily from experimental models and human studies of CKD. It also highlights the common mechanism(s) underlying the most relevant chronic nephropathies which lead to the appearance of a progressive, common renal phenotype regardless of aetiology. Based on this knowledge, a therapeutic horizon for the treatment of CKD is described. Present therapy primarily based upon renin-angiotensin inhibition, future diagnostics and therapeutic perspectives based upon anti-inflammatory, anti-fibrotic and hemodynamic approaches, new drugs targeting specific signaling pathways, and advances in gene and cell therapies, are all elaborated. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Martinez-Salgado, Carlos; Lopez Hernandez, Francisco J.] Hosp Univ Salamanca, Unidad Invest, Salamanca 37007, Spain.
[Lopez-Novoa, Jose M.; Martinez-Salgado, Carlos; Lopez Hernandez, Francisco J.] Univ Salamanca, Unidad Fisiopatol Renal & Cardiovasc, Dept Fisiol & Farmacol, E-37008 Salamanca, Spain.
[Rodriguez-Pena, Ana B.] NIH, Bethesda, MD 20892 USA.
[Lopez-Novoa, Jose M.; Martinez-Salgado, Carlos; Lopez Hernandez, Francisco J.] Fdn Inigo Alvarez de Toledo, Inst Reina Sofia Invest Nefrol, Toledo, Spain.
RP Hernandez, FJL (reprint author), Hosp Univ Salamanca, Unidad Invest, Paseo San Vicente 58-182, Salamanca 37007, Spain.
EM flopezher@usal.es
RI IBSAL, Secretaria/H-3719-2011; Martinez-Salgado, Carlos/E-7299-2012;
OI Lopez-Novoa, Jose M./0000-0002-6211-7269
NR 322
TC 29
Z9 31
U1 0
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0163-7258
J9 PHARMACOL THERAPEUT
JI Pharmacol. Ther.
PD OCT
PY 2010
VL 128
IS 1
BP 61
EP 81
DI 10.1016/j.pharmthera.2010.05.006
PG 21
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 662XE
UT WOS:000282846800003
PM 20600306
ER
PT J
AU Gerstenblith, MR
Shi, JX
Landi, MT
AF Gerstenblith, Meg R.
Shi, Jianxin
Landi, Maria Teresa
TI Genome-wide association studies of pigmentation and skin cancer: a
review and meta-analysis
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Review
DE GWAS (genome-wide association study); pigmentation; skin cancer;
melanoma; basal cell carcinoma; nevi; meta-analysis
ID MELANOCORTIN-1 RECEPTOR MC1R; BASAL-CELL CARCINOMA; CUTANEOUS
MALIGNANT-MELANOMA; GENE VARIANTS; KIT-LIGAND; EYE-COLOR; SUSCEPTIBILITY
LOCI; PANCREATIC-CANCER; GERMLINE MUTATION; SEQUENCE VARIANTS
AB P>Recent genome-wide association studies (GWAS) identified genetic loci associated with pigmentation, nevi, and skin cancer. We performed a review and meta-analysis of GWAS results, grouping them into four categories: (i) loci associated with pigmentation (hair, eye, and/or skin color), cutaneous UV-response (sun sensitivity and/or freckling), and skin cancer; (ii) loci associated with nevi and melanoma; (iii) loci associated with pigmentation and/or cutaneous UV-response but not skin cancer; and (iv) loci associated distinctly with skin cancer, mostly basal cell carcinoma, but not pigmentation or cutaneous UV-response. These findings suggest at least two pathways for melanoma development (via pigmentation and via nevi), and two pathways for basal cell carcinoma development (via pigmentation and independent of pigmentation). However, further work is necessary to separate the association with skin cancer from the association with pigmentation. As with any GWAS, the identified loci may not include the causal variants and may need confirmation by direct genome sequencing.
C1 [Gerstenblith, Meg R.; Landi, Maria Teresa] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Shi, Jianxin] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Landi, MT (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM landim@mail.nih.gov
FU NIH, National Cancer Institute, Division of Cancer Epidemiology and
Genetics
FX This study was supported by the Intramural Research Program of NIH,
National Cancer Institute, Division of Cancer Epidemiology and Genetics.
The authors thank Drs. David Duffy, Hongmei Nan, Jiali Han, Mario
Falchi, and Patrick Sulem for sharing data that allowed meta-analysis
and refined associations for specific loci, and Barbara Rogers, William
Wheeler, and Sara De Matteis for help with the graphical items.
NR 76
TC 51
Z9 54
U1 2
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD OCT
PY 2010
VL 23
IS 5
BP 587
EP 606
DI 10.1111/j.1755-148X.2010.00730.x
PG 20
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 646OO
UT WOS:000281552100007
PM 20546537
ER
PT J
AU Kauffman, GB
Pentimalli, R
Doldi, S
Hall, MD
AF Kauffman, George B.
Pentimalli, Raffaele
Doldi, Sandro
Hall, Matthew D.
TI Michele Peyrone (1813-1883), Discoverer of Cisplatin
SO PLATINUM METALS REVIEW
LA English
DT Article
AB The Italian chemist Michele Peyrone (1813-1883) was the first to synthesise cisplatin (cis-diamminedichloro-platinum (II)), the basis of today's most widely used family of anticancer drugs. This biographical article aims to present, for the first time in the English language, a summary of his life and the achievements that he made during his scientific career. Originally trained in medicine, Peyrone moved to chemistry and attended some of the most prestigious institutions in Europe in his time. He wrote several publications describing his work on 'Peyrone's chloride' (PtCl(2)(NH(3))(2)) and Magnus' green salt ([Pt(NH(3))(4)][PtCl(4)]). He later turned his attention to agricultural science where he defended important advances in the understanding of plant growth. Michele Peyrone's dedication to science is best summarised in the English translation of his first report on the synthesis of cisplatin: "I am determined to pursue this subject with all my energies, without having regard for the difficulties to be encountered at every step in so expensive and delicate a research".
C1 [Kauffman, George B.] Calif State Univ Fresno, Dept Chem, Fresno, CA 93740 USA.
[Pentimalli, Raffaele] Univ Valle Aosta, I-11100 Aosta, Italy.
[Hall, Matthew D.] NCI, NIH, Dr Michael M Gottesmans Lab, Bethesda, MD 20892 USA.
RP Kauffman, GB (reprint author), Calif State Univ Fresno, Dept Chem, Fresno, CA 93740 USA.
EM georgek@csufresno.edu; raffaele.pentimalli@virgilio.it;
hallma@mail.nih.gov
FU National Cancer Institute, National Institutes of Health, Bethesda,
Maryland, USA
FX This research was partly supported by the Intramural Research Program of
the National Cancer Institute, National Institutes of Health, Bethesda,
Maryland, USA.
NR 40
TC 10
Z9 10
U1 5
U2 23
PU JOHNSON MATTHEY PUBL LTD CO
PI LONDON
PA HATTON GARDEN, LONDON EC1N 8EE, ENGLAND
SN 1471-0676
J9 PLATIN MET REV
JI Platin. Met. Rev.
PD OCT
PY 2010
VL 54
IS 4
BP 250
EP 256
DI 10.1595/147106710X534326
PG 7
WC Chemistry, Physical
SC Chemistry
GA 663IX
UT WOS:000282878400007
ER
PT J
AU Babayan, SA
Read, AF
Lawrence, RA
Bain, O
Allen, JE
AF Babayan, Simon A.
Read, Andrew F.
Lawrence, Rachel A.
Bain, Odile
Allen, Judith E.
TI Filarial Parasites Develop Faster and Reproduce Earlier in Response to
Host Immune Effectors That Determine Filarial Life Expectancy
SO PLOS BIOLOGY
LA English
DT Article
ID VACCINE-INDUCED PROTECTION; BLOOD FLUKE DEVELOPMENT; MURINE FILARIASIS;
LITOMOSOIDES-SIGMODONTIS; BRUGIA-MALAYI; SCHISTOSOMA-MANSONI; PRIMARY
INFECTION; T-CELLS; MICE; INTERLEUKIN-5
AB Humans and other mammals mount vigorous immune assaults against helminth parasites, yet there are intriguing reports that the immune response can enhance rather than impair parasite development. It has been hypothesized that helminths, like many free-living organisms, should optimize their development and reproduction in response to cues predicting future life expectancy. However, immune-dependant development by helminth parasites has so far eluded such evolutionary explanation. By manipulating various arms of the immune response of experimental hosts, we show that filarial nematodes, the parasites responsible for debilitating diseases in humans like river blindness and elephantiasis, accelerate their development in response to the IL-5 driven eosinophilia they encounter when infecting a host. Consequently they produce microfilariae, their transmission stages, earlier and in greater numbers. Eosinophilia is a primary host determinant of filarial life expectancy, operating both at larval and at late adult stages in anatomically and temporally separate locations, and is implicated in vaccine-mediated protection. Filarial nematodes are therefore able to adjust their reproductive schedules in response to an environmental predictor of their probability of survival, as proposed by evolutionary theory, thereby mitigating the effects of the immune attack to which helminths are most susceptible. Enhancing protective immunity against filarial nematodes, for example through vaccination, may be less effective at reducing transmission than would be expected and may, at worst, lead to increased transmission and, hence, pathology.
C1 [Babayan, Simon A.; Allen, Judith E.] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland.
[Babayan, Simon A.; Read, Andrew F.; Allen, Judith E.] Univ Edinburgh, Sch Biol Sci, Inst Immunol & Infect Res, Edinburgh, Midlothian, Scotland.
[Read, Andrew F.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Read, Andrew F.] Penn State Univ, Dept Entomol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Read, Andrew F.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Lawrence, Rachel A.] Univ London Royal Vet Coll, London, England.
[Bain, Odile] Museum Natl Hist Nat, USM 307, F-75231 Paris, France.
RP Babayan, SA (reprint author), Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland.
EM s.babayan@ed.ac.uk
RI Allen, Judith/C-9198-2011; Babayan, Simon/E-1807-2011
OI Allen, Judith/0000-0002-3829-066X; Babayan, Simon/0000-0002-4949-1117
FU European Union [ICA4-CT- 1999-10002, INCO-CT-2006-03232]; Fogarty
International Center; National Institutes of Health; BBSRC; Wellcome
Trust
FX This work was funded by a European Union Marie-Curie Fellowship, EU
grants "VARBO" (INCO-DEV contract ICA4-CT- 1999-10002) and "SCOOTT"
(INCO-CT-2006-03232), the RAPIDD program of the Science & Technology
Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health, the BBSRC, and the
Wellcome Trust. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 66
TC 45
Z9 45
U1 2
U2 26
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD OCT
PY 2010
VL 8
IS 10
AR e1000525
DI 10.1371/journal.pbio.1000525
PG 9
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 671IQ
UT WOS:000283495100021
PM 20976099
ER
PT J
AU Conze, DB
Zhao, YG
Ashwell, JD
AF Conze, Dietrich B.
Zhao, Yongge
Ashwell, Jonathan D.
TI Non-Canonical NF-kappa B Activation and Abnormal B Cell Accumulation in
Mice Expressing Ubiquitin Protein Ligase-Inactive c-IAP2
SO PLOS BIOLOGY
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; LYMPHOID-TISSUE LYMPHOMAS; MALT LYMPHOMA;
TNF-ALPHA; DEPENDENT APOPTOSIS; SIGNALING PATHWAY; MULTIPLE-MYELOMA;
NF-KAPPA-B2 P100; SURVIVAL SIGNALS; TRAF2
AB Chromosomal translocations between loci encoding MALT1 and c-IAP2 are common in MALT lymphomas. The resulting fusion proteins lack the c-IAP2 RING domain, the region responsible for its ubiquitin protein ligase (E3) activity. Ectopic expression of the fusion protein activates the canonical NF-kappa B signaling cascade, but how it does so is controversial and how it promotes MALT lymphoma is unknown. Considering recent reports implicating c-IAP1 and c-IAP2 E3 activity in repression of non-canonical NF-kappa B signaling, we asked if the c-IAP2/ MALT fusion protein can initiate non-canonical NF-kappa B activation. Here we show that in addition to canonical activation, the fusion protein stabilizes NIK and activates non-canonical NF-kappa B. Canonical but not non-canonical activation depended on MALT1 paracaspase activity, and expression of E3-inactive c-IAP2 activated non-canonical NF-kappa B. Mice in which endogenous c-IAP2 was replaced with an E3-inactive mutant accumulated abnormal B cells with elevated non-canonical NF-kappa B and had increased numbers of B cells with a marginal zone phenotype, gut-associated lymphoid hyperplasia, and other features of MALT lymphoma. Thus, the c-IAP2/MALT1 fusion protein activates NF-kappa B by two distinct mechanisms, and loss of c-IAP2 E3 activity in vivo is sufficient to induce abnormalities common to MALT lymphoma.
C1 [Conze, Dietrich B.; Zhao, Yongge; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Conze, DB (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM jda@pop.nci.nih.gov
FU National Institutes of Health; Center for Cancer Research, National
Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, Center for Cancer Research, National
Cancer Institute. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 66
TC 32
Z9 32
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1544-9173
J9 PLOS BIOL
JI PLoS. Biol.
PD OCT
PY 2010
VL 8
IS 10
AR e1000518
DI 10.1371/journal.pbio.1000518
PG 13
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 671IQ
UT WOS:000283495100016
PM 21048983
ER
PT J
AU Goldfarb, T
Lichten, M
AF Goldfarb, Tamara
Lichten, Michael
TI Frequent and Efficient Use of the Sister Chromatid for DNA Double-Strand
Break Repair during Budding Yeast Meiosis
SO PLOS BIOLOGY
LA English
DT Article
ID SYNAPTONEMAL COMPLEX-FORMATION; MEIOTIC RECOMBINATION;
SACCHAROMYCES-CEREVISIAE; HOLLIDAY JUNCTIONS; JOINT MOLECULES;
INTERHOMOLOG RECOMBINATION; CROSSOVER INTERFERENCE; CHROMOSOME SYNAPSIS;
CROSSING-OVER; GENE ENCODES
AB Recombination between homologous chromosomes of different parental origin (homologs) is necessary for their accurate segregation during meiosis. It has been suggested that meiotic inter-homolog recombination is promoted by a barrier to inter-sister-chromatid recombination, imposed by meiosis-specific components of the chromosome axis. Consistent with this, measures of Holliday junction-containing recombination intermediates (joint molecules [JMs]) show a strong bias towards inter-homolog and against inter-sister JMs. However, recombination between sister chromatids also has an important role in meiosis. The genomes of diploid organisms in natural populations are highly polymorphic for insertions and deletions, and meiotic double-strand breaks (DSBs) that form within such polymorphic regions must be repaired by inter-sister recombination. Efforts to study inter-sister recombination during meiosis, in particular to determine recombination frequencies and mechanisms, have been constrained by the inability to monitor the products of inter-sister recombination. We present here molecular-level studies of inter-sister recombination during budding yeast meiosis. We examined events initiated by DSBs in regions that lack corresponding sequences on the homolog, and show that these DSBs are efficiently repaired by inter-sister recombination. This occurs with the same timing as inter-homolog recombination, but with reduced (2- to 3-fold) yields of JMs. Loss of the meiotic-chromosome-axis-associated kinase Mek1 accelerates inter-sister DSB repair and markedly increases inter-sister JM frequencies. Furthermore, inter-sister JMs formed in mek1 Delta mutants are preferentially lost, while inter-homolog JMs are maintained. These findings indicate that inter-sister recombination occurs frequently during budding yeast meiosis, with the possibility that up to one-third of all recombination events occur between sister chromatids. We suggest that a Mek1-dependent reduction in the rate of inter-sister repair, combined with the destabilization of inter-sister JMs, promotes inter-homolog recombination while retaining the capacity for inter-sister recombination when inter-homolog recombination is not possible.
C1 [Goldfarb, Tamara; Lichten, Michael] NCI, Biochem & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Goldfarb, T (reprint author), NCI, Biochem & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM lichten@helix.nih.gov
RI Lichten, Michael/C-5795-2013
OI Lichten, Michael/0000-0001-9707-2956
FU National Cancer Institute; National Institutes of Health
FX This work was supported by the Intramural Research Program at the
National Cancer Institute, National Institutes of Health. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 82
TC 65
Z9 65
U1 2
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1544-9173
J9 PLOS BIOL
JI PLoS. Biol.
PD OCT
PY 2010
VL 8
IS 10
AR e1000520
DI 10.1371/journal.pbio.1000520
PG 12
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 671IQ
UT WOS:000283495100018
PM 20976044
ER
PT J
AU Andres, AM
Dennis, MY
Kretzschmar, WW
Cannons, JL
Lee-Lin, SQ
Hurle, B
Schwartzberg, PL
Williamson, SH
Bustamante, CD
Nielsen, R
Clark, AG
Green, ED
AF Andres, Aida M.
Dennis, Megan Y.
Kretzschmar, Warren W.
Cannons, Jennifer L.
Lee-Lin, Shih-Queen
Hurle, Belen
Schwartzberg, Pamela L.
Williamson, Scott H.
Bustamante, Carlos D.
Nielsen, Rasmus
Clark, Andrew G.
Green, Eric D.
CA NISC Comparative Sequencing Progra
TI Balancing Selection Maintains a Form of ERAP2 that Undergoes
Nonsense-Mediated Decay and Affects Antigen Presentation
SO PLOS GENETICS
LA English
DT Article
ID ENDOPLASMIC-RETICULUM AMINOPEPTIDASES; CLASS-I MOLECULES;
HISTOCOMPATIBILITY COMPLEX LOCI; GENOME-WIDE ASSOCIATION;
ANKYLOSING-SPONDYLITIS; PROCESSING MACHINERY; CERVICAL-CARCINOMA;
NATURAL-SELECTION; NUCLEOTIDE SUBSTITUTION; OVERDOMINANT SELECTION
AB A remarkable characteristic of the human major histocompatibility complex (MHC) is its extreme genetic diversity, which is maintained by balancing selection. In fact, the MHC complex remains one of the best-known examples of natural selection in humans, with well-established genetic signatures and biological mechanisms for the action of selection. Here, we present genetic and functional evidence that another gene with a fundamental role in MHC class I presentation, endoplasmic reticulum aminopeptidase 2 (ERAP2), has also evolved under balancing selection and contains a variant that affects antigen presentation. Specifically, genetic analyses of six human populations revealed strong and consistent signatures of balancing selection affecting ERAP2. This selection maintains two highly differentiated haplotypes (Haplotype A and Haplotype B), with frequencies 0.44 and 0.56, respectively. We found that ERAP2 expressed from Haplotype B undergoes differential splicing and encodes a truncated protein, leading to nonsense-mediated decay of the mRNA. To investigate the consequences of ERAP2 deficiency on MHC presentation, we correlated surface MHC class I expression with ERAP2 genotypes in primary lymphocytes. Haplotype B homozygotes had lower levels of MHC class I expressed on the surface of B cells, suggesting that naturally occurring ERAP2 deficiency affects MHC presentation and immune response. Interestingly, an ERAP2 paralog, endoplasmic reticulum aminopeptidase 1 (ERAP1), also shows genetic signatures of balancing selection. Together, our findings link the genetic signatures of selection with an effect on splicing and a cellular phenotype. Although the precise selective pressure that maintains polymorphism is unknown, the demonstrated differences between the ERAP2 splice forms provide important insights into the potential mechanism for the action of selection.
C1 [Andres, Aida M.; Dennis, Megan Y.; Kretzschmar, Warren W.; Lee-Lin, Shih-Queen; Hurle, Belen; Green, Eric D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Cannons, Jennifer L.; Schwartzberg, Pamela L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Green, Eric D.; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Williamson, Scott H.; Bustamante, Carlos D.] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY USA.
[Nielsen, Rasmus] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
[Clark, Andrew G.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY USA.
RP Andres, AM (reprint author), Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, Leipzig, Germany.
EM aida.andres@eva.mpg.de
RI Nielsen, Rasmus/D-4405-2009; Andres, Aida/B-4088-2014
OI Nielsen, Rasmus/0000-0003-0513-6591; Andres, Aida/0000-0002-8590-9672
FU National Human Genome Research Institute of the National Institutes of
Health
FX This work was supported by the Intramural Research Program of the
National Human Genome Research Institute of the National Institutes of
Health. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 85
TC 72
Z9 72
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD OCT
PY 2010
VL 6
IS 10
AR e1001157
DI 10.1371/journal.pgen.1001157
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 673GP
UT WOS:000283647800028
PM 20976248
ER
PT J
AU Gaudet, MM
Kirchhoff, T
Green, T
Vijai, J
Korn, JM
Guiducci, C
Segre, AV
McGee, K
McGuffog, L
Kartsonaki, C
Morrison, J
Healey, S
Sinilnikova, OM
Stoppa-Lyonnet, D
Mazoyer, S
Gauthier-Villars, M
Sobol, H
Longy, M
Frenay, M
Hogervorst, FBL
Rookus, MA
Collee, JM
Hoogerbrugge, N
van Roozendaal, KEP
Piedmonte, M
Rubinstein, W
Nerenstone, S
Van Le, L
Blank, SV
Caldes, T
de la Hoya, M
Nevanlinna, H
Aittomaki, K
Lazaro, C
Blanco, I
Arason, A
Johannsson, OT
Barkardottir, RB
Devilee, P
Olopade, OI
Neuhausen, SL
Wang, XS
Fredericksen, ZS
Peterlongo, P
Manoukian, S
Barile, M
Viel, A
Radice, P
Phelan, CM
Narod, S
Rennert, G
Lejbkowicz, F
Flugelman, A
Andrulis, IL
Glendon, G
Ozcelik, H
Toland, AE
Montagna, M
D'Andrea, E
Friedman, E
Laitman, Y
Borg, A
Beattie, M
Ramus, SJ
Domchek, SM
Nathanson, KL
Rebbeck, T
Spurdle, AB
Chen, XQ
Holland, H
John, EM
Hopper, JL
Buys, SS
Daly, MB
Southey, MC
Terry, MB
Tung, N
Hansen, TVO
Nielsen, FC
Greene, MI
Mai, PL
Osorio, A
Duran, M
Andres, R
Benitez, J
Weitzel, JN
Garber, J
Hamann, U
Peock, S
Cook, M
Oliver, C
Frost, D
Platte, R
Evans, DG
Lalloo, F
Eeles, R
Izatt, L
Walker, L
Eason, J
Barwell, J
Godwin, AK
Schmutzler, RK
Wappenschmidt, B
Engert, S
Arnold, N
Gadzicki, D
Dean, M
Gold, B
Klein, RJ
Couch, FJ
Chenevix-Trench, G
Easton, DF
Daly, MJ
Antoniou, AC
Altshuler, DM
Offit, K
AF Gaudet, Mia M.
Kirchhoff, Tomas
Green, Todd
Vijai, Joseph
Korn, Joshua M.
Guiducci, Candace
Segre, Ayellet V.
McGee, Kate
McGuffog, Lesley
Kartsonaki, Christiana
Morrison, Jonathan
Healey, Sue
Sinilnikova, Olga M.
Stoppa-Lyonnet, Dominique
Mazoyer, Sylvie
Gauthier-Villars, Marion
Sobol, Hagay
Longy, Michel
Frenay, Marc
Hogervorst, Frans B. L.
Rookus, Matti A.
Collee, J. Margriet
Hoogerbrugge, Nicoline
van Roozendaal, Kees E. P.
Piedmonte, Marion
Rubinstein, Wendy
Nerenstone, Stacy
Van Le, Linda
Blank, Stephanie V.
Caldes, Trinidad
de la Hoya, Miguel
Nevanlinna, Heli
Aittomaki, Kristiina
Lazaro, Conxi
Blanco, Ignacio
Arason, Adalgeir
Johannsson, Oskar T.
Barkardottir, Rosa B.
Devilee, Peter
Olopade, Olofunmilayo I.
Neuhausen, Susan L.
Wang, Xianshu
Fredericksen, Zachary S.
Peterlongo, Paolo
Manoukian, Siranoush
Barile, Monica
Viel, Alessandra
Radice, Paolo
Phelan, Catherine M.
Narod, Steven
Rennert, Gad
Lejbkowicz, Flavio
Flugelman, Anath
Andrulis, Irene L.
Glendon, Gord
Ozcelik, Hilmi
Toland, Amanda E.
Montagna, Marco
D'Andrea, Emma
Friedman, Eitan
Laitman, Yael
Borg, Ake
Beattie, Mary
Ramus, Susan J.
Domchek, Susan M.
Nathanson, Katherine L.
Rebbeck, Tim
Spurdle, Amanda B.
Chen, Xiaoqing
Holland, Helene
John, Esther M.
Hopper, John L.
Buys, Saundra S.
Daly, Mary B.
Southey, Melissa C.
Terry, Mary Beth
Tung, Nadine
Hansen, Thomas V. Overeem
Nielsen, Finn C.
Greene, Mark I.
Mai, Phuong L.
Osorio, Ana
Duran, Mercedes
Andres, Raquel
Benitez, Javier
Weitzel, Jeffrey N.
Garber, Judy
Hamann, Ute
Peock, Susan
Cook, Margaret
Oliver, Clare
Frost, Debra
Platte, Radka
Evans, D. Gareth
Lalloo, Fiona
Eeles, Ros
Izatt, Louise
Walker, Lisa
Eason, Jacqueline
Barwell, Julian
Godwin, Andrew K.
Schmutzler, Rita K.
Wappenschmidt, Barbara
Engert, Stefanie
Arnold, Norbert
Gadzicki, Dorothea
Dean, Michael
Gold, Bert
Klein, Robert J.
Couch, Fergus J.
Chenevix-Trench, Georgia
Easton, Douglas F.
Daly, Mark J.
Antoniou, Antonis C.
Altshuler, David M.
Offit, Kenneth
CA GEMO Study Collaborators
HEBON Study Collaborators
OCGN
kConFab
TI Common Genetic Variants and Modification of Penetrance of
BRCA2-Associated Breast Cancer
SO PLOS GENETICS
LA English
DT Article
ID BRCA2 MUTATION CARRIERS; SUSCEPTIBILITY GENES; RECURRENT BRCA1; RISK;
POPULATION; MODEL; PREDISPOSITION; ASSOCIATION; PHENOTYPE; FREQUENCY
AB The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
C1 [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
[Gaudet, Mia M.] Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, New York, NY USA.
[Kirchhoff, Tomas; Vijai, Joseph; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Sloan Kettering Inst, Clin Genet Serv, New York, NY 10021 USA.
[Kirchhoff, Tomas] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Canc Biol & Genet Program, New York, NY 10021 USA.
[Green, Todd; Korn, Joshua M.; Guiducci, Candace; Daly, Mark J.; Altshuler, David M.] Harvard Univ, Sch Med, Broad Inst Harvard, Boston, MA USA.
[Green, Todd; Korn, Joshua M.; Guiducci, Candace; Daly, Mark J.; Altshuler, David M.] Harvard Univ, Sch Med, MIT, Boston, MA USA.
[Segre, Ayellet V.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Segre, Ayellet V.] MIT, Cambridge, MA 02139 USA.
[Segre, Ayellet V.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Segre, Ayellet V.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[McGee, Kate; Dean, Michael; Gold, Bert] NCI, Ctr Canc Res, Canc Inflammat Program, Human Genet Sect, Frederick, MD 21701 USA.
[McGuffog, Lesley; Kartsonaki, Christiana; Morrison, Jonathan; Healey, Sue; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Platte, Radka; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Sinilnikova, Olga M.] CHU Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France.
[Sinilnikova, Olga M.; Mazoyer, Sylvie] Univ Lyon, Ctr Leon Berard, CNRS UMR5201, Equipe Labellisee LIGUE 2008, Lyon, France.
[Stoppa-Lyonnet, Dominique] Univ Paris 05, INSERM U830, Serv Genet, Inst Curie, F-75248 Paris, France.
[Stoppa-Lyonnet, Dominique; Gauthier-Villars, Marion] Inst Curie, Serv Genet Oncol, Paris, France.
[Sobol, Hagay] Univ Aix Marseille 2, Inst J Paoli I Calmettes, INSERM CIC P9502, Dept Oncol Genet Prevent & Depistage, F-13284 Marseille 07, France.
[Longy, Michel] Inst Bergonie, Bordeaux, France.
[Frenay, Marc] Ctr Antoine Lacassagne, F-06054 Nice, France.
[GEMO Study Collaborators] Fed Natl Ctr Lutte Contre Canc, GEMO Study Canc Genet Network Grp Genet & Canc, Paris, France.
[Hogervorst, Frans B. L.; HEBON Study Collaborators] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands.
[Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands.
[Collee, J. Margriet] Erasmus Univ, Med Ctr, Rotterdam Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands.
[Hoogerbrugge, Nicoline] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[van Roozendaal, Kees E. P.] Univ Med Ctr, Dept Clin Genet, Maastricht, Netherlands.
[Piedmonte, Marion] Roswell Pk Canc Inst, Gynecol Oncol Grp Stat, Buffalo, NY 14263 USA.
[Piedmonte, Marion] Roswell Pk Canc Inst, Ctr Data, Buffalo, NY 14263 USA.
[Rubinstein, Wendy] NorthShore Univ Hlth Syst, Evanston, IL USA.
[Nerenstone, Stacy] Hartford Hosp, Cent Connecticut Canc Consortium, Hartford, CT 06115 USA.
[Van Le, Linda] Univ N Carolina, Chapel Hill, NC USA.
[Blank, Stephanie V.] NYU, Sch Med, New York, NY USA.
[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.
[Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland.
[Lazaro, Conxi; Blanco, Ignacio] Catalan Inst Oncol, Hereditary Canc Program, Barcelona, Spain.
[Arason, Adalgeir; Johannsson, Oskar T.; Barkardottir, Rosa B.] Landspitali LSH, Dept Oncol, Reykjavik, Iceland.
[Arason, Adalgeir; Barkardottir, Rosa B.] Landspitali LSH, Dept Pathol, Reykjavik, Iceland.
[Arason, Adalgeir; Johannsson, Oskar T.; Barkardottir, Rosa B.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Devilee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands.
[Olopade, Olofunmilayo I.] Univ Chicago, Med Ctr, Dept Med, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA.
[Neuhausen, Susan L.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA.
[Wang, Xianshu; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Fredericksen, Zachary S.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Peterlongo, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Expt Oncol & Mol Med, Unit Genet Susceptibil Canc, Milan, Italy.
[Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy.
[Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy.
[Barile, Monica] IEO, Div Canc Prevent & Genet, Milan, Italy.
[Viel, Alessandra] IRCCS, CRO, Div Expt Oncol 1, Aviano, PN, Italy.
[Phelan, Catherine M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Narod, Steven] Womens Coll Res Inst, Toronto, ON, Canada.
[Rennert, Gad; Lejbkowicz, Flavio; Flugelman, Anath] CHS Natl Canc Control Ctr, Haifa, Israel.
[Rennert, Gad; Lejbkowicz, Flavio; Flugelman, Anath] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel.
[Andrulis, Irene L.; Ozcelik, Hilmi] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; OCGN] Univ Toronto, Ontario Canc Genet Network, Toronto, ON, Canada.
[Toland, Amanda E.] Ohio State Univ, Dept Mol Virol, Columbus, OH 43210 USA.
[Toland, Amanda E.] Ohio State Univ, Dept Immunol, Columbus, OH 43210 USA.
[Toland, Amanda E.] Ohio State Univ, Dept Med Genet & Internal Med, Columbus, OH 43210 USA.
[Montagna, Marco; D'Andrea, Emma] IRCCS, Ist Oncol Veneto, Immunol & Mol Oncol Unit, Padua, Italy.
[D'Andrea, Emma] Univ Padua, Dept Oncol & Surg Sci, Padua, Italy.
[Friedman, Eitan; Laitman, Yael] Sheba Med Ctr, Inst Genet, Susan Levy Gertner Oncogenet Unit, Tel Hashomer, Israel.
[Borg, Ake] Lund Univ, Dept Oncol, Lund, Sweden.
[Beattie, Mary] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Ramus, Susan J.] UCL, UCL EGA Inst Womens Hlth, Gynaecol Oncol Unit, London WC1E 6BT, England.
[Domchek, Susan M.] Hosp Univ Penn, Dept Oncol, Philadelphia, PA 19104 USA.
[Nathanson, Katherine L.] Univ Penn, Sch Med, Dept Cell & Mol Biol, Philadelphia, PA 19104 USA.
[Rebbeck, Tim] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Spurdle, Amanda B.; Chen, Xiaoqing; Holland, Helene] Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia.
[Chenevix-Trench, Georgia; kConFab] Peter MacCallum Canc Ctr, Melbourne, Australia.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[Hopper, John L.] Univ Melbourne, Ctr Genet Epidemiol, Melbourne, Vic, Australia.
[Buys, Saundra S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Southey, Melissa C.] Univ Melbourne, Ctr Genet Epidemiol, Melbourne, Vic, Australia.
[Terry, Mary Beth] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Tung, Nadine] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA.
[Hansen, Thomas V. Overeem; Nielsen, Finn C.] Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark.
[Greene, Mark I.; Mai, Phuong L.] NCI, Clin Genet Branch, Rockville, MD USA.
[Osorio, Ana; Benitez, Javier] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain.
[Duran, Mercedes] Univ Valladolid IBGM UVA, Inst Biol & Mol Genet, Valladolid, Spain.
[Andres, Raquel] Hosp Clin Univ Lozano Blesa, Oncol Serv, Zaragoza, Spain.
[Benitez, Javier] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Genotyping Unit, Madrid, Spain.
[Weitzel, Jeffrey N.] City Hope Canc Ctr, Duarte, CA USA.
[Garber, Judy] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hamann, Ute] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany.
[Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Eeles, Ros] Inst Canc Res, Oncogenet Team, London SW3 6JB, England.
[Eeles, Ros] Royal Marsden NHS Fdn Trust, London, England.
[Izatt, Louise] Guys & St Thomas NHS Fdn Trust, London, England.
[Walker, Lisa] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England.
[Eason, Jacqueline] Nottingham Univ Hosp NHS Trust, Nottingham Clin Genet Serv, Nottingham, England.
[Barwell, Julian] Univ Hosp Leicester NHS Trust, Leicestershire Clin Genet Serv, Leicester, Leics, England.
[Godwin, Andrew K.] Fox Chase Canc Ctr, Dept Med Oncol, Womens Canc Program, Philadelphia, PA 19111 USA.
[Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Dept Obstet & Gynaecol, Cologne, Germany.
[Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, CIO, Cologne, Germany.
[Engert, Stefanie] Tech Univ Munich, Klinikum Rechts Isar, Div Tumor Genet, Dept Obstet & Gynaecol, D-8000 Munich, Germany.
[Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, Kiel, Germany.
[Gadzicki, Dorothea] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany.
RP Gaudet, MM (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
EM offitk@mskcc.org
RI Spurdle, Amanda/A-4978-2011; Radice, Paolo/O-3119-2013; Blanco,
Ignacio/D-2565-2013; Osorio, Ana/I-4324-2014; GLADIEFF,
Laurence/O-5129-2014; Ligtenberg, Marjolijn/N-9666-2013; manoukian,
siranoush/E-7132-2017; Altshuler, David/A-4476-2009; Klein,
Robert/K-1888-2013; Hoogerbrugge, Nicoline/O-1016-2013; Segre,
Ayellet/E-9800-2010; Arnold, Norbert/E-3012-2010; Toland,
Amanda/E-4202-2011; montagna, marco/E-2225-2012; Dean,
Michael/G-8172-2012; D'Andrea, Emma/B-4374-2013; Andrulis,
Irene/E-7267-2013; Joseph, Vijai/J-9158-2013
OI Evans, Gareth/0000-0002-8482-5784; Ramus, Susan/0000-0003-0005-7798;
Spurdle, Amanda/0000-0003-1337-7897; Nevanlinna,
Heli/0000-0002-0916-2976; Kirchhoff, Tomas/0000-0002-9055-2364; Blanco,
Ignacio/0000-0002-7414-7481; Osorio, Ana/0000-0001-8124-3984; GLADIEFF,
Laurence/0000-0002-6980-9719; Ligtenberg, Marjolijn/0000-0003-1290-1474;
manoukian, siranoush/0000-0002-6034-7562; Eeles,
Rosalind/0000-0002-3698-6241; Nathanson, Katherine/0000-0002-6740-0901;
Altshuler, David/0000-0002-7250-4107; Klein, Robert/0000-0003-3539-5391;
Arnold, Norbert/0000-0003-4523-8808; montagna,
marco/0000-0002-4929-2150; Dean, Michael/0000-0003-2234-0631; Joseph,
Vijai/0000-0002-7933-151X
FU Starr Cancer Research Consortium; Breast Cancer Research Foundation; NIH
NCI [P20CA103694-3]; Lymphoma Foundation; Robert and Kate Niehaus
Clinical Cancer Genetics Initiative at MSKCC
FX This study was supported by the Starr Cancer Research Consortium and the
Breast Cancer Research Foundation, as well as by NIH NCI: P20CA103694-3
and the Lymphoma Foundation. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.; The LUMC study would like to thank Hans Vasen, Inge van
Leeuwen, and Hanne Meijers for patient accrual. For the CNIO study, the
authors would like to thank R. M. Alonso, G. Pita and R. M. Milne for
their assistance. We thank IBGM, Universidad de Valladolid and
Consejeria de Sanidad Junta de Castilla y Leon. For the SWE-BRCA, the
authors would like to also acknowledge the contribution of Per Karlsson,
Margareta Nordling, Annika Bergman and Zakaria Einbeigi, Gothenburg,
Sahlgrenska University Hospital; Marie Stenmark-Askmalm and Sigrun
Liedgren Linkoping University Hospital; Ake Borg, Niklas Loman, Hakan
Olsson, Ulf Kristoffersson, Helena Jernstrom, Katja Harbst and Karin
Henriksson, Lund University Hospital; Annika Lindblom, Brita Arver, Anna
von Wachenfeldt, Annelie Liljegren, Gisela Barbany-Bustinza and Johanna
Rantala, Stockholm, Karolinska University Hospital; Beatrice Melin,
Henrik Gronberg, Eva-Lena Stattin and Monica Emanuelsson, Umea
University Hospital; Hans Ehrencrona, Richard Rosenquist Brandell and
Niklas Dahl, Uppsala University Hospital. Douglas F. Easton is the PI of
the EMBRACE study. EMBRACE Collaborating Centers are: Coordinating
Centre, Cambridge: Susan Peock, Margaret Cook, Clare Oliver, Debra
Frost. North of Scotland Regional Genetics Service, Aberdeen: Helen
Gregory, Zosia Miedzybrodzka. Northern Ireland Regional Genetics
Service, Belfast: Patrick J. Morrison, Lisa Jeffers. West Midlands
Regional Clinical Genetics Service, Birmingham: Trevor Cole, Carole
McKeown, Kai-Ren Ong, Laura Boyes. South Western Regional Genetics
Service, Bristol: Alan Donaldson. East Anglian Regional Genetics
Service, Cambridge: Joan Paterson. All Wales Medical Genetics Services,
Cardiff: Alexandra Murray, Mark T. Rogers, Emma McCann. St James's
Hospital, Dublin & National Centre for Medical Genetics, Dublin: M. John
Kennedy, David Barton. South East of Scotland Regional Genetics Service,
Edinburgh: Mary Porteous. Peninsula Clinical Genetics Service. Exeter:
Carole Brewer, Emma Kivuva, Anne Searle, Selina Goodman. West of
Scotland Regional Genetics Service, Glasgow: Rosemarie Davidson,
Victoria Murday, Nicola Bradshaw, Lesley Snadden, Mark Longmuir,
Catherine Watt, Sarah Gibson. South East Thames Regional Genetics
Service, Guys Hospital London: Louise Izatt, Gabriella Pichert, Chris
Jacobs, Caroline Langman. North West Thames Regional Genetics Service,
Kennedy-Galton Centre, Harrow: Huw Dorkins. Leicestershire Clinical
Genetics Service, Leicester: Julian Barwell. Yorkshire Regional Genetics
Service, Leeds: Carol Chu, Tim Bishop, Julie Miller. Merseyside &
Cheshire Clinical Genetics Service. Liverpool: Ian Ellis, Catherine
Houghton. Manchester Regional Genetics Service, Manchester: D Gareth
Evans, Fiona Lalloo, Felicity Holt. North East Thames Regional Genetics
Service, North East Thames: Lucy Side, Alison Male, Cheryl Berlin.
Nottingham Centre for Medical Genetics, Nottingham: Carol Gardiner.
Northern Clinical Genetics Service, Newcastle: Fiona Douglas, Oonagh
Claber. Oxford Regional Genetics Service, Oxford: Lisa Walker, Diane
McLeod, Dorothy Halliday, Sarah Durrell, Barbara Stayner. The Institute
of Cancer Research and Royal Marsden NHS Foundation Trust: Ros Eeles,
Susan Shanley, Nazneen Rahman, Richard Houlston, Elizabeth Bancroft,
Lucia D'Mello, Elizabeth Page, Audrey Ardern-Jones, Kelly Kohut,
Jennifer Wiggins. Elena Castro, Anita Mitra, Lisa Robertson. North Trent
Clinical Genetics Service, Sheffield: Jackie Cook, Oliver Quarrell,
Cathryn Bardsley. South Essex Cancer Research Network, Southend: Anne
Robinson.; South West Thames Regionl Genetics Service, London: Shirley
Hodgson, Sheila Goff, Glen Brice, Lizzie Winchester. Wessex Clinical
Genetics Service. Princess Anne Hospital, Southampton: Diana Eccles,
Anneke Lucassen, Gillian Crawford, Emma Tyler, Donna McBride. HEBCS
thanks Dr. Carl Blomqvist and Tuomas Heikkinen for their help with the
patient data and samples. Fox Chase Cancer Center (FCCC) thanks Ms.
JoEllen Weaver and Mr. John Malick for expert technical assistance. The
UCSF study would like to acknowledge Ms. Salina Chan for her database
management assistance. CONsorzio Studi Italiani Tumori Ereditari Alla
Mammella, CONSIT TEAM acknowledges Marco Pierotti, Bernard Peissel,
Daniela Zaffaroni and Carla B. Ripamonti of the Fondazione IRCCS
Istituto Nazionale dei Tumori, Milan, Italy; Bernardo Bonanni of the
Istituto Europeo di Oncologia, Milan, Italy and Loris Bernard of the
Cogentech, Consortium for Genomic Technologies, Milan, Italy. CBCS would
like to thank Bent Ejlerten, Mette K. Andersen, Susanne Kjaergaard and
Anne-Marie Gerdes for clinical data. The authors wish to thank Nichole
Hansen for help in manuscript preparation. The authors also acknowledge
support of the Robert and Kate Niehaus Clinical Cancer Genetics
Initiative at MSKCC.
NR 43
TC 56
Z9 58
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD OCT
PY 2010
VL 6
IS 10
AR e1001183
DI 10.1371/journal.pgen.1001183
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 673GP
UT WOS:000283647800014
PM 21060860
ER
PT J
AU Ikram, MK
Xueling, S
Jensen, RA
Cotch, MF
Hewitt, AW
Ikram, MA
Wang, JJ
Klein, R
Klein, BEK
Breteler, MMB
Cheung, N
Liew, G
Mitchell, P
Uitterlinden, AG
Rivadeneira, F
Hofman, A
de Jong, PTVM
van Duijn, CM
Kao, L
Cheng, CY
Smith, AV
Glazer, NL
Lumley, T
McKnight, B
Psaty, BM
Jonasson, F
Eiriksdottir, G
Aspelund, T
Harris, TB
Launer, LJ
Taylor, KD
Li, XH
Iyengar, SK
Xi, QS
Sivakumaran, TA
Mackey, DA
MacGregor, S
Martin, NG
Young, TL
Bis, JC
Wiggins, KL
Heckbert, SR
Hammond, CJ
Andrew, T
Fahy, S
Attia, J
Holliday, EG
Scott, RJ
Islam, FMA
Rotter, JI
McAuley, AK
Boerwinkle, E
Tai, ES
Gudnason, V
Siscovick, DS
Vingerling, JR
Wong, TY
AF Ikram, M. Kamran
Xueling, Sim
Jensen, Richard A.
Cotch, Mary Frances
Hewitt, Alex W.
Ikram, M. Arfan
Wang, Jie Jin
Klein, Ronald
Klein, Barbara E. K.
Breteler, Monique M. B.
Cheung, Ning
Liew, Gerald
Mitchell, Paul
Uitterlinden, Andre G.
Rivadeneira, Fernando
Hofman, Albert
de Jong, Paulus T. V. M.
van Duijn, Cornelia M.
Kao, Linda
Cheng, Ching-Yu
Smith, Albert Vernon
Glazer, Nicole L.
Lumley, Thomas
McKnight, Barbara
Psaty, Bruce M.
Jonasson, Fridbert
Eiriksdottir, Gudny
Aspelund, Thor
Harris, Tamara B.
Launer, Lenore J.
Taylor, Kent D.
Li, Xiaohui
Iyengar, Sudha K.
Xi, Quansheng
Sivakumaran, Theru A.
Mackey, David A.
MacGregor, Stuart
Martin, Nicholas G.
Young, Terri L.
Bis, Josh C.
Wiggins, Kerri L.
Heckbert, Susan R.
Hammond, Christopher J.
Andrew, Toby
Fahy, Samantha
Attia, John
Holliday, Elizabeth G.
Scott, Rodney J.
Islam, F. M. Amirul
Rotter, Jerome I.
McAuley, Annie K.
Boerwinkle, Eric
Tai, E. Shyong
Gudnason, Vilmundur
Siscovick, David S.
Vingerling, Johannes R.
Wong, Tien Y.
CA Global BPgen Consortium
TI Four Novel Loci (19q13, 6q24, 12q24, and 5q14) Influence the
Microcirculation In Vivo
SO PLOS GENETICS
LA English
DT Article
ID RETINAL VASCULAR CALIBER; GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK;
ANTIHYPERTENSIVE DRUG THERAPIES; GENOME-WIDE ASSOCIATION; VESSEL
DIAMETERS; ATHEROSCLEROSIS RISK; CHARGE CONSORTIUM; DISEASE;
METAANALYSIS; AGE
AB There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0x10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61x10(-25), within the RASIP1 locus), rs225717 (6q24; p = 1.25x10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15x10(-13), in the region of ATXN2, SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32x10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.
C1 [Ikram, M. Kamran; Ikram, M. Arfan; Breteler, Monique M. B.; Uitterlinden, Andre G.; Rivadeneira, Fernando; Hofman, Albert; van Duijn, Cornelia M.; Vingerling, Johannes R.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Ikram, M. Kamran; Vingerling, Johannes R.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands.
[Ikram, M. Kamran] Erasmus MC, Dept Neurol, Rotterdam, Netherlands.
[Xueling, Sim] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Mol Epidemiol, Singapore 117595, Singapore.
[Jensen, Richard A.; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Hewitt, Alex W.; Wang, Jie Jin; Cheung, Ning; Islam, F. M. Amirul; McAuley, Annie K.; Wong, Tien Y.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
[Wang, Jie Jin; Liew, Gerald; Mitchell, Paul; Mackey, David A.] Univ Sydney, Ctr Vision Res, Dept Ophthalmol, Sydney, NSW 2006, Australia.
[Wang, Jie Jin; Liew, Gerald; Mitchell, Paul; Mackey, David A.] Univ Sydney, Westmead Millennium Inst, Sydney, NSW 2006, Australia.
[Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[Uitterlinden, Andre G.; Rivadeneira, Fernando] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Uitterlinden, Andre G.] Erasmus MC, Dept Clin Chem, Rotterdam, Netherlands.
[de Jong, Paulus T. V. M.] Netherlands Inst Neurosci, Amsterdam, Netherlands.
[de Jong, Paulus T. V. M.] Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands.
[Kao, Linda] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Cheng, Ching-Yu] Taipei Vet Gen Hosp, Dept Ophthalmol, Taipei, Taiwan.
[Cheng, Ching-Yu] Natl Yang Ming Univ, Sch Med, Dept Ophthalmol, Taipei 112, Taiwan.
[Smith, Albert Vernon; Eiriksdottir, Gudny; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Bis, Josh C.; Wiggins, Kerri L.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Lumley, Thomas; McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth, Ctr Hlth Studies, Seattle, WA USA.
[Jonasson, Fridbert] Univ Iceland, Dept Ophthalmol, Reykjavik, Iceland.
[Jonasson, Fridbert] Landspitalinn Univ Hosp, Dept Ophthalmol, Reykjavik, Iceland.
[Aspelund, Thor] Univ Iceland, Dept Stat, Reykjavik, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Taylor, Kent D.; Li, Xiaohui; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Iyengar, Sudha K.; Xi, Quansheng; Sivakumaran, Theru A.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Mackey, David A.] Univ Western Australia, Ctr Ophthalmol & Visual Sci, Lions Eye Inst, Perth, WA 6009, Australia.
[MacGregor, Stuart; Martin, Nicholas G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Young, Terri L.] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA.
[Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Hammond, Christopher J.; Andrew, Toby; Fahy, Samantha] Kings Coll London, Sch Med, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Attia, John; Holliday, Elizabeth G.; Scott, Rodney J.] Univ Newcastle, Sch Biomed Sci, Callaghan, NSW 2308, Australia.
[Attia, John; Holliday, Elizabeth G.; Scott, Rodney J.] Hunter Med Res Inst, Newcastle, NSW, Australia.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA.
[Tai, E. Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol & Publ Hlth, Singapore 117595, Singapore.
[Tai, E. Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore.
[Wong, Tien Y.] Singapore Natl Eye Ctr, Singapore, Singapore.
[Wong, Tien Y.] Singapore Eye Res Inst, Singapore, Singapore.
[Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore.
RP Ikram, MK (reprint author), Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
EM ophwty@nus.edu.sg
RI Mackey, David/H-5340-2014; Bochud, Murielle/A-3981-2010; Grobbee,
Diederick/C-7651-2014; van der Schouw, Yvonne/F-8327-2014; Wang, Jie
Jin/P-1499-2014; Mitchell, Paul/P-1498-2014; Laan, Maris/A-4100-2011;
Onland-Moret, N. Charlotte/G-9185-2011; Gudnason, Vilmundur/K-6885-2015;
Meitinger, Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015;
Hewitt, Alex/D-1936-2013; Smith, Albert/K-5150-2015; Matullo,
Giuseppe/K-6383-2016; Fahy, Samantha/F-7966-2012; Pfeufer,
Arne/B-6634-2013; Altshuler, David/A-4476-2009; Aspelund,
Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Lucas, Gavin/D-4346-2012;
Macgregor, Stuart/C-6442-2009; Colaus, PsyColaus/K-6607-2013; Attia,
John/F-5376-2013
OI Luben, Robert/0000-0002-5088-6343; Sacerdote,
Carlotta/0000-0002-8008-5096; Klein, Ronald/0000-0002-4428-6237;
Hammond, Christopher/0000-0002-3227-2620; Ikram, Mohammad
Kamran/0000-0003-0173-9571; Tai, E Shyong/0000-0003-2929-8966; Martin,
Nicholas/0000-0003-4069-8020; Wain, Louise/0000-0003-4951-1867; Mackey,
David/0000-0001-7914-4709; Bochud, Murielle/0000-0002-5727-0218;
Seedorf, Udo/0000-0003-4652-5358; McAuley, Annie/0000-0002-6252-6185;
Zeggini, Eleftheria/0000-0003-4238-659X; Cotch, Mary
Frances/0000-0002-2046-4350; Org, Elin/0000-0003-1451-9375; Andrew,
Toby/0000-0001-8838-4384; Ikram, Mohammad Arfan/0000-0003-0372-8585;
Grobbee, Diederick/0000-0003-4472-4468; van der Schouw,
Yvonne/0000-0002-4605-435X; Wang, Jie Jin/0000-0001-9491-4898; Laan,
Maris/0000-0002-8519-243X; Gudnason, Vilmundur/0000-0001-5696-0084;
Rivadeneira, Fernando/0000-0001-9435-9441; Hewitt,
Alex/0000-0002-5123-5999; Smith, Albert/0000-0003-1942-5845; Fahy,
Samantha/0000-0002-2013-6154; Altshuler, David/0000-0002-7250-4107;
Aspelund, Thor/0000-0002-7998-5433; Macgregor,
Stuart/0000-0001-6731-8142; Attia, John/0000-0001-9800-1308
FU National Institute on Aging [Z01AG007380]; NIH [N01-AG-12100,
Z01EY000426]; National Eye Institute [Z01EY000401]; Althingi (the
Icelandic Parliament); National Heart, Lung, and Blood Institute
[N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021, N01-HC-55022, R01HL087641, N01-HC-85079, N01-HC-85086,
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
U01 HL080295, R01 HL087652, T32HL007902]; National Human Genome Research
Institute [U01HG004402]; National Institutes of Health
[HHSN268200625226C, UL1RR025005]; National Center for Research Resources
[M01RR00069]; National Institute of Diabetes and Digestive and Kidney
Diseases [DK063491]; Netherlands Genomics Initiative (NGI)/Netherlands
Organisation for Scientific Research (NWO) [050-060-810]; Erasmus
Medical Center; Erasmus University, Rotterdam; Netherlands Organization
for scientific research (NWO); Netherlands Organization for the Health
Research and Development (ZonMw); Research Institute for Diseases in the
Elderly (RIDE); Ministry of Education, Culture, and Science; Ministry
for Health, Welfare, and Sports; European commission; Municipality of
Rotterdam; Australian National Health and Medical Research Council
(NHMRC)
FX Age Gene/Environment Susceptibility - Reykjavik Study: Age,
Gene/Environment Susceptibility - Reykjavik Study received funding from
the Intramural Research Program of the National Institute on Aging
(Z01AG007380, NIH contract N01-AG-12100) and the National Eye Institute
(Z01EY000401) at the National Institutes of Health, Hjartavernd (the
Icelandic Heart Association), and the Althingi (the Icelandic
Parliament). Atherosclerosis Risk in Communities Study: The
Atherosclerosis Risk in Communities is supported by the National Heart,
Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022,
and R01HL087641; National Human Genome Research Institute award
U01HG004402; NIH Intramural Research award Z01EY000426 from the National
Eye Institute; and National Institutes of Health contract
HHSN268200625226C. Infrastructure was partly supported by Grant Number
UL1RR025005, a component of the National Institutes of Health and NIH
Roadmap for Medical Research. Cardiovascular Health Study: The CHS
research reported in this article was supported by contract numbers
N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01
HC-55222, N01-HC-75150, N01-HC-45133, grant numbers U01 HL080295 and R01
HL087652 from the National Heart, Lung, and Blood Institute, with
additional contribution from the National Institute of Neurological
Disorders and Stroke. DNA handling and genotyping was supported in part
by National Center for Research Resources grant M01RR00069 to the
Cedars-Sinai General Clinical Research Center Genotyping core and
National Institute of Diabetes and Digestive and Kidney Diseases grant
DK063491 to the Southern California Diabetes Endocrinology Research
Center. Additional support included the National Heart, Lung, and Blood
Institute Training Grant T32HL007902 (RAJ). Rotterdam Study: The GWA
database of the Rotterdam Study was funded through the Netherlands
Organization of Scientific Research NWO (no. 175.010.2005.011). This
study was further supported by the Netherlands Genomics Initiative
(NGI)/Netherlands Organisation for Scientific Research (NWO) project nr.
050-060-810. We thank Dr. Michael Moorhouse, Pascal Arp, and Mila Jhamai
for their help in creating the database. The Rotterdam Study is
supported by the Erasmus Medical Center and Erasmus University,
Rotterdam; the Netherlands Organization for scientific research (NWO);
the Netherlands Organization for the Health Research and Development
(ZonMw); The Research Institute for Diseases in the Elderly (RIDE); the
Ministry of Education, Culture, and Science; the Ministry for Health,
Welfare, and Sports; The European commission (DG XII); and the
Municipality of Rotterdam. The ophthalmic part of the Rotterdam Study
was supported by Lijf en Leven, Krimpen a/d Lek; MD Fonds, Utrecht.
Oogfonds Nederland, Utrecht; Stichting Nederlands Oogheelkundig
Onderzoek, Nijmegen/Rotterdam; Swart van Essen, Rotterdam; Netherlands
Organisation for Scientific Research (NWO); Bevordering van Volkskracht,
Rotterdam; Blindenhulp, The Hague; Rotterdamse Vereniging
Blindenbelangen, Rotterdam; OOG, The Hague; Algemene Nederlandse
Vereniging ter Voorkoming van Blindheid, Doorn; Blinden-Penning,
Amsterdam; Blindenhulp, Gravenzande; Henkes Stichting, Rotterdam; Topcon
Europe BV, Capelle aan de IJssel; Medical Workshop BV, Groningen; all in
the Netherlands; Heidelberg Engineering, Dossenheim, Germany.;
Australian Twins Study: The Australian Twin Registry is supported by an
Australian National Health and Medical Research Council (NHMRC) Enaling
Grant (2004-2009). We also thank the following organisations for their
financial support: Clifford Craig Medical Research Trust, Ophthalmic
Research Institute of Australia, Glaucoma Australia, American Health
Assistance Foundation, Peggy and Leslie Cranbourne Foundation,
Foundation for Children, NHMRC project grant (2005-2007), Jack Brockhoff
Foundation, NEI Project Grant (2007-2010).
NR 47
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PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD OCT
PY 2010
VL 6
IS 10
AR e1001184
DI 10.1371/journal.pgen.1001184
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 673GP
UT WOS:000283647800015
PM 21060863
ER
PT J
AU Lefevre, GM
Patel, SR
Kim, D
Tessarollo, L
Dressler, GR
AF Lefevre, Gaelle M.
Patel, Sanjeevkumar R.
Kim, Doyeob
Tessarollo, Lino
Dressler, Gregory R.
TI Altering a Histone H3K4 Methylation Pathway in Glomerular Podocytes
Promotes a Chronic Disease Phenotype
SO PLOS GENETICS
LA English
DT Article
ID CONTAINING PROTEIN PTIP; BRCT-DOMAIN; METHYLTRANSFERASE ACTIVITY;
TRANSGENIC MICE; MESSENGER-RNA; STEM-CELLS; EXPRESSION; CHROMATIN;
POLYCOMB; GROWTH
AB Methylation of specific lysine residues in core histone proteins is essential for embryonic development and can impart active and inactive epigenetic marks on chromatin domains. The ubiquitous nuclear protein PTIP is encoded by the Paxip1 gene and is an essential component of a histone H3 lysine 4 (H3K4) methyltransferase complex conserved in metazoans. In order to determine if PTIP and its associated complexes are necessary for maintaining stable gene expression patterns in a terminally differentiated, non-dividing cell, we conditionally deleted PTIP in glomerular podocytes in mice. Renal development and function were not impaired in young mice. However, older animals progressively exhibited proteinuria and podocyte ultra structural defects similar to chronic glomerular disease. Loss of PTIP resulted in subtle changes in gene expression patterns prior to the onset of a renal disease phenotype. Chromatin immunoprecipitation showed a loss of PTIP binding and lower H3K4 methylation at the Ntrk3 (neurotrophic tyrosine kinase receptor, type 3) locus, whose expression was significantly reduced and whose function may be essential for podocyte foot process patterning. These data demonstrate that alterations or mutations in an epigenetic regulatory pathway can alter the phenotypes of differentiated cells and lead to a chronic disease state.
C1 [Lefevre, Gaelle M.; Kim, Doyeob; Dressler, Gregory R.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Patel, Sanjeevkumar R.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Tessarollo, Lino] NCI, Neural Dev Sect, Frederick, MD 21701 USA.
RP Lefevre, GM (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM dressler@umich.edu
FU NIH [DK073722, DK054740]
FX This work was supported by NIH grant DK073722 and DK054740 to GRD. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 61
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PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD OCT
PY 2010
VL 6
IS 10
AR e1001142
DI 10.1371/journal.pgen.1001142
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 673GP
UT WOS:000283647800002
PM 21060806
ER
PT J
AU Cheung, GYC
Rigby, K
Wang, R
Queck, SY
Braughton, KR
Whitney, AR
Teintze, M
Deleo, FR
Otto, M
AF Cheung, Gordon Y. C.
Rigby, Kevin
Wang, Rong
Queck, Shu Y.
Braughton, Kevin R.
Whitney, Adeline R.
Teintze, Martin
DeLeo, Frank R.
Otto, Michael
TI Staphylococcus epidermidis Strategies to Avoid Killing by Human
Neutrophils
SO PLOS PATHOGENS
LA English
DT Article
ID PHENOL-SOLUBLE MODULIN; POLYSACCHARIDE INTERCELLULAR ADHESIN;
PEPTIDE-SENSING SYSTEM; AUREUS DELTA-TOXIN; IMMUNE EVASION;
ANTIMICROBIAL PEPTIDES; BIOFILM FORMATION; VIRULENCE; EXPRESSION; ACID
AB Staphylococcus epidermidis is a leading nosocomial pathogen. In contrast to its more aggressive relative S. aureus, it causes chronic rather than acute infections. In highly virulent S. aureus, phenol-soluble modulins (PSMs) contribute significantly to immune evasion and aggressive virulence by their strong ability to lyse human neutrophils. Members of the PSM family are also produced by S. epidermidis, but their role in immune evasion is not known. Notably, strong cytolytic capacity of S. epidermidis PSMs would be at odds with the notion that S. epidermidis is a less aggressive pathogen than S. aureus, prompting us to examine the biological activities of S. epidermidis PSMs. Surprisingly, we found that S. epidermidis has the capacity to produce PSM delta, a potent leukocyte toxin, representing the first potent cytolysin to be identified in that pathogen. However, production of strongly cytolytic PSMs was low in S. epidermidis, explaining its low cytolytic potency. Interestingly, the different approaches of S. epidermidis and S. aureus to causing human disease are thus reflected by the adaptation of biological activities within one family of virulence determinants, the PSMs. Nevertheless, S. epidermidis has the capacity to evade neutrophil killing, a phenomenon we found is partly mediated by resistance mechanisms to antimicrobial peptides (AMPs), including the protease SepA, which degrades AMPs, and the AMP sensor/resistance regulator, Aps (GraRS). These findings establish a significant function of SepA and Aps in S. epidermidis immune evasion and explain in part why S. epidermidis may evade elimination by innate host defense despite the lack of cytolytic toxin expression. Our study shows that the strategy of S. epidermidis to evade elimination by human neutrophils is characterized by a passive defense approach and provides molecular evidence to support the notion that S. epidermidis is a less aggressive pathogen than S. aureus.
C1 [Cheung, Gordon Y. C.; Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
[Rigby, Kevin; Wang, Rong; Queck, Shu Y.; Braughton, Kevin R.; Whitney, Adeline R.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT USA.
[Teintze, Martin] Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA.
RP Cheung, GYC (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
RI Cheung, Yiu Chong /K-3565-2012;
OI DeLeo, Frank/0000-0003-3150-2516; Otto, Michael/0000-0002-2222-4115
FU National Institute of Allergy and Infectious Diseases (NIAID), U.S.
National Institutes of Health (NIH)
FX This study was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases (NIAID), U.S.
National Institutes of Health (NIH). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
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SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD OCT
PY 2010
VL 6
IS 10
AR e1001133
DI 10.1371/journal.ppat.1001133
PG 10
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 673IG
UT WOS:000283652200009
PM 20949069
ER
PT J
AU Porotto, M
Rockx, B
Yokoyama, CC
Talekar, A
DeVito, I
Palermo, LM
Liu, J
Cortese, R
Lu, M
Feldmann, H
Pessi, A
Moscona, A
AF Porotto, Matteo
Rockx, Barry
Yokoyama, Christine C.
Talekar, Aparna
DeVito, Ilaria
Palermo, Laura M.
Liu, Jie
Cortese, Riccardo
Lu, Min
Feldmann, Heinz
Pessi, Antonello
Moscona, Anne
TI Inhibition of Nipah Virus Infection In Vivo: Targeting an Early Stage of
Paramyxovirus Fusion Activation during Viral Entry
SO PLOS PATHOGENS
LA English
DT Article
ID HUMAN PARAINFLUENZA VIRUS; HEMAGGLUTININ-NEURAMINIDASE PROTEIN; EMERGENT
DEADLY PARAMYXOVIRUS; HN-RECEPTOR INTERACTION; MEMBRANE-FUSION; POTENT
INHIBITORS; HAMSTER MODEL; CELL-FUSION; 4-GU-DANA ZANAMIVIR; FATAL
ENCEPHALITIS
AB In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viral and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses.
C1 [Porotto, Matteo; Yokoyama, Christine C.; Talekar, Aparna; DeVito, Ilaria; Palermo, Laura M.; Moscona, Anne] Cornell Univ, Weill Med Coll, Dept Pediat, New York, NY 10021 USA.
[Porotto, Matteo; Yokoyama, Christine C.; Talekar, Aparna; DeVito, Ilaria; Palermo, Laura M.; Moscona, Anne] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA.
[Rockx, Barry; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Liu, Jie; Lu, Min] Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA.
[Cortese, Riccardo] CEINGE, Naples, Italy.
[Pessi, Antonello] PeptiPharma, Rome, Italy.
RP Porotto, M (reprint author), Cornell Univ, Weill Med Coll, Dept Pediat, New York, NY 10021 USA.
EM Map2028@med.Cornell.edu; anm2047@med.Cornell.edu
FU National Institutes of Health (NIAID) [AI31971, AI076335, AI090354,
AI079771]; NIH (NIAID) Northeast Center of Excellence for Bio-defense
and Emerging Infectious Disease Research [U54AI057158]; Division of
Intramural Research (DIR), National Institute of Allergy and Infectious
Diseases (NIAID), National Institutes of Health (NIH)
FX This work was supported by Public Health Service grants AI31971,
AI076335, and AI090354 from the National Institutes of Health (NIAID) to
AM, AI079771 to ML, NIH (NIAID) Northeast Center of Excellence for
Bio-defense and Emerging Infectious Disease Research U54AI057158 grants
to AM and MP (PI of Center of Excellence grant: W. I. Lipkin), and
Division of Intramural Research (DIR), National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH) to HF.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
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PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD OCT
PY 2010
VL 6
IS 10
AR e1001168
DI 10.1371/journal.ppat.1001168
PG 17
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 673IG
UT WOS:000283652200040
PM 21060819
ER
PT J
AU Talbi, C
Lemey, P
Suchard, MA
Abdelatif, E
Elharrak, M
Jalal, N
Faouzi, A
Echevarria, JE
Moron, SV
Rambaut, A
Campiz, N
Tatem, AJ
Holmes, EC
Bourhy, H
AF Talbi, Chiraz
Lemey, Philippe
Suchard, Marc A.
Abdelatif, Elbia
Elharrak, Mehdi
Jalal, Nourlil
Faouzi, Abdellah
Echevarria, Juan E.
Vazquez Moron, Sonia
Rambaut, Andrew
Campiz, Nicholas
Tatem, Andrew J.
Holmes, Edward C.
Bourhy, Herve
TI Phylodynamics and Human-Mediated Dispersal of a Zoonotic Virus
SO PLOS PATHOGENS
LA English
DT Article
ID DOG RABIES VIRUS; TRANSMISSION DYNAMICS; VACCINATION CAMPAIGN;
POPULATION-DYNAMICS; MOLECULAR SEQUENCES; BITE INJURIES; CANINE RABIES;
AFRICA; EVOLUTION; DISEASE
AB Understanding the role of humans in the dispersal of predominately animal pathogens is essential for their control. We used newly developed Bayesian phylogeographic methods to unravel the dynamics and determinants of the spread of dog rabies virus (RABV) in North Africa. Each of the countries studied exhibited largely disconnected spatial dynamics with major geopolitical boundaries acting as barriers to gene flow. Road distances proved to be better predictors of the movement of dog RABV than accessibility or raw geographical distance, with occasional long distance and rapid spread within each of these countries. Using simulations that bridge phylodynamics and spatial epidemiology, we demonstrate that the contemporary viral distribution extends beyond that expected for RABV transmission in African dog populations. These results are strongly supportive of human-mediated dispersal, and demonstrate how an integrated phylogeographic approach will turn viral genetic data into a powerful asset for characterizing, predicting, and potentially controlling the spatial spread of pathogens.
C1 [Talbi, Chiraz; Bourhy, Herve] Inst Pasteur, Unit Lyssavirus Dynam & Host Adaptat, WHO Collaborating Ctr Reference & Res Rabies, Paris, France.
[Lemey, Philippe] Katholieke Univ Leuven, Rega Inst, Louvain, Belgium.
[Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA.
[Elharrak, Mehdi] Biopharma Lab, Rabat, Morocco.
[Abdelatif, Elbia] Inst Pasteur, Lab Rage Rech & Diagnost, Algiers, Algeria.
[Jalal, Nourlil; Faouzi, Abdellah] Inst Pasteur Maroc, Med Virol Lab, Casablanca, Morocco.
[Echevarria, Juan E.; Vazquez Moron, Sonia] Inst Salud Carlos III, Serv Microbiol Diagnost, Madrid, Spain.
[Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh, Midlothian, Scotland.
[Rambaut, Andrew; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Campiz, Nicholas; Tatem, Andrew J.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Tatem, Andrew J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
RP Talbi, C (reprint author), Inst Pasteur, Unit Lyssavirus Dynam & Host Adaptat, WHO Collaborating Ctr Reference & Res Rabies, Paris, France.
EM herve.bourhy@pasteur.fr
RI Vazquez Moron, Sonia/H-7019-2013; Echevarria, Juan E./F-7913-2016;
OI Vazquez Moron, Sonia/0000-0002-0977-741X; Echevarria, Juan
E./0000-0001-7522-850X; Rambaut, Andrew/0000-0003-4337-3707; Holmes,
Edward/0000-0001-9596-3552
FU European Union [INCO-CT-2006-517727]; Fund for Scientific Research (FWO)
Flanders; National Institutes of Health (NIH) [R01 GM080533, R01
GM086887]; National Science Foundation [DMS 0856099]; European Community
[260864]
FX This work was supported by the European Union Project RABMEDCONTROL (FP6
Project: INCO-CT-2006-517727). PL was supported by a postdoctoral
fellowship from the Fund for Scientific Research (FWO) Flanders. ECH was
supported by National Institutes of Health (NIH) grant R01 GM080533,
while MAS was partially supported by NIH grant R01 GM086887 and National
Science Foundation grant DMS 0856099. The European Research Council has
provided financial support under the European Community's Seventh
Framework Programme (FP7/2007-2013)/ERC grant agreement no \#260864. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 46
TC 68
Z9 68
U1 3
U2 20
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 OCT
PY 2010
VL 6
IS 10
AR e1001166
DI 10.1371/journal.ppat.1001166
PG 10
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 673IG
UT WOS:000283652200038
PM 21060816
ER
PT J
AU Zaitseva, E
Yang, ST
Melikov, K
Pourmal, S
Chernomordik, LV
AF Zaitseva, Elena
Yang, Sung-Tae
Melikov, Kamran
Pourmal, Sergei
Chernomordik, Leonid V.
TI Dengue Virus Ensures Its Fusion in Late Endosomes Using
Compartment-Specific Lipids
SO PLOS PATHOGENS
LA English
DT Article
ID SEMLIKI-FOREST-VIRUS; FLAVIVIRUS MEMBRANE-FUSION; PH-DEPENDENT FUSION;
VESICULAR STOMATITIS-VIRUS; SINDBIS VIRUS; INFLUENZA HEMAGGLUTININ;
CELL-FUSION; MONOCLONAL-ANTIBODIES; TARGET MEMBRANE; WEST-NILE
AB Many enveloped viruses invade cells via endocytosis and use different environmental factors as triggers for virus-endosome fusion that delivers viral genome into cytosol. Intriguingly, dengue virus (DEN), the most prevalent mosquito-borne virus that infects up to 100 million people each year, fuses only in late endosomes, while activation of DEN protein fusogen glycoprotein E is triggered already at pH characteristic for early endosomes. Are there any cofactors that time DEN fusion to virion entry into late endosomes? Here we show that DEN utilizes bis(monoacylglycero) phosphate, a lipid specific to late endosomes, as a co-factor for its endosomal acidification-dependent fusion machinery. Effective virus fusion to plasma-and intracellular-membranes, as well as to protein-free liposomes, requires the target membrane to contain anionic lipids such as bis(monoacylglycero) phosphate and phosphatidylserine. Anionic lipids act downstream of low-pH-dependent fusion stages and promote the advance from the earliest hemifusion intermediates to the fusion pore opening. To reach anionic lipid-enriched late endosomes, DEN travels through acidified early endosomes, but we found that low pH-dependent loss of fusogenic properties of DEN is relatively slow in the presence of anionic lipid-free target membranes. We propose that anionic lipid-dependence of DEN fusion machinery protects it against premature irreversible restructuring and inactivation and ensures viral fusion in late endosomes, where the virus encounters anionic lipids for the first time during entry. Currently there are neither vaccines nor effective therapies for DEN, and the essential role of the newly identified DEN-bis(monoacylglycero) phosphate interactions in viral genome escape from the endosome suggests a novel target for drug design.
C1 [Zaitseva, Elena; Yang, Sung-Tae; Melikov, Kamran; Pourmal, Sergei; Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD USA.
RP Zaitseva, E (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD USA.
EM chernoml@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health; NIAID, National Institutes
of Health
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health and by an NIAID, National
Institutes of Health Intramural Biodefense Research grant (both to
L.V.C.). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 66
TC 96
Z9 98
U1 1
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD OCT
PY 2010
VL 6
IS 10
AR e1001131
DI 10.1371/journal.ppat.1001131
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 673IG
UT WOS:000283652200007
PM 20949067
ER
PT J
AU Huang, J
Sun, LG
Huang, W
Wang, XM
Wang, YH
AF Huang, Jing
Sun, Liguang
Huang, Wen
Wang, Xinming
Wang, Yuhong
TI The ecosystem evolution of penguin colonies in the past 8,500 years on
Vestfold Hills, East Antarctica
SO POLAR BIOLOGY
LA English
DT Article
DE Antarctica; Penguin colony; Ecosystem evolution; Molecular marker;
Ornithogenic sediment; Fecal sterol
ID DIATOM ASSEMBLAGES; ICE-SHEET; SALINE LAKES; PRYDZ BAY; ACE LAKE;
HOLOCENE; ISLAND; SEA; POPULATIONS; OCCUPATION
AB Penguin colony is one of the Earth's simplest ecosystems. As the seabird with the largest population in Antarctica, penguin is a unique indicator of Antarctic environment and climate changes. In this study, we collected an ornithogenic sediment core from Gardner Island in Vestfold Hills, East Antarctica, reconstructed an 8,500 years variation history of penguin population and vegetation abundance on this island, and examined the evolution of the penguin colony. We used the levels of two molecular markers cholesterol and cholestanol as the proxy indicators of penguin population size. Other molecular markers, including C(24:0) alkenoic acid, C(18) n-alkanol and phytol were used as the proxy indicators of aquatic moss, algae, and general vegetation, respectively. It is shown that the growth of algae was mainly affected by the nutritional supply from penguin droppings, so their abundance was positively linked with penguin population. The growth of aquatic moss, however, was controlled more by the degree of water body transparency than by nutrient availability. Because the pollution of water body increased as penguin population grew, aquatic moss abundance showed a seesaw-like relationship with penguin population. These results suggested that penguins played a dominant role in this simple ecosystem in the Antarctic environment. The reconstructed relationship between penguin population and vegetation abundance may offer new insights to understand ancient Antarctic environment and ecology.
C1 [Huang, Jing; Sun, Liguang] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China.
[Huang, Jing; Wang, Xinming] Chinese Acad Sci, Guangzhou Inst Geochem, Guangzhou 510640, Guangdong, Peoples R China.
[Huang, Wen] Univ Wisconsin, Dept Dairy Sci, Madison, WI 53706 USA.
[Wang, Yuhong] NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China.
EM slg@ustc.edu.cn
RI Huang, Wen/B-5005-2011; Wang, Xinming/A-7388-2014
OI Wang, Xinming/0000-0002-1982-0928
FU National Natural Science Foundation of China [40730107]; National
Science and Technology [2006BAB18B07]; State Key Laboratory of Organic
Geochemistry foundation [OGL-200606]; Australia Antarctic Division
Science Project [AAD2873]
FX We thank the Chinese Arctic and Antarctic Administration, Australian
Antarctic Division, CHINARE22 team in Zhongshan Station and the members
of Davis Station for their support and assistance in the field working.
We thank Prof. Renbin Zhu for sample collection. This study was funded
by the National Natural Science Foundation of China (No. 40730107), the
National Science and Technology Supporting Program (2006BAB18B07), the
State Key Laboratory of Organic Geochemistry foundation (OGL-200606) and
the Australia Antarctic Division Science Project (AAD2873).
NR 44
TC 11
Z9 14
U1 4
U2 35
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0722-4060
J9 POLAR BIOL
JI Polar Biol.
PD OCT
PY 2010
VL 33
IS 10
BP 1399
EP 1406
DI 10.1007/s00300-010-0832-x
PG 8
WC Biodiversity Conservation; Ecology
SC Biodiversity & Conservation; Environmental Sciences & Ecology
GA 649BD
UT WOS:000281740300011
ER
PT J
AU Louis, SNS
Chow, L
Rezmann, L
Krezel, MA
Catt, KJ
Tikellis, C
Frauman, AG
Louis, WJ
AF Louis, Simon N. S.
Chow, Laurie
Rezmann, Linda
Krezel, Michael A.
Catt, Kevin J.
Tikellis, Chris
Frauman, Albert G.
Louis, William J.
TI Expression and Function of ATIP/MTUSI in Human Prostate Cancer Cell
Lines
SO PROSTATE
LA English
DT Article
DE AT(2)-receptor; AT(2)-receptor interacting protein; prostate cancer cell
line; epidermal growth factor
ID GROWTH-FACTOR RECEPTOR; ANGIOTENSIN-II RECEPTORS; CONVERTING-ENZYME; AT2
RECEPTOR; ANTIPROLIFERATIVE ACTIVITY; INTERACTING PROTEIN; TUMOR-GROWTH;
CARCINOMA; IDENTIFICATION; HYPERPLASIA
AB BACKGROUND. We have previously demonstrated Ang II type 2 (AT(2)-) receptor-mediated inhibition of EGF-induced prostate cancer cell growth in androgen-dependent (LNCaP) and independent (PC3) prostate cancer cell lines.
METHODS. To explore the signaling pathways involved in this inhibitory effect, we examined the interaction of the AT(2)-receptor with its novel regulatory partner ATIP using real time PCR, over-expression, siRNA and [(3)H] thymidine incorporation assays.
RESULTS. The results in human prostate cancer cell lines demonstrate the presence of ATIP in both cell lines examined, and suggest that (i) the AT(2)-receptor through an interaction with ATIP mediates an anti-growth factor effect in both androgen-dependent and androgen-independent cell lines; (ii) ATIP expression decreases as the rate of cell growth and androgen-independence increase; and (iii) EGF may act on cell growth in part by reducing the content of ATIP present in the cells.
CONCLUSIONS. The results support our earlier proposal in normal cell lines that ATIP is an important component of the cellular response to AT(2)-receptor activation. The results further suggest that a critical level of ATIP is required to mediate the effect of AT(2)-receptor activation to inhibit EGF mediated increases in cell growth. They also suggest that EGF may in part induce cell growth by suppressing the level of ATIP expression. Prostate 70: 1563-1574, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Louis, Simon N. S.; Chow, Laurie; Rezmann, Linda; Krezel, Michael A.; Frauman, Albert G.; Louis, William J.] Univ Melbourne, Clin Pharmacol & Therapeut Unit, Dept Med, Austin Hlth, Heidelberg, Vic 3084, Australia.
[Catt, Kevin J.] NICHD, Sect Hormonal Regulat, PEDGEN, NIH, Bethesda, MD USA.
[Tikellis, Chris] Baker Heart Res Inst, Melbourne, Vic, Australia.
RP Louis, SNS (reprint author), Univ Melbourne, Clin Pharmacol & Therapeut Unit, Dept Med, Austin Hlth, Studley Rd,Level 5 Lance Townsend Bldg, Heidelberg, Vic 3084, Australia.
EM simonnsl@unimelb.edu.au
FU INSERM/NHMRC; Sir Edward Dunlop Medical Research Foundation; Austin
Hospital Medical Research Foundation; University of Melbourne
FX This work has been kindly supported by the INSERM/NH&MRC, Sir Edward
Dunlop Medical Research Foundation, the Austin Hospital Medical Research
Foundation and the University of Melbourne. The authors would also like
to thank Dr. Clara Nahmias and Professor Pam Russell for their help in
preparing this manuscript.
NR 38
TC 14
Z9 15
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-4137
J9 PROSTATE
JI Prostate
PD OCT 1
PY 2010
VL 70
IS 14
BP 1563
EP 1574
DI 10.1002/pros.21192
PG 12
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 657IF
UT WOS:000282405700009
PM 20687230
ER
PT J
AU Yan, JS
Hereld, D
Jin, T
AF Yan, Jianshe
Hereld, Dale
Jin, Tian
TI Chemotaxis: new role for Ras revealed
SO PROTEIN & CELL
LA English
DT News Item
C1 [Yan, Jianshe; Jin, Tian] NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Hereld, Dale] NIAAA, Div Metab & Hlth Effects, NIH, Rockville, MD 20852 USA.
RP Yan, JS (reprint author), NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM yanjia@niaid.nih.gov
NR 7
TC 0
Z9 0
U1 0
U2 0
PU HIGHER EDUCATION PRESS
PI BEIJING
PA SHATANHOU ST 55, BEIJING 100009, PEOPLES R CHINA
SN 1674-800X
J9 PROTEIN CELL
JI Protein Cell
PD OCT
PY 2010
VL 1
IS 10
BP 879
EP 880
DI 10.1007/s13238-010-0119-6
PG 2
WC Cell Biology
SC Cell Biology
GA V25XV
UT WOS:000208511600001
PM 21204012
ER
PT J
AU Lu, JX
Sharpe, S
Ghirlando, R
Yau, WM
Tycko, R
AF Lu, Jun-Xia
Sharpe, Simon
Ghirlando, Rodolfo
Yau, Wai-Ming
Tycko, Robert
TI Oligomerization state and supramolecular structure of the HIV-1 Vpu
protein transmembrane segment in phospholipid bilayers
SO PROTEIN SCIENCE
LA English
DT Article
DE solid-state NMR; analytical ultracentrifugation; photochemical
crosslinking; membrane protein structure
ID PHOTOINDUCED CROSS-LINKING; ION-CHANNEL ACTIVITY; VIRUS TYPE-1 VPU;
MOLECULAR-DYNAMICS; BETA-TRCP; SEDIMENTATION-VELOCITY;
MEMBRANE-PROTEINS; NMR-SPECTROSCOPY; ANALYTICAL ULTRACENTRIFUGATION;
3-DIMENSIONAL STRUCTURE
AB HIV-1 Vpu is an 81-residue protein with a single N-terminal transmembrane (TM) helical segment that is involved in the release of new virions from host cell membranes. Vpu and its TM segment form ion channels in phospholipid bilayers, presumably by oligomerization of TM helices into a pore-like structure. We describe measurements that provide new constraints on the oligomerization state and supramolecular structure of residues 1-40 of Vpu (Vpu(1-40)), including analytical ultracentrifugation measurements to investigate oligomerization in detergent micelles, photo-induced crosslinking experiments to investigate oligomerization in bilayers, and solid-state nuclear magnetic resonance measurements to obtain constraints on intermolecular contacts between and orientations of TM helices in bilayers. From these data, we develop molecular models for Vpu TM oligomers. The data indicate that a variety of oligomers coexist in phospholipid bilayers, so that a unique supramolecular structure can not be defined. Nonetheless, since oligomers of various sizes have similar intermolecular contacts and orientations, molecular models developed from our data are most likely representative of Vpu TM oligomers that exist in host cell membranes.
C1 [Lu, Jun-Xia; Yau, Wai-Ming; Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Sharpe, Simon] Hosp Sick Children, Program Mol Struct & Funct, Toronto, ON M5G 1X8, Canada.
[Ghirlando, Rodolfo] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA.
EM robertty@mail.nih.gov
RI Ghirlando, Rodolfo/A-8880-2009
FU Intramural Research Program; National Institute of Diabetes and
Digestive and Kidney Diseases; National Institutes of Health
FX Grant sponsors: Intramural Research Program, National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health, NIH Intramural AIDS Targeted Antiviral Program.
NR 74
TC 35
Z9 35
U1 0
U2 16
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD OCT
PY 2010
VL 19
IS 10
BP 1877
EP 1896
DI 10.1002/pro.474
PG 20
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661HO
UT WOS:000282716900007
PM 20669237
ER
PT J
AU Flynn, KE
Shelby, RA
Mitchell, SA
Fawzy, MR
Hardy, NC
Husain, AM
Keefe, FJ
Krystal, AD
Porter, LS
Reeve, BB
Weinfurt, KP
AF Flynn, Kathryn E.
Shelby, Rebecca A.
Mitchell, Sandra A.
Fawzy, Maria R.
Hardy, N. Chantelle
Husain, Aatif M.
Keefe, Francis J.
Krystal, Andrew D.
Porter, Laura S.
Reeve, Bryce B.
Weinfurt, Kevin P.
TI Sleep-wake functioning along the cancer continuum: focus group results
from the Patient-Reported Outcomes Measurement Information System
(PROMIS (R))
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE cancer; focus groups; oncology; qualitative research; quality of life;
sleep
ID BREAST-CANCER; INSOMNIA SECONDARY; FATIGUE; DISTURBANCE; SURVIVORS;
SYMPTOMS; EFFICACY; THERAPY; CONTEXT; PEOPLE
AB Objective: Cancer and its treatments disturb sleep wake functioning; however, there is little information available on the characteristics and consequences of sleep problems associated with cancer. As part of an effort to improve measurement of sleep wake functioning, we explored the scope of difficulties with sleep in a diverse group of patients diagnosed with cancer.
Methods: We conducted 10 focus groups with patients recruited from the Duke University tumor registry and oncology/hematology clinics. Separate groups were held with patients scheduled to begin or currently undergoing treatment for breast, prostate, lung, colorectal, hematological, and other cancer types and with patients who were in posttreatment follow-up. The content of the focus group discussions was transcribed and analyzed for major themes by independent coders.
Results: Participants not only reported causes of sleep disturbance common in other populations, such as pain and restless legs, but they also reported causes that may be unique to cancer populations, including abnormal dreams, anxiety about cancer diagnosis and recurrence, night sweats, and problems with sleep positioning. Many participants felt that sleep problems reduced their productivity, concentration, social interactions, and overall quality of life. Many also shared beliefs about the increased importance of sleep when fighting cancer.
Conclusions: The findings underscore the need for interventions that minimize the negative impact of cancer and its treatments on sleep. This study will inform efforts now underway to develop a patient-reported measure of sleep wake functioning that reflects the breadth of concepts considered important by patients with cancer. Copyright (C) 2009 John Wiley & Sons, Ltd.
C1 [Flynn, Kathryn E.; Fawzy, Maria R.; Hardy, N. Chantelle; Weinfurt, Kevin P.] Duke Univ, Ctr Clin & Genet Econ, Sch Med, Duke Clin Res Inst, Durham, NC 27715 USA.
[Flynn, Kathryn E.; Keefe, Francis J.; Krystal, Andrew D.; Porter, Laura S.; Weinfurt, Kevin P.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27715 USA.
[Shelby, Rebecca A.; Weinfurt, Kevin P.] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27715 USA.
[Mitchell, Sandra A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Husain, Aatif M.] Duke Univ, Dept Med, Sch Med, Durham, NC 27715 USA.
[Reeve, Bryce B.] NCI, Bethesda, MD 20892 USA.
RP Flynn, KE (reprint author), Duke Univ, Ctr Clin & Genet Econ, Sch Med, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA.
EM kathryn.flynn@duke.edu
RI Krystal, Andrew/J-7109-2013; Flynn, Kathryn/M-5346-2013
OI Krystal, Andrew/0000-0002-6702-781X; Flynn, Kathryn/0000-0002-4427-3583
FU National Institutes of Health [U01AR052186]
FX This work was supported by a National Cancer Institute supplement to
grant U01AR052186 from the National Institutes of Health.
NR 37
TC 12
Z9 12
U1 0
U2 4
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1057-9249
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD OCT
PY 2010
VL 19
IS 10
BP 1086
EP 1093
DI 10.1002/pon.1664
PG 8
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 670FC
UT WOS:000283405600009
PM 20013938
ER
PT J
AU Eddy, KT
Swanson, SA
Crosby, RD
Franko, DL
Engel, S
Herzog, DB
AF Eddy, K. T.
Swanson, S. A.
Crosby, R. D.
Franko, D. L.
Engel, S.
Herzog, D. B.
TI How should DSM-V classify eating disorder not otherwise specified
(EDNOS) presentations in women with lifetime anorexia or bulimia
nervosa?
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Anorexia nervosa; bulimia nervosa; classification; eating disorder not
otherwise specified; longitudinal
ID DIAGNOSTIC CROSSOVER; PURGING DISORDER; VALIDITY; RELAPSE
AB Objective. Anorexia nervosa (AN) and bulimia nervosa (BN) are marked by longitudinal symptom fluctuations. DSM-IV-TR does not address how to classify eating disorder (ED) presentations in individuals who no longer meet full criteria for these disorders. To consider this issue, we examined subthreshold presentations in women with initial diagnoses of AN and BN.
Method. A total of 246 women with AN or BN were followed for a median of 9 years; weekly symptom data were collected at frequent intervals using the Longitudinal Interval Follow-up Evaluation of Eating Disorders (LIFE-EAT-II). Outcomes were ED presentations that were subthreshold for >= 3 months, including those narrowly missing full criteria for AN or BN, along with binge eating disorder (BED) and purging disorder.
Results. During follow-up, most women (77.6%) experienced a subthreshold presentation. Subthreshold presentation was related to intake diagnosis (Wald chi(2)=8.065, df=2, p=0.018). Individuals with AN most often developed subthreshold presentations resembling AN; those with BN were more likely to develop subthreshold BN. Purging disorder was experienced by half of those with BN and one-quarter of those with AN binge/purge type (ANBP); BED occurred in 20% with BN. Transition from AN or BN to most subthreshold types was associated with improved psychosocial functioning (p<0.001).
Conclusions. Subthreshold presentations in women with lifetime AN and BN were common, resembled the initial diagnosis, and were associated with modest improvements in psychosocial functioning. For most with lifetime AN and BN, subthreshold presentations seem to represent part of the course of illness and to fit within the original AN or BN diagnosis.
C1 [Eddy, K. T.; Franko, D. L.; Herzog, D. B.] Massachusetts Gen Hosp, Dept Psychiat, Harris Ctr, Boston, MA 02214 USA.
[Swanson, S. A.] NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA.
[Crosby, R. D.; Engel, S.] Neuropsychiat Res Inst, Fargo, ND USA.
[Crosby, R. D.; Engel, S.] Univ N Dakota, Sch Med & Hlth Sci, Dept Clin Neurosci, Fargo, ND USA.
[Franko, D. L.] Northwestern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA USA.
RP Eddy, KT (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Harris Ctr, 2 Longfellow Pl,Ste 200, Boston, MA 02214 USA.
EM keddy@partners.org
OI Crosby, Ross/0000-0001-9131-1629
FU [RO1 MH038333]; [F32 MH084396]
FX Support for this research was provided by RO1 MH038333 (PI D.B.H.) and
F32 MH084396 (PI K.T.E.).
NR 17
TC 10
Z9 10
U1 1
U2 10
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD OCT
PY 2010
VL 40
IS 10
BP 1735
EP 1744
DI 10.1017/S0033291709992200
PG 10
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 644VF
UT WOS:000281408700015
PM 20047706
ER
PT J
AU Clauser, SB
Brazier, J
Feeny, D
Revicki, DA
Kind, P
AF Clauser, Steven B.
Brazier, John
Feeny, David
Revicki, Dennis A.
Kind, Paul
TI Development and Comparisons of Alternative Preference-Based Measures of
Health
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Clauser, Steven B.] NCI, Outcomes Res Branch, Bethesda, MD 20892 USA.
[Brazier, John] Sch Hlth & Related Res, Sheffield, S Yorkshire, England.
[Feeny, David] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA.
[Revicki, Dennis A.] United BioSource Corp, Ctr Hlth Outcomes Res, Bethesda, MD USA.
[Kind, Paul] Univ York, Ctr Hlth Econ, York YO10 5DD, N Yorkshire, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2010
VL 19
SU 1
BP 2
EP 2
PG 1
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA V38QU
UT WOS:000209358700002
ER
PT J
AU Maringwa, JT
Coens, C
Quinten, C
Martinelli, F
Ringash, J
Osoba, D
Reeve, BB
King, M
Cleeland, CS
Flechtner, H
Gotay, C
Greimel, E
Taphoorn, MJ
Schumucker-von Koch, J
Weis, J
Smit, EF
van Meerbeeck, JP
Bottomley, A
AF Maringwa, John T.
Coens, Corneel
Quinten, Chantal
Martinelli, Francesca
Ringash, Jolie
Osoba, David
Reeve, Bryce B.
King, Madeleine
Cleeland, Charles S.
Flechtner, Henning
Gotay, Carolyn
Greimel, Eva
Taphoorn, Martin J.
Schumucker-von Koch, Joseph
Weis, Joachim
Smit, Egbert F.
van Meerbeeck, Jan P.
Bottomley, Andrew
TI Effect of Time Windows in Analysis of Health-Related Quality of Life
(HRQOL) Outcomes
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Maringwa, John T.; Coens, Corneel; Quinten, Chantal; Martinelli, Francesca; Bottomley, Andrew] EORTC, Qual Life, Brussels, Belgium.
[Ringash, Jolie] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada.
[Osoba, David] Qual Life Consulting, West Vancourver, BC, Canada.
[Reeve, Bryce B.] NCI, Div Canc Control & Populat Studies, NIH, Bethesda, MD 20892 USA.
[King, Madeleine] Univ Sydney, PoCoG, Sydney, NSW 2006, Australia.
[Cleeland, Charles S.] Univ Texas Houston, Symptom Res, Houston, TX USA.
[Flechtner, Henning] Otto Von Guericke Univ, Fac Med, Magdeburg, Germany.
[Gotay, Carolyn] Sch Populat & Publ Hlth, Primary Prevent, Vancouver, BC, Canada.
[Greimel, Eva] Med Univ Graz, Obstet & Gynecol, Graz, Austria.
[Taphoorn, Martin J.] Vrije Univ Amsterdam Med Ctr, Neurol, Amsterdam, Netherlands.
[Schumucker-von Koch, Joseph] Univ Regensburg, Med Eth, D-93053 Regensburg, Germany.
[Weis, Joachim] Univ Freiburg, Tumor Biol Ctr, D-79106 Freiburg, Germany.
[Smit, Egbert F.] Vrije Univ VUMC, Pulm Dis, Amsterdam, Netherlands.
[van Meerbeeck, Jan P.] Univ Ziekenhuis Gent, Thoracale Oncol, Ghent, Belgium.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2010
VL 19
SU 1
MA 1369
BP 19
EP 20
PG 2
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA V38QU
UT WOS:000209358700060
ER
PT J
AU Johnson, LL
Kurland, BF
Egleston, BL
Diehr, P
AF Johnson, Laura L.
Kurland, Brenda F.
Egleston, Brian L.
Diehr, Paula
TI Longitudinal data with follow-up truncated by death: Matching
statistical analysis to research, clinical and policy aims
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Johnson, Laura L.] US Natl Inst Hlth, NCCAM, Bethesda, MD USA.
[Kurland, Brenda F.] Fred Hutchinson Canc Res Ctr, Clin Stat, Seattle, WA 98104 USA.
[Egleston, Brian L.] Fox Chase Canc Ctr, Biostat & Bioinformat, Philadelphia, PA 19111 USA.
[Diehr, Paula] Univ Washington, Biostat & Hlth Serv, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2010
VL 19
SU 1
MA 1714
BP 20
EP 20
PG 1
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA V38QU
UT WOS:000209358700061
ER
PT J
AU Treadwell, MJ
Levine, R
Keller, S
Hassell, K
Werner, E
AF Treadwell, Marsha J.
Levine, Roger
Keller, San
Hassell, Kathryn
Werner, Ellen
TI Understanding Perspectives of Adults with Sickle Cell Disease in
Developing a Disease Specific Quality of Life Measurement System
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Treadwell, Marsha J.] Childrens Hosp & Res Ctr Oakland, Hematol Oncol, Oakland, CA USA.
[Levine, Roger] Amer Inst Res, San Mateo, CA USA.
[Keller, San] Amer Inst Res, Chapel Hill, NC USA.
[Hassell, Kathryn] Univ Colorado, Sickle Cell Treatment & Res Ctr, Denver, CO 80202 USA.
[Werner, Ellen] NHLBI, Blood Dis & Resources, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2010
VL 19
SU 1
MA 1666
BP 23
EP 23
PG 1
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA V38QU
UT WOS:000209358700071
ER
PT J
AU Bruner, DW
Hanisch, LJ
Reeve, BB
Minasian, LM
Rowland, JH
O'Mara, AM
Sit, L
Sloan, JA
Cleeland, CS
Denicoff, AM
Trimble, EL
Clauser, SB
Geoghegan, C
Paul, DB
Abernethy, AP
Schrag, D
Basch, EM
AF Bruner, Deborah Watkins
Hanisch, Laura J.
Reeve, Bryce B.
Minasian, Lori M.
Rowland, Julia H.
O'Mara, Ann M.
Sit, Laura
Sloan, Jeff A.
Cleeland, Charles S.
Denicoff, Andrea M.
Trimble, Edward L.
Clauser, Steven B.
Geoghegan, Cindy
Paul, Diane B.
Abernethy, Amy P.
Schrag, Deborah
Basch, Ethan M.
TI Perceived Barriers to Implementing the Patient-Reported Outcomes-Common
Toxicity Criteria Adverse Event (PRO-CTCAE) System in Cancer Clinical
Trials
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Bruner, Deborah Watkins] Univ Penn, Sch Nursing, Biobehav Hlth Sci Div, Philadlephia, PA USA.
[Hanisch, Laura J.] Univ Penn, Psychiat, Philadelphia, PA 19104 USA.
[Reeve, Bryce B.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Minasian, Lori M.; O'Mara, Ann M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Rowland, Julia H.; Clauser, Steven B.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Sit, Laura; Basch, Ethan M.] Mem Sloan Kettering Canc Ctr, Epidemiol & Biostat, New York, NY 10021 USA.
[Sloan, Jeff A.] Mayo Clin, Hlth Sci Res, Rochester, MN USA.
[Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Symptom Res, Houston, TX 77030 USA.
[Denicoff, Andrea M.; Trimble, Edward L.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Geoghegan, Cindy] Patient & Partners LLC, Madison, CT USA.
[Paul, Diane B.] Patient Advocate, Brooklyn, NY USA.
[Abernethy, Amy P.] Duke Univ, Sch Med, Med, Durham, NC USA.
[Schrag, Deborah] Dana Farber Canc Inst, Med, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
U1 1
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2010
VL 19
SU 1
MA 1006
BP 31
EP 32
PG 2
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA V38QU
UT WOS:000209358700096
ER
PT J
AU Basch, E
Reeve, B
Cleeland, CS
Sloan, JA
Schrag, D
Atkinson, TM
Mendoza, TR
Hay, JL
Abernethy, AP
Minasian, L
Kwitkowski, V
Trentacosti, AM
Burke, L
Sit, L
Bruner, DW
AF Basch, Ethan
Reeve, Bryce
Cleeland, Charles S.
Sloan, Jeff A.
Schrag, Deborah
Atkinson, Thomas M.
Mendoza, Tito R.
Hay, Jennifer L.
Abernethy, Amy P.
Minasian, Lori
Kwitkowski, Virginia
Trentacosti, Ann Marie
Burke, Laurie
Sit, Laura
Bruner, Deborah W.
TI Development of the Patient-Reported Version of the Common Terminology
Criteria for Adverse Events (PRO-CTCAE)
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Basch, Ethan; Sit, Laura] Mem Sloan Kettering Canc Ctr, Epidemiol & Biostat, New York, NY 10021 USA.
[Reeve, Bryce] NCI, Outcomes Res, Bethesda, MD 20892 USA.
[Cleeland, Charles S.; Mendoza, Tito R.] Univ Texas MD Anderson Canc Ctr, Symptom Res, Houston, TX 77030 USA.
[Sloan, Jeff A.] Mayo Clin, Biomed Stat & Informat, Rochester, MN USA.
[Schrag, Deborah] Dana Farber Canc Inst, Med, Boston, MA 02115 USA.
[Atkinson, Thomas M.; Hay, Jennifer L.] Mem Sloan Kettering Canc Ctr, Psychiat & Behav Sci, New York, NY 10021 USA.
[Abernethy, Amy P.] Duke Univ, Sch Med, Med, Durham, NC USA.
[Minasian, Lori] NCI, Canc Prevent, Rockville, MD USA.
[Kwitkowski, Virginia] US FDA, Drug Oncol Prod, Silver Spring, MD USA.
[Burke, Laurie] US FDA, Study Endpoints & Labeling Dev, Silver Spring, MD USA.
[Bruner, Deborah W.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2010
VL 19
SU 1
MA 161439
BP 50
EP 51
PG 2
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA V38QU
UT WOS:000209358700153
ER
PT J
AU Quinten, C
Martinelli, F
Maringwa, J
Coens, C
Reeve, B
Gotay, C
Flechtner, H
Ringash, J
Greimel, E
King, M
Osoba, D
Taphoorn, MJ
Cleeland, C
Weis, J
Schmucker-von Koch, J
Bottomley, A
AF Quinten, Chantal
Martinelli, Francesca
Maringwa, John
Coens, Corneel
Reeve, Bryce
Gotay, Caroline
Flechtner, Henning
Ringash, Jolie
Greimel, Eva
King, Madeleine
Osoba, David
Taphoorn, Martin J.
Cleeland, Charles
Weis, Joachim
Schmucker-von Koch, Joseph
Bottomley, Andrew
TI Prognostic significance of patient heterogeneity in a dataset of 10,108
cancer patients
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Quinten, Chantal; Martinelli, Francesca; Maringwa, John; Coens, Corneel; Bottomley, Andrew] EORTC, Qual Life Dept, Brussels, Belgium.
[Reeve, Bryce] NCI, Div Canc Control & Populat Studies, NIH, Bethesda, MD 20892 USA.
[Gotay, Caroline] Univ British Columbia, Primary Prevent Sch Populat, Vancouver, BC V5Z 1M9, Canada.
[Flechtner, Henning] Univ Magdeburg, Fac Med, D-39106 Magdeburg, Germany.
[Ringash, Jolie] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada.
[Greimel, Eva] Med Univ Graz, Obstet & Gynecol, Graz, Austria.
[King, Madeleine] Univ Sydney, Psychooncol Cooperat Res Grp, Sydney, NSW 2006, Australia.
[Osoba, David] Qual Life Consulting, Vancouver, BC, Canada.
[Taphoorn, Martin J.] VU Med Ctr MC Haaglanden, Neurol, The Hague, Netherlands.
[Cleeland, Charles] Univ Texas Houston, Symptom Res, Houston, TX USA.
[Weis, Joachim] Univ Freiburg, Psychooncol, D-79106 Freiburg, Germany.
[Schmucker-von Koch, Joseph] Univ Regensburg, Philosoph Fac, D-93053 Regensburg, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2010
VL 19
SU 1
MA 150/1291
BP 93
EP 93
PG 1
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA V38QU
UT WOS:000209358700287
ER
PT J
AU Victorson, D
Cavazos, J
Cella, D
Nowinski, C
Wortman, K
Moy, C
AF Victorson, David
Cavazos, Jose
Cella, David
Nowinski, Cindy
Wortman, Katy
Moy, Claudia
TI Validation of Neuro-QOL Measures for People Diagnosed with Epilepsy
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Victorson, David; Cella, David; Nowinski, Cindy; Wortman, Katy] Northwestern Univ, Feinberg Sch Med, Med Social Sci, Evanston, IL 60208 USA.
[Cavazos, Jose] Univ Texas Hlth Sci Ctr San Anto, Neurol, San Antonio, TX 78229 USA.
[Moy, Claudia] NINDS, Extramural Res, NIH, Bethesda, MD 20892 USA.
RI Cavazos, Jose/J-4122-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2010
VL 19
SU 1
MA 160/1327
BP 96
EP 97
PG 2
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA V38QU
UT WOS:000209358700297
ER
PT J
AU Miller, D
Bethoux, F
Nowinski, C
Victorson, D
Moy, C
Wortman, K
Cella, D
AF Miller, Deborah
Bethoux, Francois
Nowinski, Cindy
Victorson, David
Moy, Claudia
Wortman, Katy
Cella, David
TI Validation of Neuro-QOL Measures for People Diagnosed with Multiple
Sclerosis
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Miller, Deborah] Cleveland Clin Fdn, Neurol, Cleveland, OH USA.
[Bethoux, Francois] Cleveland Clin, Neurol, Cleveland, OH USA.
[Nowinski, Cindy; Victorson, David; Wortman, Katy; Cella, David] Northwestern Univ, Feinberg Sch Med, Med Social Sci, Evanston, IL 60208 USA.
[Moy, Claudia] NINDS, Extramural Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2010
VL 19
SU 1
MA 162/1325
BP 97
EP 97
PG 1
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA V38QU
UT WOS:000209358700299
ER
PT J
AU Flynn, KE
Jeffery, DD
Reeve, BB
Lin, L
Smith, AW
Abernethy, A
Reese, J
Weinfurt, K
AF Flynn, Kathryn E.
Jeffery, Diana D.
Reeve, Bryce B.
Lin, L.
Smith, Ashley Wilder
Abernethy, A.
Reese, J.
Weinfurt, Kevin
TI Progress on the PROMIS (R) Sexual Function Measure
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Flynn, Kathryn E.] Duke Univ, Sch Med, Psychiat & Behav Sci, Durham, NC USA.
[Reeve, Bryce B.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Lin, L.] Duke Clin Res Inst, Durham, NC USA.
[Smith, Ashley Wilder] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Abernethy, A.] Duke Clin Res Inst, Durham, NC USA.
[Reese, J.] Johns Hopkins Univ, Baltimore, MD USA.
[Weinfurt, Kevin] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2010
VL 19
SU 1
MA 166/1170
BP 98
EP 99
PG 2
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA V38QU
UT WOS:000209358700303
ER
PT J
AU Nowinski, C
Siderowf, A
Victorson, D
Cella, D
Wortman, K
Moy, C
AF Nowinski, Cindy
Siderowf, Andrew
Victorson, David
Cella, David
Wortman, Katy
Moy, Claudia
TI Clinical Validation of Neuro-QOL Measurement Tools in Parkinson's
Disease
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Nowinski, Cindy; Victorson, David; Cella, David; Wortman, Katy] Northwestern Univ, Feinberg Sch Med, Med Social Sci, Evanston, IL 60208 USA.
[Siderowf, Andrew] Univ Penn Hlth Syst, Neurol, Philadelphia, PA USA.
[Moy, Claudia] NINDS, Extramural Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2010
VL 19
SU 1
MA 164/1326
BP 98
EP 98
PG 1
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA V38QU
UT WOS:000209358700301
ER
PT J
AU Martinelli, F
Quinten, C
Maringwa, J
Coens, C
Cleeland, C
Gotay, C
Reeve, B
Ringash, J
Flechtner, H
Greimel, E
Osoba, D
King, M
Schmucker-Von Koch, J
Taphoorn, M
Weis, J
Fossa, S
Albrecht, W
Van Poppel, H
Powell, P
Johnson, M
Bottomley, A
AF Martinelli, Francesca
Quinten, Chantal
Maringwa, John
Coens, Corneel
Cleeland, Charles
Gotay, Carolyn
Reeve, Bryce
Ringash, Jolie
Flechtner, Henning
Greimel, Eva
Osoba, David
King, Madeleine
Schmucker-Von Koch, Joseph
Taphoorn, Martin
Weis, Joachim
Fossa, Sophie
Albrecht, Walter
Van Poppel, Hendrik
Powell, Philip
Johnson, Mark
Bottomley, Andrew
TI Clustering of Health-Related Quality of Life (HRQoL) items in metastatic
prostate cancer patients
SO QUALITY OF LIFE RESEARCH
LA English
DT Meeting Abstract
C1 [Martinelli, Francesca; Quinten, Chantal; Maringwa, John; Coens, Corneel; Bottomley, Andrew] EORTC, Qual Life, Brussels, Belgium.
[Cleeland, Charles] UT MD Anderson Canc Ctr, Symptom Res, Houston, TX USA.
[Gotay, Carolyn] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada.
[Reeve, Bryce] NCI, Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Ringash, Jolie] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada.
[Flechtner, Henning] Otto Von Guericke Univ, Fac Med, Child & Adolescent Psychiat & Psychotherapy, Magdeburg, Germany.
[Greimel, Eva] Graz Univ, Obstet & Gynecol, Graz, Austria.
[Osoba, David] Consulting, Qual Life, W Vancouver, BC, Canada.
[King, Madeleine] Univ Sydney, Psychooncol Cooperat Res Grp, Sidney, BC, Canada.
[Schmucker-Von Koch, Joseph] Univ Regensburg, Med Eth Philosoph Fac, D-93053 Regensburg, Germany.
[Taphoorn, Martin] Med Ctr Haaglanden, VU Med Ctr, The Hague, Netherlands.
[Weis, Joachim] Univ Freiburg, Psychooncol, D-79106 Freiburg, Germany.
[Fossa, Sophie] Oslo Univ Hosp, Clin Res, Oslo, Norway.
[Albrecht, Walter] Landesklinikum Weinviertel Mistelbach, Urol, Mistelbach, Austria.
[Van Poppel, Hendrik] Univ Hosp Leuven, Urol, Leuven, Belgium.
[Powell, Philip; Johnson, Mark] Freeman Rd Hosp, Urol, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2010
VL 19
SU 1
MA 259/1630
BP 127
EP 127
PG 1
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA V38QU
UT WOS:000209358700396
ER
PT J
AU Hays, RD
Bode, R
Rothrock, N
Riley, W
Cella, D
Gershon, R
AF Hays, Ron D.
Bode, Rita
Rothrock, Nan
Riley, William
Cella, David
Gershon, Richard
TI The impact of next and back buttons on time to complete and measurement
reliability in computer-based surveys
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE Computer-based surveys; Social/role activities; PROMIS
AB To assess the impact of including next and back buttons on response burden and measurement reliability of computer-based surveys.
A sample of 807 participants (mean age of 53; 64% women, 83% non-Hispanic white; 81% some college or college graduates) from the YouGov Polimetrix panel was administered 56 items assessing performance of social/role activities and 56 items measuring satisfaction with social/role activities. Participants were randomly assigned to either (1) automatic advance to the next question with no opportunity to go back (auto/no back); (2) automatic advance to the next questions with an opportunity to go back (auto/back); (3) next button to go to the next question with no opportunity to go back (next/no back); or (4) next button to go to the next question with an opportunity to go back (next/back).
We found no difference in missing data, internal consistency reliability, and domain scores by group. Time to complete the survey was about 50% longer when respondents were required to use a next button to go on.
Given the similarity in missing data, reliability and mean scale scores with or without use of the next button, we recommend automatic advancement to the next item with the option to go back to the previous item.
C1 [Hays, Ron D.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Bode, Rita; Rothrock, Nan; Cella, David; Gershon, Richard] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Riley, William] NHLBI, Bethesda, MD 20892 USA.
RP Hays, RD (reprint author), Univ Calif Los Angeles, Dept Med, 911 Broxton Ave,Room 110, Los Angeles, CA 90024 USA.
EM drhays@ucla.edu
RI Hays, Ronald/D-5629-2013
FU Northwestern University [U01AR52177]; Duke University [U01AR52186];
University of North Carolina [U01AR52181]; University of Pittsburgh
[U01AR52155]; Stanford University [U01AR52158]; Stony Brook University,
PI [U01AR52170]; University of Washington, PI [U01AR52171]; National
Institute on Aging [AG020679-01, P30AG021684]; NCMHD [2P20MD000182];
UCLA Older Americans Independence Center [P30-AG028748]
FX The Patient-Reported Outcomes Measurement Information System (PROMIS) is
a US National Institutes of Health (NIH) Roadmap initiative to develop a
computerized system measuring patient-reported outcomes in respondents
with a wide range of chronic diseases and demographic characteristics.
PROMIS was funded by cooperative agreements to a Statistical
Coordinating Center (Northwestern University, PI: David Cella, PhD,
U01AR52177) and six Primary Research Sites (Duke University, PI: Kevin
Weinfurt, PhD, U01AR52186; University of North Carolina, PI: Darren
DeWalt, MD, MPH, U01AR52181; University of Pittsburgh, PI: Paul A.
Pilkonis, PhD, U01AR52155; Stanford University, PI: James Fries, MD,
U01AR52158; Stony Brook University, PI: Arthur Stone, PhD, U01AR52170;
and University of Washington, PI: Dagmar Amtmann, PhD, U01AR52171). NIH
Science Officers on this project are Deborah Ader, PhD, Susan
Czajkowski, PhD, Lawrence Fine, MD, DrPH, Louis Quatrano, PhD, Bryce
Reeve, PhD, William Riley, PhD, and Susana Serrate-Sztein, PhD. Ron D.
Hays, PhD, was also supported by grants from the National Institute on
Aging (AG020679-01, P30AG021684), NCMHD (2P20MD000182), and the UCLA
Older Americans Independence Center (P30-AG028748). See the web site at
www.nihpromis.org for additional information on the PROMIS cooperative
group.
NR 4
TC 5
Z9 5
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2010
VL 19
IS 8
BP 1181
EP 1184
DI 10.1007/s11136-010-9682-9
PG 4
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 651CS
UT WOS:000281902800011
PM 20552282
ER
PT J
AU John-Aryankalayil, M
Palayoor, ST
Cerna, D
Simone, CB
Falduto, MT
Magnuson, SR
Coleman, CN
AF John-Aryankalayil, Molykutty
Palayoor, Sanjeewani T.
Cerna, David
Simone, Charles B., II
Falduto, Michael T.
Magnuson, Scott R.
Coleman, C. Norman
TI Fractionated Radiation Therapy Can Induce a Molecular Profile for
Therapeutic Targeting
SO RADIATION RESEARCH
LA English
DT Article
ID GENE-EXPRESSION PROFILES; HUMAN SUBCUTANEOUS FIBROBLASTS; HUMAN
GLIOMA-CELLS; IONIZING-RADIATION; CANCER-CELLS; TRANSCRIPTIONAL
RESPONSE; SYNTHETIC LETHALITY; MICROARRAY ANALYSIS; GAMMA-RAYS; IN-VIVO
AB To examine the possibility of using fractionated radiation in a unique way with molecular targeted therapy, gene expression profiles of prostate carcinoma cells treated with 10 Gy radiation administered either as a single dose or as fractions of 2 Gy X 5 and 1 Gy X 10 were examined by microarray analysis. Compared to the single dose, the fractionated irradiation resulted in significant increases in differentially expressed genes in both cell lines, with more robust changes in PC3 cells than in DU145 cells. The differentially expressed genes (>twofold change; P < 0.05) were clustered and their ontological annotations evaluated. In PC3 cells genes regulating immune and stress response, cell cycle and apoptosis were significantly up-regulated by multifractionated radiation compared to single-dose radiation. Ingenuity Pathway Analysis (IPA) of the differentially expressed genes revealed that immune response and cardiovascular genes were in the top functional category in PC3 cells and cell-to-cell signaling in DU145 cells. RT-PCR analysis showed that a flexure point for gene expression occurred at the 6th-8th fraction and AKT inhibitor perifosine produced enhanced cell killing after 1 Gy x 8 fractionated radiation in PC3 and DU145 cells compared to single dose. This study suggests that fractionated radiation may be a uniquely exploitable, non-oncogene-addiction stress pathway for molecular therapeutic targeting. (C) 2010 by Radiation Research Society
C1 [John-Aryankalayil, Molykutty; Palayoor, Sanjeewani T.; Cerna, David; Simone, Charles B., II; Coleman, C. Norman] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Falduto, Michael T.; Magnuson, Scott R.] Gen Us BioSyst Inc, Northbrook, IL USA.
RP John-Aryankalayil, M (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Rm B3 B 406,Bldg 10, Bethesda, MD 20892 USA.
EM Aryankalayilm@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This work was supported by the intramural research program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 41
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U1 0
U2 0
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD OCT
PY 2010
VL 174
IS 4
BP 446
EP 458
DI 10.1667/RR2105.1
PG 13
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 659BO
UT WOS:000282542200005
PM 20726711
ER
PT J
AU El Touny, LH
Henderson, F
Djakiew, D
AF El Touny, Lara H.
Henderson, Fraser
Djakiew, Daniel
TI Biochanin A Reduces Drug-Induced p75NTR Expression and Enhances Cell
Survival: A New In Vitro Assay for Screening Inhibitors of p75NTR
Expression
SO REJUVENATION RESEARCH
LA English
DT Article
ID SPINAL-CORD-INJURY; PROSTATE TUMOR-CELLS; NERVE GROWTH-FACTOR;
CASPASE-MEDIATED APOPTOSIS; NF-KAPPA-B; NEUROTROPHIN RECEPTOR;
PROTEIN-KINASE; CANCER CELL; P75(NTR); METHYLPREDNISOLONE
AB Following spinal cord injury (SCI) or peripheral neuropathy, increased levels of the p75(NTR) death receptor initiate the signal transduction cascade leading to cell death Investigations of compounds that may ameliorate neuronal cell death have largely used rodent models, which are time consuming, expensive, and cumbersome to perform Previous studies had demonstrated that steroids, particularly dexamethasone and its analog methylprednisolone sodium succinate, exhibit limited neuroprotective effects against neuronal injury Significantly, many naturally occurring nonsteroidal plant compounds exhibit structural overlap with steroids In this report, we present an in vitro cellular screen model to practically examine the efficacy of various phytoestrogens in modulating the ibuprofen-induced expression of p75(NTR) and reduced cell survival of CCFSTTG1 and U87MG cells in a rescue (postinjury) or prevention (preinjury) regimen We show that the phytoestrogen, biochanin A, and, to a lesser extent, genistein are more effective than dexamethasone at reducing p75(NTR) expression and improving the viability of U87MG and CCFSTTG1 before and after p75(NTR) induction Furthermore, these studies implicate biochanin A's inactivation of p38-MAPK as a possible contributor to reducing p75(NTR) with associated increased cell survival This new in vitro assay facilitates a more time-efficient screening of compounds to suppress p75(NTR) expression and increase neuronal cell viability prior to their evaluation in animal models of neurological diseases
C1 [Djakiew, Daniel] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Med Ctr, Washington, DC 20057 USA.
[El Touny, Lara H.] NCI, Canc Biol Lab, Bethesda, MD 20892 USA.
[Henderson, Fraser] Georgetown Univ, Dept Radiol, Med Ctr, Washington, DC 20057 USA.
[Henderson, Fraser] Doctors Community Hosp, Lanham, MD USA.
RP Djakiew, D (reprint author), Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Med Ctr, 3900 Reservoir Rd NW,Med Dent Bldg,Room C406C, Washington, DC 20057 USA.
FU U S Army [W81XWH-07-1-0366]
FX This work was funded by U S Army grant W81XWH-07-1-0366 and administered
by the Telemedicine and Advanced Technology Research Center (TATRC),
Fort Detrick, Maryland, MD The content of this paper does not
necessarily reflect the position or policy of the U S Government
NR 48
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U1 0
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1549-1684
J9 REJUV RES
JI Rejuv. Res.
PD OCT
PY 2010
VL 13
IS 5
BP 527
EP 537
DI 10.1089/rej.2009.1006
PG 11
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 689XU
UT WOS:000284965100004
PM 20818983
ER
PT J
AU Manuck, TA
Price, TM
Thom, E
Meis, PJ
Dombrowski, MP
Sibai, B
Spong, CY
Rouse, DJ
Iams, JD
Simhan, HN
O'Sullivan, MJ
Miodovnik, M
Leveno, KJ
Conway, D
Wapner, RJ
Carpenter, M
Mercer, B
Ramin, SM
Thorp, JM
Peaceman, AM
AF Manuck, Tracy A.
Price, Thomas M.
Thom, Elizabeth
Meis, Paul J.
Dombrowski, Mitchell P.
Sibai, Baha
Spong, Catherine Y.
Rouse, Dwight J.
Iams, Jay D.
Simhan, Hyagriv N.
O'Sullivan, Mary J.
Miodovnik, Menachem
Leveno, Kenneth J.
Conway, Deborah
Wapner, Ronald J.
Carpenter, Marshall
Mercer, Brian
Ramin, Susan M.
Thorp, John M.
Peaceman, Alan M.
TI Absence of Mitochondrial Progesterone Receptor Polymorphisms in Women
With Spontaneous Preterm Birth
SO REPRODUCTIVE SCIENCES
LA English
DT Article
DE mitochondria; prematurity; progesterone
ID SMOOTH-MUSCLE-CELLS; GLUCOCORTICOID-RECEPTOR; PR-M; EXPRESSION;
DELIVERY; ALPHA; BETA; MYOMETRIUM; ISOFORMS; RISK
AB Objective: The truncated mitochondrial progesterone receptor (PR-M) is homologous to nuclear PRs with the exception of an amino terminus hydrophobic membrane localization sequence, which localizes PR-M to mitochondria. Given the matrilineal inheritance of both spontaneous preterm birth (SPTB) and the mitochondrial genome, we hypothesized that (a) PR-M is polymorphic and (b) PR-M localization sequence polymorphisms could result in variable progesterone-mitochondrial effects and variable responsiveness to progesterone prophylaxis. Methods: Secondary analysis of DNA from women enrolled in a multicenter, prospective, study of 17 alpha-hydroxyprogesterone caproate (17OHPC) versus placebo for the prevention of recurrent SPTB. DNA was extracted from stored saliva. Results: The PR-M localization sequence was sequenced on 344 patients. Sequences were compared with the previously published 48 base-pair sequence, and all were identical. Conclusions: We did not detect genetic variation in the mitochondrial localization sequence of the truncated PR-M in a group of women at high risk for SPTB.
C1 [Manuck, Tracy A.; Price, Thomas M.; Thom, Elizabeth; Meis, Paul J.; Dombrowski, Mitchell P.; Sibai, Baha; Spong, Catherine Y.; Rouse, Dwight J.; Iams, Jay D.; Simhan, Hyagriv N.; O'Sullivan, Mary J.; Miodovnik, Menachem; Leveno, Kenneth J.; Conway, Deborah; Wapner, Ronald J.; Carpenter, Marshall; Mercer, Brian; Ramin, Susan M.; Thorp, John M.; Peaceman, Alan M.] Eunice Kennedy Shriver NICHD MFMU Network, Bethesda, MD USA.
RP Manuck, TA (reprint author), 30 N 1900 E,Rm 2B200, Salt Lake City, UT 84132 USA.
EM tracy.manuck@hsc.utah.edu
OI Peaceman, Alan/0000-0002-4515-4850
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD27860, HD36801, HD27917, HD21414, HD27861, HD27869,
HD27905, HD34208, HD34116, HD21410, HD27915, HD34136, HD34120, HD34122,
HD40500, HD40544, HD40560, HD40512]
FX The author(s) disclosed receipt of the following financial support for
the research and/or authorship of this article: grants from the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(HD27860, HD36801, HD27917, HD21414, HD27861, HD27869, HD27905, HD34208,
HD34116, HD21410, HD27915, HD34136, HD34210, HD34122, HD40500, HD40544,
HD34116, HD40560, HD40512) and its contents do not necessarily represent
the official view of NICHD or NIH.
NR 27
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Z9 3
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD OCT
PY 2010
VL 17
IS 10
BP 913
EP 916
DI 10.1177/1933719110374365
PG 4
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 652JQ
UT WOS:000282003100005
PM 20693499
ER
PT J
AU Kagan, JM
Rosas, S
Trochim, WMK
AF Kagan, Jonathan M.
Rosas, Scott
Trochim, William M. K.
TI Integrating utilization-focused evaluation with business process
modeling for clinical research improvement
SO RESEARCH EVALUATION
LA English
DT Article
ID COOPERATIVE-ONCOLOGY-GROUP; TRIALS; CANCER
AB New discoveries in basic science are creating extraordinary opportunities to design novel biomedical preventions and therapeutics for human disease. But the clinical evaluation of these new interventions is, in many instances, being hindered by a variety of legal, regulatory, policy and operational factors, few of which enhance research quality, the safety of study participants or research ethics. With the goal of helping increase the efficiency and effectiveness of clinical research, we have examined how the integration of utilization-focused evaluation with elements of business process modeling can reveal opportunities for systematic improvements in clinical research. Using data from the NW global HIV/AIDS clinical trials networks, we analyzed the absolute and relative times required to traverse defined phases associated with specific activities within the clinical protocol lifecycle. Using simple median duration and Kaplan-Meyer survival analysis, we show how such time-based analyses can provide a rationale for the prioritization of research process analysis and re-engineering, as well as a means for statistically assessing the impact of policy modifications, resource utilization, re-engineered processes and best practices. Successfully applied, this approach can help researchers be more efficient in capitalizing on new science to speed the development of improved interventions for human disease.
C1 [Kagan, Jonathan M.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[Rosas, Scott] Concept Syst Inc, Ithaca, NY 14850 USA.
[Trochim, William M. K.] Cornell Univ, Dept Policy Anal & Management, Ithaca, NY 14853 USA.
RP Kagan, JM (reprint author), NIAID, Div Clin Res, NIH, 6700 B Rockledge Dr,Room 1102,MSC 7609, Bethesda, MD 20892 USA.
EM jkagan@niaid.nih.gov; srosas@conceptsystems.com; wmt1@cornell.edu
OI Rosas, Scott/0000-0001-5212-1478
FU NCRR NIH HHS [UL1 RR024996, UL1 RR024996-01]; NIAID NIH HHS [N01
AI030060-11, N01 AI050022, N01AI30020, N01AI50022]
NR 33
TC 4
Z9 4
U1 2
U2 7
PU BEECH TREE PUBLISHING
PI GUILDFORD
PA 10 WATFORD CLOSE,, GUILDFORD GU1 2EP, SURREY, ENGLAND
SN 0958-2029
J9 RES EVALUAT
JI Res. Evaluat.
PD OCT
PY 2010
VL 19
IS 4
BP 239
EP 250
DI 10.3152/095820210X12827366906607
PG 12
WC Information Science & Library Science
SC Information Science & Library Science
GA 716SU
UT WOS:000286994600002
PM 21552512
ER
PT J
AU Flaxel, CJ
Edwards, AR
Aiello, LP
Arrigg, PG
Beck, RW
Bressler, NM
Bressler, SB
Ferris, FL
Gupta, SK
Haller, JA
Lazarus, HS
Qin, HJ
AF Flaxel, Christina J.
Edwards, Allison R.
Aiello, Lloyd Paul
Arrigg, Paul G.
Beck, Roy W.
Bressler, Neil M.
Bressler, Susan B.
Ferris, Frederick L., III
Gupta, Shailesh K.
Haller, Julia A.
Lazarus, Howard S.
Qin, Haijing
TI FACTORS ASSOCIATED WITH VISUAL ACUITY OUTCOMES AFTER VITRECTOMY FOR
DIABETIC MACULAR EDEMA Diabetic Retinopathy Clinical Research Network
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE diabetic macular edema; retinal thickness; visual acuity; vitrectomy
ID VITREOMACULAR TRACTION
AB Purpose: To evaluate factors associated with favorable outcomes after vitrectomy for diabetic macular edema.
Methods: Data were collected prospectively on 241 eyes undergoing vitrectomy for diabetic macular edema. Multivariate models were used to evaluate associations of 20 preoperative and intraoperative factors with 6-month outcomes of visual acuity and retinal thickness.
Results: Median central subfield thickness decreased from 412 mu m to 278 mu m at 6 months, butmedian visual acuity remained unchanged (20/80, Snellen equivalent). Greater visual acuity improvement occurred in eyes with worse baseline acuity (P < 0.001) and in eyes in which an epiretinal membrane was removed (P = 0.006). Greater reduction in central subfield thickness occurred with worse baseline visual acuity (P < 0.001), greater preoperative retinal thickness (P = 0.001), removal of internal limiting membrane (P = 0.003), and optical coherence tomography evidence of vitreoretinal abnormalities (P = 0.006). No associations with clinician's preoperative assessments of the posterior vitreous were identified.
Conclusion: These results suggest that the removal of epiretinal membranes may favorably affect visual outcome after vitrectomy. Preoperative presence of vitreoretinal abnormalities appeared to be associated with somewhat greater reductions in retinal thickness but not with visual acuity outcome. These results may be useful for future studies evaluating vitrectomy for diabetic macular edema. RETINA 30: 1488-1495, 2010
C1 [Edwards, Allison R.; Beck, Roy W.; Qin, Haijing] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA.
[Flaxel, Christina J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA.
[Bressler, Neil M.; Bressler, Susan B.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Ferris, Frederick L., III] NEI, Bethesda, MD 20892 USA.
[Ferris, Frederick L., III] NIH, Bethesda, MD 20892 USA.
[Gupta, Shailesh K.] Univ Florida, Coll Med, Dept Ophthalmol, Jacksonville, FL USA.
[Haller, Julia A.] Wills Eye Inst, Philadelphia, PA USA.
[Lazarus, Howard S.] Amer Eye Inst, Los Angeles, CA USA.
RP Edwards, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA.
EM drcrstat1@jaeb.org
FU National Eye Institute; National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health, and Department of Health
and Human Services [EY14231, EY018817, EY14229]
FX Supported through a cooperative agreement from the National Eye
Institute and the National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health, and Department of Health
and Human Services (EY14231, EY018817, and EY14229).
NR 11
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD OCT
PY 2010
VL 30
IS 9
BP 1488
EP 1495
DI 10.1097/IAE.0b013e3181e7974f
PG 8
WC Ophthalmology
SC Ophthalmology
GA 659JC
UT WOS:000282561800018
PM 20924264
ER
PT J
AU Davis, BR
Candotti, F
AF Davis, Brian R.
Candotti, Fabio
TI Mosaicism-Switch or Spectrum?
SO SCIENCE
LA English
DT Editorial Material
ID WISKOTT-ALDRICH-SYNDROME; REVERTANT MOSAICISM; 2ND-SITE MUTATIONS;
EPIDERMOLYSIS-BULLOSA; SOMATIC MOSAICISM; PATIENT; LYMPHOCYTES; SIBLINGS
C1 [Davis, Brian R.] Univ Texas Hlth Sci Ctr, Brown Fdn Inst Mol Med, Ctr Stem Cell Res, Houston, TX 77030 USA.
[Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
RP Davis, BR (reprint author), Univ Texas Hlth Sci Ctr, Brown Fdn Inst Mol Med, Ctr Stem Cell Res, Houston, TX 77030 USA.
EM brian.r.davis@uth.tmc.edu
NR 12
TC 6
Z9 7
U1 0
U2 4
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 OCT 1
PY 2010
VL 330
IS 6000
BP 46
EP 47
DI 10.1126/science.1195991
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 656KW
UT WOS:000282334500026
PM 20929800
ER
PT J
AU Arensburger, P
Megy, K
Waterhouse, RM
Abrudan, J
Amedeo, P
Antelo, B
Bartholomay, L
Bidwell, S
Caler, E
Camara, F
Campbell, CL
Campbell, KS
Casola, C
Castro, MT
Chandramouliswaran, I
Chapman, SB
Christley, S
Costas, J
Eisenstadt, E
Feschotte, C
Fraser-Liggett, C
Guigo, R
Haas, B
Hammond, M
Hansson, BS
Hemingway, J
Hill, SR
Howarth, C
Ignell, R
Kennedy, RC
Kodira, CD
Lobo, NF
Mao, CH
Mayhew, G
Michel, K
Mori, A
Liu, NN
Naveira, H
Nene, V
Nguyen, N
Pearson, MD
Pritham, EJ
Puiu, D
Qi, YM
Ranson, H
Ribeiro, JMC
Roberston, HM
Severson, DW
Shumway, M
Stanke, M
Strausberg, RL
Sun, C
Sutton, G
Tu, ZJ
Tubio, JMC
Unger, MF
Vanlandingham, DL
Vilella, AJ
White, O
White, JR
Wondji, CS
Wortman, J
Zdobnov, EM
Birren, B
Christensen, BM
Collins, FH
Cornel, A
Dimopoulos, G
Hannick, LI
Higgs, S
Lanzaro, GC
Lawson, D
Lee, NH
Muskavitch, MAT
Raikhel, AS
Atkinson, PW
AF Arensburger, Peter
Megy, Karine
Waterhouse, Robert M.
Abrudan, Jenica
Amedeo, Paolo
Antelo, Beatriz
Bartholomay, Lyric
Bidwell, Shelby
Caler, Elisabet
Camara, Francisco
Campbell, Corey L.
Campbell, Kathryn S.
Casola, Claudio
Castro, Marta T.
Chandramouliswaran, Ishwar
Chapman, Sinead B.
Christley, Scott
Costas, Javier
Eisenstadt, Eric
Feschotte, Cedric
Fraser-Liggett, Claire
Guigo, Roderic
Haas, Brian
Hammond, Martin
Hansson, Bill S.
Hemingway, Janet
Hill, Sharon R.
Howarth, Clint
Ignell, Rickard
Kennedy, Ryan C.
Kodira, Chinnappa D.
Lobo, Neil F.
Mao, Chunhong
Mayhew, George
Michel, Kristin
Mori, Akio
Liu, Nannan
Naveira, Horacio
Nene, Vishvanath
Nguyen, Nam
Pearson, Matthew D.
Pritham, Ellen J.
Puiu, Daniela
Qi, Yumin
Ranson, Hilary
Ribeiro, Jose M. C.
Roberston, Hugh M.
Severson, David W.
Shumway, Martin
Stanke, Mario
Strausberg, Robert L.
Sun, Cheng
Sutton, Granger
Tu, Zhijian (Jake)
Tubio, Jose Manuel C.
Unger, Maria F.
Vanlandingham, Dana L.
Vilella, Albert J.
White, Owen
White, Jared R.
Wondji, Charles S.
Wortman, Jennifer
Zdobnov, Evgeny M.
Birren, Bruce
Christensen, Bruce M.
Collins, Frank H.
Cornel, Anthony
Dimopoulos, George
Hannick, Linda I.
Higgs, Stephen
Lanzaro, Gregory C.
Lawson, Daniel
Lee, Norman H.
Muskavitch, Marc A. T.
Raikhel, Alexander S.
Atkinson, Peter W.
TI Sequencing of Culex quinquefasciatus Establishes a Platform for Mosquito
Comparative Genomics
SO SCIENCE
LA English
DT Article
ID AEDES-AEGYPTI; PIPIENS; VECTOR
AB Culex quinquefasciatus (the southern house mosquito) is an important mosquito vector of viruses such as West Nile virus and St. Louis encephalitis virus, as well as of nematodes that cause lymphatic filariasis. C. quinquefasciatus is one species within the Culex pipiens species complex and can be found throughout tropical and temperate climates of the world. The ability of C. quinquefasciatus to take blood meals from birds, livestock, and humans contributes to its ability to vector pathogens between species. Here, we describe the genomic sequence of C. quinquefasciatus: Its repertoire of 18,883 protein-coding genes is 22% larger than that of Aedes aegypti and 52% larger than that of Anopheles gambiae with multiple gene-family expansions, including olfactory and gustatory receptors, salivary gland genes, and genes associated with xenobiotic detoxification.
C1 [Arensburger, Peter; Raikhel, Alexander S.; Atkinson, Peter W.] Univ Calif Riverside, Ctr Dis Vector Res, Riverside, CA 92521 USA.
[Megy, Karine; Hammond, Martin; Vilella, Albert J.; Lawson, Daniel] European Bioinformat Inst EMBL EBI, Cambridge CB10 1SD, England.
[Waterhouse, Robert M.; Zdobnov, Evgeny M.] Univ Geneva, Sch Med, CH-1211 Geneva, Switzerland.
[Waterhouse, Robert M.] Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland.
[Abrudan, Jenica; Christley, Scott; Kennedy, Ryan C.; Lobo, Neil F.; Mori, Akio; Severson, David W.; Unger, Maria F.; Collins, Frank H.] Univ Notre Dame, Notre Dame, IN 46556 USA.
[Amedeo, Paolo; Caler, Elisabet; Chandramouliswaran, Ishwar; Eisenstadt, Eric; Hannick, Linda I.] J Craig Venter Inst, Rockville, MD 20850 USA.
[Tubio, Jose Manuel C.] Univ Santiago, Complexo Hosp, Santiago De Compostela 15706, Spain.
[Bartholomay, Lyric] Iowa State Univ, Ames, IA 50011 USA.
[Bidwell, Shelby; Camara, Francisco; Guigo, Roderic] Univ Pompeu Fabra, Ctr Gene Regulat, E-08003 Barcelona, Catalonia, Spain.
[Campbell, Corey L.] Colorado State Univ, Ft Collins, CO 80523 USA.
[Campbell, Kathryn S.] Harvard Univ, Cambridge, MA 02138 USA.
[Casola, Claudio] Indiana Univ, Bloomington, IN 47405 USA.
[Castro, Marta T.] Hosp Llobregat, Programa Epigenet & Biol Canc, Hosp Duran & Reynals, Barcelona 08907, Spain.
[Chapman, Sinead B.; Haas, Brian; Howarth, Clint; Pearson, Matthew D.; White, Jared R.; Birren, Bruce; Muskavitch, Marc A. T.] Broad Inst, Cambridge, MA 02142 USA.
[Costas, Javier] Fdn Publ Galega Med Xenomica Servizo Galego Saude, Santiago De Compostela 15706, Spain.
[Feschotte, Cedric; Nguyen, Nam; Pritham, Ellen J.; Sun, Cheng] Univ Texas Arlington, Arlington, TX 76019 USA.
[Fraser-Liggett, Claire; White, Owen; Wortman, Jennifer] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
[Hansson, Bill S.] Max Planck Inst Chem Ecol, D-07749 Jena, Germany.
[Hemingway, Janet; Ranson, Hilary; Wondji, Charles S.] Univ Liverpool Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England.
[Hill, Sharon R.; Ignell, Rickard] Swedish Univ Agr Sci, S-23053 Alnarp, Sweden.
[Kodira, Chinnappa D.] Roche Grp, Branford, CT 06405 USA.
[Mao, Chunhong; Qi, Yumin; Tu, Zhijian (Jake)] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA.
[Mayhew, George; Christensen, Bruce M.] Univ Wisconsin, Madison, WI 53706 USA.
[Michel, Kristin] Kansas State Univ, Manhattan, KS 66506 USA.
[Liu, Nannan] Auburn Univ, Auburn, AL 36849 USA.
[Naveira, Horacio] Univ A Coruna, Dept Bioloxia Celular & Mol, Coruna 15071 A, Spain.
[Nene, Vishvanath] Int Livestock Res Inst, Nairobi, Kenya.
[Puiu, Daniela] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
[Ribeiro, Jose M. C.; Shumway, Martin] Natl Inst Hlth, Bethesda, MD 20892 USA.
[Roberston, Hugh M.] Univ Illinois, Urbana, IL 61801 USA.
[Stanke, Mario] Univ Gottingen, D-37077 Gottingen, Germany.
[Cornel, Anthony] Univ Texas Galveston, Med Branch, Galveston, TX 77555 USA.
[Vanlandingham, Dana L.; Zdobnov, Evgeny M.; Higgs, Stephen] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England.
[Zdobnov, Evgeny M.; Lanzaro, Gregory C.] Univ Calif Davis, Parlier, CA 93648 USA.
[Dimopoulos, George] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Lee, Norman H.] George Washington Univ, Med Ctr, Washington, DC 20037 USA.
[Muskavitch, Marc A. T.] Boston Coll, Chestnut Hill, MA 02467 USA.
[Muskavitch, Marc A. T.] Harvard Sch Publ Hlth, Boston, MA 02115 USA.
RP Arensburger, P (reprint author), Univ Calif Riverside, Ctr Dis Vector Res, Riverside, CA 92521 USA.
EM arensburger@gmail.com
RI Costas, Javier/B-5016-2008; Feschotte, Cedric/C-4048-2011; Michel,
Kristin/F-3400-2011; Zdobnov, Evgeny/K-1133-2012; Hansson,
Bill/G-2774-2013; Naveira, Horacio/H-7249-2014; Camara Ferreira,
Francisco/G-9841-2015; Guigo, Roderic/D-1303-2010; Tubio,
Jose/H-5076-2015; Mayhew, George/B-4042-2016; Waterhouse,
Robert/A-1858-2010;
OI Costas, Javier/0000-0003-0306-3990; Hannick, Linda/0000-0002-8018-8466;
Wortman, Jennifer/0000-0002-8713-1227; Hansson,
Bill/0000-0002-4811-1223; Naveira, Horacio/0000-0002-3840-1569; Camara
Ferreira, Francisco/0000-0002-1971-5466; Guigo,
Roderic/0000-0002-5738-4477; Tubio, Jose/0000-0003-3540-2459; Mayhew,
George/0000-0003-0609-6018; Waterhouse, Robert/0000-0003-4199-9052;
Vilella, Albert/0000-0002-2005-2516; Lawson, Daniel/0000-0001-7765-983X;
Megy, Karyn/0000-0002-2826-3879; Fraser, Claire/0000-0003-1462-2428;
Ranson, Hilary/0000-0003-2332-8247; Hill, Sharon
Rose/0000-0002-6474-0214; Dimopoulos, George/0000-0001-6755-8111;
Hemingway, Janet/0000-0002-3200-7173; Ribeiro, Jose/0000-0002-9107-0818
FU NIH [HHSN266200400039C]; National Institute of Allergy and Infectious
Diseases, NIH, Department of Health and Human Services [N01-AI-30071,
HHSN266200400001C]
FX This work was supported by NIH grant HHSN266200400039C and by the
National Institute of Allergy and Infectious Diseases, NIH, Department
of Health and Human Services under contract numbers N01-AI-30071 and
HHSN266200400001C. The assembled genome was deposited in the GenBank
database with accession number AAWU00000000.
NR 12
TC 207
Z9 219
U1 5
U2 60
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 OCT 1
PY 2010
VL 330
IS 6000
BP 86
EP 88
DI 10.1126/science.1191864
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 656KW
UT WOS:000282334500040
PM 20929810
ER
PT J
AU Arana, ME
Kunkel, TA
AF Arana, Mercedes E.
Kunkel, Thomas A.
TI Mutator phenotypes due to DNA replication infidelity
SO SEMINARS IN CANCER BIOLOGY
LA English
DT Review
DE Fidelity; DNA polymerase; DNA replication; Mutator phenotypes;
Microsatellite instability
ID XERODERMA-PIGMENTOSUM VARIANT; POLYMERASE-ETA; MISMATCH REPAIR;
TRANSLESION SYNTHESIS; SOMATIC HYPERMUTATION; MICROSATELLITE
INSTABILITY; SACCHAROMYCES-CEREVISIAE; AFFINITY MATURATION;
COLORECTAL-CANCER; ESCHERICHIA-COLI
AB This article considers the fidelity of DNA replication performed by eukaryotic DNA polymerases involved in replicating the nuclear genome. DNA replication fidelity can vary widely depending on the DNA polymerase, the composition of the error, the flanking sequence, the presence of DNA damage and the ability to correct errors. As a consequence, defects in processes that determine DNA replication fidelity can confer strong mutator phenotypes whose specificity can help determine the molecular nature of the defect. Published by Elsevier Ltd.
C1 [Kunkel, Thomas A.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, 111 TW Alexander Dr,Res Triangle Pk, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [Z01 ES065070,
Z01 ES065089]
FX We thank Katarzyna Bebenek and Jessica Williams for thoughtful comments
on the manuscript. The research conducted in Thomas Kunkel's laboratory
is supported by the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences (Projects Z01 ES065070 and
Z01 ES065089).
NR 91
TC 36
Z9 36
U1 1
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-579X
J9 SEMIN CANCER BIOL
JI Semin. Cancer Biol.
PD OCT
PY 2010
VL 20
IS 5
BP 304
EP 311
DI 10.1016/j.semcancer.2010.10.003
PG 8
WC Oncology
SC Oncology
GA 704DL
UT WOS:000286031200004
PM 20934516
ER
PT J
AU Singer, A
AF Singer, Alfred
TI Molecular and cellular basis of T cell lineage commitment: An overview
SO SEMINARS IN IMMUNOLOGY
LA English
DT Editorial Material
C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA.
RP Singer, A (reprint author), NCI, Expt Immunol Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM singera@mail.nih.gov
NR 7
TC 1
Z9 1
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-5323
J9 SEMIN IMMUNOL
JI Semin. Immunol.
PD OCT
PY 2010
VL 22
IS 5
BP 253
EP 253
DI 10.1016/j.smim.2010.06.001
PG 1
WC Immunology
SC Immunology
GA 647BG
UT WOS:000281590100001
PM 20655758
ER
PT J
AU Wang, L
Xiong, YM
Bosselut, R
AF Wang, Lie
Xiong, Yumei
Bosselut, Remy
TI Tenuous paths in unexplored territory: From T cell receptor signaling to
effector gene expression during thymocyte selection
SO SEMINARS IN IMMUNOLOGY
LA English
DT Review
DE T cell development; Thymus; Transcription; Signaling
ID NF-KAPPA-B; DOUBLE-POSITIVE THYMOCYTES; CD8 LINEAGE COMMITMENT; ERK MAPK
CASCADE; TRANSCRIPTION FACTORS; NEGATIVE SELECTION; ANTIGEN RECEPTOR;
THYMIC SELECTION; DNA-BINDING; TCR SIGNALS
AB During the last step of alpha beta T cell development, thymocytes that have rearranged genes encoding TCR chains and express CD4 and CD8 coreceptors are selected on the basis of their TCR reactivity to escape programmed cell death and become mature CD4 or CD8 T cells. This process is triggered by intrathymic TCR signaling, that activates 'sensor' transcription factors 'constitutively' expressed in DP thymocytes. Eventually, TCR-signaled thymocytes evolve effector transcriptional circuits that control basal metabolism, migration, survival and initiation of lineage-specific gene expression. This review examines how components of the 'sensing' transcription apparatus responds to positive selection signals, and highlights important differences with mature T cell responses. In a second part, we evaluate current observations and hypotheses on the connections between sensing transcription factors and effector circuitries. (C) 2010 Published by Elsevier Ltd.
C1 [Wang, Lie; Xiong, Yumei; Bosselut, Remy] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Bosselut, R (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bldg 37,Room 3015,37 Convent Dr, Bethesda, MD 20892 USA.
EM remy@helix.nih.gov
FU National Cancer Institute, Center for Cancer Research, NIH
FX We thank Jon Ashwell, Dietz Conze, Ellen Rothenberg and Murty
Shrinivasula for stimulating discussions, and Jon Ashwell and Paul Love
for critical reading of the manuscript. Research work in the authors'
laboratory is supported by the Intramural Research Program of the
National Cancer Institute, Center for Cancer Research, NIH.
NR 158
TC 12
Z9 12
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-5323
J9 SEMIN IMMUNOL
JI Semin. Immunol.
PD OCT
PY 2010
VL 22
IS 5
BP 294
EP 302
DI 10.1016/j.smim.2010.04.013
PG 9
WC Immunology
SC Immunology
GA 647BG
UT WOS:000281590100007
PM 20537906
ER
PT J
AU Signore, C
Spong, CY
AF Signore, Caroline
Spong, Catherine Y.
TI Vaginal Birth After Cesarean: New Insights Manuscripts from an NIH
Consensus Development Conference, March 8-10, 2010
SO SEMINARS IN PERINATOLOGY
LA English
DT Editorial Material
C1 [Signore, Caroline; Spong, Catherine Y.] NIH, Pregnancy & Perinatol Branch, Bethesda, MD 20892 USA.
RP Signore, C (reprint author), NIH, Pregnancy & Perinatol Branch, 6100 Execut Blvd,Room 4B03,MSC 7510, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 HD999999]
NR 0
TC 7
Z9 7
U1 2
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 0146-0005
J9 SEMIN PERINATOL
JI Semin. Perinatol.
PD OCT
PY 2010
VL 34
IS 5
BP 309
EP 310
DI 10.1053/j.semperi.2010.05.002
PG 2
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 662TI
UT WOS:000282835100001
PM 20869544
ER
PT J
AU Bolla, KI
Lesage, SR
Gamaldo, CE
Neubauer, DN
Wang, NY
Funderburk, FR
Allen, RP
David, PM
Cadet, JL
AF Bolla, Karen I.
Lesage, Suzanne R.
Gamaldo, Charlene E.
Neubauer, David N.
Wang, Nae-Yuh
Funderburk, Frank R.
Allen, Richard P.
David, Paula M.
Cadet, Jean Lud
TI Polysomnogram changes in marijuana users who report sleep disturbances
during prior abstinence
SO SLEEP MEDICINE
LA English
DT Article
DE Sleep; Polysomnography; Periodic leg movements; Marijuana; Abstinence;
Substance abuse; Withdrawal
ID CANNABIS WITHDRAWAL; SEX-DIFFERENCES; COCAINE USERS; DEPENDENCE;
QUESTIONNAIRE; TOLERANCE; SEVERITY; PATTERNS; VALIDITY; RELAPSE
AB Background: Abrupt discontinuation of heavy marijuana (MJ) use is associated with self-reports of sleep difficulty. Disturbed sleep is clinically important because MJ users experiencing sleep problems may relapse to MJ use to improve their sleep quality. Few studies have used polysomnography (PSG) to characterize changes in sleep architecture during abrupt abstinence from heavy MJ use.
Methods: We recorded PSG measures on nights 1, 2, 7, 8, and 13 after abrupt MJ discontinuation in 18 heavy MJ users residing in an inpatient unit.
Results: Across abstinence, Total Sleep Time (TST), Sleep Efficiency (SEff), and amount of REM sleep declined, while Wake after Sleep Onset (WASO) and Periodic Limb Movements (PLM) increased. Furthermore, quantity (joints/week) and duration (years) of MJ use were positively associated with more PLMs.
Conclusion: The treatment of sleep disturbance is a potential target for the management of cannabis use disorders since poor sleep could contribute to treatment failure in heavy MJ users. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Bolla, Karen I.; Gamaldo, Charlene E.; Allen, Richard P.; David, Paula M.] Johns Hopkins Med Inst, Dept Neurol, Bayview Med Ctr, Baltimore, MD 21205 USA.
[Bolla, Karen I.; Neubauer, David N.] Johns Hopkins Med Inst, Dept Psychiat & Behav Sci, Bayview Med Ctr, Baltimore, MD 21205 USA.
[Bolla, Karen I.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA.
[Lesage, Suzanne R.] Univ Maryland, Sleep Disorders Ctr, Baltimore, MD 21201 USA.
[Wang, Nae-Yuh] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Wang, Nae-Yuh] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Funderburk, Frank R.] InCompass Syst, Columbia, MD USA.
[Cadet, Jean Lud] NIDA, Mol Neuropsychiat Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD USA.
RP Bolla, KI (reprint author), Johns Hopkins Bayview Med Ctr, Dept Neurol, 4940 Eastern Ave,B Bldg,Room 123, Baltimore, MD 21224 USA.
EM kbolla@jhmi.edu
OI Wang, Nae-Yuh/0000-0001-6513-9730
FU NIH [DA 17122]; JHBMC-GCRC-CTSA [MO1 RR02719, UL1 RR 025005]; DHH NIDA
FX Supported by NIH grants DA 17122(KB), the JHBMC-GCRC-CTSA (MO1 RR02719,
UL1 RR 025005) and the DHH NIDA Intramural Research Program.
NR 38
TC 15
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U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1389-9457
J9 SLEEP MED
JI Sleep Med.
PD OCT
PY 2010
VL 11
IS 9
BP 882
EP 889
DI 10.1016/j.sleep.2010.02.013
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 663EL
UT WOS:000282865700014
PM 20685163
ER
PT J
AU McAreavey, D
Vidal, JS
Aspelund, T
Owens, DS
Hughes, T
Garcia, M
Sigurdsson, S
Bjornsdottir, H
Harris, TB
Gudnason, V
Launer, LJ
Plehn, JF
AF McAreavey, Dorothea
Vidal, Jean-Sebastien
Aspelund, Thor
Owens, David S.
Hughes, Timothy
Garcia, Melissa
Sigurdsson, Sigurdur
Bjornsdottir, Halldora
Harris, Tamara B.
Gudnason, Vilmundur
Launer, Lenore J.
Plehn, Jonathan F.
TI Correlation of Echocardiographic Findings With Cerebral Infarction in
Elderly Adults The AGES-Reykjavik Study
SO STROKE
LA English
DT Article
DE aging; cerebral infarction; echocardiography; epidemiology; magnetic
resonance imaging
ID LEFT-VENTRICULAR HYPERTROPHY; MITRAL ANNULAR CALCIFICATION;
HEART-FAILURE; EJECTION FRACTION; STROKE; DISEASE; RISK; COHORT;
PREVALENCE; PREDICTOR
AB Background and Purpose-Chronic effects of hypertension may be observed in multiple end organs. Previous reports suggest that cardiovascular morphological features can mirror cerebral infarction. In this cross-sectional analysis of elderly subjects, we investigated the relationship of a comprehensive set of echocardiographic measures with cerebral infarction detected by MRI.
Methods-We compared echocardiographically determined left ventricular (LV) mass, left atrial volume, aortic root diameter, mitral annular calcification, and measures of diastolic function with cerebral infarction determined by MRI using logistic regression in a random sample drawn from the Age Gene/Environment Susceptibility-Reykjavik Study cohort. The model was first adjusted for age and gender, and then for age, gender, and vascular risk factors.
Results-Among 692 subjects aged 75 (standard deviation, 6) years, 28% had at least 1 cerebral infarct. When adjusted for age and gender, the presence of cerebral infarction was modestly related to LV mass (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02) and left atrial volume (OR, 1.03; 95% CI, 1.01-1.05), as well as the lowest quartile of early-to-late pulsed Doppler velocity ratio (early-to-late pulsed Doppler velocity ratio <0.75; OR, 1.87; 95% CI, 1.22-2.87). The latter relation remained significant after adjustment for vascular risk factors and LV ejection fraction (OR, 1.82; 95% CI, 1.16-2.86).
Conclusion-Of all echocardiographic parameters, LV filling abnormality as indicated by low early-to-late pulsed Doppler velocity ratio displayed the strongest association with cerebral infarction and this relationship was independent of vascular risk factors. This simple marker of cerebral infarction may be useful when evaluating older patients. (Stroke. 2010;41:2223-2228.)
C1 [McAreavey, Dorothea] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Vidal, Jean-Sebastien; Hughes, Timothy; Garcia, Melissa; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Owens, David S.; Plehn, Jonathan F.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Aspelund, Thor; Sigurdsson, Sigurdur; Bjornsdottir, Halldora; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
RP McAreavey, D (reprint author), 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA.
EM dmcareavey@cc.nih.gov
RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason,
Vilmundur/K-6885-2015; Vidal, Jean-Sebastien/D-1941-2016;
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084; Vidal,
Jean-Sebastien/0000-0001-6770-0720; Owens, David/0000-0002-7293-9688
FU National Institutes of Health [N01-AG-1-2100]; National Institute on
Aging Intramural Research Program; Hjartavernd (the Icelandic Heart
Association); Althingi (the Icelandic Parliament)
FX This study was supported by a contract from the National Institutes of
Health (N01-AG-1-2100), National Institute on Aging Intramural Research
Program, the Hjartavernd (the Icelandic Heart Association), and the
Althingi (the Icelandic Parliament).
NR 29
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Z9 7
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD OCT
PY 2010
VL 41
IS 10
BP 2223
EP 2228
DI 10.1161/STROKEAHA.110.590430
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 655CY
UT WOS:000282221700029
PM 20798368
ER
PT J
AU Taylor, A
Castle, A
Merino, JG
Hsia, A
Kidwell, CS
Warach, S
AF Taylor, Alexis
Castle, Amanda
Merino, Jose G.
Hsia, Amie
Kidwell, Chelsea S.
Warach, Steven
TI Optimizing Stroke Clinical Trial Design Estimating the Proportion of
Eligible Patients
SO STROKE
LA English
DT Article
DE acute ischemic stroke; age; clinical trial; National Institutes of
Health Stroke Scale; time factors
AB Background and Purpose-Clinical trial planning and site selection require an accurate estimate of the number of eligible patients at each site. In this study, we developed a tool to calculate the proportion of patients who would meet a specific trial's age, baseline severity, and time to treatment inclusion criteria.
Methods-From a sample of 1322 consecutive patients with acute ischemic cerebrovascular syndromes, we developed regression curves relating the proportion of patients within each range of the 3 variables. We used half the patients to develop the model and the other half to validate it by comparing predicted vs actual proportions who met the criteria for 4 current stroke trials.
Results-The predicted proportion of patients meeting inclusion criteria ranged from 6% to 28% among the different trials. The proportion of trial-eligible patients predicted from the first half of the data were within 0.4% to 1.4% of the actual proportion of eligible patients. This proportion increased logarithmically with National Institutes of Health Stroke Scale score and time from onset; lowering the baseline limits of the National Institutes of Health Stroke Scale score and extending the treatment window would have the greatest impact on the proportion of patients eligible for a stroke trial.
Conclusions-This model helps estimate the proportion of stroke patients eligible for a study based on different upper and lower limits for age, stroke severity, and time to treatment, and it may be a useful tool in clinical trial planning. (Stroke. 2010;41:2236-2238.)
C1 [Taylor, Alexis; Merino, Jose G.; Hsia, Amie; Warach, Steven] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA.
[Castle, Amanda; Hsia, Amie; Kidwell, Chelsea S.] Georgetown Univ Hosp, Dept Neurol, Washington, DC 20007 USA.
[Merino, Jose G.] Suburban Hosp Stroke Program, Bethesda, MD USA.
[Hsia, Amie; Kidwell, Chelsea S.] Washington Hosp Ctr, Stroke Ctr, Washington, DC 20010 USA.
RP Warach, S (reprint author), NINDS, Sect Stroke Diagnost & Therapeut, 10 Ctr Dr,Room B1D733,MSC 1063, Bethesda, MD 20892 USA.
EM Warachs@ninds.nih.gov
OI Merino, Jose/0000-0002-6676-0008
FU Division of Intramural Research of the National Institute of
Neurological Disorders and Stroke, National Institutes of Health
FX This research was supported by the Division of Intramural Research of
the National Institute of Neurological Disorders and Stroke, National
Institutes of Health.
NR 6
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD OCT
PY 2010
VL 41
IS 10
BP 2236
EP 2238
DI 10.1161/STROKEAHA.110.578252
PG 3
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 655CY
UT WOS:000282221700031
PM 20798375
ER
PT J
AU Lima, FO
Furie, KL
Silva, GS
Lev, MH
Camargo, ECS
Singhal, AB
Harris, GJ
Halpern, EF
Koroshetz, WJ
Smith, WS
Yoo, AJ
Nogueira, RG
AF Lima, Fabricio O.
Furie, Karen L.
Silva, Gisele S.
Lev, Michael H.
Camargo, Erica C. S.
Singhal, Aneesh B.
Harris, Gordon J.
Halpern, Elkan F.
Koroshetz, Walter J.
Smith, Wade S.
Yoo, Albert J.
Nogueira, Raul G.
TI The Pattern of Leptomeningeal Collaterals on CT Angiography Is a Strong
Predictor of Long-Term Functional Outcome in Stroke Patients With Large
Vessel Intracranial Occlusion
SO STROKE
LA English
DT Article
DE acute stroke; brain imaging; brain ischemia; leptomeningeal collaterals;
outcome
ID ACUTE ISCHEMIC-STROKE; INTRAARTERIAL THROMBOLYSIS; PROACT-II;
RECANALIZATION; CIRCULATION; PERFUSION; INFARCT; EXTENT; TRIAL; SCORE
AB Background and Purpose-The role of noninvasive methods in the evaluation of collateral circulation has yet to be defined. We hypothesized that a favorable pattern of leptomeningeal collaterals, as identified by CT angiography, correlates with improved outcomes.
Methods-Data from a prospective cohort study at 2 university-based hospitals where CT angiography was systematically performed in the acute phase of ischemic stroke were analyzed. Patients with complete occlusion of the intracranial internal carotid artery and/or the middle cerebral artery (M1 or M2 segments) were selected. The leptomeningeal collateral pattern was graded as a 3-category ordinal variable (less, equal, or greater than the unaffected contralateral hemisphere). Univariate and multivariate analyses were performed to define the independent predictors of good outcome at 6 months (modified Rankin Scale score <= 2).
Results-One hundred ninety-six patients were selected. The mean age was 69 +/- 17 years and the median National Institute of Health Stroke Scale score was 13 (interquartile range, 6 to 17). In the univariate analysis, age, baseline National Institute of Health Stroke Scale score, prestroke modified Rankin Scale score, Alberta Stroke Programme Early CT score, admission blood glucose, history of hypertension, coronary artery disease, congestive heart failure, atrial fibrillation, site of occlusion, and collateral pattern were predictors of outcome. In the multivariate analysis, age (OR, 0.95; 95% CI, 0.93 to 0.98; P=0.001), baseline National Institute of Health Stroke Scale (OR, 0.75; 0.69 to 0.83; P<0.001), prestroke modified Rankin Scale score (OR, 0.41; 0.22 to 0.76; P=0.01), intravenous recombinant tissue plasminogen activator (OR, 4.92; 1.83 to 13.25; P=0.01), diabetes (OR, 0.31; 0.01 to 0.98; P=0.046), and leptomeningeal collaterals (OR, 1.93; 1.06 to 3.34; P=0.03) were identified as independent predictors of good outcome.
Conclusion-Consistent with angiographic studies, leptomeningeal collaterals on CT angiography are also a reliable marker of good outcome in ischemic stroke. (Stroke. 2010;41:2316-2322.)
C1 [Lima, Fabricio O.; Furie, Karen L.; Silva, Gisele S.; Camargo, Erica C. S.; Singhal, Aneesh B.; Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA.
[Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Neurol, Neurocrit Care Serv, Boston, MA 02114 USA.
[Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Neurol, Intervent Neuroradiol Serv, Boston, MA 02114 USA.
[Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Radiol, Stroke Serv, Boston, MA 02114 USA.
[Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Radiol, Neurocrit Care Serv, Boston, MA 02114 USA.
[Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Radiol, Intervent Neuroradiol Serv, Boston, MA 02114 USA.
[Koroshetz, Walter J.] NINDS, Bethesda, MD 20892 USA.
[Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Yoo, Albert J.] Massachusetts Gen Hosp, Dept Radiol, Diagnost & Intervent Neuroradiol Serv, Boston, MA 02114 USA.
RP Nogueira, RG (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Blake 12,55 Fruit St, Boston, MA 02114 USA.
EM rnogueira@partners.org
RI Lima, Fabricio/E-6507-2015
OI Lima, Fabricio/0000-0002-0383-4145
FU Department of Health and Human Services, Agency for Healthcare Research
and Quality [RO1-HS011392-01A1]; GE Healthcare; National Institutes of
Health (NIH) [P50NS051343, R01NS051412, R01NS38477, R01NS059775];
Penumbra Inc
FX This research was funded by a grant from the Department of Health and
Human Services, Agency for Healthcare Research and Quality, grant number
RO1-HS011392-01A1.; M.H.L. is a speaker for GE Healthcare, receives
educational support from GE Healthcare, serves on a medical advisory
board for CoAxia Inc, is a research consultant for Vernalis Ltd
(modest), and is supported by National Institutes of Health (NIH) grant
P50NS051343 (significant). A.B.S. is supported by NIH grants
P50NS051343, R01NS051412, R01NS38477 (significant), and R01NS059775
(modest). W.S.S. has significant ownership interests and has served as a
consultant to Concentric Medical Inc (significant). A.J.Y. is supported
by a research grant from Penumbra Inc (significant). R.G.N. is a member
of the Scientific Advisory Board for Concentric Medical Inc, ev3
Neurovascular Inc, and Coaxia Inc (modest).
NR 24
TC 109
Z9 115
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD OCT
PY 2010
VL 41
IS 10
BP 2316
EP 2322
DI 10.1161/STROKEAHA.110.592303
PG 7
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 655CY
UT WOS:000282221700044
PM 20829514
ER
PT J
AU Kernan, WN
Launer, LJ
Goldstein, LB
AF Kernan, Walter N.
Launer, Lenore J.
Goldstein, Larry B.
TI What Is the Future of Stroke Prevention? Debate: Polypill Versus
Personalized Risk Factor Modification
SO STROKE
LA English
DT Article; Proceedings Paper
CT 27th Princeton Conference 2010
CY APR 22-24, 2010
CL Boston, MA
DE cerebrovascular disorders; primary prevention
ID CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; OUTCOMES; TRIAL; HEALTH;
METAANALYSIS; ASSOCIATION; OPPORTUNITY; NUTRITION; MORTALITY
AB Background and Purpose-The control of stroke risk factors remains challenging. The "polypill" concept represents a novel approach for reducing stroke and cardiovascular risk factors in the entire population. The polypill would include several components and be provided without prescription to all adults of a certain age.
Results-A polypill aimed at lowering blood pressure and cholesterol levels is estimated to potentially reduce the risk of a first ischemic stroke by 53%; this would translate to about 400 000 fewer strokes each year in the United States alone. Recommending a polypill for the entire older adult population would, however, include many individuals without the multiple risk factors targeted by its components, putting them at risk for drug-related side effects and responsible for the costs of a medication from which they would not derive benefit. Additional arguments for and against the polypill approach are discussed.
Conclusions-Only clinical trials can provide the evidence needed to determine the usefulness of the polypill approach. Issues related to defining the components of the polypill, evaluating the pharmacodynamics and pharmacokinetics of a multiple-component formulation, and establishing safety and cost-effectiveness when given to large populations, however, are not trivial. (Stroke. 2010;41[suppl 1]:S35-S38.)
C1 [Launer, Lenore J.] NIA, Neuroepidemiol Sect, NIH, Bethesda, MD 20892 USA.
[Kernan, Walter N.] Yale Univ, Dept Med, New Haven, CT 06520 USA.
[Goldstein, Larry B.] Duke Univ, Duke Stroke Ctr, Dept Med Neurol, Durham, NC 27710 USA.
Durham Dept Vet Affairs Med Ctr, Durham, NC USA.
RP Goldstein, LB (reprint author), Duke Univ, Med Ctr, Box 3651, Durham, NC 27710 USA.
EM golds004@mc.duke.edu
FU Intramural NIH HHS [Z01 AG007270-08]
NR 30
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U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD OCT
PY 2010
VL 41
IS 10
SU 1
BP S35
EP S38
DI 10.1161/STROKEAHA.110.592022
PG 4
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 655DR
UT WOS:000282224300010
PM 20876501
ER
PT J
AU Yuan, NP
Eaves, ER
Koss, MP
Polacca, M
Bletzer, K
Goldman, D
AF Yuan, Nicole P.
Eaves, Emery R.
Koss, Mary P.
Polacca, Mona
Bletzer, Keith
Goldman, David
TI "Alcohol is Something That Been With Us Like a Common Cold": Community
Perceptions of American Indian Drinking
SO SUBSTANCE USE & MISUSE
LA English
DT Article
DE American Indian; alcohol; prevention; qualitative research
ID MENTAL-HEALTH DISPARITIES; RESERVATION POPULATIONS; DISORDERS;
DEPENDENCE; PREVENTION; PREVALENCE; CULTURE; TRIBES
AB This study examined tribal members' perspectives on alcohol, risk factors, consequences, and community responses. Focus groups were conducted with five American Indian tribes between 1997 and 2001. Participants were knowledgeable of the cultural lives of their reservation communities. Although there was agreement regarding the pervasiveness of heavy drinking, participants reported different opinions about the meaning of alcohol and appropriate intervention strategies. Three dilemmas were identified, suggesting that community ambivalence may serve as a barrier to reducing problem drinking. Implications, limitations, and future research directions are discussed. The study was funded by the National Institute on Alcohol Abuse and Alcoholism.
C1 [Yuan, Nicole P.; Koss, Mary P.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85724 USA.
[Bletzer, Keith] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ USA.
[Goldman, David] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA.
[Eaves, Emery R.] Univ Arizona, Dept Family & Community Med, Tucson, AZ 85724 USA.
RP Yuan, NP (reprint author), Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, 1295 N Martin Ave,POB 245209, Tucson, AZ 85724 USA.
EM nyuan@email.arizona.edu
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU National Institute on Alcohol Abuse and Alcoholism [K23AA014606,
N01AA51012]
FX This paper was supported by Grant Number K23AA014606 from the National
Institute on Alcohol Abuse and Alcoholism to the first author. The Ten
Tribes Study was funded by Contract Number N01AA51012 from the same
institute. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institute on Alcohol Abuse and Alcoholism or the National Institutes of
Health. We express sincere gratitude to the tribal members who shared
their opinions and experiences to inform the main study design and the
tribes for providing tribal council support. Appreciation also goes to
Christiane Pretzinger and JoLene Unruh for transcribing the interviews
and Dr. Nicky Teufel-Shone for consultation on qualitative analysis.
Thanks are also due to Dr. Bonnie Duran for her insightful reading of
the manuscript.
NR 29
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U1 0
U2 9
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1082-6084
J9 SUBST USE MISUSE
JI Subst. Use Misuse
PD OCT
PY 2010
VL 45
IS 12
BP 1909
EP 1929
DI 10.3109/10826081003682115
PG 21
WC Substance Abuse; Psychiatry; Psychology
SC Substance Abuse; Psychiatry; Psychology
GA 633RP
UT WOS:000280522500005
PM 20380555
ER
PT J
AU Scheidweiler, KB
Spargo, EAK
Kelly, TL
Cone, EJ
Barnes, AJ
Huestis, MA
AF Scheidweiler, Karl B.
Spargo, Erin A. Kolbrich
Kelly, Tamsin L.
Cone, Edward J.
Barnes, Allan J.
Huestis, Marilyn A.
TI Pharmacokinetics of Cocaine and Metabolites in Human Oral Fluid and
Correlation With Plasma Concentrations After Controlled Administration
SO THERAPEUTIC DRUG MONITORING
LA English
DT Article
DE cocaine; oral fluid; clinical study; pharmacokinetics
ID HUMAN VOLUNTEERS; SALIVA; DISPOSITION; COLLECTION; CODEINE; URINE;
DRUGS; SWEAT
AB Oral fluid is an attractive alternative matrix for drug testing with a noninvasive and directly observed collection, but there are few controlled cocaine administration studies to guide interpretation.
Materials and Methods: While residing on a closed research unit for up to 10 weeks under constant medical supervision, 19 participants were administered 75 wmg/70 kg subcutaneous cocaine and 14 received 150 mg/70 kg. The disposition of cocaine, benzoylecgonine (BE), and ecgonine methyl ester (EME) into oral fluid was determined by gas chromatography-mass spectrometry for 0.08 to 48 hours after administration.
Results: In oral fluid collected by citric acid candy-stimulated expectoration, cocaine first appeared in oral fluid 0.08 to 0.32 hours after dosing and was rapidly eliminated with half-lives of 1.1 to 3.8 hours. BE and EME were first detected 0.08 to 1.0 hours after dosing with longer half-lives of 3.4 to 13.8 (BE) and 2.4 to 15.5 hours (EME) (P < 0.05). Oral fluid and plasma concentrations were significantly correlated for cocaine, BE, and EME (P < 0.0001). There were no significant differences (P. 0.05) in first and last detection times with the 8-mu g/L cutoff proposed by the Substance Abuse and Mental Health Services Administration or the 10-mu g/L cutoff from the European initiative, Driving Under the Influence of Drugs, Alcohol and Medicines. Metabolite: cocaine ratios increased after cocaine administration, potentially helpful for interpreting time of last use. Comparison of oral fluid collection through citric acid candy-stimulated expectoration, citric acid-treated Salivette, and neutral cotton Salivette devices did not reveal significant differences between devices for areas under the curve for cocaine, BE, or EME (P > 0.05).
Discussion and Conclusion: These results provide additional evidence for interpreting cocaine and metabolite concentrations in oral fluid and oral fluid's usefulness as an alternative matrix for drug testing.
C1 [Scheidweiler, Karl B.; Spargo, Erin A. Kolbrich; Barnes, Allan J.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Kelly, Tamsin L.] Univ Canberra, Fac Sci Appl, Canberra, ACT 2601, Australia.
[Cone, Edward J.] Johns Hopkins Sch Med, Baltimore, MD USA.
RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
RI Kelly, Tamsin/A-2456-2009
OI Kelly, Tamsin/0000-0002-8946-9686
FU National Institutes of Health, National Institute on Drug Abuse
FX This research was supported by funds from the National Institutes of
Health, Intramural Research Program, National Institute on Drug Abuse.
NR 26
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U1 1
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0163-4356
J9 THER DRUG MONIT
JI Ther. Drug Monit.
PD OCT
PY 2010
VL 32
IS 5
BP 628
EP 637
DI 10.1097/FTD.0b013e3181f2b729
PG 10
WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
GA 653NY
UT WOS:000282099700014
PM 20814350
ER
PT J
AU Yende, S
van der Poll, T
Lee, M
Huang, DT
Newman, AB
Kong, L
Kellum, JA
Harris, TB
Bauer, D
Satterfield, S
Angus, DC
AF Yende, Sachin
van der Poll, Tom
Lee, MinJae
Huang, David T.
Newman, Anne B.
Kong, Lan
Kellum, John A.
Harris, Tamara B.
Bauer, Doug
Satterfield, Suzanne
Angus, Derek C.
CA GenIMS Hlth ABC Study
TI The influence of pre-existing diabetes mellitus on the host immune
response and outcome of pneumonia: analysis of two multicentre cohort
studies
SO THORAX
LA English
DT Article
ID COMMUNITY-ACQUIRED PNEUMONIA; ACUTE-RENAL-FAILURE; INFLAMMATORY MARKERS;
LONG-TERM; MORTALITY; SEPSIS; RISK; PREDICTION; HYPERGLYCEMIA; DISEASE
AB Background Although diabetes mellitus is implicated in susceptibility to infection, the association of diabetes with the subsequent course and outcome is unclear.
Methods A retrospective analysis of two multicentre cohorts was carried out. The effect of pre-existing diabetes on the host immune response, acute organ function and mortality in patients hospitalised with community-acquired pneumonia (CAP) in the GenIMS study (n=1895) and on mortality following either CAP or non-infectious hospitalisations in the population-based cohort study, Health ABC (n=1639) was determined. Measurements included the mortality rate within the first year, risk of organ dysfunction, and immune responses, including circulating inflammatory (tumour necrosis factor, interleukin 6, interleukin 10), coagulation (Factor IX, thrombin-antithrombin complexes, antithrombin), fibrinolysis (plasminogen-activator inhibitor-1 and D-dimer) and cell surface markers (CD120a, CD120b, human leucocyte antigen (HLA)-DR, Toll-like receptor-2 and Toll-like receptor-4).
Results In GenIMS, diabetes increased the mortality rate within the first year after CAP (unadjusted HR 1.41, 95% CI 1.12 to 1.76, p=0.002), even after adjusting for pre-existing cardiovascular and renal disease (adjusted HR 1.3, 95% CI 1.03 to 1.65, p=0.02). In Health ABC, diabetes increased the mortality rate within the first year following CAP hospitalisation, but not after hospitalisation for non-infectious illnesses (significant interaction for diabetes and reason for hospitalisation (p=0.04); HR for diabetes on mortality over the first year after CAP 1.87, 95% CI 0.76 to 4.6, p=0.16, and after non-infectious hospitalisation 1.16, 95% CI 0.8 to 1.6, p=0.37). In GenIMS, immediate immune response was similar, as evidenced by similar circulating immune marker levels, in the emergency department and during the first week. Those with diabetes had a higher risk of acute kidney injury during hospitalisation (39.3% vs 31.7%, p-0.005) and they were more likely to die due to cardiovascular and kidney disease (34.4% vs 26.8% and 10.4% vs 4.5%, p=0.03).
Conclusions Pre-existing diabetes was associated with a higher risk of death following CAP. The mechanism is not due to an altered immune response, at least as measured by a broad panel of circulating and cell surface markers, but may be due to worsening of pre-existing cardiovascular and kidney disease.
C1 [Yende, Sachin; Lee, MinJae; Huang, David T.; Kellum, John A.; Angus, Derek C.] Univ Pittsburgh, Clin Res Invest & Syst Modeling Acute Illness Lab, Pittsburgh, PA 15261 USA.
[Yende, Sachin] Univ Pittsburgh, Dept Crit Care Med, CRISMA Lab, Pittsburgh, PA 15261 USA.
[van der Poll, Tom] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam CINIMA, NL-1105 AZ Amsterdam, Netherlands.
[van der Poll, Tom] Univ Amsterdam, Acad Med Ctr, Ctr Expt & Mol Med, NL-1105 AZ Amsterdam, Netherlands.
[Lee, MinJae; Kong, Lan] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Huang, David T.] Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA 15261 USA.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Bauer, Doug] Univ Calif San Francisco, Dept Epidemiol & Biostat & Med, San Francisco, CA 94143 USA.
[Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA.
RP Yende, S (reprint author), Univ Pittsburgh, Dept Crit Care Med, CRISMA Lab, 642A Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA.
EM yendes@upmc.edu
RI Angus, Derek/E-9671-2012; Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU NIGMS [R01 GM61992]; GlaxoSmithKline; NIA [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; NHLBI [R01HL74104]; NIAID [27913, 39482]; NIH, National
Institute on Ageing; [K23GM083215]
FX GenIMS was funded by NIGMS R01 GM61992 with additional support from
GlaxoSmithKline for enrolment and clinical data collection, and
Diagnostic Products Corporation for the cytokine assays. Health ABC was
funded by NIA (N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106), NHLBI
(R01HL74104) and NIAID (27913 and 39482). Health ABC was supported in
part by the Intramural Research Program of the NIH, National Institute
on Ageing. SY is supported by K23GM083215.
NR 35
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Z9 38
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0040-6376
J9 THORAX
JI Thorax
PD OCT
PY 2010
VL 65
IS 10
BP 870
EP 877
DI 10.1136/thx.2010.136317
PG 8
WC Respiratory System
SC Respiratory System
GA 653GI
UT WOS:000282076700008
PM 20861291
ER
PT J
AU Hatsukami, DK
Perkins, KA
LeSage, MG
Ashley, DL
Henningfield, JE
Benowitz, NL
Backinger, CL
Zeller, M
AF Hatsukami, Dorothy K.
Perkins, Kenneth A.
LeSage, Mark G.
Ashley, David L.
Henningfield, Jack E.
Benowitz, Neal L.
Backinger, Cathy L.
Zeller, Mitch
TI Nicotine reduction revisited science and future directions
SO TOBACCO CONTROL
LA English
DT Article
ID DISCRIMINATIVE STIMULUS PROPERTIES; CONDITIONED PLACE PREFERENCE;
BEHAVIORAL ECONOMIC-ANALYSIS; MONOAMINE-OXIDASE INHIBITOR;
CIGARETTE-SMOKING; TOBACCO DEPENDENCE; ADULT RATS; SEX-DIFFERENCES;
DENICOTINIZED CIGARETTES; ACETYLCHOLINE-RECEPTORS
AB Regulation of nicotine levels in cigarettes and other tobacco products is now possible with the passage of the Family Smoking Prevention and Tobacco Control Act (FSPTCA) in 2009 giving the US Food and Drug Administration (FDA) authority to regulate tobacco products and with Articles 911 of the WHO Framework Convention on Tobacco Control Both regulatory approaches allow establishing product standards for tobacco constituents including nicotine The FSPTCA does not allow nicotine levels to be decreased to rem although the FDA has the authority to reduce nicotine yields to very low presumably non addicting levels The proposal to reduce levels of nicotine to a level that is non addicting was originally suggested in 1994 Reduction of nicotine in tobacco products could potentially have a profound impact on reducing tobacco related morbidity and mortality To examine this issue two meetings were convened in the US with non tobacco industry scientists of varied disciplines tobacco control policymakers and representatives of government agencies This article provides an overview of the current science in the area of reduced nicotine content cigarettes and key conclusions and recommendations for research and policy that emerged from the deliberations of the meeting members
C1 [Hatsukami, Dorothy K.] Univ Minnesota, Tobacco Use Res Ctr, Dept Psychiat, Minneapolis, MN 55414 USA.
[Perkins, Kenneth A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[LeSage, Mark G.] Univ Minnesota, Minneapolis Med Res Fdn, Dept Med, Minneapolis, MN 55414 USA.
[Ashley, David L.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA.
[Henningfield, Jack E.; Zeller, Mitch] Pinney Associates, Bethesda, MD USA.
[Benowitz, Neal L.] Univ Calif San Francisco, Dept Med & Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Backinger, Cathy L.] Natl Canc Inst, Tobacco Control Res Branch, Rockville, MD USA.
RP Hatsukami, DK (reprint author), Univ Minnesota, Tobacco Use Res Ctr, Dept Psychiat, 717 Delaware St SE, Minneapolis, MN 55414 USA.
FU National Institute on Drug Abuse Rockville Maryland USA; National Cancer
Institute Rockville Maryland USA; Nabi Biopharmaceuticals
FX National Institute on Drug Abuse Rockville Maryland USA National Cancer
Institute Rockville Maryland USA Other Funders American Legacy
Foundation Washington DC USA; DKH has received grant funding from Nabi
Biopharmaceuticals to conduct nicotine vaccine clinical trials JEH
provides consulting support for GlaxoSmithKline Consumer Health through
Pinney Associates on an exclusive basis on issues related to tobacco
dependence treatment has financial interest in a potential new oral
nicotine replacement product and serves as an expert witness in
litigation against tobacco companies NLB serves as a consultant for
Pfizer and as an expert witness in litigation against tobacco companies
MZ provides consulting support to GlaxoSmithKline Consumer Health
through Pinney Associates on an exclusive basis on issues related to
tobacco dependence treatment KAP has served as a consultant to Cypress
Bioscience
NR 154
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Z9 45
U1 1
U2 11
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0964-4563
J9 TOB CONTROL
JI Tob. Control
PD OCT
PY 2010
VL 19
IS 5
AR e1
DI 10.1136/tc.7009.035584
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 691HN
UT WOS:000285071000024
PM 20876072
ER
PT J
AU Crawford, LW
Foley, JF
Elmore, SA
AF Crawford, Laura Wilding
Foley, Julie F.
Elmore, Susan A.
TI Histology Atlas of the Developing Mouse Hepatobiliary System with
Emphasis on Embryonic Days 9.5-18.5
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE liver; embryo; mouse; development; phenotype; atlas; hematopoiesis
ID MURINE FETAL LIVER; T-CELL PROGENITORS; HEMATOPOIETIC STEM-CELLS;
INTRAHEPATIC BILE-DUCTS; HOMEOBOX GENE HEX; B-CELL; TRANSCRIPTION
FACTOR; MICE LACKING; YOLK-SAC; ERYTHROBLASTIC ISLANDS
AB Animal model phenotyping, in utero exposure toxicity studies, and investigation into causes of embryonic, fetal, or perinatal deaths have required pathologists to recognize and diagnose developmental disorders in spontaneous and engineered mouse models of disease. In mammals, the liver is the main site of hematopoiesis during fetal development, has endocrine and exocrine functions important for maintaining homeostasis in fetal and adult life; and performs other functions including waste detoxification, production and removal of glucose, glycogen storage, triglyceride and fatty acid processing, and serum protein production. Due to its role in many critical functions, alterations in the size, morphology, or function(s) of the liver often lead to embryonic lethality. Many publications and websites describe individual aspects of hepatobiliary development at defined stages. However, no single resource provides a detailed histological evaluation of H&E-stained sections of the developing murine liver and biliary systems using high-magnification and high-resolution color images. The work herein provides a histology atlas of hepatobiliary development between embryonic days 9.5-18.5. Although the focus of this work is normal hepatobiliary development, common defects in liver development are also described as a reference for pathologists who may be asked to phenotype mice with congenital, inherited, or treatment-related hepatobiliary defects.
Authors' note: All digital images can be viewed online at https://niehsimagesepl-inc.com with the username "ToxPathLiver" and the password "embryolivers."
C1 [Crawford, Laura Wilding; Foley, Julie F.; Elmore, Susan A.] NIEHS, Cellular & Mol Pathol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Elmore, Susan A.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
RP Elmore, SA (reprint author), NIEHS, Cellular & Mol Pathol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM elmore@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences
FX This research was supported (in part) by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences.
NR 107
TC 19
Z9 20
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD OCT
PY 2010
VL 38
IS 6
BP 872
EP 906
DI 10.1177/0192623310374329
PG 35
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 707VA
UT WOS:000286315700004
PM 20805319
ER
PT J
AU Auerbach, SS
Thomas, R
Shah, R
Xu, H
Vallant, MK
Nyska, A
Dunnick, JK
AF Auerbach, Scott S.
Thomas, Reuben
Shah, Ruchir
Xu, Hong
Vallant, Molly K.
Nyska, Abraham
Dunnick, June K.
TI Comparative Phenotypic Assessment of Cardiac Pathology, Physiology, and
Gene Expression in C3H/HeJ, C57BL/6J, and B6C3F1/J Mice
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE heart; genetic susceptibly; genomics; cardiomyopathy; electrophysiology
ID ACTIVATED PROTEIN-KINASE; NATIONAL TOXICOLOGY PROGRAM; LONG-QT SYNDROME;
HEART-FAILURE; ATHEROSCLEROSIS SUSCEPTIBILITY; MICROARRAY ANALYSIS;
FAILING HEART; DISEASE; IDENTIFICATION; MITOCHONDRIAL
AB Human cardiomyopathies often lead to heart failure, a major cause of morbidity and mortality in industrialized nations. Described here is a phenotypic characterization of cardiac function and genome-wide expression from C3H/HeJ, C57BL/6J, and B6C3F1/J male mice. Histopathologic analysis identified a low-grade background cardiomyopathy (murine progressive cardiomyopathy) in eight of nine male C3H/HeJ mice (age nine to ten weeks), but not in male C57BL/6J and in only of ten male B6C3F1/J mice. The C3H/HeJ mouse had an increased heart rate and a shorter RR interval compared to the B6C3F1/J and C57BL/6J mice. Cardiac genomic studies indicated the B6C3F1/J mice exhibited an intermediate gene expression phenotype relative to the 2 parental strains. Disease-centric enrichment analysis indicated a number of cardiomyopathy-associated genes were induced in B6C3F1/J and C3H/HeJ mice, including Myh7, My14, and Lmna and also indicated differential expression of genes associated with metabolic (e. g., Pdk2) and hypoxic stress (e. g. Hif1a). A novel coexpression and integrated pathway network analysis indicated Prkaa2, Pdk2, Rhoj, and Sgcb are likely to play a central role in the pathophysiology of murine progressive cardiomyopathy in C3H/HeJ mice. Our studies indicate that genetically determined baseline differences in cardiac phenotype have the potential to influence the results of cardiotoxicity studies.
C1 [Auerbach, Scott S.; Thomas, Reuben; Xu, Hong; Vallant, Molly K.; Nyska, Abraham; Dunnick, June K.] NIEHS, Natl Toxicol Program, Div Intramural Res, Res Triangle Pk, NC 27709 USA.
[Shah, Ruchir] SRA Int, Durham, NC USA.
RP Dunnick, JK (reprint author), NIEHS, Natl Toxicol Program, Div Intramural Res, POB 12233, Res Triangle Pk, NC 27709 USA.
EM dunnickj@niehs.nih.gov
OI Xu, Hong/0000-0003-1995-4675
FU National Institute of Environmental Health Sciences, Research Triangle
Park, NC; NIEHS [N01-ES-55536, ES 55547]
FX We thank Dr. Jef French, NIEHS, and Dr. K. Shockley, NIEHS, for their
excellent review of the manuscript. We would also like to thank Dr.
Vincent VanBuren and Dr. Daniel C. Jupiter for generously providing the
cardiac gene expression correlation matrix used in the creation of the
coexpression network analysis. This work was supported by the intramural
program of the National Institute of Environmental Health Sciences
Intramural Program, Research Triangle Park, NC. The in-life portion of
this study was conducted under NIEHS contract N01-ES-55536. Statistical
support was provided under NIEHS contract ES 55547.
NR 70
TC 5
Z9 5
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD OCT
PY 2010
VL 38
IS 6
BP 923
EP 942
DI 10.1177/0192623310382864
PG 20
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 707VA
UT WOS:000286315700006
PM 21037199
ER
PT J
AU Szabo, DT
Diliberto, JJ
Hakk, H
Huwe, JK
Birnbaum, LS
AF Szabo, David T.
Diliberto, Janet J.
Hakk, Heldur
Huwe, Janice K.
Birnbaum, Linda S.
TI Toxicokinetics of the Flame Retardant Hexabromocyclododecane Gamma:
Effect of Dose, Timing, Route, Repeated Exposure, and Metabolism
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE mouse; metabolism; diastereomer; pharmacokinetics; stereoisomerization;
HBCD; ADME; risk assessment; persistent organic pollutant; brominated
flame retardant
ID POLYBROMINATED DIPHENYL ETHERS; INDOOR DUST; WISTAR RATS; ACCUMULATION;
SPECTROMETRY; TRENDS; HBCDS; MICE
AB Hexabromocyclododecane-gamma (gamma-HBCD) is the predominate diastereoisomer in the commercial HBCD mixture used as a flame retardant in a wide variety of consumer products. Three main diastereoisomers, alpha (alpha), beta (beta), and gamma (gamma), comprise the mixture. Despite the gamma-diastereoisomer being the major diastereoisomer in the mixture and environmental samples, the alpha-diastereoisomer predominates human tissue and wildlife. This study was conducted to characterize absorption, distribution, metabolism, and excretion parameters of gamma-HBCD with respect to dose and time following a single acute exposure and repeated exposure in adult female C57BL/6 mice. Results suggest that 85% of the administered dose (3 mg/kg) was absorbed after po exposure. Disposition was dose independent and did not significantly change after 10 days of exposure. Liver was the major depot (< 0.3% of dose) 4 days after treatment followed by blood, fat, and then brain. gamma-HBCD was rapidly metabolized and eliminated in the urine and feces. For the first time, in vivo stereoisomerization was observed of the gamma-diastereoisomer to the beta-diastereoisomer in liver and brain tissues and to the alpha- and beta-diastereoisomer in fat and feces. Polar metabolites in the blood and urine were a major factor in determining the initial whole-body half-life (1 day) after a single po exposure. Elimination, both whole-body and from individual tissues, was biphasic. Initial half-lives were approximately 1 day, whereas terminal half-lives were up to 4 days, suggesting limited potential for gamma-diastereoisomer bioaccumulation. The toxicokinetic behavior reported here has important implications for the extrapolation of toxicological studies of the commercial HBCD mixture to the assessment of risk.
C1 [Szabo, David T.] Univ N Carolina, Curriculum Toxicol, US EPA, Res Triangle Pk, NC 27711 USA.
[Szabo, David T.; Diliberto, Janet J.] US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
[Hakk, Heldur; Huwe, Janice K.] USDA ARS, Biosci Res Lab, Fargo, ND 58105 USA.
[Birnbaum, Linda S.] NIEHS, NCI, Res Triangle Pk, NC 27709 USA.
[Birnbaum, Linda S.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Szabo, DT (reprint author), Univ N Carolina, Curriculum Toxicol, US EPA, MD B143-01,109 TW Alexander Dr, Durham, NC 27703 USA.
EM szabo@email.unc.edu
FU University of North Carolina in Chapel Hill; United States Environmental
Protection Agency [CR 833237]
FX University of North Carolina in Chapel Hill and the United States
Environmental Protection Agency predoctoral training grants (CR 833237).
NR 32
TC 56
Z9 57
U1 8
U2 38
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD OCT
PY 2010
VL 117
IS 2
BP 282
EP 293
DI 10.1093/toxsci/kfq183
PG 12
WC Toxicology
SC Toxicology
GA 653AZ
UT WOS:000282055900005
PM 20562218
ER
PT J
AU Thackaberry, EA
Kopytek, S
Sherratt, P
Trouba, K
McIntyre, B
AF Thackaberry, Evan A.
Kopytek, Stephen
Sherratt, Phillip
Trouba, Kevin
McIntyre, Barry
TI Comprehensive Investigation of Hydroxypropyl Methylcellulose, Propylene
Glycol, Polysorbate 80, and Hydroxypropyl-Beta-Cyclodextrin for use in
General Toxicology Studies
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE propylene glycol; polysorbate 80; hydroxypropyl-beta-cyclodextrin; Tween
80; HP beta CD; safety assessment
ID SAFETY ASSESSMENT; RATS; TOXICITY; DOGS
AB This study was conducted to assess the safety and tolerability of the alternative formulation vehicles polysorbate 80 (PS80), propylene glycol (PG), and hydroxypropyl-beta-cyclodextrin (HP beta CD) in general toxicology studies in the mouse, rat, dog, and monkey. Twenty (20) mg/kg of hydroxypropyl methylcellulose (MC, control), 10 mg/kg PS80, 1000 mg/kg PG, 500 mg/kg HP beta CD, or 1000 mg/kg HP beta CD were administered by oral gavage to mice, rats, dogs, and cynomolgus monkeys for approximately 90 days. The effects of these formulations on clinical observations, body weight and food consumption parameters, clinical pathology, and histopathology were evaluated across all species. The suitability of formulations containing up to 20 mg/kg MC, 10 mg/kg PS80, and 1000 mg/kg PG for use in preclinical safety studies was confirmed by a lack of effects on all parameters examined. However, formulations containing HP beta CD produced elevated transaminase (aspartate and alanine aminotransferase) levels in rats and mice and fecal changes (loose and soft stool) in large animals. Although the etiology and toxicological significance of the transaminase elevations in rats and mice is uncertain, this finding could represent a significant liability for a preclinical formulation because of the critical importance of these biomarkers in the risk assessment of novel therapeutic agents. Based on these data, PS80 and PG are considered to be practical alternatives to MC in preclinical toxicology studies. However, formulations containing HP beta CD should be used with caution because of the elevations in rodent transaminase levels.
C1 [Thackaberry, Evan A.] Merck Res Labs, Dept Safety Assessment, Lafayette, NJ 07848 USA.
[Kopytek, Stephen; Sherratt, Phillip] Merck Res Labs, Dept Safety Assessment, Summit, NJ 07901 USA.
[Trouba, Kevin] Bristol Myers Squibb, Drug Safety Evaluat, Mount Vernon, IN 47630 USA.
[McIntyre, Barry] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Thackaberry, EA (reprint author), Merck Res Labs, Dept Safety Assessment, 44 Route 94 S, Lafayette, NJ 07848 USA.
EM methack@gmail.com
FU Merck Research Laboratories
FX Merck Research Laboratories.
NR 36
TC 20
Z9 20
U1 5
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD OCT
PY 2010
VL 117
IS 2
BP 485
EP 492
DI 10.1093/toxsci/kfq207
PG 8
WC Toxicology
SC Toxicology
GA 653AZ
UT WOS:000282055900023
PM 20643750
ER
PT J
AU Hayakawa, J
Joyal, EG
Gildner, JF
Washington, KN
Phang, OA
Uchida, N
Hsieh, MM
Tisdale, JF
AF Hayakawa, Jun
Joyal, Elizabeth G.
Gildner, Jean F.
Washington, Kareem N.
Phang, Oswald A.
Uchida, Naoya
Hsieh, Matthew M.
Tisdale, John F.
TI 5% Dimethyl sulfoxide (DMSO) and pentastarch improves cryopreservation
of cord blood cells over 10% DMSO
SO TRANSFUSION
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; SEVERE RESPIRATORY DEPRESSION; SCID
IL2R-GAMMA(NULL) MICE; PLASMA-VOLUME EXPANSION; PERIPHERAL-BLOOD;
UNRELATED DONORS; HYDROXYETHYL STARCH; PROGENITOR CELLS;
SPINAL-ANESTHESIA; CLINICAL TOXICITY
AB BACKGROUND:
Cell number and viability are important in cord blood (CB) transplantation. While 10% dimethyl sulfoxide (DMSO) is the standard medium, adding a starch to freezing medium is increasingly utilized as a cytoprotectant for the thawing process. Similar to hetastarch, pentastarch has the advantages of faster renal clearance and less effect on the coagulation system.
STUDY DESIGN AND METHODS:
We compared a lower DMSO concentration (5%) containing pentastarch with 10% DMSO and performed cell viability assay, colony-forming units (CFUs), and transplantation of CB cells in NOD/SCID IL2R gamma null mice.
RESULTS:
CB cells in 5% DMSO/pentastarch had similar CD34+, CD3+, and CD19+ cell percentages after thawing as fresh CB cells. CB cells in 5% DMSO/pentastarch had higher viability (83.3 +/- 9.23%) than those frozen in 10% DMSO (75.3 +/- 11.0%, p < 0.05). We monitored cell viability postthaw every 30 minutes. The mean loss in the first 30 minutes was less in the 5% DMSO/pentastarch group. At the end of 3 hours, the viability decreased by a mean of 7.75% for the 5% DMSO/pentastarch and 17.5% for the 10% DMSO groups. CFUs were similar between the two cryopreserved groups. Frozen CB cells engrafted equally well in IL2R gamma null mice compared to fresh CB cells up to 24 weeks, and CB cells frozen in 5% DMSO/pentastarch engrafted better than those in 10% DMSO.
CONCLUSION:
Our data indicate that the lower DMSO concentration with pentastarch represents an improvement in the CB cryopreservation process and could have wider clinical application as an alternate freezing medium over 10% DMSO.
C1 NIH, MCHB, Bethesda, MD 20892 USA.
NIDDK, NIH, Bethesda, MD USA.
NHLBI, NIH, Bethesda, MD 20892 USA.
NIH, Charles S Carter Cellular Therapy Lab, Dept Transfus Med, Bethesda, MD USA.
RP Tisdale, JF (reprint author), 9000 Rockville Pike,Bldg 10,Room 9N 116, Bethesda, MD 20892 USA.
EM johntis@mail.nih.gov
FU National Institute of Diabetes, Digestive, and Kidney diseases and the
National Heart, Lung, and Blood Institute at NIH
FX We appreciate the statistical help by Richard Chen. This work is
supported by the intramural research program of the National Institute
of Diabetes, Digestive, and Kidney diseases and the National Heart,
Lung, and Blood Institute at NIH.
NR 50
TC 18
Z9 18
U1 4
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD OCT
PY 2010
VL 50
IS 10
BP 2158
EP 2166
DI 10.1111/j.1537-2995.2010.02684.x
PG 9
WC Hematology
SC Hematology
GA 661AF
UT WOS:000282693500013
PM 20492608
ER
PT J
AU Chang, CM
Quinlan, SC
Warren, JL
Engels, EA
AF Chang, Cindy M.
Quinlan, Scott C.
Warren, Joan L.
Engels, Eric A.
TI Blood transfusions and the subsequent risk of hematologic malignancies
SO TRANSFUSION
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; POPULATION; CANCER; DONOR; ASSOCIATION;
PREVALENCE; RECIPIENTS; HEPATITIS; COHORT; WOMEN
AB BACKGROUND:
Blood transfusions are associated with viral transmission and immunomodulation, perhaps increasing subsequent risk of hematologic malignancies (HMs). Prior studies of transfusion recipients have lacked details on specific HM subtypes.
STUDY DESIGN AND METHODS:
Risk of HM after blood transfusion was evaluated in a US population-based case-control study (77,488 elderly HM cases identified through cancer registries, 154,509 controls). Transfusions were identified using linked Medicare hospitalization claims. Polytomous logistic regression was used to calculate odds ratios (ORs) associating transfusion and HM subtypes by features suggestive of a causal relationship.
RESULTS:
A history of transfusion was present in 7.9% of HM cases versus 5.9% of controls. Associations for most HM subtypes suggested reverse causality: ORs were elevated only during the shortest latency periods; ORs for unspecified anemia and gastrointestinal bleeding, which may be related to undiagnosed HM, were stronger than for surgeries, which are unlikely to be related to HM; and/or there was no dose response. In contrast, risk for lymphoplasmacytic lymphoma (1397 cases) was elevated at long latency (OR, 1.56 at 10+ years after transfusion), after transfusions related to surgeries (OR, 1.22-1.47), and in a dose-response relationship with number of transfusion-related hospitalizations (OR, 1.53 with one hospitalization; OR, 1.80 with two or more hospitalizations, p trend < 0.0001). Risk for marginal zone lymphoma (1915 cases) was also elevated at 10+ years after transfusion (OR, 1.80).
CONCLUSION:
Consistent with prior studies, blood transfusions did not increase risk of most HM subtypes. Patterns of elevated risk for lymphoplasmacytic and marginal zone lymphomas suggest an etiologic role for transfusion.
C1 [Chang, Cindy M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, DHHS, Rockville, MD 20892 USA.
NIH, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Chang, CM (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, DHHS, 6120 Execut Blvd,EPS 7074, Rockville, MD 20892 USA.
EM changcm@mail.nih.gov
RI Chang, Cindy/G-4514-2010
FU National Cancer Institute
FX This study used the linked SEER-Medicare database. The interpretation
and reporting of these data are the sole responsibility of the authors.
The authors acknowledge the efforts of the Applied Research Program,
National Cancer Institute (NCI); the Office of Research, Development,
and Information, Centers for Medicare and Medicaid Services; Information
Management Services (IMS), Inc.; and the SEER Program tumor registries
in the creation of the SEER-Medicare database. The authors thank Winnie
Ricker (Information Management Services, Rockville, MD) for assistance
with database management. This research was supported by the Intramural
Research Program of the National Cancer Institute.
NR 40
TC 10
Z9 12
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD OCT
PY 2010
VL 50
IS 10
BP 2249
EP 2257
DI 10.1111/j.1537-2995.2010.02692.x
PG 9
WC Hematology
SC Hematology
GA 661AF
UT WOS:000282693500023
PM 20497517
ER
PT J
AU Blajchman, MA
Glynn, SA
Josephson, CD
Kleinman, SH
AF Blajchman, Morris A.
Glynn, Simone A.
Josephson, Cassandra D.
Kleinman, Steve H.
CA State-Of-The Sci
TI Clinical Trial Opportunities in Transfusion Medicine: Proceedings of a
National Heart, Lung, and Blood Institute State-of-the-Science Symposium
SO TRANSFUSION MEDICINE REVIEWS
LA English
DT Review
ID ACUTE NORMOVOLEMIC HEMODILUTION; ACUTE CORONARY SYNDROMES; PROPHYLACTIC
PLATELET TRANSFUSIONS; RADICAL RETROPUBIC PROSTATECTOMY;
CHEMOTHERAPY-INDUCED ANEMIA; ARTERY-BYPASS SURGERY; BIRTH-WEIGHT
INFANTS; VERSUS-HOST-DISEASE; DARBEPOETIN ALPHA; SEVERE THROMBOCYTOPENIA
AB The use of blood products to support patients undergoing the large variety of medical and surgical interventions requiring such support has continued to escalate very significantly over time. Relevantly, significant practice variation in the use of blood products exists among practitioners and institutions, largely because of the lack of robust clinical trial data, in many instances, which are critical for providing practitioners with evidence-based guidelines for appropriate blood product utilization. Recognizing this gap, the National Heart, Lung, and Blood Institute recently established a State-of-the-Science Symposium to help define areas of clinical trial research that would enhance the opportunity for developing appropriate practice guidelines for both Transfusion Medicine and Hemostasis/Thrombosis. Such a Symposium was held in September 2009 to identify important clinical trial research issues in these 2 subject areas of endeavor. The aims of this Symposium were to specifically identify phase 2 and 3 clinical trials that, if conducted over the next 5 to 10 years, could impact the treatment of patients with hemostatic and other disorders as well as to optimize the use of blood products in patients who need such interventions. This article reports on the deliberations that were held relating to the various clinical trial concepts developed by 7 Transfusion Medicine subcommittees. This Symposium generated a rich assortment of clinical trial proposals that will undergo further refinement before final implementation into pilot or full randomized clinical trials. The various proposals identified many opportunities for clinical trial research and most importantly underscored the ongoing need for well-developed evidence-based clinical trial research in the field of Transfusion Medicine. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Blajchman, Morris A.] McMaster Univ, Dept Pathol, Hamilton, ON L8N 3Z5, Canada.
NHLBI, Bethesda, MD 20892 USA.
Emory Univ, Atlanta, GA 30322 USA.
Univ British Columbia, Victoria, BC, Canada.
RP Blajchman, MA (reprint author), McMaster Univ, Dept Pathol, 1200 Main St W,HSC-4N67, Hamilton, ON L8N 3Z5, Canada.
EM blatchma@mcmaster.ca
RI Szczepiorkowski, Zbigniew/A-1359-2007; Winters, Jeffrey/A-2000-2013
OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564; Winters,
Jeffrey/0000-0001-8654-3732
NR 76
TC 16
Z9 16
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0887-7963
J9 TRANSFUS MED REV
JI Transf. Med. Rev.
PD OCT
PY 2010
VL 24
IS 4
BP 259
EP 285
DI 10.1016/j.tmrv.2010.05.002
PG 27
WC Hematology
SC Hematology
GA 656PP
UT WOS:000282349000001
PM 20851330
ER
PT J
AU Csermely, P
Palotai, R
Nussinov, R
AF Csermely, Peter
Palotai, Robin
Nussinov, Ruth
TI Induced fit, conformational selection and independent dynamic segments:
an extended view of binding events
SO TRENDS IN BIOCHEMICAL SCIENCES
LA English
DT Review
ID PROTEIN COMPLEXES; HYDROGEN-BONDS; ENERGY LANDSCAPES; FOLDING FUNNELS;
MECHANISM; NETWORKS; WATER; RNA; FLUCTUATIONS; RECOGNITION
AB Single molecule and NMR measurements of protein dynamics increasingly uncover the complexity of binding scenarios. Here, we describe an extended conformational selection model that embraces a repertoire of selection and adjustment processes. Induced fit can be viewed as a subset of this repertoire, whose contribution is affected by the bond types stabilizing the interaction and the differences between the interacting partners. We argue that protein segments whose dynamics are distinct from the rest of the protein ('discrete breathers') can govern conformational transitions and allosteric propagation that accompany binding processes and, as such, might be more sensitive to mutational events. Additionally, we highlight the dynamic complexity of binding scenarios as they relate to events such as aggregation and signalling, and the crowded cellular environment.
C1 [Csermely, Peter; Palotai, Robin] Semmelweis Univ, Dept Med Chem, H-1444 Budapest, Hungary.
[Nussinov, Ruth] NCI Frederick, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Csermely, P (reprint author), Semmelweis Univ, Dept Med Chem, POB 260, H-1444 Budapest, Hungary.
EM csermely@eok.sote.hu
FU EU [FP6-518230]; Hungarian National Science Foundation [OTKA K69105];
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX The authors thank the anonymous referees for their helpful suggestions
and we thank Mark Bathe and Do-Nyun Kim (Massachusetts Institute of
Technology, Cambridge, MA), as well as Zaida Luthey-Shulten and John
Eargle (University of Illinois at Urbana-Champaign, Urbana IL) for the
images in Figure 2. P.C. thanks Francesco Piazza (University of
Portsmouth, UK), Yves-Henri Sanejouand (University of Nantes, France)
and Gabor Simko (Semmelweis University, Budapest, Hungary) for helpful
discussions. Funding has been provided by the EU (FP6-518230) and by the
Hungarian National Science Foundation (OTKA K69105). This project has
been funded, in part, with federal funds from the National Cancer
Institute, National Institutes of Health, under contract
HHSN261200800001E. This research was supported, in part, by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. 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 70
TC 348
Z9 352
U1 10
U2 113
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0968-0004
J9 TRENDS BIOCHEM SCI
JI Trends Biochem.Sci.
PD OCT
PY 2010
VL 35
IS 10
BP 539
EP 546
DI 10.1016/j.tibs.2010.04.009
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 670HF
UT WOS:000283411100002
PM 20541943
ER
PT J
AU Rohani, P
King, AA
AF Rohani, Pejman
King, Aaron A.
TI Never mind the length, feel the quality: the impact of long-term
epidemiological data sets on theory, application and policy
SO TRENDS IN ECOLOGY & EVOLUTION
LA English
DT Review
ID INFECTIOUS-DISEASES; POPULATION BIOLOGY; DYNAMICS; CYCLES
AB Infectious diseases have been a prime testing ground for ecological theory. However, the ecological perspective is increasingly recognized as essential in epidemiology. Long-term, spatially resolved reliable data on disease incidence and the ability to test them using mechanistic models have been critical in this cross-fertilization. Here, we review some of the key intellectual developments in epidemiology facilitated by long-term data. We identify research frontiers at the interface of ecology and epidemiology and their associated data needs.
C1 [Rohani, Pejman; King, Aaron A.] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Rohani, Pejman; King, Aaron A.] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[King, Aaron A.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA.
[Rohani, Pejman; King, Aaron A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Rohani, P (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
EM rohani@umich.edu
RI King, Aaron/B-8092-2012
OI King, Aaron/0000-0001-6159-3207
FU Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; Vaccine
Modeling Initiative of the Bill & Melinda Gates Foundation
FX We thank Marc Choisy and two anonymous reviewers for comments on the
manuscript. We are grateful to Matt Ferrari and Natalia Mantilla-Beniers
for graciously sharing Figures 1 and 2, respectively. The authors are
supported by the Research and Policy in Infectious Disease Dynamics
program of the Science and Technology Directorate, Department of
Homeland Security, and the Fogarty International Center, National
Institutes of Health. PR was also supported by the Vaccine Modeling
Initiative of the Bill & Melinda Gates Foundation.
NR 27
TC 15
Z9 15
U1 0
U2 15
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0169-5347
J9 TRENDS ECOL EVOL
JI Trends Ecol. Evol.
PD OCT
PY 2010
VL 25
IS 10
SI SI
BP 611
EP 616
DI 10.1016/j.tree.2010.07.010
PG 6
WC Ecology; Evolutionary Biology; Genetics & Heredity
SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics &
Heredity
GA 663CM
UT WOS:000282860600010
PM 20800928
ER
PT J
AU Singleton, AB
Hardy, J
Traynor, BJ
Houlden, H
AF Singleton, Andrew B.
Hardy, John
Traynor, Bryan J.
Houlden, Henry
TI Towards a complete resolution of the genetic architecture of disease
SO TRENDS IN GENETICS
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; FAMILIAL ALZHEIMERS-DISEASE; CYSTIC-FIBROSIS
GENE; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; PARKINSONS-DISEASE;
IDENTIFIES VARIANTS; MISSENSE MUTATIONS; CLONING; RISK
AB After years of linear gains in the genetic dissection of human disease we are now in a period of exponential discovery. This is particularly apparent for complex disease. Genome-wide association studies (GWAS) have provided myriad associations between common variability and disease, and have shown that common genetic variability is unlikely to explain the entire genetic predisposition to disease. Here we detail how one can expand on this success and systematically identify genetic risks that lead or predispose to disease using next-generation sequencing. Geneticists have had for many years a protocol to identify Mendelian disease. A similar set of tools is now available for the identification of rare moderate-risk loci and common low-risk variants. Whereas major challenges undoubtedly remain, particularly regarding data handling and the functional classification of variants, we suggest that these will be largely practical and not conceptual.
C1 [Singleton, Andrew B.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Hardy, John; Houlden, Henry] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Hardy, John; Houlden, Henry] Inst Neurol, Reta Lilla Weston Labs, London WC1N 3BG, England.
[Houlden, Henry] Inst Neurol, Ctr Neuromuscular Dis, MRC, London WC1N 3BG, England.
RP Singleton, AB (reprint author), NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM singleta@mail.nih.gov
RI Singleton, Andrew/C-3010-2009; Sincan, Murat /A-3794-2010; Hardy,
John/C-2451-2009; Traynor, Bryan/G-5690-2010; Houlden, Henry/C-1532-2008
OI Houlden, Henry/0000-0002-2866-7777
FU Medical Research Council [G0601943, G0701075, G0802760]
NR 47
TC 53
Z9 54
U1 0
U2 5
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0168-9525
J9 TRENDS GENET
JI Trends Genet.
PD OCT
PY 2010
VL 26
IS 10
BP 438
EP 442
DI 10.1016/j.tig.2010.07.004
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 657HG
UT WOS:000282403200003
PM 20813421
ER
PT J
AU Ahlers, JD
Belyakov, IM
AF Ahlers, Jeffrey D.
Belyakov, Igor M.
TI Molecular pathways regulating CD4(+) T cell differentiation, anergy and
memory with implications for vaccines
SO TRENDS IN MOLECULAR MEDICINE
LA English
DT Review
ID HUMAN DENDRITIC CELLS; ARYL-HYDROCARBON RECEPTOR; GROWTH-FACTOR-BETA;
HUMAN TH17 CELLS; ROR-GAMMA-T; IN-VIVO; TRANSCRIPTION FACTOR; CUTTING
EDGE; LINEAGE COMMITMENT; HELPER-CELLS
AB CD4(+) T cells occupy a central role in the induction and regulation of adaptive immune responses. Activated CD4(+) T helper (Th) cells exert immediate effector functions by producing cytokines and chemokines, providing help for the induction of CD8(+) cytotoxic T lymphocyte responses and memory, and providing help for immunoglobulin class switching, affinity maturation of antibody and B cell memory. Inherent in naive CD4(+) T cells is the flexibility to adopt alternate lineage potentials, which depend upon regulatory mechanisms that change with tissue microenvironment and upon infection. Here, we discuss lineage instructive programs that regulate CD4(+) T cell differentiation and memory and how to translate this knowledge into vaccines and immunotherapies that promote protective immune responses.
C1 [Ahlers, Jeffrey D.] NIAID, NIH, Bethesda, MD 20817 USA.
[Belyakov, Igor M.] Midwest Res Inst, Frederick, MD 21702 USA.
RP Ahlers, JD (reprint author), NIAID, NIH, Bethesda, MD 20817 USA.
EM jeffreyahlers@hotmail.com
NR 157
TC 15
Z9 17
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4914
EI 1471-499X
J9 TRENDS MOL MED
JI Trends Mol. Med
PD OCT
PY 2010
VL 16
IS 10
BP 478
EP 491
DI 10.1016/j.molmed.2010.07.007
PG 14
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 673QS
UT WOS:000283678700005
PM 20739220
ER
PT J
AU Vaisbuch, E
Romero, R
Erez, O
Kusanovic, JP
Mazaki-Tovi, S
Gotsch, F
Romero, V
Ward, C
Chaiworapongsa, T
Mittal, P
Sorokin, Y
Hassan, SS
AF Vaisbuch, E.
Romero, R.
Erez, O.
Kusanovic, J. P.
Mazaki-Tovi, S.
Gotsch, F.
Romero, V.
Ward, C.
Chaiworapongsa, T.
Mittal, P.
Sorokin, Y.
Hassan, S. S.
TI Clinical significance of early (< 20 weeks) vs. late (20-24 weeks)
detection of sonographic short cervix in asymptomatic women in the
mid-trimester
SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY
LA English
DT Article
DE amniotic fluid sludge; cervical length; pregnancy; preterm delivery;
preterm labor; transvaginal; ultrasound
ID SPONTANEOUS PRETERM DELIVERY; AMNIOTIC-FLUID SLUDGE; TRANSVAGINAL
ULTRASONOGRAPHY; GESTATIONAL-AGE; OBSTETRIC HISTORY; HIGH-RISK;
DEMOGRAPHIC CHARACTERISTICS; LENGTH MEASUREMENT; CONTROLLED-TRIAL;
PREGNANCY LOSS
AB Objective The aim of this study was to determine whether the risk of early spontaneous preterm delivery (PTD) in asymptomatic women with a sonographic cervical length of <= 15 mm in the mid-trimester changes as a function of gestational age at diagnosis.
Methods This cohort study included 109 asymptomatic patients with a sonographic cervical length of <= 15 mm diagnosed at 14-24 weeks of gestation. Women with a multifetal gestation, cerclage and a cervical dilatation of > 2 cm were excluded. The study population was stratified by gestational age at diagnosis (< 20 weeks vs. 20-24 weeks) and by cervical length (<= 10 mm vs. 11-15 mm). The primary outcome variables were PTD at < 28 and < 32 weeks of gestation and the diagnosis-to-delivery interval.
Results The median gestational age at diagnosis of a short cervix before 20 weeks and at 20-24 weeks was 18.9 and 22.7 weeks, respectively. Women diagnosed before 20 weeks had a higher rate of PTD at < 28 weeks (76.9% vs. 30.9%; P < 0.001) and at < 32 weeks (80.8% vs. 48.1%; P = 0.004), and a shorter median diagnosis-to-delivery interval (21 vs. 61.5 days, P 0.003) than those diagnosed at 20-24 weeks. The rate of amniotic fluid sludge was higher among patients diagnosed with a short cervix at < 20 weeks of gestation than in those in whom it was diagnosed between 20 and 24 weeks (92.3% vs. 48.2%; P < 0.001).
Conclusions Asymptomatic women with a sonographic cervical length of < 15 mm diagnosed before 20 weeks of gestation have a dramatic and significantly higher risk of early preterm delivery than women diagnosed at 20-24 weeks. These findings can be helpful to physicians in counseling these patients, and may suggest different mechanisms of disease leading to a sonographic short cervix before or after 20 weeks of gestation. Copyright (C) 2010 ISUOG. Published by John Wiley & Sons, Ltd.
C1 [Vaisbuch, E.; Romero, R.; Erez, O.; Kusanovic, J. P.; Mazaki-Tovi, S.; Gotsch, F.; Chaiworapongsa, T.; Mittal, P.; Hassan, S. S.] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD NIH DHHS, Bethesda, MD USA.
[Vaisbuch, E.; Erez, O.; Kusanovic, J. P.; Mazaki-Tovi, S.; Romero, V.; Ward, C.; Chaiworapongsa, T.; Mittal, P.; Sorokin, Y.; Hassan, S. S.] Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, R.; Gotsch, F.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Vaisbuch, E.; Romero, R.; Erez, O.; Kusanovic, J. P.; Mazaki-Tovi, S.; Gotsch, F.; Chaiworapongsa, T.; Mittal, P.; Hassan, S. S.] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS,Intramural Div, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS,Intramural Div, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS. The authors wish to acknowledge the
contributions of the Registered Diagnostic Medical Sonographers staff
and the Research Nurses of the Perinatology Research Branch.
NR 82
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U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0960-7692
J9 ULTRASOUND OBST GYN
JI Ultrasound Obstet. Gynecol.
PD OCT
PY 2010
VL 36
IS 4
BP 471
EP 481
DI 10.1002/uog.7673
PG 11
WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
Medical Imaging
SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
Medical Imaging
GA 669ZZ
UT WOS:000283390200014
PM 20503224
ER
PT J
AU Menotti-Raymond, M
David, VA
Pflueger, S
Roelke, ME
Kehler, J
O'Brien, SI
Narfstrom, K
AF Menotti-Raymond, M.
David, V. A.
Pflueger, S.
Roelke, M. E.
Kehler, J.
O'Brien, S. I.
Narfstrom, K.
TI Widespread retinal degenerative disease mutation (rdAc) discovered among
a large number of popular cat breeds
SO VETERINARY JOURNAL
LA English
DT Article
DE Retinal degeneration; Cat breeds; Mutation; CEP290; Photoreceptors
ID ROD-CONE DEGENERATION; GENETIC-LINKAGE MAP; ABYSSINIAN CAT; DOMESTIC
CAT; FELIS-CATUS; JOUBERT-SYNDROME; CENTROSOMAL PROTEIN; RADIATION
HYBRID; ATROPHY; DYSTROPHY
AB The recent discovery of a mutational variant in the CEP290 gene (CEP290 IVS50 + 9T>G) conferring recessive retinal degeneration in Abyssinian and Somali (long-haired Abyssinian) cats (rdAc) prompted a survey among 41 cat breeds (846 individuals) to assess the incidence frequency and clinical consequence of rdAc The rdAc allele displayed widespread distribution observed in 16/43 (37%) breeds exhibiting a high allele frequency (similar to 33%) in North American and European Siamese populations Clinical evaluations demonstrated high concordance between rdAc pathology and the CEP290 (IV550 + 9T>G) homozygous genotype (P = 1 1E-6) with clinical disease similar to affected Abyssinians/Somalis This retinal degener anon has not been reported in breeds other than the Abyssinian/Somali and poses a significant health risk particularly in the Siamese breed group Alertness of the veterinary community and the present availability of commercial diagnostic testing could synergistically enable breeders to reduce the incidence of rdAc blindness in pure-bred cat populations Published by Elsevier Ltd
C1 [Menotti-Raymond, M.; Roelke, M. E.] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Pflueger, S.] Baystate Med Ctr, Springfield, MA 01199 USA.
[Narfstrom, K.] Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Columbia, MO 65211 USA.
RP Menotti-Raymond, M (reprint author), NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA.
FU National Cancer Institute National Institutes of Health [N01-CO-12400]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute National Institutes of Health under
contract N01-CO-12400 The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services nor does mention of trade names commercial products
or organizations imply endorsement by the US Government
NR 55
TC 11
Z9 11
U1 1
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1090-0233
J9 VET J
JI Vet. J.
PD OCT
PY 2010
VL 186
IS 1
BP 32
EP 38
DI 10.1016/j.tvjl.2009.08.010
PG 7
WC Veterinary Sciences
SC Veterinary Sciences
GA 686XL
UT WOS:000284732200008
PM 19747862
ER
PT J
AU Roberts, A
Lamirande, EW
Vogel, L
Baras, B
Goossens, G
Knott, I
Chen, J
Ward, JM
Vassilev, V
Subbarao, K
AF Roberts, Anjeanette
Lamirande, Elaine W.
Vogel, Leatrice
Baras, Benoit
Goossens, Genevieve
Knott, Isabelle
Chen, Jun
Ward, Jerrold M.
Vassilev, Ventzislav
Subbarao, Kanta
TI Immunogenicity and Protective Efficacy in Mice and Hamsters of a
beta-Propiolactone Inactivated Whole Virus SARS-CoV Vaccine
SO VIRAL IMMUNOLOGY
LA English
DT Article
ID ACUTE RESPIRATORY SYNDROME; GOLDEN-SYRIAN-HAMSTERS; T-CELL RESPONSES;
SYNDROME CORONAVIRUS; IMMUNE-RESPONSES; NEUTRALIZING ANTIBODY; INFLUENZA
VACCINE; ADJUVANT SYSTEMS; HEALTHY-ADULTS; FLOW-CYTOMETRY
AB The immunogenicity and efficacy of beta-propiolactone (BPL) inactivated whole virion SARS-CoV (WI-SARS) vaccine was evaluated in BALB/c mice and golden Syrian hamsters. The vaccine preparation was tested with or without adjuvants. Adjuvant Systems AS01(B) and AS03(A) were selected and tested for their capacity to elicit high humoral and cellular immune responses to WI-SARS vaccine. We evaluated the effect of vaccine dose and each adjuvant on immunogenicity and efficacy in mice, and the effect of vaccine dose with or without the AS01(B) adjuvant on the immunogenicity and efficacy in hamsters. Efficacy was evaluated by challenge with wild-type virus at early and late time points (4 and 18 wk post-vaccination). A single dose of vaccine with or without adjuvant was poorly immunogenic in mice; a second dose resulted in a significant boost in antibody levels, even in the absence of adjuvant. The use of adjuvants resulted in higher antibody titers, with the AS01(B)-adjuvanted vaccine being slightly more immunogenic than the AS03(A)-adjuvanted vaccine. Two doses of WI-SARS with and without Adjuvant Systems were highly efficacious in mice. In hamsters, two doses of WI-SARS with and without AS01(B) were immunogenic, and two doses of 2 mu g of WI-SARS with and without the adjuvant provided complete protection from early challenge. Although antibody titers had declined in all groups of vaccinated hamsters 18 wk after the second dose, the vaccinated hamsters were still partially protected from wild-type virus challenge. Vaccine with adjuvant provided better protection than non-adjuvanted WI-SARS vaccine at this later time point. Enhanced disease was not observed in the lungs or liver of hamsters following SARS-CoV challenge, regardless of the level of serum neutralizing antibodies.
C1 [Roberts, Anjeanette; Lamirande, Elaine W.; Vogel, Leatrice; Chen, Jun; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Ward, Jerrold M.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
[Baras, Benoit; Goossens, Genevieve; Knott, Isabelle; Vassilev, Ventzislav] GlaxoSmithKline Biol, Rixensart, Belgium.
[Roberts, Anjeanette; Ward, Jerrold M.] Univ Virginia, Charlottesville, VA USA.
[Roberts, Anjeanette; Ward, Jerrold M.] NIH, Immunopathol Lab, Bethesda, MD 20892 USA.
RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, 33 North Dr,MSC 3203, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
FU NIAID, NIH
FX We thank Jadon Jackson and the staff of the Comparative Medicine Branch,
NIAID, for excellent technical support for animal studies performed at
the NIH. This research was supported in part by the Intramural Research
Program of NIAID, NIH.
NR 35
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Z9 7
U1 0
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0882-8245
J9 VIRAL IMMUNOL
JI Viral Immunol.
PD OCT
PY 2010
VL 23
IS 5
BP 509
EP 519
DI 10.1089/vim.2010.0028
PG 11
WC Immunology; Virology
SC Immunology; Virology
GA 656UD
UT WOS:000282362300007
PM 20883165
ER
PT J
AU Cmarik, J
Ruscetti, S
AF Cmarik, Joan
Ruscetti, Sandra
TI Friend Spleen Focus-Forming Virus Activates the Tyrosine Kinase sf-Stk
and the Transcription Factor PU.1 to Cause a Multi-Stage Erythroleukemia
in Mice
SO VIRUSES-BASEL
LA English
DT Review
DE friend spleen focus-forming virus; leukemia; tyrosine kinases; sf-Stk;
Epo receptor; PU.1; signal transduction pathways
ID COMPLETE NUCLEOTIDE-SEQUENCE; ERYTHROID PROGENITOR CELLS; CELLULAR P53
GENE; ERYTHROPOIETIN RECEPTOR; MEMBRANE GLYCOPROTEIN;
PHOSPHATIDYLINOSITOL 3-KINASE; TRANSMEMBRANE DOMAIN; ENVELOPE PROTEIN;
LEUKEMIA VIRUS; TRUNCATED FORM
AB Hematological malignancies in humans typically involve two types of genetic changes: those that promote hematopoietic cell proliferation and survival (often the result of activation of tyrosine kinases) and those that impair hematopoietic cell differentiation (often the result of changes in transcription factors). The multi-stage erythroleukemia induced in mice by Friend spleen focus-forming virus (SFFV) is an excellent animal model for studying the molecular basis for both of these changes. Significant progress has been made in understanding the molecular basis for the multi-stage erythroleukemia induced by Friend SFFV. In the first stage of leukemia, the envelope protein encoded by SFFV interacts with and activates the erythropoietin (Epo) receptor and the receptor tyrosine kinase sf-Stk in erythroid cells, causing their Epo-independent proliferation, differentiation and survival. In the second stage, SFFV integration into the Sfpi1 locus activates the myeloid transcription factor PU.1, blocking erythroid cell differentiation, and in conjunction with the loss of p53 tumor suppressor activity, results in the outgrowth of malignant cells. In this review, we discuss the current level of understanding of how SFFV alters the growth and differentiation of erythroid cells and results in the development of erythroleukemia. Our knowledge of how SFFV causes erythroleukemia in mice may give us clues as to how the highly related human retrovirus XMRV causes malignancies in humans.
C1 [Cmarik, Joan; Ruscetti, Sandra] NCI, Lab Canc Prevent, Frederick, MD 21702 USA.
RP Ruscetti, S (reprint author), NCI, Lab Canc Prevent, Frederick, MD 21702 USA.
EM cmarikj@mail.nih.gov; ruscetts@mail.nih.gov
NR 94
TC 6
Z9 6
U1 1
U2 4
PU MDPI AG
PI BASEL
PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD OCT
PY 2010
VL 2
IS 10
BP 2235
EP 2257
DI 10.3390/v2102235
PG 23
WC Virology
SC Virology
GA 684VQ
UT WOS:000284581900006
PM 21994618
ER
PT J
AU Brister, JR
Bao, YM
Kuiken, C
Lefkowitz, EJ
Le Mercier, P
Leplae, R
Madupu, R
Scheuermann, RH
Schobel, S
Seto, D
Shrivastava, S
Sterk, P
Zeng, QD
Klimke, W
Tatusova, T
AF Brister, James Rodney
Bao, Yiming
Kuiken, Carla
Lefkowitz, Elliot J.
Le Mercier, Philippe
Leplae, Raphael
Madupu, Ramana
Scheuermann, Richard H.
Schobel, Seth
Seto, Donald
Shrivastava, Susmita
Sterk, Peter
Zeng, Qiandong
Klimke, William
Tatusova, Tatiana
TI Towards Viral Genome Annotation Standards, Report from the 2010 NCBI
Annotation Workshop
SO VIRUSES-BASEL
LA English
DT Editorial Material
DE virus; genome; annotation
ID PROTEIN-CODING GENES; BACTERIAL; SYSTEM; DATABASE; ZCURVE
AB Improvements in DNA sequencing technologies portend a new era in virology and could possibly lead to a giant leap in our understanding of viral evolution and ecology. Yet, as viral genome sequences begin to fill the world's biological databases, it is critically important to recognize that the scientific promise of this era is dependent on consistent and comprehensive genome annotation. With this in mind, the NCBI Genome Annotation Workshop recently hosted a study group tasked with developing sequence, function, and metadata annotation standards for viral genomes. This report describes the issues involved in viral genome annotation and reviews policy recommendations presented at the NCBI Annotation Workshop.
C1 [Brister, James Rodney; Bao, Yiming; Klimke, William; Tatusova, Tatiana] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Kuiken, Carla] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
[Lefkowitz, Elliot J.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35222 USA.
[Le Mercier, Philippe] Swiss Inst Bioinformat, CH-1211 Geneva 4, Switzerland.
[Leplae, Raphael] Univ Libre Brussels, Lab Bioinformat Genomes & Reseaux, B-1050 Brussels, Belgium.
[Madupu, Ramana; Schobel, Seth; Shrivastava, Susmita] J Craig Venter Inst, Rockville, MD 20850 USA.
[Scheuermann, Richard H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA.
[Scheuermann, Richard H.] Univ Texas SW Med Ctr Dallas, Div Biomed Informat, Dallas, TX 75390 USA.
[Seto, Donald] George Mason Univ, Dept Bioinformat & Computat Biol, Manassas, VA 20110 USA.
[Sterk, Peter] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
[Zeng, Qiandong] Broad Inst, Cambridge, MA 02141 USA.
RP Brister, JR (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM jamesbr@ncbi.nlm.nih.gov; bao@ncbi.nlm.nih.gov; kuiken@lanl.gov;
elliotl@uab.edu; philippe.lemercier@isb-sib.ch; raphael@bigre.ulb.ac.be;
rmadupu@jcvi.org; richard.scheuermann@utsouthwestern.edu;
sschobel@jcvi.org; dseto@gmu.edu; sshrivastava@jcvi.org;
ps8@sanger.ac.uk; qzeng@broadinstitute.org; klimke@ncbi.nlm.nih.gov;
tatiana@ncbi.nlm.nih.gov
OI Lefkowitz, Elliot/0000-0002-4748-4925; Sterk, Peter/0000-0003-1668-7778;
Scheuermann, Richard/0000-0003-1355-892X
NR 25
TC 11
Z9 11
U1 0
U2 6
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD OCT
PY 2010
VL 2
IS 10
BP 2258
EP 2268
DI 10.3390/v2102258
PG 11
WC Virology
SC Virology
GA 684VQ
UT WOS:000284581900007
PM 21994619
ER
PT J
AU Song, SH
Kim, A
Ragoczy, T
Bender, MA
Groudine, M
Dean, A
AF Song, Sang-Hyun
Kim, AeRi
Ragoczy, Tobias
Bender, M. A.
Groudine, Mark
Dean, Ann
TI Multiple functions of Ldb1 required for beta-globin activation during
erythroid differentiation
SO BLOOD
LA English
DT Article
ID LOCUS-CONTROL REGION; RNA-POLYMERASE-II; EMBRYONIC STEM-CELLS; CHROMATIN
DOMAIN; IN-VIVO; HYPERSENSITIVE SITES; DOWNSTREAM PROMOTER;
ENHANCER-BLOCKING; GENE-EXPRESSION; TRANSCRIPTION
AB Ldb1 and erythroid partners SCL, GATA-1, and LMO2 form a complex that is required to establish spatial proximity between the beta-globin locus control region and gene and for transcription activation during erythroid differentiation. Here we show that Ldb1 controls gene expression at multiple levels. Ldb1 stabilizes its erythroid complex partners on beta-globin chromatin, even though it is not one of the DNA-binding components. In addition, Ldb1 is necessary for enrichment of key transcriptional components in the locus, including P-TEFb, which phosphorylates Ser2 of the RNA polymerase C-terminal domain for efficient elongation. Furthermore, reduction of Ldb1 results in the inability of the locus to migrate away from the nuclear periphery, which is necessary to achieve robust transcription of beta-globin in nuclear transcription factories. Ldb1 contributes these critical functions at both embryonic and adult stages of globin gene expression. These results implicate Ldb1 as a factor that facilitates nuclear relocation for transcription activation. (Blood. 2010;116(13):2356-2364)
C1 [Song, Sang-Hyun; Dean, Ann] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
[Kim, AeRi] Pusan Natl Univ, Coll Nat Sci, Pusan 609735, South Korea.
[Ragoczy, Tobias; Groudine, Mark] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA.
[Bender, M. A.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
RP Dean, A (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 50,Rm 3154,50 S Dr,MSC 8028, Bethesda, MD 20892 USA.
EM anndean@helix.nih.gov
FU National Diabetes and Digestive and Kidney Diseases, National Institutes
of Health; National Institutes of Health [DK44746, HL65440]
FX This work was supported by the Intra-mural program of the National
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health (A.D.) and extramural National Institutes of Health (grants
DK44746 and HL65440; M.G.).
NR 48
TC 47
Z9 47
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 SEP 30
PY 2010
VL 116
IS 13
BP 2356
EP 2364
DI 10.1182/blood-2010-03-272252
PG 9
WC Hematology
SC Hematology
GA 656VR
UT WOS:000282369700024
PM 20570862
ER
PT J
AU Buonanno, A
AF Buonanno, Andres
TI The neuregulin signaling pathway and schizophrenia: From genes to
synapses and neural circuits
SO BRAIN RESEARCH BULLETIN
LA English
DT Review
DE ErbB4; Neuregulin; GABAergic interneuron; Schizophrenia; Bipolar
depression; Hypoglutamatergic; Gamma oscillations; LTP; Depotentiation
ID LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; PARVALBUMIN-POSITIVE
INTERNEURONS; NMDA RECEPTOR HYPOFUNCTION; EARLY-ONSET PSYCHOSIS;
DOPAMINE D1 RECEPTOR; HIPPOCAMPUS IN-VITRO; SIZED SPINY NEURONS; ADULT
HUMAN BRAIN; TYROSINE KINASE
AB Numerous genetic linkage and association studies implicate members of the Neuregulin-ErbB receptor (NRG-ErbB) signaling pathway as schizophrenia "at risk" genes An emphasis of this review is to propose plausible neurobiological mechanisms, regulated by the Neuregulin-ErbB signaling network, that may be altered in schizophrenia and contribute to its etiology To this end, the distinct neurotransmitter pathways, neuronal subtypes and neural network systems altered in schizophrenia are initially discussed. Next, the review focuses on the possible significance of genetic studies associating NRG1 and ErbB4 with schizophrenia, in light of the functional role of this signaling pathway in regulating glutamatergic, GABAergic and dopaminergic neurotransmission, as well as modulating synaptic plasticity and gamma oscillations The Importance of restricted ErbB4 receptor expression in GABAergic interneurons is emphasized, particularly their expression at glutamatergic synapses of parvalbumin-positive fast-spiking interneurons where modulation of inhibitory drive could account for the dramatic effects of NRG-ErbB signaling on gamma oscillations and pyramidal neuron output A case is made for reasons that the NRG-ErbB signaling pathway constitutes a "biologically plausible" system for understanding the pathogenic mechanisms that may underlie the complex array of positive, negative and cognitive deficits associated with schizophrenia during development. Published by Elsevier Inc
C1 Eunice Kennedy Shriver NICHD, NIH, Mol Neurobiol Sect, Program Dev Neurobiol, Bethesda, MD 20892 USA.
RP Buonanno, A (reprint author), Eunice Kennedy Shriver NICHD, NIH, Mol Neurobiol Sect, Program Dev Neurobiol, 35 Lincoln Dr, Bethesda, MD 20892 USA.
FU Eunice Shriver Kennedy National Institute of Child Health and Human
Development
FX The author thanks Drs. Irina Karavanova and Detlef Vullhorst for
assistance with figures, and Drs. Vullhorst and Neddens for critical
reading of the manuscript. The author appreciates the continued
financial support from the Eunice Shriver Kennedy National Institute of
Child Health and Human Development Intramural Research Program.
NR 164
TC 67
Z9 70
U1 5
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0361-9230
EI 1873-2747
J9 BRAIN RES BULL
JI Brain Res. Bull.
PD SEP 30
PY 2010
VL 83
IS 3-4
SI SI
BP 122
EP 131
DI 10.1016/j.brainresbull.2010.07.012
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 665MJ
UT WOS:000283039300006
PM 20688137
ER
PT J
AU Shew, WL
Bellay, T
Plenz, D
AF Shew, Woodrow L.
Bellay, Timothy
Plenz, Dietmar
TI Simultaneous multi-electrode array recording and two-photon calcium
imaging of neural activity
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Electrophysiology; Two-photon imaging; Multi-electrode array; Calcium
imaging; Spontaneous activity; Local field potential; Acute slice;
Cortex; Rat
ID IN-VIVO; POTENTIALS; MICROSCOPY; ELECTRODES; CORTEX
AB A complete understanding of how brain circuits function will require measurement techniques which monitor large-scale network activity simultaneously with the activity of local neural populations at a small scale. Here we present a useful step towards achieving this aim: simultaneous two-photon calcium imaging and multi-electrode array (MEA) recordings. The primary challenge of this method is removing an electrical artifact from the MEA signals that is caused by the imaging laser. Here we show that artifact removal can be achieved with a simple filtering scheme. As a demonstration of this technique we compare large-scale local field potential signals to single-neuron activity in a small-scale group of cells recorded from rat acute slices under two conditions: suppressed vs. intact inhibitory interactions between neurons. Published by Elsevier B.V.
C1 [Shew, Woodrow L.; Bellay, Timothy; Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
RP Shew, WL (reprint author), NIMH, Sect Crit Brain Dynam, Porter Neurosci Res Ctr, Rm 3A-1003,35 Convent Dr, Bethesda, MD 20892 USA.
EM sheww@mail.nih.gov
OI Shew, Woodrow/0000-0003-0679-1766
FU National Institute of Mental Health
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health. The authors declare no competing
financial interests.
NR 13
TC 6
Z9 6
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD SEP 30
PY 2010
VL 192
IS 1
BP 75
EP 82
DI 10.1016/j.jneumeth.2010.07.023
PG 8
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 671CM
UT WOS:000283477500009
PM 20659501
ER
PT J
AU Crea, F
Hurt, EM
Farrar, WL
AF Crea, Francesco
Hurt, Elaine M.
Farrar, William L.
TI Clinical significance of Polycomb gene expression in brain tumors
SO MOLECULAR CANCER
LA English
DT Article
ID STEM-CELLS; INITIATING CELLS; CANCER; EPIDEMIOLOGY; RENEWAL; GLIOMAS;
BMI1
AB Polycomb group (PcG) proteins are crucial for neural cancer stem cell (NCSC) self-renewal. However, the relative expression levels of PcG genes in different subtypes of brain tumors, their prognostic role and their effects on cellular pathways have not been investigated. For this purpose, we queried the Oncomine database and found that 4 PcG genes (EZH2, RBBP7, SUZ12, YY1) are specifically expressed in brain tumors. EZH2 expression increases with tumor grade in adult and pediatric brain tumors, and is a poor prognostic factor. In glioblastoma, EZH2 inhibits differentiation, and activates cancer-, cell cycle- and cellular movement-related genes. In keeping with previously published data, our results suggest that EZH2 is both a prognostic factor and a promising therapy target in brain tumors.
C1 [Crea, Francesco; Hurt, Elaine M.; Farrar, William L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21701 USA.
[Crea, Francesco] Scuola Super StAnna, Pisa, Italy.
RP Farrar, WL (reprint author), NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21701 USA.
EM farrar@mail.ncifcrf.gov
RI Crea, Francesco /I-8383-2015;
OI Crea, Francesco/0000-0002-4903-2973
FU National Cancer Institute; National Institutes of Health NIH
[N01-CO-12400]; Center for Cancer Research
FX This publication has been funded in part with Federal funds from the
National Cancer Institute, National Institutes of Health, under contract
No. N01-CO-12400. This research was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the US Government.
NR 23
TC 42
Z9 46
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD SEP 30
PY 2010
VL 9
AR 265
DI 10.1186/1476-4598-9-265
PG 6
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 668II
UT WOS:000283261400001
PM 20920292
ER
PT J
AU Yu, AL
Gilman, AL
Ozkaynak, MF
London, WB
Kreissman, SG
Chen, HX
Smith, M
Anderson, B
Villablanca, JG
Matthay, KK
Shimada, H
Grupp, SA
Seeger, R
Reynolds, CP
Buxton, A
Reisfeld, RA
Gillies, SD
Cohn, SL
Maris, JM
Sondel, PM
AF Yu, Alice L.
Gilman, Andrew L.
Ozkaynak, M. Fevzi
London, Wendy B.
Kreissman, Susan G.
Chen, Helen X.
Smith, Malcolm
Anderson, Barry
Villablanca, Judith G.
Matthay, Katherine K.
Shimada, Hiro
Grupp, Stephan A.
Seeger, Robert
Reynolds, C. Patrick
Buxton, Allen
Reisfeld, Ralph A.
Gillies, Steven D.
Cohn, Susan L.
Maris, John M.
Sondel, Paul M.
CA Children's Oncology Grp
TI Anti-GD2 Antibody with GM-CSF, Interleukin-2, and Isotretinoin for
Neuroblastoma.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CHILDRENS ONCOLOGY GROUP; HIGH-RISK NEUROBLASTOMA; ANTIGANGLIOSIDE GD2
ANTIBODY; BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR;
C-RECEPTOR POLYMORPHISMS; PHASE-I; RECOMBINANT INTERLEUKIN-2; REFRACTORY
NEUROBLASTOMA; 13-CIS-RETINOIC ACID
AB Background: Preclinical and preliminary clinical data indicate that ch14.18, a monoclonal antibody against the tumor-associated disialoganglioside GD2, has activity against neuroblastoma and that such activity is enhanced when ch14.18 is combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2. We conducted a study to determine whether adding ch14.18, GM-CSF, and interleukin-2 to standard isotretinoin therapy after intensive multimodal therapy would improve outcomes in high-risk neuroblastoma.
Methods: Patients with high-risk neuroblastoma who had a response to induction therapy and stem-cell transplantation were randomly assigned, in a 1:1 ratio, to receive standard therapy (six cycles of isotretinoin) or immunotherapy (six cycles of isotretinoin and five concomitant cycles of ch14.18 in combination with alternating GM-csf and interleukin-2). Event-free survival and overall survival were compared between the immunotherapy group and the standard-therapy group, on an intention-to-treat basis.
Results: A total of 226 eligible patients were randomly assigned to a treatment group. In the immunotherapy group, a total of 52% of patients had pain of grade 3, 4, or 5, and 23% and 25% of patients had capillary leak syndrome and hypersensitivity reactions, respectively. With 61% of the number of expected events observed, the study met the criteria for early stopping owing to efficacy. The median duration of follow-up was 2.1 years. Immunotherapy was superior to standard therapy with regard to rates of event-free survival (66+/-5% vs. 46+/-5% at 2 years, P=0.01) and overall survival (86+/-4% vs. 75+/-5% at 2 years, P=0.02 without adjustment for interim analyses).
Conclusions: Immunotherapy with ch14.18, GM-CSF, and interleukin-2 was associated with a significantly improved outcome as compared with standard therapy in patients with high-risk neuroblastoma. (Funded by the National Institutes of Health and the Food and Drug Administration; ClinicalTrials.gov number, NCT00026312.)
N Engl J Med 2010;363:1324-34.
C1 [Yu, Alice L.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Yu, Alice L.] Moores Canc Ctr, San Diego, CA 92103 USA.
[Yu, Alice L.] Acad Sinica, Genom Res Ctr, Taipei, Taiwan.
[Gilman, Andrew L.] Levine Childrens Hosp, Charlotte, NC USA.
[Kreissman, Susan G.] Duke Univ, Med Ctr, Durham, NC USA.
[Ozkaynak, M. Fevzi] New York Med Coll, Valhalla, NY 10595 USA.
[London, Wendy B.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
[London, Wendy B.] Childrens Oncol Grp Stat & Data Ctr, Boston, MA USA.
[Chen, Helen X.; Smith, Malcolm; Anderson, Barry] NCI, Bethesda, MD 20892 USA.
[Villablanca, Judith G.; Shimada, Hiro; Seeger, Robert] Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA USA.
[Matthay, Katherine K.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Matthay, Katherine K.] Univ Calif San Francisco, Childrens Hosp, San Francisco, CA 94143 USA.
[Grupp, Stephan A.; Maris, John M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Grupp, Stephan A.; Maris, John M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Sch Med, Lubbock, TX 79430 USA.
[Buxton, Allen] Childrens Oncol Grp Stat & Data Ctr, Arcadia, CA USA.
[Reisfeld, Ralph A.] Scripps Res Inst, La Jolla, CA 92037 USA.
[Gillies, Steven D.] Provenance Biopharmaceut, Waltham, MA USA.
[Cohn, Susan L.] Univ Chicago, Chicago, IL 60637 USA.
[Sondel, Paul M.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USA.
RP Yu, AL (reprint author), Univ Calif San Diego, 200 W Arbor Dr, San Diego, CA 92103 USA.
EM aliceyu@ucsd.edu
OI Cohn, Susan/0000-0001-5749-7650
FU National Institutes of Health [U10-CA98543, U10-CA98413, U10-CA29139];
Food and Drug Administration [FD-R-002319]
FX Supported by grants from the National Institutes of Health (U10-CA98543,
U10-CA98413, and U10-CA29139) and the Food and Drug Administration
(FD-R-002319).
NR 40
TC 454
Z9 465
U1 1
U2 39
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 SEP 30
PY 2010
VL 363
IS 14
BP 1324
EP 1334
DI 10.1056/NEJMoa0911123
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 655TD
UT WOS:000282271500006
PM 20879881
ER
PT J
AU Rivera, J
Colbert, RA
AF Rivera, Juan
Colbert, Robert A.
TI Healing the Syk through Kinase Inhibitors.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID TYROSINE KINASE; RHEUMATOID-ARTHRITIS; THERAPY
C1 [Rivera, Juan; Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Rivera, J (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA.
NR 11
TC 13
Z9 14
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD SEP 30
PY 2010
VL 363
IS 14
BP 1362
EP 1364
DI 10.1056/NEJMe1006527
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 655TD
UT WOS:000282271500013
PM 20879886
ER
PT J
AU Tokar, EJ
Diwan, BA
Waalkes, MP
AF Tokar, Erik J.
Diwan, Bhalchandra A.
Waalkes, Michael P.
TI Early life inorganic lead exposure induces testicular teratoma and renal
and urinary bladder preneoplasia in adult metallothionein-knockout mice
but not in wild type mice
SO TOXICOLOGY
LA English
DT Article
DE Lead; Carcinogenesis; Mice; Metallothionein; Testes
ID INCLUSION-BODY FORMATION; POSTNATAL DIETHYLSTILBESTROL; ARSENIC
EXPOSURE; TRANSGENIC MICE; MESSENGER-RNA; HUMAN-LIVER; II GENES;
CARCINOGENESIS; SENSITIVITY; CADMIUM
AB Inorganic lead compounds are carcinogenic in animals and have carcinogenic potential in humans. In mice, lead (Pb) is a transplacental carcinogen in the kidney. Metallothionein (MT) is a metal-binding protein that can reduce the toxicity of various metals, including Pb, either by direct sequestration or as an antioxidant for metals that generate reactive oxygen species. Although MT appears to reduce Pb carcinogenicity in adult mice it is unknown how MT deficiency may affect Pb carcinogenicity from early life exposure. Thus, groups (n = 10) of pregnant MT-I/II double knockout (MT-null) or 129/SVJ MT wild type (WT) mice were exposed to Pb acetate in the drinking water (0, 2000, 4000 ppm Pb) from gestation day 8 through birth and during lactation. Maternal drinking water Pb exposure continued to wean at 4 weeks of age and the male offspring were then directly exposed to Pb until 8 weeks of age and observed until 2 years old. High dose (4000 ppm) but not low dose (2000 ppm) Pb reduced survival in the latter part of the study in both MT-null and WT mice. In MT-null mice, but not WT, early life Pb exposure caused a dose-related increase in testicular teratomas, to a maximum incidence of 28% compared to control (4%). Pb-induced renal cystic hyperplasia, considered preneoplastic, was a prominent occurrence in MT-null mice but nearly absent in WT mice. Pb dose-related increases in renal cystic hyperplasia occurred in adult MT-null with early life exposure with maximal incidence of 52%. Pb-treated MT-null mice also showed dose-related increases in urinary bladder hyperplasia with occasional papilloma that were absent in WT mice. Thus, MT deficiency made mice more sensitive to early life Pb exposure with regard to testes tumors, and renal and urinary bladder preneoplastic lesions. Published by Elsevier Ireland Ltd.
C1 [Tokar, Erik J.; Waalkes, Michael P.] NIEHS, NTP, Res Triangle Pk, NC 27709 USA.
[Tokar, Erik J.; Waalkes, Michael P.] NCI, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis, NIEHS, Res Triangle Pk, NC 27709 USA.
[Diwan, Bhalchandra A.] NCI, Basic Sci Program, SAIC Frederick, Frederick, MD 21702 USA.
RP Waalkes, MP (reprint author), NIEHS, NTP, 111 Alexander Dr,POB 12233,MD F0-09, Res Triangle Pk, NC 27709 USA.
EM waalkes@niehs.nih.gov
FU National Institute of Environmental Health Sciences (NIEHS); NIH,
National Cancer Institute, Center for Cancer Research; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]
FX The authors wish to thank Drs. L. Keefer, W. Qu, and Y. Sun for critical
evaluation of this manuscript, Dr. J. Liu for assistance with the
MT-null mice, and D. Logsdon and the Pathology and Histotechnology
Laboratory of SAIC-Frederick for expert technical assistance. This
research was supported in part by the National Toxicology Program,
National Institute of Environmental Health Sciences (NIEHS) and by the
Intramural Research program of the NIH, National Cancer Institute,
Center for Cancer Research. This article may be the work product of an
employee or group of employees of the NIEHS, National Institutes of
Health (NIEL), however, the statements contained herein do not
necessarily represent the statements, opinions or conclusions of the
NIEHS, NIH or the U.S. Government. This project was also supported 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 the 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 38
TC 14
Z9 16
U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0300-483X
J9 TOXICOLOGY
JI Toxicology
PD SEP 30
PY 2010
VL 276
IS 1
BP 5
EP 10
DI 10.1016/j.tox.2010.06.006
PG 6
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 647NI
UT WOS:000281624800002
PM 20600549
ER
PT J
AU Palkar, PS
Anderson, CR
Ferry, CH
Gonzalez, FJ
Peters, JM
AF Palkar, Prajakta S.
Anderson, Cherie R.
Ferry, Christina H.
Gonzalez, Frank J.
Peters, Jeffrey M.
TI Effect of prenatal peroxisome proliferator-activated receptor alpha
(PPAR alpha) agonism on postnatal development
SO TOXICOLOGY
LA English
DT Article
DE Peroxisome proliferator-activated receptor-alpha; Postnatal development;
Nuclear receptor; Prenatal exposure
ID PERFLUOROOCTANOIC ACID; LACTATING RATS; DIFFERENTIAL EXPRESSION;
MORPHOMETRIC-ANALYSIS; TISSUE DISTRIBUTION; KIDNEY PEROXISOMES; LIVER;
MOUSE; EXPOSURE; PUPS
AB Recent work indicates that PPAR alpha is required for perfluorooctanoic acid (PFOA)-induced postnatal lethality resulting from prenatal exposure. The present study tested the hypothesis that relatively modest activation of PPAR alpha during prenatal development will cause postnatal lethality, similar to that observed with PFOA, a relatively low affinity PPAR alpha agonist. Female wild-type and Ppar alpha-null mice were mated overnight with males of the same genotype. The presence of a copulatory plug on the morning after mating was indicative of pregnancy and considered gestation day (GD) 0. Plugged female mice were fed either a control diet or one containing clofibrate (0.5%) or Wy-14,643 (0.005%) until GD18 or until parturition. Mice were examined on GD18 or on postnatal day (PND) 20 following the prenatal exposure period. Dietary administration of clofibrate or Wy-14,643 did not affect maternal weight or weight gain, the average number of implantations, the percentage of litter loss, the average number of live/dead fetuses, average crown-rump length, or the average fetal weight on GD18 in either genotype. An increase in relative maternal liver weight and elevated expression of PPAR alpha target genes in maternal and fetal livers on GD18 were observed, indicative of PPAR alpha-dependent changes in both the maternal and fetal compartments. However, no defects in postnatal development were observed by either clofibrate or Wy-14,643 in either genotype by PND20. These results demonstrate that relatively low level activation of PPAR alpha by clofibrate or Wy-14,643 during prenatal development does not cause postnatal lethality. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Palkar, Prajakta S.; Anderson, Cherie R.; Ferry, Christina H.; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Palkar, Prajakta S.; Anderson, Cherie R.; Ferry, Christina H.; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, 312 Life Sci Bldg, University Pk, PA 16802 USA.
EM jmp21@psu.edu
RI Peters, Jeffrey/D-8847-2011
NR 40
TC 8
Z9 8
U1 0
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0300-483X
J9 TOXICOLOGY
JI Toxicology
PD SEP 30
PY 2010
VL 276
IS 1
BP 79
EP 84
DI 10.1016/j.tox.2010.07.008
PG 6
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 647NI
UT WOS:000281624800012
PM 20637823
ER
PT J
AU Easley, R
Carpio, L
Dannenberg, L
Choi, S
Alani, D
Van Duyne, R
Guendel, I
Klase, Z
Agbottah, E
Kehn-Hall, K
Kashanchi, F
AF Easley, Rebecca
Carpio, Lawrence
Dannenberg, Luke
Choi, Soyun
Alani, Dowser
Van Duyne, Rachel
Guendel, Irene
Klase, Zachary
Agbottah, Emmanuel
Kehn-Hall, Kylene
Kashanchi, Fatah
TI Transcription through the HIV-1 nucleosomes: Effects of the PBAF complex
in Tat activated transcription
SO VIROLOGY
LA English
DT Article
DE HW-1; Chromatin; BAF; PBAF; FACT; Transcription; Remodel
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHROMATIN-REMODELING COMPLEX; LONG
TERMINAL REPEAT; RNA-POLYMERASE-II; ELONGATION-FACTORS; IN-VIVO;
SACCHAROMYCES-CEREVISIAE; CHD1 INTERACTS; N-COR; PROTEIN
AB The SWI/SNF complex remodels nucleosomes, allowing RNA Polymerase II access to the HIV-1 proviral DNA. It has not been determined which SWI/SNF complex (BAF or PBAF) remodels nucleosomes at the transcription start site. These complexes differ in only three subunits and determining which subunit(s) is required could explain the regulation of Tat activated transcription. We show that PBAF is required for chromatin remodeling at the nuc-1 start site and transcriptional elongation. We find that Baf200 is required to ensure activation at the LTR level and for viral production. Interestingly, the BAF complex was observed on the LTR whereas PBAF was present on both LTR and Env regions. We found that Tat activated transcription facilitates removal of histones H2A and H2B at the LTR, and that the FACT complex may be responsible for their removal. Finally, the BAF complex may play an important role in regulating splicing of the HIV-1 genome. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Kehn-Hall, Kylene; Kashanchi, Fatah] George Mason Univ, Natl Ctr Biodef & Infect Dis, Dept Mol & Microbiol, Manassas, VA 20110 USA.
[Klase, Zachary] NIAID, NIH, Bethesda, MD 20892 USA.
RP Kashanchi, F (reprint author), George Mason Univ, Natl Ctr Biodef & Infect Dis, Dept Mol & Microbiol, Discovery Hall,Room 306,10900 Univ Blvd,MS 1H8, Manassas, VA 20110 USA.
EM rleasl@gmail.com; lawrence.carpio@gmail.com; luke.dannenberg@roche.com;
choysters@gmail.com; dalani@gmu.edu; rachel.vanduyne@gmail.com;
mtmixg@gwumc.edu; klaseza@niaid.nih.gov; bcmeta@gwumc.edu;
kkehnhal@gmu.edu; fkashanc@gmu.edu
RI Kehn-Hall, Kylene/I-5752-2013
FU George Washington University [AI043894, AI074410]
FX This work was supported by grants from the George Washington University
REF funds to FK and NIH grant AI043894 and AI074410.
NR 59
TC 15
Z9 16
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 0042-6822
J9 VIROLOGY
JI Virology
PD SEP 30
PY 2010
VL 405
IS 2
BP 322
EP 333
DI 10.1016/j.virol.2010.06.009
PG 12
WC Virology
SC Virology
GA 641MJ
UT WOS:000281130500007
PM 20599239
ER
PT J
AU Wu, TY
Datta, SAK
Mitra, M
Gorelick, RJ
Rein, A
Levin, JG
AF Wu, Tiyun
Datta, Siddhartha A. K.
Mitra, Mithun
Gorelick, Robert J.
Rein, Alan
Levin, Judith G.
TI Fundamental differences between the nucleic acid chaperone activities of
HIV-1 nucleocapsid protein and Gag or Gag-derived proteins: Biological
implications
SO VIROLOGY
LA English
DT Article
DE Nucleic acid chaperone; HIV-1; Gag; Nucleocapsid protein; Capsid
protein; Reverse transcription; Nucleic acid-driven multimerization;
Retrovirus; Minus-strand transfer
ID IMMUNODEFICIENCY-VIRUS TYPE-1; STRONG-STOP DNA; ZINC-FINGER STRUCTURES;
REVERSE TRANSCRIPTION; IN-VITRO; STRAND TRANSFER; GENOMIC RNA; CAPSID
PROTEIN; VIRAL REPLICATION; MATRIX DOMAIN
AB The HIV-1 Gag polyprotein precursor has multiple domains including nucleocapsid (NC). Although mature NC and NC embedded in Gag are nucleic acid chaperones (proteins that remodel nucleic acid structure), few studies include detailed analysis of the chaperone activity of partially processed Gag proteins and comparison with NC and Gag. Here we address this issue by using a reconstituted minus-strand transfer system. NC and NC-containing Gag proteins exhibited annealing and duplex destabilizing activities required for strand transfer. Surprisingly, unlike NC, with increasing concentrations. Gag proteins drastically inhibited the DNA elongation step. This result is consistent with "nucleic acid-driven multimerization" of Gag and the reported slow dissociation of Gag from bound nucleic acid, which prevent reverse transcriptase from traversing the template ("roadblock" mechanism). Our findings illustrate one reason why NC (and not Gag) has evolved as a critical cofactor in reverse transcription, a paradigm that might also extend to other retrovirus systems. Published by Elsevier Inc.
C1 [Wu, Tiyun; Mitra, Mithun; Levin, Judith G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Datta, Siddhartha A. K.; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Gorelick, Robert J.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Levin, JG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, Program Genom Differentiat, NIH, Bldg 6B,Room 216,6 Ctr Dr, Bethesda, MD 20892 USA.
EM levinju@mail.nih.gov
RI Mitra, Mithun/A-2133-2015;
OI Datta, Siddhartha/0000-0002-4098-7490
FU NIH; National Cancer Institute, Center for Cancer Research; National
Cancer Institute [N01-CO-12400, HHSN261200800001E]
FX We thank Christopher Aiken for the Gag cleavage mutants, David Ott for
the HIV-1 PR mutant PRD25G, Malcolm Martin for the pNL4-3
clone, which was obtained from the NIH AIDS Research and Reference
Reagent Program, and Hans Luecke, who generously allowed us to use his
Spectromax M5 instrument for the Kd determinations. We are
also indebted to Christopher Jones, Ioulia Rouzina, and Karin
Musier-Forsyth for valuable discussion and for sharing unpublished data.
This work was supported by the Intramural Research Program of the NIH
(Eunice Kennedy Shriver National Institute of Child Health and Human
Development [J.G.L.] and the National Cancer Institute, Center for
Cancer Research [A.R.]) and was funded in part with federal funds from
the National Cancer Institute under contract numbers N01-CO-12400 and
HHSN261200800001E (R.J.G.). 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 79
TC 30
Z9 30
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD SEP 30
PY 2010
VL 405
IS 2
BP 556
EP 567
DI 10.1016/j.virol.2010.06.042
PG 12
WC Virology
SC Virology
GA 641MJ
UT WOS:000281130500032
PM 20655566
ER
PT J
AU Yassine, HM
Khatri, M
Lee, CW
Saif, YM
AF Yassine, Hadi M.
Khatri, Mahesh
Lee, Chang W.
Saif, Yehia M.
TI Characterization of an H3N2 triple reassortant influenza virus with a
mutation at the receptor binding domain (D190A) that occurred upon virus
transmission from turkeys to pigs
SO VIROLOGY JOURNAL
LA English
DT Article
ID A VIRUSES; INTERSPECIES TRANSMISSION; AVIAN INFLUENZA; ACID CHANGE;
HEMAGGLUTININ; SPECIFICITY; CELLS; RECOGNITION; GENERATION; MAMMALS
AB The hemagglutinin (HA) protein of influenza virus mediates essential viral functions including the binding to host receptor and virus entry. It also has the antigenic sites required for virus neutralization by host antibodies. Here, we characterized an H3N2 triple reassortant (TR) influenza virus (A/turkey/Ohio/313053/04) with a mutation at the receptor binding domain (Asp190Ala) that occurred upon virus transmission from turkeys to pigs in an experimental infection study. The mutant virus replicated less efficiently than the parental virus in human, pig and turkey primary tracheal/bronchial epithelial cells, with more than 3-log10 difference in virus titer at 72 hours post infection. In addition, the mutant virus demonstrated lower binding efficiency to plasma membrane preparations from all three cell types compared to the parental virus. Antisera raised against the parental virus reacted equally to both homologous and heterlogous viruses, however, antisera raised against the mutant virus showed 4-8 folds lower reactivity to the parental virus.
C1 [Yassine, Hadi M.; Khatri, Mahesh; Lee, Chang W.; Saif, Yehia M.] Ohio State Univ, Food Anim Hlth Res Program, Ohio Agr Res & Dev Ctr, Wooster, OH 44691 USA.
[Yassine, Hadi M.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Saif, YM (reprint author), Ohio State Univ, Food Anim Hlth Res Program, Ohio Agr Res & Dev Ctr, 1680 Madison Ave, Wooster, OH 44691 USA.
EM saif.1@osu.edu
FU United States Department of Agriculture,; Ohio Agricultural Research and
Development Center, The Ohio State University; CSREES
FX This work was partially supported by funds from the United States
Department of Agriculture, CSREES AI-CAP project, and the Ohio
Agricultural Research and Development Center, The Ohio State University.
NR 34
TC 6
Z9 6
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-422X
J9 VIROL J
JI Virol. J.
PD SEP 30
PY 2010
VL 7
AR 258
DI 10.1186/1743-422X-7-258
PG 7
WC Virology
SC Virology
GA 670LN
UT WOS:000283423300001
PM 20920297
ER
PT J
AU Gonzalez-Islas, C
Chub, N
Garcia-Bereguiain, MA
Wenner, P
AF Gonzalez-Islas, Carlos
Chub, Nikolai
Garcia-Bereguiain, Miguel Angel
Wenner, Peter
TI GABAergic Synaptic Scaling in Embryonic Motoneurons Is Mediated by a
Shift in the Chloride Reversal Potential
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SPONTANEOUS NETWORK ACTIVITY; NEOCORTICAL NEURONS; QUANTAL AMPLITUDE;
CHICK-EMBRYO; PLASTICITY; SYNAPSES; GABA; COTRANSPORTERS; AVAILABILITY;
TRANSMISSION
AB Homeostatic synaptic plasticity ensures that networks maintain specific levels of activity by regulating synaptic strength in a compensatory manner. When spontaneous network activity was blocked in vivo in the embryonic spinal cord, compensatory increases in excitatory GABAergic synaptic inputs were observed. This homeostatic synaptic strengthening was observed as an increase in the amplitude of GABAergic miniature postsynaptic currents. We find that this process is mediated by an increase in chloride accumulation, which produces a depolarizing shift in the GABAergic reversal potential (E(GABA)). The findings demonstrate a previously unrecognized mechanism underlying homeostatic synaptic scaling. Similar shifts in E(GABA) have been described following various forms of neuronal injury, introducing the possibility that these shifts in E(GABA) represent a homeostatic response.
C1 [Gonzalez-Islas, Carlos; Garcia-Bereguiain, Miguel Angel; Wenner, Peter] Emory Univ, Sch Med, Dept Physiol, Atlanta, GA 30322 USA.
[Chub, Nikolai] Natl Inst Neurol Disorders & Stroke, Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Wenner, P (reprint author), Emory Univ, Sch Med, Dept Physiol, Room 601,Whitehead Bldg, Atlanta, GA 30322 USA.
EM pwenner@emory.edu
OI Wenner, Peter/0000-0002-7072-2194
FU National Institute of Neurological Disorders and Stroke [NS046510];
National Science Foundation [0616097]
FX This research was supported by National Institute of Neurological
Disorders and Stroke Grant NS046510 and National Science Foundation
Grant 0616097 to P.W. and by the Intramural Program of the National
Institutes of Neurological Disorders and Stroke. We thank Drs. Michael
O'Donovan and Mark Rich for their comments on the manuscript, and Dr.
Porfirio Nava for assistance with Western blots.
NR 30
TC 15
Z9 15
U1 1
U2 1
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 29
PY 2010
VL 30
IS 39
BP 13016
EP 13020
DI 10.1523/JNEUROSCI.1659-10.2010
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 659MY
UT WOS:000282571800012
PM 20881119
ER
PT J
AU Kikuchi, Y
Horwitz, B
Mishkin, M
AF Kikuchi, Yukiko
Horwitz, Barry
Mishkin, Mortimer
TI Hierarchical Auditory Processing Directed Rostrally along the Monkey's
Supratemporal Plane
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID VENTROLATERAL PREFRONTAL CORTEX; SUPERIOR TEMPORAL REGION;
RHESUS-MONKEY; MACAQUE MONKEYS; CORTICAL CONNECTIONS; BELT CORTEX;
FUNCTIONAL SPECIALIZATION; TONOTOPIC ORGANIZATION; RESPONSE PROPERTIES;
MARMOSET MONKEYS
AB Connectional anatomical evidence suggests that the auditory core, containing the tonotopic areas A1, R, and RT, constitutes the first stage of auditory cortical processing, with feedforward projections from core outward, first to the surrounding auditory belt and then to the parabelt. Connectional evidence also raises the possibility that the core itself is serially organized, with feedforward projections from A1 to R and with additional projections, although of unknown feed direction, from R to RT. We hypothesized that area RT together with more rostral parts of the supratemporal plane (rSTP) form the anterior extension of a rostrally directed stimulus quality processing stream originating in the auditory core area A1. Here, we analyzed auditory responses of single neurons in three different sectors distributed caudorostrally along the supratemporal plane (STP): sector I, mainly area A1; sector II, mainly area RT; and sector III, principally RTp (the rostrotemporal polar area), including cortex located 3 mm from the temporal tip. Mean onset latency of excitation responses and stimulus selectivity to monkey calls and other sounds, both simple and complex, increased progressively from sector I to III. Also, whereas cells in sector I responded with significantly higher firing rates to the "other" sounds than to monkey calls, those in sectors II and III responded at the same rate to both stimulus types. The pattern of results supports the proposal that the STP contains a rostrally directed, hierarchically organized auditory processing stream, with gradually increasing stimulus selectivity, and that this stream extends from the primary auditory area to the temporal pole.
C1 [Kikuchi, Yukiko] Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20057 USA.
[Kikuchi, Yukiko; Mishkin, Mortimer] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Kikuchi, Yukiko; Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA.
RP Kikuchi, Y (reprint author), Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Res Bldg WP15,3970 Reservoir Rd NW, Washington, DC 20057 USA.
EM yk254@georgetown.edu
FU National Institute of Mental Health; National Institute on Deafness and
Other Communication Disorders; Japan Society for the Promotion of
Science; National Institutes of Health [R01 NS052494]; National Science
Foundation Partnerships for International Research and Education
[OISE-0730255]
FX This work was supported by the Intramural Research Programs of the
National Institute of Mental Health and the National Institute on
Deafness and Other Communication Disorders, by the Japan Society for the
Promotion of Science, and by National Institutes of Health Grant R01
NS052494 and National Science Foundation Partnerships for International
Research and Education Grant OISE-0730255. We thank R. C. Saunders and
M. Malloy for assisting with the surgeries and the structural MRI, O.
Castillo-Aguiar for animal care and testing, K. King for audiological
screening, K. Saleem for neuroanatomical advice, and M. D. Hauser and A.
Poremba for providing monkey vocalizations.
NR 36
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U1 0
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 29
PY 2010
VL 30
IS 39
BP 13021
EP 13030
DI 10.1523/JNEUROSCI.2267-10.2010
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 659MY
UT WOS:000282571800013
PM 20881120
ER
PT J
AU Iwahara, J
Clore, GM
AF Iwahara, Junji
Clore, G. Marius
TI Structure-Independent Analysis of the Breadth of the Positional
Distribution of Disordered Groups in Macromolecules from Order
Parameters for Long, Variable-Length Vectors Using NMR Paramagnetic
Relaxation Enhancement
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID MOLECULAR-STRUCTURE DETERMINATION; TRANSIENT ENCOUNTER COMPLEXES;
PROTEIN-PROTEIN ASSOCIATION; PAIR CORRELATION-FUNCTIONS; SPIN-LATTICE
RELAXATION; TRANSLATIONAL DIFFUSION; PROTON RELAXATION;
CROSS-RELAXATION; XPLOR-NIH; DYNAMICS
AB Quantitative information regarding structurally disordered groups is crucial for a complete understanding of the relationship between structure, dynamics, and function in biological macromolecules. Experimental analysis, however, of the positional distribution of disordered groups in the macromolecular frame is extremely difficult. While NMR order parameters, S(2), for fixed-length bond vectors such as N-H and C-H are commonly used for investigations of conformational dynamics of macromolecules, these order parameters provide only angular information about internal motions and are totally insensitive to translational motions. Although analysis of S(2) for bond vectors permits identification of disordered groups in macromolecules, this type of order parameter cannot provide any information about the distribution radii of disordered groups. Here we describe an NMR approach to directly determine the distribution radius of a disordered group independent of any structural knowledge. This approach makes use of order parameters for long, variable-length vectors (including proton paramagnetic center and proton proton vectors) between a disordered group and a rigid portion of the macromolecule. We demonstrate the application of this formalism to paramagnetic relaxation enhancement vectors. In addition, the potential utility of the same formalism to (1)H-(1)H cross-relaxation rates is considered as an alternative approach for analyzing the breadth of the positional distribution of disordered groups.
C1 [Iwahara, Junji] Univ Texas Med Branch, Dept Biochem & Mol Biol, Sealy Ctr Struct Biol & Mol Biophys, Galveston, TX 77555 USA.
[Clore, G. Marius] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Iwahara, J (reprint author), Univ Texas Med Branch, Dept Biochem & Mol Biol, Sealy Ctr Struct Biol & Mol Biophys, Galveston, TX 77555 USA.
EM j.iwahara@utmb.edu; mariusc@mail.nih.gov
RI Clore, G. Marius/A-3511-2008;
OI Clore, G. Marius/0000-0003-3809-1027; Iwahara, Junji/0000-0003-4732-2173
FU Welch Foundation [H-1683]; National Science Foundation [MCB-0920238];
National Institute of Diabetes and Digestive and Kidney Diseases, NIH;
Office of the Director of the NIH
FX We thank Dr. Attila Szabo for stimulating discussions and for originally
pointing out to us that < r-6> S2 = R-6
to order R-10 for any spherical distribution centered on R.
This work was supported by Grant H-1683 from the Welch Foundation (to
J.I.), Grant MCB-0920238 from the National Science Foundation (to J.I.),
the intramural research program of the National Institute of Diabetes
and Digestive and Kidney Diseases, NIH (to G.M.C.), and the AIDS
Targeted Antiviral Program of the Office of the Director of the NIH (to
G.M.C.).
NR 48
TC 19
Z9 19
U1 1
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD SEP 29
PY 2010
VL 132
IS 38
BP 13346
EP 13356
DI 10.1021/ja1048187
PG 11
WC Chemistry, Multidisciplinary
SC Chemistry
GA 656CQ
UT WOS:000282304000059
PM 20795737
ER
PT J
AU De, S
Zhang, YQ
Garner, JR
Wang, SA
Becker, KG
AF De, Supriyo
Zhang, Yongqing
Garner, John R.
Wang, S. Alex
Becker, Kevin G.
TI Disease and phenotype gene set analysis of disease-based gene expression
in mouse and human
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE genome-wide association; microarray; common disease; disease ontology;
data integration
ID GENOME-WIDE ASSOCIATION; ENRICHMENT ANALYSIS; PATHWAYS; DATABASE;
ARCHIVE; BIOLOGY; ATLAS
AB De S, Zhang Y, Garner JR, Wang SA, Becker KG. Disease and phenotype gene set analysis of disease-based gene expression in mouse and human. Physiol Genomics 42A: 162-167, 2010. First published August 3, 2010; doi:10.1152/physiolgenomics.00008.2010.-The genetic contributions to common disease and complex disease phenotypes are pleiotropic, multifactorial, and combinatorial. Gene set analysis is a computational approach used in the analysis of microarray data to rapidly query gene combinations and multifactorial processes. Here we use novel gene sets based on population-based human genetic associations in common human disease or experimental genetic mouse models to analyze disease-related microarray studies. We developed a web-based analysis tool that uses these novel disease-and phenotype-related gene sets to analyze microarray-based gene expression data. These gene sets show disease and phenotype specificity in a species-specific and cross-species fashion. In this way, we integrate population-based common human disease genetics, mouse genetically determined phenotypes, and disease or phenotype structured ontologies, with gene expression studies relevant to human disease. This may aid in the translation of large-scale high-throughput datasets into the context of clinically relevant disease phenotypes.
C1 [De, Supriyo; Zhang, Yongqing; Garner, John R.; Becker, Kevin G.] NIA, Biomed Res Ctr, NIH, Gene Express & Genom Unit, Baltimore, MD 21224 USA.
[Wang, S. Alex] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Becker, KG (reprint author), NIA, Biomed Res Ctr, NIH, Gene Express & Genom Unit, Ste 100,Rm 4B122,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM beckerk@grc.nia.nih.gov
OI De, Supriyo/0000-0002-2075-7655; Becker, Kevin/0000-0002-6794-6656
FU National Institutes of Health (NIH); National Institute on Aging; NIH
Center for Information Technology
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Institute on Aging, and
the NIH Center for Information Technology.
NR 26
TC 11
Z9 11
U1 1
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD SEP 29
PY 2010
VL 42A
IS 2
BP 162
EP 167
DI 10.1152/physiolgenomics.00008.2010
PG 6
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA 656BY
UT WOS:000282302000009
PM 20682848
ER
PT J
AU Moore, SC
Gierach, GL
Schatzkin, A
Matthews, CE
AF Moore, S. C.
Gierach, G. L.
Schatzkin, A.
Matthews, C. E.
TI Physical activity, sedentary behaviours, and the prevention of
endometrial cancer
SO BRITISH JOURNAL OF CANCER
LA English
DT Review
DE sedentary behaviour; physical activity; endometrial cancer; epidemiology
ID LIFE-STYLE; US WOMEN; RISK; COHORT; MECHANISMS; OBESITY; HEALTH; TIME;
OVERWEIGHT; HORMONES
AB Physical activity has been hypothesised to reduce endometrial cancer risk, but this relationship has been difficult to confirm because of a limited number of prospective studies. However, recent publications from five cohort studies, which together comprise 2663 out of 3463 cases in the published literature for analyses of recreational physical activity, may help resolve this question. To synthesise these new data, we conducted a meta-analysis of prospective studies published through to December 2009. We found that physical activity was clearly associated with reduced risk of endometrial cancer, with active women having an approximately 30% lower risk than inactive women. Owing to recent interest in sedentary behaviour, we further investigated sitting time in relation to endometrial cancer risk using data from the NIH-AARP Diet and Health Study. We found that, independent of the level of moderate-vigorous physical activity, greater sitting time was associated with increased endometrial cancer risk. Thus, limiting time in sedentary behaviours may complement increasing level of moderate-vigorous physical activity as a means of reducing endometrial cancer risk. Taken together with the established biological plausibility of this relation, the totality of evidence now convincingly indicates that physical activity prevents or reduces risk of endometrial cancer. British Journal of Cancer (2010) 103, 933-938. doi:10.1038/sj.bjc.6605902 www.bjcancer.com (C) 2010 Cancer Research UK
C1 [Moore, S. C.; Gierach, G. L.; Schatzkin, A.; Matthews, C. E.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Moore, SC (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM moorest@mail.nih.gov
RI matthews, Charles/E-8073-2015; Gierach, Gretchen/E-1817-2016; Moore,
Steven/D-8760-2016
OI matthews, Charles/0000-0001-8037-3103; Gierach,
Gretchen/0000-0002-0165-5522; Moore, Steven/0000-0002-8169-1661
FU National Institutes of Health, National Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute.
NR 29
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Z9 50
U1 1
U2 7
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 SEP 28
PY 2010
VL 103
IS 7
BP 933
EP 938
DI 10.1038/sj.bjc.6605902
PG 6
WC Oncology
SC Oncology
GA 655DB
UT WOS:000282222000002
PM 20877336
ER
PT J
AU Dores, GM
Anderson, WF
Freeman, LEB
Fraumeni, JF
Curtis, RE
AF Dores, G. M.
Anderson, W. F.
Freeman, L. E. Beane
Fraumeni, J. F.
Curtis, R. E.
TI Risk of breast cancer according to clinicopathologic features among
long-term survivors of Hodgkin's lymphoma treated with radiotherapy
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE Hodgkin's lymphoma; second breast cancer; radiation-related breast
cancer
ID END RESULTS DATABASE; ESTROGEN-RECEPTOR; DISEASE; SURVEILLANCE;
RADIATION; WOMEN; EPIDEMIOLOGY
AB BACKGROUND: It is unknown whether breast cancer (BC) characteristics among young women treated with radiotherapy (RT) for Hodgkin's lymphoma (HL) differ from sporadic BC.
METHODS: Using population-based data, we calculated BC risk following HL according to clinicopathologic features.
RESULTS: Compared with BC in the general population, risks of oestrogen receptor (ER)-positive/progesterone receptor (PR)-positive and ER-negative/PR-negative BC in young, irradiated HL survivors were increased five-fold (95% confidence interval (CI) = 3.81-6.35) and nine-fold (95% CI = 6.93-12.25), respectively. Among 15-year survivors, relative risk of ER-negative/PR-negative BC exceeded by two-fold (P = 0.002) than that of ER-positive/PR-positive BC.
CONCLUSION: Radiotherapy may disproportionately contribute to the development of BC with adverse prognostic features among young HL survivors. British Journal of Cancer (2010) 103, 1081-1084. doi:10.1038/sj.bjc.6605877 www.bjcancer.com Published online 14 September 2010 (C) 2010 Cancer Research UK
C1 [Dores, G. M.] Med Serv, Dept Vet Affairs Med Ctr, Oklahoma City, OK 73104 USA.
[Dores, G. M.; Anderson, W. F.; Freeman, L. E. Beane; Fraumeni, J. F.; Curtis, R. E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Dores, GM (reprint author), Med Serv, Dept Vet Affairs Med Ctr, 921 NE 13th St, Oklahoma City, OK 73104 USA.
EM doresg@mail.nih.gov
RI Beane Freeman, Laura/C-4468-2015
OI Beane Freeman, Laura/0000-0003-1294-4124
FU National Cancer Institute, National Institutes of Health, Bethesda, MD,
USA; Department of Veterans Affairs Medical Center in Oklahoma City, OK,
USA
FX This work was supported by the Intramural Research Programme of the
National Cancer Institute, National Institutes of Health, Bethesda, MD,
USA, and by the Department of Veterans Affairs Medical Center in
Oklahoma City, OK, USA. We are grateful to Nathan Appel, Information
Management Systems Inc., Silver Spring, Maryland, USA, for computer
support.
NR 22
TC 18
Z9 19
U1 0
U2 1
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 SEP 28
PY 2010
VL 103
IS 7
BP 1081
EP 1084
DI 10.1038/sj.bjc.6605877
PG 4
WC Oncology
SC Oncology
GA 655DB
UT WOS:000282222000020
PM 20842115
ER
PT J
AU Major, JM
Stolzenberg-Solomon, RZ
Pollak, MN
Snyder, K
Virtamo, J
Albanes, D
AF Major, J. M.
Stolzenberg-Solomon, R. Z.
Pollak, M. N.
Snyder, K.
Virtamo, J.
Albanes, D.
TI Insulin-like growth factors and liver cancer risk in male smokers
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE insulin-like growth factor; IGF-I; incidence; men
ID IGF-BINDING PROTEIN-3; C VIRUS-INFECTION; FACTOR-I;
HEPATOCELLULAR-CARCINOMA; PROSTATE-CANCER; REGRESSION ANALYSIS; FACTOR
(IGF)-I; SERUM-LEVELS; MEN; EPIDEMIOLOGY
AB BACKGROUND: The liver is the primary source of circulating insulin-like growth factor (IGF)-I, yet the relation between IGFs and liver cancer is uncertain.
METHODS: In a case-cohort study within a cohort of 29 133 male smokers we examined associations of serum IGF-I and IGF binding protein (IGFBP)-3 with liver cancer (50 cases).
RESULTS: Nonlinear associations between liver cancer and IGF-I and IGFBP-3 were observed (P = 0.04 and P<0.01, respectively), strongest association at lowest levels (odds ratio (OR) = 0.2, 95% confidence interval (CI) = 0.1-0.7 for 80 vs 30 ng ml(-1) of IGF-I; OR = 0.2, 95% CI = 0.1-0.6 for 1400 vs 700 ng ml(-1) of IGFBP-3).
CONCLUSIONS: Low IGF-I and IGFBP-3 levels in male smokers are associated with increased risk of liver cancer. British Journal of Cancer (2010) 103, 1089-1092. doi:10.1038/sj.bjc.6605842 www.bjcancer.com Published online 17 August 2010 (C) 2010 Cancer Research UK
C1 [Majo