FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Vijayasarathy, C
Sui, RF
Zeng, Y
Yang, GX
Xu, F
Caruso, RC
Lewis, RA
Ziccardi, L
Sieving, PA
AF Vijayasarathy, Camasamudram
Sui, Ruifang
Zeng, Yong
Yang, Guoxing
Xu, Fei
Caruso, Rafael C.
Lewis, Richard A.
Ziccardi, Lucia
Sieving, Paul A.
TI Molecular Mechanisms Leading to Null-Protein Product from Retinoschisin
(RS1) Signal-Sequence Mutants in X-Linked Retinoschisis (XLRS) Disease
SO HUMAN MUTATION
LA English
DT Article
DE retinoschisin; X-linked retinoschisis; XLRS; signal sequence; discoidin;
splicing
ID OPTICAL COHERENCE TOMOGRAPHY; JUVENILE RETINOSCHISIS; TRANSLATION
INITIATION; ENDOPLASMIC-RETICULUM; CLINICAL-FEATURES; MAMMALIAN-CELLS;
NATURAL-HISTORY; GENE DELIVERY; SPLICE-SITE; MUTATIONS
AB Retinoschisin (RS1) is a cell-surface adhesion molecule expressed by photoreceptor and bipolar cells of the retina. The 24-kDa protein encodes two conserved sequence motifs: the initial signal sequence targets the protein for secretion while the larger discoidin domain is implicated in cell adhesion. RS1 helps to maintain the structural organization of the retinal cell layers and promotes visual signal transduction. RS1 gene mutations cause X-linked retinoschisis disease (XLRS) in males, characterized by early-onset central vision loss. We analyzed the biochemical consequences of several RS1 signal-sequence mutants (c.1A>T, c.35T>A, c.38T>C, and c.52G>A) found in our subjects. Expression analysis in COS-7 cells demonstrates that these mutations affect RS1 biosynthesis and result in an RS1 null phenotype by several different mechanisms. By comparison, discoidin-domain mutations generally lead to nonfunctional conformational variants that remain trapped inside the cell. XLRS disease has a broad heterogeneity in general, but subjects with the RS1 null-protein signal-sequence mutations are on the more severe end of the clinical phenotype. Results from the signal-sequence mutants are discussed in the context of the discoidin-domain mutations, clinical phenotypes, genotype-phenotype correlations, and implications for RS1 gene replacement therapy. Hum Mutat 31: 1251-1260, 2010. Published 2010 Wiley-Liss, Inc.
C1 [Caruso, Rafael C.; Sieving, Paul A.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Vijayasarathy, Camasamudram; Zeng, Yong; Sieving, Paul A.] Natl Inst Deafness & Other Commun Disorders, Sect Translat Res Retinal & Macular Degenerat, NIH, Bethesda, MD USA.
[Sui, Ruifang; Yang, Guoxing; Xu, Fei] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Ophthalmol, Beijing 100037, Peoples R China.
[Lewis, Richard A.] Baylor Coll Med, Cullen Eye Inst, Houston, TX 77030 USA.
[Ziccardi, Lucia] GB Bietti Eye Fdn, IRCCS, Rome, Italy.
RP Sieving, PA (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, 31 Ctr Dr,Room 6A03, Bethesda, MD 20892 USA.
EM paulsieving@nei.nih.gov
FU NIH; Foundation Fighting Blindness (FFB) [CD-CL-0808-0470-PUMCH]
FX We thank Drs. Brian Brooks and Michael Redmond of NEI/NIH for useful
discussions; Sean Finnegan for editorial assistance with manuscript
preparation, and Doug Kesselring for help with illustrations. The author
C. V. thanks Yogesh Sharma, B. E., M. S., of Patni Computer Systems,
Mumbai, India. This research was supported by the Intramural Research
Programs of the NIH. Dr. Ruifang Sui was a recipient of the Foundation
Fighting Blindness (FFB Grant No. CD-CL-0808-0470-PUMCH). Dr. Richard
Lewis is a Senior Scientific Investigator for Research to Prevent
Blindness, New York. We thank the individuals and families reported here
for their generous and continuing commitment to these programs.
NR 63
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PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD NOV
PY 2010
VL 31
IS 11
BP 1251
EP 1260
DI 10.1002/humu.21350
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 674XG
UT WOS:000283783600016
PM 20809529
ER
PT J
AU Ye, XB
Skjaerven, R
Basso, O
Baird, DD
Eggesbo, M
Uicab, LAC
Haug, K
Longnecker, MP
AF Ye, Xibiao
Skjaerven, Rolv
Basso, Olga
Baird, Donna D.
Eggesbo, Merete
Uicab, Lea Aurora Cupul
Haug, Kjell
Longnecker, Matthew P.
TI In utero exposure to tobacco smoke and subsequent reduced fertility in
females
SO HUMAN REPRODUCTION
LA English
DT Article
DE tobacco smoking; in utero exposure; fertility
ID CIGARETTE-SMOKE; NEONATAL EXPOSURE; PRENATAL EXPOSURE; PREGNANT-WOMEN;
TIME; RELIABILITY; INFERTILITY; MOTHER; ADULT; FETAL
AB Animal studies have shown that in utero exposure to chemicals in tobacco smoke reduces female fertility, but epidemiological findings have been inconsistent.
We examined the association between in utero exposure to tobacco smoke and female fertility among women in the Norwegian Mother and Child Cohort Study, enrolled from 1999 to 2007. Around the 17th week of pregnancy, participants reported how long they took to conceive (time to pregnancy), and whether their mother smoked while pregnant with the participant. This analysis included 48 319 planned pregnancies among women aged 15-44 years. We estimated fecundability odds ratios (FORs) using a discrete-time survival analysis, adjusting for age, education and adult tobacco smoking.
The adjusted FOR for in utero exposure to tobacco smoke among all subjects was 0.96 [95% confidence interval (CI): 0.93, 0.98], among subjects reporting no adult tobacco smoking or passive exposure it was 0.96 (95% CI: 0.93, 0.99) and among subjects reporting adult tobacco smoking or passive exposure it was 0.95 (95% CI: 0.91, 0.99). We performed a probabilistic sensitivity analysis to estimate the effect of exposure and outcome misclassification on the results, and, as expected, the association became more pronounced after taking misclassification into account.
This large cohort study supports a small-to-modest association between in utero exposure to tobacco smoke and reduced fertility.
C1 [Ye, Xibiao; Basso, Olga; Baird, Donna D.; Uicab, Lea Aurora Cupul; Longnecker, Matthew P.] NIEHS, Epidemiol Branch, NIH, Dept Human & Hlth Serv, Res Triangle Pk, NC 27709 USA.
[Skjaerven, Rolv; Eggesbo, Merete] Norwegian Inst Publ Hlth, Div Epidemiol, N-0473 Oslo, Norway.
[Skjaerven, Rolv; Haug, Kjell] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, N-5021 Bergen, Norway.
RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Human & Hlth Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM longnecl@niehs.nih.gov
RI Basso, Olga/E-5384-2010; Baird, Donna/D-5214-2017; CUPUL UICAB,
LEA/C-8699-2014;
OI Basso, Olga/0000-0001-9298-4921; Baird, Donna/0000-0002-5544-2653; CUPUL
UICAB, LEA/0000-0001-6190-4474; Longnecker, Matthew/0000-0001-6073-5322;
Eggesbo, Merete/0000-0002-0006-5336
FU National Institutes of Health; National Institute of Environmental
Health Sciences; Norwegian Ministry of Health; NIH/NIEHS [N01-ES-85433];
NIH/NINDS [1 UO1 NS 047537-01]; Norwegian Research Council/FUGE
[151918/S10]
FX This study was supported in part by the Intramural Research Program of
the National Institutes of Health, National Institute of Environmental
Health Sciences. The Norwegian Mother and Child Cohort Study is
supported by the Norwegian Ministry of Health, NIH/NIEHS (grant no.
N01-ES-85433), NIH/NINDS (grant no. 1 UO1 NS 047537-01) and the
Norwegian Research Council/FUGE (grant no. 151918/S10).
NR 39
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U1 2
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD NOV
PY 2010
VL 25
IS 11
BP 2901
EP 2906
DI 10.1093/humrep/deq235
PG 6
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 666OE
UT WOS:000283124000026
PM 20817739
ER
PT J
AU Wright, JT
Agodoa, LY
Appel, L
Cushman, WC
Taylor, AL
Obegdegbe, GG
Osei, K
Reed, J
AF Wright, Jackson T., Jr.
Agodoa, Lawrence Y.
Appel, Lawrence
Cushman, William C.
Taylor, Anne L.
Obegdegbe, Gbenga G.
Osei, Kwame
Reed, James
TI New Recommendations for Treating Hypertension in Black Patients Evidence
and/or Consensus?
SO HYPERTENSION
LA English
DT Editorial Material
ID BLOOD-PRESSURE CONTROL; TYPE-2 DIABETES-MELLITUS; KIDNEY-DISEASE; AASK
TRIAL; PROGRESSION
C1 [Wright, Jackson T., Jr.] Case Western Reserve Univ, Dept Med,William T Dahms Clin Res Unit,, Clin & Translat Sci Collaborat,Clin Hypertens Pro, Div Nephrol & Hypertens, Cleveland, OH 44106 USA.
[Agodoa, Lawrence Y.] NIDDK, Bethesda, MD USA.
[Appel, Lawrence] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Cushman, William C.] Vet Affairs Med Ctr, Med Serv, Prevent Med Sect, Memphis, TN USA.
[Taylor, Anne L.] Columbia Univ, Dept Med, Div Cardiol, New York, NY USA.
[Obegdegbe, Gbenga G.] NYU, Sch Med, Dept Med, Div Internal Med, New York, NY USA.
[Osei, Kwame] Ohio State Univ, Dept Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
[Reed, James] Morehouse Coll Med, Dept Med, Div Endocrinol, Atlanta, GA USA.
RP Wright, JT (reprint author), Case Western Reserve Univ, Dept Med,William T Dahms Clin Res Unit,, Clin & Translat Sci Collaborat,Clin Hypertens Pro, Div Nephrol & Hypertens, Bolwell Suite 2200,11100 Euclid Ave, Cleveland, OH 44106 USA.
EM Jackson.Wright@case.edu
FU NCRR NIH HHS [M01 RR000080]; NIDDK NIH HHS [U01 DK045381]; NIMHD NIH HHS
[P60 MD002265]
NR 14
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD NOV
PY 2010
VL 56
IS 5
BP 801
EP 803
DI 10.1161/HYPERTENSIONAHA.110.159566
PG 3
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 668AI
UT WOS:000283240400524
PM 20921426
ER
PT J
AU Tian, JA
Haller, S
Periyasamy, S
Brewster, P
Zhang, H
Adlakha, S
Fedorova, OV
Xie, ZJ
Bagrov, AY
Shapiro, JI
Cooper, CJ
AF Tian, Jiang
Haller, Steven
Periyasamy, Sankaridrug
Brewster, Pamela
Zhang, Haifeng
Adlakha, Satjit
Fedorova, Olga V.
Xie, Zi-jian
Bagrov, Alexei Y.
Shapiro, Joseph I.
Cooper, Christopher J.
TI Renal Ischemia Regulates Marinobufagenin Release in Humans
SO HYPERTENSION
LA English
DT Article
DE renal artery stenosis; hypertension; cardiotonic steroids;
marinobufagenin; renal artery stenting
ID ENDOGENOUS CARDIOTONIC STEROIDS; EXPERIMENTAL UREMIC CARDIOMYOPATHY;
OUABAIN-LIKE IMMUNOREACTIVITY; BOVINE ADRENOCORTICAL-CELLS;
CONGESTIVE-HEART-FAILURE; ARTERY STENOSIS; SODIUM-PUMP; RENOVASCULAR
DISEASE; ESSENTIAL-HYPERTENSION; ATPASE INHIBITION
AB Cardiotonic steroids, including marinobufagenin, are a group of new steroid hormones found in plasma and urine of patients with congestive heart failure, myocardial infarction, and chronic renal failure. In animal studies, partial nephrectomy induces marinobufagenin elevation, cardiac hypertrophy, and fibrosis. The objective of this study is to test the effect of renal ischemia on marinobufagenin levels in humans with renal artery stenosis (RAS). To test this, plasma marinobufagenin levels were measured in patients with RAS of the Prospective Randomized Study Comparing Renal Artery Stenting With or Without Distal Protection, non-RAS patient controls who were scheduled for coronary angiography, and normal healthy individuals. Marinobufagenin levels were significantly higher in patients with RAS compared with those of the other 2 groups. Multivariate analysis shows that occurrence of RAS is independently related to marinobufagenin levels. In addition, renal artery revascularization by stenting partially reversed marinobufagenin levels in the patients with RAS (0.77 +/- 0.06 nmol/L at baseline; 0.66 +/- 0.06 nmol/L at 24 hours; and 0.61 +/- 0.05 nmol/L at 1 month). In conclusion, we have found that marinobufagenin levels are increased in patients with RAS, whereas reversal of renal ischemia by stenting treatment reduces marinobufagenin levels. These results suggest that RAS-induced renal ischemia may be a major cause of marinobufagenin release. (Hypertension. 2010;56:914-919.)
C1 [Tian, Jiang] Univ Toledo, Dept Med, Div Cardiovasc, Coll Med, Toledo, OH 43614 USA.
[Fedorova, Olga V.; Bagrov, Alexei Y.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
RP Tian, JA (reprint author), Univ Toledo, Dept Med, Div Cardiovasc, Coll Med, 3000 Arlington Ave,MS 1118, Toledo, OH 43614 USA.
EM Jiang.tian@utoledo.edu
FU American Heart Association [0980027N]; National Institute on Aging,
National Institutes of Health; Centocor, Inc; Cordis Corp; University of
Toledo, Health Sciences Campus, Toledo, Ohio; National Institutes of
Health for the Cardiovascular Outcomes in Renal Atherosclerotic Lesions
Study [5U01HL071556-06]; Cordis Corp for RESIST
FX This work is supported by the American Heart Association (0980027N). The
work of A.Y.B. and O.V.F. was supported by the Intramural Research
Program, National Institute on Aging, National Institutes of Health. The
RAS patient samples were from the RESIST, sponsored by the University of
Toledo, Health Sciences Campus, Toledo, Ohio, and funded by Centocor Inc
and Cordis Corp, both Johnson & Johnson companies.; C.J.C. and P.B. have
received research grants from the Centocor, Inc, and Cordis Corp for
RESIST and from the National Institutes of Health for the Cardiovascular
Outcomes in Renal Atherosclerotic Lesions Study, 5U01HL071556-06.
NR 50
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD NOV
PY 2010
VL 56
IS 5
BP 914
EP 919
DI 10.1161/HYPERTENSIONAHA.110.155564
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 668AI
UT WOS:000283240400546
PM 20823380
ER
PT J
AU Fedorova, OV
Shilova, V
Bagrov, AY
AF Fedorova, Olga V.
Shilova, Victoria
Bagrov, Alexei Y.
TI Mammalian Bufadienolides Start from Bile Acids: Silencing of Cyp27a1
Gene Suppresses Synthesis of Marinobufagenin by Human Trophoblast Cells
SO HYPERTENSION
LA English
DT Meeting Abstract
CT Conference on High Blood Pressure Research
CY OCT 13-16, 2010
CL Washington, DC
C1 [Fedorova, Olga V.; Shilova, Victoria; Bagrov, Alexei Y.] NIA, NIH, Baltimore, MD 21224 USA.
NR 0
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD NOV
PY 2010
VL 56
IS 5
BP E125
EP E125
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 668AI
UT WOS:000283240400334
ER
PT J
AU Lee, CR
Pretorius, M
Schuck, RN
Burch, LH
Williams, SM
Zeldin, DC
Brown, NJ
AF Lee, Craig R.
Pretorius, Mias
Schuck, Robert N.
Burch, Lauranell H.
Williams, Scott M.
Zeldin, Darryl C.
Brown, Nancy J.
TI Genetic Variation in Soluble Epoxide Hydrolase is Associated with
Vascular Responsiveness to Bradykinin in Humans
SO HYPERTENSION
LA English
DT Meeting Abstract
CT Conference on High Blood Pressure Research
CY OCT 13-16, 2010
CL Washington, DC
C1 [Lee, Craig R.; Schuck, Robert N.] Univ N Carolina, Chapel Hill, NC USA.
[Pretorius, Mias; Williams, Scott M.; Brown, Nancy J.] Vanderbilt Univ, Nashville, TN USA.
[Burch, Lauranell H.; Zeldin, Darryl C.] NIEHS, NIH, Rsch Triangle Pk, NC USA.
NR 0
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PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD NOV
PY 2010
VL 56
IS 5
BP E148
EP E148
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 668AI
UT WOS:000283240400436
ER
PT J
AU Nikitina, E
Mikhailov, AV
Nikandrova, ES
Frolova, E
Fadeev, A
Shman, VV
Shapiro, JI
Fedorova, OV
Bagrov, AY
AF Nikitina, Elena
Mikhailov, Anton V.
Nikandrova, Ekaterina S.
Frolova, Elena
Fadeev, Artem
Shman, Vera V.
Shapiro, Joseph I.
Fedorova, Olga V.
Bagrov, Alexei Y.
TI In Preeclampsia, Endogenous Cardiotonic Steroids Induce Vascular
Fibrosis and Impairment of Vasorelaxation
SO HYPERTENSION
LA English
DT Meeting Abstract
CT Conference on High Blood Pressure Research
CY OCT 13-16, 2010
CL Washington, DC
C1 [Nikitina, Elena; Frolova, Elena; Fadeev, Artem] Sechenov Inst Evolutionary Physiol & Biochem, St Petersburg, Russia.
[Mikhailov, Anton V.] St Petersburg State Univ, Coll Med, St Petersburg, Russia.
[Mikhailov, Anton V.; Nikandrova, Ekaterina S.; Shman, Vera V.] 17 Maternal Hosp, St Petersburg, Russia.
[Shapiro, Joseph I.] Univ Toledo, Toledo, OH 43606 USA.
[Fedorova, Olga V.; Bagrov, Alexei Y.] NIA, NIH, Baltimore, MD 21224 USA.
NR 0
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD NOV
PY 2010
VL 56
IS 5
BP E92
EP E92
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 668AI
UT WOS:000283240400179
ER
PT J
AU Paredes, DA
Webster, BR
Jackson-Weaver, O
Kanagy, NL
AF Paredes, Daniel A.
Webster, Bradley R.
Jackson-Weaver, Olan
Kanagy, Nancy L.
TI Augmented Endothelin-1 Dependent Vasoconstriction of Mesenteric Arteries
from Rats Exposed to Intermittent Hypoxia Requires Phosphoinositide
Dependent Kinase-1 Activation of PKC Delta Independent from PI3K
Activation
SO HYPERTENSION
LA English
DT Meeting Abstract
CT Conference on High Blood Pressure Research
CY OCT 13-16, 2010
CL Washington, DC
C1 [Paredes, Daniel A.; Jackson-Weaver, Olan; Kanagy, Nancy L.] Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA.
[Webster, Bradley R.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD NOV
PY 2010
VL 56
IS 5
BP E144
EP E144
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 668AI
UT WOS:000283240400422
ER
PT J
AU Shibao, CA
Buchowski, MS
Chen, KY
Yu, C
Biaggioni, I
AF Shibao, Cyndya A.
Buchowski, Maciej S.
Chen, Kong Y.
Yu, Chang
Biaggioni, Italo
TI Effect of Chronic Sympathetic Attenuation on Energy Metabolism
SO HYPERTENSION
LA English
DT Meeting Abstract
CT Conference on High Blood Pressure Research
CY OCT 13-16, 2010
CL Washington, DC
C1 [Shibao, Cyndya A.; Buchowski, Maciej S.; Yu, Chang; Biaggioni, Italo] Vanderbilt Univ, Nashville, TN USA.
[Chen, Kong Y.] NIDDK, NIH, Bethesda, MD USA.
RI Buchowski, Maciej/A-2683-2008
OI Buchowski, Maciej/0000-0002-0566-1743
NR 0
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD NOV
PY 2010
VL 56
IS 5
BP E96
EP E96
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 668AI
UT WOS:000283240400198
ER
PT J
AU Spallek, B
Konkel, A
Westphal, C
Marko, L
DeGraff, LM
Schubert, C
Bradbury, JA
Dechend, R
Luft, FC
Regitz-Zagrosek, V
Zeldin, DC
Muller, DN
Schunck, WH
Fischer, R
AF Spallek, Bastian
Konkel, Anne
Westphal, Christina
Marko, Lajos
DeGraff, Laura M.
Schubert, Carola
Bradbury, J. Alyce
Dechend, Ralf
Luft, Friedrich C.
Regitz-Zagrosek, Vera
Zeldin, Darryl C.
Muller, Dominik N.
Schunck, Wolf-Hagen
Fischer, Robert
TI CYP2J2 Overexpression Protects against Arrhythmias in Two Different
Models of Cardiac Hypertrophy
SO HYPERTENSION
LA English
DT Meeting Abstract
CT Conference on High Blood Pressure Research
CY OCT 13-16, 2010
CL Washington, DC
C1 [Spallek, Bastian; Luft, Friedrich C.] Expt Clin Rsch Cntr, Berlin, Germany.
[Konkel, Anne; Marko, Lajos; Dechend, Ralf; Muller, Dominik N.; Schunck, Wolf-Hagen] Max Delbruck Ctr Mol Med, Berlin, Germany.
[Westphal, Christina; Schubert, Carola; Regitz-Zagrosek, Vera; Fischer, Robert] Charite, Inst Gender Med, Berlin, Germany.
[DeGraff, Laura M.; Bradbury, J. Alyce; Zeldin, Darryl C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
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PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD NOV
PY 2010
VL 56
IS 5
BP E78
EP E78
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 668AI
UT WOS:000283240400122
ER
PT J
AU Castro, MA
Yao, JH
Pang, YX
Lee, C
Baker, E
Butman, J
Evangelou, IE
Thomasson, D
AF Castro, Marcelo A.
Yao, Jianhua
Pang, Yuxi
Lee, Christabel
Baker, Eva
Butman, John
Evangelou, Iordanis E.
Thomasson, David
TI Template-Based B-1 Inhomogeneity Correction in 3T MRI Brain Studies
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE B-1 inhomogeneity; brain; image registration; magnetic resonance images
(MRI); T-1 mapping
ID INTENSITY NONUNIFORMITY; RETROSPECTIVE CORRECTION; TISSUE
CLASSIFICATION; RADIOFREQUENCY FIELD; AUTOMATIC CORRECTION;
STEADY-STATE; FLIP ANGLES; IMAGES; SEGMENTATION; ACCURATE
AB Low noise, high resolution, fast and accurate T-1 maps from MRI images of the brain can be performed using a dual flip angle method. However, B-1 field inhomogeneity, which is particularly problematic at high field strengths ( e. g., 3T), limits the ability of the scanner to deliver the prescribed flip angle, introducing errors into the T-1 maps that limit the accuracy of quantitative analyses based on those maps. A dual repetition time method was used for acquiring a B-1 map to correct that inhomogeneity. Additional inaccuracies due to misregistration of the acquired T-1-weighted images were corrected by rigid registration, and the effects of misalignment on the T-1 maps were compared to those of B-1 inhomogeneity in 19 normal subjects. However, since B-1 map acquisition takes up precious scanning time and most retrospective studies do not have B-1 map, we designed a template-based correction strategy. B-1 maps from different subjects were aligned using a twelve-parameter affine registration. Recomputed T-1 maps showed an important improvement with respect to the noncorrected maps: histograms of all corrected maps exhibited two peaks corresponding to white and gray matter tissues, while unimodal histograms were observed in all uncorrected maps because of the inhomogeneity. A method to detect the best nonsubject-specific B-1 correction based on a set of features was designed. The optimum set of weighting factors for those features was computed. The best available B-1 correction was detected in almost all subjects while corrections comparable to the T-1 map corrected using the B-1 map from the same subject were detected in the others.
C1 [Castro, Marcelo A.; Yao, Jianhua; Pang, Yuxi; Lee, Christabel; Baker, Eva; Butman, John; Evangelou, Iordanis E.; Thomasson, David] NIH, DR&IS, Bethesda, MD 20892 USA.
[Castro, Marcelo A.] Univ Tecnol Nacl, CONICET, Grp Invest & Desarrollo Bioingn GIBIO, RA-1179 Buenos Aires, DF, Argentina.
[Pang, Yuxi] Philips Healthcare, Cleveland, OH 44102 USA.
RP Castro, MA (reprint author), NIH, DR&IS, Bldg 10, Bethesda, MD 20892 USA.
EM castroma@cc.nih.gov; jyao@cc.nih.gov; pangyu@mail.nih.gov;
leechrist@cc.nih.gov; bakere@cc.nih.gov; jbutmana@cc.nih.gov;
evangelouI@ninds.nih.gov; dthomasson@cc.nih.gov
RI Butman, John/A-2694-2008; Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU CONICET (Argentina)
FX Manuscript received July 10, 2009; revised May 26, 2010; accepted June
07, 2010. Date of publication June 21, 2010; date of current version
November 03, 2010. The work of M. A. Castro was supported in part by
CONICET (Argentina). Asterisk indicates corresponding author.
NR 38
TC 3
Z9 3
U1 0
U2 3
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD NOV
PY 2010
VL 29
IS 11
BP 1927
EP 1941
DI 10.1109/TMI.2010.2053552
PG 15
WC Computer Science, Interdisciplinary Applications; Engineering,
Biomedical; Engineering, Electrical & Electronic; Imaging Science &
Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 676TP
UT WOS:000283941800010
PM 20570765
ER
PT J
AU Zhang, JQ
Zhou, XB
Wang, HH
Suffredini, A
Zhang, L
Huang, YF
Wong, S
AF Zhang, Jianqiu
Zhou, Xiaobo
Wang, Honghui
Suffredini, Anthony
Zhang, Lin
Huang, Yufei
Wong, Stephen
TI Bayesian Peptide Peak Detection for High Resolution TOF Mass
Spectrometry
SO IEEE TRANSACTIONS ON SIGNAL PROCESSING
LA English
DT Article
DE Bayesian methods; Markov chain Monte Carlo; mass spectrometry; peptide
peak detection; time-of-flight
ID WAVELET TRANSFORM; SPECTRA; QUANTIFICATION; MALDI; NOISE
AB In this paper, we address the issue of peptide ion peak detection for high resolution time-of-flight (TOF) mass spectrometry (MS) data. A novel Bayesian peptide ion peak detection method is proposed for TOF data with resolution of 10 000-15 000 full width at half-maximum (FWHW). MS spectra exhibit distinct characteristics at this resolution, which are captured in a novel parametric model. Based on the proposed parametric model, a Bayesian peak detection algorithm based on Markov chain Monte Carlo (MCMC) sampling is developed. The proposed algorithm is tested on both simulated and real datasets. The results show a significant improvement in detection performance over a commonly employed method. The results also agree with expert's visual inspection. Moreover, better detection consistency is achieved across MS datasets from patients with identical pathological condition.
C1 [Zhang, Jianqiu; Huang, Yufei] Univ Texas San Antonio, Dept Elect & Comp Engn, San Antonio, TX 78249 USA.
[Zhou, Xiaobo; Wong, Stephen] Texas Methodist Hosp, Res Inst, Houston, TX 77030 USA.
[Wang, Honghui; Suffredini, Anthony] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Zhang, Lin] China Univ Min Technol, Sch Informat & Elect Engn, Xuzhou 221116, Peoples R China.
[Huang, Yufei] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
RP Zhang, JQ (reprint author), Univ Texas San Antonio, Dept Elect & Comp Engn, San Antonio, TX 78249 USA.
EM michelle.zhang@utsa.edu; xzhou@tmhs.org
FU San Antonio Life Sciences Institute; National Center For Research
Resources [G12RR013646]; Methodist Hospital Scholarship; NIH
[R01LM08696, R01LM009161, R01AG028928]; NSF [CCF-0546345]; Chinese
Scholarship Council
FX The associate editor coordinating the review of this manuscript and
approving it for publication was Dr. Z. Jane Wang. The work of J. Zhang
is funded by a San Antonio Life Sciences Institute-Research Enhancement
grant and supported by a SALSI research enhancement grant and an award
G12RR013646 from the National Center For Research Resources. The work of
X. Zhou is funded in part by The Methodist Hospital Scholarship Award.
The work of X. Zhou and S. Wong are also funded in part by NIH Grants
R01LM08696, R01LM009161, and R01AG028928. The work of Y. Huang is
supported by NSF Grant CCF-0546345. The work of L. Zhang is supported by
the Chinese Scholarship Council.
NR 22
TC 2
Z9 2
U1 1
U2 5
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1053-587X
J9 IEEE T SIGNAL PROCES
JI IEEE Trans. Signal Process.
PD NOV
PY 2010
VL 58
IS 11
BP 5883
EP 5894
DI 10.1109/TSP.2010.2065226
PG 12
WC Engineering, Electrical & Electronic
SC Engineering
GA 670RI
UT WOS:000283444600032
PM 21544266
ER
PT J
AU Chai, LYA
Netea, MG
Sugui, J
Vonk, AG
van de Sande, WWJ
Warris, A
Kwon-Chung, KJ
Kullberg, BJ
AF Chai, Louis Y. A.
Netea, Mihai G.
Sugui, Janyce
Vonk, Alieke G.
van de Sande, Wendy W. J.
Warris, Adilia
Kwon-Chung, Kyung J.
Kullberg, Bart Jan
TI Aspergillus fumigatus Conidial Melanin Modulates Host Cytokine Response
SO IMMUNOBIOLOGY
LA English
DT Article
DE beta-glucan; Dectin-1; Mannose receptor; Mannan; Melanin; Modulation
ID CANDIDA-ALBICANS; CRYPTOCOCCUS-NEOFORMANS; PIGMENT BIOSYNTHESIS; IMMUNE
RECOGNITION; FUNGAL MELANINS; BETA-GLUCAN; VIRULENCE; DECTIN-1; GENE;
RECEPTOR
AB Melanin biopigments have been linked to fungal virulence. Aspergillus fumigatus conidia are melanised and are weakly immunogenic. We show that melanin pigments on the surface of resting Aspergillus fumigatus conidia may serve to mask pathogen-associated molecular patterns (PAMPs)-induced cytokine response. The albino conidia induced significantly more proinflammatory cytokines in human peripheral blood mononuclear cells (PBMC), as compared to melanised wild-type conidia. Blocking dectin-1 receptor, Toll-like receptor 4 or mannose receptor decreased cytokine production induced by the albino but not by the wild type conidia. Moreover, albino conidia stimulated less potently, cytokine production in PBMC isolated from an individual with defective dectin-1, compared to the stimulation of cells isolated from healthy donors. These results suggest that beta-glucans, but also other stimulatory PAMPs like mannan derivatives, are exposed on conidial surface in the absence of melanin. Melanin may play a modulatory role by impeding the capability of host immune cells to respond to specific ligands on A. fumigatus. (C) 2009 Elsevier GmbH. All rights reserved.
C1 [Chai, Louis Y. A.; Netea, Mihai G.; Kullberg, Bart Jan] Radboud Univ Nijmegen Med Ctr, Dept Med, NL-6525 GA Nijmegen, Netherlands.
[Chai, Louis Y. A.; Netea, Mihai G.; Warris, Adilia; Kullberg, Bart Jan] Nijmegen Inst Infect Inflammat & Immun N4i, Nijmegen, Netherlands.
[Chai, Louis Y. A.] Natl Univ Singapore Hosp, Dept Med, Singapore 119074, Singapore.
[Sugui, Janyce; Kwon-Chung, Kyung J.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Vonk, Alieke G.; van de Sande, Wendy W. J.] Erasmus MC, Univ Med Ctr Rotterdam, Dept Med Microbiol & Infect Dis, NL-3015 CE Rotterdam, Netherlands.
[Warris, Adilia] Radboud Univ Nijmegen Med Ctr, Dept Pediat, Nijmegen, Netherlands.
RP Netea, MG (reprint author), Radboud Univ Nijmegen Med Ctr, Dept Med 463, POB 9101,Geert Grootpl 8, NL-6525 GA Nijmegen, Netherlands.
EM M.Netea@aig.umcn.nl
RI Warris, Adilia/F-4882-2010; Kullberg, Bart Jan/C-8520-2013; Netea,
Mihai/N-5155-2014; Warris, A./L-4745-2015
FU Ministry of Health, Singapore; Agency for Science, Technology and
Research (A*STAR)/National Medical Research Council (NMRC), Singapore;
Netherlands Organization for Scientific Research; National Institute of
Allergy and Infectious Diseases, National Institutes of Health
FX L. Chai was supported by the Health Manpower Development Plan (HMDP)
Fellowship, Ministry of Health, Singapore and the International
Fellowship, Agency for Science, Technology and Research
(A*STAR)/National Medical Research Council (NMRC), Singapore.; M.G.
Netea was supported by a Vidi grant of the Netherlands Organization for
Scientific Research.; J.A. Sugui and K.J. Kwon-Chung were supported by
funds from the intramural program of the National Institute of Allergy
and Infectious Diseases, National Institutes of Health.
NR 33
TC 49
Z9 51
U1 0
U2 9
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0171-2985
J9 IMMUNOBIOLOGY
JI Immunobiology
PD NOV
PY 2010
VL 215
IS 11
BP 915
EP 920
DI 10.1016/j.imbio.2009.10.002
PG 6
WC Immunology
SC Immunology
GA 684AN
UT WOS:000284519500008
PM 19939494
ER
PT J
AU Zhu, JF
Paul, WE
AF Zhu, Jinfang
Paul, William E.
TI Peripheral CD4+T-cell differentiation regulated by networks of cytokines
and transcription factors
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE T-helper cells; cytokines; transcription factors; T-cell differentiation
ID FOLLICULAR-HELPER-CELLS; GROWTH-FACTOR-BETA; CD4(+) T-CELLS;
ROR-GAMMA-T; LOCUS-CONTROL REGION; HYPER-IGE SYNDROME; TGF-BETA;
GENE-EXPRESSION; TH2 CELLS; IN-VIVO
AB CD4+ T cells, also known as T-helper (Th) cells, play an important role in orchestrating adaptive immune responses to various infectious agents. They are also involved in the induction of autoimmune and allergic diseases. Upon T-cell receptor (TCR)-mediated cell activation, naive CD4+ T cells can differentiate into at least four major lineages, Th1, Th2, Th17, and iTreg cells, that participate in different types of immune responses. Networks of cytokines and transcription factors are critical for determining CD4+ T-cell fates and effector cytokine production. Here, we review collaboration and cross-regulation between various essential cytokines in the activation/induction of key transcription factors during the process of Th cell differentiation towards these distinct lineages. We also discuss the interactions of key transcription factors at both genetic and protein levels and the function of the resulting network(s) in regulating the expression of effector cytokines.
C1 [Zhu, Jinfang; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 11N311, Bethesda, MD 20892 USA.
EM jfzhu@niaid.nih.gov
RI Zhu, Jinfang/B-7574-2012
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 192
TC 214
Z9 218
U1 4
U2 29
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD NOV
PY 2010
VL 238
BP 247
EP 262
DI 10.1111/j.1600-065X.2010.00951.x
PG 16
WC Immunology
SC Immunology
GA 671MB
UT WOS:000283509100018
PM 20969597
ER
PT J
AU Mineo, TWP
Oliveira, CJF
Gutierrez, FRS
Silva, JS
AF Mineo, Tiago W. P.
Oliveira, Carlo J. F.
Gutierrez, Fredy R. S.
Silva, Joao S.
TI Recognition by toll-like receptor 2 induces antigen-presenting cell
activation and Th1 programming during infection by Neospora caninum
SO IMMUNOLOGY AND CELL BIOLOGY
LA English
DT Article
DE dendritic cells; MyD88; neosporosis; T helper 1 immune response; TLR2
ID DENDRITIC CELLS; TOXOPLASMA-GONDII; DEFINITIVE HOSTS; IMMUNE-RESPONSE;
PARASITE; MICE; GAMMA; IL-12; TOLL-LIKE-RECEPTOR-2; DIFFERENTIATION
AB Neospora caninum is an apicomplexan parasite responsible for major economic losses due to abortions in cattle. Toll-like receptors (TLRs) sense specific microbial products and direct downstream signaling pathways in immune cells, linking innate, and adaptive immunity. Here, we analyze the role of TLR2 on innate and adaptive immune responses during N. caninum infection. Inflammatory peritoneal macrophages and bone marrow-derived dendritic cells exposed to N. caninum-soluble antigens presented an upregulated expression of TLR2. Increased receptor expression was correlated to TLR2/MyD88-dependent antigen-presenting cell maturation and pro-inflammatory cytokine production after stimulation by antigens. Impaired innate responses observed after infection of mice genetically deficient for TLR2((-/-)) was followed by downregulation of adaptive T helper 1 (Th1) immunity, represented by diminished parasite-specific CD4(+) and CD8(+) T-cell proliferation, IFN-gamma:interleukin (IL)-10 ratio, and IgG subclass synthesis. In parallel, TLR2(-/-) mice presented higher parasite burden than wild-type (WT) mice at acute and chronic stages of infection. These results show that initial recognition of N. caninum by TLR2 participates in the generation of effector immune responses against N. caninum and imply that the receptor may be a target for future prophylactic strategies against neosporosis. Immunology and Cell Biology (2010) 88, 825-833; doi:10.1038/icb.2010.52; published online 20 April 2010
C1 [Mineo, Tiago W. P.] Univ Sao Paulo, FMRP, Sch Med Ribeirao Preto, Dept Biochem & Immunol,Immunoparasitol Lab, BR-14049900 Ribeirao Preto, SP, Brazil.
[Mineo, Tiago W. P.] Univ Fed Uberlandia, Inst Biomed Sci, BR-38400 Uberlandia, MG, Brazil.
[Oliveira, Carlo J. F.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Mineo, TWP (reprint author), Univ Sao Paulo, FMRP, Sch Med Ribeirao Preto, Dept Biochem & Immunol,Immunoparasitol Lab, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil.
EM tiago.mineo@pq.cnpq.br; jsdsilva@fmrp.usp.br
RI Mineo, Tiago/B-4153-2009; Silva, Joao/A-4484-2008; Gutierrez, Fredy
RS/C-3911-2009
OI Mineo, Tiago/0000-0002-2339-2743; Gutierrez, Fredy
RS/0000-0001-9873-8342
FU CNPq [473178/2007-9]; FAPESP [2006/06803-4]
FX We thank Cristiane M Milanezi, Dr Deise AO Silva, and Walter M Turato
for technical assistance and Dr Neide M Silva, Djalma S Lima Jr, and
Luciana Benevides for helpful suggestions. We also thank NIAID
intramural editor Brenda Rae Marshall for assistance. TLR2-/-
and MyD88-/- mice were originally provided by Dr Shizuo Akira
(Osaka University, Osaka, Japan). This work was supported by the
Brazilian funding agencies CNPq (473178/2007-9) and FAPESP
(2006/06803-4).
NR 39
TC 15
Z9 15
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0818-9641
EI 1440-1711
J9 IMMUNOL CELL BIOL
JI Immunol. Cell Biol.
PD NOV-DEC
PY 2010
VL 88
IS 8
BP 825
EP 833
DI 10.1038/icb.2010.52
PG 9
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 678UC
UT WOS:000284105400009
PM 20404835
ER
PT J
AU Zumbrun, SD
Hanson, L
Sinclair, JF
Freedy, J
Melton-Celsa, AR
Rodriguez-Canales, J
Hanson, JC
O'Brien, AD
AF Zumbrun, Steven D.
Hanson, Leanne
Sinclair, James F.
Freedy, James
Melton-Celsa, Angela R.
Rodriguez-Canales, Jaime
Hanson, Jeffrey C.
O'Brien, Alison D.
TI Human Intestinal Tissue and Cultured Colonic Cells Contain
Globotriaosylceramide Synthase mRNA and the Alternate Shiga Toxin
Receptor Globotetraosylceramide
SO INFECTION AND IMMUNITY
LA English
DT Article
ID ENTEROHEMORRHAGIC ESCHERICHIA-COLI; MICROVASCULAR ENDOTHELIAL-CELLS;
VEROTOXIN RECEPTORS; GLYCOLIPID BINDING; EPITHELIAL-CELLS; SHIGELLA
TOXIN; MOUSE COLON; HELA-CELLS; GLYCOSPHINGOLIPIDS; PATHOGENESIS
AB Escherichia coli O157:H7 and other Shiga toxin (Stx)-producing E. coli (STEC) bacteria are not enteroinvasive but can cause hemorrhagic colitis. In some STEC-infected individuals, a life-threatening sequela of infection called the hemolytic uremic syndrome may develop that can lead to kidney failure. This syndrome is linked to the production of Stx by the infecting organism. For Stx to reach the kidney, the toxin must first penetrate the colonic epithelial barrier. However, the Stx receptor, globotriaosylceramide (Gb3), has been thought to be absent from human intestinal epithelial cells. Thus, the mechanisms by which the toxin associates with and traverses through the intestine en route to the kidneys have been puzzling aspects of STEC pathogenesis. In this study, we initially determined that both types of Stx made by STEC, Stx1 and Stx2, do in fact bind to colonic epithelia in fresh tissue sections and to a colonic epithelial cell line (HCT-8). We also discovered that globotetraosylceramide (Gb4), a lower-affinity toxin receptor derived from Gb3, is readily detectable on the surfaces of human colonic tissue sections and HCT-8 cells. Furthermore, we found that Gb3 is present on a fraction of HCT-8 cells, where it presumably functions to bind and internalize Stx1 and Stx2. In addition, we established by quantitative real-time PCR (qRT-PCR) that both fresh colonic epithelial sections and HCT-8 cells express Gb3 synthase mRNA. Taken together, our data suggest that Gb3 may be present in small quantities in human colonic epithelia, where it may compete for Stx binding with the more abundantly expressed glycosphingolipid Gb4.
C1 [Zumbrun, Steven D.; Hanson, Leanne; Sinclair, James F.; Freedy, James; Melton-Celsa, Angela R.; O'Brien, Alison D.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
[Rodriguez-Canales, Jaime; Hanson, Jeffrey C.] NCI, Laser Capture Microdissect Core Facil, Pathol Lab, NIH, Bethesda, MD 20814 USA.
RP O'Brien, AD (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM aobrien@usuhs.mil
OI Rodriguez-Canales, Jaime/0000-0002-0885-2377; O'Brien,
Alison/0000-0002-1315-3204
FU National Institutes of Health [AI57168, AI20148]
FX This work was supported by grants AI57168 and AI20148 from the National
Institutes of Health.
NR 61
TC 26
Z9 26
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2010
VL 78
IS 11
BP 4488
EP 4499
DI 10.1128/IAI.00620-10
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 665RB
UT WOS:000283052100005
PM 20732996
ER
PT J
AU Goodman, AL
Epp, C
Moss, D
Holder, AA
Wilson, JM
Gao, GP
Long, CA
Remarque, EJ
Thomas, AW
Ammendola, V
Colloca, S
Dicks, MDJ
Biswas, S
Seibel, D
van Duivenvoorde, LM
Gilbert, SC
Hill, AVS
Draper, SJ
AF Goodman, Anna L.
Epp, C.
Moss, D.
Holder, A. A.
Wilson, J. M.
Gao, G. P.
Long, C. A.
Remarque, E. J.
Thomas, A. W.
Ammendola, V.
Colloca, S.
Dicks, M. D. J.
Biswas, S.
Seibel, D.
van Duivenvoorde, L. M.
Gilbert, S. C.
Hill, A. V. S.
Draper, S. J.
TI New Candidate Vaccines against Blood-Stage Plasmodium falciparum
Malaria: Prime-Boost Immunization Regimens Incorporating Human and
Simian Adenoviral Vectors and Poxviral Vectors Expressing an Optimized
Antigen Based on Merozoite Surface Protein 1
SO INFECTION AND IMMUNITY
LA English
DT Article
ID CARBOXYL-TERMINAL FRAGMENT; T-CELL EPITOPES; PROTECTIVE IMMUNITY;
ANTIBODY-RESPONSES; PARASITE GROWTH; RHESUS-MONKEYS; CLINICAL-TRIAL;
LIVER STAGE; IN-VITRO; YOELII
AB Although merozoite surface protein 1 (MSP-1) is a leading candidate vaccine antigen for blood-stage malaria, its efficacy in clinical trials has been limited in part by antigenic polymorphism and potentially by the inability of protein-in-adjuvant vaccines to induce strong cellular immunity. Here we report the design of novel vectored Plasmodium falciparum vaccines capable of overcoming such limitations. We optimized an antigenic insert comprising the four conserved blocks of MSP-1 fused to tandemly arranged sequences that represent both allelic forms of the dimorphic 42-kDa C-terminal region. Inserts were expressed by adenoviral and poxviral vectors and employed in heterologous prime-boost regimens. Simian adenoviral vectors were used in an effort to circumvent preexisting immunity to human adenoviruses. In preclinical studies these vaccines induced potent cellular immune responses and high-titer antibodies directed against MSP-1. The antibodies induced were found to have growth-inhibitory activity against dimorphic allelic families of P. falciparum. These vectored vaccines should allow assessment in humans of the safety and efficacy of inducing strong cellular as well as cross-strain humoral immunity to P. falciparum MSP-1.
C1 [Goodman, Anna L.; Dicks, M. D. J.; Biswas, S.; Gilbert, S. C.; Hill, A. V. S.; Draper, S. J.] Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England.
[Epp, C.; Seibel, D.] Univ Klinikum Heidelberg, Inst Hyg, Abt Parasitol, D-69120 Heidelberg, Germany.
[Moss, D.; Holder, A. A.] Natl Inst Med Res, Div Parasitol, MRC, London NW7 1AA, England.
[Gao, G. P.] Univ Penn, Gene Therapy Program, Div Transfus Med, Dept Pathol & Lab Med,Translat Res Labs, Philadelphia, PA 19104 USA.
[Long, C. A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Remarque, E. J.; Thomas, A. W.] Biomed Primate Res Ctr, NL-2288 GJ Rijswijk, Netherlands.
[Ammendola, V.; Colloca, S.] Okairos AG, I-00040 Rome, Italy.
RP Goodman, AL (reprint author), Univ Oxford, Jenner Inst, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, England.
EM anna.goodman@nhs.net
RI Draper, Simon/F-1758-2011; Holder, Anthony/A-7554-2013; Wilson,
James/F-9220-2011;
OI Draper, Simon/0000-0002-9415-1357; Holder, Anthony/0000-0002-8490-6058;
Wilson, James/0000-0002-9630-3131; Dicks, Matthew/0000-0003-1909-7095;
Gilbert, Sarah/0000-0002-6823-9750
FU Medical Research Council [G0600424, U117532067]; Division of Intramural
Research, National Institutes of Allergy and Infectious Diseases,
National Institutes of Health; PATH/Malaria Vaccine Initiative; European
Commission through the European Malaria Vaccine Development Association
[LSH-2005-037506]; NIDDK [P30 DK-47757]; ReGenX
FX This work was supported primarily by grant G0600424 and in part by
funding agreement U117532067 from the Medical Research Council. In
addition, this work was supported in part by the Division of Intramural
Research, National Institutes of Allergy and Infectious Diseases,
National Institutes of Health, and also by the PATH/Malaria Vaccine
Initiative for support of the GIA Reference Center and by the European
Commission through the European Malaria Vaccine Development Association,
contract LSH-2005-037506. This work was also funded by NIDDK grant P30
DK-47757 (J.M.W.). S.J.D. is a Junior Research Fellow of Merton College,
Oxford. A. V. S. H. is a Wellcome Trust Principal Research Fellow. A. L.
G. was an MRC clinical training fellow while undertaking this research.;
A.L.G., S. C. G., A. V. S. H., and S.J.D. are named inventors on patent
applications covering vectored malaria vaccines and immunization
regimens. Authors from Okairos are employees of and/or shareholders in
Okairos, which is developing vectored malaria vaccines. J.M.W. is a
consultant to ReGenX Holdings and is a founder of, holds equity in, and
receives a grant from affiliates of ReGenX Holdings; in addition, he is
an inventor on patents licensed to various biopharmaceutical companies,
including affiliates of ReGenX Holdings.
NR 60
TC 38
Z9 38
U1 1
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2010
VL 78
IS 11
BP 4601
EP 4612
DI 10.1128/IAI.00315-10
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 665RB
UT WOS:000283052100017
PM 20713623
ER
PT J
AU Mahajan, B
Berzofsky, JA
Boykins, RA
Majam, V
Zheng, H
Chattopadhyay, R
de la Vega, P
Moch, JK
Haynes, JD
Belyakov, IM
Nakhasi, HL
Kumar, S
AF Mahajan, Babita
Berzofsky, Jay A.
Boykins, Robert A.
Majam, Victoria
Zheng, Hong
Chattopadhyay, Rana
de la Vega, Patricia
Moch, J. Kathleen
Haynes, J. David
Belyakov, Igor M.
Nakhasi, Hira L.
Kumar, Sanjai
TI Multiple Antigen Peptide Vaccines against Plasmodium falciparum Malaria
SO INFECTION AND IMMUNITY
LA English
DT Article
ID B-CELL EPITOPES; RED-BLOOD-CELLS; CIRCUMSPOROZOITE PROTEIN; T-CELL;
SYNTHETIC PEPTIDES; SPOROZOITE VACCINE; IMMUNE-RESPONSE;
SURFACE-ANTIGEN; ANTIBODIES; IMMUNOGENICITY
AB The multiple antigen peptide (MAP) approach is an effective method to chemically synthesize and deliver multiple T-cell and B-cell epitopes as the constituents of a single immunogen. Here we report on the design, chemical synthesis, and immunogenicity of three Plasmodium falciparum MAP vaccines that incorporated antigenic epitopes from the sporozoite, liver, and blood stages of the life cycle. Antibody and cellular responses were determined in three inbred (C57BL/6, BALB/c, and A/J) strains, one congenic (HLA-A2 on the C57BL/6 background) strain, and one outbred strain (CD1) of mice. All three MAPs were immunogenic and induced both antibody and cellular responses, albeit in a somewhat genetically restricted manner. Antibodies against MAP-1, MAP-2, and MAP-3 had an antiparasite effect that was also dependent on the mouse major histocompatibility complex background. Anti-MAP-1 (CSP-based) antibodies blocked the invasion of HepG2 liver cells by P. falciparum sporozoites (highest, 95.16% in HLA-A2 C57BL/6; lowest, 11.21% in BALB/c). Furthermore, antibodies generated following immunizations with the MAP-2 (PfCSP, PfLSA-1, PfMSP-1(42), and PfMSP-3b) and MAP-3 (PfRAP-1, PfRAP-2, PfSERA, and PfMSP-1(42)) vaccines were able to reduce the growth of blood stage parasites in erythrocyte cultures to various degrees. Thus, MAP-based vaccines remain a viable option to induce effective antibody and cellular responses. These results warrant further development and preclinical and clinical testing of the next generation of candidate MAP vaccines that are based on the conserved protective epitopes from Plasmodium antigens that are widely recognized by populations of divergent HLA types from around the world.
C1 [Kumar, Sanjai] US FDA, Malaria Res Program, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Berzofsky, Jay A.; Belyakov, Igor M.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[de la Vega, Patricia; Moch, J. Kathleen; Haynes, J. David] USN, Med Res Ctr, Silver Spring, MD USA.
[de la Vega, Patricia; Moch, J. Kathleen; Haynes, J. David] Walter Reed Army Inst Res, Silver Spring, MD USA.
RP Kumar, S (reprint author), US FDA, Malaria Res Program, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
EM Sanjai.kumar@fda.hhs.gov
NR 63
TC 24
Z9 29
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2010
VL 78
IS 11
BP 4613
EP 4624
DI 10.1128/IAI.00533-10
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 665RB
UT WOS:000283052100018
PM 20823210
ER
PT J
AU Henderson, DK
Palmore, TN
AF Henderson, David K.
Palmore, Tara N.
TI Critical Gaps in Knowledge of the Epidemiology and Pathophysiology of
Healthcare-Associated Infections
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Article; Proceedings Paper
CT 5th Decennial International Conference on Healthcare Associated
Infections
CY MAR 18-22, 2010
CL Atlanta, GA
SP Soc Healthcare Epidemiol Amer, Ctr Dis Control & Prevention, Assoc Professionals Infect Control, Infect Diseases Soc Amer
AB The past decade has witnessed an intense interest in healthcare-associated infections as well as increases in legislation and reporting requirements aimed at decreasing the number of these costly infections. In the next decade, healthcare epidemiology must address major gaps in understanding of the epidemiology and pathogenesis of healthcare-associated infections and in knowledge of the efficacy of interventions for healthcare-associated infections and the efficacy in implementing such interventions.
C1 [Henderson, David K.; Palmore, Tara N.] NIH, Off Director, Ctr Clin, Bethesda, MD 20892 USA.
[Palmore, Tara N.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Henderson, DK (reprint author), NIH, Off Director, Ctr Clin, Bldg 10,Room 6-1480,10 Ctr Dr MSC 1504, Bethesda, MD 20892 USA.
EM dkh@nih.gov
NR 8
TC 10
Z9 10
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD NOV
PY 2010
VL 31
SU 1
BP S4
EP S6
DI 10.1086/655984
PG 3
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 675PE
UT WOS:000283841800002
PM 20929367
ER
PT J
AU Henderson, DK
AF Henderson, David K.
TI Opportunists and Opportunities: The 2010 SHEA Lecture
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Article; Proceedings Paper
CT 5th Decennial International Conference on Healthcare Associated
Infections
CY MAR 18-22, 2010
CL Atlanta, GA
SP Soc Healthcare Epidemiol Amer, Ctr Dis Control & Prevention, Assoc Professionals Infect Control, Infect Dis Soc Amer
ID HUMAN-IMMUNODEFICIENCY-VIRUS; LYMPHADENOPATHY-ASSOCIATED VIRUS;
HEALTH-CARE WORKERS; OCCUPATIONAL EXPOSURES; UNIVERSAL PRECAUTIONS; HIV;
PROPHYLAXIS; BLOOD; RISK
AB My experience as a hospital epidemiologist at the National Institutes of Health Clinical Center has underscored the importance of aggressively managing infection with opportunistic pathogens and of taking advantage of opportunities as they arise (most often as crises). I review selected aspects of my career and use these as examples of the opportunists and opportunities now facing healthcare epidemiology.
C1 NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Henderson, DK (reprint author), NIH, Ctr Clin, Bldg 10,Room 6-1480,10 Ctr Dr MSC 1504, Bethesda, MD 20892 USA.
EM dkh@nih.gov
NR 14
TC 0
Z9 0
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
EI 1559-6834
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD NOV
PY 2010
VL 31
SU 1
BP S66
EP S69
DI 10.1086/655983
PG 4
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 675PE
UT WOS:000283841800019
PM 20929375
ER
PT J
AU Morens, DM
Taubenberger, JK
AF Morens, David M.
Taubenberger, Jeffery K.
TI Historical thoughts on influenza viral ecosystems, or behold a pale
horse, dead dogs, failing fowl, and sick swine
SO INFLUENZA AND OTHER RESPIRATORY VIRUSES
LA English
DT Article; Proceedings Paper
CT International Symposium on Neglected Influenza Viruses
CY FEB 03-05, 2010
CL Amelia Island, FL
DE Equine; history; influenza
ID AVIAN H5N1 INFLUENZA; A VIRUSES; EQUINE INFLUENZA; PANDEMIC INFLUENZA;
CANINE INFLUENZA; RISK-ASSESSMENT; NORTH-AMERICA; WILD BIRDS;
EPIDEMIOLOGY; TRANSMISSION
AB Objectives To understand human influenza in a historical context of viral circulation in avian species, mammals, and in the environment.
Design Historical review.
Setting Global events in a variety of circumstances over more than 3,000 years time.
Sample Comprehensive review of the historical literature including all major publications on pandemic and panzootic influenza.
Main Outcome Measures Influenza pandemics, panzootics, major epidemics and epizootics, and instances of interspecies transmission of influenza A.
Results Extensive documentation of human and animal influenza over many centuries suggests that influenza A viruses have adapted to a variety of species and environmental milieu and are capable of switching between many different hosts under widely varying circumstances.
Conclusions The genetic elements of influenza A viruses circulate globally in an extensive ecosystem comprised of many avian and mammalian species and a spectrum of environments. Unstable gene constellations found in avian species become stable viruses only upon switching to secondary hosts, but may then adapt and circulate independently. It may be desirable to think of influenza A viruses as existing and evolving in a large ecosystem involving multiple hosts and environments. Implications for understanding human influenza are discusssed.
C1 [Morens, David M.] NIAID, NIH, OD, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, NIH, OD, Bldg 31,Room 7A-03, Bethesda, MD 20892 USA.
EM dm270q@nih.gov
FU Management & Delivery Branch, Document Delivery Section, NIH Library;
History of Medicine Division, National Library of Medicine
FX We thank Betty Murgolo and the staff of the Collection, Management &
Delivery Branch, Document Delivery Section, NIH Library, and the staff
of the History of Medicine Division, National Library of Medicine, for
research support; and John Weddle for assistance with image
reproduction.
NR 120
TC 36
Z9 36
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1750-2640
EI 1750-2659
J9 INFLUENZA OTHER RESP
JI Influenza Other Respir. Viruses
PD NOV
PY 2010
VL 4
IS 6
BP 327
EP 337
DI 10.1111/j.1750-2659.2010.00148.x
PG 11
WC Infectious Diseases; Virology
SC Infectious Diseases; Virology
GA 669WY
UT WOS:000283382100002
PM 20958926
ER
PT J
AU Morens, DM
Taubenberger, JK
AF Morens, David M.
Taubenberger, Jeffery K.
TI An avian outbreak associated with panzootic equine influenza in 1872: an
early example of highly pathogenic avian influenza?
SO INFLUENZA AND OTHER RESPIRATORY VIRUSES
LA English
DT Article; Proceedings Paper
CT International Symposium on Neglected Influenza Viruses
CY FEB 03-05, 2010
CL Amelia Island, FL
DE Avian influenza; epizootic; equine influenza; highly pathogenic avian
influenza; influenza poultry
ID PANDEMIC INFLUENZA
AB Background An explosive fatal epizootic in poultry, prairie chickens, turkeys, ducks and geese, occurred over much of the populated United States between 15 November and 15 December 1872. To our knowledge the scientific literature contains no mention of the nationwide 1872 poultry outbreak.
Objective To understand avian influenza in a historical context.
Results The epizootic progressed in temporal-geographic association with a well-reported panzootic of equine influenza that had begun in Canada during the last few days of September 1872. The 1872 avian epizootic was universally attributed at the time to equine influenza, a disease then of unknown etiology but widely believed to be caused by the same transmissible respiratory agent that caused human influenza.
Conclusions Another microbial agent could have caused the avian outbreak; however, its strong temporal and geographic association with the equine panzootic, and its clinical and epidemiologic features, are most consistent with highly pathogenic avian influenza. The avian epizootic could thus have been an early instance of highly pathogenic avian influenza.
C1 [Morens, David M.; Taubenberger, Jeffery K.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dm270q@nih.gov
FU NIH; NIAID
FX This work was supported by the Intramural Research Program of the NIH
and the NIAID.
NR 30
TC 8
Z9 8
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1750-2640
EI 1750-2659
J9 INFLUENZA OTHER RESP
JI Influenza Other Respir. Viruses
PD NOV
PY 2010
VL 4
IS 6
BP 373
EP 377
DI 10.1111/j.1750-2659.2010.00181.x
PG 5
WC Infectious Diseases; Virology
SC Infectious Diseases; Virology
GA 669WY
UT WOS:000283382100008
PM 20958931
ER
PT J
AU Ribeiro, JMC
Mans, BJ
Arca, B
AF Ribeiro, Jose M. C.
Mans, Ben J.
Arca, Bruno
TI An insight into the sialome of blood-feeding Nematocera
SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Review
DE Salivary glands; Hematophagy; Mosquitoes; Sand flies; Black flies;
Biting midges; Feeding; Vector
ID VECTOR ANOPHELES-GAMBIAE; FLY LUTZOMYIA-LONGIPALPIS; MOSQUITO
AEDES-AEGYPTI; ADULT FEMALE MOSQUITO; YELLOW-FEVER MOSQUITO; SALIVARY
ADENOSINE-DEAMINASE; AMERICAN VISCERAL LEISHMANIASIS; ABUNDANT SECRETED
PROTEINS; PHLEBOTOMINE SAND FLIES; TICK IXODES-SCAPULARIS
AB Within the Diptera and outside the suborder Brachycera, the blood-feeding habit occurred at least twice, producing the present day sand flies, and the Culicomorpha, including the mosquitoes (Culicidae), black flies (Simulidae), biting midges (Ceratopogonidae) and frog feeding flies (Corethrellidae). Alternatives to this scenario are also discussed. Successful blood-feeding requires adaptations to antagonize the vertebrate's mechanisms of blood clotting, platelet aggregation, vasoconstriction, pain and itching, which are triggered by tissue destruction and immune reactions to insect products. Saliva of these insects provides a complex pharmacological armamentarium to block these vertebrate reactions. With the advent of transcriptomics, the sialomes (from the Greek word sialo = saliva) of at least two species of each of these families have been studied (except for the frog feeders), allowing an insight into the diverse pathways leading to today's salivary composition within the Culicomorpha, having the sand flies as an outgroup. This review catalogs 1288 salivary proteins in 10 generic classes comprising over 150 different protein families, most of which we have no functional knowledge. These proteins and many sequence comparisons are displayed in a hyperlinked spreadsheet that hopefully will stimulate and facilitate the task of functional characterization of these proteins, and their possible use as novel pharmacological agents and epidemiological markers of insect vector exposure. Published by Elsevier Ltd.
C1 [Ribeiro, Jose M. C.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, Rockville, MD 20852 USA.
[Mans, Ben J.] Onderstepoort Vet Inst, Pretoria, South Africa.
[Mans, Ben J.] Univ Pretoria, Dept Vet Trop Dis, ZA-0002 Pretoria, South Africa.
[Arca, Bruno] Univ Federico II, Dept Struct & Funct Biol, Naples, Italy.
RP Ribeiro, JMC (reprint author), NIAID, Sect Vector Biol, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy,Room 2E32D, Rockville, MD 20852 USA.
EM Jribeiro@niaid.nih.gov
OI Arca, Bruno/0000-0002-4029-0984; Mans, Ben/0000-0002-0177-0029; Ribeiro,
Jose/0000-0002-9107-0818
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, USA
FX This work was supported in part by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, USA. Because J.M.C.R. is a government employee and
this is a government work, the work is in the public domain in the
United States. Notwithstanding any other agreements, the NIH reserves
the right to provide the work to PubMedCentral for display and use by
the public, and PubMedCentral may tag or modify the work consistent with
its customary practices. You can establish rights outside of the U.S.
subject to a government use license.
NR 173
TC 80
Z9 81
U1 2
U2 22
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0965-1748
J9 INSECT BIOCHEM MOLEC
JI Insect Biochem. Mol. Biol.
PD NOV
PY 2010
VL 40
IS 11
BP 767
EP 784
DI 10.1016/j.ibmb.2010.08.002
PG 18
WC Biochemistry & Molecular Biology; Entomology
SC Biochemistry & Molecular Biology; Entomology
GA 673EA
UT WOS:000283640700001
PM 20728537
ER
PT J
AU Song, SM
Kole, S
Precht, P
Pazin, MJ
Bernier, M
AF Song, Shaoming
Kole, Sutapa
Precht, Patricia
Pazin, Michael J.
Bernier, Michel
TI Activation of heat shock factor 1 plays a role in pyrrolidine
dithiocarbamate-mediated expression of the co-chaperone BAG3
SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
LA English
DT Article
DE Hsp90; Pyrrolidine dithiocarbamate; Transcriptional regulation; Protein
thiols; Chromatin immunoprecipitation
ID FACTOR-KAPPA-B; NITRIC-OXIDE SYNTHASE; CANCER-CELLS; TRANSCRIPTION
FACTOR-1; REPERFUSION INJURY; GENE-EXPRESSION; PROTEIN; APOPTOSIS;
INHIBITION; DIFFERENTIATION
AB Adaptive responses to physical and inflammatory stressors are mediated by transcription factors and molecular chaperones. The transcription factor heat shock factor 1 (HSF1) has been implicated in extending lifespan in part by increasing expression of heat shock response genes. Pyrrolidine dithiocarbamate (PDTC) is a small thiol compound that exerts in vivo and in vitro anti-inflammatory properties through mechanisms that remain unclear. Here we report that PDTC induced the release of monomeric HSF1 from the molecular chaperone heat shock protein 90 (Hsp90), with concomitant increase in HSF1 trimer formation, translocation to the nucleus, and binding to promoter of target genes in human HepG2 cells. siRNA-mediated silencing of HSF1 blocked BAG3 gene expression by PDTC. The protein levels of the cochaperone BAG3 and its interaction partner Hsp72 were stimulated by PDTC in a dose-dependent fashion, peaking at 6 h. Inhibition of Hsp90 function by geldanamycin derivatives and novobiocin elicited a pattern of FISH activation and BAG3 expression that was similar to PDTC. Chromatin immunoprecipitation studies showed that PDTC and the inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin enhanced the binding of HSF1 to the promoter of several target genes, including BAG3, HSPA1A, HSPA1B, FKBP4, STIP1 and UBB. Cell treatment with PDTC increased significantly the level of Hsp90 alpha thiol oxidation, a posttranslational modification known to inhibit its chaperone function. These results unravel a previously unrecognized mechanism by which PDTC and related compounds could confer cellular protection against inflammation through HSF1-induced expression of heat shock response genes. Published by Elsevier Ltd.
C1 [Song, Shaoming; Bernier, Michel] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA.
[Precht, Patricia; Pazin, Michael J.] NIA, Lab Cellular & Mol Biol, NIH, Baltimore, MD 21224 USA.
[Kole, Sutapa] MedStar Res Inst, Hyattsville, MD 20783 USA.
RP Bernier, M (reprint author), NIA, Clin Invest Lab, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM songs2@mail.nih.gov; KoleS@grc.nia.nih.gov; prechtp@mail.nih.gov;
pazinm@mail.nih.gov; Bernierm@mail.nih.gov
OI Bernier, Michel/0000-0002-5948-368X; Pazin, Michael/0000-0002-7561-3640
FU NIH, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Institute on Aging.
NR 37
TC 13
Z9 13
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1357-2725
J9 INT J BIOCHEM CELL B
JI Int. J. Biochem. Cell Biol.
PD NOV
PY 2010
VL 42
IS 11
BP 1856
EP 1863
DI 10.1016/j.biocel.2010.07.021
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 673YA
UT WOS:000283698900017
PM 20692357
ER
PT J
AU Khalili, S
Liu, YN
Sumita, Y
Maria, OM
Blank, D
Key, S
Mezey, E
Tran, SD
AF Khalili, Saeed
Liu, Younan
Sumita, Yoshinori
Maria, Ola M.
Blank, David
Key, Sharon
Mezey, Eva
Tran, Simon D.
TI Bone marrow cells are a source of undifferentiated cells to prevent
Sjogren's syndrome and to preserve salivary glands function in the
non-obese diabetic mice
SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
LA English
DT Article
DE Sjogren's syndrome; Bone marrow cells; Cell therapy; Xerostomia;
Salivary gland; Saliva
ID COLONY-STIMULATING FACTOR; MESENCHYMAL STEM-CELLS; NOD MICE; AUTOIMMUNE
EXOCRINOPATHY; EPITHELIAL-CELLS; TRANSPLANTATION; DISEASE; REVERSAL;
THERAPY; PATHOGENESIS
AB Non-obese diabetic (NOD) mice develop Sjogren's-like syndrome (Ss) and a gradual loss of saliva secretory function. Our previous study showed that injections of matched normal spleen cells with Complete Freund's Adjuvant (CFA) reversed salivary gland dysfunction in 14-week-old NOD mice, which had established Ss. The spleen and bone marrow are closely related organs, and both are among the first sites of hematopoiesis during gestation. Noticing a rapidly increasing number of clinical trials using bone marrow (BM) cells treatments for autoimmune diseases, we tested if BM cells can prevent Ss and restore salivary glands' function. We injected CFA and MHC class I-matched normal BM cells in 7-week-old NOD mice, which had not yet developed Ss. We found at week 52 post-treatment that all NOD mice receiving BM cells and CFA had a recovery of salivary flow and were protected from Ss and diabetes. BM cells-treated mice had their salivary function restored quantitatively and qualitatively. Saliva flow was higher (p < 0.05) in BM cells-transplanted mice when compared to control mice, which continued to deteriorate over time. Total proteins, epidermal growth factor, amylase, and electrolytes concentrations in saliva of BM cells-treated mice were not significantly changed at week 44 and 52 post-therapy when compared to pre-therapy (when the mice did not have Ss). Restoration of salivary flow could have resulted from a combination of rescue and paracrine effects from BM cells. This study suggests that a combined immuno- and cell-based therapy can permanently prevent Ss and restored salivary function in NOD mice. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Khalili, Saeed; Liu, Younan; Sumita, Yoshinori; Maria, Ola M.; Tran, Simon D.] McGill Univ, Fac Dent, Montreal, PQ H3A 2B2, Canada.
[Sumita, Yoshinori] Nagasaki Univ, Dept Regenerat Oral Surg, Nagasaki 852, Japan.
[Blank, David] McGill Univ, Fac Med, Montreal, PQ H3A 2B2, Canada.
[Key, Sharon; Mezey, Eva] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA.
RP Tran, SD (reprint author), McGill Univ, Fac Dent, 3640 Univ St,Room M-43, Montreal, PQ H3A 2B2, Canada.
EM saeed.khalili@mail.mcgill.ca; younan.liu@mcgill.ca;
y-sumita@nagasaki-u.ac.jp; ola.maria@mail.mcgill.ca;
david.blank@muhc.mcgill.ca; KeyS@nidcr.nih.gov; mezeye@mail.nih.gov;
simon.tran@mcgill.ca
FU Canadian Institutes of Health Research (CIHR); Canada Research Chair;
National Institute of Dental and Craniofacial Research (NIDCR), NIH
FX We wish to thank Drs. R James Turner (NIDCR/NIH, for donating the
NaKCl-cotransporter antibody), Mari Kaartinen, Dieter Reinhardt, Noreen
Jane Bider, Jose Correa, Yonit Rebibo, and Neena Hanif. We also wish to
thank the staff at the McGill University animal facility and the Centre
for Bone and Periodontal Research. This study was supported in part by
research funding from the Canadian Institutes of Health Research (CIHR),
Canada Research Chair, and the Intramural Research Program of the
National Institute of Dental and Craniofacial Research (NIDCR), NIH.
NR 39
TC 9
Z9 12
U1 1
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1357-2725
J9 INT J BIOCHEM CELL B
JI Int. J. Biochem. Cell Biol.
PD NOV
PY 2010
VL 42
IS 11
BP 1893
EP 1899
DI 10.1016/j.biocel.2010.08.008
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 673YA
UT WOS:000283698900021
PM 20732442
ER
PT J
AU Micozzi, D
Pucciarelli, S
Carpi, FM
Costanzi, S
De Sanctis, G
Polzonetti, V
Natalini, P
Santarelli, IF
Vita, A
Vincenzetti, S
AF Micozzi, Daniela
Pucciarelli, Stefania
Carpi, Francesco M.
Costanzi, Stefano
De Sanctis, Giampiero
Polzonetti, Valeria
Natalini, Paolo
Santarelli, Ivano F.
Vita, Alberto
Vincenzetti, Silvia
TI Role of tyrosine 33 residue for the stabilization of the tetrameric
structure of human cytidine deaminase
SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
LA English
DT Article
DE Cytidine deaminase; Site-directed mutagenesis; Molecular modeling;
Circular dichroism
ID CRYSTAL-STRUCTURE; PHARMACOLOGICAL CHAPERONES; CIRCULAR-DICHROISM;
GLYCEROL; PROTEIN; EXPRESSION; RESOLUTION; INHIBITOR; DISEASE; RESCUE
AB In the present work the effect of a mutation on tyrosine 33 residue (Y33G) of human cytidine deaminase (CDA) was investigated with regard to protein solubility and specific activity. Osmolytes and CDA ligands were used to increase the yield and the specific activity of the protein. The mutant enzyme was purified and subjected to a kinetic characterization and to stability studies. These investigations reinforced the hypothesis that in human CDA the side chain of Y33 is involved in intersubunit interactions with four glutamate residues (E108) forming a double latch that connects each of the two pairs of monomers of the tetrameric CDA. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Vita, Alberto; Vincenzetti, Silvia] Univ Camerino, Sch Vet Med Sci, I-62032 Camerino, MC, Italy.
[Micozzi, Daniela; Pucciarelli, Stefania; Carpi, Francesco M.; De Sanctis, Giampiero; Polzonetti, Valeria; Natalini, Paolo] Sch Biosci & Biotechnol, I-62032 Camerino, MC, Italy.
[Costanzi, Stefano] NIDDKD, Lab Biol Modeling, NIH, DHHS, Bethesda, MD 20892 USA.
[Santarelli, Ivano F.] Univ Camerino, Sch Pharm, I-62032 Camerino, MC, Italy.
RP Vincenzetti, S (reprint author), Univ Camerino, Sch Vet Med Sci, Via Gentile 3 Varano, I-62032 Camerino, MC, Italy.
EM daniela.micozzi@unicam.it; stefania.pucciarelli@unicam.it;
francesco.carpi@unicam.it; StefanoC@intra.niddk.nih.gov;
giampiero.desanctis@unicam.it; valeria.polzonetti@unicam.it;
paolo.natalini@unicam.it; ivanofranco.santarelli@unicam.it;
alberto.vita@unicam.it; silvia.vincenzetti@unicam.it
RI Costanzi, Stefano/G-8990-2013;
OI Costanzi, Stefano/0000-0003-3183-7332
FU Intramural NIH HHS
NR 27
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0141-8130
EI 1879-0003
J9 INT J BIOL MACROMOL
JI Int. J. Biol. Macromol.
PD NOV 1
PY 2010
VL 47
IS 4
BP 471
EP 482
DI 10.1016/j.ijbiomac.2010.07.001
PG 12
WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science
SC Biochemistry & Molecular Biology; Chemistry; Polymer Science
GA 665AT
UT WOS:000283007000008
PM 20637228
ER
PT J
AU Mani, H
Merino, MJ
AF Mani, Haresh
Merino, Maria J.
TI Mesothelial Neoplasms Presenting as, and Mimicking, Ovarian Cancer
SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY
LA English
DT Article
DE Ovary; Mesothelioma; Mural nodule; Mucinous tumor
ID PERITONEAL INCLUSION CYSTS; MUCINOUS TUMORS; MURAL NODULES;
CLINICOPATHOLOGICAL ANALYSIS; MULTICYSTIC MESOTHELIOMA; ANAPLASTIC
CARCINOMA; TRACT; WOMEN
AB Mesotheliomas of the abdominal cavity are rare tumors that primarily involve the peritoneum, mesentery, and omentum. The involvement of the viscera is usually secondary to bulky and extensive serosal disease. We describe 7 cases of mesothelioma in which the initial manifestation was that of an ovarian mass. All patients underwent surgery with a primary diagnosis of ovarian cancer. Clinical histories, gross features, and histology slides were reviewed. Immunostains were performed on all cases and electron microscopy was performed in 2 cases. The patients ranged in age from 22 to 52 years and the lesions ranged in size from 3.8 to 9 cm. Of the 7 cases, 4 were predominantly cystic and 3 were solid. Histologically, all cystic tumors were multicystic mesothelioma, whereas the 3 solid tumors were diffuse malignant mesotheliomas. One patient had a borderline mucinous tumor with the mesothelioma occurring as a mural nodule, an association not described earlier. The oldest patient in this series had a diffuse malignant mesothelioma of the peritoneum with predominant ovarian surface involvement. Mesothelial neoplasms can present as ovarian masses in young women. Awareness of this presentation is important to establish appropriate management.
C1 [Mani, Haresh; Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Merino, MJ (reprint author), NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM mjmerino@mail.nih.gov
FU National Cancer Institute, National Institutes of Health, Bethesda, MD
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health, Bethesda, MD.
NR 31
TC 6
Z9 9
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-1691
J9 INT J GYNECOL PATHOL
JI Int. J. Gynecol. Pathol.
PD NOV
PY 2010
VL 29
IS 6
BP 523
EP 528
DI 10.1097/PGP.0b013e3181e6a3ee
PG 6
WC Obstetrics & Gynecology; Pathology
SC Obstetrics & Gynecology; Pathology
GA 668JK
UT WOS:000283264400003
PM 20881862
ER
PT J
AU Lu, C
Chen, Z
AF Lu, Chi
Chen, Zhi
TI MOS hydrogen sensor with very fast response based on ulitra-thin thermal
SiO2 film
SO INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
LA English
DT Article
DE MOS capacitor; H-2 Sensor; Ultra thin thermal SiO2 film; Response time;
SiO2 bulk trap
ID SILICON DIOXIDE; SENSING PROPERTIES; OXIDE; INTERFACE; PALLADIUM;
DIELECTRICS; TRANSISTOR; DIODES; STATES; CELLS
AB An MOS capacitor type hydrogen gas sensor was fabricated with the structure of Ni/SiO2/Si by using conventional silicon wafer technologies Grown by dry oxidation at 900 C the thickness of the SiO2 film was only 24 A At 150 degrees C comparing to another MOS capacitor with 148 A thick oxide and otherwise identical configurations this sensor showed much faster response speed (the time interval to reach half of the magnitude of the steady state signal or t(50%) was only 4 s in response to 1% H-2 without deduction of the delay from the gas delivery system) as well as enhanced signal magnitude (about two times of the former for 1% H-2) Based on the hydrogen binding to the traps in the bulk SiO2 a mechanism was proposed to explain the very short response time on the device with the ultra thin SiO2 The gate leakage in the device is also discussed The presented sensor demonstrates a promising step in designing low cost H-2 detectors with very fast responses (C) 2010 Professor T Nejat Veziroglu Published by Elsevier Ltd All rights reserved
C1 [Lu, Chi] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
[Lu, Chi; Chen, Zhi] Univ Kentucky, Dept Elect & Comp Engn, Lexington, KY 40506 USA.
[Lu, Chi; Chen, Zhi] Univ Kentucky, Ctr Nanoscale Sci & Engn, Lexington, KY 40506 USA.
RP Lu, C (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
FU Department of Energy [DE FG26 04NT42171]; National Science Foundation
[ECS 0609064]
FX This research work was supported by the Department of Energy (DE FG26
04NT42171) and National Science Foundation (ECS 0609064) We thank Dr
Shibin Li and Ms Jing Guo for technical assistance
NR 31
TC 9
Z9 9
U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0360-3199
J9 INT J HYDROGEN ENERG
JI Int. J. Hydrog. Energy
PD NOV
PY 2010
VL 35
IS 22
SI SI
BP 12561
EP 12567
DI 10.1016/j.ijhydene.2010.08.031
PG 7
WC Chemistry, Physical; Electrochemistry; Energy & Fuels
SC Chemistry; Electrochemistry; Energy & Fuels
GA 681GA
UT WOS:000284298200046
ER
PT J
AU Xu, JJ
Yan, X
Gao, RT
Mao, LS
Cotrim, AP
Zheng, CY
Zhang, CM
Baum, BJ
Wang, SL
AF Xu, Junji
Yan, Xing
Gao, Runtao
Mao, Lisha
Cotrim, Ana P.
Zheng, Changyu
Zhang, Chunmei
Baum, Bruce J.
Wang, Songlin
TI EFFECT OF IRRADIATION ON MICROVASCULAR ENDOTHELIAL CELLS OF PAROTID
GLANDS IN THE MINIATURE PIG
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Salivary glands; Radiotherapy; Microvessel density; Endothelial cells;
Sphingomyelinase
ID RADIATION-INDUCED APOPTOSIS; ANIMAL-MODEL; ORAL-CAVITY; CERAMIDE;
SPHINGOMYELINASE; PREVENTION; PROTECTION; DAMAGE; MICE
AB Purpose: To evaluate the effect of irradiation on microvascular endothelial cells in miniature pig parotid glands.
Methods and Materials: A single 25-Gy dose of irradiation (IR) was delivered to parotid glands of 6 miniature pigs. Three other animals served as non-IR controls. Local blood flow rate in glands was measured pre- and post-IR with an ultrasonic Doppler analyzer. Samples of parotid gland tissue were taken at 4 h, 24 h, 1 week, and 2 weeks after IR for microvascular density (MVD) analysis and sphingomyelinase (SMase) assay. Histopathology and immunohistochemical staining (anti-CD31 and anti-AQP1) were used to assess morphological changes. MVD was determined by calculating the number of CD31- or AQP1-stained cells per field. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay was used to detect apoptotic cells. The activity of acid and neutral Mg2+-dependent SMase (ASMase and NSMase, respectively) was also assayed.
Results: Local parotid gland blood flow rate decreased rapidly at 4 h post-IR and remained below control levels throughout the 14-day observation period. Parotid MVD also declined from 4 to 24 hours and remained below control levels thereafter. The activity levels of ASMase and NSMase in parotid glands increased rapidly from 4 to 24 h post-IR and then declined gradually. The frequency of detecting apoptotic nuclei in the glands followed similar kinetics.
Conclusions: Single-dose IR led to a significant reduction of MVD and local blood flow rate, indicating marked damage to microvascular endothelial cells in miniature pig parotid glands. The significant and rapid increases of ASMase and NSMase activity levels may be important in this IR-induced damage. (C) 2010 Elsevier Inc.
C1 [Xu, Junji; Yan, Xing; Gao, Runtao; Mao, Lisha; Zhang, Chunmei; Wang, Songlin] Capital Med Univ, Sch Stomatol, Salivary Gland Dis Ctr, Beijing 100050, Peoples R China.
[Xu, Junji; Yan, Xing; Gao, Runtao; Mao, Lisha; Zhang, Chunmei; Wang, Songlin] Capital Med Univ, Sch Stomatol, Mol Lab Gene Therapy, Beijing 100050, Peoples R China.
[Wang, Songlin] Capital Med Univ, Dept Biochem & Mol Biol, Sch Basic Med Sci, Beijing 100050, Peoples R China.
[Cotrim, Ana P.; Zheng, Changyu; Baum, Bruce J.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, DHHS, Bethesda, MD USA.
RP Wang, SL (reprint author), Capital Med Univ, Sch Stomatol, Salivary Gland Dis Ctr, Tian Tan Xi Li 4, Beijing 100050, Peoples R China.
EM bbaum@dir.nidcr.nih.gov; slwang@ccmu.edu.cn
FU National Natural Science Foundation of China [30430690]; National
Special Foundation for Excellent Ph.D. [200778]; Division of Intramural
Research of the National Institute of Dental and Craniofacial Research
FX This study was supported by the National Natural Science Foundation of
China (Grant 30430690), the National Special Foundation for Excellent
Ph.D. paper, no. 200778, and the Division of Intramural Research of the
National Institute of Dental and Craniofacial Research.
NR 25
TC 21
Z9 22
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2010
VL 78
IS 3
BP 897
EP 903
DI 10.1016/j.ijrobp.2010.05.048
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 661MB
UT WOS:000282731300036
PM 20832188
ER
PT J
AU Edelhauser, HF
Rowe-Rendleman, CL
Robinson, MR
Dawson, DG
Chader, GJ
Grossniklaus, HE
Rittenhouse, KD
Wilson, CG
Weber, DA
Kuppermann, BD
Csaky, KG
Olsen, TW
Kompella, UB
Holers, VM
Hageman, GS
Gilger, BC
Campochiaro, PA
Whitcup, SM
Wong, WT
AF Edelhauser, Henry F.
Rowe-Rendleman, Cheryl L.
Robinson, Michael R.
Dawson, Daniel G.
Chader, Gerald J.
Grossniklaus, Hans E.
Rittenhouse, Kay D.
Wilson, Clive G.
Weber, David A.
Kuppermann, Baruch D.
Csaky, Karl G.
Olsen, Timothy W.
Kompella, Uday B.
Holers, V. Michael
Hageman, Gregory S.
Gilger, Brian C.
Campochiaro, Peter A.
Whitcup, Scott M.
Wong, Wai T.
TI Ophthalmic Drug Delivery Systems for the Treatment of Retinal Diseases:
Basic Research to Clinical Applications
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID PHOSPHATE NANOCOMPOSITE PARTICLES; ALTERNATIVE COMPLEMENT PATHWAY;
BLOOD-BRAIN-BARRIER; OPTIC-NERVE HEAD; POSTERIOR SEGMENT; CHOROIDAL
NEOVASCULARIZATION; INTRAOCULAR IMPLANTS; PIGMENT-EPITHELIUM; OCULAR
BARRIERS; BREAST-CANCER
C1 [Edelhauser, Henry F.] Emory Univ, Ctr Eye, Dept Ophthalmol, Atlanta, GA 30322 USA.
[Rowe-Rendleman, Cheryl L.] Omar Consulting Grp, Princeton Jct, NJ USA.
[Robinson, Michael R.; Whitcup, Scott M.] Allergan Pharmaceut Inc, Irvine, CA 92715 USA.
[Chader, Gerald J.] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA.
[Rittenhouse, Kay D.] Pfizer, La Jolla, CA USA.
[Wilson, Clive G.] Univ Strathclyde, Dept Pharmaceut Sci, Glasgow, Lanark, Scotland.
[Weber, David A.] Macu Sight, Union City, CA USA.
[Kuppermann, Baruch D.] Univ Calif Irvine, Sch Med, Gavin Herbert Eye Inst, Irvine, CA 92717 USA.
[Csaky, Karl G.] Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC USA.
[Kompella, Uday B.] Univ Colorado Denver, Dept Pharmaceut Sci, Aurora, CO USA.
[Holers, V. Michael] Taligen Therapeut, Boston, MA USA.
[Hageman, Gregory S.] Univ Iowa, Cell Biol & Funct Genom Lab, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
[Gilger, Brian C.] N Carolina State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC USA.
[Campochiaro, Peter A.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
[Wong, Wai T.] NEI, NIH, Bethesda, MD 20892 USA.
RP Edelhauser, HF (reprint author), Emory Univ, Ctr Eye, Dept Ophthalmol, 1365B Clifton Rd, Atlanta, GA 30322 USA.
EM ophthfe@emory.edu
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
FU NIH [5P30EY006360-23, SR24 EY017045, R24 EY017404]; Alcon Research
Institute; Research to Prevent Blindness
FX Supported by NIH Core Grant 5P30EY006360-23 (HFE, HEG, TWO), NIH Grant
SR24 EY017045 (HFE, HEG, UBK), and NIH Grant R24 EY017404 (GSH); the
Alcon Research Institute (GSH); and an unrestricted grant from Research
to Prevent Blindness (TWO).
NR 77
TC 77
Z9 80
U1 1
U2 13
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2010
VL 51
IS 11
BP 5403
EP 5420
DI 10.1167/iovs.10-5392
PG 18
WC Ophthalmology
SC Ophthalmology
GA 672BQ
UT WOS:000283558400002
PM 20980702
ER
PT J
AU Lederman, RJ
Faranesh, AZ
AF Lederman, Robert J.
Faranesh, Anthony Z.
TI Getting Closer for High-Resolution Vascular MRI
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Editorial Material
DE angiography; atherosclerosis; interventional MRI
C1 [Lederman, Robert J.; Faranesh, Anthony Z.] NHLBI, Translat Med Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Lederman, RJ (reprint author), NHLBI, Translat Med Branch, Div Intramural Res, NIH, Bldg 10,Room 2c713,MSC1538, Bethesda, MD 20892 USA.
OI lederman, robert/0000-0003-1202-6673
FU Intramural NIH HHS
NR 6
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD NOV
PY 2010
VL 3
IS 11
BP 1166
EP 1167
DI 10.1016/j.jcmg.2010.09.007
PG 2
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 683UL
UT WOS:000284501900010
PM 21071005
ER
PT J
AU Shebl, FM
Engels, EA
Goedert, JJ
Chaturvedi, AK
AF Shebl, Fatma M.
Engels, Eric A.
Goedert, James J.
Chaturvedi, Anil K.
TI Pulmonary Infections and Risk of Lung Cancer Among Persons With AIDS
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV/AIDS; inflammation; lung cancer; pulmonary infections; recurrent
pneumonia; pneumocystis jirovecii pneumonia; tuberculosis
ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; EPIDEMIOLOGIC EVIDENCE;
BACTERIAL PNEUMONIA; HIV-INFECTION; TUBERCULOSIS; SMOKING; DISEASE;
WOMEN; PEOPLE
AB Lung cancer risk is significantly increased among persons with AIDS (PWA), and increased smoking may not explain all of the elevated risk, suggesting a role for additional cofactors. We investigated whether AIDS-defining pulmonary infections (recurrent pneumonia, Pneumocystis jirovecii pneumonia, and pulmonary tuberculosis) affected the risk of subsequent lung cancer over 10 years after AIDS onset among 322,675 PWA, whose records were linked with cancer registries in 11 US regions. We assessed lung cancer hazard ratios (HRs) using Cox regression and indirectly adjusted HRs for confounding by smoking. Individuals with recurrent pneumonia (n = 5317) were at significantly higher lung cancer risk than those without [HR = 1.63, 95% confidence interval (CI) = 1.08 to 2.46, adjusted for age, race, sex, HIV acquisition mode, CD4 count, and AIDS diagnosis year]. This association was especially strong among young PWA (<50 years HR = 1.99 vs. >= 50 years HR = 1.10) and was significantly elevated during 5-10 years after recurrent pneumonia diagnosis (HR = 2.41; 95% CI = 1.07 to 5.47). Although attenuated, HRs for recurrent pneumonia remained nonsignificantly elevated after indirect adjustment for smoking. Lung cancer risk was unrelated to tuberculosis [(n = 13,878) HR = 1.12, 95% CI = 0.82 to 1.53] or Pneumocystis jirovecii pneumonia [(n = 69,771) HR = 0.97, 95% CI = 0.80 to 1.18]. The increased lung cancer risk associated with recurrent pneumonia supports the hypothesis that chronic pulmonary inflammation arising from infections contributes to lung carcinogenesis.
C1 [Shebl, Fatma M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA.
RP Shebl, FM (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, 6120 Execut Blvd, Rockville, MD 20852 USA.
FU National Cancer Institute
FX Supported by the Intramural Research Program of the National Cancer
Institute.
NR 24
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD NOV 1
PY 2010
VL 55
IS 3
BP 375
EP 379
DI 10.1097/QAI.0b013e3181eef4f7
PG 5
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 675RE
UT WOS:000283847400017
PM 20736841
ER
PT J
AU Allison, SM
Koenig, LJ
Marhefka, SL
Carter, RJ
Abrams, EJ
Bulterys, M
Tepper, V
Palumbo, PE
Bachanas, PJ
Farley, JJ
AF Allison, Susannah M.
Koenig, Linda J.
Marhefka, Stephanie L.
Carter, Rosalind J.
Abrams, Elaine J.
Bulterys, Marc
Tepper, Vicki
Palumbo, Paul E.
Bachanas, Pamela J.
Farley, John J.
TI Assessing Medication Adherence of Perinatally HIV-Infected Children
Using Caregiver Interviews
SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE
LA English
DT Article
DE adherence assessment; HIV disease; knowledge of prescribed dosing
frequency; pediatrics
ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS INFECTION;
CLINICAL MANAGEMENT; REPORTED ADHERENCE; SELF-REPORT; ADOLESCENTS;
PREDICTORS; RECOMMENDATIONS; TRANSMISSION; STRATEGIES
AB Medication adherence is critical for children's HIV treatment success, but obtaining accurate assessments is challenging when complex measurement technologies are not feasible. Our goal was to evaluate a multidimensional adherence interview designed to improve on existing adherence measures. Data from caregivers (N = 126) of perinatally infected children were analyzed to determine the ability of the revised interview guide to detect potential treatment nonadherence. Questions related to viral load (VL) on a bivariate level included proportion of doses taken in the previous 3 days and 6 months, caregivers' knowledge of prescribed dosing frequencies, and caregivers' reports of problems associated with medication administration. VL was not associated with 3-day recall of missed doses. In multivariate analyses, only caregivers' knowledge of prescribed dosing frequencies was uniquely associated with VL. Our modified interview appears to successfully identify family struggles with adherence and to have the capacity to help clinicians address medication adherence challenges. (Journal of the Association of Nurses in AIDS Care, 21, 478-488) Copyright (C) 2010 Association of Nurses in AIDS Care
C1 [Koenig, Linda J.; Bulterys, Marc] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, NCHHSTP, Atlanta, GA USA.
[Abrams, Elaine J.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Marhefka, Stephanie L.] New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, New York, NY 10032 USA.
[Carter, Rosalind J.] Med & Hlth Res Assoc NYC Inc, New York, NY USA.
[Palumbo, Paul E.] Dartmouth Hitchcock Med Ctr, Int Pediat HIV Program, Hanover, NH USA.
[Bachanas, Pamela J.] Emory Univ, Sch Med, Atlanta, GA USA.
[Tepper, Vicki] Univ Maryland, Sch Med, Pediat AIDS Care & Evaluat Clin, Baltimore, MD 21201 USA.
RP Allison, SM (reprint author), NIMH, Atlanta, GA USA.
OI Marhefka, Stephanie/0000-0001-7708-1521
FU U.S. Centers for Disease Control and Prevention through MHRA of New York
City [U64/CCU207228]; U.S. Centers for Disease Control and Prevention
through UMDNJ-New Jersey Medical School [U64/CCU202219]; U.S. Centers
for Disease Control and Prevention through University of Maryland School
of Medicine [U64/CCU306825]; U.S. Centers for Disease Control and
Prevention through Emory University School of Medicine [U64/CCU404456]
FX This study was funded as a part of PACTS and PACTS-HOPE, which were
funded by the U.S. Centers for Disease Control and Prevention through
cooperative agreements U64/CCU207228 (MHRA of New York City),
U64/CCU202219 (UMDNJ-New Jersey Medical School), U64/CCU306825
(University of Maryland School of Medicine), and U64/CCU404456 (Emory
University School of Medicine).
NR 24
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Z9 8
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1055-3290
J9 J ASSOC NURSE AIDS C
JI J. Assoc. Nurses Aids Care
PD NOV-DEC
PY 2010
VL 21
IS 6
BP 478
EP 488
DI 10.1016/j.jana.2010.02.006
PG 11
WC Nursing
SC Nursing
GA 684SX
UT WOS:000284570700006
PM 20452242
ER
PT J
AU Vogel, C
Chan, A
Gril, B
Kim, SB
Kurebayashi, J
Liu, L
Lu, YS
Moon, H
AF Vogel, Charles
Chan, Arlene
Gril, Brunilde
Kim, Sung-Bae
Kurebayashi, Junichi
Liu, Li
Lu, Yen-Shen
Moon, Hanlim
TI Management of ErbB2-positive Breast Cancer: Insights from Preclinical
and Clinical Studies with Lapatinib
SO JAPANESE JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
DE breast cancer; ErbB1; ErbB2; lapatinib; tyrosine kinase inhibitor;
review
ID TYROSINE KINASE INHIBITOR; PHASE-II TRIAL; BRAIN METASTASES; TRASTUZUMAB
RESISTANCE; PLUS CAPECITABINE; 1ST-LINE TREATMENT; CNS METASTASES;
GROWTH; RECEPTOR; THERAPY
AB The management of human epidermal growth factor receptor 2-positive (ErbB2+) breast cancer is challenging; patients with ErbB2+ breast tumors have more aggressive disease and a poor prognosis. The increasing incidence of breast cancer in Asia and the limitations of existing treatments pose additional challenges. In this review, we summarize the preclinical and clinical evidence that indicates how lapatinib, a novel inhibitor that targets the human epidermal growth factor receptor (ErbB1) and ErbB2 may help clinicians address four particularly challenging issues in the management of ErbB2+ breast cancer. These issues are: (i) trastuzumab therapy failure, (ii) development of central nervous system metastases, (iii) minimizing toxicity and (iv) selecting the most appropriate partners (chemotherapy and non-chemotherapy) for combination therapy with lapatinib. Lapatinib, in combination with chemotherapeutic agents, such as capecitabine, provides clinical benefits to patients with ErbB2+ breast cancer, including patients who develop progressive disease on trastuzumab. Lapatinib, in combination with non-chemotherapeutic agents, such as letrozole, may also provide a chemotherapy-free treatment option for postmenopausal patients with estrogen receptor-positive/ErbB2+ metastatic breast cancer. Encouraging results have also emerged regarding the synergistic effects of lapatinib in combination with other agents for the treatment of ErbB2+ breast cancer. Promising findings have also been reported for the use of lapatinib to prevent and treat central nervous system metastases. Collectively, these results indicate that the judicious use of lapatinib, an effective oral therapy with a manageable toxicity profile, can enhance the management of patients with ErbB2+ breast cancer.
C1 [Vogel, Charles] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr Deerfield Beach, Deerfield Beach, FL 33442 USA.
[Chan, Arlene] Mt Hosp, Perth, WA, Australia.
[Gril, Brunilde] NCI, Womens Canc Sect, Mol Pharmacol Lab, NIH, Rockville, MD USA.
[Kim, Sung-Bae] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea.
[Kurebayashi, Junichi] Kawasaki Med Univ, Dept Breast & Thyroid Surg, Okayama, Japan.
[Liu, Li] GlaxoSmithKline Oncol Res & Dev, Collegeville, PA USA.
[Lu, Yen-Shen] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan.
[Lu, Yen-Shen] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei, Taiwan.
[Moon, Hanlim] GlaxoSmithKline Oncol Res & Dev, Asia Pacific, Seoul, South Korea.
RP Vogel, C (reprint author), Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr Deerfield Beach, 1192 E Newport Ctr Dr, Deerfield Beach, FL 33442 USA.
EM drcvogel@aol.com
FU GlaxoSmithKline Asia Pacific; US Department of Defense; GlaxoSmithKline;
Genentech
FX To enhance reader access to this peer-reviewed article, the authors
opted for an open access publication. The open access and color printing
publication charges for this article were funded by GlaxoSmithKline Asia
Pacific.; Arlene Chan has received payments as an advisory board member
from Roche and for speaking from Roche and GlaxoSmithKline; Junichi
Kurebayashi has received payments for speaking from GlaxoSmithKline;
Brunilde Gril has received grant support from the US Department of
Defense Breast Cancer Research Program; Li Liu is an employee of and has
shares in GlaxoSmithKline; Yen-Shen Lu has received grant support and
payments for speaking from GlaxoSmithKline; Hanlim Moon is an employee
of and has shares in GlaxoSmithKline; Charles Vogel has received grant
support and payments for consulting and speaking from Genentech and
grant support and payments for consulting, speaking and participation as
a clinical trial investigator and advisory board member from
GlaxoSmithKline.
NR 76
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Z9 8
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0368-2811
EI 1465-3621
J9 JPN J CLIN ONCOL
JI Jpn. J. Clin. Oncol.
PD NOV
PY 2010
VL 40
IS 11
BP 999
EP 1013
DI 10.1093/jjco/hyq084
PG 15
WC Oncology
SC Oncology
GA 673VN
UT WOS:000283692300001
PM 20542996
ER
PT J
AU Sanislow, CA
Pine, DS
Quinn, KJ
Kozak, MJ
Garvey, MA
Heinssen, RK
Wang, PSE
Cuthbert, BN
AF Sanislow, Charles A.
Pine, Daniel S.
Quinn, Kevin J.
Kozak, Michael J.
Garvey, Marjorie A.
Heinssen, Robert K.
Wang, Philip Sung-En
Cuthbert, Bruce N.
TI Developing Constructs for Psychopathology Research: Research Domain
Criteria
SO JOURNAL OF ABNORMAL PSYCHOLOGY
LA English
DT Article
DE RDoC; psychopathology research constructs; research diagnoses
ID MEDIAL PREFRONTAL CORTEX; FEAR; COGNITION; OXYTOCIN; AUTISM;
SCHIZOPHRENIA; VASOPRESSIN; MECHANISMS; EMOTION; EXPRESSION
AB There exists a divide between findings from integrative neuroscience and clinical research focused on mechanisms of psychopathology. Specifically, a clear correspondence does not emerge between clusters of complex clinical symptoms and dysregulated neurobiological systems, with many apparent redundancies. For instance, many mental disorders involve multiple disruptions in putative mechanistic factors (e.g., excessive fear, deficient impulse control), and different disrupted mechanisms appear to play major roles in many disorders. The Research Domain Criteria (RDoC) framework is a heuristic to facilitate the incorporation of behavioral neuroscience in the study of psychopathology. Such integration might be achieved by shifting the central research focus of the field away from clinical description to more squarely examine aberrant mechanisms. RDoC first aims to identify reliable and valid psychological and biological mechanisms and their disruptions, with an eventual goal of understanding how anomalies in these mechanisms drive psychiatric symptoms. This approach will require new methods to ascertain samples, relying on hypothesized psychopathological mechanisms to define experimental groups instead of traditional diagnostic categories. RDoC, by design, uncouples research efforts from clinically familiar categories to focus directly on fundamental mechanisms of psychopathology. RDoC proposes a matrix of domains and levels of analyses and invites the field to test and refine the framework. If RDoC is successful, the domains will ultimately relate to familiar psychopathologies in ways that promote new knowledge regarding etiology and more efficient development of new preventive and treatment interventions.
C1 [Sanislow, Charles A.] Wesleyan Univ, Dept Psychol, Middletown, CT 06459 USA.
[Pine, Daniel S.] NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA.
[Quinn, Kevin J.] NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA.
[Kozak, Michael J.; Cuthbert, Bruce N.] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA.
[Garvey, Marjorie A.] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA.
[Heinssen, Robert K.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
RP Sanislow, CA (reprint author), Wesleyan Univ, Dept Psychol, Judd Hall,207 High St, Middletown, CT 06459 USA.
EM csanislow@wesleyan.edu
NR 71
TC 269
Z9 271
U1 6
U2 60
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0021-843X
J9 J ABNORM PSYCHOL
JI J. Abnorm. Psychol.
PD NOV
PY 2010
VL 119
IS 4
BP 631
EP 639
DI 10.1037/a0020909
PG 9
WC Psychology, Clinical; Psychology, Multidisciplinary
SC Psychology
GA 680PP
UT WOS:000284247200001
PM 20939653
ER
PT J
AU Ulrich, CM
Taylor, C
Soeken, K
O'Donnell, P
Farrar, A
Danis, M
Grady, C
AF Ulrich, Connie M.
Taylor, Carol
Soeken, Karen
O'Donnell, Patricia
Farrar, Adrienne
Danis, Marion
Grady, Christine
TI Everyday ethics: ethical issues and stress in nursing practice
SO JOURNAL OF ADVANCED NURSING
LA English
DT Article
DE autonomy; ethical issues; informed consent; nursing practice; patient
rights; stress; survey
ID INTENSIVE-CARE-UNIT; SOCIAL-WORKERS; MORAL DISTRESS; MANAGED CARE;
NURSES; LIFE; END; PRACTITIONERS; PHYSICIANS; CONFLICT
AB Aim. This paper is a report of a study of the type, frequency, and level of stress of ethical issues encountered by nurses in their everyday practice.
Background. Everyday ethical issues in nursing practice attract little attention but can create stress for nurses. Nurses often feel uncomfortable in addressing the ethical issues they encounter in patient care.
Methods. A self-administered survey was sent in 2004 to 1000 nurses in four states in four different census regions of the United States of America. The adjusted response rate was 52%. Data were analysed using descriptive statistics, cross-tabulations and Pearson correlations.
Results. A total of 422 questionnaires were used in the analysis. The five most frequently occurring and most stressful ethical and patient care issues were protecting patients' rights; autonomy and informed consent to treatment; staffing patterns; advanced care planning; and surrogate decision-making. Other common occurrences were unethical practices of healthcare professionals; breaches of patient confidentiality or right to privacy; and end-of-life decision-making. Younger nurses and those with fewer years of experience encountered ethical issues more frequently and reported higher levels of stress. Nurses from different regions also experienced specific types of ethical problems more commonly.
Conclusion. Nurses face daily ethical challenges in the provision of quality care. To retain nurses, targeted ethics-related interventions that address caring for an increasingly complex patient population are needed.
C1 [Ulrich, Connie M.] Univ Penn, Dept Med Eth, Nursing Ctr Bioeth, Philadelphia, PA 19104 USA.
[Ulrich, Connie M.] Univ Penn, Sch Nursing, New Courtland Ctr Transit & Hlth, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Taylor, Carol] Georgetown Univ, Ctr Bioeth, Washington, DC USA.
[Soeken, Karen] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA.
[O'Donnell, Patricia] Inova Hlth Syst, Ctr Eth, Fairfax, VA USA.
[Danis, Marion] NIH, Dept Social Work, Ctr Clin, Sect Eth & Hlth Policy, Bethesda, MD 20892 USA.
[Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Sect Human Subjects Res & Acting Chief, Bethesda, MD 20892 USA.
RP Ulrich, CM (reprint author), Univ Penn, Dept Med Eth, Nursing Ctr Bioeth, Philadelphia, PA 19104 USA.
EM culrich@nursing.upenn.edu
FU Department of Bioethics and Department of Social Work, National
Institutes of Health
FX This research was supported by the Department of Bioethics and
Department of Social Work, National Institutes of Health. The opinions
expressed in this manuscript are solely those of the authors. We would
also like to acknowledge the comments of the anonymous reviewers who
provided critical feedback on the manuscript.
NR 34
TC 32
Z9 33
U1 5
U2 27
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0309-2402
J9 J ADV NURS
JI J. Adv. Nurs.
PD NOV
PY 2010
VL 66
IS 11
BP 2510
EP 2519
DI 10.1111/j.1365-2648.2010.05425.x
PG 10
WC Nursing
SC Nursing
GA 660ZU
UT WOS:000282691600014
PM 20735502
ER
PT J
AU Bousquet, J
Mantzouranis, E
Cruz, AA
Ait-Khaled, N
Baena-Cagnani, CE
Bleecker, ER
Brightling, CE
Burney, P
Bush, A
Busse, WW
Casale, TB
Chan-Yeung, M
Chen, RC
Chowdhury, B
Chung, KF
Dahl, R
Drazen, JM
Fabbri, LM
Holgate, ST
Kauffmann, F
Haahtela, T
Khaltaev, N
Kiley, JP
Masjedi, MR
Mohammad, Y
O'Byrne, P
Partridge, MR
Rabe, KF
Togias, A
van Weel, C
Wenzel, S
Zhong, NS
Zuberbier, T
AF Bousquet, Jean
Mantzouranis, Eva
Cruz, Alvaro A.
Ait-Khaled, Nadia
Baena-Cagnani, Carlos E.
Bleecker, Eugene R.
Brightling, Chris E.
Burney, Peter
Bush, Andrew
Busse, William W.
Casale, Thomas B.
Chan-Yeung, Moira
Chen, Rongchang
Chowdhury, Badrul
Chung, Kian Fan
Dahl, Ronald
Drazen, Jeffrey M.
Fabbri, Leonardo M.
Holgate, Stephen T.
Kauffmann, Francine
Haahtela, Tari
Khaltaev, Nikolai
Kiley, James P.
Masjedi, Mohammad R.
Mohammad, Yousser
O'Byrne, Paul
Partridge, Martyn R.
Rabe, Klaus F.
Togias, Alkis
van Weel, Christiaan
Wenzel, Sally
Zhong, Nanshan
Zuberbier, Torsten
TI Uniform definition of asthma severity, control, and exacerbations:
Document presented for the World Health Organization Consultation on
Severe Asthma
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma; severity; control; risk; definition; GARD
ID TO-TREAT ASTHMA; LUNG-FUNCTION; INHALED CORTICOSTEROIDS;
PRESCHOOL-CHILDREN; CHILDHOOD ASTHMA; RESEARCH-PROGRAM; LOW-INCOME;
FOLLOW-UP; DEVELOPING-COUNTRIES; CLUSTER-ANALYSIS
AB Asthma is a global health problem affecting around 300 million individuals of all ages, ethnic groups and countries. It is estimated that around 250,000 people die prematurely each year as a result of asthma. Concepts of asthma severity and control are important in evaluating patients and their response to treatment, as well as for public health, registries, and research (clinical trials, epidemiologic, genetic, and mechanistic studies), but the terminology applied is not standardized, and terms are often used interchangeably. A common international approach is favored to define severe asthma, uncontrolled asthma, and when the 2 coincide, although adaptation may be required in accordance with local conditions. A World Health Organization meeting was convened April 5-6, 2009, to propose a uniform definition of severe asthma. An article was written by a group of experts and reviewed by the Global Alliance against Chronic Respiratory Diseases review group. Severe asthma is defined by the level of current clinical control and risks as "Uncontrolled asthma which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity (including impaired lung function or reduced lung growth in children)." Severe asthma includes 3 groups, each carrying different public health messages and challenges: (1) untreated severe asthma, (2) difficult-to-treat severe asthma, and (3) treatment-resistant severe asthma. The last group includes asthma for which control is not achieved despite the highest level of recommended treatment and asthma for which control can be maintained only with the highest level of recommended treatment. (J Allergy Clin Immunol 2010; 126: 926-38.)
C1 [Bousquet, Jean] Hop Arnaud Villeneuve, Serv Malad Resp, Univ Hosp, F-34295 Montpellier 5, France.
[Bousquet, Jean; Kauffmann, Francine] INSERM, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Villejuif, France.
[Bousquet, Jean; Kauffmann, Francine] UMRS 1018, Villejuif, France.
[Mantzouranis, Eva] WHO, Geneva, Switzerland.
[Cruz, Alvaro A.] Univ Fed Bahia, ProAR FMB, Salvador, BA, Brazil.
[Ait-Khaled, Nadia] Union, Paris, France.
[Baena-Cagnani, Carlos E.] Catholic Univ, Fac Med, Cordoba, Argentina.
[Baena-Cagnani, Carlos E.] Univ Genoa, Sch Specializat, I-16126 Genoa, Italy.
[Bleecker, Eugene R.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Brightling, Chris E.] Inst Lung Hlth, Leicester, Leics, England.
[Burney, Peter; Bush, Andrew; Chung, Kian Fan] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2AZ, England.
[Bush, Andrew] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, London SW7 2AZ, England.
[Chung, Kian Fan] Royal Brompton Hosp, Biomed Res Unit, London, England.
[Partridge, Martyn R.] Univ London Imperial Coll Sci Technol & Med, Charing Cross Hosp, NHLI Div, London SW7 2AZ, England.
[Busse, William W.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53706 USA.
[Casale, Thomas B.] Creighton Univ, Omaha, NE 68178 USA.
[Chan-Yeung, Moira] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Chen, Rongchang; Zhong, Nanshan] Guangzhou Med Coll, Guangzhou Inst Resp Dis, Guangzhou, Guangdong, Peoples R China.
[Chowdhury, Badrul] US FDA, Silver Spring, MD USA.
[Dahl, Ronald] Aarhus Univ Hosp, Aarhus, Denmark.
[Drazen, Jeffrey M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Fabbri, Leonardo M.] Univ Modena & Reggio Emilia, Modena, Italy.
[Holgate, Stephen T.] Southampton Gen Hosp, Southampton, Hants, England.
[Haahtela, Tari] Helsinki Univ Hosp, Skin & Allergy Hosp, Helsinki, Finland.
[Khaltaev, Nikolai] Global Alliance Chron Resp Dis, Geneva, Switzerland.
[Kiley, James P.] NHLBI, NIH, DHHS, Bethesda, MD 20892 USA.
[Togias, Alkis] NIAID, Bethesda, MD 20892 USA.
[Masjedi, Mohammad R.] NRITLD, CRDRC, Tehran, Iran.
[Mohammad, Yousser] Tishreen Univ, Sch Med, Latakia, Syria.
[O'Byrne, Paul] McMaster Univ, Dept Med, Hamilton, ON L8S 4L8, Canada.
[Rabe, Klaus F.] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands.
[van Weel, Christiaan] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands.
[Wenzel, Sally] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Zuberbier, Torsten] Charite Univ Med Berlin, Dept Dermatol & Allergy, Allergy Ctr Charite, Berlin, Germany.
RP Bousquet, J (reprint author), Hop Arnaud Villeneuve, Serv Malad Resp, Univ Hosp, 371 Ave Doyen Gaston Giraud, F-34295 Montpellier 5, France.
EM jean.bousquet@inserm.fr
RI Dahl, Ronahl/F-8170-2013; Casale, Thomas/K-4334-2013; van Weel,
Chris/D-4375-2009; Fabbri, Leonardo/I-4055-2012; Cruz,
Alvaro/I-1676-2012;
OI Casale, Thomas/0000-0002-3149-7377; van Weel, Chris/0000-0003-3653-4701;
Fabbri, Leonardo/0000-0001-8894-1689; Cruz, Alvaro/0000-0002-7403-3871;
O'Byrne, Paul/0000-0003-0979-281X; Masjedi,
Mohammadreza/0000-0003-4964-3851; Chung, Kian Fan/0000-0001-7101-1426
FU EU [FOOD-CT-2004-506378]; World Health Organization Collaborating Center
on Asthma and Rhinitis, Montpellier; Chiesi; Mantecorp (Brazil); CNPq
(Brazil); National Research Council; Brazilian Ministry of Health;
FAPESB State of Brazil Agency for Research; Wellcome Trust (UK);
Novartis; GlaxoSmithKline; NIH/NHLBI; MedImmune; AstraZeneca; Department
of Health (UK); NIH-NIAID; NIH-NHLBI; Ception; MRC UK; Asthma UK;
Wellcome Trust; Abbott; Boehringer Ingelheim; Merck Sharp Dohme,;
Nycomed; Roche; Pfizer; Menarini; Schering-Plough; Merck Sharp Dohme;
UCB; Italian Ministry of Health; Italian Ministry for University and
Research; Merck; Wyeth; Schering; Alexion; Forest; AZ; BI; Pearl; MSD;
AS; Dutch Asthma Foundation (NAF); Netherlands Medical Research Council
(Zon/Mw); Aerovance; Amgen
FX In collaboration with the Global Allergy and Asthma European Network
(GA2LEN), supported by the Sixth EU Framework program for
research (contract no. FOOD-CT-2004-506378) and the World Health
Organization Collaborating Center on Asthma and Rhinitis, Montpellier.;
Disclosure of potential conflict of interest: J. Bousquet has received
honorarium for scientific and advisory boards, lectures, and press
conferences from Stallergenes, Actelion, Almirall, AstraZeneca, Chiesi,
Ask, Merck, MSD, Novartis, OM Pharma, Sanofi-Aventis, Schering-Plough,
Teva, and Uriach. A. A. Cruz has given talks for Novartis and
GlaxoSmithKline; has received research support from Chiesi, Mantecorp
(Brazil), CNPq (Brazil), National Research Council, Brazilian Ministry
of Health, FAPESB State of Brazil Agency for Research, Wellcome Trust
(UK), Novartis, and GlaxoSmithKline; is a member of the Planning Group
for the Global Alliance against Chronic Respiratory Diseases; and is a
member of the Executive Committee for the Global Initiative for Asthma
and Allergic Rhinitis and its Impact on Asthma. E. R. Bleecker is a
consultant for Aerovance, AstraZeneca, Boehringer Ingelheim,
GlaxoSmithKline, and Pfizer and has received research support from the
NIH/NHLBI. C. E. Brightling is a consultant for MedImmune, AstraZeneca,
and Roche and has received research support from MedImmune, AstraZeneca,
and GlaxoSmithKline. P. Burney has received research support from the
Department of Health (UK). W. W. Busse is on the Advisory Board for
Altair, Amgen, Centocor, GlaxoSmithKline, Merck, Pfizer, Wyeth, and
Johnson & Johnson; is a consultant for AstraZeneca, Boehringer
Ingelheim, Novartis, TEVA, and GlaxoSmithKline; is a speaker for Merck;
and has received research support from NIH-NIAID, NIH-NHLBI, Novartis,
AstraZeneca, GlaxoSmithKline, MedImmune, and Ception. T. B. Casale is
executive vice president of the AAAAI and is on the board of directors
for WAO. R. Chen is a consultant on asthma and COPD for AstraZeneca and
GlaxoSmithKline and has served as an expert witness on the topic of
management of asthma. K. F. Chung is a consultant for Gilead; is on the
advisory board for Merck and GlaxoSmithKline; and has received research
support from MRC UK, Asthma UK, and Wellcome Trust. R. Dahl is a speaker
for MSD, AstraZeneca, ALK, and GlaxoSmithKline; is a speaker and is on
the advisory board for TEVA, Boehringer Ingelheim, UCB, Airsonett,
Novartis, and Pfizer; is chairman for the Danish Respiratory Society;
and is president of Interasma. L. M. Fabbri is a consultant for Nycomed,
Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Sigma Tau, AstraZeneca,
Merck Sharp & Dohme, Novartis, Roche, and Pfizer; has received paid
lecture fees from Abbott, AstraZeneca, Boehringer Ingelheim, Chiesi,
GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Nycomed, Roche, and
Pfizer; and has received research support from Nycomed, Abbott,
AstraZeneca, Boehringer Ingelheim, Menarini, Novartis, Schering-Plough,
Chiesi, GlaxoSmithKline, Merck Sharp & Dohme, UCB, Pfizer, the Italian
Ministry of Health, and the Italian Ministry for University and
Research. S. T. Holgate is a consultant for MSD, Novartis, Synergen,
Altair, Amgen, and Almiral and owns shares in Synergen. T. Haahtela has
received honoraria from Astellas, AstraZeneca, Leiras, MSD, and Orion
Pharma. P. O'Byrne is on the advisory board and has received speakers'
honoraria from AstraZeneca and GlaxoSmithKline; is on the advisory board
for Topigen, Wyeth, and Schering; and has received research support from
AstraZeneca, GlaxoSmithKline, Merck, Wyeth, Schering, and Alexion. K. F.
Rabe has received remuneration from Nycomed, Forest, AZ, BI, Chiesi,
Pearl, MSD, and GlaxoSmithKline and has received research support from
Chiesi, AS, BI, and Novartis. C.; van Weel has received research support
from Boehringer Ingelheim, GlaxoSmithline, Novartis, the Dutch Asthma
Foundation (NAF), and the Netherlands Medical Research Council (Zon/Mw).
S. Wenzel is a consultant for Altair, Merck, GlaxoSmithKline, Amgen, and
Pearl Therapeutics; is on the scientific advisory board for Amira; and
has received research support from MedImmune, GlaxoSmithKline,
Aerovance, and Amgen. T. Zuberbier is a consultant for Schering-Plough,
Novartis, Leti, Stallergenes, Bayer Schering, Ansell, Kryolan, UCB, MSD,
DST, Sanofi-Aventis, and Procter & Gamble; is on the editorial board of
the Journal of Allergy, the scientific advisory board of the German
Society for Allergy and Clinical Immunology, and the Expert Commission
"Novel Food" of the German Federal Ministry of Consumer Protection; is
chairman of the European Academy of Allergology and Clinical Immunology,
Dermatology Section; is head of the European Center for Allergy Research
Foundation; is a committee member of the WHO Initiative Allergic
Rhinitis and its Impact on Asthma; is a member of the World Allergy
Organization Communications Council; and is secretary general of the
Global Allergy and Asthma European Network. E. Mantzouranis, N.
Ait-Khaled, C. E. Baena-Cagnani, A. Bush, M. Chan-Yeung, B. Chowdhury,
J. M. Drazen, F. Kauffmann, N. Khaltaev, J. P. Kiley, M. R. Masjedi, Y.
Mohammad, M. R. Partridge, A. Togias, and N. Zhong have declared that
they have no conflict of interest.
NR 112
TC 242
Z9 251
U1 3
U2 36
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD NOV
PY 2010
VL 126
IS 5
BP 926
EP 938
DI 10.1016/j.jaci.2010.07.019
PG 13
WC Allergy; Immunology
SC Allergy; Immunology
GA 674HB
UT WOS:000283727100005
PM 20926125
ER
PT J
AU de Falco, S
Esposito, G
Venuti, P
Bornstein, MH
AF de Falco, Simona
Esposito, Gianluca
Venuti, Paola
Bornstein, Marc H.
TI Mothers and Fathers at Play with their Children with Down Syndrome:
Influence on Child Exploratory and Symbolic Activity
SO JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES
LA English
DT Article
DE Down Syndrome; father; intellectual disabilities; parent-child
interaction; play
ID YOUNG-CHILDREN; PRETEND PLAY; INVOLVEMENT; PATTERNS; LANGUAGE; PARENTS;
STRESS; COMMUNICATION; DISABILITIES; PERCEPTIONS
AB Background Through play children exercise their emerging mental abilities, and for their part, when in collaborative play, caregivers often adjust their behaviours to assist their children's progress. In this study, we focused on comparisons between play of Down Syndrome (DS) children with their two parents as well as on comparisons between the two parents' play behaviours.
Method Altogether 40 parent-child dyads participated: 20 children with DS (M age = 36.14 months) with their mothers and separately with their fathers. We coded participants' play behaviours during child solitary and mother-child and father-child collaborative sessions.
Results Although children increased exploratory play from solitary to collaborative sessions with both parents, symbolic play increased only during joint play with fathers. Fathers displayed less symbolic and more exploratory activity compared to mothers. Mothers and fathers alike were attuned to their children, although fathers showed a higher degree of attunement.
Conclusions This study shows that maternal and paternal contributions to DS child play skills are positive but different. During collaborative play children received specific and nonoverlapping scaffolding from their two parents, and fathers' contributions were unique.
C1 [de Falco, Simona; Esposito, Gianluca; Venuti, Paola] Univ Trent, Dept Cognit Sci & Educ, Trento, Italy.
[Bornstein, Marc H.] NICHHD, Dept Hlth & Human Serv, NIH, Bethesda, MD USA.
RP de Falco, S (reprint author), Dept Cognit Sci & Educ, Via Matteo Del Ben 5, I-38068 Rovereto, TN, Italy.
EM defalco@form.unitn.it
RI Esposito, Gianluca/B-1374-2012
OI Esposito, Gianluca/0000-0002-9442-0254
FU Intramural NIH HHS [ZIA HD001119-25]
NR 62
TC 5
Z9 5
U1 1
U2 8
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1360-2322
J9 J APPL RES INTELLECT
JI J. Appl. Res. Intellect. Disabil.
PD NOV
PY 2010
VL 23
IS 6
BP 597
EP 605
DI 10.1111/j.1468-3148.2010.00558.x
PG 9
WC Psychology, Educational; Rehabilitation
SC Psychology; Rehabilitation
GA 666ZQ
UT WOS:000283162400003
PM 23275758
ER
PT J
AU Mattison, DR
AF Mattison, Donald R.
TI Untitled
SO JOURNAL OF ATTENTION DISORDERS
LA English
DT Letter
C1 [Mattison, Donald R.] NICHD, NIH, Bethesda, MD 20892 USA.
EM mattisod@mail.nih.gov
RI Mattison, Donald/C-2015-2009;
OI Mattison, Donald/0000-0001-5623-0874
NR 23
TC 0
Z9 0
U1 0
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0547
J9 J ATTEN DISORD
JI J. Atten. Disord.
PD NOV
PY 2010
VL 14
IS 3
BP 203
EP 204
PG 2
WC Psychology, Developmental; Psychiatry
SC Psychology; Psychiatry
GA 671NK
UT WOS:000283512600001
PM 20978275
ER
PT J
AU Miyagawa, F
Gutermuth, J
Zhang, H
Katz, SI
AF Miyagawa, Fumi
Gutermuth, Jan
Zhang, Hong
Katz, Stephen I.
TI The use of mouse models to better understand mechanisms of autoimmunity
and tolerance
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE Autoimmunity; CD8 T cells; GvHD; Immunological tolerance; Transgenic
mouse model
ID T-CELL TOLERANCE; MAJOR HISTOCOMPATIBILITY COMPLEX; PERIPHERALLY
EXPRESSED ANTIGENS; SELF-ANTIGENS; TRANSGENIC MICE; IN-VIVO;
CROSS-PRESENTATION; DENDRITIC CELLS; STEADY-STATE; EFFECTOR FUNCTION
AB A major emphasis of our studies has been on developing a better understanding of how and why the skin serves as a target for immune reactions as well as how the skin evades becoming a target for destruction. For these studies we developed transgenic mice that express a membrane-tethered form of a model self antigen, chicken ovalbumin (mOVA), under the control of a keratin 14 (K14) promoter. K14-mOVA transgenic mice that express OVA mRNA and protein in the epithelia have been assessed for their immune responsiveness to OVA and are being used as targets for T cells obtained from OT-1 transgenic mice whose CD8+ T cells carry a V alpha 2/V beta 5-transgenic T cell receptor with specificity for the OVA(257-264)-peptides (OVAp) in association with class I MHC antigens. Some of the K14-mOVA transgenic mice develop a graft-versus-host-like disease (GvHD) when the OT-1 cells are injected while others appear to be tolerant to the OT-1 cells. We found that gamma c cytokines, especially IL-15, determine whether autoimmunity or tolerance ensues in K14-mOVA Tg mice. We also developed transgenic mice that express soluble OVA under the control of a K14 promoter (K14-sOVA) that die within 5-8 days after adoptive transfer of OT-1 cells and identified these mice as a model for more acute GvHD-like reactions. Spontaneous autoimmunity occurs when these K14-sOVA mice are crossed with the OT-I mice. In contrast, we found that preventive or therapeutic OVAp injections induced a dose-dependent increase in survival. In this review the characterization of 5 strains of K14-OVATg mice and underlying mechanisms involved in autoimmune reactions in these Tg mice are discussed. We also describe a strategy to break tolerance and describe how the autoimmunity can be obviated using OVAp. Finally, a historical overview of using transgenic mice to assess the mechanisms of tolerance is also provided. Published by Elsevier Ltd.
C1 [Miyagawa, Fumi; Gutermuth, Jan; Zhang, Hong; Katz, Stephen I.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
RP Katz, SI (reprint author), NCI, Dermatol Branch, NIH, Bldg 31,Rm4C32, Bethesda, MD 20892 USA.
EM katzs@od.niams.nih.gov
NR 60
TC 33
Z9 34
U1 2
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
J9 J AUTOIMMUN
JI J. Autoimmun.
PD NOV
PY 2010
VL 35
IS 3
SI SI
BP 192
EP 198
DI 10.1016/j.jaut.2010.06.007
PG 7
WC Immunology
SC Immunology
GA 676HV
UT WOS:000283902500005
PM 20655706
ER
PT J
AU McCullen, CA
Benhammou, JN
Majdalani, N
Gottesman, S
AF McCullen, Colleen A.
Benhammou, Jihane N.
Majdalani, Nadim
Gottesman, Susan
TI Mechanism of Positive Regulation by DsrA and RprA Small Noncoding RNAs:
Pairing Increases Translation and Protects rpoS mRNA from Degradation
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID ESCHERICHIA-COLI HFQ; BACTERIAL SMALL RNA; STAPHYLOCOCCUS-AUREUS;
ENDORIBONUCLEASE-III; SIGMA(S) SUBUNIT; ANTISENSE RNA; GROWTH-PHASE;
EXPRESSION; POLYMERASE; STABILITY
AB Small noncoding RNAs (sRNAs) regulate gene expression in Escherichia coli by base pairing with mRNAs and modulating translation and mRNA stability. The sRNAs DsrA and RprA stimulate the translation of the stress response transcription factor RpoS by base pairing with the 5' untranslated region of the rpoS mRNA. In the present study, we found that the rpoS mRNA was unstable in the absence of DsrA and RprA and that expression of these sRNAs increased both the accumulation and the half-life of the rpoS mRNA. Mutations in dsrA, rprA, or rpoS that disrupt the predicted pairing sequences and reduce translation of RpoS also destabilize the rpoS mRNA. We found that the rpoS mRNA accumulates in an RNase E mutant strain in the absence of sRNA expression and, therefore, is degraded by an RNase E-mediated mechanism. DsrA expression is required, however, for maximal translation even when rpoS mRNA is abundant. This suggests that DsrA protects rpoS mRNA from degradation by RNase E and that DsrA has a further activity in stimulating RpoS protein synthesis. rpoS mRNA is subject to degradation by an additional pathway, mediated by RNase III, which, in contrast to the RNase E-mediated pathway, occurs in the presence and absence of DsrA or RprA. rpoS mRNA and RpoS protein levels are increased in an RNase III mutant strain with or without the sRNAs, suggesting that the role of RNase III in this context is to reduce the translation of RpoS even when the sRNAs are acting to stimulate translation.
C1 [Gottesman, Susan] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Gottesman, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 5132, Bethesda, MD 20892 USA.
EM susang@helix.nih.gov
FU Center for Cancer Research, National Cancer Institute, NIH; National
Research Service (National Institutes of Health) [F32 GM075392]
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, NIH, and by a
National Research Service Award to C. A. M. (award F32 GM075392,
National Institutes of Health).
NR 64
TC 55
Z9 57
U1 1
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD NOV
PY 2010
VL 192
IS 21
BP 5559
EP 5571
DI 10.1128/JB.00464-10
PG 13
WC Microbiology
SC Microbiology
GA 662LD
UT WOS:000282807900001
PM 20802038
ER
PT J
AU James, TD
Cashel, M
Hinton, DM
AF James, Tamara D.
Cashel, Michael
Hinton, Deborah M.
TI A Mutation within the beta Subunit of Escherichia coli RNA Polymerase
Impairs Transcription from Bacteriophage T4 Middle Promoters
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID ACTIVATOR MOTA INTERACTS; SIGMA(70) SUBUNIT; ASIA PROTEIN; ANGSTROM
RESOLUTION; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; DNA-REPLICATION; FLAP
DOMAIN; T4 ASIA; GENE
AB During infection of Escherichia coli, bacteriophage T4 usurps the host transcriptional machinery, redirecting it to the expression of early, middle, and late phage genes. Middle genes, whose expression begins about 1 min postinfection, are transcribed both from the extension of early RNA into middle genes and by the activation of T4 middle promoters. Middle-promoter activation requires the T4 transcriptional activator MotA and coactivator AsiA, which are known to interact with sigma(70), the specificity subunit of RNA polymerase. T4 motA amber [motA(Am)] or asiA(Am) phage grows poorly in wild-type E. coli. However, previous work has found that T4 motA(Am) does not grow in the E. coli mutant strain TabG. We show here that the RNA polymerase in TabG contains two mutations within its beta-subunit gene: rpoB(E835K) and rpoB(G1249D). We find that the G1249D mutation is responsible for restricting the growth of either T4 motA(Am) or asiA(Am) and for impairing transcription from MotA/AsiA-activated middle promoters in vivo. With one exception, transcription from tested T4 early promoters is either unaffected or, in some cases, even increases, and there is no significant growth phenotype for the rpoB(E835K G1249D) strain in the absence of T4 infection. In reported structures of thermophilic RNA polymerase, the G1249 residue is located immediately adjacent to a hydrophobic pocket, called the switch 3 loop. This loop is thought to aid in the separation of the RNA from the DNA-RNA hybrid as RNA enters the RNA exit channel. Our results suggest that the presence of MotA and AsiA may impair the function of this loop or that this portion of the beta subunit may influence interactions among MotA, AsiA, and RNA polymerase.
C1 [James, Tamara D.; Hinton, Deborah M.] NIDDK, Gene Express & Regulat Sect, Lab Mol & Cellular Biol, NIH, Bethesda, MD 20892 USA.
[Cashel, Michael] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Microbial Regulat, NIH, Bethesda, MD 20892 USA.
RP Hinton, DM (reprint author), NIDDK, Gene Express & Regulat Sect, Lab Mol & Cellular Biol, NIH, Bldg 8,Room 2A-13, Bethesda, MD 20892 USA.
EM dhinton@helix.nih.gov
FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases;
NIH, Eunice Kennedy Schriver National Institute of Child Health and
Human Development; Ford Foundation
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Diabetes and Digestive and Kidney
Diseases (T.D.J. and D. M. H.) and by the NIH, Eunice Kennedy Schriver
National Institute of Child Health and Human Development (M. C.). T.D.J.
was also supported by a Ford Foundation predoctoral fellowship.
NR 57
TC 4
Z9 4
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD NOV
PY 2010
VL 192
IS 21
BP 5580
EP 5587
DI 10.1128/JB.00338-10
PG 8
WC Microbiology
SC Microbiology
GA 662LD
UT WOS:000282807900003
PM 20729353
ER
PT J
AU Gandjbakhche, A
Tromberg, B
Kainerstorfer, JM
AF Gandjbakhche, Amir
Tromberg, Bruce
Kainerstorfer, Jana Maria
TI Optical Diagnostic and Biophotonic Methods from Bench to Bedside
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Editorial Material
C1 [Gandjbakhche, Amir; Kainerstorfer, Jana Maria] NIH, Bethesda, MD 20892 USA.
[Tromberg, Bruce] Univ Calif Irvine, Irvine, CA USA.
RP Gandjbakhche, A (reprint author), NIH, Bethesda, MD 20892 USA.
FU NCRR NIH HHS [P41 RR001192-30, P41 RR001192-31, P41 RR001192, P41
RR001192-29]
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD NOV-DEC
PY 2010
VL 15
IS 6
AR 061701
DI 10.1117/1.3528224
PG 1
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 719AI
UT WOS:000287171100008
PM 21198149
ER
PT J
AU Medvedev, AV
Kainerstorfer, JM
Borisov, SV
Gandjbakhche, AH
VanMeter, J
AF Medvedev, Andrei V.
Kainerstorfer, Jana M.
Borisov, Sergey V.
Gandjbakhche, Amir H.
VanMeter, John
TI "Seeing" electroencephalogram through the skull: imaging prefrontal
cortex with fast optical signal
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE near-infrared spectroscopy; fast optical signal; event-related signal;
electroencephalogram; independent component anaysis; visual object
detection
ID NEAR-INFRARED SPECTROSCOPY; INDEPENDENT COMPONENT ANALYSIS; TOP-DOWN
FACILITATION; HUMAN BRAIN; LIGHT-SCATTERING; OBJECT RECOGNITION;
VISUAL-CORTEX; MOTOR CORTEX; HUMAN ADULT; STIMULATION
AB Near-infrared spectroscopy is a novel imaging technique potentially sensitive to both brain hemodynamics (slow signal) and neuronal activity (fast optical signal, FOS). The big challenge of measuring FOS noninvasively lies in the presumably low signal-to-noise ratio. Thus, detectability of the FOS has been controversially discussed. We present reliable detection of FOS from 11 individuals concurrently with electroencephalogram (EEG) during a Go-NoGo task. Probes were placed bilaterally over prefrontal cortex. Independent component analysis (ICA) was used for artifact removal. Correlation coefficient in the best correlated FOS EEG ICA pairs was highly significant (p < 10(-8)), and event-related optical signal (EROS) was found in all subjects. Several EROS components were similar to the event-related potential (ERP) components. The most robust "optical N200" at t = 225 ms coincided with the N200 ERP; both signals showed significant difference between targets and nontargets, and their timing correlated with subject's reaction time. Correlation between FOS and EEG even in single trials provides further evidence that at least some FOS components "reflect" electrical brain processes directly. The data provide evidence for the early involvement of prefrontal cortex in rapid object recognition. EROS is highly localized and can provide cost-effective imaging tools for cortical mapping of cognitive processes. (C) 2010 Society of Photo-Optical Instrumentation Engineers, [DO: 10.1117/1.3505007]
C1 [Medvedev, Andrei V.; Borisov, Sergey V.; VanMeter, John] GUMC, CFMI, Washington, DC 20057 USA.
[Kainerstorfer, Jana M.] Univ Vienna, Dept Phys, Vienna, Austria.
[Kainerstorfer, Jana M.; Gandjbakhche, Amir H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Sect Analyt & Funct Biophoton, Program Pediat Imaging & Tissue Sci, Bethesda, MD 20892 USA.
RP Medvedev, AV (reprint author), GUMC, CFMI, Preclin Sci Bldg,LM 14,3900 Reservoir Rd NW, Washington, DC 20057 USA.
EM am236@georgetown.edu
FU NIH [R01 EB006589]; DARPA [HB1582-05-C-0045]; Nancy Lurie Marks Family
Foundation; Eunice Kennedy Shriver National Institute of Child Health
and Human Development at the National Institutes of Health
FX This work was supported by the NIH (Grant No. R01 EB006589 to A.M.),
DARPA (Grant No. HB1582-05-C-0045 to J.V.), and The Nancy Lurie Marks
Family Foundation. The work was also partially funded by the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development at the National Institutes of Health.
NR 42
TC 13
Z9 13
U1 0
U2 8
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD NOV-DEC
PY 2010
VL 15
IS 6
AR 061702
DI 10.1117/1.3505007
PG 12
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 719AI
UT WOS:000287171100009
PM 21198150
ER
PT J
AU Baldwin, JT
Mann, DL
AF Baldwin, J. Timothy
Mann, Douglas L.
TI NHLBI's Program for VAD Therapy for Moderately Advanced Heart Failure:
The REVIVE-IT Pilot Trial
SO JOURNAL OF CARDIAC FAILURE
LA English
DT Article
DE Mechanical circulatory; support destination therapy; functional
impairment; quality of life
ID VENTRICULAR ASSIST DEVICE
AB Background Ventricular assist devices (VADs) are used to bridge heart failure patients to transplantation to allow their own hearts to recover or as permanent (destination) therapy To date the use of VADs has been limited to late-stage heart failure patients because of the associated device risks In 2008 a National Heart Lung and Blood Institute (NHLBI) working group met to evaluate the treatment of heart failure using VADs and to advise the institute on how therapy for heart failure may be best advanced by clinical trials involving the devices
Methods and Results Recognizing the improvements in VAD technology and in patient care and selection over the past decade the working group recommended that a trial be performed to assess the use of chronic VAD therapy in patients who are less ill than those currently eligible for destination therapy The hypothesis proposed for the trial is that VAD therapy may improve both survival and quality of life in moderately advanced heart failure patients who are neither inotrope-dependent nor exercise-intolerant and have not yet developed serious consequences such as malnourishment end-organ damage and immobility
Conclusion Based on the group's recommendations NHLBI issued an RFP in 2009 for the REVIVE-IT Pilot Trail, which will serve to test the hypothesis and inform the pivotal trial (J Cardiac Fail 2010 16 855-858)
C1 [Baldwin, J. Timothy] NHLBI, Adv Technol & Surg Branch, Basic & Early Technol Res Program, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Mann, Douglas L.] Washington Univ, Sch Med, Div Cardiovasc, St Louis, MO 63110 USA.
RP Baldwin, JT (reprint author), NHLBI, Adv Technol & Surg Branch, Basic & Early Technol Res Program, Div Cardiovasc Sci, 2 Rockledge Ctr,Room 8206,6701 Rockledge Dr, Bethesda, MD 20892 USA.
OI Mann, Douglas /0000-0002-2516-0145
NR 5
TC 52
Z9 53
U1 0
U2 1
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 NOV
PY 2010
VL 16
IS 11
BP 855
EP 858
DI 10.1016/j.cardfail.2010.06.0414
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 680PT
UT WOS:000284247600001
PM 21055648
ER
PT J
AU Nguyen, TL
Xu, XM
Gussio, R
Ghosh, AK
Hamel, E
AF Nguyen, Tam Luong
Xu, Xiaoming
Gussio, Rick
Ghosh, Arun K.
Hamel, Ernest
TI The Assembly-Inducing Laulimalide/Peloruside A Binding Site on Tubulin:
Molecular Modeling and Biochemical Studies with [H-3]Peloruside A
SO JOURNAL OF CHEMICAL INFORMATION AND MODELING
LA English
DT Article
ID MICROTUBULE-STABILIZING AGENTS; BIOLOGICAL EVALUATION; TAXOID SITE;
PELORUSIDE-A; BETA-TUBULIN; COMMON PHARMACOPHORE; PURIFIED TUBULIN;
CELLS RESISTANT; PACLITAXEL; ANALOGS
AB We used synthetic peloruside A for the commercial preparation of [H-3]peloruside A. The radiolabeled compound bound to preformed tubulin polymer in amounts stoichiometric with the polymer's tubulin content, with an apparent K-d value of 0.35 mu M. A less active peloruside A analogue, (11-R)-peloruside A and laulimalide acted as competitive inhibitors of the binding of the [H-3]peloruside A, with apparent K-i values of 9.3 and 0.25 mu M, respectively. Paclitaxel, epothilone B, and discodermolide had essentially no ability to inhibit [H-3]peloruside A binding, confirming that these compounds bind to a different site on tubulin polymer. We modeled both laulimalide and peloruside A into the binding site on beta-tubulin that was identified by Huzil et al. (J. Mol. Biol. 2008, 378, 1016-1030), but our model provides a more reasonable structural basis for the protein-ligand interaction. There is a more complete desolvation of the peloruside A ligand and a greater array of favorable hydrophobic and electrostatic interactions exhibited by peloruside A at its beta-tubulin binding site. In addition, the protein architecture in our peloruside A binding model was suitable for binding laulimalide. With the generation of both laulimalide and peloruside A binding models, it was possible to delineate the structural basis for the greater activity of laulimalide relative to peloruside A and to rationalize the known structure-activity relationship data for both compounds.
C1 [Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
[Nguyen, Tam Luong] NCI, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Xu, Xiaoming; Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Xu, Xiaoming; Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
[Gussio, Rick] NCI, Informat Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
RP Hamel, E (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
EM hamele@mail.nih.gov
OI zaraat, javad/0000-0001-5341-7481
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
National Institutes of Health [GM53386]; Division of Cancer Treatment
and Diagnosis of the National Cancer Institute
FX This project has been funded 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 U.S. Government. This research
was supported in part by the Developmental Therapeutics Program in the
Division of Cancer Treatment and Diagnosis of the National Cancer
Institute. This work was also funded in part by the National Institutes
of Health (A.K.G., GM53386).
NR 42
TC 28
Z9 29
U1 0
U2 7
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 NOV
PY 2010
VL 50
IS 11
BP 2019
EP 2028
DI 10.1021/ci1002894
PG 10
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science,
Information Systems; Computer Science, Interdisciplinary Applications
SC Pharmacology & Pharmacy; Chemistry; Computer Science
GA 681VU
UT WOS:000284350300010
PM 21028850
ER
PT J
AU Ma, ZY
Ma, Y
Sun, XL
Ye, YP
Shen, BZ
Chen, XY
Ito, Y
AF Ma, Zhiyong
Ma, Ying
Sun, Xilin
Ye, Yunpeng
Shen, Baozhong
Chen, Xiaoyuan
Ito, Yoichiro
TI Purification of optical imaging ligand-Cybesin by high-speed
counter-current chromatography
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
AND LIFE SCIENCES
LA English
DT Article
DE High-speed counter current chromatography; Spiral tube assembly;
Isolation and purification; Cybesin; Cypate Bombesin Peptide Analogue;
Conjugate; Pancreas tumor
ID TUMORS
AB Fluorescent Cybesin (Cypate-Bombesin Peptide Analogue Conjugate) was synthesized from Indocyanine Green (ICG) and the bombesin receptor ligand as a contrast agent for detecting pancreas tumors However the LC-MS analysis indicated that the target compound was only a minor component in the reaction mixture Since preparative HPLC can hardly separate such a small amount of the target compound directly from the original crude reaction mixture without a considerable adsorptive loss onto the solid support high-speed counter-current chromatography (HSCCC) was used for purification since the method uses no solid support and promises high sample recovery A suitable two-phase solvent system composed of hexane/ethyl acetate/methanol/methyl t-butyl ether/acetonitnle/water) at a volume ratio of 1 1 1 4 4 7 was selected based on the partition coefficient of Cybesin (K approximate to 0 9) determined by LC-MS The separation was performed in two steps using the same solvent system with lower aqueous mobile phase From 400 mg of the crude reaction mixture the first separation yielded 7 7 mg of fractions containing the target compound at 12 8% purity and in the second run 1 mg of Cybesin was obtained at purity of 94 0% with a sample recovery rate of over 95% based on the LC-MS analysis Published by Elsevier B V
C1 [Ma, Ying; Sun, Xilin; Ye, Yunpeng; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Ma, Zhiyong] Harbin Med Coll, Coll Pharm, Harbin 150081, Peoples R China.
[Ma, Zhiyong; Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Sun, Xilin; Shen, Baozhong] Harbin Med Coll, Affiliated Hosp 4, Dept Med Imaging & Nucl Med, Harbin 150001, Peoples R China.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, 31 Ctr Dr 31-1C22, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [ZIA HL005107-02]
NR 10
TC 1
Z9 1
U1 1
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD NOV 1
PY 2010
VL 878
IS 29
BP 3039
EP 3043
DI 10.1016/j.jchromb.2010.09.007
PG 5
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 679CP
UT WOS:000284137300013
PM 20933483
ER
PT J
AU Vogelzangs, N
Beekman, ATF
Milaneschi, Y
Bandinelli, S
Ferrucci, L
Penninx, BWJH
AF Vogelzangs, Nicole
Beekman, Aartjan T. F.
Milaneschi, Yuri
Bandinelli, Stefania
Ferrucci, Luigi
Penninx, Brenda W. J. H.
TI Urinary Cortisol and Six-Year Risk of All-Cause and Cardiovascular
Mortality
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID PITUITARY-ADRENAL AXIS; METABOLIC SYNDROME; MYOCARDIAL-INFARCTION;
ADIPOSE-TISSUE; BLOOD-PRESSURE; STRESS; DISEASE; CALCIFICATION;
INFLAMMATION; DECLINE
AB Context: The stress hormone cortisol has been linked with unfavorable cardiovascular risk factors, but longitudinal studies examining whether high levels of cortisol predict cardiovascular mortality are largely absent.
Objective: The aim of this study was to examine whether urinary cortisol levels predict all-cause and cardiovascular mortality over 6 yr of follow-up in a general population of older persons.
Design and Setting: Participants were part of the InCHIANTI study, a prospective cohort study in the older general population with 6 yr of follow-up.
Participants: We studied 861 participants aged 65 yr and older.
Main Outcome Measure: Twenty-four-hour urinary cortisol levels were assessed at baseline. In the following 6 yr, all-cause and cardiovascular mortality was ascertained from death certificates. Cardiovascular mortality included deaths due to ischemic heart disease and cerebrovascular disease.
Results: During a mean follow-up of 5.7 (SD = 1.2) yr, 183 persons died, of whom 41 died from cardiovascular disease. After adjustment for sociodemographics, health indicators, and baseline cardiovascular disease, urinary cortisol did not increase the risk of noncardiovascular mortality, but it did increase cardiovascular mortality risk. Persons in the highest tertile of urinary cortisol had a five times increased risk of dying of cardiovascular disease (hazard ratio = 5.00; 95% confidence interval = 2.02-12.37). This effect was found to be consistent across persons with and without cardiovascular disease at baseline (p interaction = 0.78).
Conclusions: High cortisol levels strongly predict cardiovascular death among persons both with and without preexisting cardiovascular disease. The specific link with cardiovascular mortality, and not other causes of mortality, suggests that high cortisol levels might be particularly damaging to the cardiovascular system. (J Clin Endocrinol Metab 95: 4959-4964, 2010)
C1 [Vogelzangs, Nicole; Beekman, Aartjan T. F.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, NL-1081 HL Amsterdam, Netherlands.
[Vogelzangs, Nicole; Beekman, Aartjan T. F.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, NL-1081 HL Amsterdam, Netherlands.
[Milaneschi, Yuri; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21225 USA.
[Milaneschi, Yuri] Tuscany Hlth Reg Agcy, I-50125 Florence, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil, I-50122 Florence, Italy.
RP Vogelzangs, N (reprint author), AJ Ernststr 1187, NL-1081 HL Amsterdam, Netherlands.
EM n.vogelzangs@vumc.nl
FU Italian Ministry of Health [ICS 110.1/RS97.71]; U.S. National Institute
on Aging [263 MD 916413, 263 MD 821336]; National Heart, Lung, and Blood
Institute [1R01-HL972972]; Laboratory of Epidemiology, Demography, and
Biometry, National Institute on Aging
FX The InCHIANTI study was supported as a targeted project (Grant ICS
110.1/RS97.71) by the Italian Ministry of Health and in part by the U.S.
National Institute on Aging (Grants 263 MD 916413 and 263 MD 821336).
Data analyses were supported through Grant 1R01-HL972972 from the
National Heart, Lung, and Blood Institute. Cortisol assays were
supported by a professional services contract from the Laboratory of
Epidemiology, Demography, and Biometry, National Institute on Aging.
NR 36
TC 53
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U1 1
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 NOV
PY 2010
VL 95
IS 11
BP 4959
EP 4964
DI 10.1210/jc.2010-0192
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 675QB
UT WOS:000283844400040
PM 20739384
ER
PT J
AU Esparza-Romero, J
Valencia, ME
Martinez, ME
Ravussin, E
Schulz, LO
Bennett, PH
AF Esparza-Romero, Julian
Valencia, Mauro E.
Martinez, Maria Elena
Ravussin, Eric
Schulz, Leslie O.
Bennett, Peter H.
TI Differences in Insulin Resistance in Mexican and U.S. Pima Indians with
Normal Glucose Tolerance
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID DIABETES-MELLITUS; PHYSICAL-ACTIVITY; ENZYMATIC DETERMINATION;
PLASMA-GLUCOSE; PATHOGENESIS; CHOLESTEROL; POPULATIONS; DYSFUNCTION;
OBESITY; RISK
AB Context: Insulin resistance is a major risk factor for the development of type 2 diabetes in Pima Indians, a population with the highest prevalence of type 2 diabetes mellitus in the world. Their Mexican counterpart, living a traditional lifestyle in the mountains of Sonora, have at least 5 times less diabetes than the U. S. Pima Indians.
Objective: We evaluated whether Mexican Pima Indians had lower insulin resistance than U. S. Pima Indians.
Design and Patients: We compared fasting insulin and homeostasis model assessment for insulin resistance (HOMA-IR) in 194 Mexican Pima Indians (100 females, 94 males) and 449 U. S. Pima Indians (246 females, 203 males) with normal glucose tolerance from a cross-sectional study. Adjusted differences of log-transformed outcomes (fasting insulin and HOMA-IR) between groups were evaluated using multiple linear regression models and paired t test in a matched subset.
Results: Unadjusted fasting insulin and HOMA-IR were much lower in the Mexican Pima Indians than in their U. S. counterparts. After adjusting by obesity, age, and sex, mean (95% confidence interval) for fasting insulin was 6.22 (5.34-7.24) vs. 13.56 mu U/ml (12.27-14.97) and for HOMA-IR 1.40 (1.20-1.64) vs. 3.07 (2.77-3.40), respectively, for Mexican Pima and U. S. Pima Indians. Results were confirmed in subset matched for age, sex, and body fat.
Conclusion: Our results indicate that Mexican Pima Indians have lower insulin resistance in comparison with their genetically related U. S. counterparts, even after controlling for differences in obesity, age, and sex. This finding underscores the importance of lifestyle factors as protecting factors against insulin resistance in individuals with a high propensity to develop diabetes. (J Clin Endocrinol Metab 95: E358-E362, 2010)
C1 [Esparza-Romero, Julian; Valencia, Mauro E.] AC, Ctr Invest Alimentac & Desarrollo, Hermosillo 83000, Sonora, Mexico.
[Esparza-Romero, Julian; Martinez, Maria Elena] Univ Arizona, Div Epidemiol & Biostat, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85724 USA.
[Martinez, Maria Elena] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA.
[Ravussin, Eric] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
[Schulz, Leslie O.] No Arizona Univ, Coll Hlth & Human Serv, Flagstaff, AZ 86011 USA.
[Bennett, Peter H.] NIDDK, Phoenix Epidemiol & Clin Res Brach, NIH, Phoenix, AZ 85014 USA.
RP Esparza-Romero, J (reprint author), Ctr Invest Alimentac & Desarrollo AC, Carretera la Victoria Km 0-6,Apartado Postal 1735, Hermosillo 83000, Sonora, Mexico.
EM julian@ciad.mx
NR 19
TC 13
Z9 13
U1 0
U2 4
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 NOV
PY 2010
VL 95
IS 11
BP E358
EP E362
DI 10.1210/jc.2010-0297
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 675QB
UT WOS:000283844400012
PM 20668044
ER
PT J
AU Schafer, AL
Vittinghoff, E
Lang, TF
Sellmeyer, DE
Harris, TB
Kanaya, AM
Strotmeyer, ES
Cawthon, PM
Cummings, SR
Tylavsky, FA
Scherzinger, AL
Schwartz, AV
AF Schafer, Anne L.
Vittinghoff, Eric
Lang, Thomas F.
Sellmeyer, Deborah E.
Harris, Tamara B.
Kanaya, Alka M.
Strotmeyer, Elsa S.
Cawthon, Peggy M.
Cummings, Steven R.
Tylavsky, Frances A.
Scherzinger, Ann L.
Schwartz, Ann V.
CA Hlth Aging Body Composition Hlth
TI Fat Infiltration of Muscle, Diabetes, and Clinical Fracture Risk in
Older Adults
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ADIPOSE-TISSUE DISTRIBUTION; BODY-COMPOSITION; SKELETAL-MUSCLE; HIP
FRACTURE; COMPUTED-TOMOGRAPHY; BLACK ADULTS; HEALTH; WOMEN; MEN;
ATTENUATION
AB Context: Older adults with type 2 diabetes are at higher risk for fracture compared with nondiabetic adults after adjustment for their higher bone mineral density. Infiltration of muscle by fat predicts increased risk of hip fracture.
Objective: We investigated whether fat infiltration of muscle, which is greater in diabetic adults, is associated with all clinical fracture and whether it accounts for the increased fracture risk in those with diabetes.
Design, Setting, and Participants: Data were analyzed from the Health, Aging, and Body Composition Study, a cohort of community-dwelling adults aged 70-79 yr. Glucose metabolism status and x-ray attenuation of thigh muscle were determined at baseline for 2762 participants.
Main Outcome Measures: During a mean 8.2 +/- 2.3 yr follow-up, 331 participants reported at least one clinical fracture.
Results: Fat infiltration of muscle was higher in those with diabetes or impaired glucose metabolism than in those with normal glucose metabolism (P < 0.001). Fat infiltration of muscle was independently associated with a 19% increased risk of incident clinical fracture (multivariate hazard ratio = 1.19; 95% confidence interval = 1.04-1.36); this association did not differ across glucose metabolism groups (P for interaction = 0.65). As previously reported, diabetes was associated with a greater fracture risk compared with normal glucose metabolism (hazard ratio = 1.42; 95% confidence interval = 1.07-1.89) after adjustment for bone mineral density, but further adjustment for fat infiltration of muscle did not attenuate this association.
Conclusions: Fat infiltration of muscle predicts clinical fracture in older adults. Although fat infiltration of muscle is higher among those with diabetes, it does not account for their increased fracture risk. (J Clin Endocrinol Metab 95: E368-E372, 2010)
C1 [Schafer, Anne L.; Kanaya, Alka M.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Vittinghoff, Eric; Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Lang, Thomas F.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA.
[Sellmeyer, Deborah E.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Strotmeyer, Elsa S.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Cawthon, Peggy M.; Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA.
[Tylavsky, Frances A.] Univ Tennessee, Dept Prevent Med, Memphis, TN 38105 USA.
[Scherzinger, Ann L.] Univ Colorado, Dept Radiol, Denver, CO 80045 USA.
RP Schafer, AL (reprint author), 2200 Post St,Room C-409, San Francisco, CA 94115 USA.
EM anne.schafer@ucsf.edu
RI Lang, Thomas/B-2685-2012; Strotmeyer, Elsa/F-3015-2014;
OI Lang, Thomas/0000-0002-3720-8038; Strotmeyer, Elsa/0000-0002-4093-6036
FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; National Institutes of Health National Institute on
Aging; Merck
FX This work was supported by the National Institute on Aging under
contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. This research
was supported in part by the Intramural Research Program of the National
Institutes of Health National Institute on Aging.; A.L.S., E.V., D.E.S.,
T.B.H., A.M.K., E.S.S., S.R.C., F.A.T., A.L.S., and A.V.S. have nothing
to disclose. T.F.L. has received grant support from Merck. P.M.C.
consults for Merck and Amgen.
NR 20
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U1 2
U2 4
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 NOV
PY 2010
VL 95
IS 11
BP E368
EP E372
DI 10.1210/jc.2010-0780
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 675QB
UT WOS:000283844400014
PM 20668037
ER
PT J
AU Lie, HH
Cella, D
Gershon, R
Shen, J
Morales, LS
Riley, W
Hays, RD
AF Lie, Honghu
Cella, David
Gershon, Richard
Shen, Jie
Morales, Leo S.
Riley, William
Hays, Ron D.
TI Representativeness of the Patient-Reported Outcomes Measurement
Information System Internet panel
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE PROMIS; Patient-reported outcomes; Resampling; Weighting; Raking;
Equivalence testing
ID WORLD-WIDE-WEB; DATA-COLLECTION; MAILED QUESTIONNAIRES; EQUIVALENCE;
TESTS; DIFFERENCE; ONLINE; PROMIS; MODEL; EQ-5D
AB Objectives: To evaluate the Patient-Reported Outcomes Measurement Information System (PROMIS), which collected data from an Internet polling panel, and to compare PROMIS with national norms.
Study Design and Setting: We compared demographics and self-rated health of the PROMIS general Internet sample (N = 11,796) and one of its subsamples (n = 2,196) selected to approximate the joint distribution of demographics from the 2000 U.S. Census, with three national surveys and U.S. Census data. The comparisons were conducted using equivalence testing with weights created for PROMIS by raking.
Results: The weighted PROMIS population and subsample had similar demographics compared with the 2000 U.S. Census, except that the subsample had a higher percentage of people with higher education than high school. Equivalence testing shows similarity between PROMIS general population and national norms with regard to body mass index, EQ-5D health index (EuroQol group defined descriptive system of health-related quality of life states consisting of five dimensions including mobility, self-care, usual activities, pain/discomfort, anxiety/depression), and self-rating of general health.
Conclusion: Self-rated health of the PROMIS general population is similar to that of existing samples from the general U.S. population. The weighted PROMIS general population is more comparable to national norms than the unweighted population with regard to subject characteristics. The findings suggest that the representativeness of the Internet data is comparable to those from probability-based general population samples. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Lie, Honghu; Hays, Ron D.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, UCLA Dept Med, Los Angeles, CA 90095 USA.
[Cella, David; Gershon, Richard] Northwestern Univ, Inst Healthcare Studies, Chicago, IL 60611 USA.
[Shen, Jie] Univ Calif Los Angeles, UCLA Dept Stat, Los Angeles, CA 90095 USA.
[Morales, Leo S.] Grp Hlth Res Inst, Seattle, WA USA.
[Riley, William] NIMH, Div AIDS & Hlth Behav Res, Bethesda, MD 20892 USA.
RP Lie, HH (reprint author), Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, UCLA Dept Med, 911 Broxton Plaza,Room 202, Los Angeles, CA 90095 USA.
EM hhliu@ucla.edu
RI Hays, Ronald/D-5629-2013
FU National Institutes of Health (NIH) through the NIH Roadmap for Medical
Research [1U01-AR052177]
FX This work was funded by the National Institutes of Health (NIH) through
the NIH Roadmap for Medical Research Cooperative Agreement
(1U01-AR052177).
NR 43
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Z9 8
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0895-4356
EI 1878-5921
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD NOV
PY 2010
VL 63
IS 11
BP 1169
EP 1178
DI 10.1016/j.jclinepi.2009.11.021
PG 10
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 663CW
UT WOS:000282861600003
ER
PT J
AU Cella, D
Riley, W
Stone, A
Rothrock, N
Reeve, B
Yount, S
Amtmann, D
Bode, R
Buysse, D
Choi, S
Cook, K
DeVellis, R
DeWalt, D
Fries, JF
Gershon, R
Hahn, EA
Lai, JS
Pilkonis, P
Revicki, D
Rose, M
Weinfurt, K
Hays, R
AF Cella, David
Riley, William
Stone, Arthur
Rothrock, Nan
Reeve, Bryce
Yount, Susan
Amtmann, Dagmar
Bode, Rita
Buysse, Daniel
Choi, Seung
Cook, Karon
DeVellis, Robert
DeWalt, Darren
Fries, James F.
Gershon, Richard
Hahn, Elizabeth A.
Lai, Jin-Shei
Pilkonis, Paul
Revicki, Dennis
Rose, Matthias
Weinfurt, Kevin
Hays, Ron
CA PROMIS Cooperative Grp
TI The Patient-Reported Outcomes Measurement Information System (PROMIS)
developed and tested its first wave of adult self-reported health
outcome item banks: 2005-2008
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE Outcome measures; Quality of life; Chronic disease; Item response
theory; Patient-reported outcomes; PROMIS
ID QUALITY-OF-LIFE; PHYSICAL FUNCTION; CLINICAL-TRIALS; SHORT-FORMS; PAIN;
MODEL; SCHIZOPHRENIA; DISABILITY; SYMPTOMS; FATIGUE
AB Objectives: Patient-reported outcomes (PROs) are essential when evaluating many new treatments in health care; yet, current measures have been limited by a lack of precision, standardization, and comparability of scores across studies and diseases. The Patient-Reported Outcomes Measurement Information System (PROMIS) provides item banks that offer the potential for efficient (minimizes item number without compromising reliability), flexible (enables optional use of interchangeable items), and precise (has minimal error in estimate) measurement of commonly studied PROs. We report results from the first large-scale testing of PROMIS items.
Study Design and Setting: Fourteen item pools were tested in the U.S. general population and clinical groups using an online panel and clinic recruitment. A scale-setting subsample was created reflecting demographics proportional to the 2000 U.S. census.
Results: Using item-response theory (graded response model), 11 item banks were calibrated on a sample of 21,133, measuring components of self-reported physical, mental, and social health, along with a 10-item Global Health Scale. Short forms from each bank were developed and compared with the overall bank and with other well-validated and widely accepted ("legacy") measures. All item banks demonstrated good reliability across most of the score distributions. Construct validity was supported by moderate to strong correlations with legacy measures.
Conclusion: PROMIS item banks and their short forms provide evidence that they are reliable and precise measures of generic symptoms and functional reports comparable to legacy instruments. Further testing will continue to validate and test PROMIS items and banks in diverse clinical populations. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Cella, David] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
[Riley, William] NHLBI, Bethesda, MD 20892 USA.
[Stone, Arthur] SUNY Stony Brook, Stony Brook, NY 11794 USA.
[Reeve, Bryce] NCI, Bethesda, MD 20892 USA.
[Amtmann, Dagmar; Cook, Karon] Univ Washington, Seattle, WA 98195 USA.
[Buysse, Daniel; Pilkonis, Paul] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[DeVellis, Robert] Univ N Carolina, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA.
[DeWalt, Darren] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC USA.
[Fries, James F.] Stanford Univ, Dept Med, Palo Alto, CA 94304 USA.
[Revicki, Dennis] United BioSource Corp, Bethesda, MD USA.
[Rose, Matthias] Univ Hamburg, Dept Med, Hamburg, Germany.
[Weinfurt, Kevin] Duke Univ, Sch Med, Durham, NC USA.
[Hays, Ron] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
RP Cella, D (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, 710 N Lake Shore Dr, Chicago, IL 60611 USA.
EM d-cella@northwestern.edu
RI Hays, Ronald/D-5629-2013; Rose, Matthias/A-8920-2015; Fries,
James/F-6271-2011;
OI DeWalt, Darren/0000-0003-2270-751X
FU Northwestern University, PI: David Cella, PhD [U02AR52177]; 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]; University of Washington, PI: Dagmar Amtmann,
PhD [U01AR52171]
FX The Patient-Reported Outcomes Measurement Information System (PROMIS) is
an NIH Roadmap initiative to develop a computerized system measuring
PROs in respondents with a wide range of chronic diseases and
demographic characteristics. This work was funded by cooperative
agreements to a Statistical Coordinating Center (Northwestern
University, PI: David Cella, PhD, U02AR52177) 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 have
included Deborah Ader, PhD, Susan Czajkowski, PhD, Lawrence Fine, MD,
DrPH, Louis Quatrano, PhD, Bryce Reeve, PhD, William Riley, PhD, Susana
Serrate-Sztein, MD, and James Witter, MD, PhD. This manuscript was
reviewed by the PROMIS Publications Subcommittee before external peer
review. See the Web site at www.nihpromis. org for additional
information on the PROM IS initiative.
NR 44
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Z9 519
U1 2
U2 45
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-4356
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD NOV
PY 2010
VL 63
IS 11
BP 1179
EP 1194
DI 10.1016/j.jclinepi.2010.04.011
PG 16
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 663CW
UT WOS:000282861600004
PM 20685078
ER
PT J
AU Rothrock, NE
Hays, RD
Spritzer, K
Yount, SE
Riley, W
Cella, D
AF Rothrock, Nan E.
Hays, Ron D.
Spritzer, Karen
Yount, Susan E.
Riley, William
Cella, David
TI Relative to the general US population, chronic diseases are associated
with poorer health-related quality of life as measured by the
Patient-Reported Outcomes Measurement Information System (PROMIS)
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE Chronic disease; Comorbidity; Quality of life; Outcome measures; Patient
outcome assessment; Item response theory
ID FUNCTIONAL ASSESSMENT; CANCER; THERAPY; COMORBIDITIES; ARTHRITIS;
PROGRESS; FATIGUE; SCALE
AB Objectives: The Patient-Reported Outcomes Measurement Information System (PROMIS) allows assessment of the impact of chronic conditions on health-related quality of life (HRQL) across diseases. We report on the HRQL impact of individual and comorbid conditions as well as conditions that are described as limiting activity.
Study Design and Setting: Data were collected through online and clinic recruitment as part of the PROMIS item calibration sample (n = 21,133). Participants reported the presence or absence of 24 chronic health conditions and whether their activity was limited by each condition.
Results: Across health status domains, the presence of a chronic condition was associated with poorer scores than those without a diagnosis, particularly for those individuals who reported that their condition was disabling. The magnitude of detriment in HRQL was more pronounced for individuals with two or more chronic conditions and could not be explained by sociodemographic factors. Patterns of HRQL deficits varied across disease and comorbidity status.
Conclusion: The impact of chronic conditions, particularly when experienced with comorbid disease, is associated with detriments in HRQL. The negative impact on HRQL varies across symptoms and functional areas within a given condition. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Rothrock, Nan E.; Yount, Susan E.; Cella, David] Northwestern Univ, Dept Med Social Sci, Chicago, IL 60611 USA.
[Hays, Ron D.; Spritzer, Karen] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Riley, William] NHLBI, Bethesda, MD 20892 USA.
RP Rothrock, NE (reprint author), Northwestern Univ, Dept Med Social Sci, 625 N Michigan Ave,Suite 2700, Chicago, IL 60611 USA.
EM n-rothrock@northwestern.edu
RI Hays, Ronald/D-5629-2013
FU Northwestern University, PI: David Cella, PhD [U01AR52177]; 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]; University of Washington, PI: Dagmar Amtmann,
PhD [U01AR52171]
FX The PROM IS is an NIH Roadmap initiative to develop a computerized
system measuring PROs 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. This manuscript was reviewed by the
PROMIS Publications Subcommittee before external peer review; see the
Web site at www.nihpromis.org for additional information on the PROMIS
cooperative group.
NR 33
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U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-4356
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD NOV
PY 2010
VL 63
IS 11
BP 1195
EP 1204
DI 10.1016/j.jclinepi.2010.04.012
PG 10
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 663CW
UT WOS:000282861600005
PM 20688471
ER
PT J
AU Glynn, SA
Boersma, BJ
Dorsey, TH
Yi, M
Yfantis, HG
Ridnour, LA
Martin, DN
Switzer, CH
Hudson, RS
Wink, DA
Lee, DH
Stephens, RM
Ambs, S
AF Glynn, Sharon A.
Boersma, Brenda J.
Dorsey, Tiffany H.
Yi, Ming
Yfantis, Harris G.
Ridnour, Lisa A.
Martin, Damali N.
Switzer, Christopher H.
Hudson, Robert S.
Wink, David A.
Lee, Dong H.
Stephens, Robert M.
Ambs, Stefan
TI Increased NOS2 predicts poor survival in estrogen receptor-negative
breast cancer patients
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; ENDOTHELIAL GROWTH-FACTOR; SQUAMOUS-CELL
CARCINOMA; BASAL-LIKE SUBTYPE; WILD-TYPE P53; GENE-EXPRESSION; TUMOR
ANGIOGENESIS; P-CADHERIN; MACROPHAGE INFILTRATION; IL-8 EXPRESSION
AB Inducible nitric oxide synthase (NOS2) is involved in wound healing, angiogenesis, and carcinogenesis. NOS2 upregulation and increased nitric oxide (NO) production affect the redox state of cells and can induce protein, lipid, and DNA modifications. To investigate whether NOS2 levels influence survival of breast cancer patients, we examined NOS2 expression and its association with tumor markers and survival in 248 breast tumors. In multivariable survival analysis, increased NOS2 predicted inferior survival in women with estrogen receptor alpha-negative (ER-negative) tumors. Microdissected tumor epithelium from ER-negative tumors with high NOS2 had increased IL-8 and a gene expression signature characteristic of basal-like breast cancer with poor prognosis. In cell culture, NO only induced selected signature genes in ER-negative breast cancer cells. ER transgene expression in ER-negative cells inhibited NO-induced upregulation of the stem cell marker CD44 and other proteins encoded by signature genes, but not of IL-8. Exposure to NO also enhanced cell motility and invasion of ER-negative cells. Last, pathway analysis linked the tumor NOS2 gene signature to c-Myc activation. Thus, NOS2 is associated with a basal-like transcription pattern and poor survival of ER-negative patients.
C1 [Glynn, Sharon A.; Boersma, Brenda J.; Dorsey, Tiffany H.; Martin, Damali N.; Hudson, Robert S.; Ambs, Stefan] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Glynn, Sharon A.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA.
[Yi, Ming; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Yfantis, Harris G.; Lee, Dong H.] Baltimore Vet Affairs Med Ctr, Baltimore, MD USA.
[Ridnour, Lisa A.; Switzer, Christopher H.; Wink, David A.] NCI, Tumor Biol Sect, Radiat Biol Branch, CCR, Bethesda, MD 20892 USA.
RP Ambs, S (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, Room 3050B,37 Convent Dr MSC 4258, Bethesda, MD 20892 USA.
EM ambss@mail.nih.gov
RI Glynn, Sharon/D-7136-2013; Switzer, Christopher/D-9203-2013; Boersma,
Brenda/A-9270-2009
OI Glynn, Sharon/0000-0003-1459-2580; Boersma, Brenda/0000-0002-8992-2735
FU NIH; National Cancer Institute; Center for Cancer Research; National
Cancer Institute Cancer Prevention Fellowship; Health Research Board of
Ireland
FX This research was supported by the Intramural Research Program of the
NIH, the National Cancer Institute, and the Center for Cancer Research.
We thank Raymond Jones, Audrey Salabes, Leoni Leondaridis, Glennwood
Trivers, Elise Bowman, and personnel at the University of Maryland and
the Baltimore Veterans Administration and the Surgery and Pathology
Departments at the University of Maryland Medical Center, Baltimore
Veterans Affairs Medical Center, Union Memorial Hospital, Mercy Medical
Center, and Sinai Hospital for their contributions. Sharon A. Glynn is
the recipient of an All-Ireland Cancer Consortium National Cancer
Institute Cancer Prevention Fellowship, sponsored in part by the Health
Research Board of Ireland.
NR 79
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U2 6
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD NOV
PY 2010
VL 120
IS 11
BP 3843
EP 3854
DI 10.1172/JCI42059
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 672XU
UT WOS:000283621800019
PM 20978357
ER
PT J
AU Chinnasamy, D
Yu, ZY
Theoret, MR
Zhao, YB
Shrimali, RK
Morgan, RA
Feldman, SA
Restifo, NP
Rosenberg, SA
AF Chinnasamy, Dhanalakshmi
Yu, Zhiya
Theoret, Marc R.
Zhao, Yangbing
Shrimali, Rajeev K.
Morgan, Richard A.
Feldman, Steven A.
Restifo, Nicholas P.
Rosenberg, Steven A.
TI Gene therapy using genetically modified lymphocytes targeting VEGFR-2
inhibits the growth of vascularized syngenic tumors in mice
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID CHIMERIC ANTIGEN RECEPTOR; CYTOTOXIC T-LYMPHOCYTES; CELL TRANSFER
THERAPY; ADOPTIVE IMMUNOTHERAPY; ANTITUMOR-ACTIVITY; CANCER REGRESSION;
IN-VIVO; ANTIANGIOGENIC THERAPY; ENDOTHELIAL GROWTH-FACTOR-RECEPTOR-2;
METASTATIC MELANOMA
AB Immunotherapies based on adoptive cell transfer are highly effective in the treatment of metastatic melanoma, but the use of this approach in other cancer histologies has been hampered by the identification of appropriate target molecules. Immunologic approaches targeting tumor vasculature provide a means for the therapy of multiple solid tumor types. We developed a method to target tumor vasculature, using genetically redirected syngeneic or autologous T cells. Mouse and human T cells were engineered to express a chimeric antigen receptor (CAR) targeted against VEGFR-2, which is overexpressed in tumor vasculature and is responsible for VEGF-mediated tumor progression and metastasis. Mouse and human T cells expressing the relevant VEGFR-2 CARs mediated specific immune responses against VEGFR-2 protein as well as VEGFR-2-expressing cells in vitro. A single dose of VEGFR-2 CAR-engineered mouse T cells plus exogenous IL-2 significantly inhibited the growth of 5 different types of established, vascularized syngeneic tumors in 2 different strains of mice and prolonged the survival of mice. T cells transduced. with VEGFR-2 CAR showed durable and increased tumor infiltration, correlating with their antitumor effect. This approach provides a potential method for the gene therapy of a variety of human cancers:
C1 [Chinnasamy, Dhanalakshmi; Yu, Zhiya; Theoret, Marc R.; Zhao, Yangbing; Shrimali, Rajeev K.; Morgan, Richard A.; Feldman, Steven A.; Restifo, Nicholas P.; Rosenberg, Steven A.] NCI, Surg Branch, Clin Res Ctr, Bethesda, MD 20892 USA.
[Zhao, Yangbing] Univ Penn, Dept Pathol & Lab Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
RP Rosenberg, SA (reprint author), NCI, Surg Branch, Clin Res Ctr, Bldg 10 CRC,Room 3-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM SAR@mail.nih.gov
RI Restifo, Nicholas/A-5713-2008;
OI Restifo, Nicholas P./0000-0003-4229-4580
NR 87
TC 70
Z9 74
U1 0
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 NOV
PY 2010
VL 120
IS 11
BP 3953
EP 3968
DI 10.1172/JCI43490
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 672XU
UT WOS:000283621800029
PM 20978347
ER
PT J
AU Hiby, SE
Apps, R
Sharkey, AM
Farrell, LE
Gardner, L
Mulder, A
Claas, FH
Walker, JJ
Redman, CC
Morgan, L
Tower, C
Regan, L
Moore, GE
Carrington, M
Moffett, A
AF Hiby, Susan E.
Apps, Richard
Sharkey, Andrew M.
Farrell, Lydia E.
Gardner, Lucy
Mulder, Arend
Claas, Frans H.
Walker, James J.
Redman, Christopher C.
Morgan, Linda
Tower, Clare
Regan, Lesley
Moore, Gudrun E.
Carrington, Mary
Moffett, Ashley
TI Maternal activating KIRs protect against human reproductive failure
mediated by fetal HLA-C2
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID NATURAL-KILLER-CELLS; IMMUNOGLOBULIN-LIKE RECEPTORS; CLASS-I MOLECULES;
UTERINE NK CELLS; RECURRENT MISCARRIAGE; INHIBITORY RECEPTORS; SURFACE
EXPRESSION; MONOCLONAL-ANTIBODIES; TROPHOBLAST CELLS; HUMAN-PREGNANCY
AB Many common disorders of pregnancy are attributed to insufficient invasion of the uterine lining by trophoblast, fetal cells that are the major cell type of the placenta. Interactions between fetal trophoblast and maternal uterine NK (uNK) cells - specifically interactions between HLA-C molecules expressed by the fetal trophoblast cells and killer Ig-like receptors (KIRs) on the maternal uNK cells - influence placentation in human pregnancy. Consistent with this, pregnancies are at increased risk of preeclampsia in mothers homozygous for KIR haplotype A (KIR AA). In this study, we have demonstrated that trophoblast expresses both paternally and maternally inherited HLA-C surface proteins and that maternal KIR AA frequencies are increased in affected pregnancies only when the fetus has more group 2 HLA-C genes (C2) than the mother. These data raise the possibility that there is a deleterious allogeneic effect stemming from paternal C2. We found that this effect also occurred in other pregnancy disorders (fetal growth restriction and recurrent miscarriage), indicating a role early in gestation for these receptor/ligand pairs in the pathogenesis of reproductive failure. Notably, pregnancy disorders were less frequent in mothers that possessed the telomeric end of the KIR B haplotype, which contains activating KIR2DS1. In addition, uNK cells expressed KIR2DS1, which bound specifically to C2(+) trophoblast cells. These findings highlight the complexity and central importance of specific combinations of activating KIR and HLA-C in maternal-fetal immune interactions that determine reproductive success.
C1 [Hiby, Susan E.; Apps, Richard; Sharkey, Andrew M.; Farrell, Lydia E.; Gardner, Lucy; Moffett, Ashley] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Hiby, Susan E.; Apps, Richard; Sharkey, Andrew M.; Farrell, Lydia E.; Gardner, Lucy; Moffett, Ashley] Ctr Trophoblast Res, Cambridge, England.
[Apps, Richard; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, Frederick, MD 21701 USA.
[Apps, Richard; Carrington, Mary] Ragon Inst MGH MIT & Harvard, Boston, MA USA.
[Mulder, Arend; Claas, Frans H.] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands.
[Walker, James J.] Univ Leeds, St James Univ Hosp, Leeds Inst Mol Med, Perinatal Res Grp, Leeds, W Yorkshire, England.
[Walker, James J.; Redman, Christopher C.; Morgan, Linda] Univ Oxford, Genet Preeclampsia GOPEC Consortium, Oxford, England.
[Redman, Christopher C.] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England.
[Morgan, Linda] Univ Nottingham, Dept Clin Chem, Inst Genet, Nottingham NG7 2RD, England.
[Tower, Clare] St Marys Hosp, Maternal & Fetal Hlth Res Ctr, Manchester M13 0JH, Lancs, England.
[Regan, Lesley] St Marys Hosp, Sch Med, Dept Obstet & Gynaecol, London W2 1PG, England.
[Moore, Gudrun E.] UCL, Clin & Mol Genet Unit, Inst Child Hlth, London, England.
RP Moffett, A (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England.
EM am485@cam.ac.uk
RI Sharkey, Andrew/H-7015-2013; Moffett, Ashley/J-9754-2013; Moore,
Gudrun/A-2092-2009;
OI Sharkey, Andrew/0000-0002-5072-7748; Walker, James/0000-0002-8922-083X;
Farrell, Lydia/0000-0002-7643-6009
FU Wellcome Trust; British Heart Foundation; Wellbeing of Women; Centre for
Trophoblast Research; King's College, University of Cambridge; National
Cancer Institute, NIH [HHSN261200800001E]; Center for Cancer Research
(National Cancer Institute, NIH
FX These studies have been supported by the Wellcome Trust, the British
Heart Foundation, Wellbeing of Women, Centre for Trophoblast Research,
and King's College, University of Cambridge. We are grateful to Graham
Burton and Charlie Loke for helpful discussions and Ying Qi for
statistical advice. We would like to thank all the donors, the GOPEC
Consortium, and research nurses for providing the samples, and the
Anthony Nolan Trust for HLA-C typing and Luminex bead studies. This
project was funded in whole or in part with federal funds from the
National Cancer Institute, NIH, under contract HHSN261200800001E. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
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 Center for Cancer Research
(National Cancer Institute, NIH).
NR 63
TC 172
Z9 178
U1 4
U2 17
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 NOV
PY 2010
VL 120
IS 11
BP 4102
EP 4110
DI 10.1172/JCI43998
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 672XU
UT WOS:000283621800041
PM 20972337
ER
PT J
AU Salit, RB
Shea, YR
Gea-Banacloche, J
Fahle, GA
Abu-Asab, M
Sugui, JA
Carpenter, AE
Quezado, MM
Bishop, MR
Kwon-Chung, KJ
AF Salit, R. B.
Shea, Y. R.
Gea-Banacloche, J.
Fahle, G. A.
Abu-Asab, M.
Sugui, J. A.
Carpenter, A. E.
Quezado, M. M.
Bishop, M. R.
Kwon-Chung, K. J.
TI Death by Edible Mushroom: First Report of Volvariella volvacea as an
Etiologic Agent of Invasive Disease in a Patient following Double
Umbilical Cord Blood Transplantation
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID BASIDIOMYCETOUS FUNGI; ADULT PATIENTS; IDENTIFICATION
AB We describe a case of invasive fungal infection caused by Volvariella volvacea following double umbilical cord blood transplantation (UCBT). Although infections caused by several mushroom species have been documented, we believe this to be the first published report of invasive infection with Volvariella volvacea, an edible mushroom belonging to Agaricales.
C1 [Salit, R. B.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20982 USA.
[Shea, Y. R.; Fahle, G. A.] NCI, Dept Lab Med, NIH, Bethesda, MD 20982 USA.
[Gea-Banacloche, J.; Carpenter, A. E.; Bishop, M. R.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20982 USA.
[Abu-Asab, M.; Quezado, M. M.] NCI, Pathol Lab, NIH, Bethesda, MD 20982 USA.
[Sugui, J. A.; Kwon-Chung, K. J.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20982 USA.
RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM june_kwon-chung@nih.gov
OI Abu-Asab, Mones/0000-0002-4047-1232
FU NIH, National Cancer Institute; National Institute of Allergy and
Infectious Diseases; Department of Laboratory Medicine, Clinical Center,
NIH
FX This study was supported by funds from the Intramural Research Program
of the NIH, National Cancer Institute and National Institute of Allergy
and Infectious Diseases, and the Department of Laboratory Medicine,
Clinical Center, NIH.
NR 16
TC 4
Z9 4
U1 0
U2 3
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 NOV
PY 2010
VL 48
IS 11
BP 4329
EP 4332
DI 10.1128/JCM.01222-10
PG 4
WC Microbiology
SC Microbiology
GA 672MK
UT WOS:000283588500087
PM 20826647
ER
PT J
AU Smith, SM
van Besien, K
Karrison, T
Dancey, J
McLaughlin, P
Younes, A
Smith, S
Stiff, P
Lester, E
Modi, S
Doyle, LA
Vokes, EE
Pro, B
AF Smith, Sonali M.
van Besien, Koen
Karrison, Theodore
Dancey, Janet
McLaughlin, Peter
Younes, Anas
Smith, Scott
Stiff, Patrick
Lester, Eric
Modi, Sanjiv
Doyle, L. Austin
Vokes, Everett E.
Pro, Barbara
TI Temsirolimus Has Activity in Non-Mantle Cell Non-Hodgkin's Lymphoma
Subtypes: The University of Chicago Phase II Consortium
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RAPAMYCIN INHIBITOR EVEROLIMUS; MAMMALIAN TARGET; FOLLICULAR LYMPHOMA;
CYCLIN D1; C-MYC; MTOR; CANCER; TRIAL; ACTIVATION; EXPRESSION
AB Purpose
Despite high initial remission rates, most lymphomas relapse and require further therapy. The mammalian target of rapamycin (mTOR) pathway is a validated target in mantle cell lymphoma, but has not been extensively evaluated in other lymphomas.
Patients and Methods
We performed a phase II trial of single-agent temsirolimus 25-mg weekly in patients with relapsed aggressive and indolent lymphomas. The primary objective was overall and complete response rate. Patients were stratified by histology: group A (diffuse large B-cell lymphoma, transformed follicular lymphoma), group B (follicular lymphoma), and group C (chronic lymphocytic leukemia/small lymphocytic lymphoma, and other indolent lymphomas).
Results
Eighty-nine patients were treated, with outcome strongly dependent on histology. Group A had an overall and complete response rate of 28.1% and 12.5%, respectively, and median progression-free survival (PFS) of 2.6 months and median overall survival (OS) of 7.2 months. Group B had overall and complete response rates of 53.8% and 25.6%, respectively, and median PFS of 12.7 months; median OS has not yet been reached. Group C had a partial response rate of 11% with no complete responders. Toxicity was mainly mild and/or reversible myelosuppression and mucositis; however, four patients developed pneumonitis.
Conclusions
Single-agent temsirolimus has significant activity in both diffuse large B-cell lymphoma and follicular lymphoma, although the durability of responses and PFS are longer for patients with follicular lymphoma. This is the first report of substantial activity of temsirolimus in lymphomas other than mantle cell lymphoma, and supports further evaluation of mTOR as a target in these diseases. J Clin Oncol 28: 4740-4746. (C) 2010 by American Society of Clinical Oncology
C1 [Smith, Sonali M.] Univ Chicago, Chicago, IL 60637 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Oncol Care Associates, St Joseph, MI USA.
Joliet Oncol Hematol Associates, Joliet, IL USA.
NCI, Bethesda, MD 20892 USA.
Loyola Univ, Med Ctr, Chicago, IL 60611 USA.
RP Smith, SM (reprint author), Univ Chicago, 5841 S Maryland Ave MC2115, Chicago, IL 60637 USA.
EM smsmith@medicine.bsd.uchicago.edu
RI van Besien, Koen/G-4221-2012
OI van Besien, Koen/0000-0002-8164-6211
FU Wyeth; National Institutes of Health [N01-CM17102, NCT00290472]
FX Research Funding: Sonali M. Smith, Wyeth; Supported by Grants No.
N01-CM17102 and NCT00290472 from the National Institutes of Health.
NR 31
TC 90
Z9 92
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD NOV 1
PY 2010
VL 28
IS 31
BP 4740
EP 4746
DI 10.1200/JCO.2010.29.2813
PG 7
WC Oncology
SC Oncology
GA 672LQ
UT WOS:000283585200027
PM 20837940
ER
PT J
AU Salvadore, G
Quiroz, JA
Machado-Vieira, R
Henter, ID
Manji, HK
Zarate, CA
AF Salvadore, Giacomo
Quiroz, Jorge A.
Machado-Vieira, Rodrigo
Henter, Ioline D.
Manji, Husseini K.
Zarate, Carlos A., Jr.
TI The Neurobiology of the Switch Process in Bipolar Disorder: A Review
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Review
ID ANTIDEPRESSANT-INDUCED MANIA; REM-SLEEP DEPRIVATION; CELLULAR PLASTICITY
CASCADES; FAMILY-BASED ASSOCIATION; NEUROTROPHIC FACTOR GENE; LONG-TERM
TREATMENT; DEPRESSED-PATIENTS; DOUBLE-BLIND; CYCLE ACCELERATION; I
DISORDER
AB Objective: The singular phenomenon of switching from depression to its opposite state of mania or hypomania, and vice versa, distinguishes bipolar disorder from all other psychiatric disorders. Despite the fact that it is a core aspect of the clinical presentation of bipolar disorder, the neurobiology of the switch process is still poorly understood. In this review, we summarize the clinical evidence regarding somatic interventions associated with switching, with a particular focus on the biologic underpinnings presumably involved in the switch process.
Data Sources: Literature for this review was obtained through a search of the MEDLINE database (1966-2008) using the following keywords and phrases: switch, bipolar disorder, bipolar depression, antidepressant, SSRIs, tricyclic antidepressants, norepinephrine, serotonin, treatment emergent affective switch, mania, hypomania, HPA-axis, glucocorticoids, amphetamine, dopamine, and sleep deprivation.
Study Selection: All English-language, peer-reviewed, published literature, including randomized controlled studies, naturalistic and open-label studies, and case reports, were eligible for inclusion.
Data Synthesis: Converging evidence suggests that certain pharmacologic and nonpharmacologic interventions with very different mechanisms of action, such as sleep deprivation, exogenous corticosteroids, and dopaminergic agonists, can trigger mood episode switches in patients with bipolar disorder. The switch-inducing potential of antidepressants is unclear, although tricyclic antidepressants, which confer higher risk of switching than other classes of antidepressants, are a possible exception. Several neurobiological factors appear to be associated with both spontaneous and treatment-emergent mood episode switches; these include abnormalities in catecholamine levels, up-regulation of neurotrophic and neuroplastic factors, hypothalamic-pituitary-adrenal axis hyperactivity, and circadian rhythms.
Conclusions: There is a clear need to improve our understanding of the neurobiology of the switch process; research in this field would benefit from the systematic and integrated assessment of variables associated with switching. J Clin Psychiatry 2010;71(11):1488-1501 (C) Copyright 2010 Physicians Postgraduate Press, Inc.
C1 [Zarate, Carlos A., Jr.] NIMH, Expt Therapeut Mood & Anxiety Disorders Program, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
[Quiroz, Jorge A.] Roche Pharmaceut, New York, NY USA.
RP Zarate, CA (reprint author), NIMH, Expt Therapeut Mood & Anxiety Disorders Program, Mark O Hatfield Clin Res Ctr, 10 Ctr Dr,Unit 7SE,Rm 7-3445, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190
FU National Institute of Mental Health (Bethesda, Maryland); NARSAD
FX This study was supported by the Intramural Research Program of the
National Institute of Mental Health (Bethesda, Maryland) and a NARSAD
Award (Dr Zarate).
NR 158
TC 73
Z9 74
U1 3
U2 17
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD NOV
PY 2010
VL 71
IS 11
BP 1488
EP 1501
DI 10.4088/JCP.09r05259gre
PG 14
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 693MK
UT WOS:000285228000011
PM 20492846
ER
PT J
AU Dolle, RE
Le Bourdonnec, B
Worm, K
Morales, GA
Thomas, CJ
Zhang, W
AF Dolle, Roland E.
Le Bourdonnec, Bertrand
Worm, Karin
Morales, Guillermo A.
Thomas, Craig J.
Zhang, Wei
TI Comprehensive Survey of Chemical Libraries for Drug Discovery and
Chemical Biology: 2009
SO JOURNAL OF COMBINATORIAL CHEMISTRY
LA English
DT Review
ID SOLID-PHASE SYNTHESIS; MICROWAVE-ASSISTED SYNTHESIS; DIVERSITY-ORIENTED
SYNTHESIS; 3-COMPONENT COUPLING REACTION; PYRROLE-IMIDAZOLE POLYAMIDES;
FLUOROUS-MIXTURE SYNTHESIS; ONE-POT SYNTHESIS; PARALLEL SYNTHESIS;
SMALL-MOLECULE; MULTICOMPONENT REACTIONS
C1 [Dolle, Roland E.; Le Bourdonnec, Bertrand; Worm, Karin] Adolor Corp, Exton, PA 19341 USA.
[Morales, Guillermo A.] Morales Consulting LLC, Carmel, IN 46032 USA.
[Thomas, Craig J.] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA.
[Zhang, Wei] Univ Massachusetts, Dept Chem, Boston, MA 02125 USA.
RP Dolle, RE (reprint author), Adolor Corp, 700 Penn Dr, Exton, PA 19341 USA.
EM roland.e.dolle@gmail.com
FU Intramural NIH HHS [ZIB TR000004-02]
NR 382
TC 49
Z9 49
U1 1
U2 36
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-4766
J9 J COMB CHEM
JI J. Comb. Chem.
PD NOV-DEC
PY 2010
VL 12
IS 6
BP 765
EP 806
DI 10.1021/cc100128w
PG 42
WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary
SC Chemistry; Pharmacology & Pharmacy
GA 675FB
UT WOS:000283810600001
PM 20923157
ER
PT J
AU Dimitrov, E
Usdin, TB
AF Dimitrov, Eugene
Usdin, Ted Bjoern
TI Tuberoinfundibular Peptide of 39 Residues Modulates the Mouse
Hypothalamic-Pituitary-Adrenal Axis Via Paraventricular Glutamatergic
Neurons
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE neuropeptide; presynaptic facilitation; stress; paraventricular nucleus;
parathyroid hormone 2 receptor; neuroendocrine
ID THYROTROPIN-RELEASING-HORMONE; VASOACTIVE-INTESTINAL-PEPTIDE;
CENTRAL-NERVOUS-SYSTEM; PROLACTIN SECRETION; RAT-BRAIN; MESSENGER-RNA;
NORADRENERGIC EXCITATION; MAGNOCELLULAR NEURONS; TYROSINE-HYDROXYLASE;
MONOCLONAL-ANTIBODY
AB Neurons in the subparafascicular area at the caudal border of the thalamus that contain the neuropeptide tuberoinfundibular peptide of 39 residues (TIP39) densely innervate several hypothalamic areas, including the paraventricular nucleus (PVN). These areas contain a matching distribution of TIP39's receptor, the parathyroid hormone receptor 2 (PTH2R). Frequent PTH2R coexpression with a vesicular glutamate transporter (VGlut2) suggests that TIP39 could presynaptically regulate glutamate release. By using immunohistochemistry we found CRH-ir neurons surrounded by PTH2R-ir fibers and TIP39-ir axonal projections in the PVN area of the mouse brain. Labeling hypothalamic neuroendocrine neurons by peripheral injection of fluorogold in PTH2-RlacZ knock-in mice showed that most PTH2Rs are on PVN and peri-PVN interneurons and not on neuroendocrine cells. Double fluorescent in situ hybridization revealed a high level of coexpression between PTH2R and VGlut2 mRNA by cells located in the PVN and nearby brain areas. Local TIP39 infusion (100 pmol) robustly increased pCREB-ir in the PVN and adjacent perinuclear zone. It also increased plasma corticosterone and decreased plasma prolactin. These effects of TIP39 on pCREB-ir, corticosterone, and prolactin were abolished by coinfusion of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphonopentanoic acid (AP-5; 30 pmol each) and were absent in PTH2R knockout mice. Basal plasma corticosterone was slightly decreased in TIP39 knockout mice just before onset of their active phase. The present data indicate that the TIP39 ligand/PTH2 receptor system provides facilitatory regulation of the hypothalamic-pituitary-adrenal axis via hypothalamic glutamatergic neurons and that it may regulate other neuroendocrine systems by a similar mechanism. J. Comp. Neurol. 518: 4375-4394, 2010. Published 2010 Wiley-Liss, Inc.(dagger)
C1 [Dimitrov, Eugene; Usdin, Ted Bjoern] NIMH, Sect Fundamental Neurosci, Bethesda, MD 20892 USA.
RP Usdin, TB (reprint author), Bldg 35,Room 1B-215,35 Convent Dr,MSC 3728, Bethesda, MD 20892 USA.
EM usdint@mail.nih.gov
FU National Institute of Mental Health, NIH [ZIA MH002685-16]
FX Grant sponsor: Intramural Program of the National Institute of Mental
Health, NIH; Grant number: ZIA MH002685-16.
NR 79
TC 11
Z9 11
U1 1
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0021-9967
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD NOV 1
PY 2010
VL 518
IS 21
BP 4375
EP 4394
DI 10.1002/cne.22462
PG 20
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA 655MD
UT WOS:000282253200008
PM 20853513
ER
PT J
AU Walker, MP
DiAugustine, RP
Zeringue, E
Bunger, MK
Schmitt, M
Archer, TK
Richards, RG
AF Walker, Michael P.
DiAugustine, Richard P.
Zeringue, Ernest
Bunger, Maureen K.
Schmitt, Martina
Archer, Trevor K.
Richards, R. Gregg
TI An IGF1/insulin receptor substrate-1 pathway stimulates a mitotic kinase
(cdk1) in the uterine epithelium during the proliferative response to
estradiol
SO JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID CYCLIN-DEPENDENT KINASES; FACTOR-I RECEPTOR; CELL-CYCLE; GROWTH-FACTOR;
HISTONE H1; M-PHASE; TARGETED DISRUPTION; SIGNAL-TRANSDUCTION; NULL
MUTATION; RAT UTERUS
AB Estrogens are potent mitogens for some target organs, such as the uterus, and cancers that develop in this organ might be linked to the proliferative action of these hormones. However, the mechanism by which estrogens influence the cell cycle machinery is not known. We found that a null mutation for the insulin receptor substrate (IRS)-1, a docking protein that is important for IGF1 signaling, compromised hormone-induced mitosis in the uterine epithelium; BrdU incorporation was not affected. This selective effect on mitosis was associated with a reduction in uterine cyclin B-associated kinase activity; cyclin A-associated kinase activity was not changed. The null mutation also reduced the extent of hormone-induced phosphorylation of endogenous uterine histone H1, as determined with phospho-specific antiserum. Uterine epithelial cyclin dependent kinase (cdk)1 was induced in response to hormone, but the level of the kinase protein, as determined by immunoblotting, was noticeably less in the irs1 null mutant than that in the wild-type (WT) mouse, especially around the time of peak mitosis (24 h). Since IRS-1 binds/activates phosphatidylinositol 3-kinase (PI3K), the absence of this docking protein could impair signaling of a known pathway downstream of AKT that stimulates translation of cell cycle components. Indeed, we found that phosphorylation of uterine AKT (Ser473) in irs1 null mutants was less than that in WTs following treatment. Based on earlier studies, it is also possible that an IGF1/IRS-1/PI3K/AKT pathway regulates posttranslational changes in cdk1. This model may provide insights as to how a growth factor pathway can mediate hormone action on cell proliferation. Journal of Endocrinology (2010) 207, 225-235
C1 [Walker, Michael P.; DiAugustine, Richard P.; Zeringue, Ernest; Bunger, Maureen K.; Schmitt, Martina; Archer, Trevor K.; Richards, R. Gregg] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Archer, TK (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, Mail Drop D4-01,POB 12233, Res Triangle Pk, NC 27709 USA.
EM archer1@niehs.nih.gov
FU National Institute of Environmental Health Sciences, NIH [Z01
ES071006-09]
FX This research was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, NIH; project number
Z01 ES071006-09.
NR 56
TC 8
Z9 8
U1 1
U2 1
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0022-0795
J9 J ENDOCRINOL
JI J. Endocrinol.
PD NOV
PY 2010
VL 207
IS 2
BP 225
EP 235
DI 10.1677/JOE-10-0102
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 662RH
UT WOS:000282828700011
PM 20798132
ER
PT J
AU Price, RA
AF Price, Rebecca Anhang
TI Association Between Physician Specialty and Uptake of New Medical
Technologies: HPV Tests in Florida Medicaid
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE clinical guidelines; appropriate use; disparities; cancer screening;
technology adoption
ID CLINICAL-PRACTICE GUIDELINES; EARLY-DETECTION PROGRAM; UNITED-STATES;
RACIAL DISPARITIES; CERVICAL CYTOLOGY; NATIONAL BREAST; CANCER;
MANAGEMENT; ADOPTION; WOMEN
AB BACKGROUND: It is well established that specialists often adopt new medical technologies earlier than generalists, and that racial and ethnic minority patients are less likely than White patients to receive many procedures and prescription drugs. However, little is known about the role that specialists or generalists may play in reducing racial and ethnic disparities in uptake of new medical technologies. Human papillomavirus (HPV) DNA tests, introduced as a cervical cancer screening tool in 2000, present a rich context for exploring patterns of use across patient and provider subgroups.
OBJECTIVE: To identify patient characteristics and the provider specially associated with overall and appropriate use of HPV DNA tests over time, and to examine the associations between clinical guidelines and adoption of the test in an underserved population.
DESIGN: Retrospective longitudinal study using Florida Medicaid administrative claims data.
PARTICIPANTS: Cervical cancer screening test claims for 415,239 female beneficiaries ages 21 to 64 from July 2001 through June 2006.
MAIN MEASURES: Overall and appropriate use of HPV DNA tests.
KEY RESULTS: Although minority women were initially less likely than White women to receive HPV DNA tests, test use grew more rapidly among Black and Hispanic women compared to White women. Obstetricians/gynecologists were significantly more likely than primary care providers to administer HPV DNA tests. Release of the first set of clinical guidelines was associated with a large increase in the use of HPV DNA tests (adjusted odds ratio: 2.46, p<0.0001); subsequent guidelines were associated with more modest increases.
CONCLUSIONS: Uptake of new cervical cancer screening protocols can occur quickly among traditionally underserved groups and may be aided by early adoption by specialists.
C1 [Price, Rebecca Anhang] NCI, Clin Res Directorate, Clin Monitoring Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Price, Rebecca Anhang] NCI, Appl Canc Screening Res Branch, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
RP Price, RA (reprint author), NCI, Clin Res Directorate, Clin Monitoring Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM ranhang@post.harvard.edu
FU Foundation for Informed Medical Decision Making; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]
FX The author gratefully acknowledges Paul Cleary, Richard Frank, and Sue
Goldie for their thoughtful comments on earlier drafts of the
manuscript, and Christina Fu for outstanding technical assistance. The
author was supported, in part, by a George Bennett Fellowship from the
Foundation for Informed Medical Decision Making.; 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 40
TC 4
Z9 4
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2010
VL 25
IS 11
BP 1178
EP 1185
DI 10.1007/s11606-010-1415-9
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 672YN
UT WOS:000283624000010
PM 20582485
ER
PT J
AU Caplan, LJ
Ivins, B
Poole, JH
Vanderploeg, RD
Jaffee, MS
Schwab, K
AF Caplan, Leslie J.
Ivins, Brian
Poole, John H.
Vanderploeg, Rodney D.
Jaffee, Michael S.
Schwab, Karen
TI The Structure of Postconcussive Symptoms in 3 US Military Samples
SO JOURNAL OF HEAD TRAUMA REHABILITATION
LA English
DT Article
DE concussion; neuropsychology; postconcussive symptoms; traumatic brain
injury
ID TRAUMATIC BRAIN-INJURY; HEAD-INJURY; COMPUTER; INTERVIEW; QUESTIONNAIRE;
NUMBER; RISK
AB Objective: To evaluate alternative models of symptom clusters for the 22-item Neurobehavioral Symptom Inventory. Participants: Three military samples, including 2 nonclinical samples (n = 2420, n = 4244) and 1 sample of individuals with recent head injury (n = 617). Methods: In the first sample, exploratory factor analysis of Neurobehavioral Symptom Inventory responses was performed with tests of significant factors and model fit. In the other 2 samples, confirmatory factor analysis evaluated the fit of 3 models: 2- and 3-factor models based on the initial exploratory factor analysis, and a 9-factor model based on prior research. Main Outcome Measures: The exploratory factor analysis used 2 tests for the number of factors: Parallel Analysis and Minimum Average Partial test. Confirmatory factor analysis models were evaluated using 2 measures of model fit, Root Mean Square Error of Approximation and Comparative Fit Index. Results: Postconcussive symptoms can be described accurately by the 9 factors. However, the model of 3 intercorrelated factors, reflecting cognitive, affective, and somatic/sensory symptoms, fits the data more parsimoniously with little loss in model fit. Conclusion: Although the 9-cluster result from prior research provides a valid description of the relations among items of the inventory, a 3-factor model, consisting of somatic/sensory, affective, and cognitive factors, provides nearly as good a fit to the data, with greater parsimony. We encourage clinicians and researchers to conceptualize the Neurobehavioral Symptom Inventory in terms of 3 coherent clusters of symptoms rather than as 22 individual items.
C1 [Caplan, Leslie J.] NIMH, NIH, Bethesda, MD 20892 USA.
[Ivins, Brian; Jaffee, Michael S.; Schwab, Karen] Def & Vet Brain Injury Ctr, Washington, DC USA.
[Poole, John H.] Vet Affairs Hlth Care Syst, Palo Alto, CA USA.
[Vanderploeg, Rodney D.] Def & Vet Brain Injury Ctr, James A Haley Vet Affairs Med Ctr, Palo Alto, CA USA.
[Vanderploeg, Rodney D.] Univ S Florida, Dept Psychiat, Tampa, FL USA.
[Vanderploeg, Rodney D.] Univ S Florida, Dept Behav Sci & Psychol, Tampa, FL USA.
RP Caplan, LJ (reprint author), US Dept Educ, Natl Inst Disabil & Rehabil Res, 400 Maryland Ave SW, Washington, DC 20202 USA.
EM Leslie.Caplan@ed.gov
NR 29
TC 42
Z9 42
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-9701
J9 J HEAD TRAUMA REHAB
JI J. Head Trauma Rehabil.
PD NOV-DEC
PY 2010
VL 25
IS 6
BP 447
EP 458
DI 10.1097/HTR.0b013e3181d5bdbd
PG 12
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 679HA
UT WOS:000284151300007
ER
PT J
AU Danis, M
Kotwani, N
Garrett, J
Rivera, I
Davies-Cole, J
Carter-Nolan, P
AF Danis, Marion
Kotwani, Namrata
Garrett, Joanne
Rivera, Ivonne
Davies-Cole, John
Carter-Nolan, Pamela
TI Priorities of Low-Income Urban Residents for Interventions to Address
the Socio-Economic Determinants of Health
SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED
LA English
DT Article
DE Health status disparity; health promotion; poverty; resource allocation;
public participation
ID PARTNERSHIP; PATHWAYS; PROGRAM; ADULTS
AB Objectives. To determine the priorities of low-income urban residents for interventions that address the socio-economic determinants of health. Methods. We selected and estimated the cost of 16 interventions related to education, housing, nutrition, employment, health care, healthy behavior, neighborhood improvement, and transportation. Low-income residents of Washington, D.C. (N=431) participated in decision exercises to prioritize these interventions. Results. Given a budget valued at approximately twice an estimated cost of medical and dental care ($885), the interventions ultimately prioritized by the greatest percentage of individuals were: health insurance (95%), housing vouchers (82%) dental care (82%), job training (72%), adult education (63%), counseling (68%), healthy behavior incentives (68%), and job placement (67%). The percentages of respondents who received support for housing, adult education, and job training and placement were far less than the percentage who prioritized these interventions. Conclusions. Poor and low-income residents' priorities may usefully inform allocation of social services that affect health.
C1 [Danis, Marion] NIH, Sect Eth & Hlth Policy, Bioeth Consultat Serv, Dept Bioeth,Clin Ctr, Bethesda, MD 20892 USA.
[Garrett, Joanne] Univ N Carolina, Chapel Hill, NC USA.
[Carter-Nolan, Pamela] Howard Univ, Washington, DC USA.
RP Danis, M (reprint author), NIH, Sect Eth & Hlth Policy, Bioeth Consultat Serv, Dept Bioeth,Clin Ctr, Bldg 10,Rm 1C118, Bethesda, MD 20892 USA.
EM mdanis@nih.gov
FU Intramural NIH HHS [ZIA CL010527-06]
NR 51
TC 4
Z9 4
U1 1
U2 11
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1049-2089
J9 J HEALTH CARE POOR U
JI J. Health Care Poor Underserved
PD NOV
PY 2010
VL 21
IS 4
BP 1318
EP 1339
PG 22
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 672YC
UT WOS:000283622700021
PM 21099082
ER
PT J
AU Ji, JF
Wang, XW
AF Ji, Junfang
Wang, Xin Wei
TI A Yin-Yang balancing act of the lin28/let-7 link in tumorigenesis
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Lin28; Let-7; Human malignancy; Hepatocellular carcinoma
ID HEPATOCELLULAR-CARCINOMA; CANCER; CELLS; IDENTIFICATION
AB Multiple members of the let-7 family of miRNAs are often repressed in human cancers, thereby promoting oncogenesis by derepressing targets such as HMGA2, K-Ras and c-Myc. However, the mechanism by which let-7 miRNAs are coordinately repressed is unclear. The RNA-binding proteins lin28 and lin28B block let-7 precursors from being processed to mature miRNAs, suggesting that their overexpression might promote malignancy through repression of let-7. Here we show that lin28 and lin28B are overexpressed in primary human tumors and human cancer cell lines (overall frequency approximately 15%), and that overexpression is linked to repression of let-7 family miRNAs and derepression of let-7 targets. lin28 and lin28b facilitate cellular transformation in vitro, and overexpression is associated with advanced disease across multiple tumor types. Our work provides a mechanism for the coordinate repression of let-7 miRNAs observed in a subset of human cancers, and associates activation of lin28 and lin28B with poor clinical prognosis. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Ji, Junfang; Wang, Xin Wei] NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Wang, XW (reprint author), NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM xw3u@nih.gov
RI Wang, Xin/B-6162-2009
NR 10
TC 18
Z9 21
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD NOV
PY 2010
VL 53
IS 5
BP 974
EP 975
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 673ZK
UT WOS:000283702500027
PM 20739081
ER
PT J
AU Atha, DH
Manne, U
Grizzle, WE
Wagner, PD
Srivastava, S
Reipa, V
AF Atha, Donald H.
Manne, Upender
Grizzle, William E.
Wagner, Paul D.
Srivastava, Sudhir
Reipa, Vytas
TI Standards for Immunohistochemical Imaging: A Protein Reference Device
for Biomarker Quantitation
SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
LA English
DT Article
DE p53; immunohistochemistry; standards; cancer biomarker quantitation;
molecular imaging; protein immobilization; spectroscopy; microscopy
ID STORED PARAFFIN SLIDES; STRAND CONFORMATION POLYMORPHISM;
MARKER-IMMUNOSTAINING INTENSITY; P53 POINT MUTATIONS;
CAPILLARY-ELECTROPHORESIS; NUCLEAR ACCUMULATION; COLORECTAL
ADENOCARCINOMA; PROGNOSTIC-SIGNIFICANCE; SILICON NANOPARTICLES;
TELOMERASE ACTIVITY
AB We are developing a reference device to be used in the validation of immunohistochemical imaging of biomarkers by microscopy. The prototype device consists of p53 protein immobilized at various concentrations on a glass slide. The device is designed as a reference control to be used with assays that incorporate commercially available anti-p53 antibodies. p53 protein was characterized by mass spectrometry and covalently immobilized through amide linkage to the (3-aminopropyl)trietoxysilane-modified glass surface. This procedure is reproducible and provides a chemically stable product in high yield. The surface-bound protein was shown to be immunoreactive by its specific interaction with anti-p53 antibody (Ab) and detection by absorbance and fluorescence spectroscopy. Also, comparison was made with microscopic images of Ab-stained tissue samples, known to stain positive for p53. Further development will be required to establish accurate surface protein concentrations in the range required for specific clinical applications. (J Histochem Cytochem 58:1005-1014, 2010)
C1 [Atha, Donald H.; Reipa, Vytas] Natl Inst Stand & Technol, Div Biochem Sci, Gaithersburg, MD 20899 USA.
[Manne, Upender; Grizzle, William E.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA.
[Wagner, Paul D.; Srivastava, Sudhir] NCI, Canc Prevent Div, Rockville, MD USA.
RP Atha, DH (reprint author), Natl Inst Stand & Technol, Div Biochem Sci, Bldg 227,Room A243,Mail Stop 8311,100 Bur Dr, Gaithersburg, MD 20899 USA.
EM donald.atha@nist.gov
FU National Cancer Institute-Early Detection Research Network (EDRN);
National Institute of Standards and Technology (NIST)-Biochemical
Science Division [YI-CN5001]; EDRN Reference Laboratory at UAB
[5U24CA086359-10]
FX This work was funded in part by National Cancer Institute-Early
Detection Research Network (EDRN) and National Institute of Standards
and Technology (NIST)-Biochemical Science Division jointly under
interagency agreement no. YI-CN5001 and by the EDRN Reference Laboratory
at UAB (5U24CA086359-10).
NR 46
TC 0
Z9 0
U1 0
U2 6
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0022-1554
J9 J HISTOCHEM CYTOCHEM
JI J. Histochem. Cytochem.
PD NOV
PY 2010
VL 58
IS 11
BP 1005
EP 1014
DI 10.1369/jhc.2010.956342
PG 10
WC Cell Biology
SC Cell Biology
GA 666JV
UT WOS:000283111900006
PM 20805583
ER
PT J
AU Xing, JJ
Wu, FQ
Wang, SA
Krensky, AM
Mody, CH
Zheng, CF
AF Xing, Junji
Wu, Fuqing
Wang, Shuai
Krensky, Alan M.
Mody, Christopher H.
Zheng, Chunfu
TI Granulysin Production and Anticryptococcal Activity Is Dependent upon a
Far Upstream Enhancer That Binds STAT5 in Human Peripheral Blood CD4(+)
T Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CRYPTOCOCCUS-NEOFORMANS; MYCOBACTERIUM-TUBERCULOSIS; REQUIRES
GRANULYSIN; SIGNALING PATHWAYS; GENE-EXPRESSION; NATURAL-KILLER;
DNA-BINDING; IFN-ALPHA; NK CELLS; ACTIVATION
AB Previous studies have demonstrated that STAT5 is critical for expression of granulysin and antimicrobial activity. Because the signaling pathway and the resultant microbicidal activity are defective in HIV-infected patients, the mechanism by which STAT5 leads to granulysin expression is of great interest. In the current study, IL-2-stimulated CRL-2105 CD4(+) T cells expressed granulysin and killed Cryptococcus neoformans similar to primary CD4(+) T cells. The enhancer activity of the upstream element of the granulysin promoter was analyzed in primary CD4(+) T cells and CRL-2105 T cells with a luciferase reporter assay, and a STAT5 binding site, 18,302 to 18,177 bp upstream of the transcription start site, was identified as an enhancer. Additionally, the enhancer functioned in the context of heterologous SV40 promoter irrespective of its transcriptional orientation. Chromatin immunoprecipitation and EMSAs demonstrated that the enhancer element bound STAT5 both in vivo and in vitro, and mutation of the STAT5 binding site abrogated its enhancer activity. Furthermore, overexpression of a dominant negative STAT5a abolished the enhancer activity of the STAT5 binding site and abrogated the anticryptococcal activity of IL-2-stimulated primary CD4(+) T cells. Taken together, these data provide details about the complex regulation leading to granulysin expression and anticryptococcal activity in primary CD4(+) T cells. The Journal of Immunology, 2010, 185: 5074-5081.
C1 [Xing, Junji; Wu, Fuqing; Wang, Shuai; Zheng, Chunfu] Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Peoples R China.
[Krensky, Alan M.] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Mody, Christopher H.] Univ Calgary, Dept Internal Med, Calgary, AB T2N 4N1, Canada.
[Mody, Christopher H.] Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada.
RP Zheng, CF (reprint author), Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, 44 Xiaohongshan, Wuhan 430071, Peoples R China.
EM zheng.alan@hotmail.com
OI Xing, Junji/0000-0002-3392-5427; Mody, Christopher
H./0000-0001-7264-3679
FU National Natural Science Foundation of China [30972670]; Chinese Academy
of Sciences [20071010-141]; Canadian Institutes for Health Research;
National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This work was supported by grants from the National Natural Science
Foundation of China (30972670) and the Start-up Fund of the Hundred
Talents Program of the Chinese Academy of Sciences (20071010-141) (to
C.Z.), the Canadian Institutes for Health Research (to C. H. M.), and
the Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research (to A.M.K.).
NR 40
TC 2
Z9 2
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD NOV 1
PY 2010
VL 185
IS 9
BP 5074
EP 5081
DI 10.4049/jimmunol.1001725
PG 8
WC Immunology
SC Immunology
GA 668DL
UT WOS:000283248700020
PM 20889547
ER
PT J
AU Gordon, SN
Cervasi, B
Odorizzi, P
Silverman, R
Aberra, F
Ginsberg, G
Estes, JD
Paiardini, M
Frank, I
Silvestri, G
AF Gordon, Shari N.
Cervasi, Barbara
Odorizzi, Pamela
Silverman, Randee
Aberra, Faten
Ginsberg, Gregory
Estes, Jacob D.
Paiardini, Mirko
Frank, Ian
Silvestri, Guido
TI Disruption of Intestinal CD4(+) T Cell Homeostasis Is a Key Marker of
Systemic CD4(+) T Cell Activation in HIV-Infected Individuals
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID IMMUNODEFICIENCY VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY;
LYMPHOID-TISSUE; GASTROINTESTINAL-TRACT; IMMUNE ACTIVATION; MICROBIAL
TRANSLOCATION; AIDS PATHOGENESIS; TYPE-1 INFECTION; SIV INFECTION; SOOTY
MANGABEYS
AB HIV infection is associated with depletion of intestinal CD4(+) T cells, resulting in mucosal immune dysfunction, microbial translocation, chronic immune activation, and progressive immunodeficiency. In this study, we examined HIV-infected individuals with active virus replication (n = 15), treated with antiretroviral therapy (n = 13), and healthy controls (n = 11) and conducted a comparative analysis of T cells derived from blood and four gastrointestinal (GI) sites (terminal ileum, right colon, left colon, and sigmoid colon). As expected, we found that HIV infection is associated with depletion of total CD4(+) T cells as well as CD4(+) CCR5(+) T cells in all GI sites, with higher levels of these cells found in ART-treated individuals than in those with active virus replication. While the levels of both CD4(+) and CD8(+) T cell proliferation were higher in the blood of untreated HIV-infected individuals, only CD4(+) T cell proliferation was significantly increased in the gut of the same patients. We also noted that the levels of CD4(+) T cells and the percentages of CD4(+)Ki67(+) proliferating T cells are inversely correlated in both blood and intestinal tissues, thus suggesting that CD4(+) T cell homeostasis is similarly affected by HIV infection in these distinct anatomic compartments. Importantly, the level of intestinal CD4(+) T cells (both total and Th17 cells) was inversely correlated with the percentage of circulating CD4(+)Ki67(+) T cells. Collectively, these data confirm that the GI tract is a key player in the immunopathogenesis of HIV infection, and they reveal a strong association between the destruction of intestinal CD4(+) T cell homeostasis in the gut and the level of systemic CD4(+) T cell activation. The Journal of Immunology, 2010, 185: 5169-5179.
C1 [Silvestri, Guido] Emory Univ, Div Microbiol & Immunol, Yerkes Natl Primate Res Ctr, Dept Pathol & Lab Med,Sch Med, Atlanta, GA 30329 USA.
[Gordon, Shari N.; Cervasi, Barbara; Odorizzi, Pamela; Silverman, Randee; Aberra, Faten; Ginsberg, Gregory; Paiardini, Mirko; Frank, Ian; Silvestri, Guido] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Gordon, Shari N.; Cervasi, Barbara; Odorizzi, Pamela; Silverman, Randee; Aberra, Faten; Ginsberg, Gregory; Paiardini, Mirko; Frank, Ian; Silvestri, Guido] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Gordon, Shari N.] NCI, Anim Models & Vaccine Sect, NIH, Bethesda, MD 20892 USA.
[Estes, Jacob D.] NCI, AIDS Vaccine Sect, SAIC Frederick, NIH, Bethesda, MD 20892 USA.
RP Silvestri, G (reprint author), Emory Univ, Div Microbiol & Immunol, Yerkes Natl Primate Res Ctr, Dept Pathol & Lab Med,Sch Med, 929 Gatewood Rd, Atlanta, GA 30329 USA.
EM gsilves@emory.edu
FU University of Pennsylvania Center for AIDS Research; National Institutes
of Health [R01 AI084836, P60DA005186]; W.W. Smith Foundation; National
Cancer Institute, National Institutes of Health [HHSN261200800001E]
FX This work was supported in part by the University of Pennsylvania Center
for AIDS Research, by National Institutes of Health Grants R01 AI084836
(to M.P.) and P60DA005186 (to I.F.), and by the W.W. Smith Foundation
(to G.S.). This work was funded in part with federal funds from National
Cancer Institute, National Institutes of Health Contract No.
HHSN261200800001E.
NR 46
TC 60
Z9 60
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD NOV 1
PY 2010
VL 185
IS 9
BP 5169
EP 5179
DI 10.4049/jimmunol.1001801
PG 11
WC Immunology
SC Immunology
GA 668DL
UT WOS:000283248700030
PM 20889546
ER
PT J
AU Park, KU
Jin, P
Sabatino, M
Feng, J
Civini, S
Khuu, H
Berg, M
Childs, R
Stroncek, D
AF Park, Kyoung Un
Jin, Ping
Sabatino, Marianna
Feng, Ji
Civini, Sara
Khuu, Hanh
Berg, Maria
Childs, Richard
Stroncek, David
TI Gene Expression Analysis of Ex Vivo Expanded and Freshly Isolated NK
Cells From Cancer Patients
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE consistency; expansion; gene and microRNA; natural killer cells; potency
ID NATURAL-KILLER-CELLS; TUMOR-NECROSIS-FACTOR; EMBRYONIC STEM-CELLS;
IN-VIVO; T-CELL; IMMUNOTHERAPY; LYMPHOTOXIN; DIFFERENTIATION; GRANZYMES;
PATTERNS
AB The infusion of natural killer (NK) cells is a promising therapy for patients with advanced malignancies. Clinical expanded NK-cell products were compared with freshly isolated NK cells. Autologous peripheral blood mononuclear cells were collected by apheresis from 8 patients. NK cells were isolated by anti-CD3-negative selection followed by anti-CD56-positive selection. They were then expanded by co-culture with interleukin-2 and an irradiated Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line (EBV-TM-LCL) to produce 14 NK-cell products. Molecular changes in the 14 NK-cell products were characterized using gene and microRNA expression microarrays. EBV-TM-LCL feeder cells from 3 lots were also analyzed as they were expanded for over 90 days and each lot was used for multiple NK-cell expansions. The gene expression profiles among the 3 EBV-TM-LCL lots used showed no differences and were not affected by their time in culture. Freshly isolated and expanded NK cells had distinct gene and microRNA expression profiles. Compared with fresh NK cells, expanded NK cells overexpressed 1098 genes and 28 human microRNAs. Genes in the crosstalk between dendritic and NK cells and metabolic pathways were up-regulated in expanded NK cells, whereas genes in a number of immune function pathways were down-regulated. Among all the most up-regulated genes were the NK cell-activating receptor natural cytotoxicity triggering receptor 3, myxovirus restistance 1, lymphotoxin beta, and BCL2-associated X protein. Although some expanded NK-cell product variability was observed, perhaps related to patient factors, further studies on larger numbers of products will be needed to determine the impact of these differences on clinical outcomes.
C1 [Park, Kyoung Un; Jin, Ping; Sabatino, Marianna; Feng, Ji; Civini, Sara; Khuu, Hanh; Stroncek, David] NHLBI, Dept Transfus Med, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Berg, Maria; Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Park, Kyoung Un] Seoul Natl Univ Bundang Hosp, Dept Lab Med, Songnam, South Korea.
RP Stroncek, D (reprint author), NHLBI, Dept Transfus Med, Ctr Clin, NIH, Bldg 10,Room 1C711, Bethesda, MD 20892 USA.
EM dstroncek@cc.nih.gov
RI Park, Kyoung Un/J-5473-2012
FU Intramural NIH HHS [ZIA CL002119-03]
NR 30
TC 8
Z9 8
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 NOV-DEC
PY 2010
VL 33
IS 9
BP 945
EP 955
DI 10.1097/CJI.0b013e3181f71b81
PG 11
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 671HS
UT WOS:000283492300003
PM 20948442
ER
PT J
AU Inozume, T
Hanada, KI
Wang, QJ
Ahmadzadeh, M
Wunderlich, JR
Rosenberg, SA
Yang, JC
AF Inozume, Takashi
Hanada, Ken-ichi
Wang, Qiong J.
Ahmadzadeh, Mojgan
Wunderlich, John R.
Rosenberg, Steven A.
Yang, James C.
TI Selection of CD8(+)PD-1(+) Lymphocytes in Fresh Human Melanomas Enriches
for Tumor-reactive T Cells
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE PD-1; PD-L1; TIL; tumor immunity; melanoma; tumor digest; tumor
microenvironment
ID INDUCED EXPRESSION; PD-1; CANCER; THERAPY; ANTIGEN; ACTIVATION;
IMMUNOTHERAPY; CARCINOMA; RECEPTOR; MEMBER
AB CD8(+) tumor-infiltrating lymphocytes (TILs) in human melanomas express high levels of PD-1 and are functionally impaired. However, adoptive cell therapy using in vitro-expanded TIL can be a highly effective therapy for patients with advanced melanoma. This discrepancy led us to further analyze the CD8(+)PD-1(+) TILs. We found that the percentage of PD-1-expressing CD8(+) T cells was higher in the tumor digests that generate tumor-reactive TILs after in vitro culture in interleukin-2 (P=0.0007). Also sorted and expanded CD8(+)PD-1(+) T cells in tumor digests showed much higher tumor-specific interferon-gamma production compared with CD8(+) PD-1(-) T cells. These results suggested that tumor-specific CD8(+) T cells in melanoma tumor digests are largely PD-1(+), and this population can recover function after culturing in interleukin-2. PD-1 has been reported as an inhibitory receptor on T cells. We found that the in vitro functional suppression of cultured-TILs from native levels of PD-L1 expression on melanomas was minimal, and moreover expression level of PD-1 on CD8(+) tumor-specific TILs decreased during the culture. As a consequence, the PD-1 receptor can be a useful biomarker for enriching tumor-specific T cells from fresh melanomas.
C1 [Inozume, Takashi; Hanada, Ken-ichi; Wang, Qiong J.; Ahmadzadeh, Mojgan; Wunderlich, John R.; Rosenberg, Steven A.; Yang, James C.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Yang, JC (reprint author), NCI, Surg Branch, NIH, 9000 Rockville Pike,Bldg 10 CRC,Rm 3W-3840, Bethesda, MD 20892 USA.
EM JamesYang@mail.nih.gov
RI Hanada, Ken-ichi/L-2481-2013
OI Hanada, Ken-ichi/0000-0003-2959-1257
NR 24
TC 31
Z9 30
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2010
VL 33
IS 9
BP 956
EP 964
DI 10.1097/CJI.0b013e3181fad2b0
PG 9
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 671HS
UT WOS:000283492300004
PM 20948441
ER
PT J
AU Biryahwaho, B
Dollard, SC
Pfeiffer, RM
Shebl, FM
Munuo, S
Amin, MM
Hladik, W
Parsons, R
Mbulaiteye, SM
AF Biryahwaho, Benon
Dollard, Sheila C.
Pfeiffer, Ruth M.
Shebl, Fatma M.
Munuo, Stella
Amin, Minal M.
Hladik, Wolfgang
Parsons, Ruth
Mbulaiteye, Sam M.
TI Sex and Geographic Patterns of Human Herpesvirus 8 Infection in a
Nationally Representative Population-Based Sample in Uganda
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID SARCOMA-ASSOCIATED HERPESVIRUS; SUB-SAHARAN AFRICA; KAPOSIS-SARCOMA;
RISK-FACTORS; TRANSMISSION; SEROPREVALENCE; PREVALENCE; PARASITES;
CANCER; ADULTS
AB Background. Human herpesvirus 8 (HHV8), the infectious cause of Kaposi sarcoma, varies dramatically across Africa, suggesting that cofactors correlated with large-area geographic or environmental characteristics may influence risk of infection. Variation in HHV8 seropositivity across small-area regions within countries in Africa is unknown. We investigated this issue in Uganda, where Kaposi sarcoma distribution is uneven and well described.
Methods. Archival samples from individuals aged 15-59 years randomly selected from a nationally representative 2004-2005 human immunodeficiency virus-AIDS serobehavioral survey were tested for HHV8 seropositivity with use of enzyme immunoassays based on synthetic peptides from the K8.1 and orf65 viral genes. Adjusted odds ratios and 95% confidence intervals (CIs) of association of HHV8 seropositivity with demographic risk factors were estimated.
Results. Among 2681 individuals tested, HHV8 seropositivity was 55.4%. HHV8 seropositivity was lower in female than in male persons (adjusted odds ratio, 0.82 [95% CI, 0.69-0.97]) and increased 2.2% (95% CI, 1.0%-3.6%) in female persons and 1.2% (95% CI, 1.0%-2.3%) in male persons per year of age. HHV8 seropositivity was inversely associated with education (P = .01, for trend) and was elevated in the West Nile region, compared with the Central region (adjusted odds ratio, 1.49 [95% CI, 1.02-2.18]) but not with other regions.
Conclusions. Our findings suggest that HHV8 seropositivity in Uganda may be influenced by cofactors correlated with small-area geography, age, sex, and education.
C1 [Biryahwaho, Benon] Uganda Virus Res Inst, Entebbe, Uganda.
[Hladik, Wolfgang] Ctr Dis Control & Prevent, Entebbe, Uganda.
[Dollard, Sheila C.; Amin, Minal M.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Pfeiffer, Ruth M.; Shebl, Fatma M.; Mbulaiteye, Sam M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Munuo, Stella; Parsons, Ruth] Informat Management Serv Inc, Rockville, MD USA.
RP Mbulaiteye, SM (reprint author), 6120 Execut Blvd,Execut Plaza S,Rm 7080,MSC 7248, Rockville, MD 20852 USA.
EM mbulaits@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011
FU National Cancer Institute (NCI), National Institutes of Health,
Department of Health and Human Services [HHSN2612009004060P,
N02-CP-31003]; NCI; Centers for Disease Control and Prevention [IAA
Y1CP903801]
FX Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute (NCI), National Institutes of
Health, Department of Health and Human Services (contract
HHSN2612009004060P and Support Services contract N02-CP-31003);
Inter-Agency Agreement between NCI and the Centers for Disease Control
and Prevention (IAA Y1CP903801).
NR 35
TC 13
Z9 13
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2010
VL 202
IS 9
BP 1347
EP 1353
DI 10.1086/656525
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 656VB
UT WOS:000282367900008
PM 20863232
ER
PT J
AU Apetrei, C
Gaufin, T
Gautam, R
Vinton, C
Hirsch, V
Lewis, M
Brenchley, J
Pandrea, I
AF Apetrei, Cristian
Gaufin, Thaidra
Gautam, Rajeev
Vinton, Carol
Hirsch, Vanessa
Lewis, Mark
Brenchley, Jason
Pandrea, Ivona
TI Pattern of SIVagm Infection in Patas Monkeys Suggests that Host
Adaptation to Simian Immunodeficiency Virus Infection May Result in
Resistance to Infection and Virus Extinction
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT International Symposium on Natural Immunity to HIV
CY NOV 15-17, 2009
CL Winnipeg, CANADA
ID AFRICAN-GREEN MONKEYS; NONHUMAN PRIMATE HOSTS; CD4(+) T-CELLS; NATURAL
HOSTS; WILD; TRANSMISSION; REPLICATION; PAUCITY; AIDS
AB Patas monkeys were not reported to carry species-specific simian immunodeficiency virus (SIV), but cross-species transmission of SIVagm to patas monkeys occurred in the wild. We report that patas monkeys share immunophenotypic features with natural hosts of SIV; that is, low levels of CD4(+) T cells and low CCR5 expression on CD4(+) T cells. In 1 patas monkey with undetectable levels of CD4(+) T cells, experimental exposure to SIVagm did not result in infection. The other experimentally infected patas monkeys showed an infection pattern similar to SIV infection in natural hosts. Thus, down-regulation of CD4 and CCR5 expression on CD4(+) T cells may effectively control human immunodeficiency virus acquisition and result in SIV extinction.
C1 [Apetrei, Cristian; Pandrea, Ivona] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15261 USA.
[Apetrei, Cristian; Gaufin, Thaidra; Gautam, Rajeev] Tulane Natl Primate Res Ctr, Div Microbiol, Covington, LA USA.
[Apetrei, Cristian; Gaufin, Thaidra; Gautam, Rajeev] Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA USA.
[Apetrei, Cristian] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA.
[Pandrea, Ivona] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA.
[Vinton, Carol; Hirsch, Vanessa; Brenchley, Jason] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Lewis, Mark; Pandrea, Ivona] Bioqual, Rockville, MD USA.
RP Apetrei, C (reprint author), Univ Pittsburgh, Ctr Vaccine Res, 9044 Biol Sci Tower 3,3501 5th Ave, Pittsburgh, PA 15261 USA.
EM apetreic@pitt.edu
FU National Institute of Allergy and Infectious Diseases and National
Center for Research Resources, National Institutes of Health [R01
AI064066, R21 AI069935, R01 AI065325, R01 RR025781, RR-00168]; Bill and
Melinda Gates Foundation; University of Manitoba
FX National Institute of Allergy and Infectious Diseases and National
Center for Research Resources, National Institutes of Health (grants R01
AI064066 and R21 AI069935, to I.P.; grant R01 AI065325, to C.A.; grant
R01 RR025781, to C.A. and I.P.; and grant RR-00168, to the Tulane
National Primate Research Center).; This article is part of a supplement
entitled "Natural Immunity to HIV-1 Infection," sponsored by the Bill
and Melinda Gates Foundation and the University of Manitoba.
NR 16
TC 18
Z9 18
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2010
VL 202
SU 3
BP S371
EP S376
DI 10.1086/655970
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 656VK
UT WOS:000282369000010
PM 20887227
ER
PT J
AU Lederman, MM
Alter, G
Daskalakis, DC
Rodriguez, B
Sieg, SF
Hardy, G
Cho, M
Anthony, D
Harding, C
Weinberg, A
Silverman, RH
Douek, DC
Margolis, L
Goldstein, DB
Carrington, M
Goedert, JJ
AF Lederman, Michael M.
Alter, Galit
Daskalakis, Demetre C.
Rodriguez, Benigno
Sieg, Scott F.
Hardy, Gareth
Cho, Michael
Anthony, Donald
Harding, Clifford
Weinberg, Aaron
Silverman, Robert H.
Douek, Daniel C.
Margolis, Leonid
Goldstein, David B.
Carrington, Mary
Goedert, James J.
TI Determinants of Protection among HIV-Exposed Seronegative Persons: An
Overview
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT International Symposium on Natural Immunity to HIV
CY NOV 15-17, 2009
CL Winnipeg, CANADA
ID SIMIAN IMMUNODEFICIENCY VIRUS; KENYAN SEX WORKERS; DISEASE PROGRESSION;
TYPE-1 INFECTION; T-CELLS; VAGINAL TRANSMISSION; GENETIC-VARIATION;
BOOSTING REGIMEN; RESISTANCE; SUSCEPTIBILITY
AB Both clinical experience and a growing medical literature indicate that some persons who have been exposed to human immunodeficiency virus (HIV) infection remain uninfected. Although in some instances this may represent good fortune, cohorts of uninfected persons have been reported who are considered at high risk for infection. In these cohorts a variety of characteristics have been proposed as mediating protection, but to date only the 32-base pair deletion in the chemokine (C-C motif) receptor 5 gene, which results in complete failure of cell surface expression of this coreceptor, has been associated with high-level protection from HIV infection. With this in mind, there are probably many other factors that may individually or in combination provide some level of protection from acquisition of HIV infection. Because some of these factors are probably incompletely protective or inconsistently active, identifying them with confidence will be difficult. Nonetheless, clarifying the determinants of protection against HIV infection is a high priority that will require careful selection of high-risk uninfected cohorts, who should undergo targeted studies of plausible mediators and broad screening for unexpected determinants of protection.
C1 [Lederman, Michael M.; Rodriguez, Benigno; Sieg, Scott F.; Hardy, Gareth; Anthony, Donald; Harding, Clifford] Case Western Reserve Univ, Sch Med, Univ Hosp Case Med Ctr, Ctr AIDS Res, Cleveland, OH 44106 USA.
[Weinberg, Aaron] Case Western Reserve Univ, Sch Dent, Cleveland, OH 44106 USA.
[Silverman, Robert H.] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA.
[Alter, Galit] Harvard Univ, Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02115 USA.
[Daskalakis, Demetre C.] NYU, Sch Med, Div Infect Dis & Immunol, New York, NY USA.
[Cho, Michael] Iowa State Univ, Coll Vet Med, Ames, IA USA.
[Douek, Daniel C.] Natl Inst Allergy Immunol & Infect Dis, Human Immunol Sect, Vaccine Res Ctr, Bethesda, MD USA.
[Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Carrington, Mary] NCI, Expt Immunol Lab, SAIC Frederick, NIH, Frederick, MD 21701 USA.
[Goldstein, David B.] Duke Univ, Inst Genome Sci & Policy, Ctr Human Genome Variat, Durham, NC USA.
RP Lederman, MM (reprint author), Case Western Reserve Univ, 2061 Cornell Rd, Cleveland, OH 44106 USA.
EM MXL6@case.edu
RI Rodriguez, Benigno/C-3365-2009
OI Rodriguez, Benigno/0000-0001-9736-7957
FU Center for AIDS Research at Case Western Reserve University, University
Hospitals / Case Medical Center [AI -36219]; Bill and Melinda Gates
Foundation; University of Manitoba
FX Center for AIDS Research at Case Western Reserve University, University
Hospitals / Case Medical Center (grant AI -36219).; This article is part
of a supplement entitled "Natural Immunity to HIV-1 Infection,"
sponsored by the Bill and Melinda Gates Foundation and the University of
Manitoba.
NR 54
TC 29
Z9 30
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2010
VL 202
SU 3
BP S333
EP S338
DI 10.1086/655967
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 656VK
UT WOS:000282369000003
PM 20887220
ER
PT J
AU Shearer, G
Clerici, M
AF Shearer, Gene
Clerici, Mario
TI Historical Perspective on HIV-Exposed Seronegative Individuals: Has
Nature Done the Experiment for Us?
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT International Symposium on Natural Immunity to HIV
CY NOV 15-17, 2009
CL Winnipeg, CANADA
ID T-LYMPHOCYTE RESPONSES; PERIPHERAL-BLOOD; DRUG-USERS; INFECTION; TYPE-1;
TRANSMISSION; IMMUNITY; MUCOSAL; IMMUNOPATHOGENESIS; PROSTITUTES
AB Multiple and frequent exposure to the human immunodeficiency virus (HIV) does not necessarily result in HIV infection. Approximately 15% of HIV exposed seronegative individuals repeatedly resist infection, a phenomenon that has been observed in all investigated HIV-exposed cohorts. This brief report provides a limited historic perspective of the discovery of these cohorts and outlines some of the immunologic and genetic parameters that are associated with resistance. We raise the possibility that assessing immunologic parameters of the phenomenon might provide insights that might be relevant for effective AIDS vaccine design.
C1 [Clerici, Mario] Univ Milan, Cattedra Immunol, Sch Med, DISP LITA Vialba,Dept Biomed Sci & Technol, I-20157 Milan, Italy.
[Shearer, Gene] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Clerici, Mario] IRECS, Don C Gnocchi Fdn, Milan, Italy.
RP Clerici, M (reprint author), Univ Milan, Cattedra Immunol, Sch Med, DISP LITA Vialba,Dept Biomed Sci & Technol, Via GB Grassi 74, I-20157 Milan, Italy.
EM mario.clerici@unimi.it
OI Clerici, Mario/0000-0001-5920-6191
FU National Cancer Institute; Bill and Melinda Gates Foundation; University
of Manitoba
FX Intramural Research Program, National Cancer Institute.; This article is
part of a supplement entitled "Natural Immunity to HIV-1 Infection,"
sponsored by the Bill and Melinda Gates Foundation and the University of
Manitoba.
NR 25
TC 14
Z9 14
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2010
VL 202
SU 3
BP S329
EP S332
DI 10.1086/655974
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 656VK
UT WOS:000282369000002
PM 20887219
ER
PT J
AU Bagashev, A
Fitzgerald, MC
LaRosa, DF
Rose, PP
Cherry, S
Johnson, AC
Sullivan, KE
AF Bagashev, Asen
Fitzgerald, Michael C.
LaRosa, David F.
Rose, Patrick P.
Cherry, Sara
Johnson, Alfred C.
Sullivan, Kathleen E.
TI Leucine-Rich Repeat (in Flightless I) Interacting Protein-1 Regulates a
Rapid Type I Interferon Response
SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
LA English
DT Article
ID INFLUENZA-A-VIRUS; RIG-I; NS1 PROTEIN; ANTIVIRAL RESPONSES; INNATE
IMMUNITY; BETA-INTERFERON; RNA; INFECTION; CELLS; PATHWAY
AB The cell autonomous response to viral infection is carefully regulated to induce type I interferons (IFNs), which in turn induce the establishment of an antiviral state. Leucine-rich repeat (in Flightless I) interacting protein-1 (LRRFIP1) and LRRFIP2 are 2 related proteins that have been identified as interacting with MyD88 and Flightless I homolog, a leucine-rich repeat protein. LRRFIP2 positively regulates NFkB and macrophage cytokine production after lipopolysaccharide, but less is known about LRRFIP1. We hypothesized that LRRFIP1 could be more important in antiviral responses, as overexpression led to type I IFN production in a pilot study. The induction of type I IFNs occurred even in the absence of virus, but was enhanced by the presence of virus. Conversely, knockdown of LRRFIP1 compromised IFN expression. We found that LRRFIP1 was rapidly recruited to influenza-containing early endosomes in a p38-dependent fashion. This was specific for virus-containing endosomes as there was almost no colocalization of LRRFIP1 with early endosomes in the absence of virus. Further, LRRFIP1 was recruited to RNA-containing vesicles. Taken together, these data suggest that LRRFIP1 participates in cell responses to virus at early time points and is important for type I IFN induction.
C1 [Bagashev, Asen; Fitzgerald, Michael C.; Sullivan, Kathleen E.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Allergy Immunol, Philadelphia, PA 19104 USA.
[LaRosa, David F.] Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19104 USA.
[Rose, Patrick P.; Cherry, Sara] Univ Penn, Penn Genom Inst, Dept Microbiol, Philadelphia, PA 19104 USA.
[Johnson, Alfred C.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Sullivan, KE (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Allergy Immunol, Philadelphia, PA 19104 USA.
EM sullivak@mail.med.upenn.edu
RI Bagashev, Asen/D-2913-2011;
OI Bagashev, Asen/0000-0001-9900-8106; Sullivan,
Kathleen/0000-0003-4018-1646
FU NIH [RO1 RO1AI44127, NO1AI50024]
FX The work reported in this article was supported by NIH RO1 RO1AI44127
and NO1AI50024. The authors would like to thank Bruce Beutler for the
gift of the Unc-93B expression plasmid, and Michael Gale Jr. and Shizuo
Akira for the RIG-I knockout and control MEFs. The authors also thank
Phillip Johnson, Jeff Bergelson, and Joan Durbin for critical readings
of the article.
NR 37
TC 9
Z9 10
U1 0
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1079-9907
J9 J INTERF CYTOK RES
JI J. Interferon Cytokine Res.
PD NOV
PY 2010
VL 30
IS 11
BP 843
EP 852
DI 10.1089/jir.2010.0017
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 675UH
UT WOS:000283862400007
PM 20586614
ER
PT J
AU Li, QL
Sadowski, S
Frank, M
Chai, CL
Varadi, A
Ho, SY
Lou, H
Dean, M
Thisse, C
Thisse, B
Uitto, J
AF Li, Qiaoli
Sadowski, Sara
Frank, Michael
Chai, Chunli
Varadi, Andras
Ho, Shiu-Ying
Lou, Hong
Dean, Michael
Thisse, Christine
Thisse, Bernard
Uitto, Jouni
TI The abcc6a Gene Expression Is Required for Normal Zebrafish Development
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID PSEUDOXANTHOMA-ELASTICUM; MOLECULAR-GENETICS; PUTATIVE PATHOMECHANISMS;
TOPOLOGY PREDICTION; CONNECTIVE TISSUES; DISEASE; TRANSPORTERS;
PHENOTYPE; HETEROZYGOSITY; MINERALIZATION
AB Pseudoxanthoma elasticum (PXE) is caused by mutations in the ABCC6 gene, which encodes a putative efflux transporter, ABCC6. The zebrafish (Danio rerio) has two ABCC6-related sequences. To study the function of abcc6 during zebrafish development, the mRNA expression levels were measured using RT-PCR and in situ hybridization. The abcc6a showed a relatively high level of expression at 5 days post-fertilization (d.p.f.) and the expression was specific to the Kupffer's vesicles. The abcc6b expression was evident at 6 hours post-fertilization (h.p.f.) and remained high up to 8 d.p.f., corresponding to embryonic kidney proximal tubules. Morpholinos were designed to both genes to prevent pre-mRNA splicing and block translation. Injection of the abcc6a morpholinos into 1-4 cell zebrafish embryos decreased gene expression by 54-81%, and induced a phenotype, pericardial edema and curled tail associated with death at around 8 d.p.f. Microinjecting zebrafish embryos with full-length mouse Abcc6 mRNA together with the morpholino completely rescued this phenotype. No phenotypic changes were observed when the abcc6b gene morpholino was injected into embryos with knockdown efficiency of 100%. These results suggest that abcc6a is an essential gene for normal zebrafish development and provide insight into the function of ABCC6, the gene mutated in PXE.
C1 [Li, Qiaoli; Sadowski, Sara; Frank, Michael; Uitto, Jouni] Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA.
[Li, Qiaoli; Sadowski, Sara; Frank, Michael; Uitto, Jouni] Thomas Jefferson Univ, Jefferson Inst Mol Med, Philadelphia, PA 19107 USA.
[Chai, Chunli; Thisse, Christine; Thisse, Bernard] Univ Virginia, Sch Med, Dept Cell Biol, Charlottesville, VA 22908 USA.
[Varadi, Andras] Hungarian Acad Sci, Inst Enzymol, Budapest, Hungary.
[Ho, Shiu-Ying; Uitto, Jouni] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA.
[Lou, Hong] SAIC Frederick, Frederick, MD USA.
[Dean, Michael] NCI FCRDC, Human Genet Sect, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA.
[Chai, Chunli] Southwest Univ, Coll Biotechnol, Chongqing 40076, Peoples R China.
RP Uitto, J (reprint author), Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, 233 S,10th St,Suite 450 BLSB, Philadelphia, PA 19107 USA.
EM Jouni.uitto@jefferson.edu
RI Varadi, Andras/A-2055-2012; Dean, Michael/G-8172-2012; Li,
Qiaoli/F-8383-2013
OI Dean, Michael/0000-0003-2234-0631;
FU DHHS, NIH/NIAMS [R01 AR28450, R01 AR55225]; OTKA of Hungary [NI-68950];
University of Virginia
FX We thank HsingYin Liu and Reid Oldenburg for technical assistance; Terry
Hyslop and Jocelyn Andrel (Division of Biostatistics, Department of
Pharmacology and Experimental Therapeutics, Thomas Jefferson
University), and GianPaolo Guercio and Carol Kelly for help in the
article preparation. These studies were supported by DHHS, NIH/NIAMS
grants R01 AR28450 and R01 AR55225 (to JU), by OTKA NI-68950 of Hungary
(to AV), and by the University of Virginia (to CT and BT).
NR 30
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U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD NOV
PY 2010
VL 130
IS 11
BP 2561
EP 2568
DI 10.1038/jid.2010.174
PG 8
WC Dermatology
SC Dermatology
GA 664MC
UT WOS:000282963600008
PM 20596085
ER
PT J
AU Kronenberg, K
Brosch, S
Butsch, F
Tada, Y
Shibagaki, N
Udey, MC
von Stebut, E
AF Kronenberg, Katharina
Brosch, Sven
Butsch, Florian
Tada, Yayoi
Shibagaki, Naotaka
Udey, Mark C.
von Stebut, Esther
TI Vaccination with TAT-Antigen Fusion Protein Induces Protective, CD8(+) T
Cell-Mediated Immunity Against Leishmania Major
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID FC-GAMMA RECEPTORS; DENDRITIC CELLS; CLASS-II; CPG
OLIGODEOXYNUCLEOTIDES; INTRACELLULAR PATHOGEN; MURINE LEISHMANIASIS;
PERSISTENT PARASITES; ANTITUMOR IMMUNITY; INTERFERON-GAMMA; EX-VIVO
AB In murine leishmaniasis, healing is mediated by IFN-gamma-producing CD4(+) and CD8(+) T cells. Thus, an efficacious vaccine should induce Th1 and Tc1 cells. Dendritic cells (DCs) pulsed with exogenous proteins primarily induce strong CD4-dependent immunity; induction of CD8 responses has proven to be difficult. We evaluated the immunogenicity of fusion proteins comprising the protein transduction domain of HIV-1 TAT and the Leishmania antigen LACK (Leishmania homolog of receptors for activated C kinase), as TAT-fusion proteins facilitate major histocompatibility complex class I-dependent antigen presentation. In vitro, TAT-LACK-pulsed DCs induced stronger proliferation of Leishmania-specific CD8(+) T cells compared with DCs incubated with LACK alone. Vaccination with TAT-LACK-pulsed DCs or fusion proteins plus adjuvant in vivo significantly improved disease outcome in Leishmania major-infected mice and was superior to vaccination with DCs treated with LACK alone. Vaccination with DC+TAT-LACK resulted in stronger proliferation of CD8(+) T cells when compared with immunization with DC+LACK. Upon depletion of CD4(+) or CD8(+) T cells, TAT-LACK-mediated protection was lost. TAT-LACK-pulsed IL-12p40-deficient DCs did not promote protection in vivo. In summary, these data show that TAT-fusion proteins are superior in activating Leishmania-specific Tc1 cells when compared with antigen alone and suggest that IL-12-dependent preferential induction of antigen-specific CD8(+) cells promotes significant protection against this important human pathogen.
C1 [Kronenberg, Katharina; Brosch, Sven; Butsch, Florian; von Stebut, Esther] Johannes Gutenberg Univ Mainz, Dept Dermatol, D-55131 Mainz, Germany.
[Tada, Yayoi; Shibagaki, Naotaka; Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP von Stebut, E (reprint author), Johannes Gutenberg Univ Mainz, Dept Dermatol, D-55131 Mainz, Germany.
EM vonstebu@mail.uni-mainz.de
FU World Health Organization (WHO); Deutsche Forschungsgemeinschaft [SFB
490, 548]; Johannes Gutenberg-University of Mainz; NIH, Center for
Cancer Research, National Cancer Institute; Boehringer Ingelheim Fonds
FX We thank Dr Steven Dowdy for supplying the TAT-HA protein-encoding
plasmids and for helpful discussions, Dr David L Sacks for providing
LACK plasmids, and Drs K Steinbrink and H Jonuleit for critically
reading this paper. This work was supported in part by grants from the
Special Programme for Research and Training in Tropical Diseases (TDR)
of the World Health Organization (WHO) (to EvS/MCU), the Deutsche
Forschungsgemeinschaft (SFB 490 and 548), the MAIFOR program of the
Johannes Gutenberg-University of Mainz (to EvS), the Intramural Program
of the NIH, Center for Cancer Research, National Cancer Institute (to
MCU), and the Boehringer Ingelheim Fonds (Bifond Travel Grant; to KK).
NR 46
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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 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD NOV
PY 2010
VL 130
IS 11
BP 2602
EP 2610
DI 10.1038/jid.2010.171
PG 9
WC Dermatology
SC Dermatology
GA 664MC
UT WOS:000282963600013
PM 20574442
ER
PT J
AU Suzuki, R
Liu, XB
Olivera, A
Aguiniga, L
Yamashita, Y
Blank, U
Ambudkar, I
Rivera, J
AF Suzuki, Ryo
Liu, Xibao
Olivera, Ana
Aguiniga, Lizath
Yamashita, Yumi
Blank, Ulrich
Ambudkar, Indu
Rivera, Juan
TI Loss of TRPC1-mediated Ca2+ influx contributes to impaired degranulation
in Fyn-deficient mouse bone marrow-derived mast cells
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE calcium; IgE; transient receptor potential cation channel 1
ID FC-EPSILON-RI; OPERATED CALCIUM-ENTRY; HIGH-AFFINITY RECEPTOR; TYROSINE
PHOSPHORYLATION; IMMUNOGLOBULIN-E; IGE RECEPTOR; ACTIN MICROFILAMENTS;
PLASMA-MEMBRANE; GENE-EXPRESSION; PORE SUBUNIT
AB MC degranulation requires the influx of calcium from the extracellular environment. Orai1/STIM1 is essential to MC SOCE, as shown in rat peritoneal MCs, the rat MC lines (RBL-2H3), or in Orai1 null embryo liver-derived, cultured MCs. However, minimal information exists about the role of other calcium channels expressed on these cells. Here, we demonstrate that the nonselective TRPC1 participates in Fc epsilon RI-mediated calcium entry in mouse BMMCs. We found that Fyn null MCs, which have an impaired degranulation response, expressed reduced levels of TRPC1, had normal depletion of intracellular calcium stores but an impaired calcium influx, and failed to depolymerize cortical F-actin (a key step for granule-plasma membrane fusion). Partial RNAi silencing of TRPC1 expression in WT MCs (to the level of Fyn null MCs) mimicked the Fyn null defect in calcium influx, cortical F-actin depolymerization, and MC degranulation. Ectopic expression of Fyn or TRPC1 in Fyn null MCs restored calcium responses and cortical F-actin depolymerization and increased MC degranulation. Together with our findings that expression of Orai1 is not altered in Fyn null MCs, our findings suggest that TRPC1 participates in calcium influx and other key events required for MC degranulation. This demonstrates that in addition to a role described previously for Orai1 in promoting MC degranulation, nonselective cation channels participate in promoting the exocytotic response. J. Leukoc. Biol. 88: 863-875; 2010.
C1 [Suzuki, Ryo; Olivera, Ana; Aguiniga, Lizath; Yamashita, Yumi; Rivera, Juan] NIAMSD, Mol Immunol Sect, Immunogenet Mol Lab, Bethesda, MD 20892 USA.
[Liu, Xibao; Ambudkar, Indu] Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD USA.
[Blank, Ulrich] INSERM, U699, Paris, France.
[Blank, Ulrich] Univ Paris 07, Fac Med, Paris, France.
RP Rivera, J (reprint author), NIAMS, NIH, Bldg 10,Room 13C103, Bethesda, MD 20892 USA.
EM juan_rivera@nih.gov
FU NIAMS; National Institute of Dental and Craniofacial Research, NIH;
Office of Science and Technology, NIAMS
FX This research was supported by the Intramural Research Programs of the
NIAMS and the National Institute of Dental and Craniofacial Research,
NIH. We are grateful for the support of the Flow Cytometry Section, the
Laboratory Animal Care and Use Section, and the Light Imaging Section of
the Office of Science and Technology, NIAMS. We thank Drs. Nevenka
Medic, Dean D. Metcalfe, and Alasdair Gilfillan (NIAID, NIH) for
personal communication.
NR 71
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U1 1
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 NOV
PY 2010
VL 88
IS 5
BP 863
EP 875
DI 10.1189/jlb.0510253
PG 13
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 692YG
UT WOS:000285191200006
PM 20571036
ER
PT J
AU Basselin, M
Rosa, AO
Ramadan, E
Cheon, Y
Chang, L
Chen, M
Greenstein, D
Wohltmann, M
Turk, J
Rapoport, SI
AF Basselin, Mireille
Rosa, Angelo O.
Ramadan, Epolia
Cheon, Yewon
Chang, Lisa
Chen, Mei
Greenstein, Deanna
Wohltmann, Mary
Turk, John
Rapoport, Stanley I.
TI Imaging decreased brain docosahexaenoic acid metabolism and signaling in
iPLA(2)beta (VIA)-deficient mice
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE Ca2+-independent phospholipase A(2); iPLA(2) knockout mouse; brain
imaging; muscarinic receptor; arecoline
ID INDEPENDENT PHOSPHOLIPASE A(2); MUSCARINIC ACETYLCHOLINE-RECEPTORS;
ARACHIDONIC-ACID; FATTY-ACIDS; IN-VIVO; RAT HIPPOCAMPUS;
DYSTONIA-PARKINSONISM; UNANESTHETIZED RATS; OXIDATIVE STRESS; EXPRESS
GROUP
AB Ca2+-independent phospholipase A(2)beta (iPLA(2)beta) selectively hydrolyzes docosahexaenoic acid (DHA, 22:6n-3) in vitro from phospholipid. Mutations in the PLA2G6 gene encoding this enzyme occur in patients with idiopathic neurodegeneration plus brain iron accumulation and dystoniaparkinsonism without iron accumulation, whereas mice lacking PLA2G6 show neurological dysfunction and neuropathology after 13 months. We hypothesized that brain DHA metabolism and signaling would be reduced in 4-month-old iPLA(2)beta-deficient mice without overt neuropathology. Saline or the cholinergic muscarinic M 1,3,5 receptor agonist arecoline (30 mg/kg) was administered to unanesthetized iPLA(2)beta(-/-), iPLA(2)beta(+/-), and iPLA(2)beta(+/+) mice, and [1-C-14]DHA was infused intravenously. DHA incorporation coefficients k* and rates J(in), representing DHA metabolism, were determined using quantitative autoradiography in 81 brain regions. iPLA(2)beta(-/-) or iPLA(2)beta(+/-) compared with iPLA(2)beta(+/+) mice showed widespread and significant baseline reductions in k* and J(in) for DHA. Arecoline increased both parameters in brain regions of iPLA(2)beta(+/+) mice but quantitatively less so in iPLA(2)beta(-/-) and iPLA(2)beta(+/-) mice. Consistent with iPLA(2)beta's reported ability to selectively hydrolyze DHA from phospholipid in vitro, iPLA(2)beta deficiency reduces brain DHA metabolism and signaling in vivo at baseline and following M 1,3,5 receptor activation. Positron emission tomography might be used to image disturbed brain DHA metabolism in patients with PLA2G6 mutations.-Basselin, M., A. O. Rosa, E. Ramadan, Y. Cheon, L. Chang, M. Chen, D. Greenstein, M. Wohltmann, J. Turk, and S. I. Rapoport. Imaging decreased brain docosahexaenoic acid metabolism and signaling in iPLA(2)beta (VIA)-deficient mice. J. Lipid Res. 51: 3166-3173.
C1 [Basselin, Mireille; Rosa, Angelo O.; Ramadan, Epolia; Cheon, Yewon; Chang, Lisa; Chen, Mei; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA.
[Greenstein, Deanna] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Wohltmann, Mary; Turk, John] Washington Univ, Sch Med, Dept Med, Mass Spectrometry Facil, St Louis, MO 63110 USA.
Washington Univ, Sch Med, Div Endocrinol Metab & Lipid Res, St Louis, MO USA.
RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA.
EM sir@helix.nih.gov
FU National Institute on Aging; National Institutes of Health; United
States Public Health Service [R37-DK34388, P41-RR00954, P60-DK20579,
P30-DK56341]
FX This research was supported by the Intramural Research Program of the
National Institute on Aging, the National Institutes of Health, and by
United States Public Health Service Grants R37-DK34388, P41-RR00954,
P60-DK20579, and P30-DK56341 to J.T. Its contents are solely the
responsibility of the authors and do not necessarily represent the
official views of the National Institutes of Health or USPHS.
NR 69
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U1 0
U2 3
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 NOV
PY 2010
VL 51
IS 11
BP 3166
EP 3173
DI 10.1194/jlr.M008334
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 662LG
UT WOS:000282808200009
PM 20686114
ER
PT J
AU Zhu, XW
Owen, JS
Wilson, MD
Li, HT
Griffiths, GL
Thomas, MJ
Hiltbold, EM
Fessler, MB
Parks, JS
AF Zhu, Xuewei
Owen, John S.
Wilson, Martha D.
Li, Haitao
Griffiths, Gary L.
Thomas, Michael J.
Hiltbold, Elizabeth M.
Fessler, Michael B.
Parks, John S.
TI Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking
to lipid rafts by reduction of lipid raft cholesterol
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE free cholesterol; cytokines; immunology; lipid droplets; lymphocytes;
retinoids
ID INNATE IMMUNE RECOGNITION; CASSETTE TRANSPORTER A1; TANGIER-DISEASE;
ABCA1-DEFICIENT MACROPHAGES; PLASMA-MEMBRANE; APOA-I; ATHEROSCLEROSIS;
ACTIVATION; EXPRESSION; ACCUMULATION
AB We previously showed that macrophages from macrophage-specifi c ATP-binding cassette transporter A1 (ABCA1) knockout (Abca1(-M/-M)) mice had an enhanced proinflammatory response to the Toll-like receptor (TLR) 4 agonist, lipopolysaccharide (LPS), compared with wild-type (WT) mice. In the present study, we demonstrate a direct association between free cholesterol (FC), lipid raft content, and hyper-responsiveness of macrophages to LPS in WT mice. Abca1(-M/-M) macrophages were also hyper-responsive to specific agonists to TLR2, TLR7, and TLR9, but not TLR3, compared with WT macrophages. We hypothesized that ABCA1 regulates macrophage responsiveness to TLR agonists by modulation of lipid raft cholesterol and TLR mobilization to lipid rafts. We demonstrated that Abca1(-M/-M) vs. WT macrophages contained 23% more FC in isolated lipid rafts. Further, mass spectrometric analysis suggested raft phospholipid composition was unchanged. Although cell surface expression of TLR4 was similar between Abca1(-M/-M) and WT macrophages, significantly more TLR4 was distributed in membrane lipid rafts in Abca1(-M/-M) macrophages. Abca1(-M/-M) macrophages also exhibited increased trafficking of the predominantly intracellular TLR9 into lipid rafts in response to TLR9-specifi c agonist (CpG). Collectively, our data suggest that macrophage ABCA1 dampens inflammation by reducing MyD88-dependent TLRs trafficking to lipid rafts by selective reduction of FC content in lipid rafts.-Zhu, X., J. S. Owen, M. D. Wilson, H. Li, G. L. Griffiths, M. J. Thomas, E. M. Hiltbold, M. B. Fessler, and J. S. Parks. Macrophage ABCA1 reduces MyD88-dependent Toll-like
C1 [Zhu, Xuewei; Wilson, Martha D.; Parks, John S.] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol Lipid Sci, Winston Salem, NC 27106 USA.
[Owen, John S.; Thomas, Michael J.; Parks, John S.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC 27103 USA.
[Hiltbold, Elizabeth M.] Wake Forest Univ, Bowman Gray Sch Med, Dept Microbiol & Immunol, Winston Salem, NC 27103 USA.
[Li, Haitao; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Bethesda, MD 20892 USA.
[Fessler, Michael B.] NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA.
RP Parks, JS (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol Lipid Sci, 300 S Hawthorne Rd, Winston Salem, NC 27106 USA.
EM jparks@wfubmc.edu
FU National Institutes of Health [HL-49373, HL-094525, AT-27820]; American
Heart Association [09POST2250225]; National Institutes of Health,
National Institute of Environmental Health Sciences [Z01 ES102005];
National Institutes of Health Roadmap for Medical Research Initiative
FX This work was supported by National Institutes of Health Grants
HL-49373, HL-094525, and AT-27820 (J.S.P.), American Heart Association
fellowship 09POST2250225 (X.Z.), and the Intramural Research Program of
the National Institutes of Health, National Institute of Environmental
Health Sciences Z01 ES102005 (M.B.F.). The fPEG-cholesterol synthesis
was supported by the National Institutes of Health Roadmap for Medical
Research Initiative through its establishment of the Imaging Probe
Development Center, administered by the National Heart, Lung, and Blood
Institute. Its contents are solely the responsibility of the authors and
do not necessarily represent the official views of the National
Institutes of Health.
NR 46
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U1 1
U2 11
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 NOV
PY 2010
VL 51
IS 11
BP 3196
EP 3206
DI 10.1194/jlr.M006486
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 662LG
UT WOS:000282808200012
PM 20650929
ER
PT J
AU Madelin, G
Lee, JS
Inati, S
Jerschow, A
Regatte, RR
AF Madelin, Guillaume
Lee, Jae-Seung
Inati, Souheil
Jerschow, Alexej
Regatte, Ravinder R.
TI Sodium inversion recovery MRI of the knee joint in vivo at 7T
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Osteoarthritis; Cartilage; Sodium; Magnetic resonance imaging; Inversion
recovery; Adiabatic inversion
ID BOVINE ARTICULAR-CARTILAGE; FIXED CHARGE-DENSITY; MAGNETIC-RESONANCE;
ADIABATIC PULSES; HUMAN BRAIN; NA-23 MRI; NMR
AB The loss of proteoglycans (PG) in the articular cartilage is an early signature of osteoarthritis (OA). The ensuing changes in the fixed charge density in the cartilage can be directly linked to sodium concentration via charge balance. Sodium ions in the knee joint appear in two pools: in the synovial fluids or joint effusion where the ions are in free motion and bound within the cartilage tissue where the Na(+) ions have a restricted motion. The ions in these two compartments have therefore different T(1) and T(2) relaxation times. The purpose of this study is to demonstrate the feasibility of a fluid-suppressed 3D ultrashort TE radial sodium sequence by implementing an inversion recovery (IR) preparation of the magnetization at 7T. This method could allow a more accurate and more sensitive quantification of loss of PG in patients with OA. It is shown that adiabatic pulses offer significantly improved performance in terms of robustness to B(1) and B(0) inhomogeneities when compared to the hard pulse sequence. Power deposition considerations further pose a limit to the RF inversion power, and we demonstrate in simulations and experiments how a practical compromise can be struck between clean suppression of fluid signals and power deposition levels. Two IR sequences with different types of inversion pulses (a rectangular pulse and an adiabatic pulse) were tested on a liquid phantom, ex vivo on a human knee cadaver and then in vivo on five healthy volunteers, with a (Nyquist) resolution of similar to 3.6 mm and a signal-to-noise ratio of similar to 30 in cartilage without IR and similar to 20 with IR. Due to specific absorption rate limitations, the total acquisition time was similar to 17 min for the 3D radial sequence without inversion or with the rectangular IR, and 24:30 min for the adiabatic IR sequence. It is shown that the adiabatic IR sequence generates a more uniform fluid suppression over the whole sample than the rectangular IR sequence. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Madelin, Guillaume; Lee, Jae-Seung; Jerschow, Alexej] NYU, Dept Chem, New York, NY 10012 USA.
[Madelin, Guillaume; Lee, Jae-Seung; Regatte, Ravinder R.] NYU, Med Ctr, Ctr Biomed Imaging, New York, NY 10012 USA.
[Inati, Souheil] NIH, Bethesda, MD 20892 USA.
RP Jerschow, A (reprint author), NYU, Dept Chem, 550 1St Ave, New York, NY 10012 USA.
EM alexej.jerschow@nyu.edu; ravinder.regatte@nyumc.org
RI Regatte, Ravinder/K-2364-2014; Lee, Jae-Seung/A-5669-2009;
OI Regatte, Ravinder/0000-0002-4607-7682; Lee,
Jae-Seung/0000-0002-8571-0663; Jerschow, Alexej/0000-0003-1521-9219;
Inati, Souheil/0000-0001-5596-9554; Madelin,
Guillaume/0000-0002-5556-5792
FU US NIH [1RO1AR053133, 1R01AR056260, 1R21AR055724]
FX This work was supported by US NIH Grants 1RO1AR053133, 1R01AR056260 and
1R21AR055724. The authors would like to thank Graham Wiggins and Ryan
Brown for repairing and optimizing the sodium knee coil prior to the in
vivo experiments.
NR 30
TC 39
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U1 1
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
J9 J MAGN RESON
JI J. Magn. Reson.
PD NOV
PY 2010
VL 207
IS 1
BP 42
EP 52
DI 10.1016/j.jmr.2010.08.003
PG 11
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA 673AU
UT WOS:000283631400006
PM 20813569
ER
PT J
AU McCoy, BN
Raffel, SJ
Lopez, JE
Schwan, TG
AF McCoy, Brandi N.
Raffel, Sandra J.
Lopez, Job E.
Schwan, Tom G.
TI Bloodmeal Size and Spirochete Acquisition of Ornithodoros hermsi (Acari:
Argasidae) During Feeding
SO JOURNAL OF MEDICAL ENTOMOLOGY
LA English
DT Article
DE Borrelia hermsii; relapsing fever; ticks; quantitative PCR
ID SUBGENUS PERSICARGAS IXODOIDEA; RELAPSING FEVER; BORRELIA-BURGDORFERI;
MAJOR SEROTYPES; MEAL WEIGHT; TICK; MOUBATA; GROWTH
AB Ornithodoros hermsi Wheeler (Acari: Argasidae) is the vector of Borrelia hermsii, the primary cause of tick-borne relapsing fever in North America. This tick is one of the smallest Ornithodoros species involved with the biological transmission of spirochetes; yet, the amount of blood ingested while feeding is unknown. Therefore, we determined the amount of blood O. hermsi ingested during a bloodmeal to establish its potential for spirochete acquisition while feeding on an infected host. Ticks at different developmental stages were weighed before and after feeding and the volume of blood ingested was calculated. Females ingested the most blood, averaging approximate to 15 mu l per meal, but late-stage nymphs took in the most blood in proportion to unfed body weight. A cohort of nymphs was weighed three more times during the 48 h after feeding, which demonstrated that O. hermsi may have excreted coxal fluid ranging from 24 -36% of the bloodmeal weight. We also developed a quantitative polymerase chain reaction method to determine the number of spirochetes ingested and maintained within the ticks after feeding. The density of spirochetes in ticks having just engorged was slightly less than in the host's blood, hi the first 5 d after feeding, the number of spirochetes within the ticks declined from the number initially ingested but then remained constant through 15 d. These observations establish a basis for future studies to determine the minimum number of spirochetes required in the host's blood to allow O. hermsi to become persistently infected and transmit during subsequent bloodmeals.
C1 [McCoy, Brandi N.; Raffel, Sandra J.; Lopez, Job E.; Schwan, Tom G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Schwan, TG (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM tschwan@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX We thank Paul Policastro for providing the RML colony ticks used in this
study, Michael Fay for statistical help, and Philip Stewart and Joseph
Hinnebusch for review of the manuscript. This work was supported by the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 31
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U1 0
U2 5
PU ENTOMOLOGICAL SOC AMER
PI LANHAM
PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA
SN 0022-2585
J9 J MED ENTOMOL
JI J. Med. Entomol.
PD NOV
PY 2010
VL 47
IS 6
BP 1164
EP 1172
DI 10.1603/ME10175
PG 9
WC Entomology; Veterinary Sciences
SC Entomology; Veterinary Sciences
GA 684RR
UT WOS:000284567500027
PM 21175068
ER
PT J
AU Sharma, A
Rodrigues, J
Kajla, MK
Agrawal, N
Adak, T
Bhatnagar, RK
AF Sharma, Anil
Rodrigues, Janneth
Kajla, Mayur K.
Agrawal, Neema
Adak, T.
Bhatnagar, Raj K.
TI Expression Profile of Prophenoloxidase-Encoding (acppo6) Gene of
Plasmodium vivax-Refractory Strain of Anopheles culicifacies
SO JOURNAL OF MEDICAL ENTOMOLOGY
LA English
DT Article
DE Anopheles culicifacies; prophenoloxidase; refractory; Plasmodium vinckei
petteri
ID MOSQUITO AEDES-AEGYPTI; BOMBYX-MORI; HEMOCYTES; MELANIZATION;
PHENOLOXIDASE; INFECTIONS; GAMBIAE; PHAGOCYTOSIS; PURIFICATION; SILKWORM
AB Anopheles culicifacies is the main vector for transmission of Plasmodium vicar malaria in the Indian subcontinent. A strain of Art. culicifacies isolated from its natural niche displayed complete refractoriness to P. vicar by melanotic encapsulation of ookinetes. Prophenoloxidases are key components of the phenoloxidase cascade that leads to recognition and melanization of invading organisms. We isolated and cloned prophenoloxidase-encoding acppo6 gene of An. culicifacies and analyzed its expression profile under various regimens of immune challenge. The aeppo6 was differentially expressed during various stages of larval development. The acppo6 transcription was also up-regulated in response to bacteria and Plasmodium vinckei petteri challenge. The transcript levels of the acppo6 gene were higher in naive adult refractory female mosquitoes as compared with female susceptible mosquitoes. Furthermore, the induction of acppo6 in the susceptible strain upon Plasmodium infection was negligible as compared with that of the refractory strain. The observation is suggestive of the role of acppo6 in effectuating a melanotic response in Plasmodium-incompetent naturally occurring refractory An. culicifacies strain.
C1 [Sharma, Anil; Rodrigues, Janneth; Agrawal, Neema; Bhatnagar, Raj K.] Int Ctr Genet Engn & Biotechnol, Insect Resistance Grp, New Delhi 110067, India.
[Sharma, Anil; Adak, T.] Natl Inst Malaria Res, Sector 8, New Delhi 110077, India.
[Rodrigues, Janneth] NIH, Lab Malaria & Vector Res, Rockville, MD 20852 USA.
[Kajla, Mayur K.] Univ Wisconsin, Dept Entomol, Madison, WI 53706 USA.
RP Bhatnagar, RK (reprint author), Int Ctr Genet Engn & Biotechnol, Insect Resistance Grp, PO 10504,Aruna Asaf Ali Marg, New Delhi 110067, India.
EM raj@icgeb.res.in
RI Adak, Tridibes/C-2501-2011; khan, raja/B-5726-2012; Sharma,
Anil/F-4248-2011;
OI Sharma, Anil/0000-0003-2264-2007
FU Indian Council of Medical Research; University Grant Commission
FX This work was supported by a project grant from the Indian Council of
Medical Research. A.S. was supported by the Research Fellowship of
University Grant Commission.
NR 27
TC 1
Z9 1
U1 0
U2 1
PU ENTOMOLOGICAL SOC AMER
PI LANHAM
PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA
SN 0022-2585
J9 J MED ENTOMOL
JI J. Med. Entomol.
PD NOV
PY 2010
VL 47
IS 6
BP 1220
EP 1226
DI 10.1603/ME10033
PG 7
WC Entomology; Veterinary Sciences
SC Entomology; Veterinary Sciences
GA 684RR
UT WOS:000284567500034
PM 21175075
ER
PT J
AU Killian, JK
Walker, RL
Suuriniemi, M
Jones, L
Scurci, S
Singh, P
Cornelison, R
Harmon, S
Boisvert, N
Zhu, J
Wang, YH
Bilke, S
Davis, S
Giaccone, G
Smith, WI
Meltzer, PS
AF Killian, J. Keith
Walker, Robert L.
Suuriniemi, Miia
Jones, Laura
Scurci, Stephanie
Singh, Parvati
Cornelison, Robert
Harmon, Shannon
Boisvert, Nichole
Zhu, Jack
Wang, Yonghong
Bilke, Sven
Davis, Sean
Giaccone, Giuseppe
Smith, William I., Jr.
Meltzer, Paul S.
TI Archival Fine-Needle Aspiration Cytopathology (FNAC) Samples Untapped
Resource for Clinical Molecular Profiling
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Article
ID POLYMERASE-CHAIN-REACTION; FOLLICULAR LYMPHOMA; STAINS
AB Microarray technologies provide high resolution maps of chromosome imbalances and epigenomic aberrations in the cancer cell genome Such assays are often sensitive to sample DNA integrity, voiding the utility of many archival pathology specimens and necessitating the special handling of prospective clinical specimens We have identified the remarkable preservation of higher molecular weight DNA m archival fine needle aspiration cytopathology specimens from patients greater than 10 years of age We further demonstrate the outstanding technical performance of 57 fine needle aspiration cytopathology samples for aberration detection on high resolution comparative genomic hybridization array, DNA methylation, and single nucleotide polymorphism genotyping platforms Forty four of 46 malignant aspirates in this study manifested unequivocal genomic aberrations Importantly, matched Papanicolaou and Diff Quik fine needle aspiration cytopathology samples showed critical differences in DNA preservation and DNA integrity Overall, this study identifies a largely untapped reserve of human pathology specimens for molecular profiling studies, with ramifications for the prospective collection of clinical biospecimens (J Mol Diagn 2010, 12, 739-745, DOI 10.2353/jmoldx.2010.090238)
C1 [Killian, J. Keith; Walker, Robert L.; Suuriniemi, Miia; Jones, Laura; Scurci, Stephanie; Singh, Parvati; Cornelison, Robert; Harmon, Shannon; Boisvert, Nichole; Zhu, Jack; Wang, Yonghong; Bilke, Sven; Davis, Sean; Meltzer, Paul S.] NCI, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA.
[Giaccone, Giuseppe] NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA.
[Smith, William I., Jr.] Suburban Hosp, Dept Pathol, Bethesda, MD USA.
RP Meltzer, PS (reprint author), 37 Convent Dr,BG 37,RM 6138,MSC 4265, Bethesda, MD 20892 USA.
RI Giaccone, Giuseppe/E-8297-2017;
OI Giaccone, Giuseppe/0000-0002-5023-7562; Davis, Sean/0000-0002-8991-6458
FU NIH National Cancer Institute Center for Cancer Research
FX Supported in part by the Intramural Research Program of the NIH National
Cancer Institute Center for Cancer Research
NR 12
TC 41
Z9 41
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2010
VL 12
IS 6
BP 739
EP 745
DI 10.2353/jmoldx.2010.090233
PG 7
WC Pathology
SC Pathology
GA 677FE
UT WOS:000283973700002
PM 20959611
ER
PT J
AU Xi, L
Pham, T
Pham, T
Giaccone, G
Raffeld, M
AF Xi, L.
Pham, T.
Pham, T.
Giaccone, G.
Raffeld, M.
TI Implementation of Novel Pyrosequencing and Capillary Electrophoresis
Assays to Screen for Common Mutations of EGFR in Non Small Cell Lung
Cancer
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology
CY NOV 18-20, 2010
CL San Jose, CA
SP Assoc Mol Pathol
C1 [Xi, L.; Pham, T.; Pham, T.; Giaccone, G.; Raffeld, M.] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2010
VL 12
IS 6
BP 904
EP 905
PG 2
WC Pathology
SC Pathology
GA 677FE
UT WOS:000283973700227
ER
PT J
AU Leary, TJO
Fowler, CB
Waybright, TJ
Veenstra, TD
Mason, JT
AF Leary, T. J. O.
Fowler, C. B.
Waybright, T. J.
Veenstra, T. D.
Mason, J. T.
TI High Pressure Assisted Extraction for the Improved Proteomic Analysis of
Formalin Fixed Paraffin Embedded Tissue
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology
CY NOV 18-20, 2010
CL San Jose, CA
SP Assoc Mol Pathol
C1 [Leary, T. J. O.] Vet Hlth Adm, Washington, DC USA.
[Fowler, C. B.; Mason, J. T.] Armed Forces Inst Pathol, Rockville, MD USA.
[Fowler, C. B.] Maryland VA Hlth Care Syst, Rockville, MD USA.
[Waybright, T. J.; Veenstra, T. D.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2010
VL 12
IS 6
BP 914
EP 914
PG 1
WC Pathology
SC Pathology
GA 677FE
UT WOS:000283973700269
ER
PT J
AU Eiden, L
Ait-Ali, D
Holighaus, Y
Mustafa, T
Stroth, N
AF Eiden, Lee
Ait-Ali, Djida
Holighaus, Yvonne
Mustafa, Tomris
Stroth, Nikolas
TI PACAP signaling to target genes through cyclic AMP and calcium during
the stress response
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT 9th International Symposium on VIP, PACAP and Related Peptides
CY OCT 05-08, 2009
CL Kagoshima, JAPAN
C1 [Eiden, Lee; Ait-Ali, Djida; Holighaus, Yvonne; Mustafa, Tomris; Stroth, Nikolas] NIMH, Mol Neurosci Sect, Intramural Res Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2010
VL 42
IS 3
SI SI
BP 296
EP 297
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 666EL
UT WOS:000283095400051
ER
PT J
AU Eiden, L
Samal, B
Braxton, R
Akala, M
Ait-Ali, D
AF Eiden, Lee
Samal, Babru
Braxton, Richard
Akala, Mariam
Ait-Ali, Djida
TI Signaling pathways involved in PACAP and cytokine interactions
regulating adrenomedullary neuropeptide biosynthesis
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT 9th International Symposium on VIP, PACAP and Related Peptides
CY OCT 05-08, 2009
CL Kagoshima, JAPAN
C1 [Eiden, Lee; Samal, Babru; Braxton, Richard; Akala, Mariam; Ait-Ali, Djida] NIMH, Mol Neurosci Sect, Intramural Res Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2010
VL 42
IS 3
SI SI
BP 315
EP 315
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 666EL
UT WOS:000283095400093
ER
PT J
AU Pan, L
Kardono, LBS
Riswan, S
Chai, H
de Blanco, EJC
Pannell, CM
Soejarto, DD
McCloud, TG
Newman, DJ
Kinghorn, AD
AF Pan, Li
Kardono, Leonardus B. S.
Riswan, Soedarsono
Chai, Heebyung
de Blanco, Esperanza J. Carcache
Pannell, Caroline M.
Soejarto, Djaja Doel
McCloud, Thomas G.
Newman, David J.
Kinghorn, A. Douglas
TI Isolation and Characterization of Minor Analogues of Silvestrol and
Other Constituents from a Large-Scale Re-collection of Aglaia foveolata
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID (-)-SILVESTROL; DERIVATIVES; TRITERPENES; (-)-EPISILVESTROL;
CONFORMATION; REVISION; CELLS
AB Two new minor silvestrol analogues [2 '''-episilvestrol (1) and 2 ''',5 '''-diepisilvestrol (2)], together with a new 21-norbaccharane-type triterpene (3), two new 3,4-secodammarane triterpenes (4 and 5), and a new eudesmane sesquiterpene (6), as well as nine known compounds, were isolated from a large-scale re-collection of the CHCl(3)-soluble extract of the stem bark of Aglaia foveolata obtained in Kalimantan, Indonesia. The structures of the new compounds were established by interpretation of their spectroscopic data. All of the isolates were tested for cytotoxicity against HT-29 cells. The new silvestrol analogues, 1 and 2, were considerably less active as cytotoxic agents than silvestrol (7) and episilvestrol (5 '''-episilvestrol) (8) against this cell line, showing the importance of the configuration at C-2 ''' in mediating such activity within this compound class. Several of the compounds isolated were also evaluated in a NF-kappa B (p65) inhibition assay.
C1 Ohio State Univ, Div Med Chem, Coll Pharm, Columbus, OH 43210 USA.
[Kardono, Leonardus B. S.] Indonesian Inst Sci, Res Ctr Chem, Tangerang 15310, Indonesia.
[Riswan, Soedarsono] Indonesian Inst Sci, Herbarium Bogoriense, Biol Res Ctr, Bogor 16122, Indonesia.
[de Blanco, Esperanza J. Carcache] Ohio State Univ, Coll Pharm, Div Pharm Practice & Adm, Columbus, OH 43210 USA.
[Pannell, Caroline M.] Univ Oxford, Dept Plant Sci, Oxford OX1 3RA, England.
[Soejarto, Djaja Doel] Univ Illinois, Program Collaborat Res Pharmaceut Sci, Coll Pharm, Chicago, IL 60612 USA.
[Soejarto, Djaja Doel] Univ Illinois, Dept Med Chem & Pharmacognosy, Coll Pharm, Chicago, IL 60612 USA.
[McCloud, Thomas G.] SAIC Frederick Inc, Frederick, MD 21702 USA.
[Newman, David J.] NCI Frederick, Fairview Ctr, Frederick, MD 21702 USA.
RP Kinghorn, AD (reprint author), Ohio State Univ, Div Med Chem & Pharmacognosy, Coll Pharm, Columbus, OH 43210 USA.
EM kinghorn.4@osu.edu
RI Pan, Li/G-4943-2011;
OI zaraat, javad/0000-0001-5341-7481; Kinghorn, A.
Douglas/0000-0002-6647-8707
FU NCI, NIH [U19 CA52956, P01 CA125066]
FX This study was supported, in part, by grants U19 CA52956 and P01 CA
125066 (awarded to A.D.K.) from NCI, NIH. We are grateful to Dr. J.
Orjala and Mr. M. Totura of the University of Illinois at Chicago for
performing an initial large-scale extraction of the plant material. Mr.
M. Harris, SAIC-Frederick, Inc., is acknowledged for assistance with
plant fractionation studies. We thank Mr. J. Fowble, College of
Pharmacy, The Ohio State University, and Dr. C.-H. Yuan, OSU Campus
Chemical Instrument Center, for facilitating the acquisition of the 400
and 600 MHz NMR spectra. We acknowledge Dr. M. Apsega, Campus Chemical
Instrument Center, The Ohio State University, for the mass spectrometric
data.
NR 24
TC 33
Z9 33
U1 1
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD NOV
PY 2010
VL 73
IS 11
BP 1873
EP 1878
DI 10.1021/np100503q
PG 6
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 684OL
UT WOS:000284559100022
PM 20939540
ER
PT J
AU Hirata, Y
Shimokawa, N
Oh-hashi, K
Yu, ZX
Kiuchi, K
AF Hirata, Yoko
Shimokawa, Norihiro
Oh-hashi, Kentaro
Yu, Zu-Xi
Kiuchi, Kazutoshi
TI Acidification of the Golgi apparatus is indispensable for maturation but
not for cell surface delivery of Ret
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE bafilomycin A1; concanamycin A; EGFR; PC12 cells; Ret
ID GROWTH-FACTOR RECEPTOR; PROTOONCOGENE PRODUCTS; LIGAND-BINDING;
BREFELDIN-A; H+-ATPASE; GLYCOSYLATION; TRAFFICKING; INHIBITION;
EXPRESSION; MUTATIONS
AB P>We examined the effect of concanamycin A and bafilomycin A1, inhibitors of the vacuolar proton-ATPase, on maturation and expression of Ret, a tyrosine kinase receptor for glial cell line-derived neurotrophic factor. Ret appeared as 150- and 170-kDa bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels and both forms were sensitive to peptide-N-glycosidase F. Western and immunocytochemical analyses revealed that the 150-kDa immature form of Ret accumulated in the Golgi apparatus upon treatment with vacuolar proton-ATPase inhibitors, whereas, the 170-kDa mature form of Ret was dramatically decreased. The result suggests that glycosylation of Ret during the conversion from immature forms to mature forms is pH sensitive, and is likely initiated in the acidic trans-Golgi apparatus. In contrast, glycosylation of nascent receptors to become immature receptors appeared to be pH insensitive, and are likely to take place in the endoplasmic reticulum. The immature form of Ret was present in the plasma membrane when the cells were treated with the vacuolar proton-ATPase inhibitors. In conclusion, the acidification of the Golgi apparatus is crucial for maturation of Ret but not indispensable for trafficking of receptors to the membrane.
C1 [Hirata, Yoko; Shimokawa, Norihiro; Oh-hashi, Kentaro; Kiuchi, Kazutoshi] Gifu Univ, Fac Engn, Dept Biomol Sci, Gifu 50111, Japan.
[Yu, Zu-Xi] NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA.
[Hirata, Yoko; Kiuchi, Kazutoshi] Gifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, Gifu, Japan.
RP Hirata, Y (reprint author), 1-1 Yanagido, Gifu 5011193, Japan.
EM yokoh@gifu-u.ac.jp
FU Japan Society for the Promotion of Science
FX This work was supported in part by the Grants-in-Aid for Scientific
Research (C) from Japan Society for the Promotion of Science.
NR 30
TC 5
Z9 5
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD NOV
PY 2010
VL 115
IS 3
BP 606
EP 613
DI 10.1111/j.1471-4159.2010.06966.x
PG 8
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 664RE
UT WOS:000282979400006
PM 20796177
ER
PT J
AU Connaughton, VP
Nelson, R
AF Connaughton, Victoria P.
Nelson, Ralph
TI Spectral Responses in Zebrafish Horizontal Cells Include a Tetraphasic
Response and a Novel UV-Dominated Triphasic Response
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID CYPRINID FISH RETINA; TURTLE RETINA; CARP RETINA; SENSITIVE CONES;
GOLDFISH RETINA; COLOR OPPONENCY; OIL DROPLETS; WAVELENGTH
DISCRIMINATION; ULTRAVIOLET SENSITIVITY; SYNAPTIC CONTACTS
AB Connaughton VP, Nelson R. Spectral responses in zebrafish horizontal cells include a tetraphasic response and a novel UV-dominated triphasic response. J Neurophysiol 104: 2407-2422, 2010. First published July 7, 2010; doi:10.1152/jn.00644.2009. Zebrafish are tetra-chromats with red (R, 570 nm), green (G, 480 nm), blue (B, 415 nm), and UV (U, 362 nm) cones. Although neurons in other cyprinid retinas are rich in color processing neural circuitry, spectral responses of individual neurons in zebrafish retina, a genetic model for vertebrate color vision, are yet to be studied. Using dye-filled sharp microelectrodes, horizontal cell voltage responses to light stimuli of different wavelengths and irradiances were recorded in a superfused eyecup. Spectral properties were assessed both qualitatively and quantitatively. Six spectral classes of horizontal cell were distinguished. Two monophasic response types (L1 and L2) hyperpolarized at all wavelengths. L1 sensitivities peaked at 493 nm, near the G cone absorbance maximum. Modeled spectra suggest equally weighted inputs from both R and G cones and, in addition, a "hidden opponency" from blue cones. These were classified as R-/G-/(b+). L2 sensitivities were maximal at 563 nm near the R cone absorbance peak; modeled spectra were dominated by R cones, with lesser G cone contributions. B and UV cone signals were small or absent. These are R-/g-. Four chromatic (C-type) horizontal cells were either depolarized (+) or hyperpolarized (-) depending on stimulus wavelength. These types are biphasic (R+/G-/B-) with peak excitation at 467 nm, between G and B cone absorbance peaks, UV triphasic (r-/G+/U-) with peak excitation at 362 nm similar to UV cones, and blue triphasic (r-/G+/B-/u-) and blue tetraphasic (r-/G+/B-/u+), with peak excitation at 409 and 411 nm, respectively, similar to B cones. UV triphasic and blue tetraphasic horizontal cell spectral responses are unique and were not anticipated in previous models of distal color circuitry in cyprinids.
C1 [Connaughton, Victoria P.] American Univ, Dept Biol, Washington, DC 20016 USA.
[Nelson, Ralph] Natl Inst Neurol Disorders & Stroke, Neural Circuitry Unit, NIH, Rockville, MD USA.
RP Connaughton, VP (reprint author), American Univ, Dept Biol, 4400 Massachusetts Ave, Washington, DC 20016 USA.
EM vconn@american.edu
FU National Institute of Neurological Disorders and Stroke
FX This research was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke.
NR 59
TC 17
Z9 17
U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD NOV
PY 2010
VL 104
IS 5
BP 2407
EP 2422
DI 10.1152/jn.00644.2009
PG 16
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 695SD
UT WOS:000285392000010
PM 20610786
ER
PT J
AU Molkov, YI
Abdala, APL
Bacak, BJ
Smith, JC
Paton, JFR
Rybak, IA
AF Molkov, Yaroslav I.
Abdala, Ana P. L.
Bacak, Bartholomew J.
Smith, Jeffrey C.
Paton, Julian F. R.
Rybak, Ilya A.
TI Late-Expiratory Activity: Emergence and Interactions With the
Respiratory CPG
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID STEM-SPINAL-CORD; PRE-BOTZINGER COMPLEX; MAMMALIAN BRAIN-STEM; RHYTHM
GENERATION; IN-VITRO; NEWBORN RAT; RETROTRAPEZOID NUCLEUS; PREBOTZINGER
COMPLEX; PACEMAKER NEURONS; FUNCTIONAL ARCHITECTURE
AB Molkov YI, Abdala APL, Bacak BJ, Smith JC, Paton JFR, Rybak IA. Late-expiratory activity: emergence and interactions with the respiratory CPG. J Neurophysiol 104: 2713-2729, 2010. First published September 8, 2010; doi:10.1152/jn.00334.2010. The respiratory rhythm and motor pattern are hypothesized to be generated by a brain stem respiratory network with a rhythmogenic core consisting of neural populations interacting within and between the pre-Botzinger (pre-BotC) and Botzinger (BotC) complexes and controlled by drives from other brain stem compartments. Our previous large-scale computational model reproduced the behavior of this network under many different conditions but did not consider neural oscillations that were proposed to emerge within the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) and drive preinspiratory (or late-expiratory, late-E) discharges in the abdominal motor output. Here we extend the analysis of our previously published data and consider new data on the generation of abdominal late-E activity as the basis for extending our computational model. The extended model incorporates an additional late-E population in RTN/pFRG, representing a source of late-E oscillatory activity. In the proposed model, under normal metabolic conditions, this RTN/pFRG oscillator is inhibited by BotC/pre-BotC circuits, and the late-E oscillations can be released by either hypercapnia-evoked activation of RTN/pFRG or by hypoxia-dependent suppression of RTN/pFRG inhibition by BotC/pre-BotC. The proposed interactions between BotC/pre-BotC and RTN/pFRG allow the model to reproduce several experimentally observed behaviors, including quantal acceleration of abdominal late-E oscillations with progressive hypercapnia and quantal slowing of phrenic activity with progressive suppression of pre-BotC excitability, as well as to predict a release of late-E oscillations by disinhibition of RTN/pFRG under normal conditions. The extended model proposes mechanistic explanations for the emergence of RTN/pFRG oscillations and their interaction with the brain stem respiratory network.
C1 [Molkov, Yaroslav I.; Bacak, Bartholomew J.; Rybak, Ilya A.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA.
[Abdala, Ana P. L.; Paton, Julian F. R.] Univ Bristol, Sch Med Sci, Bristol Heart Inst, Dept Physiol & Pharmacol, Bristol BS8 1TD, Avon, England.
[Smith, Jeffrey C.] Natl Inst Neurol Disorders & Stroke, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD USA.
RP Rybak, IA (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, 2900 Queen Ln, Philadelphia, PA 19129 USA.
EM rybak@drexel.edu
RI Abdala, Ana Paula/G-9104-2014;
OI Abdala, Ana Paula/0000-0001-6051-2591; Paton, Julian/0000-0001-7410-2913
FU National Institute of Neurological Disorders and Stroke [R01 NS-057815];
NIH, NINS; Royal Society
FX This study was supported by National Institute of Neurological Disorders
and Stroke Grant R01 NS-057815 to I. A. Rybak and in part by the
Intramural Research Program of the NIH, NINS funding to J. C. Smith.
J.F.R. Paton is the recipient of a Royal Society Wolfson Research Merit
Award.
NR 73
TC 43
Z9 43
U1 0
U2 10
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD NOV
PY 2010
VL 104
IS 5
BP 2713
EP 2729
DI 10.1152/jn.00334.2010
PG 17
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 695SD
UT WOS:000285392000036
PM 20884764
ER
PT J
AU Kelly, TAN
Katagiri, Y
Vartanian, KB
Kumar, P
Chen, II
Rosoff, WJ
Urbach, JS
Geller, HM
AF Kelly, Terri-Ann N.
Katagiri, Yasuhiro
Vartanian, Keri B.
Kumar, Pramukta
Chen, Inn-Inn
Rosoff, William J.
Urbach, Jeffery S.
Geller, Herbert M.
TI Localized Alteration of Microtubule Polymerization in Response to
Guidance Cues
SO JOURNAL OF NEUROSCIENCE RESEARCH
LA English
DT Article
DE axonal guidance; CSPG; EB3; particle tracking; PC12 cells; NGF
ID CHONDROITIN SULFATE PROTEOGLYCANS; NERVE GROWTH-FACTOR;
SPINAL-CORD-INJURY; NEURITE OUTGROWTH; AXONAL GROWTH; PHEOCHROMOCYTOMA
CELLS; QUANTITATIVE-ANALYSIS; CONE GUIDANCE; NEURONS; RHO
AB Inhibition of microtubule dynamic instability prevents growth cone turning in response to guidance cues, yet specific changes in microtubule polymerization as growth cones encounter boundaries have not been investigated. In this study, we examined the rate and direction of microtubule polymerization in response to soluble nerve growth factor (NGF) and immobilized chondroitin sulfate proteoglycans (CSPGs) by expressing enhanced GFP-EB3 in rat pheochromocytoma (PC12) cells. GFP-EB3 comets were monitored in live cells using time-lapse epifluorescent microscopy. With an automated tracking system, the rate of microtubule polymerization was calculated as the frame-to-frame displacement of EB3 comets. Our results demonstrate that the rate of microtubule polymerization is increased following NGF treatment, whereas contact with CSPGs decreases microtubule polymerization rates. This reduction in microtubule polymerization rates was specifically localized to neurites in direct contact with CSPGs and not at noncontacting neurites. Additionally, we found an increase in the percentage of microtubules polymerizing in the retrograde direction in neurites at CSPG boundaries, with a concomitant decrease in the rate of retrograde microtubule polymerization. These results implicate localized changes in microtubule dynamics as an important component of the growth cone response to guidance cues. (c) 2010 Wiley-Liss, Inc.
C1 [Kelly, Terri-Ann N.; Katagiri, Yasuhiro; Vartanian, Keri B.; Chen, Inn-Inn; Geller, Herbert M.] NHLBI, Dev Neurobiol Sect, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
[Kelly, Terri-Ann N.; Kumar, Pramukta; Rosoff, William J.; Urbach, Jeffery S.] Georgetown Univ, Dept Phys, Washington, DC 20057 USA.
RP Geller, HM (reprint author), NHLBI, Dev Neurobiol Sect, Cell Biol & Physiol Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM geller@helix.nih.gov
OI Urbach, Jeffrey/0000-0002-1593-520X; Geller, Herbert/0000-0002-7048-6144
FU Intramural NIH HHS [ZIA HL006021-01]
NR 51
TC 15
Z9 17
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0360-4012
J9 J NEUROSCI RES
JI J. Neurosci. Res.
PD NOV 1
PY 2010
VL 88
IS 14
BP 3024
EP 3033
DI 10.1002/jnr.22478
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 662GK
UT WOS:000282795200004
PM 20806407
ER
PT J
AU Chen, ZY
Wang, L
Asavaritkrai, P
Noguchi, CT
AF Chen, Zhi-Yong
Wang, Li
Asavaritkrai, Pundit
Noguchi, Constance Tom
TI Up-Regulation of Erythropoietin Receptor by Nitric Oxide Mediates
Hypoxia Preconditioning
SO JOURNAL OF NEUROSCIENCE RESEARCH
LA English
DT Article
DE erythropoietin; nitric oxide; hypoxia; neuroprotection; receptor
expression
ID NF-KAPPA-B; RETINAL DEGENERATION; CEREBRAL-ISCHEMIA; TRANSGENIC MICE;
ACUTE STROKE; IN-VITRO; EXPRESSION; BRAIN; PROTECTS; NEUROPROTECTION
AB Erythropoietin (Epo), known to stimulate erythroid progenitor cell survival, proliferation, and differentiation, has been shown to be neuroprotective against brain ischemia in animal models. Both Epo and Epo receptor (EpoR) are expressed in the brain and are up-regulated by hypoxia. Brain Epo signaling can stimulate neural cell survival and prevent neuron apoptosis. Neurons from EpoR null mice exhibit marked increased sensitivity to hypoxia. In endothelial cells, Epo has been shown to stimulate nitric oxide (NO) production, particularly at low pO(2). We found here that the EpoR expression on neural cells and Epo's neuroprotective effect were regulated by NO. Hypoxia increased NO production as well as EpoR expression, and inhibition of NOS activity reduced the proportion of EpoR-expressing neurons induced at low pO(2). Conversely, addition of NO donor to cultures grown under normoxia induced EpoR. Similarly, NO donor increased EpoR promoter activity in a reporter gene assay, suggesting that NO regulates EpoR at the transcription level. Preincubation of neurons with NO results in induction of EpoR, which gives rise to protection against hypoxia even in the absence of exogenous Epo, although at high concentration NO is toxic. These data provide evidence of a role for NO in Epo activity in brain and suggest links between NO production, EpoR expression, and Epo signaling in neuroprotection. Published 2010 Wiley-Liss, Inc.(dagger)
C1 [Chen, Zhi-Yong; Wang, Li; Asavaritkrai, Pundit; Noguchi, Constance Tom] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
RP Noguchi, CT (reprint author), NIDDK, Mol Med Branch, NIH, Bldg 10,Room 9N319,10 Ctr Dr,MSC 1822, Bethesda, MD 20892 USA.
EM cnoguchi@helix.nih.gov
NR 40
TC 12
Z9 14
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0360-4012
J9 J NEUROSCI RES
JI J. Neurosci. Res.
PD NOV 1
PY 2010
VL 88
IS 14
BP 3180
EP 3188
DI 10.1002/jnr.22473
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 662GK
UT WOS:000282795200019
PM 20806411
ER
PT J
AU Niu, G
Chen, XY
AF Niu, Gang
Chen, Xiaoyuan
TI Apoptosis Imaging: Beyond Annexin V
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE apoptosis; molecular imaging; phosphatidylserine; caspases; optical
imaging; PET
AB Induction of apoptosis is the primary mechanism through which most chemotherapies cause tumor cell death. Early assessment of tumor response is required to manage patients in terms of quality of life versus intensive chemotherapy. Although imaging with radiolabeled annexin V has been intensively investigated, it is still not sufficiently mature for clinical application. This article will summarize various alternative imaging techniques for visualization of phosphatidylserine externalization, activity of caspases, and mitochondrial membrane potential. Such imaging studies will promote the identification of novel molecular targets and the development of highly specific apoptosis-detecting imaging probes with potential clinical applications. It is highly possible that quantitative imaging of apoptosis will greatly improve clinical decision making in apoptosis-related diseases.
C1 [Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Niu, Gang] Ctr Clin, Imaging Sci Training Program, Bethesda, MD USA.
RP Niu, G (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, 9 Mem Dr,9-1W111, Bethesda, MD 20892 USA.
EM niug@mail.nih.gov; shawn.chen@nih.gov
FU Radiology and Imaging Sciences Department of NIH Clinical Center; NIBIB,
NIH
FX This work is supported in part by an Imaging Sciences Training
Fellowship jointly funded by the Radiology and Imaging Sciences
Department of NIH Clinical Center and by the Intramural Research
Program, NIBIB, NIH. We thank Dr. Henry S. Eden for proofreading the
manuscript.
NR 6
TC 60
Z9 67
U1 0
U2 13
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD NOV
PY 2010
VL 51
IS 11
BP 1659
EP 1662
DI 10.2967/jnumed.110.078584
PG 4
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 674RQ
UT WOS:000283766000029
PM 20956479
ER
PT J
AU Jacobson, O
Weiss, ID
Kiesewetter, DO
Farber, JM
Chen, XY
AF Jacobson, Orit
Weiss, Ido D.
Kiesewetter, Dale O.
Farber, Joshua M.
Chen, Xiaoyuan
TI PET of Tumor CXCR4 Expression with 4-F-18-T140
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE T140 peptide; CXCR4; PET; F-18-fluoride
ID CHEMOKINE RECEPTOR CXCR4; CANCER METASTASIS; BREAST-CANCER; BONE-MARROW;
ANTAGONISTS; MICROENVIRONMENT; CELLS; XENOGRAFTS; GROWTH; T140
AB Expression of the chemokine receptor CXCR4 by cancers has been shown to correlate with tumor aggressiveness and poor prognosis and may also contribute to metastatic seeding of organs that express its ligand SDF-1. However, fully optimized PET agents for determining CXCR4 expression by tumor cells in vivo are not yet available. This study aims to develop a stable, F-18-labeled peptide that enables in vivo quantification of CXCR4 in cancer. Methods: 4-F-benzoyl-TN14003 (4-F-T140), a short peptide antagonist of CXCR4 with 1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl protecting groups on the E-amino groups of the lysine residues, was labeled with F-18-fluoride via N-succinimidyl-4-F-18-fluorobenzoate conjugation, followed by deprotection to give 4-F-18-T140 that was exclusively labeled on the alpha-amine at the N terminus. Cell binding, migration, biodistribution, and small-animal PET studies of 4-F-18-T140 were performed. Results: 4-F-T140 was radiolabeled by coupling with N-succinimidyl-4-F-18-fluorobenzoate, with an overall decay-corrected radiochemical yield of 15% +/- 5% calculated from the start of synthesis. The mean measured specific activity (+/- SD) was 7 +/- 2 GBq/mu mol (0.19 +/- 0.05 Ci/mu mol), and radiochemical purity was greater than 99%. 4-F-18-T140 was found to bind specifically to red blood cells in vitro and in vivo. The binding of 4-F-18-T140 to red blood cells was blocked with a small amount of cold 4-F-T140, which led to higher uptake of 4-F-18-T140 by Chinese hamster ovarian (CHO)-CXCR4 tumors. Biodistribution experiments at 3 h after injection with the addition of 10 mu g of cold 4-F-T140 showed a 3.03 +/- 0.31 percentage injected dose per gram uptake in CHO-CXCR4 tumors, with a tumor-to-blood ratio of 27.1 +/- 8.7 and a tumor-to-muscle ratio of 21.6 +/- 7.1. PET studies demonstrated clear visualization of CXCR4-transfected, but not CXCR4-negative, CHO tumors. Conclusion: 4-F-18-T140 can be used as a PET tracer to image tumor expression of CXCR4, with a high tumor-to-background ratio. The knowledge of whether tumors express or do not express CXCR4 might be beneficial in determining appropriate treatment and monitoring.
C1 [Jacobson, Orit; Kiesewetter, Dale O.; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Weiss, Ido D.; Farber, Joshua M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed, NIH, Bldg 31,Room 1C22,31 Ctr Dr MSC 2281, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
FU National Institute of Biomedical Imaging and Bioengineering (NIBIB);
National Institute of Allergy and Infectious Diseases (NIAID) of the
National Institutes of Health (NIH)
FX We thank Dr. Amnon Peled from Hadassah-Hebrew University Medical Center,
Jerusalem, Israel, for fruitful discussions. We also thank Dr. Henry S.
Eden for proof-reading this manuscript. This research was supported by
the Intramural Research Program (IRP) of the National Institute of
Biomedical Imaging and Bioengineering (NIBIB) and the National Institute
of Allergy and Infectious Diseases (NIAID) of the National Institutes of
Health (NIH).
NR 33
TC 44
Z9 45
U1 0
U2 18
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD NOV
PY 2010
VL 51
IS 11
BP 1796
EP 1804
DI 10.2967/jnumed.110.079418
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 674RQ
UT WOS:000283766000048
PM 20956475
ER
PT J
AU Kalisch, BJ
Lee, H
Rochman, M
AF Kalisch, Beatrice J.
Lee, Hyunhwa
Rochman, Monica
TI Nursing staff teamwork and job satisfaction
SO JOURNAL OF NURSING MANAGEMENT
LA English
DT Article
DE job satisfaction; nurse staffing; nursing assistant; nursing teamwork;
registered nurse
ID REGISTERED NURSES; WORK; CARE; PERCEPTIONS; ASSISTANTS; TURNOVER;
SUPPORT; AGE; METAANALYSIS; ATTITUDES
AB Aim The aim of the present study was to explore the influence of unit characteristics, staff characteristics and teamwork on job satisfaction with current position and occupation.
Background Teamwork has been associated with a higher level of job satisfaction but few studies have focused on the acute care inpatient hospital nursing team. Methods This was a cross-sectional study with a sample of 3675 nursing staff from five hospitals and 80 patient care units. Participants completed the Nursing Teamwork Survey (NTS).
Results Participants' levels of job satisfaction with current position and satisfaction with occupation were both higher when they rated their teamwork higher (P < 0.001) and perceived their staffing as adequate more often (P < 0.001). Type of unit influenced both satisfaction variables (P < 0.05). Additionally, education, gender and job title influenced satisfaction with occupation (P < 0.05) but not with current position.
Conclusions Results of this present study demonstrate that within nursing teams on acute care patient units, a higher level of teamwork and perceptions of adequate staffing leads to greater job satisfaction with current position and occupation.
Implications for Nursing Management Findings suggest that efforts to improve teamwork and ensure adequate staffing in acute care settings would have a major impact on staff satisfaction.
C1 [Kalisch, Beatrice J.; Rochman, Monica] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA.
[Kalisch, Beatrice J.; Lee, Hyunhwa] NINR, NIH, Div Intramural Res, Bethesda, MD 20892 USA.
RP Kalisch, BJ (reprint author), Univ Michigan, Sch Nursing, 400 N Ingalls St, Ann Arbor, MI 48109 USA.
EM bkalisch@umich.edu
FU Michigan Center for Health Intervention, University of Michigan School
of Nursing; National Institutes of Health, National Institute of Nursing
Research [P30 NR009000]
FX This project was funded by The Michigan Center for Health Intervention,
University of Michigan School of Nursing, National Institutes of Health,
National Institute of Nursing Research (P30 NR009000).
NR 53
TC 47
Z9 51
U1 7
U2 34
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0966-0429
J9 J NURS MANAGE
JI J. Nurs. Manag.
PD NOV
PY 2010
VL 18
IS 8
SI SI
BP 938
EP 947
DI 10.1111/j.1365-2834.2010.01153.x
PG 10
WC Management; Nursing
SC Business & Economics; Nursing
GA 680ZB
UT WOS:000284274900007
PM 21073567
ER
PT J
AU Yetley, EA
Pfeiffer, CM
Schleicher, RL
Phinney, KW
Lacher, DA
Christakos, S
Eckfeldt, JH
Fleet, JC
Howard, G
Hoofnagle, AN
Hui, SL
Lensmeyer, GL
Massaro, J
Peacock, M
Rosner, B
Wiebe, D
Bailey, RL
Coates, PM
Looker, AC
Sempos, C
Johnson, CL
Picciano, MF
AF Yetley, Elizabeth A.
Pfeiffer, Christine M.
Schleicher, Rosemary L.
Phinney, Karen W.
Lacher, David A.
Christakos, Sylvia
Eckfeldt, John H.
Fleet, James C.
Howard, George
Hoofnagle, Andrew N.
Hui, Siu L.
Lensmeyer, Gary L.
Massaro, Joseph
Peacock, Munro
Rosner, Bernard
Wiebe, Donald
Bailey, Regan L.
Coates, Paul M.
Looker, Anne C.
Sempos, Christopher
Johnson, Clifford L.
Picciano, Mary Frances
CA Vitamin D Roundtable NHANES
TI NHANES Monitoring of Serum 25-Hydroxyvitamin D: A Roundtable Summary
SO JOURNAL OF NUTRITION
LA English
DT Article; Proceedings Paper
CT Conference on NHANES Monitoring of Serum 25(OH)D - Assay Challenges and
Options for Resolving Them
CY JUL 27-28, 2009
CL Rockville, MD
ID TANDEM MASS-SPECTROMETRY; CIRCULATING 25-HYDROXYVITAMIN-D; ASSAYS;
ACCURACY; STANDARDIZATION; DISEASE; D-3
AB A roundtable to discuss monitoring of serum 25-hydroxyvitamin D [25(OH)D] in the NHANES was held in late July 2009. Topics included the following: 1) options for dealing with assay fluctuations in serum 25(OH)D in the NHANES conducted between 1988 and 2006; 2) approaches for transitioning between the RIA used in the NHANES between 1988 and 2006 to the liquid chromatography tandem MS (LC-MS/MS) measurement procedure to be used in NHANES 2007 and later; 31 approaches for integrating the recently available standard reference material for vitamin D in human serum (SAM 972) from the National Institute of Standards and Technology (NIST) into the NHANES; 41 questions regarding whether the C-3 epimer of 25-hydroxyvitamin D3 [3-epi-25(OH)D3] should be measured in NHANES 2007 and later; and 5) identification of research and educational needs. The roundtable experts agreed that the NHANES data needed to be adjusted to control for assay fluctuations and offered several options for addressing this issue. The experts suggested that the LC-MS/MS measurement procedure developed by NIST could serve as a higher order reference measurement procedure. They noted the need for a commutability study for the recently released NIST SRM 972 across a range of measurement procedures. They suggested that federal agencies and professional organizations work with manufacturers to improve the quality and comparability of measurement procedures across all laboratories. The experts noted the preliminary nature of the evidence of the 3-epi-25(OH)D3 but felt that it should be measured in 2007 NHANES and later. J. Nutr. 140: 2030S-2045S, 2010.
C1 [Yetley, Elizabeth A.; Bailey, Regan L.; Coates, Paul M.; Sempos, Christopher; Picciano, Mary Frances] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Pfeiffer, Christine M.; Schleicher, Rosemary L.] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA.
[Phinney, Karen W.] NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA.
[Lacher, David A.; Looker, Anne C.; Johnson, Clifford L.] Ctr Dis Control & Prevent, Div Hlth & Nutr Examinat Surveys, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Christakos, Sylvia] Univ Med & Dent New Jersey, Dept Biochem & Mol Biol, Newark, NJ 07103 USA.
[Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Fleet, James C.] Purdue Univ, Dept Foods & Nutr, W Lafayette, IN 47906 USA.
[Howard, George] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA.
[Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Hui, Siu L.; Peacock, Munro] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA.
[Lensmeyer, Gary L.] Univ Wisconsin Hosp & Clin, Clin Toxicol Lab, Madison, WI 53792 USA.
[Massaro, Joseph] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Rosner, Bernard] Harvard Univ, Channing Lab, Harvard Med Sch, Boston, MA 02155 USA.
[Wiebe, Donald] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53792 USA.
RP Yetley, EA (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA.
EM beth@yetley.com
OI Fleet, James/0000-0002-0142-9517
FU NIDDK NIH HHS [R01 DK038961, R01 DK038961-22]
NR 40
TC 62
Z9 64
U1 1
U2 6
PU AMER SOC NUTRITIONAL SCIENCE
PI BETHESDA
PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD NOV
PY 2010
VL 140
IS 11
BP 2030S
EP 2045S
DI 10.3945/jn.110.121483
PG 16
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 671RD
UT WOS:000283525700020
PM 20881084
ER
PT J
AU Koutros, S
Alavanja, MCR
Lubin, JH
Sandler, DP
Hoppin, JA
Lynch, CF
Knott, C
Blair, A
Freeman, LEB
AF Koutros, Stella
Alavanja, Michael C. R.
Lubin, Jay H.
Sandler, Dale P.
Hoppin, Jane A.
Lynch, Charles F.
Knott, Charles
Blair, Aaron
Freeman, Laura E. Beane
TI An Update of Cancer Incidence in the Agricultural Health Study
SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID FARMER PESTICIDE APPLICATORS; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA;
PHYSICAL-ACTIVITY; OCCUPATIONAL-EXPOSURE; LUNG-CANCER; PROSTATE-CANCER;
CUTANEOUS MELANOMA; MULTIPLE-MYELOMA; LIP CANCER
AB Objective: Our objective is to reevaluate cancer incidence among Agricultural Health Study participants. Methods: Standardized incidence ratios (SIRs) and relative standardized ratios were calculated. Results: A significant excess of prostate cancer was seen for private and commercial applicators (SIR = 1.19, 95% CI 1.14, 1.25 and SIR = 1.28, 95% CI = 1.00, 1.61, respectively). Excesses were observed for lip cancer (SIR = 1.97, 95% CI = 1.02, 3.44) and multiple myeloma (SIR = 1.42, 95% CI = 1.00, 1.95) among private applicators from North Carolina and for marginal zone lymphoma among Iowa spouses (SIR = 2.34, 95% CI = 1.21, 4.09). Conclusions: Although lower rates of smoking and increased physical activity probably contribute to the lower overall cancer incidence, agricultural exposures including pesticides, viruses, bacteria, sunlight, and other chemicals may increase risks for specific cancer sites.
C1 [Koutros, Stella] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Sandler, Dale P.; Hoppin, Jane A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA.
[Knott, Charles] Battelle Mem Inst, Durham, NC USA.
RP Koutros, S (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8115,MSC 7240, Rockville, MD 20852 USA.
EM koutross@mail.nih.gov
OI Sandler, Dale/0000-0002-6776-0018
FU NIH, National Cancer Institute, Division of Cancer Epidemiology and
Genetics [Z01CP010119]; National Institute of Environmental Health
Sciences [Z01ES049030]
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Division of Cancer Epidemiology and
Genetics (Z01CP010119) and National Institute of Environmental Health
Sciences (Z01ES049030).
NR 71
TC 62
Z9 62
U1 1
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1076-2752
J9 J OCCUP ENVIRON MED
JI J. Occup. Environ. Med.
PD NOV
PY 2010
VL 52
IS 11
BP 1098
EP 1105
DI 10.1097/JOM.0b013e3181f72b7c
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 678GD
UT WOS:000284061200006
PM 21063187
ER
PT J
AU Wang, J
Iannotti, RJ
Luk, JW
Nansel, TR
AF Wang, Jing
Iannotti, Ronald J.
Luk, Jeremy W.
Nansel, Tonja R.
TI Co-occurrence of Victimization from Five Subtypes of Bullying: Physical,
Verbal, Social Exclusion, Spreading Rumors, and Cyber
SO JOURNAL OF PEDIATRIC PSYCHOLOGY
LA English
DT Article
DE cyber victimization; latent class analysis; physical and psychological
problems; victimization
ID LATENT CLASS ANALYSIS; PEER VICTIMIZATION; INDIRECT AGGRESSION; SCHOOL;
ADOLESCENTS; PREVALENCE; ASSOCIATION; INVOLVEMENT; ADJUSTMENT; CHILDREN
AB Objective To examine co-occurrence of five subtypes of peer victimization. Methods Data were obtained from a national sample of 7,475 US adolescents in grades 6 through 10 in the 2005/2006 Health Behavior in School-Aged Children (HBSC) study. Latent class analyses (LCA) were conducted on victimization by physical, verbal, social exclusion, spreading rumors, and cyber bullying. Results Three latent classes were identified, including an all-types victims class (9.7% of males and 6.2% of females), a verbal/relational victims class (28.1% of males and 35.1% of females), and a nonvictim class (62.2% of males and 58.7% of females). Males were more likely to be all-type victims. There was a graded relationship between the three latent classes and level of depression, frequency of medically attended injuries, and medicine use, especially among females. Conclusions Increased co-occurrence of victimization types put adolescents at greater risks for poorer physical and psychological outcomes.
C1 [Wang, Jing] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Bethesda, MD 20892 USA.
[Luk, Jeremy W.] Univ Washington, Seattle, WA 98195 USA.
RP Wang, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, 6100 Bldg Room,7B13 MSC 7510, Bethesda, MD 20892 USA.
EM wangji2@mail.nih.gov
RI castro, teresa/G-2533-2011;
OI castro, teresa/0000-0002-7148-9443; Nansel, Tonja/0000-0002-8298-7595
FU Intramural NIH HHS [Z99 HD999999]
NR 29
TC 74
Z9 78
U1 4
U2 28
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0146-8693
J9 J PEDIATR PSYCHOL
JI J. Pediatr. Psychol.
PD NOV-DEC
PY 2010
VL 35
IS 10
BP 1103
EP 1112
DI 10.1093/jpepsy/jsq048
PG 10
WC Psychology, Developmental
SC Psychology
GA 666MI
UT WOS:000283119100005
PM 20488883
ER
PT J
AU Davis, AS
Hintz, SR
Van Meurs, KP
Li, L
Das, A
Stoll, BJ
Walsh, MC
Pappas, A
Bell, EF
Laptook, AR
Higgins, RD
AF Davis, Alexis S.
Hintz, Susan R.
Van Meurs, Krisa P.
Li, Lei
Das, Abhik
Stoll, Barbara J.
Walsh, Michele C.
Pappas, Athina
Bell, Edward F.
Laptook, Abbot R.
Higgins, Rosemary D.
CA Eunice Kennedy Shriver Natl Inst C
TI Seizures in Extremely Low Birth Weight Infants Are Associated with
Adverse Outcome
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID NEONATAL SEIZURES; ELECTROGRAPHIC SEIZURES; DEVELOPING BRAIN; PRETERM
INFANTS; CEREBRAL-PALSY; UNITED-STATES; AGE; CHILDREN; RISK
AB Objective To examine risk factors for neonatal clinical seizures and to determine the independent association with death or neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants.
Study design A total of 6499 ELBW infants (401-1000 g) surviving to 36 weeks postmenstrual age (PMA) were included in this retrospective study. Unadjusted comparisons were performed between infants with (n = 414) and without (n = 6085) clinical seizures during the initial hospitalization. Using multivariate logistic regression modeling, we examined the independent association of seizures with late death (after 36 weeks PMA) or NDI after controlling for multiple demographic, perinatal, and neonatal variables.
Results Infants with clinical seizures had a greater proportion of neonatal morbidities associated with poor outcome, including severe intraventricular hemorrhage, sepsis, meningitis, and cystic periventricular leukomalacia (all P < .01). Survivors were more likely to have NDI or moderate-severe cerebral palsy at 18 to 22 months corrected age (both P < .01). After adjusting for multiple confounders, clinical seizures remained significantly associated with late death or NDI (odds ratio, 3.15; 95% CI, 2.37-4.19).
Conclusion ELBW infants with clinical seizures are at increased risk for adverse neurodevelopmental outcome, independent of multiple confounding factors. (J Pediatr 2010; 157: 720-5).
C1 [Davis, Alexis S.; Hintz, Susan R.; Van Meurs, Krisa P.] Stanford Univ, Div Neonatal Dev Med, Stanford, CA 94305 USA.
[Li, Lei] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Walsh, Michele C.] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA.
[Pappas, Athina] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Bell, Edward F.] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA.
[Laptook, Abbot R.] Brown Univ, Dept Pediat, Providence, RI 02912 USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA.
RP Davis, AS (reprint author), Stanford Univ, Sch Med, Div Neonatol, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA.
EM alexis.davis@stanford.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD)
FX Supported by the National Institutes of Health and the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
for the Neonatal Research Network's Generic Database Study and Follow-up
Study. The authors declare no conflicts of interest.
NR 34
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U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD NOV
PY 2010
VL 157
IS 5
BP 720
EP U47
DI 10.1016/j.jpeds.2010.04.065
PG 8
WC Pediatrics
SC Pediatrics
GA 665OS
UT WOS:000283045900008
PM 20542294
ER
PT J
AU Mittal, P
Romero, R
Tarca, AL
Gonzalez, J
Draghici, S
Xu, Y
Dong, Z
Nhan-Chang, CL
Chaiworapongsa, T
Lye, S
Kusanovic, JP
Lipovich, L
Mazaki-Tovi, S
Hassan, SS
Mesiano, S
Kim, CJ
AF Mittal, Pooja
Romero, Roberto
Tarca, Adi L.
Gonzalez, Juan
Draghici, Sorin
Xu, Yi
Dong, Zhong
Nhan-Chang, Chia-Ling
Chaiworapongsa, Tinnakorn
Lye, Stephen
Kusanovic, Juan Pedro
Lipovich, Leonard
Mazaki-Tovi, Shali
Hassan, Sonia S.
Mesiano, Sam
Kim, Chong Jai
TI Characterization of the myometrial transcriptome and biological pathways
of spontaneous human labor at term
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Article
DE Aldehyde dehydrogenase (ALDH2); chemokine C-C motif ligand 2
(CCL2/MCP-1); chemokine C-X-C motif ligand 6 (CXCL6/GCP2); FK506
binding-protein 5 (FKBP5); heparin binding EGF-like growth factor
(HBEGF); inflammasome; inflammation; interleukin (IL)-6,-8; leukocyte
immunoglobulin-like receptor, subfamily A, member 5 (LIL-RA5/LIR9);
microarray; nuclear factor of kappa light chain gene enhancer in B-cells
inhibitor zeta (NFKBIZ); parturition; pregnancy; progesterone;
prostaglandin-endoperoxide synthase-2 (PTGS2/COX2); suppressor of
cytokine signaling 3 (SOCS3); systems biology
ID HUMAN-FETAL MEMBRANES; SMOOTH-MUSCLE-CELLS; FACTOR-KAPPA-B;
TUMOR-NECROSIS-FACTOR; FUNCTIONAL PROGESTERONE WITHDRAWAL;
CORTICOTROPIN-RELEASING HORMONE; SPONTANEOUS PRETERM LABOR; INFLAMMATORY
RESPONSE SYNDROME; AMNIOTIC-FLUID INTERLEUKIN-6; MESSENGER-RNA
EXPRESSION
AB Aims: To characterize the transcriptome of human myometrium during spontaneous labor at term.
Methods: Myometrium was obtained from women with (n=19) and without labor (n=20). Illumina (R) HumanHT-12 microarrays were utilized. Moderated t-tests and false discovery rate adjustment of P-values were applied. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for a select set of differentially expressed genes in a separate set of samples. Enzyme-linked immunosorbent assay and Western blot were utilized to confirm differential protein production in a third sample set.
Results: 1) Four hundred and seventy-one genes were differentially expressed; 2) gene ontology analysis indicated enrichment of 103 biological processes and 18 molecular functions including: a) inflammatory response; b) cytokine activity; and c) chemokine activity; 3) systems biology pathway analysis using signaling pathway impact analysis indicated six significant pathways: a) cytokine-cytokine receptor interaction; b) Jak-STAT signaling; and c) complement and coagulation cascades; d) NOD-like receptor signaling pathway; e) systemic lupus erythematosus; and f) chemokine signaling pathway; 4) qRT-PCR confirmed over-expression of prostaglandin-endoperoxide synthase-2, heparin binding epidermal growth factor (EGF)-like growth factor, chemokine C-C motif ligand 2 (CCL2/MCP1), leukocyte immunoglobulin-like receptor, subfamily A member 5, interleukin (IL)-8, IL-6, chemokine C-X-C motif ligand 6 (CXCL6/GCP2), nuclear factor of kappa light chain gene enhancer in B-cells inhibitor zeta, suppressor of cytokine signaling 3 (SOCS3) and decreased expression of FK506 binding-protein 5 and aldehyde dehydrogenase in labor; 5) IL-6, CXCL6, CCL2 and SOCS3 protein expression was significantly higher in the term labor group compared to the term not in labor group.
Conclusions: Myometrium of women in spontaneous labor at term is characterized by a stereotypic gene expression pattern consistent with over-expression of the inflammatory response and leukocyte chemotaxis. Differential gene expression identified with microarray was confirmed with qRT-PCR using an independent set of samples. This study represents an unbiased description of the biological processes involved in spontaneous labor at term based on transcriptomics.
C1 [Mittal, Pooja; Romero, Roberto; Tarca, Adi L.; Gonzalez, Juan; Draghici, Sorin; Xu, Yi; Dong, Zhong; Nhan-Chang, Chia-Ling; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Hassan, Sonia S.; Kim, Chong Jai] Wayne State Univ, Hutzel Womens Hosp, NICHD, Perinatol Res Branch,NIH,DHHS, Detroit, MI 48201 USA.
[Mittal, Pooja; Romero, Roberto; Tarca, Adi L.; Gonzalez, Juan; Draghici, Sorin; Xu, Yi; Dong, Zhong; Nhan-Chang, Chia-Ling; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Hassan, Sonia S.; Kim, Chong Jai] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Mittal, Pooja; Romero, Roberto; Gonzalez, Juan; Nhan-Chang, Chia-Ling; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, Roberto; Tarca, Adi L.; Lipovich, Leonard] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Tarca, Adi L.; Draghici, Sorin] Wayne State Univ, Sch Med, Dept Comp Sci, Detroit, MI 48201 USA.
[Lye, Stephen] Univ Toronto, Dept Obstet & Gynecol, Toronto, ON, Canada.
[Lipovich, Leonard] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA.
[Mesiano, Sam] Case Western Reserve Univ, Dept Reprod Biol, Cleveland, OH 44106 USA.
[Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA.
RP Mittal, P (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, Perinatol Res Branch,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM pmittal@med.wayne.edu; prbchiefstaff@med.wayne.edu
RI Draghici, Sorin/B-3074-2013; Lye, Stephen/E-7269-2013
OI Draghici, Sorin/0000-0002-0786-8377;
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. We wish to
thank Dr. Susan Land and Dan Lott at the Applied Genomics Technology
Center of Wayne State University for performing the microarrays and to
acknowledge the contributions of the nursing staff of the Perinatology
Research Branch and Hutzel Women's Hospital.
NR 343
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U2 19
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0300-5577
EI 1619-3997
J9 J PERINAT MED
JI J. Perinat. Med.
PD NOV
PY 2010
VL 38
IS 6
BP 617
EP 643
DI 10.1515/JPM.2010.097
PG 27
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 678TB
UT WOS:000284102500010
PM 20629487
ER
PT J
AU Forbes, CE
Schmader, T
AF Forbes, Chad E.
Schmader, Toni
TI Retraining Attitudes and Stereotypes to Affect Motivation and Cognitive
Capacity Under Stereotype Threat
SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY
LA English
DT Article
DE stereotype threat; attitudes; stereotypes; motivation; working memory
ID WOMENS MATH PERFORMANCE; WORKING-MEMORY CAPACITY;
ACHIEVEMENT-MOTIVATION; MERE EFFORT; IMPLICIT; ASSOCIATIONS;
PERSPECTIVE; ACTIVATION; SETTINGS; BEHAVIOR
AB In a series of experiments, a retraining paradigm was used to test the effects of attitudes and stereotypes on individuals' motivation and cognitive capacity in stereotype-threatening contexts. Women trained to have a more positive math attitude exhibited increased math motivation (Study 1). This effect was not observed for men but was magnified among women when negative stereotypes were either primed subtly (Study 2) or indirectly reinforced (Study 3). Although attitudes had no effect on working memory capacity, women retrained to associate their gender with being good at math exhibited increased working memory capacity (Studies 3 and 4), which in turn mediated increased math performance (Study 4) in a stereotype-threatening context. Results suggest that although positive attitudes can motivate stigmatized individuals to engage with threatening domains, stereotypes need to be retrained to give them the cognitive capacity critical for success. Implications for interventions to reduce stereotype threat are discussed.
C1 [Forbes, Chad E.] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA.
[Schmader, Toni] Univ British Columbia, Dept Psychol, Vancouver, BC, Canada.
RP Forbes, CE (reprint author), NIH, Dept Radiol & Imaging Sci, Bldg 10,Room 7D49,10 Ctr Dr, Bethesda, MD 20892 USA.
EM forbesce@cc.nih.gov
FU NIMH NIH HHS [R01 MH071749, 1R01MH071749]
NR 60
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U1 2
U2 36
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-3514
J9 J PERS SOC PSYCHOL
JI J. Pers. Soc. Psychol.
PD NOV
PY 2010
VL 99
IS 5
BP 740
EP 754
DI 10.1037/a0020971
PG 15
WC Psychology, Social
SC Psychology
GA 679WO
UT WOS:000284191700002
PM 20822288
ER
PT J
AU Chattopadhyay, M
Velazquez, CA
Pruski, A
Nia, KV
Abdellatif, KR
Keefer, LK
Kashfi, K
AF Chattopadhyay, Mitali
Velazquez, Carlos A.
Pruski, April
Nia, Kamran V.
Abdellatif, Khaled R.
Keefer, Larry K.
Kashfi, Khosrow
TI Comparison between 3-Nitrooxyphenyl acetylsalicylate (NO-ASA) and
O-2-(acetylsalicyloxymethyl)-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate
(NONO-ASA) as Safe Anti-Inflammatory, Analgesic, Antipyretic,
Antioxidant Prodrugs
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID NITRIC-OXIDE RELEASE; GASTROINTESTINAL SAFETY; BIOLOGICAL EVALUATION;
COLORECTAL-CANCER; ASPIRIN; NSAIDS; DRUGS; RISK; RAT; INFLAMMATION
AB Chronic inflammation is an underlying etiological factor in carcinogenesis; nonsteroidal anti-inflammatory drugs (NSAIDs) and their chemically modified NO-releasing prodrugs (NO-NSAIDs) are promising chemopreventive agents. The aim of this study was to conduct a head-to-head comparison between two NO-ASAs possessing different NO donor groups, an organic nitrate [3-nitrooxyphenyl acetylsalicylate (NO-ASA; NCX-4016)] and an N-diazeniumdiolate [NONO-ASA, O-2-(acetylsalicyloxymethyl)-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (NONO-ASA; CVM-01)], as antiulcerogenic, analgesic, anti-inflammatory, and antipyretic agents. All drugs were administered orally at equimolar doses. For antiulcerogenic study, 6 h after administration, the number and size of hemorrhagic lesions in stomachs from euthanized animals were counted. Tissue samples were frozen for prostaglandin E-2 (PGE(2)), superoxide dismutase (SOD), and malondialdehyde determination. For anti-inflammatory study, 1 h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 6 h. For antipyretic study, 1 h after dosing, fever was induced by intraperitoneal LPS, and body core temperatures measured for 5 h. For analgesic study, time-dependent analgesic effect of prodrugs was evaluated by carrageenan-induced hyperalgesia. Drugs were administered 30 min after carrageenan. NO-ASA and NONO-ASA were equipotent as analgesic and anti-inflammatory agents but were better than aspirin. Despite a drastic reduction of PGE(2) in stomach tissue, both prodrugs were devoid of gastric side effects. Lipid peroxidation induced by aspirin was higher than that observed by prodrugs. SOD activity induced by both prodrugs was similar, but approximately 2-fold higher than that induced by aspirin. CVM-01 is as effective as NCX-4016 in anti-inflammatory, analgesic, and antipyretic assays in vivo, and it showed an equivalent safety profile in the stomach. These results underscore the use of N-diazeniumdiolate moieties in drug design.
C1 [Chattopadhyay, Mitali; Pruski, April; Nia, Kamran V.; Kashfi, Khosrow] CUNY, Dept Physiol & Pharmacol, Sch Med, New York, NY 10031 USA.
[Velazquez, Carlos A.; Abdellatif, Khaled R.] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada.
[Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA.
RP Kashfi, K (reprint author), CUNY, Dept Physiol & Pharmacol, Sch Med, 138th St & Convent Ave, New York, NY 10031 USA.
EM kashfi@med.cuny.edu
RI Keefer, Larry/N-3247-2014;
OI Keefer, Larry/0000-0001-7489-9555; Abdellatif,
Khaled/0000-0002-5815-9677
FU National Institutes of Health National Cancer Institute, Division of
Basic Sciences, Center for Cancer Research [ZIA-BC005673]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health National Cancer Institute, Division of
Basic Sciences, Center for Cancer Research [Project ZIA-BC005673].
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U2 6
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD NOV
PY 2010
VL 335
IS 2
BP 443
EP 450
DI 10.1124/jpet.110.171017
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 666TM
UT WOS:000283143200020
PM 20679133
ER
PT J
AU Banks, ML
Rice, KC
Negus, SS
AF Banks, Matthew L.
Rice, Kenner C.
Negus, S. Stevens
TI Antinociceptive Interactions between Mu-Opioid Receptor Agonists and the
Serotonin Uptake Inhibitor Clomipramine in Rhesus Monkeys: Role of Mu
Agonist Efficacy
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID TAIL-WITHDRAWAL PROCEDURE; FORMALIN TEST; THERMAL HYPERALGESIA; PAIN
MODULATION; SPINAL-CORD; MORPHINE; RATS; NOCICEPTION; ANALGESIA;
PATHWAYS
AB Mu-opioid agonists are effective analgesics but have undesirable effects such as sedation and abuse liability that limit their clinical effectiveness. Serotonergic systems also modulate nociception, and serotonin uptake inhibitors may be useful as adjuncts to enhance analgesic effects and/or attenuate undesirable effects of mu agonists. This study examined the effects of the serotonin uptake inhibitor clomipramine on behavioral effects produced in rhesus monkeys by mu agonists with varying efficacy at mu receptors (nalbuphine < morphine < methadone). Clomipramine and each mu agonist were studied alone and in fixed-proportion mixtures in assays of schedule-controlled responding, thermal nociception, and capsaicin-induced thermal allodynia. In the assay of schedule-controlled responding, all mu agonists dose-dependently decreased response rates. Clomipramine was inactive alone and did not alter the effects of mu agonists. In the assay of thermal nociception, all mu agonists produced dose-dependent antinociception. Clomipramine was inactive alone but produced a proportion-dependent enhancement of the antinociceptive effects of nalbuphine > morphine > methadone. In the assay of capsaicin-induced allodynia, nalbuphine produced dose-dependent antiallodynia. Clomipramine alone was inactive, but as in the assay of thermal nociception, it produced a proportion-dependent enhancement in the effects of nalbuphine. These findings suggest that serotonin uptake inhibitors can selectively enhance the antinociceptive effects of mu agonists in nonhuman primates. These effects of serotonin uptake inhibitors may depend on the proportion of the serotonin uptake inhibitor and the efficacy of the mu agonist. The greatest enhancement was observed with intermediate proportions of clomipramine in combination with the low-efficacy mu agonist nalbuphine.
C1 [Banks, Matthew L.; Negus, S. Stevens] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA.
[Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Rice, Kenner C.] NIAAA, NIH, Bethesda, MD USA.
RP Negus, SS (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 N 12th St,POB 980613, Richmond, VA 23298 USA.
EM ssnegus@vcu.edu
RI Banks, Matthew/K-4429-2014
OI Banks, Matthew/0000-0003-4949-5246
FU National Institutes of Health National Institute on Drug Abuse
[R01-DA011460, T32-DA007027]; National Institute on Drug Abuse; National
Institute on Alcohol Abuse and Alcoholism
FX This research was supported by the National Institutes of Health
National Institute on Drug Abuse [Grants R01-DA011460, T32-DA007027];
the Intramural Research Programs of the National Institute on Drug
Abuse; and the National Institute on Alcohol Abuse and Alcoholism.
NR 40
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U1 0
U2 2
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD NOV
PY 2010
VL 335
IS 2
BP 497
EP 505
DI 10.1124/jpet.110.169276
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 666TM
UT WOS:000283143200027
PM 20675432
ER
PT J
AU Spruijt-Metz, D
Troiano, R
Thornquist, M
Sirard, J
Redline, S
Berrigan, D
AF Spruijt-Metz, Donna
Troiano, Richard
Thornquist, Mark
Sirard, John
Redline, Susan
Berrigan, David
TI Objective and Subjective Measures of Physical Activity in Youth:
Emerging Challenges for Analysis and Interpretation
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Meeting Abstract
DE accelerometry; self-report; adolescents; sleep; measurement
ID UNITED-STATES; EXERCISE; SLEEP
C1 [Spruijt-Metz, Donna] Univ So Calif, Los Angeles, CA USA.
[Troiano, Richard; Berrigan, David] NCI, NIH, Bethesda, MD 20892 USA.
[Thornquist, Mark] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Sirard, John] Univ Minnesota, Minneapolis, MN USA.
[Redline, Susan] Case Western Reserve Univ, Cleveland, OH 44106 USA.
NR 5
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U1 0
U2 5
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD NOV
PY 2010
VL 7
SU 3
BP S322
EP S324
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 679RR
UT WOS:000284179000013
ER
PT J
AU Perez-Rodriguez, MM
Weinstein, S
New, AS
Bevilacqua, L
Yuan, QP
Zhou, ZF
Hodgkinson, C
Goodman, M
Koenigsberg, HW
Goldman, D
Siever, LJ
AF Perez-Rodriguez, M. Mercedes
Weinstein, Shauna
New, Antonia S.
Bevilacqua, Laura
Yuan, Qiaoping
Zhou, Zhifeng
Hodgkinson, Colin
Goodman, Marianne
Koenigsberg, Harold W.
Goldman, David
Siever, Larry J.
TI Tryptophan-hydroxylase 2 haplotype association with borderline
personality disorder and aggression in a sample of patients with
personality disorders and healthy controls
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Borderline personality disorder; TPH2; Suicidal behavior; Affective
instability; Impulsive aggression
ID CENTRAL SEROTONERGIC FUNCTION; ISOFORM TPH2 GENE; IMPULSIVE-AGGRESSION;
PROLACTIN RESPONSE; D-FENFLURAMINE; CEREBROSPINAL-FLUID; VIOLENT
OFFENDERS; MAJOR DEPRESSION; TRANSMISSION DISEQUILIBRIUM; POLYMORPHIC
VARIANTS
AB Background There is a decreased serotonergic function in impulsive aggression and borderline personality disorder (BPD) and genetic association studies suggest a role of serotonergic genes in impulsive aggression and BPD Only one study has analyzed the association between the tryptophan-hydroxylase 2 (TPH2) gene and BPD A TPH2 "risk" haplotype has been described that is associated with anxiety depression and suicidal behavior
Methods We assessed the relationship between the previously identified risk" haplotype at the TPH2 locus and BPD diagnosis impulsive aggression affective lability and suicidal/parasuicidal behaviors in a well-characterized clinical sample of 103 healthy controls (HCs) and 251 patients with personality disorders (109 with BPD) A logistic regression including measures of depression affective lability and aggression scores in predicting risk" haplotype was conducted
Results The prevalence of the "risk" haplotype was significantly higher in patients with BPD compared to HCs Those with the "risk" haplotype have higher aggression and affect lability scores and more suicidal/parasuicidal behaviors than those without it In the logistic regression model affect lability was the only significant predictor and it correctly classified 83 1% of the subjects as risk or non-risk haplotype carriers
Conclusions We found an association between the previously described TPH2 risk haplotype and BPD diagnosis affective lability suicidal/parasuicidal behavior and aggression scores (C) 2010 Elsevier Ltd All rights reserved
C1 [Perez-Rodriguez, M. Mercedes; Weinstein, Shauna; New, Antonia S.; Goodman, Marianne; Koenigsberg, Harold W.; Siever, Larry J.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
[Weinstein, Shauna; New, Antonia S.; Goodman, Marianne; Koenigsberg, Harold W.; Siever, Larry J.] James J Peters Vet Affairs Med Ctr, Mental Hlth Patient Care Ctr, Bronx, NY 10468 USA.
[Bevilacqua, Laura; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Siever, LJ (reprint author), James J Peters Vet Adm Med Ctr, 3rd Floor,Room 3B,20 130 W Kingsbridge Rd, Bronx, NY 10468 USA.
RI Perez Rodriguez, Maria/B-9410-2013; Goldman, David/F-9772-2010
OI Perez Rodriguez, Maria/0000-0001-5137-1993; Goldman,
David/0000-0002-1724-5405
FU National Institute of Mental Health [MH56140, MH63875]; Veterans Affairs
[7609-028, 9001-03-0051]; Veterans Affairs VISN 3 Mental Illness
Research Education & Clinical Center; National Center for Research
Resources (NCRR) [MO1-RR-00071]
FX This research was supported by Grants MH56140 & MH63875 from the
National Institute of Mental Health to Larry J Siever by a Veterans
Affairs Merit Review Grant (7609-028) to Larry J Siever and by the
Veterans Affairs VISN 3 Mental Illness Research Education & Clinical
Center; This publication was made possible by Grant Number MO1-RR-00071
from the National Center for Research Resources (NCRR) a component of
the National Institutes of Health (NIH) Its contents are solely the
responsibility of the authors and do not necessarily represent the
official views of NCRR or NIH; This work was supported in part by a VA
Merit award to Dr New (9001-03-0051) New (PI)- Intermediate Phenotypes
for Borderline Personality Disorder and a VA Career Development Award to
Dr Goodman
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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 NOV
PY 2010
VL 44
IS 15
BP 1075
EP 1081
DI 10.1016/j.jpsychires.2010.03.014
PG 7
WC Psychiatry
SC Psychiatry
GA 684RJ
UT WOS:000284566700013
PM 20451217
ER
PT J
AU Matabosch, X
Ying, L
Serra, M
Wassif, CA
Porter, FD
Shackleton, C
Watson, G
AF Matabosch, Xavier
Ying, Lee
Serra, Montserrat
Wassif, Christopher A.
Porter, Forbes D.
Shackleton, Cedric
Watson, Gordon
TI Increasing cholesterol synthesis in 7-dehydrosterol reductase (DHCR7)
deficient mouse models through gene transfer
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE Smith-Lemli-Opitz syndrome (SLOS); DHCR7; AAV; Gene therapy
ID LEMLI-OPITZ-SYNDROME; RECOMBINANT ADENOASSOCIATED VIRUS;
PRENATAL-DIAGNOSIS; SYNDROME SLOS; VII MICE; DIETARY-CHOLESTEROL;
CARRIER FREQUENCY; MASS-SPECTROMETRY; LYSOSOMAL STORAGE; INBORN-ERRORS
AB Smith-Lemli-Opitz syndrome (SLOS) is caused by deficiency in the terminal step of cholesterol biosynthesis: the conversion of 7-dehydrocholesterol (7DHC) to cholesterol (C), catalyzed by 7-dehydrocholesterol reductase (DHCR7). This disorder exhibits several phenotypic traits including dysmorphia and mental retardation with a broad range of severity. There are few proven treatment options. That most commonly used is a high cholesterol diet that seems to enhance the quality of life and improve behavioral characteristics of patients, although these positive effects are controversial. The goal of our study was to investigate the possibility of restoring DHCR7 activity by gene transfer. We constructed an adeno-associated virus (MV) vector containing the DHCR7 gene. After we infused this vector into affected mice, the introduced DHCR7 gene could be identified in liver, mRNA was expressed and a functional enzyme was produced. Evidence of functionality came from the ability to partially normalize the serum ratio of 7DHC/C in treated animals, apparently by increasing cholesterol production with concomitant decrease in 7DHC precursor. By 5 weeks after treatment the mean ratio (for 7 animals) had fallen to 0.05 while the ratio for untreated littermate controls had risen to 0.14. This provides proof of principle that gene transfer can ameliorate the genetic defect causing SLOS and provides a new experimental tool for studying the pathogenesis of this disease. If effective in humans, it might also offer a possible alternative to exogenous cholesterol therapy. However, it would not offer a complete cure for the disorder as many of the negative implications of defective synthesis are already established during prenatal development. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Matabosch, Xavier; Ying, Lee; Serra, Montserrat; Shackleton, Cedric; Watson, Gordon] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA.
[Wassif, Christopher A.; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Shackleton, Cedric] Univ Birmingham, CEDAM, Inst Biomed Res, Birmingham B15 2TT, W Midlands, England.
RP Watson, G (reprint author), Childrens Hosp, Oakland Res Inst, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA.
EM gwatson@chori.org
OI Serra, Montserrat/0000-0002-5528-2418; Matabosch,
Xavier/0000-0001-8442-7957; Wassif, Christopher/0000-0002-2524-1420
FU National Institutes of Health [R01HD053036]; Smith-Lemli-Opitz/RSH
Foundation; Eunice Kennedy Shriver National Institute of Child Health
and Human Development; Generalitat de Catalunya [2007 BP-A 00101];
Howard Hughes Medical Institute's Undergraduate Biological Science
Education Initiative
FX We thank Kevin Hua for technical help and Dr. Berna Watson for
statistical analysis. This work was supported by National Institutes of
Health Grant R01HD053036 (CS) and a grant from the Smith-Lemli-Opitz/RSH
Foundation (GW). This work was also supported by the intramural program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development. Dr. Serra was awarded a Beatriu de Pinos postdoctoral
fellowship from Generalitat de Catalunya (2007 BP-A 00101). Amb el
suport del Comissionat per a Universitats i Recerca del Departament
d'Innovacio, Universitats i Empresa de la Generalitat de Catalunya. Lee
Ying was awarded a fellowship from Howard Hughes Medical Institute's
Undergraduate Biological Science Education Initiative; Biology Fellows
Program at University of California Berkeley.
NR 41
TC 5
Z9 6
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 NOV
PY 2010
VL 122
IS 5
BP 303
EP 309
DI 10.1016/j.jsbmb.2010.08.004
PG 7
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 682ZU
UT WOS:000284442300001
PM 20800683
ER
PT J
AU Dull, A
Goncharova, E
Hager, G
McMahon, JB
AF Dull, Angie
Goncharova, Ekaterina
Hager, Gordon
McMahon, James B.
TI Development of an image analysis screen for estrogen receptor alpha (ER
alpha) ligands through measurement of nuclear translocation dynamics
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE Estrogen receptor; High-content screening; Cell-based assay; Nuclear
translocation; Cytotoxicity
ID HEALTHY POSTMENOPAUSAL WOMEN; BREAST EPITHELIAL-CELLS; NONALCOHOLIC
STEATOHEPATITIS; PLUS PROGESTIN; TAMOXIFEN; CANCER; TRIAL; CARCINOGENS;
KIDNEY; LIVER
AB We have developed a robust high-content assay to screen for novel estrogen receptor alpha (ER alpha) agonists and antagonists by quantitation of cytoplasmic to nuclear translocation of an estrogen receptor chimera in 384-well plates. The screen utilizes a green fluorescent protein tagged-glucocorticoid/estrogen receptor (GFP-GRER) chimera which consisted of the N-terminus of the glucocorticoid receptor fused to the human ER ligand binding domain. The GFP-GRER exhibited cytoplasmic localization in the absence of ER alpha ligands, and translocated to the nucleus in response to stimulation with ER alpha agonists or antagonists. The BD Pathway 435 imaging system was used for image acquisition, analysis of translocation dynamics, and cytotoxicity measurements. The assay was validated with known ER alpha agonists and antagonists, and the Library of Pharmacologically Active Compounds (LOPAC 1280). Additionally, screening of crude natural product extracts demonstrated the robustness of the assay, and the ability to quantitate the effects of toxicity on nuclear translocation dynamics. The GFP-GRER nuclear translocation assay was very robust, with z' values >0.7, CVs <5%, and has been validated with known ER ligands, and inclusion of cytotoxicity filters will facilitate screening of natural product extracts. This assay has been developed for future primary screening of synthetic, pure natural products, and natural product extracts libraries available at the National Cancer Institute at Frederick. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Dull, Angie] NCI, Mol Targets Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Goncharova, Ekaterina] NCI, Data Management Serv Inc, Frederick, MD 21702 USA.
[Hager, Gordon] NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, Frederick, MD 21702 USA.
[McMahon, James B.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Dull, A (reprint author), NCI, Mol Targets Lab, SAIC Frederick Inc, Mailstop 538-01, Frederick, MD 21702 USA.
EM dulla@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This Research was supported [in part] by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
NR 21
TC 8
Z9 8
U1 0
U2 5
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 NOV
PY 2010
VL 122
IS 5
BP 341
EP 351
DI 10.1016/j.jsbmb.2010.08.009
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 682ZU
UT WOS:000284442300006
PM 20816963
ER
PT J
AU Vu, HN
Miller, WJ
O'Connor, SA
He, M
Schafer, PH
Payvandi, F
Muller, GW
Stirling, DI
Libutti, SK
AF Vu, Huan N.
Miller, Walter J.
O'Connor, Sarah A.
He, Mei
Schafer, Peter H.
Payvandi, Faribourz
Muller, George W.
Stirling, David I.
Libutti, Steven K.
TI CC-5079: A Small Molecule with MKP1, Antiangiogenic, and Antitumor
Activity
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE angiogenesis; Selcids; small molecule inhibitor
ID CELL-PROLIFERATION; AGENTS; ANGIOGENESIS; BEVACIZUMAB; INHIBITION;
MECHANISM; TUBULIN; CANCER
AB Introduction. CC-5079, a small molecule inhibitor of tubulin polymerization and phosphodiesterase-4 activity, was evaluated for antiangiogenic and antitumor activities.
Materials and Methods. First, CC-5079 in vitro activity on human umbilical vein endothelial cells (HU-VECs), fibroblasts, and MC38 were evaluated by proliferation, migration, and invasion assays. Second, CC-5079 effect on microvessel formation was evaluated ex vivo by chick chorioallantoic membrane (CAM), rat aortic rings assays, and with directed in vivo angiogenesis assay (DIVAA). Third, CC-5079 antitumor effect was determined in treatment of C57BL/6 mice with MC38 tumors. Finally, CC-5079 modulation of MKP1 in HUVECs, human fibroblast, and MC38 were determined by RNA isolation for qRT-PCR.
Results. At the 0.1 mu M concentration CC-5079 significantly inhibited HUVEC, fibroblast, and MC38 proliferation and migration (all P < 0.001). At the 0.1 mu M concentration, CC-5079 also inhibited HUVEC invasion (P < 0.05) but not fibroblast. In the CAM and rat aortic ring assays, CC-5079 at 0.1 mu M inhibited microvessel formation (P < 0.05). By DIVAA, CC-5079 at 1 mg/kg/d continuous delivered inhibited microvessel formation (P < 0.05). Intraperitoneal CC-5079 was well tolerated and inhibited the growth of subcutaneous MC38 at 100 mg/kg/d (P < 0.01). By qRT-PCR, CC-5079 stimulated MKP1 expression in HUVEC and fibroblast.
Conclusion. CC-5079 demonstrated stimulation of MKP1 antiangiogenic, and antitumor properties. Published by Elsevier Inc.
C1 [Vu, Huan N.; Miller, Walter J.; O'Connor, Sarah A.; He, Mei; Libutti, Steven K.] NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Schafer, Peter H.; Payvandi, Faribourz; Muller, George W.; Stirling, David I.] Celgene Corp, Summit, NJ USA.
RP Vu, HN (reprint author), VCU Surg Oncol, W Hosp 7-406B,1200 E Broad St, Richmond, VA 23298 USA.
EM HNVU@VCU.EDU
FU Celgene Corporation; NIH, National Cancer Institute, Center for Cancer
Research
FX This research was supported in part by the Celgene Corporation and the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research, and performed at the Surgery Branch, Center
for Cancer Research, National Cancer Institute, Bethesda, Maryland.
NR 18
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 0022-4804
J9 J SURG RES
JI J. Surg. Res.
PD NOV
PY 2010
VL 164
IS 1
BP 116
EP 125
DI 10.1016/j.jss.2009.01.031
PG 10
WC Surgery
SC Surgery
GA 672XX
UT WOS:000283622100021
PM 19726061
ER
PT J
AU Beachkofsky, TM
Sapp, JC
Biesecker, LG
Darling, TN
AF Beachkofsky, Thomas M.
Sapp, Julie C.
Biesecker, Leslie G.
Darling, Thomas N.
TI Progressive overgrowth of the cerebriform connective tissue nevus in
patients with Proteus syndrome
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
DE cerebriform connective tissue nevus; overgrowth; progression; Proteus
syndrome
ID DIAGNOSTIC-CRITERIA; MANAGEMENT; SKIN
AB Background: Proteus syndrome is a rare overgrowth disorder that almost always affects the skin.
Objective: Our purpose was to evaluate progression of skin lesion:; in patients with Proteus syndrome.
Methods: Skin findings were documented in 36 patients with Proteus syndrome. Progression of skin lesions in 16 of these patients was assessed by comparing photographs obtained on repeated visits for an average total duration of 53 months.
Results: The skin lesion most characteristic of Proteus syndrome, the cerebriform connective tissue nevus, showed progression in 13 children but not in 3 adults. The cerebriform connective tissue nevus progressed by expansion into previously uninvolved skin, increased thickness, and development of new lesions. Lipomas increased in size, number, or both in 8 of 10 children with lipomas. In contrast, epidermal nevi and Vascular malformations generally did not spread or increase in number.
Limitations: Only 3 adults with Proteus syndrome were evaluated longitudinally.
Conclusion: The cerebriform connective tissue nevus in Proteus syndrome grows throughout childhood but tends to remain stable in adulthood. (J Am Acad Dermatol 2010;63:799-804.)
C1 [Beachkofsky, Thomas M.; Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA.
[Sapp, Julie C.; Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP Darling, TN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Dermatol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM tdarling@usuhs.mil
OI Darling, Thomas/0000-0002-5161-1974
FU Sulzberger Laboratory for Dermatologic Research; National Institutes of
Health, National Human Genome Research Institute
FX Supported by Sulzberger Laboratory for Dermatologic Research, and the
Intramural Research Program of the National Institutes of Health,
National Human Genome Research Institute.
NR 19
TC 11
Z9 12
U1 0
U2 0
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 NOV
PY 2010
VL 63
IS 5
BP 799
EP 804
DI 10.1016/j.jaad.2009.12.012
PG 6
WC Dermatology
SC Dermatology
GA 675EP
UT WOS:000283809300008
PM 20709429
ER
PT J
AU Hoggle, LB
Yadrick, MM
Ayres, EJ
AF Hoggle, Lindsey Blevins
Yadrick, Martin M.
Ayres, Elaine J.
TI A Decade of Work Coming Together: Nutrition Care, Electronic Health
Records, and the HITECH Act
SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION
LA English
DT Editorial Material
C1 [Hoggle, Lindsey Blevins] Hlth Project Partners LLC, Gaithersburg, MD USA.
[Yadrick, Martin M.] Computrition Inc, Nutr Informat, Los Angeles, CA USA.
[Ayres, Elaine J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA.
RP Hoggle, LB (reprint author), Hlth Project Partners LLC, Gaithersburg, MD USA.
NR 10
TC 6
Z9 6
U1 0
U2 3
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 NOV
PY 2010
VL 110
IS 11
BP 1606
EP +
DI 10.1016/j.jada.2010.09.019
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 675JF
UT WOS:000283825700002
PM 21034868
ER
PT J
AU Xue, QL
Beamer, BA
Chaves, PHM
Guralnik, JM
Fried, LP
AF Xue, Qian-Li
Beamer, Brock A.
Chaves, Paulo H. M.
Guralnik, Jack M.
Fried, Linda P.
TI Heterogeneity in Rate of Decline in Grip, Hip, and Knee Strength and the
Risk of All-Cause Mortality: The Women's Health and Aging Study II
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE handgrip strength; hip strength; knee strength; mortality; older women
ID RANDOMIZED CONTROLLED-TRIAL; MUSCLE STRENGTH; OLDER WOMEN; HANDGRIP
STRENGTH; SKELETAL-MUSCLE; PHYSICAL-ACTIVITY; MEN; ADULTS; MASS;
PREDICTORS
AB OBJECTIVES: To assess the relationship between rate of change in muscle strength and all-cause mortality.
DESIGN: Prospective observational study of the causes and course of physical disability.
SETTING: Twelve contiguous ZIP code areas in Baltimore, Maryland.
PARTICIPANTS: Three hundred seven community-dwelling women aged 70 to 79 at study baseline.
MEASUREMENTS: The outcome was all-cause mortality (1994-2009); predictors included up to seven repeated measurements of handgrip, knee extension, and hip flexion strength, with a median follow-up time of 10 years. Demographic factors, body mass index, smoking status, number of chronic diseases, depressive symptoms, physical activity, interleukin-6, and albumin were assessed at baseline and included as confounders. The associations between declining muscle strength and mortality were assessed using a joint longitudinal and survival model.
RESULTS: Grip and hip strength declined an average of 1.10 and 1.31 kg/year between age 70 and 75 and 0.50 and 0.39 kg/year thereafter, respectively; knee strength declined at a constant rate of 0.57 kg/year. Faster rates of decline in grip and hip strength, but not knee strength, independently predicted mortality after accounting for baseline levels and potential confounders (hazard ratio (HR) = 51.33, 95% confidence interval (95%) CI = 1.06-1.67, HR = 1.14, 95% CI = 0.91-1.41, and 2.62, 95% CI = 1.43-4.78 for every 0.5 standard deviation increase in rate of decline in grip, knee, and hip strength, respectively).
CONCLUSION: Monitoring the rate of decline in grip and hip flexion strength in addition to absolute levels may greatly improve the identification of women most at risk of dying. J Am Geriatr Soc 58:2076-2084, 2010.
C1 [Xue, Qian-Li; Chaves, Paulo H. M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Xue, Qian-Li; Chaves, Paulo H. M.] Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD USA.
[Beamer, Brock A.] Univ Maryland, Sch Med, Div Gerontol, Baltimore, MD 21201 USA.
[Fried, Linda P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Guralnik, Jack M.] NIA, NIH, Bethesda, MD 20892 USA.
RP Xue, QL (reprint author), 2024 E Monument St,Suite 2-700, Baltimore, MD 21205 USA.
EM qxue@jhsph.edu
FU National Institute on Aging (NIA), National Institutes of Health (NIH)
[P30-AG02133, R01-AG11703, R01-AG023701]
FX This study was supported by the Johns Hopkins Older Americans
Independence Center under Contracts P30-AG02133, R01-AG11703, and
R01-AG023701 from the National Institute on Aging (NIA), National
Institutes of Health (NIH). Dr. Guralnik was supported in part by the
Intramural Research Program, NIA, NIH.
NR 34
TC 31
Z9 32
U1 2
U2 11
PU WILEY-BLACKWELL PUBLISHING, INC
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 NOV
PY 2010
VL 58
IS 11
BP 2076
EP 2084
DI 10.1111/j.1532-5415.2010.03154.x
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 676WT
UT WOS:000283950100004
PM 21054287
ER
PT J
AU Alley, DE
Koster, A
Mackey, D
Cawthon, P
Ferrucci, L
Simonsick, EM
Yu, BB
Hardy, S
Goodpaster, B
Sarkisian, C
Houston, DK
Kritchevsky, SB
Cummings, S
Lee, JS
Tylavsky, FA
Newman, A
Harris, T
AF Alley, Dawn E.
Koster, Annemarie
Mackey, Dawn
Cawthon, Peggy
Ferrucci, Luigi
Simonsick, Eleanor M.
Yu, Binbing
Hardy, Susan
Goodpaster, Bret
Sarkisian, Catherine
Houston, Denise K.
Kritchevsky, Stephen B.
Cummings, Steven
Lee, Jung-Sun
Tylavsky, Frances A.
Newman, Anne
Harris, Tamara
CA Hlth Aging & Body Composition Stud
TI Hospitalization and Change in Body Composition and Strength in a
Population-Based Cohort of Older Persons
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE lean mass; weight loss; function; hospitalization; strength
ID BED REST; WEIGHT CHANGE; MUSCLE MASS; ADULTS; FRAILTY; HEALTH; WOMEN;
DISABILITY; MORTALITY; RECOVERY
AB OBJECTIVES: To examine the association between hospitalization and annual changes in body composition and strength in older adults.
DESIGN: Cohort study.
SETTING: Clinic examinations in Pittsburgh, Pennsylvania, or Memphis, Tennessee.
PARTICIPANTS: Well-functioning adults aged 70 to 79 who participated in the Health, Aging and Body Composition Study.
MEASUREMENTS: Hospitalizations were reported at annual clinic visits and in semiannual phone interviews. In the event of death or reported hospitalization, hospitalizations were adjudicated according to medical record review. Dual X-ray absorptiometry (DXA) assessments of total, lean, and fat mass were conducted in six annual examinations, and measures of knee extensor strength were conducted in two annual examinations.
RESULTS: DXA assessments followed 2,309 hospitalizations. In men and women, hospitalization in the previous year was associated with greater declines in total mass (- 0.76 and -0.81 kg, respectively), fat mass (-0.41 and -0.54 kg), and lean mass (-0.33 and -0.25 kg) (P < .001 for all) than in nonhospitalized participants, after adjustment for demographics and baseline values. Hospitalization was associated with strength declines in men (-4.02 Nm, P = .046) but not in women. Relationships were similar after adjusting for health behaviors and chronic conditions, although the association between hospitalization and strength was attenuated. Associations increased with number of days hospitalized; hospitalizations totaling 8 days or more in the previous year were associated with significantly greater loss of total, lean, and fat mass and loss of strength in both sexes than in nonhospitalized participants.
CONCLUSION: Hospitalization is associated with significant changes in body composition and strength in older persons. These effects appear particularly important in persons hospitalized for 8 or more days per year. J Am Geriatr Soc 58:2085-2091, 2010.
C1 [Alley, Dawn E.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Koster, Annemarie; Yu, Binbing; Harris, Tamara] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Mackey, Dawn; Cawthon, Peggy; Cummings, Steven] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Ferrucci, Luigi; Simonsick, Eleanor M.] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
[Hardy, Susan; Goodpaster, Bret; Newman, Anne] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Newman, Anne] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA.
[Sarkisian, Catherine] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA.
[Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Lee, Jung-Sun] Univ Georgia, Coll Publ Hlth, Athens, GA 30602 USA.
[Tylavsky, Frances A.] Univ Tennessee, Dept Epidemiol, Memphis, TN USA.
RP Alley, DE (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
EM dalley@epi.umaryland.edu
RI Koster, Annemarie/E-7438-2010; Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Kritchevsky,
Stephen/0000-0003-3336-6781
FU National Institutes of Health, National Institute on Aging (NIA);
Organized Research Center on Aging at the University of Maryland,
Baltimore; NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-2106]
FX D. Houston received a speaker honorarium from Abbott Nutrition Health
Institute. All other authors have no financial disclosure to report.
This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging (NIA)
and by the Organized Research Center on Aging at the University of
Maryland, Baltimore. The Health ABC Study is funded under NIA Contracts
N01-AG-6-2101, N01-AG-6-2103, and N01-AG-2106.
NR 25
TC 22
Z9 23
U1 4
U2 9
PU WILEY-BLACKWELL PUBLISHING, INC
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 NOV
PY 2010
VL 58
IS 11
BP 2085
EP 2091
DI 10.1111/j.1532-5415.2010.03144.x
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 676WT
UT WOS:000283950100005
PM 21054288
ER
PT J
AU Young, Y
Boyd, CM
Guralnik, JM
Fried, LP
AF Young, Yuchi
Boyd, Cynthia M.
Guralnik, Jack M.
Fried, Linda P.
TI Does Self-Reported Function Correspond to Objective Measures of
Functional Impairment?
SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION
LA English
DT Article
DE Aging; disability; impairments
ID PHYSICAL PERFORMANCE; OLDER-ADULTS; PRECLINICAL DISABILITY; WOMENS
HEALTH; MOBILITY DISABILITY; RISK; DEPENDENCE; VALIDITY; DECLINE;
DISEASE
AB Introduction: The relationship between self-reported function and objective measures of physiological function among disabled older women was analyzed to determine the validity of self-reported function, and to identify the hierarchy of self-reported task difficulty most associated with loss of independence as a basis to inform treatment progress goals.
Methods: A randomly selected population of older women with moderate to high disability was selected from community-dwelling women 65 to 101 years old from the Women's Health and Aging Study I baseline evaluation (n = 987). Cross-sectional analyses evaluated the association of self-reported function with objective physiological impairment measures.
Results: The results indicated that (1) disabled older women self-reported a broad range of physical function levels; (2) self-reported function correlated closely with objective measures of physiological impairments; (3) "preclinical disability," as measured by self-reported modification of task performance in the absence of perceived difficulty, has validity even in a disabled population, and identifies a group intermediate between those who are high functioning in a task and those with difficulty; and (4) there is an apparent gradation in physiological impairment measures with reported loss of functional independence.
Conclusion: These findings suggest the validity of self-report functional disability measures and the potential to use these measures to identify already-disabled older adults at risk for further functional degradation and potential targets for intervention. (1 Am Med Dir Assoc 2010; 11: 645-653)
C1 [Young, Yuchi] SUNY Albany, Sch Publ Hlth, Rensselaer, NY 12144 USA.
[Fried, Linda P.] Columbia Univ, Joseph L Mailman Sch Publ Hlth, New York, NY USA.
[Guralnik, Jack M.; Fried, Linda P.] Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA.
[Boyd, Cynthia M.; Fried, Linda P.] Johns Hopkins Med Inst, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA.
[Guralnik, Jack M.] NIA, Bethesda, MD 20892 USA.
RP Young, Y (reprint author), SUNY Albany, Sch Publ Hlth, 1 Univ Pl,Room 171, Rensselaer, NY 12144 USA.
EM yyoung@albany.edu
FU National Institutes of Health [R37-AG 19905, N01AG1-2112]; National
Institute on Aging, National Institutes of Health
FX This work was supported by National Institutes of Health grant R37-AG
19905 and contract N01AG1-2112. Supported in part by the Intramural
Research Program, National Institute on Aging, National Institutes of
Health.
NR 29
TC 14
Z9 14
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-8610
J9 J AM MED DIR ASSOC
JI J. Am. Med. Dir. Assoc.
PD NOV
PY 2010
VL 11
IS 9
BP 645
EP 653
DI 10.1016/j.jamda.2009.12.084
PG 9
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 681UA
UT WOS:000284344100006
PM 21029999
ER
PT J
AU Fung, KW
McDonald, C
Srinivasan, S
AF Fung, Kin Wah
McDonald, Clement
Srinivasan, Suresh
TI The UMLS-CORE project: a study of the problem list terminologies used in
large healthcare institutions
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID MEDICAL LANGUAGE SYSTEM; VOCABULARY; TOOL
AB Objective To study existing problem list terminologies (PLTs), and to identify a subset of concepts based on standard terminologies that occur frequently in problem list data.
Design Problem list terms and their usage frequencies were collected from large healthcare institutions.
Measurement The pattern of usage of the terms was analyzed. The local terms were mapped to the Unified Medical Language System (UMLS). Based on the mapped UMLS concepts, the degree of overlap between the PLTs was analyzed.
Results Six institutions submitted 76 237 terms and their usage frequencies in 14 million patients. The distribution of usage was highly skewed. On average, 21% of unique terms already covered 95% of usage. The most frequently used 14 395 terms, representing the union of terms that covered 95% of usage in each institution, were exhaustively mapped to the UMLS. 13 261 terms were successfully mapped to 6776 UMLS concepts. Less frequently used terms were generally less 'mappable' to the UMLS. The mean pairwise overlap of the PLTs was only 21% (median 19%). Concepts that were shared among institutions were used eight times more often than concepts unique to one institution. A SNOMED Problem List Subset of frequently used problem list concepts was identified.
Conclusions Most of the frequently used problem list terms could be found in standard terminologies. The overlap between existing PLTs was low. The use of the SNOMED Problem List Subset will save developmental effort, reduce variability of PLTs, and enhance interoperability of problem list data.
C1 [Fung, Kin Wah; McDonald, Clement; Srinivasan, Suresh] Natl Lib Med, Bethesda, MD 20894 USA.
RP Fung, KW (reprint author), Natl Lib Med, Bldg 38A,Rm9S914,MSC-3826,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM kfung@mail.nih.gov
FU National Institutes of Health; National Library of Medicine
FX This work was supported by the Intramural Research Program of the
National Institutes of Health and the National Library of Medicine.
NR 22
TC 19
Z9 19
U1 0
U2 7
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD NOV
PY 2010
VL 17
IS 6
BP 675
EP 680
DI 10.1136/jamia.2010.007047
PG 6
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Information Science & Library Science;
Medical Informatics
SC Computer Science; Information Science & Library Science; Medical
Informatics
GA 676GV
UT WOS:000283899900011
PM 20962130
ER
PT J
AU Johnson, SB
Whitney, G
McAuliffe, M
Wang, HL
McCreedy, E
Rozenblit, L
Evans, CC
AF Johnson, Stephen B.
Whitney, Glen
McAuliffe, Matthew
Wang, Hailong
McCreedy, Evan
Rozenblit, Leon
Evans, Clark C.
TI Using global unique identifiers to link autism collections
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID PERSONAL IDENTIFIERS
AB Objective To propose a centralized method for generating global unique identifiers to link collections of research data and specimens.
Design The work is a collaboration between the Simons Foundation Autism Research Initiative and the National Database for Autism Research. The system is implemented as a web service: an investigator inputs identifying information about a participant into a client application and sends encrypted information to a server application, which returns a generated global unique identifier. The authors evaluated the system using a volume test of one million simulated individuals and a field test on 2000 families (over 8000 individual participants) in an autism study.
Measurements Inverse probability of hash codes; rate of false identity of two individuals; rate of false split of single individual; percentage of subjects for which identifying information could be collected; percentage of hash codes generated successfully.
Results Large-volume simulation generated no false splits or false identity. Field testing in the Simons Foundation Autism Research Initiative Simplex Collection produced identifiers for 96% of children in the study and 77% of parents. On average, four out of five hash codes per subject were generated perfectly (only one perfect hash is required for subsequent matching).
Discussion The system must achieve balance among the competing goals of distinguishing individuals, collecting accurate information for matching, and protecting confidentiality. Considerable effort is required to obtain approval from institutional review boards, obtain consent from participants, and to achieve compliance from sites during a multicenter study.
Conclusion Generic unique identifiers have the potential to link collections of research data, augment the amount and types of data available for individuals, support detection of overlap between collections, and facilitate replication of research findings.
C1 [Johnson, Stephen B.] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA.
[Johnson, Stephen B.; Whitney, Glen] Simons Fdn, New York, NY USA.
[McAuliffe, Matthew; Wang, Hailong; McCreedy, Evan] NIH, Bethesda, MD 20892 USA.
[Rozenblit, Leon; Evans, Clark C.] Prometheus Res LLC, New Haven, CT USA.
RP Johnson, SB (reprint author), Columbia Univ, Dept Biomed Informat, 622 W 168th St,VC 558, New York, NY 10032 USA.
EM sbj2@columbia.edu
OI Rozenblit, Leon/0000-0001-5243-6752
FU Simons Foundation Autism Research Initiative (SFARI); National Database
for Autism Research (NDAR); National Institute of Mental Health; NIH
FX This work was supported by the Simons Foundation Autism Research
Initiative (SFARI) and the National Database for Autism Research (NDAR),
National Institute of Mental Health. Other Funders: NIH; Simons
Foundation Autism Research Initiative; National Database for Autism
Research; National Institute of Mental Health.
NR 17
TC 34
Z9 34
U1 1
U2 7
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD NOV
PY 2010
VL 17
IS 6
BP 689
EP 695
DI 10.1136/jamia.2009.002063
PG 7
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Health Care Sciences & Services;
Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
Library Science; Medical Informatics
GA 676GV
UT WOS:000283899900013
PM 20962132
ER
PT J
AU Pathak, J
Peters, L
Chute, CG
Bodenreider, O
AF Pathak, Jyotishman
Peters, Lee
Chute, Christopher G.
Bodenreider, Olivier
TI Comparing and evaluating terminology services application programming
interfaces: RxNav, UMLSKS and LexBIG
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID MEDICAL LANGUAGE SYSTEM
AB To facilitate the integration of terminologies into applications, various terminology services application programming interfaces (API) have been developed in the recent past. In this study, three publicly available terminology services API, RxNav, UMLSKS and LexBIG, are compared and functionally evaluated with respect to the retrieval of information from one biomedical terminology, RxNorm, to which all three services provide access. A list of queries is established covering a wide spectrum of terminology services functionalities such as finding RxNorm concepts by their name, or navigating different types of relationships. Test data were generated from the RxNorm dataset to evaluate the implementation of the functionalities in the three API. The results revealed issues with various aspects of the API implementation (eg, handling of obsolete terms by LexBIG) and documentation (eg, navigational paths used in RxNav) that were subsequently addressed by the development teams of the three API investigated. Knowledge about such discrepancies helps inform the choice of an API for a given use case.
C1 [Pathak, Jyotishman; Chute, Christopher G.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
[Peters, Lee; Bodenreider, Olivier] US Natl Lib Med, Bethesda, MD USA.
RP Pathak, J (reprint author), Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
EM pathak.jyotishman@mayo.edu
RI lyp, maggie/G-1471-2011
FU NHGRI [U01HG04599]; NLM
FX This research is supported in part by NHGRI grant U01HG04599 (eMERGE)
and the Intramural Research Program at NLM.
NR 11
TC 1
Z9 1
U1 0
U2 4
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD NOV
PY 2010
VL 17
IS 6
BP 714
EP 719
DI 10.1136/jamia.2009.001149
PG 6
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Information Science & Library Science;
Medical Informatics
SC Computer Science; Information Science & Library Science; Medical
Informatics
GA 676GV
UT WOS:000283899900017
PM 20962136
ER
PT J
AU Calcagno, AM
Salcido, CD
Gillet, JP
Wu, CP
Fostel, JM
Mumau, MD
Gottesman, MM
Varticovski, L
Ambudkar, SV
AF Calcagno, Anna Maria
Salcido, Crystal D.
Gillet, Jean-Pierre
Wu, Chung-Pu
Fostel, Jennifer M.
Mumau, Melanie D.
Gottesman, Michael M.
Varticovski, Lyuba
Ambudkar, Suresh V.
TI Prolonged Drug Selection of Breast Cancer Cells and Enrichment of Cancer
Stem Cell Characteristics
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; ALDEHYDE DEHYDROGENASE-ACTIVITY;
MULTIDRUG-RESISTANCE; CARCINOMA-CELLS; P-GLYCOPROTEIN; GLUCOSYLCERAMIDE
SYNTHASE; LUNG-CANCER; NUDE-MICE; IN-VITRO; EXPRESSION
AB Background Cancer stem cells are presumed to have virtually unlimited proliferative and self-renewal abilities and to be highly resistant to chemotherapy, a feature that is associated with overexpression of ATP-binding cassette transporters. We investigated whether prolonged continuous selection of cells for drug resistance enriches cultures for cancer stem-like cells.
Methods Cancer stem cells were defined as CD44+/CD24- cells that could self-renew (ie, generate cells with the tumorigenic CD44+/CCD24- phenotype), differentiate, invade, and form tumors in vivo. We used doxorubicin-selected MCF-7/ADR cells, weakly tumorigenic parental MCF-7 cells, and MCF-7/MDR, an MCF-7 subline with forced expression of ABCB1 protein. Cells were examined for cell surface markers and side-population fractions by microarray and flow cytometry, with in vitro invasion assays, and for ability to form mammospheres. Xenograft tumors were generated in mice to examine tumorigenicity (n = 52). The mRNA expression of multidrug resistance genes was examined in putative cancer stem cells and pathway analysis of statistically significantly differentially expressed genes was performed. All statistical tests were two-sided.
Results Pathway analysis showed that MCF-7/ADR cells express mRNAs from ABCB1 and other genes also found in breast cancer stem cells (eg, CD44, TGFB1, and SNAI1). MCF-7/ADR cells were highly invasive, formed mammospheres, and were tumorigenic in mice. In contrast to parental MCF-7 cells, more than 30% of MCF-7/ADR cells had a CD44+/CCD24- phenotype, could self-renew, and differentiate (ie, produce CD44+/CCD24- and CD44+/CD24+ cells) and overexpressed various multidrug resistance-linked genes (including ABCB1, CCNE1, and MMP9). MCF-7/ADR cells were statistically significantly more invasive in Matrigel than parental MCF-7 cells (MCF-7 cells = 0.82 cell per field and MCF-7/ADR = 7.51 cells per field, difference = 6.69 cells per field, 95% confidence interval = 4.82 to 8.55 cells per field, P < .001). No enrichment in the CD44+/CCD24- or CD133+ population was detected in MCF-7/MDR.
Conclusion The cell population with cancer stem cell characteristics increased after prolonged continuous selection for doxorubicin resistance.
C1 [Calcagno, Anna Maria; Gillet, Jean-Pierre; Wu, Chung-Pu; Gottesman, Michael M.; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Salcido, Crystal D.; Mumau, Melanie D.; Varticovski, Lyuba] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Fostel, Jennifer M.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 2120, Bethesda, MD 20892 USA.
EM ambudkar@helix.nih.gov
RI gillet, jean-pierre/A-3714-2012; Calcagno, Anna Maria/A-5617-2012;
OI Calcagno, Anna Maria/0000-0002-0804-2753
FU National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research; NIGMS; NIH; National Institutes of Environmental
Health Sciences [HHSN273200700046U]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research. A. M. C. was supported by the NIGMS Pharmacology
Research Associate (PRAT) Program. J.F. was supported by the Intramural
Research Program of the NIH and National Institutes of Environmental
Health Sciences, contract HHSN273200700046U.
NR 71
TC 112
Z9 122
U1 6
U2 20
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 NOV
PY 2010
VL 102
IS 21
BP 1637
EP 1652
DI 10.1093/jnci/djq361
PG 16
WC Oncology
SC Oncology
GA 676PA
UT WOS:000283923300009
PM 20935265
ER
PT J
AU Safaeian, M
Porras, C
Schiffman, M
Rodriguez, AC
Wacholder, S
Gonzalez, P
Quint, W
van Doorn, LJ
Sherman, ME
Xhenseval, V
Herrero, R
Hildesheim, A
AF Safaeian, Mahboobeh
Porras, Carolina
Schiffman, Mark
Rodriguez, Ana Cecilia
Wacholder, Sholom
Gonzalez, Paula
Quint, Wim
van Doorn, Leen-Jan
Sherman, Mark E.
Xhenseval, Valerie
Herrero, Rolando
Hildesheim, Allan
CA Costa Rican Vaccine Trial Grp
TI Epidemiological Study of Anti-HPV16/18 Seropositivity and Subsequent
Risk of HPV16 and -18 Infections
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS TYPE-16; RANDOMIZED CONTROLLED-TRIAL; VIRUS-LIKE
PARTICLES; AGED 16-26 YEARS; COSTA-RICA; QUADRIVALENT VACCINE;
ANTIBODY-RESPONSE; CERVICAL-CANCER; BROAD-SPECTRUM; DOUBLE-BLIND
AB Background Infection with human papillomavirus (HPV) 16 or HPV18 elicits an antibody response, but whether the elicited antibodies protect women against subsequent infection by a homologous HPV type compared with seronegative women is unknown.
Methods Study participants were women aged 18-25 years at enrollment in the control group of the ongoing National Cancer Institute-sponsored, community-based, randomized HPV16/18 Costa Rica Vaccine Trial. At enrollment, 2813 participants were negative for cervical HPV16 DNA and 2950 for HPV18 DNA. Women were interviewed regarding sociodemographic data and medical and health history. Medical and pelvic examinations were conducted for all consenting sexually experienced women. Serum samples taken at enrollment were tested for total HPV16/18 antibodies with a polyclonal enzyme-linked immunosorbent assay, and cervical specimens were tested for type-specific HPV DNA over 4 years of follow-up. Using Poisson regression, we compared rate ratios of newly detected cervical HPV16 or HPV18 infection among homologous HPV-seropositive and HPV-seronegative women, adjusting for age, education, marital status, lifetime number of sexual partners, and smoking.
Results There were 231 newly detected HPV16 infections during 5886 person-years among HPV16-seronegative women compared with 12 newly detected HPV16 infections during 581 person-years among HPV16-seropositive women with the highest HPV16 sero-levels. There were 136 newly detected HPV18 infections during 6352 person-years among HPV18-seronegative women compared with six new infections detected during 675 person-years among HPV18 seropositives with the highest sero-levels. After controlling for risk factors associated with newly detected HPV infection, having high HPV16 antibody titer at enrollment was associated with a reduced risk of subsequent HPV16 infection (women in the highest tertile of HPV16 antibody titers, adjusted rate ratio = 0.50, 95% confidence interval = 0.26 to 0.86 vs HPV16-seronegative women). Similarly, having high HPV18 antibody titer at enrollment was associated with a reduced risk of subsequent HPV18 infection (women in the highest tertile of HPV18 antibody titers, adjusted rate ratio = 0.36, 95% confidence interval = 0.14 to 0.76 vs HPV18-seronegative women).
Conclusion In this study population, having high antibody levels against HPV16 and HPV18 following natural infection was associated with reduced risk of subsequent HPV16 and HPV18 infections.
C1 [Safaeian, Mahboobeh] NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, NIH, Rockville, MD 20852 USA.
[Porras, Carolina; Rodriguez, Ana Cecilia; Gonzalez, Paula; Herrero, Rolando] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica.
[Quint, Wim; van Doorn, Leen-Jan] DDL Diagnost Lab, Voorburg, Netherlands.
[Xhenseval, Valerie] GlaxoSmithKline Biol, Rixensart, Belgium.
RP Safaeian, M (reprint author), NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, NIH, 6120 Execut Blvd,Ste 550, Rockville, MD 20852 USA.
EM safaeianm@mail.nih.gov
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU National Cancer Institute, National Institutes of Health; National
Institutes of Health Office of Research on Women's Health
FX Intramural Research Program of the National Cancer Institute, National
Institutes of Health. National Institutes of Health Office of Research
on Women's Health.
NR 26
TC 91
Z9 92
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 NOV
PY 2010
VL 102
IS 21
BP 1653
EP 1662
DI 10.1093/jnci/djq384
PG 10
WC Oncology
SC Oncology
GA 676PA
UT WOS:000283923300010
PM 20944077
ER
PT J
AU Subramanian, J
Simon, R
AF Subramanian, Jyothi
Simon, Richard
TI Re: Gene Expression-Based Prognostic Signatures in Lung Cancer: Ready
for Clinical Use? Response
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
C1 [Subramanian, Jyothi; Simon, Richard] NCI, Biometr Res Branch, Dept Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Simon, R (reprint author), NCI, Biometr Res Branch, Dept Canc Treatment & Diag, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rsimon@mail.nih.gov
NR 3
TC 1
Z9 1
U1 1
U2 2
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 NOV
PY 2010
VL 102
IS 21
BP 1678
EP 1679
DI 10.1093/jnci/djq386
PG 2
WC Oncology
SC Oncology
GA 676PA
UT WOS:000283923300015
ER
PT J
AU Gierach, GL
Brinton, LA
Sherman, ME
AF Gierach, Gretchen L.
Brinton, Louise A.
Sherman, Mark E.
TI Lobular Involution, Mammographic Density, and Breast Cancer Risk:
Visualizing the Future?
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID TISSUE COMPOSITION; ASSOCIATION; WOMEN; AGE
C1 [Gierach, Gretchen L.; Brinton, Louise A.; Sherman, Mark E.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
RP Gierach, GL (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Ste 550,Rm 5016,MSC 7234, Rockville, MD 20852 USA.
EM gierachg@mail.nih.gov
RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016
OI Brinton, Louise/0000-0003-3853-8562; Gierach,
Gretchen/0000-0002-0165-5522
FU Intramural NIH HHS
NR 19
TC 1
Z9 2
U1 0
U2 1
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 NOV
PY 2010
VL 102
IS 22
BP 1685
EP U18
DI 10.1093/jnci/djq433
PG 3
WC Oncology
SC Oncology
GA 682VW
UT WOS:000284432100002
PM 21037117
ER
PT J
AU Freedman, AN
Sansbury, LB
Figg, WD
Potosky, AL
Smith, SRW
Khoury, MJ
Nelson, SA
Weinshilboum, RM
Ratain, MJ
McLeod, HL
Epstein, RS
Ginsburg, GS
Schilsky, RL
Liu, G
Flockhart, DA
Ulrich, CM
Davis, RL
Lesko, LJ
Zineh, I
Randhawa, G
Ambrosone, CB
Relling, MV
Rothman, N
Xie, H
Spitz, MR
Ballard-Barbash, R
Doroshow, JH
Minasian, LM
AF Freedman, Andrew N.
Sansbury, Leah B.
Figg, William D.
Potosky, Arnold L.
Smith, Sheila R. Weiss
Khoury, Muin J.
Nelson, Stefanie A.
Weinshilboum, Richard M.
Ratain, Mark J.
McLeod, Howard L.
Epstein, Robert S.
Ginsburg, Geoffrey S.
Schilsky, Richard L.
Liu, Geoffrey
Flockhart, David A.
Ulrich, Cornelia M.
Davis, Robert L.
Lesko, Lawrence J.
Zineh, Issam
Randhawa, Gurvaneet
Ambrosone, Christine B.
Relling, Mary V.
Rothman, Nat
Xie, Heng
Spitz, Margaret R.
Ballard-Barbash, Rachel
Doroshow, James H.
Minasian, Lori M.
TI Cancer Pharmacogenomics and Pharmacoepidemiology: Setting a Research
Agenda to Accelerate Translation
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID RECEIVING ADJUVANT TAMOXIFEN; BREAST-CANCER; COLORECTAL-CANCER;
LUNG-CANCER; THERAPY; CYP2D6; SURVIVAL; CYP2D6-ASTERISK-10; ASSOCIATION;
MUTATIONS
AB Recent advances in genomic research have demonstrated a substantial role for genomic factors in predicting response to cancer therapies. Researchers in the fields of cancer pharmacogenomics and pharmacoepidemiology seek to understand why individuals respond differently to drug therapy, in terms of both adverse effects and treatment efficacy. To identify research priorities as well as the resources and infrastructure needed to advance these fields, the National Cancer Institute (NCI) sponsored a workshop titled "Cancer Pharmacogenomics: Setting a Research Agenda to Accelerate Translation" on July 21, 2009, in Bethesda, MD. In this commentary, we summarize and discuss five science-based recommendations and four infrastructure-based recommendations that were identified as a result of discussions held during this workshop. Key recommendations include 1) supporting the routine collection of germline and tumor biospecimens in NCI-sponsored clinical trials and in some observational and population-based studies; 2) incorporating pharmacogenomic markers into clinical trials; 3) addressing the ethical, legal, social, and biospecimen- and data-sharing implications of pharmacogenomic and pharmacoepidemiologic research; and 4) establishing partnerships across NCI, with other federal agencies, and with industry. Together, these recommendations will facilitate the discovery and validation of clinical, sociodemographic, lifestyle, and genomic markers related to cancer treatment response and adverse events, and they will improve both the speed and efficiency by which new pharmacogenomic and pharmacoepidemiologic information is translated into clinical practice.
C1 [Freedman, Andrew N.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Rothman, Nat] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Minasian, Lori M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Potosky, Arnold L.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Hlth Serv Res, Washington, DC USA.
[Smith, Sheila R. Weiss] Univ Maryland, Sch Pharm, Ctr Drug Safety, Baltimore, MD 21201 USA.
[Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
[Weinshilboum, Richard M.] Mayo Clin, Coll Med, Div Clin Pharmacol, Rochester, MN USA.
[Ratain, Mark J.] Univ Chicago, Med Ctr, Canc Res Ctr, Chicago, IL 60637 USA.
[McLeod, Howard L.] Univ N Carolina, UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC USA.
[Epstein, Robert S.] Medco Hlth Solut Inc, Franklin Lakes, NJ USA.
[Ginsburg, Geoffrey S.] Duke Univ, Duke Inst Genome Sci & Policy, Ctr Genom Med, Durham, NC USA.
[Schilsky, Richard L.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA.
[Liu, Geoffrey] Univ Toronto, Ontario Canc Inst, Princess Margaret Hosp, Toronto, ON, Canada.
[Flockhart, David A.] Indiana Univ, Sch Med, Indianapolis, IN USA.
[Ulrich, Cornelia M.] German Canc Res Ctr, Div Prevent Oncol, D-6900 Heidelberg, Germany.
[Ulrich, Cornelia M.] Natl Ctr Tumor Dis, Heidelberg, Germany.
[Ulrich, Cornelia M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Davis, Robert L.] Kaiser Permanente, Ctr Hlth Res, Atlanta, GA USA.
[Lesko, Lawrence J.; Zineh, Issam] US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Randhawa, Gurvaneet] Agcy Healthcare Res & Qual, Ctr Outcomes & Evidence, Rockville, MD USA.
[Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Relling, Mary V.] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
[Xie, Heng] NIH, Natl Ctr Res Resources, Div Clin Res Resources, Bethesda, MD 20892 USA.
[Spitz, Margaret R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Freedman, AN (reprint author), NCI, Div Canc Control & Populat Sci, NIH, 6130 Execut Blvd,Rm 5128, Bethesda, MD 20892 USA.
EM andrew_freedman@nih.gov
RI Figg Sr, William/M-2411-2016
FU NCI NIH HHS [R01 CA132780]
NR 22
TC 26
Z9 26
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD NOV
PY 2010
VL 102
IS 22
BP 1698
EP 1705
DI 10.1093/jnci/djq390
PG 8
WC Oncology
SC Oncology
GA 682VW
UT WOS:000284432100008
PM 20944079
ER
PT J
AU Annunziata, CM
Birrer, MJ
AF Annunziata, Christina M.
Birrer, Michael J.
TI Re: CD157 in Ovarian Carcinoma: How Does It Help Us? Response
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
C1 [Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA.
[Annunziata, Christina M.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Birrer, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA.
EM mbirrer@partners.org
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
NR 3
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD NOV
PY 2010
VL 102
IS 22
BP 1741
EP U79
DI 10.1093/jnci/djq395
PG 2
WC Oncology
SC Oncology
GA 682VW
UT WOS:000284432100013
ER
PT J
AU Ballas, SK
Bauserman, RL
McCarthy, WF
Waclawiw, MA
AF Ballas, Samir K.
Bauserman, Robert L.
McCarthy, William F.
Waclawiw, Myron A.
CA Investigators Multictr Study
TI The Impact of Hydroxyurea on Career and Employment of Patients With
Sickle Cell Anemia
SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
LA English
DT Article
DE sickle cell anemia; hydroxyurea
ID RANDOMIZED CONTROLLED-TRIAL; DISEASE; QUALITY; LIFE; PAIN; HEMOGLOBIN;
GABAPENTIN; NEUROPATHY
AB The purpose of this study was to determine the association between hydroxyurea treatment and changes in employment status if any among patients with sickle cell anemia enrolled in the Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH)
To that end we compared the employment status among treatment responders treatment nonresponders and placebo groups of patients enrolled in MSH during the clinical trial and follow up periods Treatment with hydroxyurea did not significantly (p > 05) affect employment status but there was a trend for more consistent employment in the hydroxyurea group Given the fact that patients enrolled in MSH had moderate to severe disease with irreversible complications such as avascular necrosis it would be attractive to hypothesize that future treatment of young patients with hydroxyurea could prevent or mitigate the incidence of complications of sickle cell anemia and hence improve the employment status of treated patients
C1 [Ballas, Samir K.] Thomas Jefferson Univ, Dept Med, Cardeza Fdn, Philadelphia, PA 19107 USA.
[Bauserman, Robert L.; McCarthy, William F.] Maryland Med Res Inst, Baltimore, MD USA.
[Bauserman, Robert L.] NHLBI, Bethesda, MD 20892 USA.
RP Ballas, SK (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Cardeza Fdn Hematol Res, Sickle Cell Ctr, 1015 Walnut St, Philadelphia, PA 19107 USA.
FU National Heart Lung and Blood Institute [NO1 HB 67129, UO1 HL45696]
FX This study was funded by National Heart Lung and Blood Institute
contracts NO1 HB 67129 and UO1 HL45696
NR 27
TC 9
Z9 9
U1 0
U2 1
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 NOV
PY 2010
VL 102
IS 11
BP 993
EP 999
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 689HC
UT WOS:000284917700003
PM 21141286
ER
PT J
AU Kemp, CD
Kitano, M
Kerkar, S
Ripley, RT
Marquardt, JU
Schrump, DS
Avital, I
AF Kemp, Clinton D.
Kitano, Mio
Kerkar, Sid
Ripley, R. Taylor
Marquardt, Jens U.
Schrump, David S.
Avital, Itzhak
TI Pulmonary Resection for Metastatic Gastric Cancer
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE Gastric; Cancer; Lung; Pulmonary; Metastasectomy
ID LONG-TERM SURVIVAL; PHASE-II TRIAL; COLORECTAL-CARCINOMA; SURGICAL
RESECTION; METASTASECTOMY; ADENOCARCINOMA; OXALIPLATIN; GASTRECTOMY;
RECURRENCE; SURGERY
AB Introduction: Sixteen percent of patients with gastric cancer will develop pulmonary metastases. Standard of care for these patients is systemic chemotherapy with a median survival of 6 months and a 5-year survival of only 2%. Our aim was to critically evaluate the published data on pulmonary resection for metastatic gastric cancer (MGC) and to analyze the potential rationale for surgical management to determine which patients may benefit from this approach.
Methods: The Pubmed and SCOPUS databases were queried for all studies reporting on pulmonary resections for MGC. All available clinicopathologic data were analyzed.
Results: Twenty-one studies from 1975 to 2008 reported 48 pulmonary resections in 43 patients including five repeat resections and four extrapulmonary metastasectomies. Eighty-two percent (34/43) of patients had solitary lesions with a median size of 24 mm (4-90 mm). Median time from gastrectomy to pulmonary resection was 35 months (0-120 months). At a median follow-up of 23 months, 15 of 43 (35%) patients were alive without disease, and two patients died without disease. Median survival was 29 months (3-84 months) after pulmonary metastasectomy and 65 months (5-180 months) after gastrectomy. Fifty-six percent (24/43) of patients had another recurrence at a median of 12 months (range: 6-48 months) after resection including 30% (13/43) of patients with pulmonary recurrences. Overall 5-year survival was 33%.
Conclusions: Pulmonary metastasectomy for MGC can potentially result in long-term survival in a highly selected group of patients and should be considered for those who present with small, isolated lesions after a prolonged disease-free interval.
C1 [Kemp, Clinton D.; Kitano, Mio; Kerkar, Sid; Ripley, R. Taylor; Schrump, David S.; Avital, Itzhak] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Marquardt, Jens U.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Avital, I (reprint author), NCI, Surg Branch, NIH, Bldg 10 Hatfield CRC,Room 4-3961,10 Ctr Dr, Bethesda, MD 20892 USA.
EM avitali@mail.nih.gov
NR 40
TC 15
Z9 16
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 NOV
PY 2010
VL 5
IS 11
BP 1796
EP 1805
DI 10.1097/JTO.0b013e3181ed3514
PG 10
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 671HG
UT WOS:000283491100014
PM 20881648
ER
PT J
AU Espinoza, J
Lee, W
Comstock, C
Romero, R
Yeo, L
Rizzo, G
Paladini, D
Vinals, F
Achiron, R
Gindes, L
Abuhamad, A
Sinkovskaya, E
Russell, E
Yagel, S
AF Espinoza, Jimmy
Lee, Wesley
Comstock, Christine
Romero, Roberto
Yeo, Lami
Rizzo, Giuseppe
Paladini, Dario
Vinals, Fernando
Achiron, Reuven
Gindes, Liat
Abuhamad, Alfred
Sinkovskaya, Elena
Russell, Evie
Yagel, Simcha
TI Collaborative Study on 4-Dimensional Echocardiography for the Diagnosis
of Fetal Heart Defects The COFEHD Study
SO JOURNAL OF ULTRASOUND IN MEDICINE
LA English
DT Article
DE congenital heart defects; fetal echocardiography; 4-dimensional
ultrasonography; prenatal diagnosis
ID SPATIOTEMPORAL IMAGE CORRELATION; COLOR DOPPLER ULTRASOUND; VENTRICULAR
SEPTAL-DEFECT; PRENATAL-DIAGNOSIS; 3-DIMENSIONAL ECHOCARDIOGRAPHY;
CONOTRUNCAL ANOMALIES; PULMONARY-ARTERIES; INVERSION MODE; 3D
SONOGRAPHY; INTERNET LINK
AB Objective. Congenital anomalies are the leading cause of infant mortality in the United States, and congenital heart defects (CHDs) are the most common type of birth defects. Recently, 4-dimensional ultrasonography (4DUS) with spatiotemporal image correlation (STIC) has been introduced for fetal echocardiography. Accumulating evidence indicates that 4DUS with STIC may facilitate the examination of the fetal heart. Our objectives were to determine the accuracy of 4DUS for the diagnosis of CHDs and the agreement among centers. Methods. This study included 7 centers with expertise in 4D fetal echocardiography. Fetuses with and without confirmed heart defects were scanned between 18 and 26 weeks, and their volume data sets were uploaded onto a centralized file transfer protocol server. Intercenter agreement was determined using a kappa statistic for multiple raters. Results. Ninety volume data sets were randomly selected for blinded analysis. Overall, the median (range) sensitivity, specificity, positive and negative predictive values, and false-positive and -negative rates for the identification of fetuses with CHDs were 93% (77%-100%), 96% (84%-100%), 96% (83%-100%), 93% (79%-100%), 4.8% (2.7%-25%), and 6.8% (5%-22%), respectively. The most frequent CHDs were conotruncal anomalies (36%). There was excellent intercenter agreement (kappa = 0.97). Conclusions. (1) Four-dimensional volume data sets can be remotely acquired and accurately interpreted by different centers. (2) Among centers with technical expertise, 4DUS is an accurate and reliable method for fetal echocardiography.
C1 [Espinoza, Jimmy; Lee, Wesley; Comstock, Christine; Russell, Evie] William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48073 USA.
[Romero, Roberto; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA.
[Romero, Roberto; Yeo, Lami] Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA.
[Rizzo, Giuseppe] Univ Roma Tor Vergata, Dept Obstet & Gynecol, Rome, Italy.
[Paladini, Dario] Univ Naples Federico 2, Dept Obstet & Gynecol, Naples, Italy.
[Vinals, Fernando] Ctr AGB Ultrasonog, Clin Sanat Aleman, Concepcion, Chile.
[Achiron, Reuven; Gindes, Liat] Chaim Sheba Med Ctr, Dept Obstet & Gynecol, IL-52621 Tel Hashomer, Israel.
[Abuhamad, Alfred; Sinkovskaya, Elena] Eastern Virginia Med Sch, Dept Obstet & Gynecol, Norfolk, VA 23501 USA.
[Yagel, Simcha] Hebrew Univ Jerusalem, Dept Obstet & Gynecol, Hadassah Med Ctr, Jerusalem, Israel.
RP Espinoza, J (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3501 W 13 Mile Rd, Royal Oak, MI 48073 USA.
EM jimmy.espinoza@beaumont.edu
RI Paladini, Dario/E-1784-2013;
OI RIZZO, Giuseppe/0000-0002-5525-4353
NR 84
TC 26
Z9 28
U1 0
U2 2
PU AMER INST ULTRASOUND MEDICINE
PI LAUREL
PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906
USA
SN 0278-4297
J9 J ULTRAS MED
JI J. Ultrasound Med.
PD NOV
PY 2010
VL 29
IS 11
BP 1573
EP 1580
PG 8
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 685ZP
UT WOS:000284666900006
PM 20966468
ER
PT J
AU Benhammou, JN
Boris, RS
Pacak, K
Pinto, PA
Linehan, WM
Bratslavsky, G
AF Benhammou, Jihane N.
Boris, Ronald S.
Pacak, Karel
Pinto, Peter A.
Linehan, W. Marston
Bratslavsky, Gennady
TI Functional and Oncologic Outcomes of Partial Adrenalectomy for
Pheochromocytoma in Patients With von Hippel-Lindau Syndrome After at
Least 5 Years of Followup
SO JOURNAL OF UROLOGY
LA English
DT Article
DE pheochromocytoma; von Hippel-Lindau disease; adrenalectomy; neoplastic
syndromes, hereditary
ID LAPAROSCOPIC PARTIAL ADRENALECTOMY; SPARING-SURGERY; HEREDITARY
PHEOCHROMOCYTOMA; PARTIAL NEPHRECTOMY; NATURAL-HISTORY; DISEASE;
EXPERIENCE; PARAGANGLIOMAS; SCINTIGRAPHY; FEASIBILITY
AB Purpose: Although the safety and feasibility of partial adrenalectomy in patients with von Hippel-Lindau syndrome have been established, long-term outcomes have not been examined. In this study we evaluate the recurrence and functional outcomes in a von Hippel-Lindau syndrome cohort treated for pheochromocytoma with partial adrenalectomy with a followup of at least 5 years.
Materials and Methods: We reviewed the records of patients with von Hippel-Lindau syndrome treated with partial adrenalectomy for pheochromocytoma at the National Cancer Institute. Demographic, germline mutation status, surgical indication, oncologic and functional outcome data were collected. Local recurrence was defined as radiographic evidence of recurrent tumor on the ipsilateral side of partial adrenalectomy. Patients were considered steroid dependent if they required steroids at most recent followup.
Results: A total of 36 partial adrenalectomies for pheochromocytoma were performed in 26 patients with von Hippel-Lindau syndrome between September 1995 and December 2003. Of these cases 23 were performed open and 13 were performed laparoscopically. Prior surgical history was obtained for all patients. At a median followup of 9.25 years (range 5 to 46) metastatic pheochromocytoma had not developed in any patients. In 3 patients (11%) there were 5 local recurrences treated with surgical extirpation or active surveillance. All recurrences were asymptomatic and detected by radiographic imaging on followup. In addition, 3 of 26 patients (11%) subsequently required partial adrenalectomy for pheochromocytoma on the contralateral adrenal gland. In the entire cohort only 3 patients became steroid dependent (11%).
Conclusions: Outcomes of partial adrenalectomy in patients with von Hippel-Lindau syndrome with pheochromocytoma are encouraging at long-term followup and should be recommended as a primary surgical approach whenever possible. Adrenal sparing surgery can obviate the need for steroid replacement in the majority of patients. Local recurrence rates appear to be infrequent and can be managed successfully with subsequent observation or intervention.
C1 [Benhammou, Jihane N.; Boris, Ronald S.; Pacak, Karel; Pinto, Peter A.; Linehan, W. Marston; Bratslavsky, Gennady] NCI, Urol Oncol Branch, Ctr Canc Res, NIH,Dept Hlth Human Serv, Bethesda, MD 20892 USA.
RP Bratslavsky, G (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH,Dept Hlth Human Serv, Bldg 10 Room 1-5940, Bethesda, MD 20892 USA.
EM bratslag@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX Supported by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 25
TC 18
Z9 19
U1 0
U2 0
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 NOV
PY 2010
VL 184
IS 5
BP 1855
EP 1859
DI 10.1016/j.juro.2010.06.102
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 660XG
UT WOS:000282679200009
PM 20846682
ER
PT J
AU Pinto, PA
AF Pinto, Peter A.
TI Laparoscopic Partial Adrenalectomy
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
NR 4
TC 1
Z9 1
U1 0
U2 0
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 NOV
PY 2010
VL 184
IS 5
BP 1860
EP 1860
DI 10.1016/j.juro.2010.08.051
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 660XG
UT WOS:000282679200010
PM 20880555
ER
PT J
AU Venkatesan, AM
Kundu, S
Sacks, D
Wallace, MJ
Wojak, JC
Rose, SC
Clark, TWI
d'Othee, BJ
Itkin, M
Jones, RS
Miller, DL
Owens, CA
Rajan, DK
Stokes, LS
Swan, TL
Towbin, RB
Cardella, JF
AF Venkatesan, Aradhana M.
Kundu, Sanjoy
Sacks, David
Wallace, Michael J.
Wojak, Joan C.
Rose, Steven C.
Clark, Timothy W. I.
d'Othee, B. Janne
Itkin, Maxim
Jones, Robert S.
Miller, Donald L.
Owens, Charles A.
Rajan, Dheeraj K.
Stokes, LeAnn S.
Swan, Timothy L.
Towbin, Richard B.
Cardella, John F.
TI Practice Guideline for Adult Antibiotic Prophylaxis during Vascular and
Interventional Radiology Procedures
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Editorial Material
ID UTERINE ARTERY EMBOLIZATION; INTRAHEPATIC PORTOSYSTEMIC SHUNTS;
PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; RESISTANT STAPHYLOCOCCUS-AUREUS;
QUALITY IMPROVEMENT GUIDELINES; CLINICAL-PRACTICE GUIDELINES;
AMERICAN-HEART-ASSOCIATION; SURGICAL-WOUND-INFECTION; BLOOD-STREAM
INFECTIONS; LIVER-ABSCESS FORMATION
C1 [Venkatesan, Aradhana M.] NIH, Ctr Intervent Oncol Ridiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Miller, Donald L.] Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, Bethesda, MD 20814 USA.
[Miller, Donald L.] Natl Naval Med Ctr, Dept Radiol, Bethesda, MD USA.
[d'Othee, B. Janne] Univ Maryland, Med Ctr, Dept Radiol, Div Intervent Radiol, Baltimore, MD 21201 USA.
[Kundu, Sanjoy] Scarborough Gen Hosp, Dept Med Imaging, Scarborough, ON, Canada.
[Rajan, Dheeraj K.] Univ Toronto, Univ Hlth Network, Div Vasc & Intervent Radiol, Dept Med Imaging, Toronto, ON, Canada.
[Sacks, David] Reading Hosp Med Ctr, Dept Intervent Radiol, W Reading, England.
[Jones, Robert S.] Reading Hosp Med Ctr, Infect Dis Sect, W Reading, England.
[Itkin, Maxim] Univ Penn, Med Ctr, Dept Radiol, Div Intervent Radiol, Philadelphia, PA 19104 USA.
[Cardella, John F.] Geisinger Hlth Syst, Dept Radiol, Danville, PA USA.
[Wallace, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Intervent Radiol, Houston, TX 77030 USA.
[Wojak, Joan C.] Our Lady Lourdes Med Ctr, Dept Radiol, Lafayette, LA USA.
[Rose, Steven C.] Univ Calif San Diego, Med Ctr, Dept Radiol, San Diego, CA 92103 USA.
[Clark, Timothy W. I.] NYU, Sch Med, NYU Med Ctr, Dept Intervent Radiol, New York, NY USA.
[Owens, Charles A.] Univ Illinois, Med Ctr, Dept Radiol, Chicago, IL USA.
[Owens, Charles A.] Univ Illinois, Dept Surg, Med Ctr, Chicago, IL 60680 USA.
[Stokes, LeAnn S.] Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA.
[Swan, Timothy L.] Marshfield Clin Fdn Med Res & Educ, Dept Radiol, Marshfield, WI USA.
[Towbin, Richard B.] Phoenix Childrens Hosp, Dept Radiol, Phoenix, AZ USA.
RP Venkatesan, AM (reprint author), Care of Katsarelis D, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA.
RI Janne d'Othee, Bertrand/E-8467-2010
NR 125
TC 68
Z9 77
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD NOV
PY 2010
VL 21
IS 11
BP 1611
EP 1630
DI 10.1016/j.jvir.2010.07.018
PG 20
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 680OL
UT WOS:000284244200001
PM 21029949
ER
PT J
AU Miyagi, E
Brown, CR
Opi, S
Khan, M
Goila-Gaur, R
Kao, S
Walker, RC
Hirsch, V
Strebel, K
AF Miyagi, Eri
Brown, Charles R.
Opi, Sandrine
Khan, Mohammad
Goila-Gaur, Ritu
Kao, Sandra
Walker, Robert C., Jr.
Hirsch, Vanessa
Strebel, Klaus
TI Stably Expressed APOBEC3F Has Negligible Antiviral Activity
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4(+) T-CELLS; REVERSE TRANSCRIPTION;
VIRAL-RNA; ANTIRETROVIRAL FACTOR; CYTIDINE DEAMINATION; HIV-1
REPLICATION; A MUTATIONS; VIF PROTEIN; DNA
AB APOBEC3F (A3F) is a member of the family of cytidine deaminases that is often coexpressed with APOBEC3G (A3G) in cells susceptible to HIV infection. A3F has been shown to have strong antiviral activity in transient-expression studies, and together with A3G, it is considered the most potent cytidine deaminase targeting HIV. Previous analyses suggested that the antiviral properties of A3F can be dissociated from its catalytic deaminase activity. We were able to confirm the deaminase-independent antiviral activity of exogenously expressed A3F; however, we also noted that exogenous expression was associated with very high A3F mRNA and protein levels. In analogy to our previous study of A3G, we produced stable HeLa cell lines constitutively expressing wild-type or deaminase-defective A3F at levels that were more in line with the levels of endogenous A3F in H9 cells. A3F expressed in stable HeLa cells was packaged into Vif-deficient viral particles with an efficiency similar to that of A3G and was properly targeted to the viral nucleoprotein complex. Surprisingly, however, neither wild-type nor deaminase-defective A3F inhibited HIV-1 infectivity. These results imply that the antiviral activity of endogenous A3F is negligible compared to that of A3G.
C1 [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 Antibodies to Vif (MAb 319) and A3F were obtained from Michael Malim
through the NIH AIDS Research and Reference Reagent Program. The vector
for expression of A3F was obtained from Matija Peterlin and Yong-Hui
Zheng through the NIH AIDS Research and Reference Reagent Program. 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 57
TC 32
Z9 32
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 NOV
PY 2010
VL 84
IS 21
BP 11067
EP 11075
DI 10.1128/JVI.01249-10
PG 9
WC Virology
SC Virology
GA 660LE
UT WOS:000282643400013
PM 20702622
ER
PT J
AU Du, M
Butchi, NB
Woods, T
Morgan, TW
Peterson, KE
AF Du, Min
Butchi, Niranjan B.
Woods, Tyson
Morgan, Timothy W.
Peterson, Karin E.
TI Neuropeptide Y Has a Protective Role during Murine Retrovirus-Induced
Neurological Disease
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; VIRUS-INFECTION; BRAIN DISEASE; IMMUNE-SYSTEM;
RECEPTORS; MICE; PROTEIN; NEUROPATHOGENESIS; SEIZURES; CONTRIBUTE
AB Viral infections in the central nervous system (CNS) can lead to neurological disease either directly by infection of neurons or indirectly through activation of glial cells and production of neurotoxic molecules. Understanding the effects of virus-mediated insults on neuronal responses and neurotrophic support is important in elucidating the underlying mechanisms of viral diseases of the CNS. In the current study, we examined the expression of neurotrophin-and neurotransmitter-related genes during infection of mice with neurovirulent polytropic retrovirus. In this model, virus-induced neuropathogenesis is indirect, as the virus predominantly infects macrophages and microglia and does not productively infect neurons or astrocytes. Virus infection is associated with glial cell activation and the production of proinflammatory cytokines in the CNS. In the current study, we identified increased expression of neuropeptide Y (NPY), a pleiotropic growth factor which can regulate both immune cells and neuronal cells, as a correlate with neurovirulent virus infection. Increased levels of Npy mRNA were consistently associated with neurological disease in multiple strains of mice and were induced only by neurovirulent, not avirulent, virus infection. NPY protein expression was primarily detected in neurons near areas of virus-infected cells. Interestingly, mice deficient in NPY developed neurological disease at a faster rate than wild-type mice, indicating a protective role for NPY. Analysis of NPY-deficient mice indicated that NPY may have multiple mechanisms by which it influences virus-induced neurological disease, including regulating the entry of virus-infected cells into the CNS.
C1 [Du, Min; Butchi, Niranjan B.; Woods, Tyson; Peterson, Karin E.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA.
[Morgan, Timothy W.] Louisiana State Univ, Dept Pathobiol Sci, Sch Vet Med, Baton Rouge, LA 70803 USA.
RP Peterson, KE (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA.
EM petersonka@niaid.nih.gov
RI Peterson, Karin/D-1492-2016
OI Peterson, Karin/0000-0003-4177-7249
FU NIH; National Center for Research Resources [IP20RR020159]
FX This work was supported in part by the Intramural Research Program of
the NIH and in part by National Center for Research Resources grant
IP20RR020159.
NR 38
TC 16
Z9 16
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 NOV
PY 2010
VL 84
IS 21
BP 11076
EP 11088
DI 10.1128/JVI.01022-10
PG 13
WC Virology
SC Virology
GA 660LE
UT WOS:000282643400014
PM 20702619
ER
PT J
AU Yu, C
Boon, D
McDonald, SL
Myers, TG
Tomioka, K
Nguyen, H
Engle, RE
Govindarajan, S
Emerson, SU
Purcell, RH
AF Yu, Claro
Boon, Denali
McDonald, Shannon L.
Myers, Timothy G.
Tomioka, Keiko
Nguyen, Hanh
Engle, Ronald E.
Govindarajan, Sugantha
Emerson, Suzanne U.
Purcell, Robert H.
TI Pathogenesis of Hepatitis E Virus and Hepatitis C Virus in Chimpanzees:
Similarities and Differences
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID GENE-EXPRESSION; NUCLEOTIDE-SEQUENCE; IMMUNE-RESPONSES; INFECTION;
PROTEIN; RNA; IDENTIFICATION; CELLS; LIVER; HISTOLOGY
AB The chimpanzee is the only animal model for investigating the pathogenesis of viral hepatitis types A through E in humans. Studies of the host response, including microarray analyses, have relied on the close relationship between these two primate species: chimpanzee samples are commonly tested with human-based reagents. In this study, the host responses to two dissimilar viruses, hepatitis E virus (HEV) and hepatitis C virus (HCV), were compared in multiple experimentally infected chimpanzees. Affymetrix U133 + 2.0 human microarray chips were used to assess the entire transcriptome in serial liver biopsies obtained over the course of the infections. Respecting the limitations of microarray probes designed for human target transcripts to effectively assay chimpanzee transcripts, we conducted probe-level analysis of the microarray data in conjunction with a custom mapping of the probe sequences to the most recent human and chimpanzee genome sequences. Time points for statistical comparison were chosen based on independently measured viremia levels. Regardless of the viral infection, the alignment of differentially expressed genes to the human genome sequence resulted in a larger number of genes being identified when compared with alignment to the chimpanzee genome sequence. This probably reflects the lesser refinement of gene annotation for chimpanzees. In general, the two viruses demonstrated very distinct temporal changes in host response genes, although both RNA viruses induced genes that were involved in many of the same biological systems, including interferon-induced genes. The host response to HCV infection was more robust in the magnitude and number of differentially expressed genes compared to HEV infection.
C1 [Yu, Claro; Boon, Denali; McDonald, Shannon L.; Tomioka, Keiko; Nguyen, Hanh; Engle, Ronald E.; Emerson, Suzanne U.; Purcell, Robert H.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Myers, Timothy G.] NIAID, Res & Technol Branch, NIH, Bethesda, MD 20892 USA.
[Govindarajan, Sugantha] Rancho Los Amigos Med Ctr, Dept Pathol, Downey, CA 90241 USA.
RP Purcell, RH (reprint author), NIAID, Infect Dis Lab, NIH, 50 South Dr,Bldg 50,Rm 6523, Bethesda, MD 20892 USA.
EM rpurcell@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases; Laboratory of Immunopathogenesis and Bioinformatics
at SAIC-Frederick, Inc.
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.; We thank Stacy Ricklefs and Karin Bok for
providing guidance on developing the qRT-PCR procedure. We are grateful
to Jun Yang, Brandie Fullmer, Marjorie Bosche, and Wuxing Yuan, the
Laboratory of Immunopathogenesis and Bioinformatics at SAIC-Frederick,
Inc., for their support and for performing the chip hybridization; and
Kathleen Meyer for assisting with the GEO submission. Lastly, we thank
Marisa St. Claire, Max Shapiro, and Charlene Shaver for the care and
handling of the chimpanzees in this study.
NR 48
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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 NOV
PY 2010
VL 84
IS 21
BP 11264
EP 11278
DI 10.1128/JVI.01205-10
PG 15
WC Virology
SC Virology
GA 660LE
UT WOS:000282643400032
PM 20739520
ER
PT J
AU Kim, S
Kim, N
Presson, AP
An, DS
Mao, SH
Bonifacino, AC
Donahue, RE
Chow, SA
Chen, ISY
AF Kim, Sanggu
Kim, Namshin
Presson, Angela P.
An, Dong Sung
Mao, Si Hua
Bonifacino, Aylin C.
Donahue, Robert E.
Chow, Samson A.
Chen, Irvin S. Y.
TI High-Throughput, Sensitive Quantification of Repopulating Hematopoietic
Stem Cell Clones
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SEVERE COMBINED IMMUNODEFICIENCY; CHRONIC GRANULOMATOUS-DISEASE;
GENE-THERAPY; VECTOR INTEGRATION; RETROVIRAL VECTORS; LENTIVIRAL VECTOR;
CD34(+) CELLS; SCID-X1; EXPRESSION; PROLIFERATION
AB Retroviral vector-mediated gene therapy has been successfully used to correct genetic diseases. However, a number of studies have shown a subsequent risk of cancer development or aberrant clonal growths due to vector insertion near or within proto-oncogenes. Recent advances in the sequencing technology enable high-throughput clonality analysis via vector integration site (VIS) sequencing, which is particularly useful for studying complex polyclonal hematopoietic progenitor/stem cell (HPSC) repopulation. However, clonal repopulation analysis using the current methods is typically semiquantitative. Here, we present a novel system and standards for accurate clonality analysis using 454 pyrosequencing. We developed a bidirectional VIS PCR method to improve VIS detection by concurrently analyzing both the 5' and the 3' vector-host junctions and optimized the conditions for the quantitative VIS sequencing. The assay was validated by quantifying the relative frequencies of hundreds of repopulating HPSC clones in a nonhuman primate. The reliability and sensitivity of the assay were assessed using clone-specific real-time PCR. The majority of tested clones showed a strong correlation between the two methods. This assay permits high-throughput and sensitive assessment of clonal populations and hence will be useful for a broad range of gene therapy, stem cell, and cancer research applications.
C1 [Chen, Irvin S. Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
[Chow, Samson A.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Presson, Angela P.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA.
[Mao, Si Hua; Chen, Irvin S. Y.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA.
[Presson, Angela P.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90095 USA.
[Kim, Sanggu; Presson, Angela P.; An, Dong Sung; Mao, Si Hua; Chow, Samson A.; Chen, Irvin S. Y.] Univ Calif Los Angeles, UCLA AIDS Inst, Los Angeles, CA 90095 USA.
[An, Dong Sung] Univ Calif Los Angeles, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Kim, Namshin] Korea Res Inst Biosci & Biotechnol, Taejon 305806, South Korea.
[Bonifacino, Aylin C.; Donahue, Robert E.] NHLBI, Hematol Branch, NIH, Rockville, MD 20850 USA.
RP Chen, ISY (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, 615 Charles E Young Dr S,BSRB 173, Los Angeles, CA 90095 USA.
EM syuchen@mednet.ucla.edu
FU NIH [AI055281-06A2, CA68859]; California Institute of Regenerative
Medicine [RS1-00172-01]; UCLA AIDS Institute/Center for AIDS Research
[AI28697]; National Heart, Lung, and Blood Institute, NIH
FX This study was partly funded by the NIH (AI055281-06A2 and CA68859), the
California Institute of Regenerative Medicine (RS1-00172-01), and the
UCLA AIDS Institute/Center for AIDS Research (AI28697) and was supported
in part by the Intramural Research Program of the National Heart, Lung,
and Blood Institute, NIH.
NR 36
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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 NOV
PY 2010
VL 84
IS 22
BP 11771
EP 11780
DI 10.1128/JVI.01355-10
PG 10
WC Virology
SC Virology
GA 670KM
UT WOS:000283420500016
PM 20844053
ER
PT J
AU Levine, JR
Prescott, J
Brown, KS
Best, SM
Ebihara, H
Feldmann, H
AF Levine, Jessica R.
Prescott, Joseph
Brown, Kyle S.
Best, Sonja M.
Ebihara, Hideki
Feldmann, Heinz
TI Antagonism of Type I Interferon Responses by New World Hantaviruses
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SIN-NOMBRE HANTAVIRUS; INNATE IMMUNE-RESPONSES; TO-PERSON TRANSMISSION;
HEPATITIS-C VIRUS; INFLUENZA-A VIRUS; RIG-I; NUCLEOCAPSID PROTEIN;
PULMONARY SYNDROME; NS1 PROTEIN; ANDES VIRUS
AB Evasion of interferon (IFN)-mediated antiviral signaling is a common defense strategy for pathogenic RNA viruses. To date, research on IFN antagonism by hantaviruses is limited and has focused on only a subset of the numerous recognized hantavirus species. The host IFN response has two phases, an initiation phase, resulting in the induction of alpha/beta IFN (IFN-alpha/beta), and an amplification phase, whereby IFN-alpha/beta signals through the Jak/STAT pathway, resulting in the establishment of the cellular antiviral state. We examined interactions between these critical host responses and the New World hantaviruses. We observed delayed cellular responses in both Andes virus (ANDV)- and Sin Nombre virus (SNV)-infected A549 and Huh7-TLR3 cells. We found that IFN-beta induction is inhibited by coexpression of ANDV nucleocapsid protein (NP) and glycoprotein precursor (GPC) and is robustly inhibited by SNV GPC alone. Downstream amplification by Jak/STAT signaling is also inhibited by SNV GPC and by either NP or GPC of ANDV. Therefore, ANDV- and SNV-encoded proteins have the potential for inhibiting both IFN-beta induction and signaling, with SNV exhibiting the more potent antagonism ability. Herein we identify ANDV NP, a previously unrecognized inhibitor of Jak/STAT signaling, and show that IFN antagonism by ANDV relies on expression of both the glycoproteins and NP, whereas the glycoproteins appear to be sufficient for antagonism by SNV. These data suggest that IFN antagonism strategies by hantaviruses are quite variable, even between species with similar disease phenotypes, and may help to better elucidate species-specific pathogenesis.
C1 [Ebihara, Hideki] NIAID, Rocky Mt Labs, Virol Lab, Div Intramural Res,NIH, Hamilton, MT 59840 USA.
[Levine, Jessica R.] Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA.
[Levine, Jessica R.; Brown, Kyle S.; Ebihara, Hideki; Feldmann, Heinz] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB R3E 3R2, Canada.
[Brown, Kyle S.; Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0J9, Canada.
RP Ebihara, H (reprint author), NIAID, Rocky Mt Labs, Virol Lab, Div Intramural Res,NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM ebiharah@niaid.nih.gov; feldmannh@niaid.nih.gov
OI Spengler, Jessica R./0000-0002-5383-0513
FU Division of Intramural Research, National Institute of Allergy and
Infectious Disease, National Institutes of Health; Public Health Agency
of Canada; University of California, Davis, School of Veterinary
Medicine
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Disease, National Institutes of
Health, and the Public Health Agency of Canada. J.L. was supported by
funding from the Veterinary Scientist Training Program and the Students
Training in Advanced Research programs of the University of California,
Davis, School of Veterinary Medicine.
NR 63
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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 NOV
PY 2010
VL 84
IS 22
BP 11790
EP 11801
DI 10.1128/JVI.00916-10
PG 12
WC Virology
SC Virology
GA 670KM
UT WOS:000283420500018
PM 20844031
ER
PT J
AU Chutinimitkul, S
Herfst, S
Steel, J
Lowen, AC
Ye, JQ
van Riel, D
Schrauwen, EJA
Bestebroer, TM
Koel, B
Burke, DF
Sutherland-Cash, KH
Whittleston, CS
Russell, CA
Wales, DJ
Smith, DJ
Jonges, M
Meijer, A
Koopmans, M
Rimmelzwaan, GF
Kuiken, T
Osterhaus, ADME
Garcia-Sastre, A
Perez, DR
Fouchier, RAM
AF Chutinimitkul, Salin
Herfst, Sander
Steel, John
Lowen, Anice C.
Ye, Jianqiang
van Riel, Debby
Schrauwen, Eefje J. A.
Bestebroer, Theo M.
Koel, Bjorn
Burke, David F.
Sutherland-Cash, Kyle H.
Whittleston, Chris S.
Russell, Colin A.
Wales, David J.
Smith, Derek J.
Jonges, Marcel
Meijer, Adam
Koopmans, Marion
Rimmelzwaan, Guus F.
Kuiken, Thijs
Osterhaus, Albert D. M. E.
Garcia-Sastre, Adolfo
Perez, Daniel R.
Fouchier, Ron A. M.
TI Virulence-Associated Substitution D222G in the Hemagglutinin of 2009
Pandemic Influenza A(H1N1) Virus Affects Receptor Binding
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SINGLE AMINO-ACID; LOWER RESPIRATORY-TRACT; A H1N1 VIRUS;
MOLECULAR-BASIS; SEVERE DISEASE; H5N1 VIRUSES; HUMAN AIRWAY; HONG-KONG;
HUMANS; TRANSMISSION
AB The clinical impact of the 2009 pandemic influenza A(H1N1) virus (pdmH1N1) has been relatively low. However, amino acid substitution D222G in the hemagglutinin of pdmH1N1 has been associated with cases of severe disease and fatalities. D222G was introduced in a prototype pdmH1N1 by reverse genetics, and the effect on virus receptor binding, replication, antigenic properties, and pathogenesis and transmission in animal models was investigated. pdmH1N1 with D222G caused ocular disease in mice without further indications of enhanced virulence in mice and ferrets. pdmH1N1 with D222G retained transmissibility via aerosols or respiratory droplets in ferrets and guinea pigs. The virus displayed changes in attachment to human respiratory tissues in vitro, in particular increased binding to macrophages and type II pneumocytes in the alveoli and to tracheal and bronchial submucosal glands. Virus attachment studies further indicated that pdmH1N1 with D222G acquired dual receptor specificity for complex alpha 2,3- and alpha 2,6-linked sialic acids. Molecular dynamics modeling of the hemagglutinin structure provided an explanation for the retention of alpha 2,6 binding. Altered receptor specificity of the virus with D222G thus affected interaction with cells of the human lower respiratory tract, possibly explaining the observed association with enhanced disease in humans.
C1 [Chutinimitkul, Salin; Herfst, Sander; van Riel, Debby; Schrauwen, Eefje J. A.; Bestebroer, Theo M.; Koel, Bjorn; Smith, Derek J.; Rimmelzwaan, Guus F.; Kuiken, Thijs; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.] Erasmus MC, Natl Influenza Ctr, Rotterdam, Netherlands.
[Chutinimitkul, Salin; Herfst, Sander; van Riel, Debby; Schrauwen, Eefje J. A.; Bestebroer, Theo M.; Koel, Bjorn; Smith, Derek J.; Rimmelzwaan, Guus F.; Kuiken, Thijs; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.] Erasmus MC, Dept Virol, Rotterdam, Netherlands.
[Steel, John; Lowen, Anice C.; Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Microbiol, New York, NY USA.
[Ye, Jianqiang; Perez, Daniel R.] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA.
[Burke, David F.; Russell, Colin A.; Smith, Derek J.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
[Sutherland-Cash, Kyle H.; Whittleston, Chris S.; Wales, David J.] Univ Cambridge, Univ Chem Labs, Cambridge CB2 1EW, England.
[Jonges, Marcel; Meijer, Adam; Koopmans, Marion] Natl Inst Publ Hlth & Environm, Lab Infect Dis & Screening, NL-3720 BA Bilthoven, Netherlands.
[Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Div Infect Dis, Dept Med, New York, NY USA.
[Osterhaus, Albert D. M. E.] Mt Sinai Sch Med, Global Hlth & Emerging Pathogens Inst, New York, NY USA.
[Russell, Colin A.; Smith, Derek J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Fouchier, RAM (reprint author), Erasmus MC, Dept Virol, POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM r.fouchier@erasmusmc.nl
RI burke, david/C-2091-2013; Wei, Jianjian/F-7788-2011; Fouchier,
Ron/A-1911-2014;
OI Wei, Jianjian/0000-0001-8859-8462; Fouchier, Ron/0000-0001-8095-2869;
burke, david/0000-0001-8830-3951; Osterhaus, Albert/0000-0002-6074-1172;
Garcia-Sastre, Adolfo/0000-0002-6551-1827; Russell,
Colin/0000-0002-2113-162X; Perez, Daniel/0000-0002-6569-5689
FU NIAID-NIH [HHSN266200700010C]; European Union [223498]; NIH
[DP1-OD000490-01]; HFSP; EPSRC
FX This study was financed through NIAID-NIH contract HHSN266200700010C and
by the European Union FP7 European Management Platform for Emerging and
Re-emerging Infectious Disease Entities (EMPERIE) project (223498).
D.J.S. and D. F. B. were supported by NIH Director's Pioneer Award
DP1-OD000490-01. C. A. R. thanks the HFSP for support, and C. S. W. and
D.J.W. thank the EPSRC for support.
NR 56
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U1 3
U2 18
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 NOV
PY 2010
VL 84
IS 22
BP 11802
EP 11813
DI 10.1128/JVI.01136-10
PG 12
WC Virology
SC Virology
GA 670KM
UT WOS:000283420500019
PM 20844044
ER
PT J
AU Horton, DL
McElhinney, LM
Marston, DA
Wood, JLN
Russell, CA
Lewis, N
Kuzmin, IV
Fouchier, RAM
Osterhaus, ADME
Fooks, AR
Smith, DJ
AF Horton, D. L.
McElhinney, L. M.
Marston, D. A.
Wood, J. L. N.
Russell, C. A.
Lewis, N.
Kuzmin, I. V.
Fouchier, R. A. M.
Osterhaus, A. D. M. E.
Fooks, A. R.
Smith, D. J.
TI Quantifying Antigenic Relationships among the Lyssaviruses
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RABIES VIRUS GLYCOPROTEIN; LAGOS-BAT-VIRUS; A H3N2 VIRUSES; DUVENHAGE
VIRUS; PHYLOGENETIC-RELATIONSHIPS; GENETIC EVOLUTION; CROSS-PROTECTION;
INFLUENZA; DYNAMICS; VACCINES
AB All lyssaviruses cause fatal encephalitis in mammals. There is sufficient antigenic variation within the genus to cause variable vaccine efficacy, but this variation is difficult to characterize quantitatively: sequence analysis cannot yet provide detailed antigenic information, and antigenic neutralization data have been refractory to high-resolution robust interpretation. Here, we address these issues by using state-of-the-art antigenic analyses to generate a high-resolution antigenic map of a global panel of 25 lyssaviruses. We compared the calculated antigenic distances with viral glycoprotein ectodomain sequence data. Although 67% of antigenic variation was predictable from the glycoprotein amino acid sequence, there are in some cases substantial differences between genetic and antigenic distances, thus highlighting the risk of inferring antigenic relationships solely from sequence data at this time. These differences included epidemiologically important antigenic differences between vaccine strains and wild-type rabies viruses. Further, we quantitatively assessed the antigenic relationships measured by using rabbit, mouse, and human sera, validating the use of nonhuman experimental animals as a model for determining antigenic variation in humans. The use of passive immune globulin is a crucial component of rabies postexposure prophylaxis, and here we also show that it is possible to predict the reactivity of immune globulin against divergent lyssaviruses.
C1 [Horton, D. L.; McElhinney, L. M.; Marston, D. A.; Fooks, A. R.] Vet Labs Agcy Weybridge, Addlestone KT15 3NB, Surrey, England.
[Horton, D. L.; Wood, J. L. N.; Lewis, N.] Cambridge Infect Dis Consortium, Dept Vet Med, Cambridge CB2 1DQ, England.
[Horton, D. L.; Russell, C. A.; Lewis, N.; Smith, D. J.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
[Kuzmin, I. V.] Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA.
[Fouchier, R. A. M.; Osterhaus, A. D. M. E.; Smith, D. J.] Erasmus MC, Dept Virol, NL-3015 GE Rotterdam, Netherlands.
[Russell, C. A.; Smith, D. J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[McElhinney, L. M.; Fooks, A. R.] Univ Liverpool, Natl Ctr Zoonosis Res, Neston CH64 7TE, England.
RP Horton, DL (reprint author), Vet Labs Agcy Weybridge, Addlestone KT15 3NB, Surrey, England.
EM d.horton@vla.defra.gsi.gov.uk
RI McElhinney, Lorraine/C-7997-2011; Marston, Denise/D-7993-2011; Horton,
Daniel/D-9909-2011; Wood, James/A-1626-2008; APHA, Staff
publications/E-6082-2010; Fooks, Anthony/F-5418-2010; Fouchier,
Ron/A-1911-2014;
OI McElhinney, Lorraine/0000-0002-6022-348X; Marston,
Denise/0000-0001-9215-088X; Horton, Daniel/0000-0002-9126-2756; Wood,
James/0000-0002-0258-3188; Fouchier, Ron/0000-0001-8095-2869; Russell,
Colin/0000-0002-2113-162X
FU Cambridge Infectious Diseases Consortium; DEFRA Veterinary Training and
Research Initiative; DEFRA [SEO420, SEO423, SEO424]; NIH part of the NIH
road map for medical research [DP1-OD000490-01, 223498]; European Union;
Human Frontier Science Program [P0050/2008]; Alborada Trust; Science and
Technology Directorate, Department of Homeland Security; Royal Society,
London; Clare College, Cambridge
FX D. L. H., J.L.N.W., and N.L. were supported by the Cambridge Infectious
Diseases Consortium, a DEFRA Veterinary Training and Research
Initiative. D. A. M., L. M. M., and A. R. F. were supported by DEFRA
grants SEO420, SEO423, and SEO424. D.J.S. and C. A. R. were supported by
an NIH Director's Pioneer Award, part of the NIH road map for medical
research, through grant DP1-OD000490-01; 223498 EMPERIE, an FP7 grant
from the European Union; and program grant P0050/2008 from the Human
Frontier Science Program. J.L.N.W. was also supported by the Alborada
Trust and the RAPIDD program of the Science and Technology Directorate,
Department of Homeland Security. C. A. R. was also supported by a
University Research Fellowship from the Royal Society, London, and a
research fellowship from Clare College, Cambridge. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 55
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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 NOV
PY 2010
VL 84
IS 22
BP 11841
EP 11848
DI 10.1128/JVI.01153-10
PG 8
WC Virology
SC Virology
GA 670KM
UT WOS:000283420500023
PM 20826698
ER
PT J
AU Min, JY
Vogel, L
Matsuoka, Y
Lu, B
Swayne, D
Jin, H
Kemble, G
Subbarao, K
AF Min, Ji-Young
Vogel, Leatrice
Matsuoka, Yumiko
Lu, Bin
Swayne, David
Jin, Hong
Kemble, George
Subbarao, Kanta
TI A Live Attenuated H7N7 Candidate Vaccine Virus Induces Neutralizing
Antibody That Confers Protection from Challenge in Mice, Ferrets, and
Monkeys
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID INFLUENZA-A VIRUS; AVIAN-INFLUENZA; PANDEMIC INFLUENZA; HEALTHY-ADULTS;
TEMPERATURE SENSITIVITY; COMMERCIAL POULTRY; BRITISH-COLUMBIA;
HEMAGGLUTININ; PATHOGENICITY; GENERATION
AB A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (HA) and neuraminidase (NA) genes of highly pathogenic (HP) A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca) (H2N2) virus. The reassortant H7N7 NL/03 ca vaccine virus was temperature sensitive and attenuated in mice, ferrets, and African green monkeys (AGMs). Intranasal (i.n.) administration of a single dose of the H7N7 NL/03 ca vaccine virus fully protected mice from lethal challenge with homologous and heterologous H7 viruses from Eurasian and North American lineages. Two doses of the H7N7 NL/03 ca vaccine induced neutralizing antibodies in serum and provided complete protection from pulmonary replication of homologous and heterologous wild-type H7 challenge viruses in mice and ferrets. One dose of the H7N7 NL/03 ca vaccine elicited an antibody response in one of three AGMs that was completely protected from pulmonary replication of the homologous wild-type H7 challenge virus. The contribution of CD8(+) and/or CD4(+) T cells to the vaccine-induced protection of mice was evaluated by T-cell depletion; T lymphocytes were not essential for the vaccine-induced protection from lethal challenge with H7 wt viruses. Additionally, passively transferred neutralizing antibody induced by the H7N7 NL/03 ca virus protected mice from lethality following challenge with H7 wt viruses. The safety, immunogenicity, and efficacy of the H7N7 NL/03 ca vaccine virus in mice, ferrets, and AGMs support the evaluation of this vaccine virus in phase I clinical trials.
C1 [Min, Ji-Young; Vogel, Leatrice; Matsuoka, Yumiko; Subbarao, Kanta] NIAID, LID, NIH, Bethesda, MD 20892 USA.
[Lu, Bin; Jin, Hong; Kemble, George] Medimmune Inc, Mountain View, CA 94043 USA.
[Swayne, David] ARS, SE Poultry Res Lab, USDA, Athens, GA 30605 USA.
RP Subbarao, K (reprint author), NIAID, LID, NIH, 33 North Dr,MSC 3203,Room 3E13C1, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
FU NIAID, NIH
FX This research was performed as part of a Cooperative Research and
Development Agreement (CRADA) between the Laboratory of Infectious
Diseases, NIAID, and MedImmune and was supported in part by the
Intramural Research Program of the NIAID, NIH.
NR 42
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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 NOV
PY 2010
VL 84
IS 22
BP 11950
EP 11960
DI 10.1128/JVI.01305-10
PG 11
WC Virology
SC Virology
GA 670KM
UT WOS:000283420500034
PM 20810733
ER
PT J
AU Koh, Y
Amano, M
Towata, T
Danish, M
Leshchenko-Yashchuk, S
Das, D
Nakayama, M
Tojo, Y
Ghosh, AK
Mitsuya, H
AF Koh, Yasuhiro
Amano, Masayuki
Towata, Tomomi
Danish, Matthew
Leshchenko-Yashchuk, Sofiya
Das, Debananda
Nakayama, Maki
Tojo, Yasushi
Ghosh, Arun K.
Mitsuya, Hiroaki
TI In Vitro Selection of Highly Darunavir-Resistant and
Replication-Competent HIV-1 Variants by Using a Mixture of Clinical
HIV-1 Isolates Resistant to Multiple Conventional Protease Inhibitors
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID POTENT ACTIVITY; GAG PROTEIN; RECOMBINATION; PI; MUTATIONS;
SUBSTITUTIONS; PREVALENCE; EMERGENCE; TMC114; LIGAND
AB We attempted to select HIV-1 variants resistant to darunavir (DRV), which potently inhibits the enzymatic activity and dimerization of protease and has a high genetic barrier to HIV-1 development of resistance to DRV. We conducted selection using a mixture of 8 highly multi-protease inhibitor (PI)-resistant, DRV-susceptible clinical HIV-1 variants (HIV-1(MIX)) containing 9 to 14 PI resistance-associated amino acid substitutions in protease. HIV-1MIX became highly resistant to DRV, with a 50% effective concentration (EC50) similar to 333-fold greater than that against HIV-1(NL4-3). HIV-1(MIX) at passage 51 (HIV-1(MIXP51)) replicated well in the presence of 5 mu M DRV and contained 14 mutations. HIV-1(MIXP51) was highly resistant to amprenavir, indinavir, nelfinavir, ritonavir, lopinavir, and atazanavir and moderately resistant to saquinavir and tipranavir. HIV-1(MIXP51) had a resemblance with HIV-1(C) of the HIV-1(MIX) population, and selection using HIV-1(C) was also performed; however, its DRV resistance acquisition was substantially delayed. The H219Q and I223V substitutions in Gag, lacking in HIV-1(CP51), likely contributed to conferring a replication advantage on HIV-1(MIXP51) by reducing intravirion cyclophilin A content. HIV-1(MIXP51) apparently acquired the substitutions from another HIV-1 strain(s) of HIV-1(MIX) through possible homologous recombination. The present data suggest that the use of multiple drug-resistant HIV-1 isolates is of utility in selecting drug-resistant variants and that DRV would not easily permit HIV-1 to develop significant resistance; however, HIV-1 can develop high levels of DRV resistance when a variety of PI-resistant HIV-1 strains are generated, as seen in patients experiencing sequential PI failure, and ensuing homologous recombination takes place. HIV-1(MIXP51) should be useful in elucidating the mechanisms of HIV-1 resistance to DRV and related agents.
C1 [Koh, Yasuhiro; Amano, Masayuki; Towata, Tomomi; Danish, Matthew; Nakayama, Maki; Tojo, Yasushi; Mitsuya, Hiroaki] Kumamoto Univ, Dept Infect Dis, Grad Sch Med & Pharmaceut Sci, Kumamoto 8608556, Japan.
[Koh, Yasuhiro; Amano, Masayuki; Towata, Tomomi; Danish, Matthew; Nakayama, Maki; Tojo, Yasushi; Mitsuya, Hiroaki] Kumamoto Univ, Dept Hematol, Grad Sch Med & Pharmaceut Sci, Kumamoto 8608556, Japan.
[Leshchenko-Yashchuk, Sofiya; Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Leshchenko-Yashchuk, Sofiya; Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
[Das, Debananda; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, Malignancy Branch, NIH, Bethesda, MD 20892 USA.
RP Mitsuya, H (reprint author), Kumamoto Univ, Dept Infect Dis, Sch Med, 1-1-1 Honjo, Kumamoto 8608556, Japan.
EM hmitsuya@helix.nih.gov
RI Amano, Masayuki/N-7407-2016
OI Amano, Masayuki/0000-0003-0516-9502
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health; National Institutes of Health [GM 53386]; Japan
Society for the Promotion of Science (JSPS-RFTF) [97L00705]; Ministry of
Education, Culture, Sports, Science, and Technology of Japan; Ministry
of Health, Labor and Welfare of Japan
FX This work was supported in part by the Intramural Research Program of
the Center for Cancer Research, National Cancer Institute, National
Institutes of Health (D.D. and H.M.), a grant from the National
Institutes of Health (GM 53386, to A.K.G.), a grant from a Research for
the Future Program of Japan Society for the Promotion of Science
(JSPS-RFTF 97L00705, to H.M.), a Grant-in-Aid for Scientific Research
(Priority Areas, to H.M.) from the Ministry of Education, Culture,
Sports, Science, and Technology (Monbu-Kagakusho) of Japan (H.M.), and a
Grant for Promotion of AIDS Research from the Ministry of Health, Labor
and Welfare (Kosei-Rodosho) of Japan (to H.M.).
NR 26
TC 31
Z9 31
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD NOV
PY 2010
VL 84
IS 22
BP 11961
EP 11969
DI 10.1128/JVI.00967-10
PG 9
WC Virology
SC Virology
GA 670KM
UT WOS:000283420500035
PM 20810732
ER
PT J
AU Yan, YH
Liu, QP
Wollenberg, K
Martin, C
Buckler-White, A
Kozak, CA
AF Yan, Yuhe
Liu, Qingping
Wollenberg, Kurt
Martin, Carrie
Buckler-White, Alicia
Kozak, Christine A.
TI Evolution of Functional and Sequence Variants of the Mammalian XPR1
Receptor for Mouse Xenotropic Gammaretroviruses and the Human-Derived
Retrovirus XMRV
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MURINE LEUKEMIA VIRUSES; CELL-SURFACE RECEPTOR;
CHRONIC-FATIGUE-SYNDROME; MUS-MUSCULUS-MOLOSSINUS; HOST-RANGE;
INFECTIOUS RETROVIRUS; MAXIMUM-LIKELIHOOD; GENUS MUS; WILD MICE; C
VIRUSES
AB Genetic conflicts between retroviruses and their receptors result in the evolution of novel host entry restrictions and novel virus envelopes, and such variants can influence trans-species transmission. We screened rodents and other mammals for sequence variation in the Xpr1 receptor for the mouse xenotropic or polytropic mouse leukemia viruses (X-MLVs or P-MLVs, respectively) of the gammaretrovirus family and for susceptibility to mouse-derived X/P-MLVs and to XMRV (xenotropic murine leukemia virus-related virus), an X-MLV-like virus isolated from humans with prostate cancer and chronic fatigue syndrome. We identified multiple distinct susceptibility phenotypes; these include the four known Xpr1 variants in Mus and a novel fifth Xpr1 gene found in Mus molossinus and Mus musculus. We describe the geographic and species distribution of the Mus Xpr1 variants but failed to find the X-MLV-restrictive laboratory mouse allele in any wild mouse. We used mutagenesis and phylogenetic analysis to evaluate the functional contributions made by constrained, variable, and deleted residues. Rodent Xpr1 is under positive selection, indicating a history of host-pathogen conflicts; several codons under selection have known roles in virus entry. All non-Mus mammals are susceptible to mouse X-MLVs, but some restrict other members of the X/P-MLV family, and the resistance of hamster and gerbil cells to XMRV indicates that XMRV has unique receptor requirements. We show that the hypervariable fourth extracellular XPR1 loop (ECL4) contains three evolutionarily constrained residues that do not contribute to receptor function, we identify two novel residues important for virus entry (I579 and T583), and we describe a unique pattern of ECL4 variation in the three virus-restrictive Xpr1 variants found in MLV-infected house mice; these mice carry different deletions in ECL4, suggesting either that these sites or loop size affects receptor function.
C1 [Yan, Yuhe; Liu, Qingping; Martin, Carrie; Buckler-White, Alicia; Kozak, Christine A.] NIAID, NIH, LMM, Bethesda, MD 20892 USA.
[Wollenberg, Kurt] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, Bethesda, MD 20892 USA.
RP Kozak, CA (reprint author), NIAID, NIH, LMM, Bldg 4,Room 329,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA.
EM ckozak@niaid.nih.gov
OI Blanchard, Carrie/0000-0002-1236-4245
FU NIH, NIAID
FX This research was supported by the Intramural Research Program of the
NIH, NIAID.
NR 54
TC 24
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U1 1
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD NOV
PY 2010
VL 84
IS 22
BP 11970
EP 11980
DI 10.1128/JVI.01549-10
PG 11
WC Virology
SC Virology
GA 670KM
UT WOS:000283420500036
PM 20844050
ER
PT J
AU Murray, SM
Down, CM
Boulware, DR
Stauffer, WM
Cavert, WP
Schacker, TW
Brenchley, JM
Douek, DC
AF Murray, Shannon M.
Down, Carrie M.
Boulware, David R.
Stauffer, William M.
Cavert, Winston P.
Schacker, Timothy W.
Brenchley, Jason M.
Douek, Daniel C.
TI Reduction of Immune Activation with Chloroquine Therapy during Chronic
HIV Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL-ACTIVATION; LYMPHOCYTE-ACTIVATION;
HYDROXYCHLOROQUINE; CD4(+); CD38; ZIDOVUDINE
AB Increased levels of activated T cells are a hallmark of the chronic stage of human immunodeficiency virus (HIV) infection and are highly correlated with HIV disease progression. We evaluated chloroquine (CQ) as a potential therapy to reduce immune activation during HIV infection. We found that the frequency of CD38(+) HLA-DR(+) CD8 T cells, as well as Ki-67 expression in CD8 and CD4 T cells, was significantly reduced during CQ treatment. Our data indicate that treatment with CQ reduces systemic T-cell immune activation and, thus, that its use may be beneficial for certain groups of HIV-infected individuals.
C1 [Murray, Shannon M.; Down, Carrie M.; Brenchley, Jason M.; Douek, Daniel C.] NIAID, Human Immunol Sect, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Boulware, David R.; Stauffer, William M.; Cavert, Winston P.; Schacker, Timothy W.] Univ Minnesota, Dept Med, Div Infect Dis & Int Med, Minneapolis, MN 55455 USA.
RP Douek, DC (reprint author), NIAID, Human Immunol Sect, NIH, Vaccine Res Ctr, 40 Convent Dr,Room 4500, Bethesda, MD 20892 USA.
EM ddouek@mail.nih.gov
RI Boulware, David/B-5516-2011; Boulware, David/I-4533-2013;
OI Boulware, David/0000-0002-4715-0060
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [5U01-AI1027661-19]; Minnesota Medical Foundation;
International Center for Antiviral Research and Epidemiology
FX This work was supported in part by the Intramural Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health (5U01-AI1027661-19); the Minnesota Medical
Foundation; and the International Center for Antiviral Research and
Epidemiology (I CARE).
NR 22
TC 70
Z9 71
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 NOV
PY 2010
VL 84
IS 22
BP 12082
EP 12086
DI 10.1128/JVI.01466-10
PG 5
WC Virology
SC Virology
GA 670KM
UT WOS:000283420500048
PM 20844049
ER
PT J
AU Muniyappa, R
Veldhuis, JD
Harman, SM
Sorkin, JD
Blackman, MR
AF Muniyappa, Ranganath
Veldhuis, Johannes D.
Harman, S. Mitchell
Sorkin, John D.
Blackman, Marc R.
TI Effects of Testosterone Administration on Nocturnal Cortisol Secretion
in Healthy Older Men
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Aging; Testosterone; Cortisol
ID PITUITARY-ADRENAL AXIS; RANDOMIZED CONTROLLED-TRIAL; SEX-DIFFERENCES;
GROWTH-HORMONE; DEHYDROEPIANDROSTERONE SECRETION; PSYCHOSOCIAL STRESS;
PLASMA-CORTISOL; STEROID-HORMONE; AGED WOMEN; GENDER
AB In animal studies, testosterone decreases, whereas estrogen increases, cortisol production. In one clinical study, short-term testosterone replacement attenuated corticotrophin-releasing hormone-stimulated cortisol secretion during leuprolide-induced hypogonadism in young men. The effects of longer term testosterone treatment on spontaneous cortisol secretion in younger or older men are unknown. In a randomized, double-masked placebo-controlled study, we assessed the effects of testosterone supplementation (100 mg intramuscular every 2 week) for 26 weeks on nocturnal cortisol secretory dynamics in healthy older men. Testosterone administration increased early morning serum concentrations of free testosterone by 34%, decreased sex hormone-binding globulin by 20%, and did not alter early morning concentrations of cortisol-binding globulin or cortisol compared with placebo treatment. Testosterone did not significantly alter nocturnal mean and integrated cortisol concentrations, cortisol burst frequency, mass/burst, basal secretion, pulsatile cortisol production rate, pattern regularity, or approximate entropy. We conclude that low-dose testosterone supplementation for 26 weeks does not affect spontaneous nocturnal cortisol secretion in healthy older men.
C1 [Muniyappa, Ranganath] Natl Ctr Complementary & Alternat Med, Diabet Unit, Clin Invest Lab, Natl Inst Hlth, Bethesda, MD USA.
[Veldhuis, Johannes D.] Mayo Clin, Clin Translat Res Ctr, Mayo Sch Grad Med Educ, Endocrine Res Unit, Rochester, MN USA.
[Harman, S. Mitchell; Blackman, Marc R.] NIA, Endocrinol Sect, Clin Invest Lab, Natl Inst Hlth, Baltimore, MD 21224 USA.
[Harman, S. Mitchell] Kronos Longev Res Inst, Phoenix, AZ USA.
[Sorkin, John D.] NIA, Metab Sect, Clin Invest Lab, Natl Inst Hlth, Baltimore, MD USA.
[Sorkin, John D.; Blackman, Marc R.] Baltimore Vet Affairs Med Ctr Geriatr Res Educ &, Dept Vet Affairs, Baltimore, MD USA.
[Sorkin, John D.] Univ Maryland, Sch Med, Claude D Pepper Older Amer Independence Ctr, Baltimore, MD 21201 USA.
[Blackman, Marc R.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Blackman, Marc R.] Vet Affairs Med Ctr, Res Serv, Washington, DC 20422 USA.
RP Blackman, MR (reprint author), Washington DC VA Med Ctr, Res Serv 151, 50 Irving St, Washington, DC 20422 USA.
EM marc.blackman@va.gov
FU National Center for Complementary and Alternative Medicine, Bethesda,
Maryland; National Institute on Aging, Baltimore, Maryland; National
Institutes of Health [RO-1 AG11005, DK073148]; National Center for
Research Resources, National Institutes of Health, Bethesda, Maryland
[MO-1-RR-02719]; Department of Veterans Affairs and Veterans Affairs
Medical Center Baltimore Geriatrics Research, Education and Clinical
Center; Claude D. Pepper Older Americans Independence Center at the
University of Maryland [P60-AG-12583]; Research Service, Veterans
Affairs Medical Center, Washington DC
FX Intramural Research Programs of the National Center for Complementary
and Alternative Medicine to R. M., Bethesda, Maryland and the National
Institute on Aging, Baltimore, Maryland; National Institutes of Health
Research Grants RO-1 AG11005 to M. R. B. and DK073148 to J.D.V.; General
Clinical Research Center Grant MO-1-RR-02719 to M. R. B. from the
National Center for Research Resources, National Institutes of Health,
Bethesda, Maryland; Department of Veterans Affairs and Veterans Affairs
Medical Center Baltimore Geriatrics Research, Education and Clinical
Center; Claude D. Pepper Older Americans Independence Center Grant
P60-AG-12583 to J.D.S. at the University of Maryland; and the Research
Service, Veterans Affairs Medical Center, Washington DC to M.R.B.
NR 49
TC 4
Z9 4
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD NOV
PY 2010
VL 65
IS 11
BP 1185
EP 1192
DI 10.1093/gerona/glq128
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 666PW
UT WOS:000283129300005
PM 20675620
ER
PT J
AU Cannon, CZ
Kissling, GE
Hoenerhoff, MJ
King-Herbert, AP
Blankenship-Paris, T
AF Cannon, Coralie Zegre
Kissling, Grace E.
Hoenerhoff, Mark J.
King-Herbert, Angela P.
Blankenship-Paris, Terry
TI Evaluation of dosages and routes of administration of tramadol analgesia
in rats using hot-plate and tail-flick tests
SO LAB ANIMAL
LA English
DT Article
ID TRANS-O-DEMETHYLTRAMADOL; ACTIVE METABOLITE; IN-VITRO; PAIN; MODEL;
EFFICACY; BUPRENORPHINE; MORPHINE; MOUSE; PHARMACOKINETICS
AB Tramadol is an opioid-Like analgesic with relatively mild side effects. Because it is inexpensive and is not classified as a controlled substance by the US federal government, the authors wanted to evaluate its applicability as a practical and effective analgesic in male Sprague Dawley rats. They measured the efficacy of four dosages (4, 12.5, 25 or 50 mg tramadol per kg body weight) and three routes of administration (per os (p.o.) in a flavored gelatin cube, subcutaneous (s.c.) or intraperitoneal (i.p.)) using the hot-plate test and the tail-flick test, which were carried out 1 week apart. Rats that were dosed p.o. were given flavored gelatin cubes without tramadol on the 2 d before testing to help them become acclimated to the gelatin, in an effort to increase the likelihood that they would consume the gelatin on the testing day. Results from the hot-plate and tail-flick tests for rats that were given tramadol p.o. were similar before and after administration, regardless of tramadol dosage, suggesting that this route of administration was not effective. The s.c. route of administration was effective at dosages of 25 mg and 50 mg tramadol per kg body weight, although these dosages also resulted in sedation and skin lesions. The i.p. route of administration was also effective at dosages of 12.5 mg, 25 mg and 50 mg tramadol per kg body weight, though sedation was observed at dosages of 25 mg and 50 mg per kg body weight. Intraperitoneal administration of 12.5 mg tramadol per kg body weight had no notable side effects, and the authors plan to further study this dosage and route of administration in a rodent surgical model of pain.
C1 [Cannon, Coralie Zegre; Hoenerhoff, Mark J.; King-Herbert, Angela P.] Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, Res Triangle Pk, NC USA.
[Kissling, Grace E.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA.
[Blankenship-Paris, Terry] Natl Inst Environm Hlth Sci, Comparat Med Branch, Res Triangle Pk, NC USA.
RP Cannon, CZ (reprint author), Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, Res Triangle Pk, NC USA.
EM cannonc@niehs.nih.gov
FU National Institutes of Health; National Institute of Environmental
Health Sciences
FX We thank Danielle Waxer, Page Myers, James Clark, Sandy Hackney, Jenetta
Jackson and Keisha Chavis for their assistance and support of the
research and care of the animals. We thank Dr. Larry Wright for
assistance in literature evaluation. We thank Dr. Sheryl Moy, Dr. Greg
Travlos and Dr. Gregory Cannon for their extensive reviews of the
manuscript. This research was supported by the Intramural Research
Program of the National Institutes of Health and the National Institute
of Environmental Health Sciences.
NR 47
TC 13
Z9 13
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
J9 LAB ANIMAL
JI Lab Anim.
PD NOV
PY 2010
VL 39
IS 11
BP 342
EP 351
PG 12
WC Veterinary Sciences
SC Veterinary Sciences
GA 674RR
UT WOS:000283766100011
PM 20962760
ER
PT J
AU Morisot, S
Wayne, AS
Bohana-Kashtan, O
Kaplan, IM
Gocke, CD
Hildreth, R
Stetler-Stevenson, M
Walker, RL
Davis, S
Meltzer, PS
Wheelan, SJ
Brown, P
Jones, RJ
Shultz, LD
Civin, CI
AF Morisot, S.
Wayne, A. S.
Bohana-Kashtan, O.
Kaplan, I. M.
Gocke, C. D.
Hildreth, R.
Stetler-Stevenson, M.
Walker, R. L.
Davis, S.
Meltzer, P. S.
Wheelan, S. J.
Brown, P.
Jones, R. J.
Shultz, L. D.
Civin, C. I.
TI High frequencies of leukemia stem cells in poor-outcome childhood
precursor-B acute lymphoblastic leukemias
SO LEUKEMIA
LA English
DT Article
DE childhood acute lymphoblastic leukemia; leukemia stem cells; xenograft
ID ACUTE MYELOID-LEUKEMIA; PRIMITIVE HEMATOPOIETIC-CELL; TUMOR-GROWTH NEED;
NOD-SCID MICE; INITIATING CELLS; NOD/SCID MICE; BONE-MARROW; CANCER;
ENGRAFTMENT; MOUSE
AB In order to develop a xenograft model to determine the efficacy of new therapies against primary human precursor-B acute lymphoblastic leukemia (ALL) stem cells (LSCs), we used the highly immunodeficient non-obese diabetic (NOD). Cg-Prkdc(scid) IL2rg(tmlWjl)/SzJ (NOD-severe combined immune deficient (scid) IL2rg(-/-)) mouse strain. Intravenous transplantation of 2 of 2 ALL cell lines and 9 of 14 primary ALL cases generated leukemia-like proliferations in recipient mice by 1-7 months after transplant. Leukemias were retransplantable, and the immunophenotypes, gene rearrangements and expression profiles were identical or similar to those of the original primary samples. NOD-scid mice transplanted with the same primary samples developed similar leukemias with only a slightly longer latency than did NOD-scid-IL2Rg(-/-) mice. In this highly sensitive NOD-scid-IL2Rg(-/-) -based assay, 1-100 unsorted primary human ALL cells from five of five tested patients, four of whom eventually experienced leukemia relapse, generated leukemias in recipient mice. This very high frequency of LSCs suggests that a hierarchical LSC model is not valuable for poor-outcome ALL. Leukemia (2010) 24, 1859-1866; doi:10.1038/leu.2010.184; published online 26 August 2010
C1 [Morisot, S.; Bohana-Kashtan, O.; Kaplan, I. M.; Hildreth, R.; Civin, C. I.] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA.
[Morisot, S.; Bohana-Kashtan, O.; Kaplan, I. M.; Hildreth, R.; Civin, C. I.] Univ Maryland, Sch Med, Ctr Stem Cell Biol & Regenerat Med, Baltimore, MD 21201 USA.
[Wayne, A. S.] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gocke, C. D.] Johns Hopkins Med Inst, Dept Pathol, Mol Diagnost Lab, Baltimore, MD 21205 USA.
[Gocke, C. D.] Johns Hopkins Med Inst, Dept Oncol, Mol Diagnost Lab, Baltimore, MD 21205 USA.
[Stetler-Stevenson, M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Walker, R. L.; Davis, S.; Meltzer, P. S.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Wheelan, S. J.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Div Biostat & Bioinformat, Baltimore, MD USA.
[Brown, P.] Johns Hopkins Univ, Sch Med, Div Pediat Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Jones, R. J.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Div Hematol Malignancies, Baltimore, MD USA.
[Shultz, L. D.] Jackson Lab, Bar Harbor, ME 04609 USA.
RP Civin, CI (reprint author), Univ Maryland, Sch Med, Dept Pediat, BRB 14-023,655 W Baltimore St, Baltimore, MD 21201 USA.
EM CCivin@som.umaryland.edu
OI Davis, Sean/0000-0002-8991-6458
FU Leukemia & Lymphoma Society [6082-08]; National Foundation for Cancer
Research, National Institutes of Health [P01CA070970]; CIC [CA34196];
NIH; National Cancer Institute and Center for Cancer Research
FX This research was supported in part by grants from the Leukemia &
Lymphoma Society (Translational Grant 6082-08), National Foundation for
Cancer Research, National Institutes of Health (P01CA070970) to CIC and
CA34196 to the Jackson Lab. This research was supported in part by the
Intramural Research Program of the NIH, National Cancer Institute and
Center for Cancer Research.
NR 57
TC 27
Z9 27
U1 2
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD NOV
PY 2010
VL 24
IS 11
BP 1859
EP 1866
DI 10.1038/leu.2010.184
PG 8
WC Oncology; Hematology
SC Oncology; Hematology
GA 678EV
UT WOS:000284057400005
PM 20739953
ER
PT J
AU Mailankody, S
Mena, E
Yuan, CM
Balakumaran, A
Kuehl, WM
Landgren, O
AF Mailankody, Sham
Mena, Esther
Yuan, Constance M.
Balakumaran, Arun
Kuehl, W. Michael
Landgren, Ola
TI Molecular and biologic markers of progression in monoclonal gammopathy
of undetermined significance to multiple myeloma
SO LEUKEMIA & LYMPHOMA
LA English
DT Review
DE Myeloma; MGUS; smoldering myeloma; prognosis; molecular imaging;
molecular profiling
ID GENE-EXPRESSION PROFILES; INDEPENDENT RISK-FACTOR; PLASMA-CELL
DYSCRASIAS; LIGHT-CHAIN RATIO; CHROMOSOMAL-ABNORMALITIES; SIGNIFICANCE
MGUS; LEUKEMIA GENOME; RAS MUTATIONS; UNITED-STATES; LONG-TERM
AB Multiple myeloma (MM) is a malignant plasma cell dyscrasia localized in the bone marrow. Recent studies have shown that MM is preceded in virtually all cases by a premalignant state called monoclonal gammopathy of undetermined significance (MGUS). This review focuses on non-IgM MGUS and its progression to MM. Although certain clinical markers of MGUS progression have been identified, it currently is not possible to accurately determine individual risk of progression. This review focuses on the various biologic and molecular markers that could be used to determine the risk of MM progression. A better understanding of the pathogenesis will allow us to define the biological high-risk precursor disease and, ultimately, to develop early intervention strategies designed to delay and prevent full-blown MM.= 3 MET.min(-1) for >= 10 min (moderate-to vigorous-intensity PA (MVPA)) and >= 6 MET.min(-1) for >= 10 min (vigorous-intensity PA (VPA)). Self-reported PA was also assessed with a questionnaire. Accelerometry and self-reported PA data were compared across categories of BMI, sex, race, age, fitness, diabetes medication usage, and history of cardiovascular disease. Results: Self-reported PA was lower at higher levels of BMI, was higher in males, was lowest for African-American/black, and was positively associated with fitness. Multivariate analyses for accelerometer-measured MVPA and VPA showed that more PA bouts per day, minutes per bout, METs per minute, and MET-minutes were associated with higher fitness. For MVPA, bouts per day were higher in men, and METs per minute were higher in women. For VPA, bouts per day was positively associated with increasing age and differed by race/ethnicity. METs per minute were significantly lower at higher levels of BMI and in women. Diabetes medication usage and history of cardiovascular disease were not associated with patterns of PA examined. Conclusions: Results provide information on factors that contribute to PA patterns in adults with T2DM when PA is assessed using both objective and subjective measures. These data may inform interventions to improve PA in adults with T2DM.
C1 [Jakicic, John M.] Univ Pittsburgh, Dept Hlth & Phys Act, Phys Act & Weight Management Res Ctr, Pittsburgh, PA 15260 USA.
[Gregg, Edward] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA.
[Knowler, William] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA.
[Kelley, David E.] Merck & Co Inc, Rahway, NJ 07065 USA.
[Lang, Wei; Walkup, Michael P.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Miller, Gary D.; Rejeski, W. Jack; Ribisl, Paul] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27109 USA.
[Pi-Sunyer, F. Xavier] St Lukes Roosevelt Hosp, Dept Med, New York, NY USA.
[Regensteiner, Judith G.] Univ Colorado Denver, Sch Med, Aurora, CO USA.
RP Jakicic, JM (reprint author), Univ Pittsburgh, Dept Hlth & Phys Act, Phys Act & Weight Management Res Ctr, 140 Trees Hall, Pittsburgh, PA 15260 USA.
EM jjakicic@pitt.edu
FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [M01 RR001346, M01 RR000051,
M01 RR000056, M01 RR001066, M01 RR002719]; NHLBI NIH HHS [R01 HL070257,
R01 HL070257-01A1]; NIDDK NIH HHS [P30 DK017047, P30 DK046204, P30
DK048520, U01 DK056990, U01 DK056992, U01 DK057002, U01 DK057008, U01
DK057078, U01 DK057131, U01 DK057135, U01 DK057136, U01 DK057149, U01
DK057151, U01 DK057154, U01 DK057171, U01 DK057177, U01 DK057178, U01
DK057182, U01 DK057219]
NR 21
TC 28
Z9 29
U1 0
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD NOV
PY 2010
VL 42
IS 11
BP 1995
EP 2005
DI 10.1249/MSS.0b013e3181e054f0
PG 11
WC Sport Sciences
SC Sport Sciences
GA 667XZ
UT WOS:000283231900004
PM 20386337
ER
PT J
AU Tom, SE
Kuh, D
Guralnik, JM
Mishra, GD
AF Tom, Sarah E.
Kuh, Diana
Guralnik, Jack M.
Mishra, Gita D.
TI Self-reported sleep difficulty during the menopausal transition: results
from a prospective cohort study
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE Menopause; Hysterectomy; Sleep; Longitudinal; Menopausal symptoms
ID WOMENS HEALTH; NATURAL MENOPAUSE; MULTIETHNIC COMMUNITY; RISK-FACTOR;
SYMPTOMS; MIDLIFE; DISTURBANCE; QUALITY; AGE; HYSTERECTOMY
AB Objective: The aim of this study was to examine the relationship between menopausal transition status and self-reported sleep difficulty.
Methods: With the use of data on women participating in the Medical Research Council National Survey of Health and Development who have been followed up from birth in March 1946 (n = 962), relationships between menopausal transition status and self-reported sleep difficulty were assessed annually in women between ages 48 and 54 years.
Results: Menopausal transition status was related to severe self-reported sleep difficulty. The odds of reporting severe self-reported sleep difficulty were increased approximately by 2- to 3.5-fold (95% CI ranges from 1.08-3.27 to 1.99-6.04) for women in most menopausal transition statuses compared with women who remained premenopausal. After adjustment for current psychological, vasomotor, and somatic symptoms and waking frequently at night to use the toilet, only women who had a hysterectomy remained at an increased risk for moderate sleep difficulty.
Conclusions: The modest relationship between menopausal transition status and moderate sleep difficulty may be related to greater variation in individual definitions of moderate difficulty. Attention to the level of sleep difficulty in this group of women will assist in the decision to address current health symptoms versus sleep itself. Women without prior health problems may experience severe self-reported sleeping difficulty during the menopausal transition and require tailored care from health professionals.
C1 [Tom, Sarah E.] Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Kuh, Diana; Mishra, Gita D.] Royal Free & Univ Coll Med Sch, MRC, Unit Lifelong Hlth & Ageing, London WC1E 6BT, England.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Tom, SE (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA.
EM tom.s@ghc.org
RI Mishra, Gita/F-8052-2011
OI Mishra, Gita/0000-0001-9610-5904
FU National Institute on Aging, National Institutes of Health; Medical
Research Council, United Kingdom
FX This study was supported in part by the Intramural Research Program,
National Institute on Aging, National Institutes of Health and the
Medical Research Council, United Kingdom.
NR 35
TC 23
Z9 23
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD NOV-DEC
PY 2010
VL 17
IS 6
BP 1128
EP 1135
DI 10.1097/gme.0b013e3181dd55b0
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 677LK
UT WOS:000283993700010
PM 20551846
ER
PT J
AU Allison, MA
Manson, JE
Aragaki, A
Langer, RD
Rossouw, J
Curb, D
Martin, LW
Phillips, L
Stefanick, ML
Cochrane, BB
Sarto, G
Barnhart, J
O'Sullivan, MJ
Johnson, KC
Gass, M
Trevisan, M
Woods, NF
AF Allison, Matthew A.
Manson, JoAnn E.
Aragaki, Aaron
Langer, Robert D.
Rossouw, Jacques
Curb, David
Martin, Lisa W.
Phillips, Lawrence
Stefanick, Marcia L.
Cochrane, Barbara B.
Sarto, Gloria
Barnhart, Janice
O'Sullivan, Mary Jo
Johnson, Karen C.
Gass, Margery
Trevisan, Maurizio
Woods, Nancy F.
TI Vasomotor symptoms and coronary artery calcium in postmenopausal women
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE Calcium; Coronary; Vasomotor symptoms; Women; Menopause; Atherosclerosis
ID RANDOMIZED CONTROLLED-TRIAL; AMERICAN-HEART-ASSOCIATION; BONE-MINERAL
DENSITY; VASCULAR CALCIFICATION; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS
MESA; COMPUTED-TOMOGRAPHY; RANCHO BERNARDO; HORMONE-THERAPY;
RISK-FACTORS
AB Objective: We assessed whether vasomotor symptoms (VMS) are associated with coronary artery calcium (CAC) and how hormone therapy (HT) may influence this association.
Methods: Participants were a subset of women aged 50 to 59 years with a history of hysterectomy who were enrolled in the Women's Health Initiative (WHI) estrogen-alone clinical trial and underwent a CT scan of the chest at the end of the trial to determine CAC. Participants provided information about VMS (hot flashes and/or night sweats), as well as HT use, on self-administered questionnaires at trial baseline.
Results: The sample consisted of 918 women with a mean (SD) age of 55.1 (2.8) years at WHI randomization and 64.8 (2.9) years at CAC ascertainment. The prevalence of a CAC score higher than 0 was 46%, whereas the prevalence of a CAC score of 10 or higher and higher than 100 was 39% and 19%, respectively. At randomization, 77% reported a history of any VMS at any time before or at enrollment in the WHI, whereas 20% reported any VMS present only at enrollment. Compared with those without a history of any VMS and after adjustment for potential confounders, a history of any VMS at any time up to and including WHI enrollment was associated with significantly reduced odds for CAC higher than 0 (odds ratio, 0.66; 95% CI, 0.45-0.98). Moreover, as duration of HT increased, the inverse association between any VMS and CAC moved toward the null.
Conclusions: A history of any VMS was significantly associated with reduced odds for CAC independent of traditional cardiovascular disease risk factors and other relevant covariates. This association seems to be influenced by duration of HT.
C1 [Allison, Matthew A.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Manson, JoAnn E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Aragaki, Aaron] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Langer, Robert D.] Jackson Hole Ctr Prevent Med, Jackson, WY USA.
[Rossouw, Jacques] NHLBI, NIH, Bethesda, MD 20892 USA.
[Curb, David] Univ Hawaii, Honolulu, HI 96822 USA.
[Martin, Lisa W.] George Washington Univ, Washington, DC USA.
[Phillips, Lawrence] Emory Univ, Atlanta, GA 30322 USA.
[Stefanick, Marcia L.] Stanford Univ, Stanford, CA 94305 USA.
[Cochrane, Barbara B.; Woods, Nancy F.] Univ Washington, Seattle, WA 98195 USA.
[Sarto, Gloria] Univ Wisconsin, Madison, WI USA.
[Barnhart, Janice] Albert Einstein Univ, Bronx, NY USA.
[O'Sullivan, Mary Jo] Univ Miami, Miami, FL USA.
[Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Gass, Margery] Univ Cincinnati, Cincinnati, OH USA.
[Trevisan, Maurizio] Hlth Sci Syst Nevada Syst Higher Educ, Las Vegas, NV USA.
RP Allison, MA (reprint author), 9500 Gilman Dr,Mailcode 0965, La Jolla, CA 92093 USA.
EM mallison@ucsd.edu
OI Martin, Lisa Warsinger/0000-0003-4352-0914; Allison,
Matthew/0000-0003-0777-8272
FU National Institutes of Health; American Heart Association; National
Heart, Lung, and Blood Institute; US Department of Health and Human
Services
FX Support for this research was provided by contracts with the National
Institutes of Health and a grant from the American Heart Association.
The National Heart, Lung, and Blood Institute and =US Department of
Health and Human Services funds the Women's Health Initiative (WHI)
program and provided support for the WHI Coronary Artery Calcium Study
ancillary study. Wyeth provided study pills (active and placebo) for the
WHI Conjugated Equine Estrogens trial but had no other role in the
study. This work was also supported in part by a grant from the American
Heart Association (M.A. Allison). The authors had full access to all of
the data in the study and take responsibility for the integrity of the
data and the accuracy of the data analysis.
NR 44
TC 21
Z9 21
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD NOV-DEC
PY 2010
VL 17
IS 6
BP 1136
EP 1145
DI 10.1097/gme.0b013e3181e664dc
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 677LK
UT WOS:000283993700011
PM 20651617
ER
PT J
AU Wickerham, DL
AF Wickerham, D. L.
TI Counseling Women On Ways To Prevent Breast Cancer
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Meeting Abstract
CT 21st Annual Meeting of the North-American-Menopause-Society
CY OCT 06-09, 2010
CL Chicago, IL
SP N Amer Menopause Soc
C1 [Wickerham, D. L.] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD NOV-DEC
PY 2010
VL 17
IS 6
BP 1211
EP 1211
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 677LK
UT WOS:000283993700031
ER
PT J
AU Nelson, LM
AF Nelson, Lawrence M.
TI Primary Ovarian Insufficiency is Not an Early Menopause
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Meeting Abstract
CT 21st Annual Meeting of the North-American-Menopause-Society
CY OCT 06-09, 2010
CL Chicago, IL
SP N Amer Menopause Soc
C1 [Nelson, Lawrence M.] NICHD, Intramural Res Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD NOV-DEC
PY 2010
VL 17
IS 6
BP 1212
EP 1213
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 677LK
UT WOS:000283993700040
ER
PT J
AU Huang, B
Troese, MJ
Howe, D
Ye, SJ
Sims, JT
Heinzen, RA
Borjesson, DL
Carlyon, JA
AF Huang, Bernice
Troese, Matthew J.
Howe, Dale
Ye, Shaojing
Sims, Jonathan T.
Heinzen, Robert A.
Borjesson, Dori L.
Carlyon, Jason A.
TI Anaplasma phagocytophilum APH_0032 is expressed late during infection
and localizes to the pathogen-occupied vacuolar membrane
SO MICROBIAL PATHOGENESIS
LA English
DT Article
DE Pathogenesis; Anaplasma; Ehrlichia; Pathogen-occupied vacuole;
Intravacuolar pathogen
ID IV SECRETION SYSTEM; MAJOR SURFACE PROTEIN-2; EHRLICHIA-CHAFFEENSIS;
INCLUSION MEMBRANE; TANDEM REPEATS; EVASION MECHANISMS; MESSENGER-RNA;
NADPH OXIDASE; CELLS; GENE
AB Anaplasma phagocytophilum infects neutrophils and myeloid, endothelial, and tick cell lines to reside within a host cell-derived vacuole that is indispensible for its survival. Here, we identify APH_0032 as an Anaplasma-derived protein that associates with the A. phagocytophilum-occupied vacuolar membrane (AVM). APH_0032 is a 66.1 kDa acidic protein that electrophoretically migrates with an apparent molecular weight of 130 kDa. It contains a predicted transmembrane domain and tandemly arranged direct repeats that comprise 46% of the protein. APH_0032 is undetectable on Anaplasma organisms bound to the surfaces of HL-60 cells, but is detected on the AVM and surfaces of intravacuolar bacteria beginning 24 h post-infection. APH_0032 localizes to the AVM in HL-60, THP-1, HMEC-1, and ISE6 cells. APH_0032, along with APH_1387, which encodes a confirmed AVM protein, is transcribed during A. phagocytophilum infection of tick salivary glands and murine neutrophils. APH_0032 localizes to the AVM in neutrophils recovered from infected mice. The Legionella pneumophila Dot/IcM type IV secretion system (T4SS) can heterologously secrete a CyaA-tagged version of the A. phagocytophilum VirB/D T4SS effector, AnkA, but fails to secrete CyaA-tagged APH_0032 or APH_1387. These data confirm APH_0032 as an Anaplasma-derived AVM protein and hint that neither it nor APH_1387 are T4SS effectors. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Huang, Bernice; Troese, Matthew J.; Carlyon, Jason A.] Virginia Commonwealth Univ, Sch Med, Dept Microbiol & Immunol, Richmond, VA 23298 USA.
[Howe, Dale; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Ye, Shaojing; Sims, Jonathan T.] Univ Kentucky, Coll Med, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40504 USA.
[Borjesson, Dori L.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA.
RP Carlyon, JA (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Microbiol & Immunol, Mol Med Res Bldg,1220 E Broad St,Room 4052,POB 98, Richmond, VA 23298 USA.
EM jacarlyon@vcu.edu
FU NIH-NINDS Center [5P30NS047463]; NIH [DK065039, AI072683]; National
Research Fund for Tick-Borne Diseases
FX We acknowledge Curtis Nelson for openly discussing his unpublished
observations; Erol Fikrig for providing HGA patient antisera and
seronegative sera; J. Stephen Dumler for providing mAb 20B4; Sukanya
Narasimhan for providing RNA isolated from uninfected and A.
phagocytophilum-infected tick salivary glands; Ulrike Munderloh for
providing A. phagocytophilum-infected ISE6 cells; Howard Shuman for
providing L pneumophila JR32 and LELA3118 strains; Jere W. McBride and
Richard T. Marconi for helpful discussions; and Naomi Walker, Dexter
Reneer, and Aaron Wolen for technical assistance. The Virginia
Commonwealth University Department of Neurobiology & Anatomy Microscopy
Facility is supported, in part, by funding from NIH-NINDS Center core
grant 5P30NS047463.; Supported by NIH grants DK065039 and AI072683 and
funding from the National Research Fund for Tick-Borne Diseases.
NR 57
TC 27
Z9 28
U1 0
U2 3
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 NOV
PY 2010
VL 49
IS 5
BP 273
EP 284
DI 10.1016/j.micpath.2010.06.009
PG 12
WC Immunology; Microbiology
SC Immunology; Microbiology
GA 641KL
UT WOS:000281124100008
PM 20600793
ER
PT J
AU Zou, TT
Rao, JN
Liu, L
Xiao, L
Yu, TX
Jiang, P
Gorospe, M
Wang, JY
AF Zou, Tongtong
Rao, Jaladanki N.
Liu, Lan
Xiao, Lan
Yu, Ting-Xi
Jiang, Ping
Gorospe, Myriam
Wang, Jian-Ying
TI Polyamines Regulate the Stability of JunD mRNA by Modulating the
Competitive Binding of Its 3 ' Untranslated Region to HuR and AUF1
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID INTESTINAL EPITHELIAL-CELLS; REPRESSES CDK4 TRANSCRIPTION; PROXIMAL
PROMOTER REGION; C-MYC EXPRESSION; PROTEIN HUR; OXIDATIVE STRESS;
GENE-EXPRESSION; MUCOSAL GROWTH; DEPLETION; P53
AB Polyamines critically regulate all mammalian cell growth and proliferation by mechanisms such as the repression of growth-inhibitory proteins, including JunD. Decreasing the levels of cellular polyamines stabilizes JunD mRNA without affecting its transcription, but the exact mechanism whereby polyamines regulate JunD mRNA degradation has not been elucidated. RNA-binding proteins HuR and AUF1 associate with labile mRNAs bearing AU-rich elements located in the 3' untranslated regions (3'-UTRs) and modulate their stability. Here, we show that JunD mRNA is a target of HuR and AUF1 and that polyamines modulate JunD mRNA degradation by altering the competitive binding of HuR and AUF1 to the JunD 3'-UTR. The depletion of cellular polyamines enhanced HuR binding to JunD mRNA and decreased the levels of JunD transcript associated with AUF1, thus stabilizing JunD mRNA. The silencing of HuR increased AUF1 binding to the JunD mRNA, decreased the abundance of HuR-JunD mRNA complexes, rendered the JunD mRNA unstable, and prevented increases in JunD mRNA and protein in polyamine-deficient cells. Conversely, increasing the cellular polyamines repressed JunD mRNA interaction with HuR and enhanced its association with AUF1, resulting in an inhibition of JunD expression. These results indicate that polyamines modulate the stability of JunD mRNA in intestinal epithelial cells through HuR and AUF1 and provide new insight into the molecular functions of cellular polyamines.
C1 [Zou, Tongtong; Rao, Jaladanki N.; Liu, Lan; Xiao, Lan; Yu, Ting-Xi; Jiang, Ping; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA.
[Zou, Tongtong; Rao, Jaladanki N.; Liu, Lan; Xiao, Lan; Yu, Ting-Xi; Jiang, Ping; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Zou, Tongtong; Rao, Jaladanki N.; Liu, Lan; Yu, Ting-Xi; Jiang, Ping; Wang, Jian-Ying] Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA.
[Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA.
RP Wang, JY (reprint author), Baltimore Vet Affairs Med Ctr 112, 10 N Greene St, Baltimore, MD 21201 USA.
EM jwang@smail.umaryland.edu
FU Department of Veterans Affairs; NIH [DK-57819, DK-61972, DK-68491];
NIA-IRP, NIH
FX This work was supported by a merit review grant (to J.-Y.W.) from the
Department of Veterans Affairs and by NIH grants DK-57819, DK-61972, and
DK-68491 (to J.-Y.W.). J.-Y.W. is a Research Career Scientist, Medical
Research Service, U.S. Department of Veterans Affairs. M. G. is
supported by the NIA-IRP, NIH.
NR 64
TC 36
Z9 37
U1 0
U2 2
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 NOV
PY 2010
VL 30
IS 21
BP 5021
EP 5032
DI 10.1128/MCB.00807-10
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 661SO
UT WOS:000282748600004
PM 20805360
ER
PT J
AU Suzuki, Y
Holmes, JB
Cerritelli, SM
Sakhuja, K
Minczuk, M
Holt, IJ
Crouch, RJ
AF Suzuki, Yutaka
Holmes, J. Bradley
Cerritelli, Susana M.
Sakhuja, Kiran
Minczuk, Michal
Holt, Ian J.
Crouch, Robert J.
TI An Upstream Open Reading Frame and the Context of the Two AUG Codons
Affect the Abundance of Mitochondrial and Nuclear RNase H1
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
AB RNase H1 in mammalian cells is present in nuclei and mitochondria. Its absence in mitochondria results in embryonic lethality due to the failure to amplify mitochondrial DNA (mtDNA). Dual localization to mitochondria and nuclei results from differential translation initiation at two in-frame AUGs (M1 and M27) of a single mRNA. Here we show that expression levels of the two isoforms depend on the efficiency of translation initiation at each AUG codon and on the presence of a short upstream open reading frame (uORF) resulting in the mitochondrial isoform being about 10% as abundant as the nuclear form. Translation initiation at the M1 AUG is restricted by the uORF, while expression of the nuclear isoform requires reinitiation of ribosomes at the M27 AUG after termination of uORF translation or new initiation by ribosomes skipping the uORF and the M1 AUG. Such translational organization of RNase H1 allows tight control of expression of RNase H1 in mitochondria, where its excess or absence can lead to cell death, without affecting the expression of the nuclear RNase H1.
C1 [Suzuki, Yutaka; Holmes, J. Bradley; Cerritelli, Susana M.; Sakhuja, Kiran; Crouch, Robert J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Holmes, J. Bradley; Minczuk, Michal; Holt, Ian J.] MRC, Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
RP Crouch, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, 6 Ctr Dr,MSC2790, Bethesda, MD 20892 USA.
EM robert_crouch@nih.gov
OI Suzuki, Yutaka/0000-0001-7504-9464
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health; U.K. Medical Research
Council
FX This work was supported in part by the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health. Yutaka Suzuki was a Japan
Society for the Promotion of Science Research Fellow in Biomedical and
Behavioral Research at the National Institutes of Health. J. Bradley
Holmes is a National Institutes of Health-Cambridge University
Biomedical Research Scholar. Michal Minczuk and Ian Holt are supported
by the U.K. Medical Research Council.
NR 37
TC 28
Z9 28
U1 0
U2 3
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 NOV
PY 2010
VL 30
IS 21
BP 5123
EP 5134
DI 10.1128/MCB.00619-10
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 661SO
UT WOS:000282748600012
PM 20823270
ER
PT J
AU Dev, K
Qiu, HF
Dong, JS
Zhang, F
Barthlme, D
Hinnebusch, AG
AF Dev, Kamal
Qiu, Hongfang
Dong, Jinsheng
Zhang, Fan
Barthlme, Dominik
Hinnebusch, Alan G.
TI The beta/Gcd7 Subunit of Eukaryotic Translation Initiation Factor 2B
(eIF2B), a Guanine Nucleotide Exchange Factor, Is Crucial for Binding
eIF2 In Vivo
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
AB Eukaryotic translation initiation factor 2B (eIF2B) is the guanine nucleotide exchange factor (GEF) for eukaryotic translation initiation factor 2, which stimulates formation of the eIF2-GTP-Met-tRNA(i)(Met) ternary complex (TC) in a manner inhibited by phosphorylated eIF2 [eIF2(alpha P)]. While eIF2B contains five subunits, the epsilon/Gcd6 subunit is sufficient for GEF activity in vitro. The delta/Gcd2 and beta/Gcd7 subunits function with alpha/Gcn3 in the eIF2B regulatory subcomplex that mediates tight, inhibitory binding of eIF2(alpha P)-GDP, but the essential functions of delta/Gcd2 and beta/Gcd7 are not well understood. We show that the depletion of wild-type beta/Gcd7, three lethal beta/Gcd7 amino acid substitutions, and a synthetically lethal combination of substitutions in beta/Gcd7 and eIF2 alpha all impair eIF2 binding to eIF2B without reducing epsilon/Gcd6 abundance in the native eIF2B-eIF2 holo-complex. Additionally, beta/Gcd7 mutations that impair eIF2B function display extensive allele-specific interactions with mutations in the S1 domain of eIF2 alpha (harboring the phosphorylation site), which binds to eIF2B directly. Consistent with this, beta/Gcd7 can overcome the toxicity of eIF2(alpha P) and rescue native eIF2B function when overexpressed with delta/Gcd2 or gamma/Gcd1. In aggregate, these findings provide compelling evidence that beta/Gcd7 is crucial for binding of substrate by eIF2B in vivo, beyond its dispensable regulatory role in the inhibition of eIF2B by eIF (alpha P).
C1 [Dev, Kamal; Qiu, Hongfang; Dong, Jinsheng; Zhang, Fan; Barthlme, Dominik; Hinnebusch, Alan G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA.
RP Hinnebusch, AG (reprint author), NIH, Bldg 6,Room 230, Bethesda, MD 20892 USA.
EM ahinnebusch@nih.gov
RI Barthelme, Dominik/E-8452-2010; university, shoolini/K-9336-2015
FU NIH
FX This work was supported in part by the Intramural Research Program of
the NIH.
NR 50
TC 12
Z9 12
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD NOV
PY 2010
VL 30
IS 21
BP 5218
EP 5233
DI 10.1128/MCB.00265-10
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 661SO
UT WOS:000282748600020
PM 20805354
ER
PT J
AU Duffy, SP
Shing, J
Saraon, P
Berger, LC
Eiden, MV
Wilde, A
Tailor, CS
AF Duffy, Simon P.
Shing, Jennifer
Saraon, Punit
Berger, Lloyd C.
Eiden, Maribeth V.
Wilde, Andrew
Tailor, Chetankumar S.
TI The Fowler Syndrome-Associated Protein FLVCR2 Is an Importer of Heme
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID FELINE-LEUKEMIA-VIRUS; DIAMOND-BLACKFAN ANEMIA; AMINO-ACID TRANSPORTER;
HYDRANENCEPHALIC-HYDROCEPHALIC SYNDROME; CELL-SURFACE RECEPTORS;
MEGALOBLASTIC-ANEMIA; PROLIFERATIVE VASCULOPATHY; THIAMINE TRANSPORTER;
IRON HOMEOSTASIS; SUBGROUP C
AB Mutations in FLVCR2, a cell surface protein related by homology and membrane topology to the heme exporter/retroviral receptor FLVCR1, have recently been associated with Fowler syndrome, a vascular disorder of the brain. We previously identified FLVCR2 to function as a receptor for FY981 feline leukemia virus (FeLV). However, the cellular function of FLVCR2 remains unresolved. Here, we report the cellular function of FLVCR2 as an importer of heme, based on the following observations. First, FLVCR2 binds to hemin-conjugated agarose, and binding is competed by free hemin. Second, mammalian cells and Xenopus laevis oocytes expressing FLVCR2 display enhanced heme uptake. Third, heme import is reduced after the expression of FLVCR2-specific small interfering RNA (siRNA) or after the binding of the FY981 FeLV envelope protein to the FLVCR2 receptor. Finally, cells overexpressing FLVCR2 are more sensitive to heme toxicity, a finding most likely attributable to enhanced heme uptake. Tissue expression analysis indicates that FLVCR2 is expressed in a broad range of human tissues, including liver, placenta, brain, and kidney. The identification of a cellular function for FLVCR2 will have important implications in elucidating the pathogenic mechanisms of Fowler syndrome and of phenotypically associated disorders.
C1 [Duffy, Simon P.; Shing, Jennifer; Saraon, Punit; Tailor, Chetankumar S.] Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1X8, Canada.
[Duffy, Simon P.; Berger, Lloyd C.; Wilde, Andrew; Tailor, Chetankumar S.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
[Eiden, Maribeth V.] NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
RP Tailor, CS (reprint author), Hosp Sick Children, Cell Biol Program, Room 7129,Elm Wing,555 Univ Ave, Toronto, ON M5G 1X8, Canada.
EM chetankumar.tailor@sickkids.ca
OI Duffy, Simon/0000-0002-1301-6031
FU Canadian Institutes of Health Research [MOP-79541]; Sickkids Foundation
[XG07-028R]; Hospital for Sick Children
FX This work was supported by Canadian Institutes of Health Research grant
MOP-79541, by Sickkids Foundation grant XG07-028R, and by a Restracomp
award to S.P.D. provided by the Hospital for Sick Children.
NR 49
TC 28
Z9 30
U1 0
U2 2
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 NOV
PY 2010
VL 30
IS 22
BP 5318
EP 5324
DI 10.1128/MCB.00690-10
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 673JX
UT WOS:000283656700006
PM 20823265
ER
PT J
AU Swanwick, CC
Shapiro, ME
Vicini, S
Wenthold, RJ
AF Swanwick, Catherine Croft
Shapiro, Marietta E.
Vicini, Stefano
Wenthold, Robert J.
TI Flotillin-1 mediates neurite branching induced by synaptic adhesion-like
molecule 4 in hippocampal neurons
SO MOLECULAR AND CELLULAR NEUROSCIENCE
LA English
DT Article
DE Rat; Lipid rafts; Dendritic arborization; Development; Adhesion
molecules
ID LIPID-RAFT PROTEINS; EXOCYST COMPLEX; MEMBRANE MICRODOMAINS;
RHO-GTPASES; REGGIE/FLOTILLIN PROTEINS; SIGNAL-TRANSDUCTION; FILOPODIA
FORMATION; AXON REGENERATION; NMDA-RECEPTORS; PDZ PROTEINS
AB Proper development of neurons in the hippocampus is essential for learning and memory. Our laboratory previously discovered a family of synaptic adhesion-like molecules (SALMs) which induce neurite outgrowth in this brain region (Wang et al., 2006). Here we establish flotillin-1 (flot-1) as a molecular mediator of neurite branching for SALM4. Knockdown of flot-1 alone in cultured hippocampal neurons using siRNA from 3-7 days in vitro (DIV) impaired neurite branching, whereas overexpression of flot-1 during the same time period increased the number of processes and branching. We show that induction of neurite outgrowth by flot-1 depends on amino acids 134-151 as well as lipid raft microdomains, SoHo proteins to regulate the actin cytoskeleton, and the exocyst complex to deliver new membrane proteins to growing neurites. When each of SALMs 1-5 was overexpressed, siRNA knockdown of flot-1 prevented neurite branching by SALM4. Overall, our data reveal a flot-1 signaling pathway for hippocampal neurite branching that is regulated by SALM4. (C) 2010 Published by Elsevier Inc.
C1 [Swanwick, Catherine Croft; Shapiro, Marietta E.; Wenthold, Robert J.] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
[Vicini, Stefano] Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA.
RP Swanwick, CC (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bldg 50,Room 4146,50 South Dr, Bethesda, MD 20892 USA.
EM swanwickc@mail.nih.gov
FU National Institute of General Medical Sciences
FX We thank Ya-Xian Wang for culturing the hippocampal neurons. We are also
grateful to Alan Saltiel, Benjamin Nichols, Pietro DeCamilli, Dorit Ron,
and Eunjoon Kim for cDNA constructs and to Shu-Chan Hsu for antibodies
and cDNA constructs. In addition, we thank members of the Wenthold Lab
for providing comments and suggestions on this manuscript. This study
was funded by the Intramural Research Program of the National Institute
on Deafness and Other Communication Disorders and a Pharmacology
Research Associate (PRAT) Fellowship from the National Institute of
General Medical Sciences.
NR 68
TC 10
Z9 12
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 1044-7431
J9 MOL CELL NEUROSCI
JI Mol. Cell. Neurosci.
PD NOV
PY 2010
VL 45
IS 3
BP 213
EP 225
DI 10.1016/j.mcn.2010.06.012
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 654YP
UT WOS:000282207500002
PM 20600927
ER
PT J
AU Fukuda, Y
Berry, TL
Nelson, M
Hunter, CL
Fukuhara, K
Imai, H
Ito, S
Granholm-Bentley, AC
Kaplan, AP
Mutoh, T
AF Fukuda, Yu
Berry, Thomas L.
Nelson, Matthew
Hunter, Christopher L.
Fukuhara, Koki
Imai, Hideki
Ito, Shinji
Granholm-Bentley, Ann-Charlotte
Kaplan, Allen P.
Mutoh, Tatsuro
TI Stimulated neuronal expression of brain-derived neurotrophic factor by
Neurotropin
SO MOLECULAR AND CELLULAR NEUROSCIENCE
LA English
DT Article
DE Neurotropin; Brain-derived neurotrophic factor; CREB pathway; TrkB;
Ts65Dn mice; Down's syndrome; Radial-arm maze
ID NERVE GROWTH-FACTOR; ADULT HIPPOCAMPAL NEUROGENESIS; AMYLOID PRECURSOR
PROTEIN; SPINAL DORSAL-HORN; GENE-EXPRESSION; MOUSE MODEL;
WORKING-MEMORY; DOWNS-SYNDROME; CNS DISORDERS; CHRONIC PAIN
AB Expression of brain-derived neurotrophic factor (BDNF) was stimulated in human neuroblastoma SH-SY5Y cells by a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin (R)), an analgesic widely used in Japan for treatment of disorders associated with chronic pain, with the optimal dosage at 10 mNU/mL This stimulation was accompanied by activations of p42/44 MAP kinase, CREB and c-Fos expression. Inhibitors of MAP kinases or PI 3-kinase prevented the stimulatory action of Neurotropin, indicating that neuronal TrkB/CREB pathway mediates the action. Repetitive oral administration of Neurotropin (200 NU/kg/day, 3 months) prevented the age-dependent decline in hippocampal BDNF expression in Ts65Dn mice, a model of Down's syndrome. This effect was associated with the improvement of spatial cognition of the mice. These results open an intriguing new strategy in which Neurotropin may prove beneficial treatment for neurodegenerative disorders. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Fukuda, Yu; Ito, Shinji; Mutoh, Tatsuro] Fajita Hlth Univ, Sch Med, Dept Neurol, Toyoake, Aichi 4701192, Japan.
[Fukuda, Yu; Berry, Thomas L.; Fukuhara, Koki; Kaplan, Allen P.] Med Univ S Carolina, Konishi MUSC Inst Inflammat Res, Charleston, SC 29425 USA.
[Fukuda, Yu; Berry, Thomas L.; Fukuhara, Koki; Kaplan, Allen P.] Med Univ S Carolina, Dept Med, Div Pulm & Crit Care Med Allergy & Clin Immunol, Charleston, SC 29425 USA.
[Nelson, Matthew; Hunter, Christopher L.; Granholm-Bentley, Ann-Charlotte] Med Univ S Carolina, Dept Neurosci, Ctr Aging, Charleston, SC 29425 USA.
[Fukuhara, Koki] NINR, NIH, Bethesda, MD 20892 USA.
[Fukuda, Yu; Fukuhara, Koki; Imai, Hideki] Nippon Zoki Pharmaceut Co Ltd, Chuo Ku, Osaka 5410046, Japan.
RP Mutoh, T (reprint author), Fajita Hlth Univ, Sch Med, Dept Neurol, Kutsukake Cho, Toyoake, Aichi 4701192, Japan.
EM tmutoh@fujita-hu.ac.jp
NR 59
TC 15
Z9 18
U1 2
U2 8
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 NOV
PY 2010
VL 45
IS 3
BP 226
EP 233
DI 10.1016/j.mcn.2010.06.013
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 654YP
UT WOS:000282207500003
PM 20600926
ER
PT J
AU Cooper, O
Hargus, G
Deleidi, M
Blak, A
Osborn, T
Marlow, E
Lee, K
Levy, A
Perez-Torres, E
Yow, A
Isacson, O
AF Cooper, Oliver
Hargus, Gunnar
Deleidi, Michela
Blak, Alexandra
Osborn, Teresia
Marlow, Elizabeth
Lee, Kristen
Levy, Adam
Perez-Torres, Eduardo
Yow, Alyssa
Isacson, Ole
TI Differentiation of human ES and Parkinson's disease iPS cells into
ventral midbrain dopaminergic neurons requires a high activity form of
SHH, FGF8a and specific regionalization by retinoic acid
SO MOLECULAR AND CELLULAR NEUROSCIENCE
LA English
DT Article
DE FOXA2; HNF3b; A9; A10; Splice variant; Induced; Pluripotent; Stem;
Embryonic; Neural
ID EMBRYONIC STEM-CELLS; SONIC HEDGEHOG; FLOOR PLATE; GENE-EXPRESSION;
SUBSTANTIA-NIGRA; SPINAL-CORD; RAT MODEL; IN-VITRO; IDENTITY; INDUCTION
AB The cardinal motor symptoms of Parkinson's disease (PD) are caused by the vulnerability to dysfunction and degeneration of ventral midbrain (VM) dopaminergic (DA) neurons. A major limitation for experimental studies of current ES/iPS cell differentiation protocols is the lack of VM DA neurons with a stable phenotype as defined by an expression marker code of FOXA2/TH/beta-tubulin. Here we demonstrate a combination of three modifications that were required to produce VM DA neurons. Firstly, early and specific exposure to 10(-8) M (low dose) retinoic acid improved the regional identity of neural progenitor cells derived from human ES cells, PD or healthy subject-specific iPS cells. Secondly, a high activity form of human sonic hedgehog established a sizeable FOXA2(+) neural progenitor cell population in vitro. Thirdly, early exposure to FGF8a, rather than Fgf8b, and WNT1 was required for robust differentiation of the FOXA2(+) floor plate-like human neural progenitor cells into FOXA2(+) DA neurons. FOXA2(+) DA neurons were also generated when this protocol was adapted to feeder-free conditions. In summary, this new human ES and iPS cell differentiation protocol using FGF8a, WNT1, low dose retinoic acid and a high activity form of SHH can generate human VM DA neurons that are required for relevant new bioassays, drug discovery and cell based therapies for PD. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Cooper, Oliver] Harvard Univ, Sch Med, NINDS Udall Parkinsons Dis Res Ctr Excellence, McLean Hosp,Neuroregenerat Labs,Ctr Neuroregenera, Belmont, MA 02478 USA.
RP Cooper, O (reprint author), Harvard Univ, Sch Med, NINDS Udall Parkinsons Dis Res Ctr Excellence, McLean Hosp,Neuroregenerat Labs,Ctr Neuroregenera, MRC 103,115 Mill St, Belmont, MA 02478 USA.
EM ocooper@mclean.harvard.edu
OI Cooper, Oliver/0000-0001-6567-7491
FU Udall Parkinson's Disease Center of Excellence [P50 NS39793]; Michael
Stern Foundation [WX81XWH-05-1-0555]; Orchard Foundation; Consolidated
Anti-Aging Foundation; Harold and Ronna Cooper Family; Deutsche
Forschungsgemeinschaft [HA5589/1-1]; Harvard Medical School/National
Institute on Aging [5T32AG00222-17]
FX During the review of this paper, another paper providing mechanistic
data for human FOXA2 expressing neural precursor cell differentiation
from ES cells was published (Fasano et al., 2010). Our study was
supported by the Udall Parkinson's Disease Center of Excellence Grant
P50 NS39793, Michael Stern Foundation (WX81XWH-05-1-0555), Orchard
Foundation, the Consolidated Anti-Aging Foundation and the Harold and
Ronna Cooper Family. G.H. received a postdoctoral fellowship from the
Deutsche Forschungsgemeinschaft (HA5589/1-1). T.O. received a Molecular
Biology of Neurodegeneration postdoctoral fellowship from Harvard
Medical School/National Institute on Aging (5T32AG00222-17).
NR 56
TC 92
Z9 95
U1 6
U2 37
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 NOV
PY 2010
VL 45
IS 3
BP 258
EP 266
DI 10.1016/j.mcn.2010.06.017
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 654YP
UT WOS:000282207500006
PM 20603216
ER
PT J
AU Wei, XM
Prickett, TD
Viloria, CG
Molinolo, A
Lin, JC
Cardenas-Navia, I
Cruz, P
Rosenberg, SA
Davies, MA
Gershenwald, JE
Lopez-Otin, C
Samuels, Y
AF Wei, Xiaomu
Prickett, Todd D.
Viloria, Cristina G.
Molinolo, Alfredo
Lin, Jimmy C.
Cardenas-Navia, Isabel
Cruz, Pedro
Rosenberg, Steven A.
Davies, Michael A.
Gershenwald, Jeffrey E.
Lopez-Otin, Carlos
Samuels, Yardena
CA NISC Comparative Sequencing Progra
TI Mutational and Functional Analysis Reveals ADAMTS18 Metalloproteinase as
a Novel Driver in Melanoma
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID TUMOR-SUPPRESSOR; PROTEOLYTIC ACTIVITIES; COLORECTAL CANCERS; EMERGING
ROLES; HUMAN BREAST; IDENTIFICATION; MULTIPLE; MATRIX; INACTIVATION;
METASTASIS
AB The disintegrin-metalloproteinases with thrombospondin domains (ADAMTS) genes have been suggested to function as tumor suppressors as several have been found to be epigenetically silenced in various cancers. We performed a mutational analysis of the ADAMTS gene family in human melanoma and identified a large fraction of melanomas to harbor somatic mutations. To evaluate the functional consequences of the most commonly mutated gene, ADAMTS18, six of its mutations were biologically examined. ADAMTS18 mutations had little effect on melanoma cell growth under standard conditions, but reduced cell dependence on growth factors. ADAMTS18 mutations also reduced adhesion to laminin and increased migration in vitro and metastasis in vivo. Melanoma cells expressing mutant ADAMTS18 had reduced cell migration after short hairpin RNA-mediated knockdown of ADAMTS18, suggesting that ADAMTS18 mutations promote growth, migration, and metastasis in melanoma. Mol Cancer Res; 8(11); 1513-25. (C) 2010 AACR.
C1 [Wei, Xiaomu; Prickett, Todd D.; Cardenas-Navia, Isabel; Cruz, Pedro; Samuels, Yardena; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Molinolo, Alfredo] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Rosenberg, Steven A.] NCI, NIH, Bethesda, MD 20892 USA.
[Viloria, Cristina G.; Lopez-Otin, Carlos] Univ Oviedo, Dept Bioquim & Biol Mol, Inst Univ Oncol, Oviedo, Spain.
[Lin, Jimmy C.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD USA.
[Lin, Jimmy C.] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD USA.
[Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA.
[Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
[Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
RP Samuels, Y (reprint author), NHGRI, NIH Intramural Sequencing Ctr, NIH, Room 5140,Bldg 50,50 South Dr,MSC 8000, Bethesda, MD 20892 USA.
EM samuelsy@mail.nih.gov
RI Lopez-Otin, Carlos/C-6657-2013
OI Lopez-Otin, Carlos/0000-0001-6964-1904
FU National Human Genome Research Institute, NIH; Ministerio de Ciencia e
Innovacion-Spain; Fundacion "M. Botin"; European Union; University of
Texas; M.D. Anderson Cancer Center; Melanoma Informatics, Tissue
Resource, and Pathology Core [P50 CA93459]
FX National Human Genome Research Institute, NIH (Y. Samuels); Ministerio
de Ciencia e Innovacion-Spain, Fundacion "M. Botin", European Union (FP7
Micro-EnviMet; C. Lopez-Otin); and in part by the University of Texas
M.D. Anderson Cancer Center Melanoma Specialized Programs of Research
Excellence and the Melanoma Informatics, Tissue Resource, and Pathology
Core (grant P50 CA93459).
NR 47
TC 21
Z9 23
U1 1
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD NOV
PY 2010
VL 8
IS 11
BP 1513
EP 1525
DI 10.1158/1541-7786.MCR-10-0262
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 684TF
UT WOS:000284571500007
PM 21047771
ER
PT J
AU Wang, YA
James, M
Wen, WD
Lu, Y
Szabo, E
Lubet, RA
You, M
AF Wang, Yian
James, Michael
Wen, Weidong
Lu, Yan
Szabo, Eva
Lubet, Ronald A.
You, Ming
TI Chemopreventive Effects of Pioglitazone on Chemically Induced Lung
Carcinogenesis in Mice
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID ACTIVATED RECEPTOR-GAMMA; SQUAMOUS-CELL CARCINOMA; PPAR-GAMMA; A/J MICE;
COLON CARCINOGENESIS; TRANSGENIC MICE; BREAST-CANCER; CHINESE HERBS;
MOUSE MODELS; P53
AB Pioglitazone [(RS)-5-(4-[2-(5-ethylpyridin-2-yl) ethoxy] benzyl) thiazolidine-2,4-dione] is a ligand of nuclear receptor peroxisome proliferator-activated receptor. that is approved for the treatment of type II diabetes mellitus. Activation of peroxisome proliferator-activated receptor. has been associated with anticancer activities in a variety of cancer cell lines through inhibition of proliferation and promotion of apoptosis. We examined the effect of pioglitazone on lung cancer development in carcinogen-induced lung adenocarcinoma and squamous cell carcinoma (SCC). When pioglitazone was administered beginning 8 weeks after the first carcinogen treatment when microscopic adenomas already existed, pioglitazone significantly inhibited tumor load (sum of tumor volume per lung in average) by 64% (P < 0.05) in p53(wt/wt) mice and 50% (P < 0.05) in p53(wt/Ala135Val) mice in the lung adenocarcinoma model. Delayed administration of pioglitazone caused a limited (35%, P < 0.05) decrease in lung SCC. Induction of apoptosis occurred in both model systems. These data show that pioglitazone significantly inhibited progression of both adenocarcinoma and SCC in the two mouse model systems. Mol Cancer Ther; 9(11); 3074-82. (C) 2010 AACR.
C1 [Wang, Yian; James, Michael; Wen, Weidong; Lu, Yan; You, Ming] Washington Univ, Dept Surg, Sch Med, St Louis, MO 63110 USA.
[Szabo, Eva; Lubet, Ronald A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Wang, Yian; James, Michael; Wen, Weidong; Lu, Yan; You, Ming] Washington Univ, Alvin J Siteman Canc Ctr, Sch Med, St Louis, MO 63110 USA.
RP Wang, YA (reprint author), Washington Univ, Dept Surg, Sch Med, Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA.
EM wangyi@wustl.edu
NR 46
TC 25
Z9 26
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD NOV
PY 2010
VL 9
IS 11
BP 3074
EP 3082
DI 10.1158/1535-7163.MCT-10-0510
PG 9
WC Oncology
SC Oncology
GA 677ND
UT WOS:000283998200022
PM 21045137
ER
PT J
AU Poltoratsky, V
Heacock, M
Kissling, GE
Prasad, R
Wilson, SH
AF Poltoratsky, Vladimir
Heacock, Michelle
Kissling, Grace E.
Prasad, Rajendra
Wilson, Samuel H.
TI Mutagenesis dependent upon the combination of activation-induced
deaminase expression and a double-strand break
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Activation induced deaminase; AID; Base excision repair; Somatic
hypermutation; Double strand breaks; Mutagenesis
ID INDUCED CYTIDINE DEAMINASE; CLASS SWITCH RECOMBINATION; BASE
EXCISION-REPAIR; SOMATIC HYPERMUTATION; IMMUNOGLOBULIN GENES; HOMOLOGOUS
RECOMBINATION; SACCHAROMYCES-CEREVISIAE; ANTIBODY REPERTOIRE; DNA
DEAMINATION; URACIL EXCISION
AB We explored DNA metabolic events potentially relevant to somatic hypermutation (SHM) of immunoglobulin genes using a yeast model system Double-strand break (DSB) formation has been discussed as a possible component of the SHM process during immunoglobulin gene maturation Yet possible mechanisms linking DSB formation with mutagenesis have not been well understood In the present study a linkage between mutagenesis in a reporter gene and a double-strand break at a distal site was examined as a function of activation-induced deaminase (AID) expression Induction of the DSB was found to be associated with mutagenesis in a genomic marker gene located 7 kb upstream of the break site mutagenesis was strongest with the combination of AID expression and DSB induction The mutation spectrum of this DSB and AID-mediated mutagenesis was characteristic of replicative bypass of uracil in one strand and was dependent on expression of DNA polymerase delta (Pol delta) These results in a yeast model system illustrate that the combination of DSB induction and AID expression could be associated with mutagenesis observed in SHM Implications of these findings for SHM of immunoglobulin genes in human B cells are discussed Published by Elsevier Ltd
C1 [Poltoratsky, Vladimir; Heacock, Michelle; Prasad, Rajendra; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Kissling, Grace E.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr,POB 12233,MD F1 12, Res Triangle Pk, NC 27709 USA.
FU NIH National Institute of Environmental Health Sciences [Z01-ES050158,
Z01-ES050159]
FX We thank Michael Resnick and Dmitry Gordenin for useful comments on the
manuscript and Bonnie Mesmer for editorial assistance This research was
supported by the Intramural Research Program of the NIH National
Institute of Environmental Health Sciences (Z01-ES050158 & Z01-ES050159)
NR 54
TC 5
Z9 6
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD NOV-DEC
PY 2010
VL 48
IS 1-3
BP 164
EP 170
DI 10.1016/j.molimm.2010.08.013
PG 7
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 701GI
UT WOS:000285806000018
PM 20828826
ER
PT J
AU Uhl, GR
Drgon, T
Johnson, C
Ramoni, MF
Behm, FM
Rose, JE
AF Uhl, George R.
Drgon, Tomas
Johnson, Catherine
Ramoni, Marco F.
Behm, Frederique M.
Rose, Jed E.
TI Genome-Wide Association for Smoking Cessation Success in a Trial of
Precessation Nicotine Replacement
SO MOLECULAR MEDICINE
LA English
DT Article
ID SAMPLE-SIZE CALCULATIONS; MOLECULAR-GENETICS; LUNG-CANCER; DEPENDENCE;
BEHAVIOR; GENES; METAANALYSIS; ADDICTION; DISEASE; POWER
AB Abilities to successfully quit smoking display substantial evidence for heritability in classic and molecular genetic studies. Genome-wide association (GWA) studies have demonstrated single-nucleotide polymorphisms (SNPs) and haplotypes that distinguish successful quitters from individuals who were unable to quit smoking in clinical trial participants and in community samples. Many of the subjects in these clinical trial samples were aided by nicotine replacement therapy (NRI). We now report novel GWA results from participants in a clinical trial that sought dose/response relationships for "precessation" NRT. In this trial, 369 European-American smokers were randomized to 21 or 42 mg NRT, initiated 2 wks before target quit dates. Ten-week continuous smoking abstinence was assessed on the basis of self-reports and carbon monoxide levels. SNP genotyping used Affymetrix 6.0 arrays. GWA results for smoking cessation success provided no P value that reached "genome-wide" significance. Compared with chance, these results do identify (a) more clustering of nominally positive results within small genomic regions, (b) more overlap between these genomic regions and those identified in six prior successful smoking cessation GWA studies and (c) sets of genes that fall into gene ontology categories that appear to be biologically relevant. The 1,000 SNPs with the strongest associations form a plausible Bayesian network; no such network is formed by randomly selected sets of SNPs. The data provide independent support, based on individual genotyping, for many loci previously nominated on the basis of data from genotyping in pooled DNA samples. These results provide further support for the idea that aid for smoking cessation may be personalized on the basis of genetic predictors of outcome. (C) 2010 The Feinstein Institute for Medical Research, www.feinsteininstitute.org
C1 [Uhl, George R.; Drgon, Tomas; Johnson, Catherine] NIDA, Mol Neurobiol Branch, Natl Inst Hlth Intramural Res Program, NIH IRP, Baltimore, MD USA.
[Ramoni, Marco F.] Harvard Massachusetts Inst Technol MIT, Childrens Hosp Informat Program, Div Hlth Sci & Technol, Boston, MA USA.
[Behm, Frederique M.; Rose, Jed E.] Duke Univ, Dept Psychiat, Durham, NC 27706 USA.
[Behm, Frederique M.; Rose, Jed E.] Duke Univ, Ctr Nicotine & Smoking Cessat Res, Durham, NC 27706 USA.
RP Uhl, GR (reprint author), Box 5180, Baltimore, MD 21224 USA.
EM guhl@intra.nida.nih.gov; rose0003@mc.duke.edu
FU National Institutes of Health (NIH), National Institute on Drug Abuse,
Department of Health and Human Services; Philip Morris USA (Richmond,
VA, USA)
FX This study was supported by the National Institutes of Health
(NIH)-Intramural Research Program, National Institute on Drug Abuse,
Department of Health and Human Services (GRU); a grant to Duke
University (JE Rose, principal investigator) from Philip Morris USA
(Richmond, VA, USA). The funders had no role in the planning or
execution of the study, data analysis or publication of results. We are
grateful for help from Joseph E. Herskovic, PhD, Eric C. Westman, MD,
Qing-Rong Liu, PhD, and Donna Walther, MS. The underlying clinical trial
was registered with clinicaltrials. gov (ID# NCT00734617). This study
used BioBase (http: / /biobase-international. corn), installed on the
Helix System at the Center for Information Technology (CIT), National
Institutes of Health, Bethesda, Maryland (http:/ /helix.nih.gov).
NR 31
TC 30
Z9 31
U1 1
U2 7
PU FEINSTEIN INST MED RES
PI MANHASSET
PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA
SN 1076-1551
J9 MOL MED
JI Mol. Med.
PD NOV-DEC
PY 2010
VL 16
IS 11-12
BP 513
EP 526
DI 10.2119/molmed.2010.00052
PG 14
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 679TL
UT WOS:000284183600008
PM 20811658
ER
PT J
AU Sharifi, N
Qi, J
Bane, S
Sharma, S
Li, R
Robey, R
Figg, WD
Farrar, WL
Kingston, DGI
AF Sharifi, Nima
Qi, Jun
Bane, Susan
Sharma, Shubhada
Li, Rui
Robey, Robert
Figg, William D.
Farrar, William L.
Kingston, David G. I.
TI Survivin Is Not Induced by Novel Taxanes
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE Taxanes; chemotherapy; survivin; paclitaxel; prostate cancer; breast
cancer; lung cancer
ID BREAST-CANCER CELLS; PROSTATE-CANCER; LUNG-CANCER; CHEMOTHERAPY;
EXPRESSION; MITOXANTRONE; PREDNISONE; PACLITAXEL; DOCETAXEL; APOPTOSIS
AB Taxanes are a critical component of chemotherapy for breast, prostate, lung and other cancers. Initial or acquired tumor resistance to taxanes is therefore one of the most important issues in oncology. Survivin is a prosurvival gene whose expression is a poor prognostic feature. Survivin is induced acutely upon exposure to taxanes and coordinates resistance to taxane-mediated cell death, although the exact mechanism of taxane-mediated survivin induction is not clear. Here, we describe the synthesis of a series of novel taxanes, with modifications on the 7- or 10-position of the taxane backbone, as well as the side chain. We found that the novel taxanes with modifications at the 10-position have robust tubulin binding and tubulin polymerization activity. Gene expression profiling and quantitative PCR of cells treated with the 10-position conjugates reveals that the effect of treatment with a subset of these novel taxanes lacks a gene expression signature, including survivin induction, which is characteristically induced with paclitaxel treatment. Furthermore, we show that this gene expression signature is not due to differences in G2/M arrest. Cell sensitivity studies suggest that the inability to induce survivin is associated with increased drug cytotoxicity and apoptosis. This work suggests that taxanes that effectively bind tubulin need not invariably induce survivin as a mechanism of drug resistance.
C1 [Sharifi, Nima; Li, Rui] Univ Texas SW Med Ctr Dallas, Div Hematol Oncol, Dallas, TX 75390 USA.
[Qi, Jun; Kingston, David G. I.] Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA.
[Bane, Susan; Sharma, Shubhada] SUNY Binghamton, Dept Chem, Binghamton, NY 13902 USA.
[Robey, Robert; Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Farrar, William L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
RP Sharifi, N (reprint author), Univ Texas SW Med Ctr Dallas, Div Hematol & Oncol, Dept Internal Med, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM nima.sharifi@utsouthwestern.edu
RI Bane, Susan/C-1414-2013; Figg Sr, William/M-2411-2016;
OI Bane, Susan/0000-0002-4270-6314; Kingston, David/0000-0001-8944-246X
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
U.S. Army Medical Research and Materiel Command [PC050292]; Howard
Hughes Medical Institute; Prostate Cancer Foundation
FX This publication was funded in part with Federal funds from the National
Cancer Institute, National Institutes of Health, under Contract No.
N01-CO-12400, with funds from Grant No. PC050292 from the U.S. Army
Medical Research and Materiel Command, a Howard Hughes Medical Institute
Physician-Scientist Early Career Award, and with a Prostate Cancer
Foundation Young Investigator Award. This research was also supported in
part by the Intramural Research Program of the NIH, National Cancer
Institute. 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 4
Z9 4
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD NOV-DEC
PY 2010
VL 7
IS 6
BP 2216
EP 2223
DI 10.1021/mp100211k
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 688QG
UT WOS:000284865900032
PM 20863081
ER
PT J
AU Arcos-Burgos, M
Jain, M
Acosta, MT
Shively, S
Stanescu, H
Wallis, D
Domene, S
Velez, JI
Karkera, JD
Balog, J
Berg, K
Kleta, R
Gahl, WA
Roessler, E
Long, R
Lie, J
Pineda, D
Londono, AC
Palacio, JD
Arbelaez, A
Lopera, F
Elia, J
Hakonarson, H
Johansson, S
Knappskog, PM
Haavik, J
Ribases, M
Cormand, B
Bayes, M
Casas, M
Ramos-Quiroga, JA
Hervas, A
Maher, BS
Faraone, SV
Seitz, C
Freitag, CM
Palmason, H
Meyer, J
Romanos, M
Walitza, S
Hemminger, U
Warnke, A
Romanos, J
Renner, T
Jacob, C
Lesch, KP
Swanson, J
Vortmeyer, A
Bailey-Wilson, JE
Castellanos, FX
Muenke, M
AF Arcos-Burgos, M.
Jain, M.
Acosta, M. T.
Shively, S.
Stanescu, H.
Wallis, D.
Domene, S.
Velez, J. I.
Karkera, J. D.
Balog, J.
Berg, K.
Kleta, R.
Gahl, W. A.
Roessler, E.
Long, R.
Lie, J.
Pineda, D.
Londono, A. C.
Palacio, J. D.
Arbelaez, A.
Lopera, F.
Elia, J.
Hakonarson, H.
Johansson, S.
Knappskog, P. M.
Haavik, J.
Ribases, M.
Cormand, B.
Bayes, M.
Casas, M.
Ramos-Quiroga, J. A.
Hervas, A.
Maher, B. S.
Faraone, S. V.
Seitz, C.
Freitag, C. M.
Palmason, H.
Meyer, J.
Romanos, M.
Walitza, S.
Hemminger, U.
Warnke, A.
Romanos, J.
Renner, T.
Jacob, C.
Lesch, K-P
Swanson, J.
Vortmeyer, A.
Bailey-Wilson, J. E.
Castellanos, F. X.
Muenke, M.
TI A common variant of the latrophilin 3 gene, LPHN3, confers
susceptibility to ADHD and predicts effectiveness of stimulant
medication
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE ADHD; complex trait; gene; LPHN3; genetics; latrophilin
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY
DISORDER; GENOME-WIDE ASSOCIATION; H-1-MAGNETIC RESONANCE SPECTROSCOPY;
ALPHA-LATROTOXIN RECEPTOR; LINKAGE DISEQUILIBRIUM; FOLLOW-UP; CHILDREN;
RISK; POLYMORPHISM
AB Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started with a linkage study based on large multigenerational families in a population isolate, followed by fine mapping of targeted regions using a family-based design. Family- and population-based association studies in five samples from disparate regions of the world were used for replication. Brain imaging studies were performed to evaluate gene function. The linkage study discovered a genome region harbored in the Latrophilin 3 gene (LPHN3). In the world-wide samples (total n=6360, with 2627 ADHD cases and 2531 controls) statistical association of LPHN3 and ADHD was confirmed. Functional studies revealed that LPHN3 variants are expressed in key brain regions related to attention and activity, affect metabolism in neural circuits implicated in ADHD, and are associated with response to stimulant medication. Linkage and replicated association of ADHD with a novel non-candidate gene (LPHN3) provide new insights into the genetics, neurobiology, and treatment of ADHD. Molecular Psychiatry (2010) 15, 1053-1066; doi:10.1038/mp.2010.6; published online 16 February 2010
C1 [Arcos-Burgos, M.; Jain, M.; Acosta, M. T.; Shively, S.; Stanescu, H.; Wallis, D.; Domene, S.; Velez, J. I.; Karkera, J. D.; Balog, J.; Berg, K.; Kleta, R.; Gahl, W. A.; Roessler, E.; Long, R.; Bailey-Wilson, J. E.; Muenke, M.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Shively, S.; Lie, J.; Vortmeyer, A.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Pineda, D.; Londono, A. C.; Palacio, J. D.; Arbelaez, A.; Lopera, F.] Univ Antioquia, Neurosci Grp, Medellin, Colombia.
[Elia, J.; Hakonarson, H.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Johansson, S.; Knappskog, P. M.; Haavik, J.] Univ Bergen, Dept Biomed, Sect Biochem & Mol Biol, Bergen, Norway.
[Ribases, M.; Casas, M.; Ramos-Quiroga, J. A.] Hosp Univ Vall dHebron, Dept Psychiat, Barcelona, Catalonia, Spain.
[Cormand, B.] Univ Barcelona, Fac Biol, Dept Genet, CIBER ER,IBUB, Barcelona, Catalonia, Spain.
[Bayes, M.] Ctr Nacl Genotipado CeGen, Genes & Dis Program, CRG, CIBER ESP, Barcelona, Catalonia, Spain.
[Casas, M.; Ramos-Quiroga, J. A.] Univ Autonoma Barcelona, Dept Psychiat & Legal Med, Catalonia, Spain.
[Hervas, A.] Hosp Mutua de Terrassa, Child & Adolescent Mental Hlth Unit, Barcelona, Catalonia, Spain.
[Maher, B. S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA USA.
[Maher, B. S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Human Genet, Richmond, VA USA.
[Faraone, S. V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA.
[Seitz, C.; Freitag, C. M.] Saarland Univ Hosp, Dept Child & Adolescent Psychiat, Homburg, Saar, Germany.
[Palmason, H.; Meyer, J.] Univ Trier, Grad Sch Psychobiol, Div Neurobehav Genet, Trier, Germany.
[Romanos, M.; Walitza, S.; Hemminger, U.; Warnke, A.; Renner, T.; Lesch, K-P] Univ Wurzburg, Dept Child & Adolescent Psychiat & Psychotherapy, Wurzburg, Germany.
[Romanos, J.; Renner, T.; Jacob, C.; Lesch, K-P] Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany.
[Renner, T.; Lesch, K-P] Univ Wurzburg, Dept Mol & Psychobiol, Wurzburg, Germany.
[Swanson, J.] Univ Calif Irvine, UCI Child Dev Ctr, Irvine, CA USA.
[Castellanos, F. X.] NYU, Ctr Child Study, New York, NY USA.
RP Muenke, M (reprint author), NHGRI, NIH, 35 Convent Dr,Bldg 35,Room 1B203, Bethesda, MD 20892 USA.
EM mamuenke@mail.nih.gov
RI Renner, Tobias/I-2120-2013; Maher, Brion/F-9185-2010; Johansson,
Stefan/C-4394-2011; Cormand, Bru/H-5338-2015; Lesch,
Klaus-Peter/J-4906-2013; Romanos, Marcel/D-7695-2017;
OI Haavik, Jan/0000-0001-7865-2808; Ramos-Quiroga, Josep
Antoni/0000-0003-1622-0350; Ribases, Marta/0000-0003-1039-1116;
Castellanos, Francisco/0000-0001-9192-9437; Faraone,
Stephen/0000-0002-9217-3982; Johansson, Stefan/0000-0002-2298-7008;
Cormand, Bru/0000-0001-5318-4382; Lesch,
Klaus-Peter/0000-0001-8348-153X; Bailey-Wilson,
Joan/0000-0002-9153-2920; Walitza, Susanne/0000-0002-8161-8683
FU Division of Intramural Research, NHGRI, NIH; COLCIENCIAS [1115-04-12010,
11150418083]; Deutsche Forschungsgemeinschaft [KFO 125/1-1, SFB 581];
'Ministerio de Sanidad y Politica Social', Spain; Instituto de Salud
Carlos III-FIS [PI041267, PI042010, PI040524, PI080519]; Agencia de
Gestio d'Ajuts Universitaris i de Recerca-AGAUR [2009GR971]
FX We are grateful to the families who participated in this research. This
research was supported by the Division of Intramural Research, NHGRI,
NIH and in part by COLCIENCIAS, Grants 1115-04-12010, 11150418083, and
by the Deutsche Forschungsgemeinschaft (KFO 125/1-1, SFB 581). This
study used the high-performance computational capabilities of the SGI
Origin 2000 system at the Center for Information Technology, National
Institutes of Health, Bethesda, MD and the services of the NHGRI
Genomics Core under the supervision of Marypat S Jones and Chandra
Settara. Darryl Leja provided graphical assistance to the figures. N
Steigerwald provided technical assistance in the DNA German sample
processing. Mahim Jain, Sharon B Shively and Sabina Domene are doctoral
students in the NIH Graduate Partnerships Program, at Oxford University,
George Washington University and the University of Buenos Aires,
respectively. Some of this work is to be presented to the above programs
in partial fulfillment of the requirements for the PhD degree. Authors
from Spain are grateful to Anna Bielsa, Xavier Gastaminza, Rosa Bosch,
Monica Fernandez Anguiano and Silvia Rodriguez-Ben for their
participation in the clinical assessment and to Cristina Sanchez-Mora
for laboratory assistance. MR is a recipient of a Miguel de Servet
contract from the 'Ministerio de Sanidad y Politica Social', Spain.
Financial support was received from 'Instituto de Salud Carlos III-FIS'
(PI041267, PI042010, PI040524, PI080519) and 'Agencia de Gestio d'Ajuts
Universitaris i de Recerca-AGAUR' (2009GR971). SNP genotyping of the
Spanish samples was performed at the Barcelona node of the 'Centro
Nacional de Genotipado' (CEGEN; www.cegen.org).
NR 59
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U1 8
U2 14
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 NOV
PY 2010
VL 15
IS 11
BP 1053
EP 1066
DI 10.1038/mp.2010.6
PG 14
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 669LP
UT WOS:000283352400002
PM 20157310
ER
PT J
AU Nierenberg, AA
Akiskal, HS
Angst, J
Hirschfeld, RM
Merikangas, KR
Petukhova, M
Kessler, RC
AF Nierenberg, A. A.
Akiskal, H. S.
Angst, J.
Hirschfeld, R. M.
Merikangas, K. R.
Petukhova, M.
Kessler, R. C.
TI Bipolar disorder with frequent mood episodes in the national comorbidity
survey replication (NCS-R)
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE bipolar disorder; rapid-cycling bipolar disorder; mania; hypomania;
national comorbidity survey replication (NCS-R); comorbidity; treatment
ID TREATMENT ENHANCEMENT PROGRAM; WORLD-HEALTH-ORGANIZATION; WEEKLY
SYMPTOMATIC STATUS; DSM-IV; NATURAL-HISTORY; RATING-SCALE; VALIDITY;
VERSION; PREVALENCE; DISABILITY
AB Virtually nothing is known about the epidemiology of rapid cycling bipolar disorder (BPD) in community samples. Nationally representative data are reported here for the prevalence and correlates of a surrogate measure of DSM-IV rapid cycling BPD from the National Comorbidity survey Replication (NCS-R), a national survey of the US household population. DSM-IV disorders were assessed in the NCS-R with the WHO Composite International Diagnostic Interview (CIDI). Although the CIDI did not assess rapid cycling, it did assess the broader category of 12-month BPD with frequent mood episodes (FMEs), having at least four episodes of mania/hypomania or major depression in the 12 months before interview. Roughly one-third of NCS-R respondents with lifetime DSM-IV BPD and half with 12-month BPD met criteria for FME. FME was associated with younger age-of-onset (of BP-I, but not BP-II) and higher annual persistence (73% of the years since first onset of illness with an episode) than non-FME BPD. No substantial associations of FME vs non-FME BPD were found with socio-demographics, childhood risk factors (parental mental disorders, other childhood adversities) or comorbid DSM-IV disorders. However, FME manic episodes had greater clinical severity than non-FME episodes (assessed with a fully structured version of the Young Mania Rating Scale) and FME hypomanic episodes had greater role impairment than non-FME episodes (assessed with the Sheehan Disability Scales). Whether these indicators of severity merely reflect attenuated effects of rapid cycling or independent effects of sub-threshold rapid cycling warrants further study given the high proportion of lifetime cases who met criteria for FME. Molecular Psychiatry (2010) 15, 1075-1087; doi:10.1038/mp.2009.61; published online 30 June 2009
C1 [Petukhova, M.; Kessler, R. C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Nierenberg, A. A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Akiskal, H. S.] Univ Calif San Diego, Int Mood Ctr, San Diego, CA 92103 USA.
[Akiskal, H. S.] VA Psychiat Serv, San Diego, CA USA.
[Angst, J.] Univ Zurich, Hosp Psychiat, Zurich, Switzerland.
[Hirschfeld, R. M.] Univ Texas Med Branch, Dept Psychiat & Behav Sci, Galveston, TX USA.
[Merikangas, K. R.] NIMH, Intramural Res Program, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM kessler@hcp.med.harvard.edu
FU National Institute of Mental Health (NIMH) [U01-MH60220]; National
Institute of Drug Abuse, the Substance Abuse and Mental Health Services
Administration; Robert Wood Johnson Foundation [044780]; John W Alden
Trust; John D and Catherine T MacArthur Foundation; Pfizer Foundation;
US Public Health Service [R13 MH066849, R01 MH069864, R01 DA016558]; Eli
Lilly and Company; Glaxo-SmithKline; Ortho-McNeil Pharmaceutical, Inc;
Pan American Health Organization
FX The National Comorbidity Survey Replication (NCS-R) is supported by the
National Institute of Mental Health (NIMH; U01-MH60220) with
supplemental support from the National Institute of Drug Abuse, the
Substance Abuse and Mental Health Services Administration, the Robert
Wood Johnson Foundation (Grant #044780) and the John W Alden Trust.
Additional support for preparation of this paper was provided by
Ortho-McNeil Janssen Scientific Affairs, LLC. Collaborating NCS-R
investigators include Ronald C Kessler (Principal Investigator, Harvard
Medical School), Kathleen Merikangas (Co-Principal Investigator, NIMH),
James Anthony (Michigan State University), William Eaton (The Johns
Hopkins University), Meyer Glantz (NIDA), Doreen Koretz (Harvard
University), Jane McLeod (Indiana University), Mark Olfson (Columbia
University College of Physicians and Surgeons), Harold Pincus
(University of Pittsburgh), Greg Simon (Group Health Cooperative), T
Bedirhan Ustun (World Health Organization), Michael Von Korff (Group
Health Cooperative), Philip Wang (Harvard Medical School), Kenneth Wells
(UCLA), Elaine Wethington (Cornell University) and Hans-Ulrich Wittchen
(Max Planck Institute of Psychiatry). The views and opinions expressed
in this report are those of the authors and should not be construed to
represent the views of any of the sponsoring organizations, agencies or
US Government. A complete list of NCS publications and the full text of
all NCS-R instruments can be found at
http://www.hcp.med.harvard.edu/ncs. Send correspondence to
NCS@hcp.med.harvard.edu. The NCS-R is carried out in conjunction with
the World Health Organization World Mental Health (WMH) Survey
Initiative. We thank the staff of the WMH Data Collection and Data
Analysis Coordination Centers for assistance with instrumentation,
fieldwork and consultation on data analysis. These activities were
supported by the John D and Catherine T MacArthur Foundation, the Pfizer
Foundation, the US Public Health Service (R13 MH066849, R01 MH069864,
and R01 DA016558), Eli Lilly and Company, Glaxo-SmithKline, Ortho-McNeil
Pharmaceutical, Inc. and the Pan American Health Organization. A
complete list of WMH publications and instruments can be found at
(http://www.hcp.med.harvard.edu/wmhcidi). The views expressed in this
article do not necessarily represent the view of the NIMH, NIH or HHS of
the US Government.
NR 41
TC 12
Z9 12
U1 2
U2 5
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 NOV
PY 2010
VL 15
IS 11
BP 1075
EP 1087
DI 10.1038/mp.2009.61
PG 13
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 669LP
UT WOS:000283352400004
PM 19564874
ER
PT J
AU Sul, J
Fine, HA
AF Sul, Joohee
Fine, Howard A.
TI Malignant Gliomas: New Translational Therapies
SO MOUNT SINAI JOURNAL OF MEDICINE
LA English
DT Article
DE angiogenesis; epigenencs; glioblastoma; glioma stem cells;
immunotherapy; malignant glioma; molecular profiles; signal transduction
pathways; translational research; tyrosine kinase inhibitors
ID PHASE-II TRIAL; HUMAN-BRAIN-TUMORS; O-6-ALKYLGUANINE-DNA
ALKYLTRANSFERASE ACTIVITY; RECURRENT GLIOBLASTOMA-MULTIFORME;
NEWLY-DIAGNOSED GLIOBLASTOMA; GROWTH-FACTOR-BETA; CANCER STEM-CELL;
CD8(+) T-CELLS; DENDRITIC CELLS; IN-VIVO
AB Malignant gliomas ale the most common primary brain tumors in adults and carry a dismal piognosis Despite aggressive therapy with maximal safe surgical resection, radiation and chemotherapy, these tumors invariably are refractory to or become resistant to treatment and recur Gliomas are highly infiltrative cancers and display remarkable genetic heterogeneity making them challenging to treat Recent progress has been made in understanding the molecular and genetic composition of these tumors and from this, promising new targets for therapy have emerged In particular, anti-angiogenesis therapies have led to modest success in disease control In addition, the growing body of research in cancer immunology as well as cancer stem cells has made inroads in our understanding of tumorgenesis Translational research has been particularly crucial to the development of these therapies as much preclinical and clinical work is needed to develop the rationale for treatments, to develop biomarkers of drug activity and to elucidate mechanisms of resistance This brief overview will discuss some of the pivotal advances made in the pursuit of improved outcomes and survival for patients with this devastating disease Mt Sinai J Med 77 655-666, 2010 (C) 2010 Mount Sinai School of Medicine
C1 [Sul, Joohee; Fine, Howard A.] NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA.
RP Fine, HA (reprint author), NINDS, Neurooncol Branch, NCI, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 95
TC 12
Z9 12
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0027-2507
EI 1931-7581
J9 MT SINAI J MED
JI Mt. Sinai J. Med.
PD NOV-DEC
PY 2010
VL 77
IS 6
BP 655
EP 666
DI 10.1002/msj.20223
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 691KY
UT WOS:000285079900008
PM 21105127
ER
PT J
AU Dai, H
Navath, RS
Balakrishnan, B
Guru, BR
Mishra, MK
Romero, R
Kannan, RM
Kannan, S
AF Dai, Hui
Navath, Raghavendra S.
Balakrishnan, Bindu
Guru, Bharath Raja
Mishra, Manoj K.
Romero, Roberto
Kannan, Rangaramanujam M.
Kannan, Sujatha
TI Intrinsic targeting of inflammatory cells in the brain by polyamidoamine
dendrimers upon subarachnoid administration
SO NANOMEDICINE
LA English
DT Article
DE cerebral palsy; microglia-targeted drug delivery to the brain
neuroinflammation; PAMAM dendrimers
ID CENTRAL-NERVOUS-SYSTEM; MICROGLIAL CELLS; RAT-BRAIN; IN-VIVO; SCAVENGER
RECEPTOR; DELIVERY; BIODISTRIBUTION; NANOPARTICLES; AGENTS;
PHARMACOKINETICS
AB Aim: Understanding the interactions between nanomaterials and disease processes is crucial for designing effective therapeutic approaches. This article explores the unusual neuroinflammation targeting of dendrimers (with no targeting ligands) in the brain, with significant consequences for nanoscale materials in medicine. Method: The in vivo biodistribution of fluorescent-labeled neutral generation-4-polyamidoamine dendrimers (similar to 4 nm) in a rabbit model of cerebral palsy was explored following subarachnoid administration. Results: These dendrimers, with no targeting ligands, were localizing in activated microglia and astrocytes (cells responsible for neuroinflammation), even in regions far moved from the site of injection, in newborn rabbits with maternal inflammation-induced cerebral palsy. Conclusion: This intrinsic ability of dendrimers to localize inactivated microglia and astrocytes can enable targeted delivery of therapeutics in disorders such as cerebral palsy, Alzheimer's and multiple sclerosis.
C1 [Dai, Hui; Navath, Raghavendra S.; Guru, Bharath Raja; Romero, Roberto; Kannan, Rangaramanujam M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinotol Res Branch, NIH, Detroit, MI 48201 USA.
[Dai, Hui; Navath, Raghavendra S.; Guru, Bharath Raja; Romero, Roberto; Kannan, Rangaramanujam M.] NICHD, NIH, DHHS, Detroit, MI 48201 USA.
[Dai, Hui; Balakrishnan, Bindu; Kannan, Sujatha] Wayne State Univ, Childrens Hosp Michigan, Dept Pediat Crit Care Med, Detroit, MI 48201 USA.
[Navath, Raghavendra S.; Mishra, Manoj K.; Kannan, Rangaramanujam M.] Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA.
RP Kannan, RM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinotol Res Branch, NIH, Detroit, MI 48201 USA.
EM rkannan.wsu@gmail.com
RI Guru, Bharath/G-8822-2015; Guru, Bharath/P-6333-2015
OI Guru, Bharath/0000-0003-2542-7740; Guru, Bharath/0000-0001-6735-2180
FU NICHD; NIH; Perinatology Research Branch, Eunice Kennedy Shriver NICHD;
DHHS; Ralph C Wilson Medical Research Foundation; [IK08HD050652]
FX This work is funded in part by IK08HD050652, NICHD, NIH and the
Perinatology Research Branch, Eunice Kennedy Shriver NICHD, NIH, DHHS,
and the Ralph C Wilson Medical Research Foundation. 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 46
TC 42
Z9 42
U1 1
U2 5
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 NOV
PY 2010
VL 5
IS 9
BP 1317
EP 1329
DI 10.2217/NNM.10.89
PG 13
WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology
SC Biotechnology & Applied Microbiology; Science & Technology - Other
Topics
GA 705KR
UT WOS:000286127800007
PM 21128716
ER
PT J
AU Oberdoerffer, P
AF Oberdoerffer, Philipp
TI An age of fewer histones
SO NATURE CELL BIOLOGY
LA English
DT Editorial Material
ID GENE-EXPRESSION; LIFE-SPAN; HUMAN-CELLS; ACETYLATION; SENESCENCE;
TELOMERES
C1 NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Oberdoerffer, P (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM oberdoerfferp@mail.nih.gov
NR 16
TC 4
Z9 4
U1 0
U2 4
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 NOV
PY 2010
VL 12
IS 11
BP 1029
EP 1031
DI 10.1038/ncb1110-1029
PG 3
WC Cell Biology
SC Cell Biology
GA 674CO
UT WOS:000283711500004
PM 21045802
ER
PT J
AU Hummer, G
AF Hummer, Gerhard
TI MOLECULAR BINDING Under water's influence
SO NATURE CHEMISTRY
LA English
DT News Item
ID LIGAND-BINDING; CAVITY; SITE
C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM Gerhard.Hummer@nih.gov
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
FU Intramural NIH HHS [ZIA DK029036-04]
NR 9
TC 62
Z9 62
U1 3
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1755-4330
J9 NAT CHEM
JI Nat. Chem.
PD NOV
PY 2010
VL 2
IS 11
BP 906
EP 907
DI 10.1038/nchem.885
PG 3
WC Chemistry, Multidisciplinary
SC Chemistry
GA 669MG
UT WOS:000283354300003
PM 20966940
ER
PT J
AU Ryazanova, LV
Rondon, LJ
Zierler, S
Hu, ZX
Galli, J
Yamaguchi, TP
Mazur, A
Fleig, A
Ryazanov, AG
AF Ryazanova, Lillia V.
Rondon, Lusliany J.
Zierler, Susanna
Hu, Zhixian
Galli, Joanna
Yamaguchi, Terry P.
Mazur, Andrzej
Fleig, Andrea
Ryazanov, Alexey G.
TI TRPM7 is essential for Mg2+ homeostasis in mammals
SO NATURE COMMUNICATIONS
LA English
DT Article
ID SECONDARY HYPOCALCEMIA; ION-CHANNEL; PROTEIN-KINASES; ALPHA-KINASES;
MAGNESIUM; HYPOMAGNESEMIA; MUTATION; DOMAIN; CELL; CURRENTS
AB Mg2+ is the second-most abundant cation in animal cells and is an essential cofactor in numerous enzymatic reactions. The molecular mechanisms controlling Mg2+ balance in the organism are not well understood. In this study, we report identification of TRPM7, a bifunctional protein containing a protein kinase fused to an ion channel, as a key regulator of whole body Mg2+ homeostasis in mammals. We generated TRPM7-deficient mice with the deletion of the kinase domain. Homozygous TRPM7(Delta kinase) mice demonstrated early embryonic lethality, whereas heterozygous mice were viable, but developed signs of hypomagnesaemia and revealed a defect in intestinal Mg2+ absorption. Cells derived from heterozygous TRPM7(Delta kinase) mice demonstrated reduced TRPM7 currents that had increased sensitivity to the inhibition by Mg2+. Embryonic stem cells lacking TRPM7 kinase domain displayed a proliferation arrest phenotype that can be rescued by Mg2+ supplementation. Our results demonstrate that TRPM7 is essential for the control of cellular and whole body Mg2+ homeostasis.
C1 [Ryazanova, Lillia V.; Hu, Zhixian; Ryazanov, Alexey G.] Univ Med & Dent New Jersey, Dept Pharmacol, RW Johnson Med Sch, Piscataway, NJ 08854 USA.
[Rondon, Lusliany J.; Galli, Joanna; Mazur, Andrzej] Univ Auvergne, UNH, INRA, UMR 1019,CRNH Auvergne, F-63000 Clermont Ferrand, France.
[Rondon, Lusliany J.; Galli, Joanna; Mazur, Andrzej] Univ Auvergne, Clermont Univ, Unite Nutr Humaine, F-63000 Clermont Ferrand, France.
[Zierler, Susanna; Fleig, Andrea] Univ Hawaii, Queens Ctr Biomed Res, Lab Cell & Mol Signaling, Queens Ctr Biomed Res, Honolulu, HI 96813 USA.
[Zierler, Susanna; Fleig, Andrea] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96813 USA.
[Galli, Joanna] Wroclaw Univ Environm & Life Sci, Fac Vet Med, PL-50375 Wroclaw, Poland.
[Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH Frederick, Frederick, MD 21702 USA.
RP Ryazanov, AG (reprint author), Univ Med & Dent New Jersey, Dept Pharmacol, RW Johnson Med Sch, 675 Hoes Lane, Piscataway, NJ 08854 USA.
EM ryazanag@umdnj.edu
RI Zierler, Susanna/E-2070-2012
OI Zierler, Susanna/0000-0002-4684-0385
FU NIH [P01GM078195]; Austrian Science Fund (F.W.F.) [J2784]
FX We thank Stephanie Johne, Dominique Bayle, Jean-Claude Tressol,
Catherine Besson and Severine Thien for technical support. We are
grateful to Reinhold Penner for stimulating discussions, Maxim Dorovkov
and Inna Nikonorova for their help and advice, and to Jonathan
Eggenschwiler for critical reading of the manuscript. This study was
supported by NIH Grant P01GM078195 (A. G. R., A. F.) and Austrian
Science Fund (F.W.F.) Grant J2784 (S.Z.).
NR 30
TC 99
Z9 102
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD NOV
PY 2010
VL 1
AR 109
DI 10.1038/ncomms1108
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732YE
UT WOS:000288224800007
PM 21045827
ER
PT J
AU Peterson, J
Campbell, J
AF Peterson, Jane
Campbell, Joseph
TI Marker papers and data citation
SO NATURE GENETICS
LA English
DT Letter
C1 [Peterson, Jane; Campbell, Joseph] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Peterson, J (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 2
Z9 2
U1 1
U2 18
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 NOV
PY 2010
VL 42
IS 11
BP 919
EP 919
DI 10.1038/ng1110-919
PG 1
WC Genetics & Heredity
SC Genetics & Heredity
GA 671VW
UT WOS:000283540500003
PM 20980982
ER
PT J
AU Speliotes, EK
Willer, CJ
Berndt, SI
Monda, KL
Thorleifsson, G
Jackson, AU
Allen, HL
Lindgren, CM
Luan, J
Magi, R
Randall, JC
Vedantam, S
Winkler, TW
Qi, L
Workalemahu, T
Heid, IM
Steinthorsdottir, V
Stringham, HM
Weedon, MN
Wheeler, E
Wood, AR
Ferreira, T
Weyant, RJ
Segre, AV
Estrada, K
Liang, LM
Nemesh, J
Park, JH
Gustafsson, S
Kilpelanen, TO
Yang, JA
Bouatia-Naji, N
Esko, T
Feitosa, MF
Kutalik, Z
Mangino, M
Raychaudhuri, S
Scherag, A
Smith, AV
Welch, R
Zhao, JH
Aben, KK
Absher, DM
Amin, N
Dixon, AL
Fisher, E
Glazer, NL
Goddard, ME
Heard-Costa, NL
Hoesel, V
Hottenga, JJ
Johansson, A
Johnson, T
Ketkar, S
Lamina, C
Li, SX
Moffatt, MF
Myers, RH
Narisu, N
Perry, JRB
Peters, MJ
Preuss, M
Ripatti, S
Rivadeneira, F
Sandholt, C
Scott, LJ
Timpson, NJ
Tyrer, JP
van Wingerden, S
Watanabe, RM
White, CC
Wiklund, F
Barlassina, C
Chasman, DI
Cooper, MN
Jansson, JO
Lawrence, RW
Pellikka, N
Prokopenko, I
Shi, JX
Thiering, E
Alavere, H
Alibrandi, MTS
Almgren, P
Arnold, AM
Aspelund, T
Atwood, LD
Balkau, B
Balmforth, AJ
Bennett, AJ
Ben-Shlomo, Y
Bergman, RN
Bergmann, S
Biebermann, H
Blakemore, AIF
Boes, T
Bonnycastle, LL
Bornstein, SR
Brown, MJ
Buchanan, TA
Busonero, F
Campbell, H
Cappuccio, FP
Cavalcanti-Proenca, C
Chen, YDI
Chen, CM
Chines, PS
Clarke, R
Coin, L
Connell, J
Day, INM
den Heijer, M
Duan, JB
Ebrahim, S
Elliott, P
Elosua, R
Eiriksdottir, G
Erdos, MR
Eriksson, JG
Facheris, MF
Felix, SB
Fischer-Posovszky, P
Folsom, AR
Friedrich, N
Freimer, NB
Fu, M
Gaget, S
Gejman, PV
Geus, EJC
Gieger, C
Gjesing, AP
Goel, A
Goyette, P
Grallert, H
Grassler, J
Greenawalt, DM
Groves, CJ
Gudnason, V
Guiducci, C
Hartikainen, AL
Hassanali, N
Hall, AS
Havulinna, AS
Hayward, C
Heath, AC
Hengstenberg, C
Hicks, AA
Hinney, A
Hofman, A
Homuth, G
Hui, J
Igl, W
Iribarren, C
Isomaa, B
Jacobs, KB
Jarick, I
Jewell, E
John, U
Jorgensen, T
Jousilahti, P
Jula, A
Kaakinen, M
Kajantie, E
Kaplan, LM
Kathiresan, S
Kettunen, J
Kinnunen, L
Knowles, JW
Kolcic, I
Konig, IR
Koskinen, S
Kovacs, P
Kuusisto, J
Kraft, P
Kvaloy, K
Laitinen, J
Lantieri, O
Lanzani, C
Launer, LJ
Lecoeur, C
Lehtimaki, T
Lettre, G
Liu, JJ
Lokki, ML
Lorentzon, M
Luben, RN
Ludwig, B
Manunta, P
Marek, D
Marre, M
Martin, NG
McArdle, WL
McCarthy, A
McKnight, B
Meitinger, T
Melander, O
Meyre, D
Midthjell, K
Montgomery, GW
Morken, MA
Morris, AP
Mulic, R
Ngwa, JS
Nelis, M
Neville, MJ
Nyholt, DR
O'Donnell, CJ
O'Rahilly, S
Ong, KK
Oostra, B
Pare, G
Parker, AN
Perola, M
Pichler, I
Pietilainen, KH
Platou, CGP
Polasek, O
Pouta, A
Rafelt, S
Raitakari, O
Rayner, NW
Ridderstrale, M
Rief, W
Ruokonen, A
Robertson, NR
Rzehak, P
Salomaa, V
Sanders, AR
Sandhu, MS
Sanna, S
Saramies, J
Savolainen, MJ
Scherag, S
Schipf, S
Schreiber, S
Schunkert, H
Silander, K
Sinisalo, J
Siscovick, DS
Smit, JH
Soranzo, N
Sovio, U
Stephens, J
Surakka, I
Swift, AJ
Tammesoo, ML
Tardif, JC
Teder-Laving, M
Teslovich, TM
Thompson, JR
Thomson, B
Tonjes, A
Tuomi, T
van Meurs, JBJ
van Ommen, GJ
Vatin, V
Viikari, J
Visvikis-Siest, S
Vitart, V
Vogel, CIG
Voight, BF
Waite, LL
Wallaschofski, H
Walters, GB
Widen, E
Wiegand, S
Wild, SH
Willemsen, G
Witte, DR
Witteman, JC
Xu, JF
Zhang, QY
Zgaga, L
Ziegler, A
Zitting, P
Beilby, JP
Farooqi, IS
Hebebrand, J
Huikuri, HV
James, AL
Kahonen, M
Levinson, DF
Macciardi, F
Nieminen, MS
Ohlsson, C
Palmer, LJ
Ridker, PM
Stumvoll, M
Beckmann, JS
Boeing, H
Boerwinkle, E
Boomsma, DI
Caulfield, MJ
Chanock, SJ
Collins, FS
Cupples, LA
Smith, GD
Erdmann, J
Froguel, P
Gronberg, H
Gyllensten, U
Hall, P
Hansen, T
Harris, TB
Hattersley, AT
Hayes, RB
Heinrich, J
Hu, FB
Hveem, K
Illig, T
Jarvelin, MR
Kaprio, J
Karpe, F
Khaw, KT
Kiemeney, LA
Krude, H
Laakso, M
Lawlor, DA
Metspalu, A
Munroe, PB
Ouwehand, WH
Pedersen, O
Penninx, BW
Peters, A
Pramstaller, PP
Quertermous, T
Reinehr, T
Rissanen, A
Rudan, I
Samani, NJ
Schwarz, PEH
Shuldiner, AR
Spector, TD
Tuomilehto, J
Uda, M
Uitterlinden, A
Valle, TT
Wabitsch, M
Waeber, G
Wareham, NJ
Watkins, H
Wilson, JF
Wright, AF
Zillikens, MC
Chatterjee, N
McCarroll, SA
Purcell, S
Schadt, EE
Visscher, PM
Assimes, TL
Borecki, IB
Deloukas, P
Fox, CS
Groop, LC
Haritunians, T
Hunter, DJ
Kaplan, RC
Mohlke, KL
O'Connell, JR
Peltonen, L
Schlessinger, D
Strachan, DP
van Duijn, CM
Wichmann, HE
Frayling, TM
Thorsteinsdottir, U
Abecasis, GR
Barroso, I
Boehnke, M
Stefansson, K
North, KE
McCarthy, MI
Hirschhorn, JN
Ingelsson, E
Loos, RJF
AF Speliotes, Elizabeth K.
Willer, Cristen J.
Berndt, Sonja I.
Monda, Keri L.
Thorleifsson, Gudmar
Jackson, Anne U.
Allen, Hana Lango
Lindgren, Cecilia M.
Luan, Jian'an
Maegi, Reedik
Randall, Joshua C.
Vedantam, Sailaja
Winkler, Thomas W.
Qi, Lu
Workalemahu, Tsegaselassie
Heid, Iris M.
Steinthorsdottir, Valgerdur
Stringham, Heather M.
Weedon, Michael N.
Wheeler, Eleanor
Wood, Andrew R.
Ferreira, Teresa
Weyant, Robert J.
Segre, Ayellet V.
Estrada, Karol
Liang, Liming
Nemesh, James
Park, Ju-Hyun
Gustafsson, Stefan
Kilpelaenen, Tuomas O.
Yang, Jian
Bouatia-Naji, Nabila
Esko, Tonu
Feitosa, Mary F.
Kutalik, Zoltan
Mangino, Massimo
Raychaudhuri, Soumya
Scherag, Andre
Smith, Albert Vernon
Welch, Ryan
Zhao, Jing Hua
Aben, Katja K.
Absher, Devin M.
Amin, Najaf
Dixon, Anna L.
Fisher, Eva
Glazer, Nicole L.
Goddard, Michael E.
Heard-Costa, Nancy L.
Hoesel, Volker
Hottenga, Jouke-Jan
Johansson, Asa
Johnson, Toby
Ketkar, Shamika
Lamina, Claudia
Li, Shengxu
Moffatt, Miriam F.
Myers, Richard H.
Narisu, Narisu
Perry, John R. B.
Peters, Marjolein J.
Preuss, Michael
Ripatti, Samuli
Rivadeneira, Fernando
Sandholt, Camilla
Scott, Laura J.
Timpson, Nicholas J.
Tyrer, Jonathan P.
van Wingerden, Sophie
Watanabe, Richard M.
White, Charles C.
Wiklund, Fredrik
Barlassina, Christina
Chasman, Daniel I.
Cooper, Matthew N.
Jansson, John-Olov
Lawrence, Robert W.
Pellikka, Niina
Prokopenko, Inga
Shi, Jianxin
Thiering, Elisabeth
Alavere, Helene
Alibrandi, Maria T. S.
Almgren, Peter
Arnold, Alice M.
Aspelund, Thor
Atwood, Larry D.
Balkau, Beverley
Balmforth, Anthony J.
Bennett, Amanda J.
Ben-Shlomo, Yoav
Bergman, Richard N.
Bergmann, Sven
Biebermann, Heike
Blakemore, Alexandra I. F.
Boes, Tanja
Bonnycastle, Lori L.
Bornstein, Stefan R.
Brown, Morris J.
Buchanan, Thomas A.
Busonero, Fabio
Campbell, Harry
Cappuccio, Francesco P.
Cavalcanti-Proenca, Christine
Chen, Yii-Der Ida
Chen, Chih-Mei
Chines, Peter S.
Clarke, Robert
Coin, Lachlan
Connell, John
Day, Ian N. M.
den Heijer, Martin
Duan, Jubao
Ebrahim, Shah
Elliott, Paul
Elosua, Roberto
Eiriksdottir, Gudny
Erdos, Michael R.
Eriksson, Johan G.
Facheris, Maurizio F.
Felix, Stephan B.
Fischer-Posovszky, Pamela
Folsom, Aaron R.
Friedrich, Nele
Freimer, Nelson B.
Fu, Mao
Gaget, Stefan
Gejman, Pablo V.
Geus, Eco J. C.
Gieger, Christian
Gjesing, Anette P.
Goel, Anuj
Goyette, Philippe
Grallert, Harald
Graessler, Juergen
Greenawalt, Danielle M.
Groves, Christopher J.
Gudnason, Vilmundur
Guiducci, Candace
Hartikainen, Anna-Liisa
Hassanali, Neelam
Hall, Alistair S.
Havulinna, Aki S.
Hayward, Caroline
Heath, Andrew C.
Hengstenberg, Christian
Hicks, Andrew A.
Hinney, Anke
Hofman, Albert
Homuth, Georg
Hui, Jennie
Igl, Wilmar
Iribarren, Carlos
Isomaa, Bo
Jacobs, Kevin B.
Jarick, Ivonne
Jewell, Elizabeth
John, Ulrich
Jorgensen, Torben
Jousilahti, Pekka
Jula, Antti
Kaakinen, Marika
Kajantie, Eero
Kaplan, Lee M.
Kathiresan, Sekar
Kettunen, Johannes
Kinnunen, Leena
Knowles, Joshua W.
Kolcic, Ivana
Koenig, Inke R.
Koskinen, Seppo
Kovacs, Peter
Kuusisto, Johanna
Kraft, Peter
Kvaloy, Kirsti
Laitinen, Jaana
Lantieri, Olivier
Lanzani, Chiara
Launer, Lenore J.
Lecoeur, Cecile
Lehtimaeki, Terho
Lettre, Guillaume
Liu, Jianjun
Lokki, Marja-Liisa
Lorentzon, Mattias
Luben, Robert N.
Ludwig, Barbara
Manunta, Paolo
Marek, Diana
Marre, Michel
Martin, Nicholas G.
McArdle, Wendy L.
McCarthy, Anne
McKnight, Barbara
Meitinger, Thomas
Melander, Olle
Meyre, David
Midthjell, Kristian
Montgomery, Grant W.
Morken, Mario A.
Morris, Andrew P.
Mulic, Rosanda
Ngwa, Julius S.
Nelis, Mari
Neville, Matt J.
Nyholt, Dale R.
O'Donnell, Christopher J.
O'Rahilly, Stephen
Ong, Ken K.
Oostra, Ben
Pare, Guillaume
Parker, Alex N.
Perola, Markus
Pichler, Irene
Pietilaeinen, Kirsi H.
Platou, Carl G. P.
Polasek, Ozren
Pouta, Anneli
Rafelt, Suzanne
Raitakari, Olli
Rayner, Nigel W.
Ridderstrale, Martin
Rief, Winfried
Ruokonen, Aimo
Robertson, Neil R.
Rzehak, Peter
Salomaa, Veikko
Sanders, Alan R.
Sandhu, Manjinder S.
Sanna, Serena
Saramies, Jouko
Savolainen, Markku J.
Scherag, Susann
Schipf, Sabine
Schreiber, Stefan
Schunkert, Heribert
Silander, Kaisa
Sinisalo, Juha
Siscovick, David S.
Smit, Jan H.
Soranzo, Nicole
Sovio, Ulla
Stephens, Jonathan
Surakka, Ida
Swift, Amy J.
Tammesoo, Mari-Liis
Tardif, Jean-Claude
Teder-Laving, Maris
Teslovich, Tanya M.
Thompson, John R.
Thomson, Brian
Toenjes, Anke
Tuomi, Tiinamaija
van Meurs, Joyce B. J.
van Ommen, Gert-Jan
Vatin, Vincent
Viikari, Jorma
Visvikis-Siest, Sophie
Vitart, Veronique
Vogel, Carla I. G.
Voight, Benjamin F.
Waite, Lindsay L.
Wallaschofski, Henri
Walters, G. Bragi
Widen, Elisabeth
Wiegand, Susanna
Wild, Sarah H.
Willemsen, Gonneke
Witte, Daniel R.
Witteman, Jacqueline C.
Xu, Jianfeng
Zhang, Qunyuan
Zgaga, Lina
Ziegler, Andreas
Zitting, Paavo
Beilby, John P.
Farooqi, I. Sadaf
Hebebrand, Johannes
Huikuri, Heikki V.
James, Alan L.
Kaehoenen, Mika
Levinson, Douglas F.
Macciardi, Fabio
Nieminen, Markku S.
Ohlsson, Claes
Palmer, Lyle J.
Ridker, Paul M.
Stumvoll, Michael
Beckmann, Jacques S.
Boeing, Heiner
Boerwinkle, Eric
Boomsma, Dorret I.
Caulfield, Mark J.
Chanock, Stephen J.
Collins, Francis S.
Cupples, L. Adrienne
Smith, George Davey
Erdmann, Jeanette
Froguel, Philippe
Greonberg, Henrik
Gyllensten, Ulf
Hall, Per
Hansen, Torben
Harris, Tamara B.
Hattersley, Andrew T.
Hayes, Richard B.
Heinrich, Joachim
Hu, Frank B.
Hveem, Kristian
Illig, Thomas
Jarvelin, Marjo-Riitta
Kaprio, Jaakko
Karpe, Fredrik
Khaw, Kay-Tee
Kiemeney, Lambertus A.
Krude, Heiko
Laakso, Markku
Lawlor, Debbie A.
Metspalu, Andres
Munroe, Patricia B.
Ouwehand, Willem H.
Pedersen, Oluf
Penninx, Brenda W.
Peters, Annette
Pramstaller, Peter P.
Quertermous, Thomas
Reinehr, Thomas
Rissanen, Aila
Rudan, Igor
Samani, Nilesh J.
Schwarz, Peter E. H.
Shuldiner, Alan R.
Spector, Timothy D.
Tuomilehto, Jaakko
Uda, Manuela
Uitterlinden, Andre
Valle, Timo T.
Wabitsch, Martin
Waeber, Gerard
Wareham, Nicholas J.
Watkins, Hugh
Wilson, James F.
Wright, Alan F.
Zillikens, M. Carola
Chatterjee, Nilanjan
McCarroll, Steven A.
Purcell, Shaun
Schadt, Eric E.
Visscher, Peter M.
Assimes, Themistocles L.
Borecki, Ingrid B.
Deloukas, Panos
Fox, Caroline S.
Groop, Leif C.
Haritunians, Talin
Hunter, David J.
Kaplan, Robert C.
Mohlke, Karen L.
O'Connell, Jeffrey R.
Peltonen, Leena
Schlessinger, David
Strachan, David P.
van Duijn, Cornelia M.
Wichmann, H-Erich
Frayling, Timothy M.
Thorsteinsdottir, Unnur
Abecasis, Goncalo R.
Barroso, Ines
Boehnke, Michael
Stefansson, Kari
North, Kari E.
McCarthy, Mark I.
Hirschhorn, Joel N.
Ingelsson, Erik
Loos, Ruth J. F.
CA MAGIC
TI Association analyses of 249,796 individuals reveal 18 new loci
associated with body mass index
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GASTRIC-INHIBITORY POLYPEPTIDE; MELANOCORTIN-4
RECEPTOR GENE; GLUCOSE-HOMEOSTASIS; COMMON VARIANTS; ADULT OBESITY;
EARLY-ONSET; FTO GENE; FAT MASS; RISK
AB Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
C1 [Brown, Morris J.] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge, England.
[Speliotes, Elizabeth K.; Vedantam, Sailaja; Guiducci, Candace; Thomson, Brian; Hirschhorn, Joel N.] Broad Inst, Metab Initiat & Program Med & Populat Genet, Cambridge, MA USA.
[Speliotes, Elizabeth K.; Kaplan, Lee M.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Willer, Cristen J.; Jackson, Anne U.; Stringham, Heather M.; Weyant, Robert J.; Welch, Ryan; Scott, Laura J.; Jewell, Elizabeth; Teslovich, Tanya M.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Berndt, Sonja I.; Park, Ju-Hyun; Shi, Jianxin; Chanock, Stephen J.; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Monda, Keri L.; North, Kari E.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Walters, G. Bragi; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
[Allen, Hana Lango; Weedon, Michael N.; Wood, Andrew R.; Perry, John R. B.; Hattersley, Andrew T.; Frayling, Timothy M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England.
[Lindgren, Cecilia M.; Maegi, Reedik; Randall, Joshua C.; Ferreira, Teresa; Prokopenko, Inga; Goel, Anuj; Morris, Andrew P.; Rayner, Nigel W.; Robertson, Neil R.; Watkins, Hugh; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Lindgren, Cecilia M.; Prokopenko, Inga; Bennett, Amanda J.; Groves, Christopher J.; Hassanali, Neelam; Neville, Matt J.; Rayner, Nigel W.; Robertson, Neil R.; Karpe, Fredrik; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Luan, Jian'an; Kilpelaenen, Tuomas O.; Zhao, Jing Hua; Ong, Ken K.; Sandhu, Manjinder S.; Wareham, Nicholas J.; Loos, Ruth J. F.] Addenbrookes Hosp, MRC, Epidemiol Unit, Inst Metab Sci, Cambridge, England.
[Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Winkler, Thomas W.; Heid, Iris M.] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany.
[Qi, Lu; Workalemahu, Tsegaselassie; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Qi, Lu; Hu, Frank B.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Qi, Lu; Chasman, Daniel I.; Kaplan, Lee M.; Ridker, Paul M.; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA.
[Heid, Iris M.; Lamina, Claudia; Thiering, Elisabeth; Chen, Chih-Mei; Gieger, Christian; Grallert, Harald; Rzehak, Peter; Heinrich, Joachim; Illig, Thomas; Peters, Annette; Wichmann, H-Erich] Helmholtz Zentrum Munchen, German Res Ctr, Inst Epidemiol, Neuherberg, Germany.
[Wheeler, Eleanor; Sandhu, Manjinder S.; Soranzo, Nicole; Ouwehand, Willem H.; Deloukas, Panos; Peltonen, Leena; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge, England.
[Segre, Ayellet V.; Kathiresan, Sekar; Voight, Benjamin F.; McCarroll, Steven A.; Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Segre, Ayellet V.; Nemesh, James; Raychaudhuri, Soumya; Kathiresan, Sekar] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Nemesh, James; Raychaudhuri, Soumya; Kathiresan, Sekar] MIT, Cambridge, MA 02139 USA.
[Segre, Ayellet V.; Voight, Benjamin F.; McCarroll, Steven A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Estrada, Karol; Amin, Najaf; Rivadeneira, Fernando; van Wingerden, Sophie; Hofman, Albert; van Meurs, Joyce B. J.; Witteman, Jacqueline C.; Uitterlinden, Andre; van Duijn, Cornelia M.] Erasmus Med Ctr MC, Dept Epidemiol, Rotterdam, Netherlands.
[Estrada, Karol; Peters, Marjolein J.; Rivadeneira, Fernando; van Meurs, Joyce B. J.; Uitterlinden, Andre; Zillikens, M. Carola] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Estrada, Karol; Peters, Marjolein J.; Rivadeneira, Fernando; Hofman, Albert; van Meurs, Joyce B. J.; Witteman, Jacqueline C.; Uitterlinden, Andre; Zillikens, M. Carola; van Duijn, Cornelia M.] Netherlands Consortium Healthy Aging NCHA, Netherlands Genom Initiat NGI Sponsored, Rotterdam, Netherlands.
[Liang, Liming; Kraft, Peter; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Liang, Liming; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Gustafsson, Stefan; Wiklund, Fredrik; Greonberg, Henrik; Hall, Per; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Yang, Jian; Visscher, Peter M.] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia.
[Bouatia-Naji, Nabila; Cavalcanti-Proenca, Christine; Gaget, Stefan; Lecoeur, Cecile; Meyre, David; Vatin, Vincent; Froguel, Philippe] Inst Pasteur, CNRS, UMR8199, IBL, F-59019 Lille, France.
[Bouatia-Naji, Nabila; Cavalcanti-Proenca, Christine; Gaget, Stefan; Lecoeur, Cecile; Meyre, David; Nelis, Mari; Vatin, Vincent; Froguel, Philippe] Univ Lille Nord France, Lille, France.
[Esko, Tonu; Alavere, Helene; Nelis, Mari; Tammesoo, Mari-Liis; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Teder-Laving, Maris; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Esko, Tonu; Nelis, Mari; Teder-Laving, Maris; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Feitosa, Mary F.; Ketkar, Shamika; Zhang, Qunyuan; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Kutalik, Zoltan; Johnson, Toby; Bergmann, Sven; Folsom, Aaron R.; Marek, Diana; Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Kutalik, Zoltan; Johnson, Toby; Bergmann, Sven; Marek, Diana] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Mangino, Massimo; Soranzo, Nicole; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
[Raychaudhuri, Soumya] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA USA.
[Scherag, Andre; Boes, Tanja] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany.
[Smith, Albert Vernon; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert Vernon; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Aben, Katja K.; Kiemeney, Lambertus A.] Comprehens Canc Ctr E, Nijmegen, Netherlands.
[Absher, Devin M.; Waite, Lindsay L.] Hudson Alpha Inst Biotechnol, Huntsville, AL USA.
[Dixon, Anna L.] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England.
[Fisher, Eva; Boeing, Heiner] German Inst Human Nutr, Dept Epidemiol, Potsdam, Nuthetal, Germany.
[Glazer, Nicole L.] Univ Washington, Dept Med, Seattle, WA USA.
[Glazer, Nicole L.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Goddard, Michael E.] Univ Melbourne, Parkville, Vic 3052, Australia.
[Goddard, Michael E.] Dept Primary Ind, Melbourne, Australia.
[Heard-Costa, Nancy L.; Atwood, Larry D.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Hoesel, Volker] Tech Univ Munich, Chair Biomath, D-8046 Garching, Germany.
[Hottenga, Jouke-Jan; Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ VU Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Johansson, Asa; Igl, Wilmar; Gyllensten, Ulf] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden.
[Johansson, Asa] Norwegian Univ Sci & Technol NTNU, Fac Med, Dept Canc Res & Mol Med, Trondheim, Norway.
[Johnson, Toby] Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
[Johnson, Toby; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Genome Ctr, London, England.
[Johnson, Toby; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
[Lamina, Claudia] Innsbruck Med Univ3, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
[Moffatt, Miriam F.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Narisu, Narisu; Bonnycastle, Lori L.; Chines, Peter S.; Erdos, Michael R.; Morken, Mario A.; Swift, Amy J.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Preuss, Michael; Koenig, Inke R.; Ziegler, Andreas] Univ Klinikum Schleswig Holstein, Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany.
[Ripatti, Samuli; Pellikka, Niina; Kettunen, Johannes; Perola, Markus; Silander, Kaisa; Surakka, Ida; Widen, Elisabeth; Kaprio, Jaakko; Peltonen, Leena] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Ripatti, Samuli; Pellikka, Niina; Kettunen, Johannes; Perola, Markus; Silander, Kaisa; Surakka, Ida; Peltonen, Leena] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Unit Publ Hlth Genom, Helsinki, Finland.
[Sandholt, Camilla; Gjesing, Anette P.; Hansen, Torben; Pedersen, Oluf] Hagedorn Res Inst, Gentofte, Denmark.
[Timpson, Nicholas J.; Day, Ian N. M.; Smith, George Davey; Lawlor, Debbie A.] MRC Ctr Causal Anal Translat Epidemiol, Dept Social Med, Bristol, Avon, England.
[Tyrer, Jonathan P.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Watanabe, Richard M.; Bergman, Richard N.; Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[White, Charles C.; Ngwa, Julius S.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Barlassina, Christina; Macciardi, Fabio] Univ Milan, Dept Med Surg & Dent, Milan, Italy.
[Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Cooper, Matthew N.; Lawrence, Robert W.; Hui, Jennie; Palmer, Lyle J.] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Crawley, WA, Australia.
[Jansson, John-Olov] Univ Gothenburg, Dept Physiol, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden.
[Alibrandi, Maria T. S.; Lanzani, Chiara; Manunta, Paolo] Univ Vita Salute San Raffaele, Div Nephrol & Dialysis, Milan, Italy.
[Almgren, Peter; Groop, Leif C.] Lund Univ, Dept Clin Sci, Ctr Diabet, Malmo, Sweden.
[Arnold, Alice M.; McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Arnold, Alice M.] Collaborat Hlth Studies Coordinating Ctr, Seattle, WA USA.
[Balkau, Beverley] Ctr Res Epidemiol & Publ Hlth, INSERM, Ctr Rech Epidimiol & Sante Populat CESP, U1018, Villejuif, France.
[Balkau, Beverley] Univ Paris 11, UMRS 1018, Villejuif, France.
[Balmforth, Anthony J.; Hall, Alistair S.] Univ Leeds, LIGHT, MCRC, Leeds, W Yorkshire, England.
[Ben-Shlomo, Yoav] Univ Bristol, Dept Social Med, Bristol, Avon, England.
[Biebermann, Heike; Wiegand, Susanna; Krude, Heiko] Charite, Inst Expt Paediat Endocrinol, D-13353 Berlin, Germany.
[Blakemore, Alexandra I. F.; Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England.
[Bornstein, Stefan R.; Ludwig, Barbara] Univ Dresden, Dept Med 3, Dresden, Germany.
[Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Div Endocrinol, Los Angeles, CA 90033 USA.
[Busonero, Fabio; Sanna, Serena; Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy.
[Campbell, Harry; Wild, Sarah H.; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Cappuccio, Francesco P.] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
[Chen, Yii-Der Ida; Haritunians, Talin] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Clarke, Robert] Radcliffe Infirm, Clin Trial Serv Unit, Oxford OX2 6HE, England.
[Coin, Lachlan; Elliott, Paul; Sovio, Ulla; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Fac Med, Dept Epidemiol & Biostat, London, England.
[Connell, John] Univ Dundee, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Scotland.
[den Heijer, Martin; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6525 ED Nijmegen, Netherlands.
[den Heijer, Martin] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands.
[Duan, Jubao; Gejman, Pablo V.; Sanders, Alan R.] Northshore Univ Healthsyst, Evanston, IL USA.
[Ebrahim, Shah] London Sch Hyg & Trop Med, London WC1, England.
[Ebrahim, Shah] S Asia Network Chron Dis, New Delhi, India.
[Elliott, Paul] Ctr Environm & Hlth, MRC Hlth Protect Agcy HPA, London, England.
[Elosua, Roberto] Ctr Invest Biomed Red CIBER Epidemiol & Salud Pub, Barcelona, Spain.
[Elosua, Roberto] Inst Municipal Invest Med, E-08003 Barcelona, Spain.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland.
[Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland.
[Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland.
[Facheris, Maurizio F.; Hicks, Andrew A.; Pichler, Irene; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy.
[Facheris, Maurizio F.; Hicks, Andrew A.; Pichler, Irene; Pramstaller, Peter P.] Univ Lubeck, Lubeck, Germany.
[Facheris, Maurizio F.; Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy.
[Felix, Stephan B.] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, Greifswald, Germany.
[Fischer-Posovszky, Pamela; Wabitsch, Martin] Dept Pediat & Adolescent Med, Pediat Endocrinol Diabet & Obes Unit, Ulm, Germany.
[Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Friedrich, Nele; Schipf, Sabine; Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Inst Klin Chem & Lab Med, Greifswald, Germany.
[Freimer, Nelson B.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA.
[Fu, Mao; Shuldiner, Alan R.; O'Connell, Jeffrey R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Goel, Anuj; Watkins, Hugh] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England.
[Goyette, Philippe; Lettre, Guillaume; Tardif, Jean-Claude] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Graessler, Juergen] Univ Dresden, Dept Med 3, Dresden, Germany.
[Greenawalt, Danielle M.] Merck & Co Inc, Merck Res Labs, Boston, MA USA.
[Hartikainen, Anna-Liisa; Pouta, Anneli] Univ Oulu, Dept Clin Sci Obstet & Gynecol, Oulu, Finland.
[Havulinna, Aki S.; Jousilahti, Pekka; Koskinen, Seppo; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Chron Dis Epidemiol & Prevent Unit, Helsinki, Finland.
[Hayward, Caroline; Vitart, Veronique; Wright, Alan F.] Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
[Heath, Andrew C.] Washington Univ, Sch Med, Dept Psychiat & Midwest Alcoholism Res Ctr, St Louis, MO USA.
[Hengstenberg, Christian] Univ Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany.
[Hengstenberg, Christian] Univ Regensburg, Med Ctr, Regensburg, Germany.
[Hinney, Anke; Scherag, Susann; Vogel, Carla I. G.; Hebebrand, Johannes] Univ Duisburg Essen, Dept Child & Adolescent Psychiat, Essen, Germany.
[Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Hui, Jennie; Beilby, John P.; Stumvoll, Michael] PathWest Lab Western Australia, Dept Mol Genet, QEII Med Ctr, Nedlands, WA, Australia.
[Hui, Jennie; Beilby, John P.; James, Alan L.; Palmer, Lyle J.] Sir Charles Gairdner Hosp, Busselton Populat Med Res Fdn Inc, Nedlands, WA 6009, Australia.
[Iribarren, Carlos] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Iribarren, Carlos] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland.
[Jacobs, Kevin B.] NCI, SAIC Frederick Inc, Core Genotyping Facil, Frederick, MD 21701 USA.
[Jarick, Ivonne] Univ Marburg, Inst Med Biometry & Epidemiol, Marburg, Germany.
[John, Ulrich] Ernst Moritz Arndt Univ Greifswald, Inst Epidemiol & Sozialmed, Greifswald, Germany.
[Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.
[Jorgensen, Torben] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark.
[Jula, Antti] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Populat Studies Unit, Turku, Finland.
[Kaakinen, Marika; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Kaakinen, Marika; Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Kajantie, Eero] Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland.
[Kajantie, Eero] Univ Helsinki, Hosp Dist Helsinki & Uusimaa HUS, Helsinki, Finland.
[Kaplan, Lee M.] Massachusetts Gen Hosp, Massachusetts Gen Hosp MGH Weight Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[O'Donnell, Christopher J.] Boston Univ, Framingham, MA USA.
[Kathiresan, Sekar; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA.
[Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Kinnunen, Leena; Tuomilehto, Jaakko; Valle, Timo T.] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.
[Knowles, Joshua W.; Quertermous, Thomas; Assimes, Themistocles L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Kolcic, Ivana; Polasek, Ozren; Zgaga, Lina] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41000, Croatia.
[Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany.
[Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland.
[Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Kvaloy, Kirsti; Midthjell, Kristian; Platou, Carl G. P.; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Nord Trondelag Hlth Study HUNT Res Ctr, Levanger, Norway.
[Laitinen, Jaana] Finnish Inst Occupat Hlth, Oulu, Finland.
[Lantieri, Olivier] Inst Interreg Sante IRSA, La Riche, France.
[Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA.
[Lehtimaeki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Lehtimaeki, Terho] Tampere Univ Hosp, Tampere, Finland.
[Lettre, Guillaume; Tardif, Jean-Claude] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada.
[Liu, Jianjun] Genome Inst Singapore, Singapore, Singapore.
[Lokki, Marja-Liisa] Univ Helsinki, Transplantat Lab, Haartman Inst, Helsinki, Finland.
[Lorentzon, Mattias; Ohlsson, Claes] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, Gothenburg, Sweden.
[Luben, Robert N.; Sandhu, Manjinder S.; Khaw, Kay-Tee] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England.
[Marre, Michel] Bichat Claude Bernard Univ Hosp, AP HP, Dept Endocrinol Diabetol & Nutr, Paris, France.
[Marre, Michel] Univ Nancy 1, Cardiovasc Genet Res Unit, Nancy, France.
[Martin, Nicholas G.] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4006, Australia.
[McArdle, Wendy L.] Univ Bristol, Dept Social Med, Avon Longitudinal Study Parents & Children ALSPAC, Bristol, Avon, England.
[McCarthy, Anne] Bord Taighde Slainte, Res Board, Div Hlth, Dublin, Ireland.
[Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany.
[Meitinger, Thomas] Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Human Genet, Neuherberg, Germany.
[Melander, Olle; Ridderstrale, Martin] Lund Univ, Dept Clin Sci, Malmo, Sweden.
[Montgomery, Grant W.] Queensland Inst Med Res, Mol Epidemiol Lab, Brisbane, Qld 4006, Australia.
[Mulic, Rosanda; Rudan, Igor] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia.
[Nyholt, Dale R.] Queensland Inst Med Res, Neurogenet Lab, Brisbane, Qld 4006, Australia.
[O'Donnell, Christopher J.] NHLBI, NIH, Framingham, MA USA.
[O'Rahilly, Stephen; Farooqi, I. Sadaf] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England.
[Oostra, Ben] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Pare, Guillaume] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada.
[Parker, Alex N.] Amgen Inc, Cambridge, MA USA.
[Pietilaeinen, Kirsi H.; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.
[Pietilaeinen, Kirsi H.; Rissanen, Aila] Univ Helsinki, Cent Hosp, Dept Psychiat, Obes Res Unit, Helsinki, Finland.
[Platou, Carl G. P.] Nord Trondelag Hlth Trust, Levanger Hosp, Dept Med, Levanger, Norway.
[Polasek, Ozren] Gen Info Ltd, Zagreb, Croatia.
[Pouta, Anneli; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Oulu, Finland.
[Rafelt, Suzanne; Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland.
[Rief, Winfried] Univ Marburg, Marburg, Germany.
[Ruokonen, Aimo] Univ Oulu, Dept Clin Sci & Clin Chem, Oulu, Finland.
[Rzehak, Peter; Wichmann, H-Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Saramies, Jouko] S Karelia Cent Hosp, Lappeenranta, Finland.
[Savolainen, Markku J.] Univ Oulu, Dept Clin Sci & Internal Med, Oulu, Finland.
[Schipf, Sabine] Inst Community Med, Greifswald, Germany.
[Schreiber, Stefan] Univ Kiel, Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, Kiel, Germany.
[Schreiber, Stefan] Univ Kiel, Dept Internal Med 1, Kiel, Germany.
[Schunkert, Heribert; Erdmann, Jeanette] Univ Lubeck, Med Klin 2, Lubeck, Germany.
[Sinisalo, Juha; Nieminen, Markku S.] Univ Helsinki, Cent Hosp, Cardiovasc Lab, Div Cardiol, Helsinki, Finland.
[Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA USA.
[Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA USA.
[Smit, Jan H.; Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, Inst Extramuraal Geneeskundig Onderzoek EMGO Inst, Dept Psychiat, Amsterdam, Netherlands.
[Stephens, Jonathan; Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England.
[Stephens, Jonathan; Ouwehand, Willem H.] Natl Hlth Serv NHS Blood & Transplant, Cambridge Ctr, Cambridge, England.
[Thompson, John R.; Samani, Nilesh J.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc, Leicester, Leics, England.
[Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, Leipzig, Germany.
[Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[Toenjes, Anke] Univ Leipzig, Coordinat Ctr Clin Trials, Leipzig, Germany.
[Tuomi, Tiinamaija] Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland.
[Tuomi, Tiinamaija] Univ Helsinki, Res Program Mol Med, Helsinki, Finland.
[van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
[van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Ctr Med Syst Biol, Leiden, Netherlands.
[Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland.
[Viikari, Jorma] Turku Univ Hosp, FIN-20520 Turku, Finland.
[Visvikis-Siest, Sophie] INSERM, Cardiovasc Genet team, CIC 9501, Nancy, France.
[Witte, Daniel R.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
[Xu, Jianfeng] Wake Forest Univ, Ctr Human Genom, Winston Salem, NC 27109 USA.
[Zitting, Paavo] Lapland Cent Hosp, Dept Physiatr, Rovaniemi, Finland.
[Beilby, John P.] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia.
[Huikuri, Heikki V.] Univ Oulu, Dept Internal Med, SF-90220 Oulu, Finland.
[James, Alan L.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Kaehoenen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland.
[Kaehoenen, Mika] Tampere Univ Hosp, Tampere, Finland.
[Levinson, Douglas F.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Macciardi, Fabio] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA.
Univ Leipzig, Leipziger Interdisziplinarer Forsch Komplex Mol U, Leipzig, Germany.
[Beckmann, Jacques S.] Univ Hosp, CHUV, Serv Med Genet, Lausanne, Switzerland.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA.
[Hansen, Torben] Univ So Denmark, Fac Hlth Sci, Odense, Denmark.
[Hayes, Richard B.] NYU, Med Ctr, New York, NY 10016 USA.
[Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth & Substance Abuse Serv, Unit Child & Adolescent Mental Hlth, Helsinki, Finland.
[Karpe, Fredrik; McCarthy, Mark I.] Churchill Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 7LJ, England.
[Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands.
[Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark.
[Pedersen, Oluf] Univ Copenhagen, Inst Biomed Sci, Copenhagen, Denmark.
[Penninx, Brenda W.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.
[Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands.
[Pramstaller, Peter P.] Univ Lubeck, Dept Neurol, Lubeck, Germany.
[Reinehr, Thomas] Univ Witten Herdecke, Vest Hosp Children & Adolescents, Inst Paediat Nutr Med, Datteln, Germany.
[Schwarz, Peter E. H.] Univ Dresden, Dept Med 3, Dresden, Germany.
[Tuomilehto, Jaakko] Baltimore Vet Adm, Geriatr Res & Educ Clin Ctr, Med Ctr, Baltimore, MD USA.
[Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland.
[Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland.
[Shuldiner, Alan R.; Waeber, Gerard] Univ Hosp, CHUV, Dept Internal Med, Lausanne, Switzerland.
[Purcell, Shaun; Peltonen, Leena] MIT, Cambridge, MA 02139 USA.
[Purcell, Shaun; Peltonen, Leena] Broad Inst Harvard, Cambridge, MA 02139 USA.
[Purcell, Shaun] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Schadt, Eric E.] Pacific Biosci, Menlo Pk, CA USA.
[Schadt, Eric E.] Sage Bionetworks, Seattle, WA USA.
[Borecki, Ingrid B.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham, MA USA.
[Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
[Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Peltonen, Leena] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
[Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
[Strachan, David P.] Univ London, Div Community Hlth Sci, London, England.
[Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England.
[North, Kari E.] Univ N Carolina, Sch Publ Hlth, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
RP Brown, MJ (reprint author), Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge, England.
EM boehnke@umich.edu; kstefans@decode.is; kari_north@unc.edu;
mark.mccarthy@drl.ox.ac.uk; joelh@broadinstitute.org;
erik.ingelsson@ki.se; ruth.loos@mrc-epid.cam.ac.uk
RI kinnunen, leena/B-7059-2012; Li, Shengxu/D-8915-2012; Spector,
Tim/F-6533-2012; Ridderstrale, Martin/F-7678-2012; Kilpelainen,
Tuomas/F-8569-2012; Lango Allen, Hana/G-9026-2012; Rudan,
Igor/I-1467-2012; Johansson, Asa/G-5270-2011; Deloukas,
Panos/B-2922-2013; Thiering, Elisabeth/B-3342-2013; Grallert,
Harald/B-3424-2013; Nyholt, Dale/C-8384-2013; Colaus,
PsyColaus/K-6607-2013; Lamina, Claudia/F-7608-2010; Kaplan,
Robert/A-2526-2011; Hinney, Anke/D-6953-2011; Meyre, David/D-7315-2011;
Beckmann, Jacques S /A-9772-2008; Peters, Annette/A-6117-2011; Abecasis,
Goncalo/B-7840-2010; Polasek, Ozren/B-6002-2011; Schreiber,
Stefan/B-6748-2008; Voight, Benjamin/F-1775-2011; Aspelund,
Thor/F-4826-2011; Segre, Ayellet/E-9800-2010; Aspelund,
Thor/C-5983-2008; Kiemeney, Lambertus/D-3357-2009; Visvikis-Siest,
Sophie/H-2324-2014; Pramstaller, Peter/C-2357-2008; Cooper,
Matthew/J-4420-2014; Palmer, Lyle/K-3196-2014; Witte,
Daniel/C-1722-2008; Gudnason, Vilmundur/K-6885-2015; Ripatti,
Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Montgomery,
Grant/B-7148-2008; Meitinger, Thomas/O-1318-2015; Rivadeneira,
Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; Ziegler,
Andreas/G-4246-2012; Macciardi, Fabio/N-3768-2014; Aben,
Katja/G-9686-2016; Yang, Jian/A-5852-2010; Smith, Albert/K-5150-2015;
mangino, massimo/F-5134-2011; Hayward, Caroline/M-8818-2016;
BOUATIA-NAJI, NABILA/D-5863-2013; Coin, Lachlan/A-9001-2014; Schwarz,
Peter/B-5127-2013; Konig, Inke/A-4544-2009; Erdmann,
Jeanette/A-4417-2009; Davey Smith, George/A-7407-2013; Mulic,
Rosanda/D-6914-2017; Kolcic, Ivana/E-2713-2017; Feitosa,
Mary/K-8044-2012; Hicks, Andrew/E-9518-2017;
OI kinnunen, leena/0000-0001-8739-4812; Lango Allen,
Hana/0000-0002-7803-8688; Rudan, Igor/0000-0001-6993-6884; Johansson,
Asa/0000-0002-2915-4498; Deloukas, Panos/0000-0001-9251-070X; Hinney,
Anke/0000-0001-5659-0706; Beckmann, Jacques S /0000-0002-9741-1900;
Polasek, Ozren/0000-0002-5765-1862; Schreiber,
Stefan/0000-0003-2254-7771; Aspelund, Thor/0000-0002-7998-5433;
Kiemeney, Lambertus/0000-0002-2368-1326; Visvikis-Siest,
Sophie/0000-0001-8104-8425; Cooper, Matthew/0000-0003-1139-3682; Palmer,
Lyle/0000-0002-1628-3055; Witte, Daniel/0000-0002-0769-2922; Gudnason,
Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202;
Wilson, James F/0000-0001-5751-9178; Montgomery,
Grant/0000-0002-4140-8139; Rivadeneira, Fernando/0000-0001-9435-9441;
Prokopenko, Inga/0000-0003-1624-7457; Ziegler,
Andreas/0000-0002-8386-5397; Macciardi, Fabio/0000-0003-0537-4266; Aben,
Katja/0000-0002-0214-2147; Yang, Jian/0000-0003-2001-2474; Smith,
Albert/0000-0003-1942-5845; mangino, massimo/0000-0002-2167-7470;
Hayward, Caroline/0000-0002-9405-9550; Coin,
Lachlan/0000-0002-4300-455X; Schwarz, Peter/0000-0001-6317-7880; Davey
Smith, George/0000-0002-1407-8314; Kolcic, Ivana/0000-0001-7918-6052;
Feitosa, Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411;
Thiering, Elisabeth/0000-0002-5429-9584; Soranzo,
Nicole/0000-0003-1095-3852; Peters, Marjolein/0000-0003-3167-9063;
Bouatia-Naji, Nabila/0000-0001-5424-2134; Willer,
Cristen/0000-0001-5645-4966; Kaakinen, Marika/0000-0002-9228-0462;
Pichler, Irene/0000-0001-8251-0757; Heard-Costa,
Nancy/0000-0001-9730-0306; Goddard, Michael/0000-0001-9917-7946; Magi,
Reedik/0000-0002-2964-6011; Marre, Michel/0000-0002-3071-1837; sanna,
serena/0000-0002-3768-1749; Monsalve, Beatriz Elena/0000-0002-5994-866X;
Johnson, Toby/0000-0002-5998-3270; Cappuccio, Francesco
Paolo/0000-0002-7842-5493; Myers, Richard/0000-0002-8365-2674; Cupples,
L. Adrienne/0000-0003-0273-7965; Brown, Matthew A/0000-0003-0538-8211;
Abecasis, Goncalo/0000-0003-1509-1825; Esko, Tonu/0000-0003-1982-6569;
Manunta, Paolo/0000-0003-3976-9696; Zgaga, Lina/0000-0003-4089-9703;
Luben, Robert/0000-0002-5088-6343; Gieger,
Christian/0000-0001-6986-9554; Scherag, Andre/0000-0002-9406-4704;
Hayes, Richard/0000-0002-0918-661X; Jarvelin,
Marjo-Riitta/0000-0002-2149-0630; Tuomi, Tiinamaija/0000-0002-8306-6202;
John, Ulrich/0000-0003-0587-5298; Karpe, Fredrik/0000-0002-2751-1770;
Jorgensen, Torben/0000-0001-9453-2830; Watkins,
Hugh/0000-0002-5287-9016; Perola, Markus/0000-0003-4842-1667; Visscher,
Peter/0000-0002-2143-8760; Eriksson, Johan/0000-0002-2516-2060;
Ouwehand, Willem/0000-0002-7744-1790; Kaprio,
Jaakko/0000-0002-3716-2455; Timpson, Nicholas/0000-0002-7141-9189;
Lawlor, Debbie A/0000-0002-6793-2262; Bergmann,
Sven/0000-0002-6785-9034; Sinisalo, Juha/0000-0002-0169-5137; de Geus,
Eco/0000-0001-6022-2666; Martin, Nicholas/0000-0003-4069-8020; Farooqi,
Sadaf/0000-0001-7609-3504
FU Academy of Finland [10404, 77299, 104781, 114382, 117797, 120315]; ADA;
Amgen; Agency for Science, Technology and Research of Singapore
(AstarSTAR); ALF/LUA; Althingi (the Icelandic Parliament);
AstraZeneca; Augustinus Foundation; Australian National Health and
Medical Research Council [241944, 389875, 389891, 389892, 389938,
442915, 442981, 496739, 496688, 552485, 613672]; Australian Research
Council (ARC) [DP0770096]; Becket Foundation; Biocenter (Finland);
Biomedicum Helsinki Foundation; Boston Obesity Nutrition Research
Center; British Diabetes Association [1192]; British Heart Foundation
[97020, PG/02/128]; Busselton Population Medical Research Foundation;
Cambridge Institute for Medical Research; Cambridge National Institute
of Health Research (NIHR) Comprehensive Biomedical Research Centre;
CamStrad (UK); Cancer Research UK; Centre for Medical Systems Biology
(The Netherlands); Centre for Neurogenomics and Cognitive Research (The
Netherlands); Chief Scientist Office of the Scottish Government; Contrat
Plan Etat Region (France); Danish Centre for Health Technology
Assessment; Danish Diabetes Association; Danish Heart Foundation; Danish
Pharmaceutical Association; Danish Research Council; Deutsche
Forschungsgemeinschaft (DFG) [HE 1446/4-1]; Department of Health (UK);
Diabetes UK; Diabetes and Inflammation Laboratory; Donald W. Reynolds
Foundation; Dresden University of Technology; Emil and Vera Cornell
Foundation; Erasmus Medical Center (Rotterdam); Erasmus University
(Rotterdam); European Commission [QLG1-CT-2000-01643,
QLG2-CT-2002-01254, LSHC-CT-2005, LSHG-CT-2006-018947,
LSHG-CT-2004-518153, LSH-2006-037593, LSHM-CT-2007-037273, HEALTH-
F2-2008-ENGAGE, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550, 205419,
212111, 245536, SOC 9520140805F02, WLRT-2001-01254]; Federal Ministry of
Education and Research (Germany) [01AK803, 01EA9401, 01GI0823, 01GI0826,
01GP0209, 01GP0259, 01GS0820, 01GS0823, 01GS0824, 01GS0825, 01GS0830,
01GS0831, 01IG07015, 01KU0903, 01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012];
Federal State of Mecklenburg-West Pomerania; European Social Fund; Eve
Appeal; Finnish Diabetes Research Foundation; Finnish Foundation for
Cardiovascular Research; Finnish Foundation for Pediatric Research,
Finnish Medical Society; Finska Lakaresallskapet, Paivikki and Sakari
Sohlberg Foundation, Folkhalsan Research Foundation; Fond Europeen pour
le Developpement Regional (France); Fondation LeDucq (Paris, France);
Foundation for Life and Health in Finland; Foundation for Strategic
Research (Sweden); Genetic Association Information Network; German
Research Council [KFO-152]; German National Genome Research Net
'NGFNplus' [FKZ 01GS0823]; German Research Center for Environmental
Health; Giorgi-Cavaglieri Foundation; GlaxoSmithKline; Goteborg Medical
Society; Great Wine Estates Auctions; Gyllenberg Foundation; Health Care
Centers in Vasa, Narpes and Korsholm; Healthway, Western Australia;
Helmholtz Center Munich; Helsinki University Central Hospital,
Hjartavernd (the Icelandic Heart Association); INSERM (France); Ib
Henriksen Foundation; Interdisziplinares Zentrum fur Klinische Forschung
(IZKF) [B27]; Jalmari and Rauha Ahokas Foundation; Juho Vainio
Foundation; Juvenile Diabetes Research Foundation International (JDRF);
Karolinska Institute; Knut and Alice Wallenberg Foundation; Leenaards
Foundation; Lundbeck Foundation Centre of Applied Medical Genomics for
Personalized Disease Prediction, Prevention and Care (LUCAMP); Lundberg
Foundation; Marie Curie Intra-European Fellowship; Medical Research
Council (UK) [G0000649, G0000934, G9521010D, G0500539, G0600331,
G0601261]; Ministry of Cultural Affairs and Social Ministry of the
Federal State of Mecklenburg-West Pomerania; Ministry for Health,
Welfare and Sports (The Netherlands); Ministry of Education (Finland);
Ministry of Education, Culture and Science (The Netherlands); Ministry
of Internal Affairs and Health (Denmark); Ministry of Science, Education
and Sport of the Republic of Croatia [216-1080315-0302]; Ministry of
Science, Research and the Arts Baden-Wurttemberg; Montreal Heart
Institute Foundation; Municipal Health Care Center and Hospital in
Jakobstad; Municipality of Rotterdam; Narpes Health Care Foundation;
National Cancer Institute; National Health and Medical Research Council
of Australia; National Institute for Health Research Cambridge
Biomedical Research Centre; National Institute for Health Research
Oxford Biomedical Research Centre
FX Funding was provided by Academy of Finland (10404, 77299, 104781,
114382, 117797, 120315, 121584, 124243, 126775, 126925, 127437, 129255,
129269, 129306, 129494, 129680, 130326, 209072, 210595, 213225, 213506
and 216374); ADA Mentor-Based Postdoctoral Fellowship; Amgen; Agency for
Science, Technology and Research of Singapore (A*STAR); ALF/LUA research
grant in Gothenburg; Althingi (the Icelandic Parliament); AstraZeneca;
Augustinus Foundation; Australian National Health and Medical Research
Council (241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739,
496688, 552485 and 613672); Australian Research Council (ARC grant
DP0770096); Becket Foundation; Biocenter (Finland); Biomedicum Helsinki
Foundation; Boston Obesity Nutrition Research Center; British Diabetes
Association (1192); British Heart Foundation (97020; PG/02/128);
Busselton Population Medical Research Foundation; Cambridge Institute
for Medical Research; Cambridge National Institute of Health Research
(NIHR) Comprehensive Biomedical Research Centre; CamStrad (UK); Cancer
Research UK; Centre for Medical Systems Biology (The Netherlands);
Centre for Neurogenomics and Cognitive Research (The Netherlands); Chief
Scientist Office of the Scottish Government; Contrat Plan Etat Rrgion
(France); Danish Centre for Health Technology Assessment; Danish
Diabetes Association; Danish Heart Foundation; Danish Pharmaceutical
Association; Danish Research Council; Deutsche Forschungsgemeinschaft
(DFG; HE 1446/4-1); Department of Health (UK); Diabetes UK; Diabetes and
Inflammation Laboratory; Donald W.; Reynolds Foundation; Dresden
University of Technology Funding Grant; Emil and Vera Cornell
Foundation; Erasmus Medical Center (Rotterdam); Erasmus University
(Rotterdam); European Commission (DG XII; QLG1-CT-2000-01643,
QLG2-CT-2002-01254, LSHC-CT-2005, LSHG-CT-2006-018947,
LSHG-CT-2004-518153, LSH-2006-037593, LSHM-CT-2007-037273,
HEALTH-F2-2008ENGAGE, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550,
FP7/2007-2013, 205419, 212111, 245536, SOC 95201408 05F02 and
WLRT-2001-01254); Federal Ministry of Education and Research (Germany)
(01AK803, 01EA9401, 01GI0823, 01GI0826, 01GP0209, 01GP0259, 01GS0820,
01GS0823, 01GS0824, 01GS0825, 01GS0830, 01GS0831, 01IG07015, 01KU0903,
01ZZ9603, 01ZZ0103, 01ZZ0403 and 03ZIK012); Federal State of
Mecklenburg-West Pomerania; European Social Fund; Eve Appeal; Finnish
Diabetes Research Foundation; Finnish Foundation for Cardiovascular
Research; Finnish Foundation for Pediatric Research, Finnish Medical
Society; Finska Lakaresallskapet, Paivikki and Sakari Sohlberg
Foundation, Folkhalsan Research Foundation; Fond Europeen pour le
Developpement Regional (France); Fondation LeDucq (Paris, France);
Foundation for Life and Health in Finland; Foundation for Strategic
Research (Sweden); Genetic Association Information Network; German
Research Council (KFO-152); German National Genome Research Net
'NGFNplus' (FKZ 01GS0823); German Research Center for Environmental
Health; Giorgi-Cavaglieri Foundation; GlaxoSmithKline; Goteborg Medical
Society; Great Wine Estates Auctions; Gyllenberg Foundation; Health Care
Centers in Vasa, Narpes and Korsholm; Healthway, Western Australia;
Helmholtz Center Munich; Helsinki University Central Hospital,
Hjartavernd (the Icelandic Heart Association); INSERM (France); Ib
Henriksen Foundation; Interdisziplinares Zentrum fur Klinische Forschung
(IZKF) (B27); Jalmari and Rauha Ahokas Foundation; Juho Vainio
Foundation; Juvenile Diabetes Research Foundation International (JDRF);
Karolinska Institute; Knut and Alice Wallenberg Foundation; Leenards
Foundation; Lundbeck Foundation Centre of Applied Medical Genomics for
Personalized Disease Prediction, Prevention and Care (LUCAMP); Lundberg
Foundation; Marie Curie Intra-European Fellowship; Medical Research
Council (UK) (G0000649, G0000934, G9521010D, G0500539, G0600331 and
G0601261, PrevMetSyn); Ministry of Cultural Affairs and Social Ministry
of the Federal State of Mecklenburg-West Pomerania; Ministry for Health,
Welfare and Sports (The Netherlands); Ministry of Education (Finland);
Ministry of Education, Culture and Science (The Netherlands); Ministry
of Internal Affairs and Health (Denmark); Ministry of Science, Education
and Sport of the Republic of Croatia (216-1080315-0302); Ministry of
Science, Research and the Arts Baden-Wurttemberg; Montreal Heart
Institute Foundation; Municipal Health Care Center and Hospital in
Jakobstad; Municipality of Rotterdam; Narpes Health Care Foundation;
National Cancer Institute; National Health and Medical Research Council
of Australia; National Institute for Health Research Cambridge
Biomedical Research Centre; National Institute for Health Research
Oxford Biomedical Research Centre; National Institute for Health
Research comprehensive Biomedical Research Centre; US National
Institutes of Health (263-MA-410953, AA07535, AA10248, AA014041,
AA13320, AA13321, AA13326, CA047988, CA65725, CA87969, CA49449, CA67262,
CA50385, DA12854, DK58845, DK46200, DK062370, DK063491, DK072193,
HG002651, HL084729, HHSN268200625226C, HL71981, K23-DK080145,
K99-HL094535, M01-RR00425, MH084698, N01-AG12100, NO1-AG12109, N01-H;
15103, N01-HC25195, N01-HC35129, N01-HC45133, N01-HC55015, N01-HC55016,
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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 NOV
PY 2010
VL 42
IS 11
BP 937
EP U53
DI 10.1038/ng.686
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 671VW
UT WOS:000283540500010
PM 20935630
ER
PT J
AU Heid, IM
Jackson, AU
Randall, JC
Winkler, TW
Qi, L
Steinthorsdottir, V
Thorleifsson, G
Zillikens, MC
Speliotes, EK
Magi, R
Workalemahu, T
White, CC
Bouatia-Naji, N
Harris, TB
Berndt, SI
Ingelsson, E
Willer, CJ
Weedon, MN
Luan, JA
Vedantam, S
Esko, T
Kilpelainen, TO
Kutalik, Z
Li, SX
Monda, KL
Dixon, AL
Holmes, CC
Kaplan, LM
Liang, LM
Min, JL
Moffatt, MF
Molony, C
Nicholson, G
Schadt, EE
Zondervan, KT
Feitosa, MF
Ferreira, T
Allen, HL
Weyant, RJ
Wheeler, E
Wood, AR
Estrada, K
Goddard, ME
Lettre, G
Mangino, M
Nyholt, DR
Purcell, S
Smith, AV
Visscher, PM
Yang, JA
McCarroll, SA
Nemesh, J
Voight, BF
Absher, D
Amin, N
Aspelund, T
Coin, L
Glazer, NL
Hayward, C
Heard-Costa, NL
Hottenga, JJ
Johansson, A
Johnson, T
Kaakinen, M
Kapur, K
Ketkar, S
Knowles, JW
Kraft, P
Kraja, AT
Lamina, C
Leitzmann, MF
McKnight, B
Morris, AP
Ong, KK
Perry, JRB
Peters, MJ
Polasek, O
Prokopenko, I
Rayner, NW
Ripatti, S
Rivadeneira, F
Robertson, NR
Sanna, S
Sovio, U
Surakka, I
Teumer, A
van Wingerden, S
Vitart, V
Zhao, JH
Cavalcanti-Proenca, C
Chines, PS
Fisher, E
Kulzer, JR
Lecoeur, C
Narisu, N
Sandholt, C
Scott, LJ
Silander, K
Stark, K
Tammesoo, ML
Teslovich, TM
Timpson, NJ
Watanabe, RM
Welch, R
Chasman, DI
Cooper, MN
Jansson, JO
Kettunen, J
Lawrence, RW
Pellikka, N
Perola, M
Vandenput, L
Alavere, H
Almgren, P
Atwood, LD
Bennett, AJ
Biffar, R
Bonnycastle, LL
Bornstein, SR
Buchanan, TA
Campbell, H
Day, INM
Dei, M
Dorr, M
Elliott, P
Erdos, MR
Eriksson, JG
Freimer, NB
Fu, M
Gaget, S
Geus, EJC
Gjesing, AP
Grallert, H
Grassler, J
Groves, CJ
Guiducci, C
Hartikainen, AL
Hassanali, N
Havulinna, AS
Herzig, KH
Hicks, AA
Hui, JN
Igl, W
Jousilahti, P
Jula, A
Kajantie, E
Kinnunen, L
Kolcic, I
Koskinen, S
Kovacs, P
Kroemer, HK
Krzelj, V
Kuusisto, J
Kvaloy, K
Laitinen, J
Lantieri, O
Lathrop, GM
Lokki, ML
Luben, RN
Ludwig, B
McArdle, WL
McCarthy, A
Morken, MA
Nelis, M
Neville, MJ
Pare, G
Parker, AN
Peden, JF
Pichler, I
Pietilainen, KH
Platou, CGP
Pouta, A
Ridderstrale, M
Samani, NJ
Saramies, J
Sinisalo, J
Smit, JH
Strawbridge, RJ
Stringham, HM
Swift, AJ
Teder-Laving, M
Thomson, B
Usala, G
van Meurs, JBJ
van Ommen, GJ
Vatin, V
Volpato, CB
Wallaschofski, H
Walters, GB
Widen, E
Wild, SH
Willemsen, G
Witte, DR
Zgaga, L
Zitting, P
Beilby, JP
James, AL
Kahonen, M
Lehtimaki, T
Nieminen, MS
Ohlsson, C
Palmer, LJ
Raitakari, O
Ridker, PM
Stumvoll, M
Tonjes, A
Viikari, J
Balkau, B
Ben-Shlomo, Y
Bergman, RN
Boeing, H
Smith, GD
Ebrahim, S
Froguel, P
Hansen, T
Hengstenberg, C
Hveem, K
Isomaa, B
Jorgensen, T
Karpe, F
Khaw, KT
Laakso, M
Lawlor, DA
Marre, M
Meitinger, T
Metspalu, A
Midthjell, K
Pedersen, O
Salomaa, V
Schwarz, PEH
Tuomi, T
Tuomilehto, J
Valle, TT
Wareham, NJ
Arnold, AM
Beckmann, JS
Bergmann, S
Boerwinkle, E
Boomsma, DI
Caulfield, MJ
Collins, FS
Eiriksdottir, G
Gudnason, V
Gyllensten, U
Hamsten, A
Hattersley, AT
Hofman, A
Hu, FB
Illig, T
Iribarren, C
Jarvelin, MR
Kao, WHL
Kaprio, J
Launer, LJ
Munroe, PB
Oostra, B
Penninx, BW
Pramstaller, PP
Psaty, BM
Quertermous, T
Rissanen, A
Rudan, I
Shuldiner, AR
Soranzo, N
Spector, TD
Syvanen, AC
Uda, M
Uitterlinden, A
Volzke, H
Vollenweider, P
Wilson, JF
Witteman, JC
Wright, AF
Abecasis, GR
Boehnke, M
Borecki, IB
Deloukas, P
Frayling, TM
Groop, LC
Haritunians, T
Hunter, DJ
Kaplan, RC
North, KE
O'Connell, JR
Peltonen, L
Schlessinger, D
Strachan, DP
Hirschhorn, JN
Assimes, TL
Wichmann, HE
Thorsteinsdottir, U
van Duijn, CM
Stefansson, K
Cupples, LA
Loos, RJF
Barroso, I
McCarthy, MI
Fox, CS
Mohlke, KL
Lindgren, CM
AF Heid, Iris M.
Jackson, Anne U.
Randall, Joshua C.
Winkler, Thomas W.
Qi, Lu
Steinthorsdottir, Valgerdur
Thorleifsson, Gudmar
Zillikens, M. Carola
Speliotes, Elizabeth K.
Maegi, Reedik
Workalemahu, Tsegaselassie
White, Charles C.
Bouatia-Naji, Nabila
Harris, Tamara B.
Berndt, Sonja I.
Ingelsson, Erik
Willer, Cristen J.
Weedon, Michael N.
Luan, Jianan
Vedantam, Sailaja
Esko, Tonu
Kilpelaeinen, Tuomas O.
Kutalik, Zoltan
Li, Shengxu
Monda, Keri L.
Dixon, Anna L.
Holmes, Christopher C.
Kaplan, Lee M.
Liang, Liming
Min, Josine L.
Moffatt, Miriam F.
Molony, Cliona
Nicholson, George
Schadt, Eric E.
Zondervan, Krina T.
Feitosa, Mary F.
Ferreira, Teresa
Allen, Hana Lango
Weyant, Robert J.
Wheeler, Eleanor
Wood, Andrew R.
Estrada, Karol
Goddard, Michael E.
Lettre, Guillaume
Mangino, Massimo
Nyholt, Dale R.
Purcell, Shaun
Smith, Albert Vernon
Visscher, Peter M.
Yang, Jian
McCarroll, Steven A.
Nemesh, James
Voight, Benjamin F.
Absher, Devin
Amin, Najaf
Aspelund, Thor
Coin, Lachlan
Glazer, Nicole L.
Hayward, Caroline
Heard-Costa, Nancy L.
Hottenga, Jouke-Jan
Johansson, Asa
Johnson, Toby
Kaakinen, Marika
Kapur, Karen
Ketkar, Shamika
Knowles, Joshua W.
Kraft, Peter
Kraja, Aldi T.
Lamina, Claudia
Leitzmann, Michael F.
McKnight, Barbara
Morris, Andrew P.
Ong, Ken K.
Perry, John R. B.
Peters, Marjolein J.
Polasek, Ozren
Prokopenko, Inga
Rayner, Nigel W.
Ripatti, Samuli
Rivadeneira, Fernando
Robertson, Neil R.
Sanna, Serena
Sovio, Ulla
Surakka, Ida
Teumer, Alexander
van Wingerden, Sophie
Vitart, Veronique
Zhao, Jing Hua
Cavalcanti-Proenca, Christine
Chines, Peter S.
Fisher, Eva
Kulzer, Jennifer R.
Lecoeur, Cecile
Narisu, Narisu
Sandholt, Camilla
Scott, Laura J.
Silander, Kaisa
Stark, Klaus
Tammesoo, Mari-Liis
Teslovich, Tanya M.
Timpson, Nicholas John
Watanabe, Richard M.
Welch, Ryan
Chasman, Daniel I.
Cooper, Matthew N.
Jansson, John-Olov
Kettunen, Johannes
Lawrence, Robert W.
Pellikka, Niina
Perola, Markus
Vandenput, Liesbeth
Alavere, Helene
Almgren, Peter
Atwood, Larry D.
Bennett, Amanda J.
Biffar, Reiner
Bonnycastle, Lori L.
Bornstein, Stefan R.
Buchanan, Thomas A.
Campbell, Harry
Day, Ian N. M.
Dei, Mariano
Doerr, Marcus
Elliott, Paul
Erdos, Michael R.
Eriksson, Johan G.
Freimer, Nelson B.
Fu, Mao
Gaget, Stefan
Geus, Eco J. C.
Gjesing, Anette P.
Grallert, Harald
Graessler, Juergen
Groves, Christopher J.
Guiducci, Candace
Hartikainen, Anna-Liisa
Hassanali, Neelam
Havulinna, Aki S.
Herzig, Karl-Heinz
Hicks, Andrew A.
Hui, Jennie
Igl, Wilmar
Jousilahti, Pekka
Jula, Antti
Kajantie, Eero
Kinnunen, Leena
Kolcic, Ivana
Koskinen, Seppo
Kovacs, Peter
Kroemer, Heyo K.
Krzelj, Vjekoslav
Kuusisto, Johanna
Kvaloy, Kirsti
Laitinen, Jaana
Lantieri, Olivier
Lathrop, G. Mark
Lokki, Marja-Liisa
Luben, Robert N.
Ludwig, Barbara
McArdle, Wendy L.
McCarthy, Anne
Morken, Mario A.
Nelis, Mari
Neville, Matt J.
Pare, Guillaume
Parker, Alex N.
Peden, John F.
Pichler, Irene
Pietilainen, Kirsi H.
Platou, Carl G. P.
Pouta, Anneli
Ridderstrale, Martin
Samani, Nilesh J.
Saramies, Jouko
Sinisalo, Juha
Smit, Jan H.
Strawbridge, Rona J.
Stringham, Heather M.
Swift, Amy J.
Teder-Laving, Maris
Thomson, Brian
Usala, Gianluca
van Meurs, Joyce B. J.
van Ommen, Gert-Jan
Vatin, Vincent
Volpato, Claudia B.
Wallaschofski, Henri
Walters, G. Bragi
Widen, Elisabeth
Wild, Sarah H.
Willemsen, Gonneke
Witte, Daniel R.
Zgaga, Lina
Zitting, Paavo
Beilby, John P.
James, Alan L.
Kahonen, Mika
Lehtimaki, Terho
Nieminen, Markku S.
Ohlsson, Claes
Palmer, Lyle J.
Raitakari, Olli
Ridker, Paul M.
Stumvoll, Michael
Toenjes, Anke
Viikari, Jorma
Balkau, Beverley
Ben-Shlomo, Yoav
Bergman, Richard N.
Boeing, Heiner
Smith, George Davey
Ebrahim, Shah
Froguel, Philippe
Hansen, Torben
Hengstenberg, Christian
Hveem, Kristian
Isomaa, Bo
Jorgensen, Torben
Karpe, Fredrik
Khaw, Kay-Tee
Laakso, Markku
Lawlor, Debbie A.
Marre, Michel
Meitinger, Thomas
Metspalu, Andres
Midthjell, Kristian
Pedersen, Oluf
Salomaa, Veikko
Schwarz, Peter E. H.
Tuomi, Tiinamaija
Tuomilehto, Jaakko
Valle, Timo T.
Wareham, Nicholas J.
Arnold, Alice M.
Beckmann, Jacques S.
Bergmann, Sven
Boerwinkle, Eric
Boomsma, Dorret I.
Caulfield, Mark J.
Collins, Francis S.
Eiriksdottir, Gudny
Gudnason, Vilmundur
Gyllensten, Ulf
Hamsten, Anders
Hattersley, Andrew T.
Hofman, Albert
Hu, Frank B.
Illig, Thomas
Iribarren, Carlos
Jarvelin, Marjo-Riitta
Kao, W. H. Linda
Kaprio, Jaakko
Launer, Lenore J.
Munroe, Patricia B.
Oostra, Ben
Penninx, Brenda W.
Pramstaller, Peter P.
Psaty, Bruce M.
Quertermous, Thomas
Rissanen, Aila
Rudan, Igor
Shuldiner, Alan R.
Soranzo, Nicole
Spector, Timothy D.
Syvanen, Ann-Christine
Uda, Manuela
Uitterlinden, Andre
Voelzke, Henry
Vollenweider, Peter
Wilson, James F.
Witteman, Jacqueline C.
Wright, Alan F.
Abecasis, Goncalo R.
Boehnke, Michael
Borecki, Ingrid B.
Deloukas, Panos
Frayling, Timothy M.
Groop, Leif C.
Haritunians, Talin
Hunter, David J.
Kaplan, Robert C.
North, Kari E.
O'Connell, Jeffrey R.
Peltonen, Leena
Schlessinger, David
Strachan, David P.
Hirschhorn, Joel N.
Assimes, Themistocles L.
Wichmann, H-Erich
Thorsteinsdottir, Unnur
van Duijn, Cornelia M.
Stefansson, Kari
Cupples, L. Adrienne
Loos, Ruth J. F.
Barroso, Ines
McCarthy, Mark I.
Fox, Caroline S.
Mohlke, Karen L.
Lindgren, Cecilia M.
CA MAGIC
TI Meta-analysis identifies 13 new loci associated with waist-hip ratio and
reveals sexual dimorphism in the genetic basis of fat distribution
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; BODY-FAT; METABOLIC
RISK; ABDOMINAL ADIPOSITY; GLUCOSE-HOMEOSTASIS; SUSCEPTIBILITY LOCI;
INSULIN-RESISTANCE; COMMON VARIANTS; OBESITY
AB Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 x 10(-3) to P = 1.2 x 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
C1 [Randall, Joshua C.; Maegi, Reedik; Ferreira, Teresa; Morris, Andrew P.; Prokopenko, Inga; Rayner, Nigel W.; Robertson, Neil R.; Peden, John F.; McCarthy, Mark I.; Lindgren, Cecilia M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Heid, Iris M.; Winkler, Thomas W.; Leitzmann, Michael F.] Regensburg Univ Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany.
[Heid, Iris M.; Lamina, Claudia; Grallert, Harald; Illig, Thomas; Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Jackson, Anne U.; Willer, Cristen J.; Weyant, Robert J.; Scott, Laura J.; Teslovich, Tanya M.; Welch, Ryan; Stringham, Heather M.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Qi, Lu; Workalemahu, Tsegaselassie; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Qi, Lu; Kaplan, Lee M.; Chasman, Daniel I.; Ridker, Paul M.; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA.
[Qi, Lu; Hu, Frank B.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Walters, G. Bragi; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
[Zillikens, M. Carola; Estrada, Karol; Peters, Marjolein J.; Rivadeneira, Fernando; van Meurs, Joyce B. J.; Uitterlinden, Andre] Erasmus Med Ctr MC, Dept Internal Med, Rotterdam, Netherlands.
[Zillikens, M. Carola; Estrada, Karol; Peters, Marjolein J.; Rivadeneira, Fernando; van Meurs, Joyce B. J.; Hofman, Albert; Uitterlinden, Andre; Witteman, Jacqueline C.; van Duijn, Cornelia M.] NGI, NCHA, Rotterdam, Netherlands.
[Speliotes, Elizabeth K.; Vedantam, Sailaja; Guiducci, Candace; Thomson, Brian; Hirschhorn, Joel N.] Broad Inst, Metab Initiat, Cambridge, MA USA.
[Speliotes, Elizabeth K.; Vedantam, Sailaja; Guiducci, Candace; Thomson, Brian; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Speliotes, Elizabeth K.; Kaplan, Lee M.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[White, Charles C.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Bouatia-Naji, Nabila; Cavalcanti-Proenca, Christine; Lecoeur, Cecile; Gaget, Stefan; Vatin, Vincent; Froguel, Philippe] Inst Pasteur, IBL, UMR8199, CNRS, F-59019 Lille, France.
[Bouatia-Naji, Nabila; Cavalcanti-Proenca, Christine; Lecoeur, Cecile; Gaget, Stefan; Vatin, Vincent; Froguel, Philippe] Univ Lille Nord France, Lille, France.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA.
[Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Weedon, Michael N.; Allen, Hana Lango; Wood, Andrew R.; Perry, John R. B.; Hattersley, Andrew T.; Frayling, Timothy M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England.
[Luan, Jianan; Kilpelaeinen, Tuomas O.; Li, Shengxu; Ong, Ken K.; Zhao, Jing Hua; Wareham, Nicholas J.; Loos, Ruth J. F.] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England.
[Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Esko, Tonu; Tammesoo, Mari-Liis; Alavere, Helene; Nelis, Mari; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Esko, Tonu; Nelis, Mari; Teder-Laving, Maris; Metspalu, Andres] Estonian Bioctr, Tartu, Estonia.
[Esko, Tonu; Nelis, Mari; Teder-Laving, Maris; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Kutalik, Zoltan; Johnson, Toby; Kapur, Karen; Beckmann, Jacques S.; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Kutalik, Zoltan; Johnson, Toby; Kapur, Karen; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Monda, Keri L.; North, Kari E.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Dixon, Anna L.] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England.
[Holmes, Christopher C.] MRC Harwell, Oxford, England.
[Holmes, Christopher C.; Nicholson, George] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
[Kaplan, Lee M.] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA.
[Liang, Liming; Kraft, Peter; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Liang, Liming; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Min, Josine L.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Moffatt, Miriam F.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[Molony, Cliona] Merck & Co Inc, Merck Res Labs, Boston, MA USA.
[Schadt, Eric E.] Pacific Biosci, Menlo Pk, CA USA.
[Schadt, Eric E.] Sage Bionetworks, Seattle, WA USA.
[Zondervan, Krina T.] Wellcome Trust Ctr Human Genet, Genet & Genom Epidemiol Unit, Oxford, England.
[Feitosa, Mary F.; Ketkar, Shamika; Kraja, Aldi T.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Wheeler, Eleanor; Soranzo, Nicole; Deloukas, Panos; Peltonen, Leena; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge, England.
[Estrada, Karol; Amin, Najaf; Rivadeneira, Fernando; van Wingerden, Sophie; van Meurs, Joyce B. J.; Hofman, Albert; Uitterlinden, Andre; Witteman, Jacqueline C.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Goddard, Michael E.] Univ Melbourne, Parkville, Vic 3052, Australia.
[Goddard, Michael E.] Dept Primary Ind, Melbourne, Vic, Australia.
[Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Lettre, Guillaume] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada.
[Mangino, Massimo; Soranzo, Nicole; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Nyholt, Dale R.] Queensland Inst Med Res, Neurogenet Lab, Brisbane, Qld 4006, Australia.
[Purcell, Shaun; McCarroll, Steven A.; Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Purcell, Shaun; McCarroll, Steven A.; Nemesh, James; Voight, Benjamin F.; Peltonen, Leena] MIT, Cambridge, MA 02139 USA.
[Purcell, Shaun] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Smith, Albert Vernon; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert Vernon; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Visscher, Peter M.; Yang, Jian] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia.
[McCarroll, Steven A.; Nemesh, James; Voight, Benjamin F.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[McCarroll, Steven A.; Voight, Benjamin F.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Absher, Devin] Hudson Alpha Inst Biotechnol, Huntsville, AL USA.
[Coin, Lachlan; Sovio, Ulla; Elliott, Paul; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Glazer, Nicole L.] Univ Washington, Dept Med, Seattle, WA USA.
[Glazer, Nicole L.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Hayward, Caroline; Vitart, Veronique; Wright, Alan F.] Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
[Heard-Costa, Nancy L.; Atwood, Larry D.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Hottenga, Jouke-Jan; Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.] Univ Amsterdam, Vrije Univ, Dept Biol Psychol, Amsterdam, Netherlands.
[Johansson, Asa; Igl, Wilmar; Gyllensten, Ulf] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden.
[Johansson, Asa] Norwegian Univ Sci & Technol NTNU, Fac Med, Dept Canc Res & Mol Med, Trondheim, Norway.
[Johnson, Toby] Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
[Johnson, Toby; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, Barts & London Genome Ctr, London, England.
[Kaakinen, Marika; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Kaakinen, Marika; Herzig, Karl-Heinz; Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Knowles, Joshua W.; Quertermous, Thomas; Assimes, Themistocles L.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Lamina, Claudia] Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
[McKnight, Barbara; Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Polasek, Ozren; Kolcic, Ivana; Zgaga, Lina] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41001, Croatia.
[Polasek, Ozren] Gen Info Ltd, Zagreb, Croatia.
[Prokopenko, Inga; Rayner, Nigel W.; Robertson, Neil R.; Bennett, Amanda J.; Groves, Christopher J.; Hassanali, Neelam; Neville, Matt J.; Karpe, Fredrik; McCarthy, Mark I.; Lindgren, Cecilia M.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Ripatti, Samuli; Surakka, Ida; Silander, Kaisa; Kettunen, Johannes; Pellikka, Niina; Perola, Markus; Widen, Elisabeth; Kaprio, Jaakko; Peltonen, Leena] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Ripatti, Samuli; Surakka, Ida; Silander, Kaisa; Kettunen, Johannes; Pellikka, Niina; Perola, Markus] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Unit Publ Hlth Genom, Helsinki, Finland.
[Sanna, Serena; Dei, Mariano; Usala, Gianluca; Uda, Manuela] Ist Neurogenet & Neurofarmacol CNR, Cagliari, Italy.
[Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Chines, Peter S.; Narisu, Narisu; Bonnycastle, Lori L.; Erdos, Michael R.; Morken, Mario A.; Swift, Amy J.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Fisher, Eva; Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany.
[Kulzer, Jennifer R.; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Sandholt, Camilla; Gjesing, Anette P.; Hansen, Torben; Pedersen, Oluf] Hagedorn Res Inst, Gentofte, Denmark.
[Stark, Klaus] Univ Regensburg, Med Ctr, Clin & Policlin Internal Med 2, Regensburg, Germany.
[Timpson, Nicholas John; Day, Ian N. M.; Smith, George Davey; Lawlor, Debbie A.] MRC Ctr Causal Anal Translat Epidemiol, Dept Social Med, Bristol, Avon, England.
[Watanabe, Richard M.; Buchanan, Thomas A.; Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Phys & Biophys, Los Angeles, CA 90033 USA.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Cooper, Matthew N.; Lawrence, Robert W.; Hui, Jennie; Palmer, Lyle J.] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Crawley, WA, Australia.
[Jansson, John-Olov] Univ Gothenburg, Inst Neurosci & Physiol, Dept Physiol, Sahlgrenska Acad, Gothenburg, Sweden.
[Vandenput, Liesbeth; Ohlsson, Claes] Univ Gothenburg, Inst Med, Dept Internal Med, Sahlgrenska Acad, Gothenburg, Sweden.
[Almgren, Peter; Groop, Leif C.] Lund Univ, Ctr Diabet, Dept Clin Sci, Malmo, Sweden.
[Biffar, Reiner] Zentrum Zahn Mund & Kieferheilkunde, Greifswald, Germany.
[Bornstein, Stefan R.; Graessler, Juergen; Ludwig, Barbara] Univ Dresden, Dept Med 3, Dresden, Germany.
[Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Div Endocrinol, Los Angeles, CA 90033 USA.
[Campbell, Harry; Wild, Sarah H.; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Doerr, Marcus] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, Greifswald, Germany.
[Elliott, Paul] Ctr Environm & Hlth, MRC Hlth Protect Agcy HPA, London, England.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Eriksson, Johan G.; Kajantie, Eero; Peltonen, Leena] Natl Inst Hlth & Welf, Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland.
[Eriksson, Johan G.; Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland.
[Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland.
[Freimer, Nelson B.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA.
[Fu, Mao; Shuldiner, Alan R.; O'Connell, Jeffrey R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Hartikainen, Anna-Liisa; Pouta, Anneli] Univ Oulu, Dept Clin Sci Obstet & Gynecol, Oulu, Finland.
[Havulinna, Aki S.; Jousilahti, Pekka; Koskinen, Seppo; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Chron Dis Epidemiol & Prevent Unit, Helsinki, Finland.
[Herzig, Karl-Heinz] Univ Oulu, Dept Physiol, Inst Biomed, Oulu, Finland.
[Herzig, Karl-Heinz] Kuopio Univ Hosp, Dept Psychiat, SF-70210 Kuopio, Finland.
[Hicks, Andrew A.; Pichler, Irene; Volpato, Claudia B.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy.
[Hui, Jennie; Beilby, John P.] QEII Med Ctr, Dept Mol Genet, PathW Lab Western Australia, Nedlands, WA, Australia.
[Hicks, Andrew A.; Pichler, Irene; Volpato, Claudia B.; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, Lubeck, Germany.
[Hui, Jennie; Beilby, John P.; James, Alan L.; Palmer, Lyle J.] Sir Charles Gairdner Hosp, Busselton Populat Med Res Fdn Inc, Nedlands, WA, Australia.
[Jula, Antti] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Populat Studies Unit, Turku, Finland.
[Kajantie, Eero] Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland.
[Kinnunen, Leena; Tuomilehto, Jaakko; Valle, Timo T.] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.
[Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany.
[Kroemer, Heyo K.] Ernst Moritz Arndt Univ Greifswald, Inst Pharmakol, Greifswald, Germany.
[Krzelj, Vjekoslav; Rudan, Igor] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia.
[Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland.
[Kvaloy, Kirsti; Platou, Carl G. P.; Hveem, Kristian; Midthjell, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Nord Trondelag Hlth Study HUNT Res Ctr, Levanger, Norway.
[Laitinen, Jaana] Finnish Inst Occupat Hlth, Oulu, Finland.
[Lantieri, Olivier] Inst Interreg Sante IRSA, La Riche, France.
[Lathrop, G. Mark] Ctr Natl Genotypage, Paris, France.
[Lokki, Marja-Liisa] Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki, Finland.
[Luben, Robert N.; Khaw, Kay-Tee] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England.
[McArdle, Wendy L.] Univ Bristol, Dept Social Med, Avon Longitudinal Study Parents & Children ALSPAC, Bristol, Avon, England.
[McCarthy, Anne] Res Board, Div Hlth, Dublin, Ireland.
[Pare, Guillaume] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada.
[Parker, Alex N.] Amgen Inc, Cambridge, MA USA.
[Peden, John F.] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England.
[Pietilainen, Kirsi H.; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Finnish Twin Cohort Study, Helsinki, Finland.
[Pietilainen, Kirsi H.; Rissanen, Aila] Univ Helsinki, Cent Hosp, Dept Psychiat, Obes Res Unit, Helsinki, Finland.
[Platou, Carl G. P.] Levanger Hosp, Nord Trondelag Hlth Trust, Dept Med, Levanger, Norway.
[Ridderstrale, Martin] Lund Univ, Dept Clin Sci, Malmo, Sweden.
[Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.
[Samani, Nilesh J.] Glenfield Hosp, Biomed Res Unit Cardiovasc Dis, Leicester Natl Inst Hlth Res NIHR, Leicester, Leics, England.
[Saramies, Jouko] S Karelia Cent Hosp, Lappeenranta, Finland.
[Sinisalo, Juha; Nieminen, Markku S.] Univ Helsinki, Cent Hosp, Cardiovasc Lab, Div Cardiol, Helsinki, Finland.
[Smit, Jan H.; Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Inst Extramuraal Geneeskundig Onderzoek EMGO Inst, Amsterdam, Netherlands.
[Strawbridge, Rona J.; Hamsten, Anders] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Atherosclerosis Res Unit, Stockholm, Sweden.
[van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
[van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Ctr Med Syst Biol, Leiden, Netherlands.
[Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Inst Klin Chem & Lab Med, Greifswald, Germany.
[Witte, Daniel R.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
[Zitting, Paavo] Lapland Cent Hosp, Dept Physiatr, Rovaniemi, Finland.
[Beilby, John P.] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia.
[James, Alan L.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland.
[Kahonen, Mika; Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland.
[Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland.
[Stumvoll, Michael; Toenjes, Anke] Univ Leipzig, Dept Med, Leipzig, Germany.
[Stumvoll, Michael] Univ Leipzig, Leipziger Interdisziplinarer Forschungskomplex Mo, Leipzig, Germany.
[Toenjes, Anke] Univ Leipzig, Coordinat Ctr Clin Trials, Leipzig, Germany.
[Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland.
[Balkau, Beverley] INSERM Ctr Rech Epidemiol & Sante Populat CESP, F-01018 Villejuif, France.
[Balkau, Beverley] Univ Paris Sud 11, Unit Mixte Rech Sante UMRS 1018, Villejuif, France.
[Ben-Shlomo, Yoav] Univ Bristol, Dept Social Med, Bristol, Avon, England.
[Ebrahim, Shah] London Sch Hyg & Trop Med, London WC1, England.
[Ebrahim, Shah] S Asia Network Chron Dis, New Delhi, India.
[Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England.
[Hansen, Torben] Univ So Denmark, Fac Hlth Sci, Odense, Denmark.
[Hengstenberg, Christian] Univ Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany.
[Hengstenberg, Christian] Univ Regensburg, Med Ctr, Innere Med 2, Regensburg, Germany.
[Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland.
[Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.
[Jorgensen, Torben] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark.
[Karpe, Fredrik; McCarthy, Mark I.] Churchill Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 7LJ, England.
[Marre, Michel] Bichat Claude Bernard Univ Hosp, AP HP, Dept Endocrinol Diabetol & Nutr, Paris, France.
[Marre, Michel] Univ Henri Poincar Nancy 1, Cardiovasc Genet Res Unit, Nancy, France.
[Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany.
[Meitinger, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Pedersen, Oluf] Univ Copenhagen, Inst Biomed Sci, Copenhagen, Denmark.
[Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark.
[Schwarz, Peter E. H.] Univ Dresden, Dept Med Prevent & Care Diabet 3, Dresden, Germany.
[Tuomi, Tiinamaija] Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland.
[Tuomi, Tiinamaija] Univ Helsinki, Res Program Mol Med, Helsinki, Finland.
[Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland.
[Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland.
[Arnold, Alice M.] Collaborat Hlth Studies Coordinating Ctr, Seattle, WA USA.
[Beckmann, Jacques S.] Univ Lausanne Hosp, CHUV, Serv Med Genet, Lausanne, Switzerland.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Iribarren, Carlos] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Iribarren, Carlos] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol & Med, Baltimore, MD USA.
[Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth, Helsinki, Finland.
[Kaprio, Jaakko] Unit Child & Adolescent Mental Hlth, Substance Abuse Serv, Helsinki, Finland.
[Oostra, Ben] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Penninx, Brenda W.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.
[Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands.
[Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy.
[Pramstaller, Peter P.] Univ Lubeck, Dept Neurol, Lubeck, Germany.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA.
[Shuldiner, Alan R.] Baltimore Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA.
[Syvanen, Ann-Christine] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Voelzke, Henry] Inst Community Med, Greifswald, Germany.
[Vollenweider, Peter] Univ Lausanne Hosp, CHUV, Dept Internal Med, Lausanne, Switzerland.
[Borecki, Ingrid B.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Haritunians, Talin] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA.
[Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[North, Kari E.] Univ N Carolina, Sch Publ Hlth, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Peltonen, Leena] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
[Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
[Strachan, David P.] Univ London, Div Community Hlth Sci, London, England.
[Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Barroso, Ines] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Addenbrookes Hosp, Cambridge, England.
[Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham Heart Study, Framingham, MA USA.
RP Lindgren, CM (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
EM iris.heid@klinik.uni-regensburg.de; mark.mccarthy@drl.ox.ac.uk;
foxca@nhlbi.nih.gov; mohlke@med.unc.edu; celi@well.ox.ac.uk
RI Schwarz, Peter/B-5127-2013; Davey Smith, George/A-7407-2013; Krzelj,
Vjekoslav/D-6491-2017; Kolcic, Ivana/E-2713-2017; Feitosa,
Mary/K-8044-2012; Hicks, Andrew/E-9518-2017; Witte, Daniel/C-1722-2008;
Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Wilson,
James F/A-5704-2009; Meitinger, Thomas/O-1318-2015; Rivadeneira,
Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; Yang,
Jian/A-5852-2010; Smith, Albert/K-5150-2015; mangino,
massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; BOUATIA-NAJI,
NABILA/D-5863-2013; Coin, Lachlan/A-9001-2014; Lango Allen,
Hana/G-9026-2012; Lamina, Claudia/F-7608-2010; Rudan, Igor/I-1467-2012;
Deloukas, Panos/B-2922-2013; Grallert, Harald/B-3424-2013; Nyholt,
Dale/C-8384-2013; Colaus, PsyColaus/K-6607-2013; Zondervan,
Krina/M-1143-2013; Pramstaller, Peter/C-2357-2008; Cooper,
Matthew/J-4420-2014; Strawbridge, Rona/H-5422-2012; Johansson,
Asa/G-5270-2011; Palmer, Lyle/K-3196-2014; Polasek, Ozren/B-6002-2011;
Beckmann, Jacques S /A-9772-2008; Voight, Benjamin/F-1775-2011;
Aspelund, Thor/F-4826-2011; Stark, Klaus/D-3813-2009; Aspelund,
Thor/C-5983-2008; kinnunen, leena/B-7059-2012; Li, Shengxu/D-8915-2012;
Spector, Tim/F-6533-2012; Ridderstrale, Martin/F-7678-2012; Kilpelainen,
Tuomas/F-8569-2012; Kaplan, Robert/A-2526-2011; Abecasis,
Goncalo/B-7840-2010;
OI Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Tuomi,
Tiinamaija/0000-0002-8306-6202; Vandenput, Liesbeth/0000-0002-1712-6131;
Karpe, Fredrik/0000-0002-2751-1770; Jorgensen,
Torben/0000-0001-9453-2830; Visscher, Peter/0000-0002-2143-8760;
Abecasis, Goncalo/0000-0003-1509-1825; Esko, Tonu/0000-0003-1982-6569;
Peters, Marjolein/0000-0003-3167-9063; Luben,
Robert/0000-0002-5088-6343; Kaakinen, Marika/0000-0002-9228-0462;
Pichler, Irene/0000-0001-8251-0757; Heard-Costa,
Nancy/0000-0001-9730-0306; Goddard, Michael/0000-0001-9917-7946; Magi,
Reedik/0000-0002-2964-6011; Marre, Michel/0000-0002-3071-1837; sanna,
serena/0000-0002-3768-1749; Johnson, Toby/0000-0002-5998-3270; Cupples,
L. Adrienne/0000-0003-0273-7965; Schwarz, Peter/0000-0001-6317-7880;
Davey Smith, George/0000-0002-1407-8314; Kolcic,
Ivana/0000-0001-7918-6052; Feitosa, Mary/0000-0002-0933-2410; Hicks,
Andrew/0000-0001-6320-0411; Soranzo, Nicole/0000-0003-1095-3852; Zgaga,
Lina/0000-0003-4089-9703; Bouatia-Naji, Nabila/0000-0001-5424-2134;
Willer, Cristen/0000-0001-5645-4966; Witte, Daniel/0000-0002-0769-2922;
Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti,
Samuli/0000-0002-0504-1202; Wilson, James F/0000-0001-5751-9178;
Rivadeneira, Fernando/0000-0001-9435-9441; Prokopenko,
Inga/0000-0003-1624-7457; Yang, Jian/0000-0003-2001-2474; Smith,
Albert/0000-0003-1942-5845; mangino, massimo/0000-0002-2167-7470;
Hayward, Caroline/0000-0002-9405-9550; Coin,
Lachlan/0000-0002-4300-455X; Lango Allen, Hana/0000-0002-7803-8688;
Rudan, Igor/0000-0001-6993-6884; Deloukas, Panos/0000-0001-9251-070X;
Zondervan, Krina/0000-0002-0275-9905; Cooper,
Matthew/0000-0003-1139-3682; Strawbridge, Rona/0000-0001-8506-3585;
Johansson, Asa/0000-0002-2915-4498; Palmer, Lyle/0000-0002-1628-3055;
Polasek, Ozren/0000-0002-5765-1862; Beckmann, Jacques S
/0000-0002-9741-1900; Stark, Klaus/0000-0002-7832-1942; Aspelund,
Thor/0000-0002-7998-5433; kinnunen, leena/0000-0001-8739-4812; Eriksson,
Johan/0000-0002-2516-2060; Kaprio, Jaakko/0000-0002-3716-2455; Timpson,
Nicholas/0000-0002-7141-9189; Lawlor, Debbie A/0000-0002-6793-2262;
Bergmann, Sven/0000-0002-6785-9034; Sinisalo, Juha/0000-0002-0169-5137;
de Geus, Eco/0000-0001-6022-2666
FU Academy of Finland [104781, 120315, 129269, 117797, 121584, 126925,
129418, 129568, 77299, 124243, 129680, 129494, 10404, 213506, 114382,
126775, 127437, 129255, 129306, 130326, 209072, 210595, 213225, 216374];
ADA [N02-HL-6-4278]; ALF/LUA Gothenburg; Althingi (the Icelandic
Parliament); Amgen; Augustinus Foundation; Becket Foundation; Biocentrum
Helsinki; Biomedicum Helsinki Foundation; Boston Obesity Nutrition
Research Center [DK46200]; British Diabetes Association [1192]; British
Diabetic Association Research; British Heart Foundation [97020,
PG/02/128]; Busselton Population Medical Research Foundation; Cambridge
NIHR Comprehensive Biomedical Research Centre; CamStrad; Chief Scientist
Office of the Scottish Government; Contrat Plan Etat Region de France;
Danish Centre for Health Technology Assessment; Danish Diabetes
Association; Danish Ministry of Internal Affairs and Health; Danish
Heart Foundation; Danish Pharmaceutical Association; Danish Research
Council; DIAB Core (German Network of Diabetes); Diabetes UK; Donald W.
Reynolds Foundation; Dresden University of Technology; Med Drive; EMGO+
institute; Emil and Vera Cornell Foundation; Erasmus Medical Center and
Erasmus University, Rotterdam, The Netherlands; Estonian Government
[SF0180142s08]; European Commission [2004310, 212111, 205419, 245536, DG
XII, HEALTH-F4-2007-201413, FP7/2007-2013, QLG1-CT-2000-01643,
QLG2-CT-2002-01254, LSHG-CT-2006-018947, LSHG-CT-2006-01947,
LSHG-CT-2004-512066, LSHM-CT-2007-037273, EU/WLRT-2001-01254,
LSHG-CT-2004-518153, SOC 95201408 05F02]; Federal Ministry of Education
and Research, Germany [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012, 01 EA
9401]; Federal State of Mecklenburg-West Pomerania; Finnish Diabetes
Research Foundation; Finnish Diabetes Research Society; Finnish
Foundation for Pediatric Research; Finnish Foundation of Cardiovascular
Research; Finnish Medical Society; Finska Lakaresallskapet; Finnish
Ministry of Education; Folkhalsan Research Foundation; Fond Europeen
pour le Developpement Regional; Fondation LeDucq; Foundation for Life
and Health in Finland; GEN-AU 'GOLD' from Austria; German
Bundesministerium fuer Forschung und Technology [01 AK 803 A-H, 01 IG
07015 G]; German National Genome Research Net NGFN2 and NGFNplus
[01GS0823, FKZ 01GS0823]; German Research Council [KFO-152];
GlaxoSmithKline; Goteborg Medical Society; Gyllenberg Foundation; Health
Care Center in Vasa; Healthway, Western Australia; Helmholtz Center
Munich; Helsinki University Central Hospital; Hjartavernd (the Icelandic
Heart Association); Ib Henriksen Foundation; IZKF [B27]; Jalmari and
Rauha Ahokas Foundation; Juho Vainio Foundation; Juvenile Diabetes
Research Foundation International (JDRF); Karolinska Institute and the
Stockholm County Council [560183]; Knut and Alice Wallenberg Foundation;
Lundbeck Foundation Centre of Applied Medical Genomics; Knut Krohn,
Microarray Core Facility of the Interdisciplinary Centre for Clinical
Research (IZKF), University of Leipzig, Germany; MC Health; Ministry of
Cultural Affairs of the Federal State of Mecklenburg-West Pomerania,
Germany; South Tyrol Ministry of Health; Ministry of Science, Education
and Sport of the Republic of Croatia [216-1080315-0302]; Medical
Research Council UK [G0000649, G0601261, G9521010D, G0000934, G0500539,
G0600331]; Montreal Heart Institute Foundation; MRC Centre for
Obesity-Related Metabolic Disease; Municipal Health Care Center and
Hospital in Jakobstad; Municipality of Rotterdam; Narpes Health Care
Foundation; National Health and Medical Research Council of Australia
and the Great Wine Estates Auctions; Netherlands Centre for Medical
Systems Biology [SPI 56-464-1419]; Netherlands Ministry for Health;
Welfare and Sports; Netherlands Ministry of Education, Culture and
Science; Netherlands Genomics Initiative; Netherlands Consortium
[050-060-810]; Netherlands Organisation of Scientific Research
Netherlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)
Investments [175.010.2005.011, 911-03-012, 904-61-090, 904-61-193,
480-04-004, 400-05-717]; National Institute on Aging; US National
Institutes of Health [CA047988, CA65725, CA87969, CA49449, CA67262,
CA50385, DK075787, DK062370, DK58845, DK072193, K23-DK080145,
K99HL094535, N01-HC85079, N01-HC85086, N01-HG-65403, N01-AG-12100,
N01-HC-25195, N01-HC35129, N01-HC15103, N01-HC55222, N01-HC75150,
N01-HC45133, N01-HC55015, N01-HC55016, N01-HC-55018, N01-HC-55019,
N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-AG-1-2109, HL71981,
HG005581, HG002651, HL084729, HL043851, HHSN268200625226C, MH084698,
P30-DK072488, R01 HL087652, R01-HL087641, R01-HL59367, R01-HL086694,
R01-HL087647, R01-HL087679, R01-HL087700, R01-AG031890, R01-HL088119,
R01-DK068336, R01-DK075681, R01-DK-073490, R01-DK075787, R01-MH63706,
U01-HL72515, U01-GM074518, U01-HL084756, U01-HG004399, UO1-CA098233,
UL1-RR025005, U01-HG004402, U01-DK062418, U01 HL080295, T32-HG00040,
263-MA-410953, 1RL1-MH083268-01, 1Z01-HG000024]; National Institute for
Health Research (NIHR); Neuroscience Campus Amsterdam; Novo Nordisk
Foundation; Novo Nordisk Inc.; Ollqvist Foundation; Paavo Nurmi
Foundation; Paivikki and Sakari Sohlberg Foundation; Pew Scholarship for
the Biomedical Sciences; Perklen Foundation; Petrus and Augusta Hedlunds
Foundation; Research Institute for Diseases in the Elderly [014-93-015];
Sahlgrenska Center for Cardiovascular and Metabolic Research (CMR)
[A305:188]; Siemens Healthcare, Erlangen, Germany; Signe and Ane
Gyllenberg Foundation; Sigrid Juselius Foundation; Social Insurance
Institution of Finland; Social Ministry of the Federal State of
Mecklenburg-West Pomerania, Germany; South Tyrolean Sparkasse
Foundation; State of Bavaria, Germany; Support for Science Funding
programme; Swedish Cultural Foundation in Finland; Swedish Foundation
for Strategic Research (SSF); Swedish Medical Research Council [8691,
K2007-66X-20270-01-3, K2010-54X-09894-19-3]; Swedish Society of
Medicine; Swiss National Science Foundation [33CSCO-122661]; Royal
Society; Royal Swedish Academy of Science; Torsten and Ragnar
Soderberg's Foundation; Turku University Hospitals; UK Department of
Health Policy Research Programme; University and Research of the
Autonomous Province of Bolzano; University Hospital Medical; University
Hospital Oulu, Biocenter, University of Oulu, Finland [75617]; Vastra
Gotaland Foundation; Wellcome Trust [077016/Z/05/Z, 068545/Z/02, 072960,
076113, 083270, 085301, 079557, 081682, 075491, 076113/B/04/Z,
091746/Z/10/Z, 079895, WT086596/Z/08/Z]; Western Australian Genetic
Epidemiology Resource; Western Australian DNA Bank (both National Health
and Medical Research Council of Australia Enabling Facilities); Yrjo
Jahnsson Foundation; AstraZeneca AB; Lundberg Foundation; Swedish
Heart-Lung Foundation; Research Foundation of Copenhagen County; Health
care center in Nerpes; Health care center in Korsholm
FX Funding for this study was provided by the Academy of Finland (grants
104781, 120315, 129269, 117797, 121584, 126925, 129418, 129568, 77299,
124243, 213506, 129680, 129494, 10404, 213506, 129680, 114382, 126775,
127437, 129255, 129306, 130326, 209072, 210595, 213225 and 216374); an
ADA Mentor-Based Postdoctoral Fellowship grant; Affymetrix, Inc., for
genotyping services (N02-HL-6-4278); ALF/LUA Gothenburg; Althingi (the
Icelandic Parliament); Amgen; AstraZeneca AB; Augustinus Foundation;
Becket Foundation; Biocentrum Helsinki; Biomedicum Helsinki Foundation;
Boston Obesity Nutrition Research Center (DK46200); British Diabetes
Association (1192); British Diabetic Association Research; British Heart
Foundation (97020, PG/02/128); Busselton Population Medical Research
Foundation; Cambridge NIHR Comprehensive Biomedical Research Centre;
CamStrad; Chief Scientist Office of the Scottish Government; Contrat
Plan Etat Region de France; Danish Centre for Health Technology
Assessment; Danish Diabetes Association; Danish Ministry of Internal
Affairs and Health; Danish Heart Foundation; Danish Pharmaceutical
Association; Danish Research Council; DIAB Core (German Network of
Diabetes); Diabetes UK; Donald W.; Reynolds Foundation; Dresden
University of Technology Funding Grant, Med Drive; EMGO+ institute; Emil
and Vera Cornell Foundation; Erasmus Medical Center and Erasmus
University, Rotterdam, The Netherlands; Estonian Government
SF0180142s08; European Commission (2004310, 212111, 205419, 245536, DG
XII, HEALTH-F4-2007-201413, FP7/2007-2013, QLG1-CT-2000-01643,
QLG2-CT-2002-01254, LSHG-CT-2006-018947, LSHG-CT-2006-01947,
LSHG-CT-2004-512066, LSHM-CT-2007-037273, EU/WLRT-2001-01254,
LSHG-CT-2004-518153, SOC 95201408 05F02, Marie Curie Intra-European
Fellowship); Federal Ministry of Education and Research, Germany
(01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012, 01 EA 9401); Federal State of
Mecklenburg-West Pomerania; Finnish Diabetes Research Foundation;
Finnish Diabetes Research Society; Finnish Foundation for Pediatric
Research; Finnish Foundation of Cardiovascular Research; Finnish Medical
Society; Finska Lakaresallskapet; Finnish Ministry of Education;
Folkhalsan Research Foundation; Fond Europeen pour le Developpement
Regional; Fondation LeDucq; Foundation for Life and Health in Finland;
GEN-AU 'GOLD' from Austria; German Bundesministerium fuer Forschung und
Technology (# 01 AK 803 A-H, # 01 IG 07015 G); German National Genome
Research Net NGFN2 and NGFNplus (01GS0823, FKZ 01GS0823); German
Research Council (KFO-152); GlaxoSmithKline; Goteborg Medical Society;
Gyllenberg Foundation; Health Care Centers in Vasa, Narpes and Korsholm;
Healthway, Western Australia; Helmholtz Center Munich; Helsinki
University Central Hospital; Hjartavernd ( the Icelandic Heart
Association); Ib Henriksen Foundation; IZKF (B27); Jalmari and Rauha
Ahokas Foundation; Juho Vainio Foundation; Juvenile Diabetes Research
Foundation International (JDRF); Karolinska Institute and the Stockholm
County Council (560183); Knut and Alice Wallenberg Foundation; Lundbeck
Foundation Centre of Applied Medical Genomics for Personalized Disease
Prediction, Prevention and Care; Knut Krohn, Microarray Core Facility of
the Interdisciplinary Centre for Clinical Research (IZKF), University of
Leipzig, Germany; Lundberg Foundation; MC Health; Ministry of Cultural
Affairs of the Federal State of Mecklenburg-West Pomerania, Germany;
South Tyrol Ministry of Health; Ministry of Science, Education and Sport
of the Republic of Croatia (216-1080315-0302); Medical Research Council
UK (G0000649, G0601261, 9521010D, G0000934, G0500539, G0600331,
PrevMetSyn); Montreal Heart Institute Foundation; MRC Centre for
Obesity-Related Metabolic Disease; Municipal Health Care Center and
Hospital in Jakobstad; Municipality of Rotterdam; Narpes Health Care
Foundation; National Health and Medical Research Council of Australia
and the Great Wine Estates Auctions; Netherlands Centre for Medical
Systems Biology (SPI 56-464-1419); Netherlands Ministry for Health,
Welfare and Sports; Netherlands Ministry of Education, Culture and
Science; Netherlands Genomics Initiative; Netherlands Consortium for
Healthy Aging (050-060-810); Netherlands Organisation of Scientific
Research Netherlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)
Investments (175.010.2005.; 011, 911-03-012, 904-61-090, 904-61-193,
480-04-004, 400-05-717); National Institute on Aging Intramural Research
Program; US National Institutes of Health (CA047988, CA65725, CA87969,
CA49449, CA67262, CA50385, DK075787, DK062370, DK58845, DK072193,
K23-DK080145, K99HL094535, N01-HC85079 through N01-HC85086,
N01-HG-65403, N01-AG-12100, N01-HC-25195, N01-HC35129, N01-HC15103,
N01-HC55222, N01-HC75150, N01-HC45133, N01-HC55015, N01-HC55016,
N01-HC-55018, N01-HC-5019, N01-HC-55020, N01-HC-55021, N01-HC-55022,
N01-AG-1-2109, HL71981, HG005581, HG002651, HL084729, HL043851,
HHSN268200625226C, K23-DK080145, MH084698, P30-DK072488, R01-DK075787,
R01 HL087652, R01-HL087641, R01-HL59367, R01-HL086694, R01-HL087647,
R01-HL087679, R01-HL087700, R01-AG031890, R01-HL088119, R01-DK068336,
R01-DK075681, R01-DK-073490, R01-DK075787, R01-MH63706, U01-HL72515,
U01-GM074518, U01-HL084756, U01-HG004399, UO1-CA098233, UL1-RR025005,
UL1-RR025005, U01-HG004402, U01-DK062418, U01 HL080295, T32-HG00040,
263-MA-410953, 1RL1-MH083268-01, intramural project 1Z01-HG000024);
National Institute for Health Research (NIHR); Neuroscience Campus
Amsterdam; Novo Nordisk Foundation; Novo Nordisk Inc., Research
Foundation of Copenhagen County; Ollqvist Foundation; Paavo Nurmi
Foundation; Paivikki and Sakari Sohlberg Foundation; Pew Scholarship for
the Biomedical Sciences; Perklen Foundation; Petrus and Augusta Hedlunds
Foundation; Research Institute for Diseases in the Elderly (014-93-015,
RIDE, RIDE2); Sahlgrenska Center for Cardiovascular and Metabolic
Research (CMR, A305:188); Siemens Healthcare, Erlangen, Germany; Signe
and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Social
Insurance Institution of Finland; Social Ministry of the Federal State
of Mecklenburg-West Pomerania, Germany; South Tyrolean Sparkasse
Foundation; State of Bavaria, Germany; Support for Science Funding
programme; Swedish Cultural Foundation in Finland; Swedish Foundation
for Strategic Research (SSF); Swedish Heart-Lung Foundation; Swedish
Medical Research Council (8691, K2007-66X-20270-01-3,
K2010-54X-09894-19-3); Swedish Society of Medicine; Swiss National
Science Foundation (33CSCO-122661); the Royal Society; the Royal Swedish
Academy of Science; Torsten and Ragnar Soderberg's Foundation; Turku
University Hospitals; UK Department of Health Policy Research Programme;
University and Research of the Autonomous Province of Bolzano;
University Hospital Medical funds to Tampere; University Hospital Oulu,
Biocenter, University of Oulu, Finland (75617); Vastra Gotaland
Foundation; Wellcome Trust (077016/Z/05/Z, 068545/Z/02, 072960, 076113,
083270, 085301, 079557, 081682, 075491, 076113/B/04/Z, 091746/Z/10/Z,
079895, WT086596/Z/08/Z, WT Research Career Development Fellowship; WT
Career Development Award); Western Australian Genetic Epidemiology
Resource and the Western Australian DNA Bank (both National Health and
Medical Research Council of Australia Enabling Facilities); Yrjo
Jahnsson Foundation.
NR 61
TC 408
Z9 419
U1 9
U2 79
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 NOV
PY 2010
VL 42
IS 11
BP 949
EP U160
DI 10.1038/ng.685
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 671VW
UT WOS:000283540500011
PM 20935629
ER
PT J
AU Rothman, N
Garcia-Closas, M
Chatterjee, N
Malats, N
Wu, XF
Figueroa, JD
Real, FX
Van den Berg, D
Matullo, G
Baris, D
Thun, M
Kiemeney, LA
Vineis, P
De Vivo, I
Albanes, D
Purdue, MP
Rafnar, T
Hildebrandt, MAT
Kiltie, AE
Cussenot, O
Golka, K
Kumar, R
Taylor, JA
Mayordomo, JI
Jacobs, KB
Kogevinas, M
Hutchinson, A
Wang, ZW
Fu, YP
Prokunina-Olsson, L
Burdett, L
Yeager, M
Wheeler, W
Tardon, A
Serra, C
Carrato, A
Garcia-Closas, R
Lloreta, J
Johnson, A
Schwenn, M
Karagas, MR
Schned, A
Andriole, G
Grubb, R
Black, A
Jacobs, EJ
Diver, WR
Gapstur, SM
Weinstein, SJ
Virtamo, J
Cortessis, VK
Gago-Dominguez, M
Pike, MC
Stern, MC
Yuan, JM
Hunter, DJ
McGrath, M
Dinney, CP
Czerniak, B
Chen, M
Yang, HS
Vermeulen, SH
Aben, KK
Witjes, JA
Makkinje, RR
Sulem, P
Besenbacher, S
Stefansson, K
Riboli, E
Brennan, P
Panico, S
Navarro, C
Allen, NE
Bueno-De-Mesquita, HB
Trichopoulos, D
Caporaso, N
Landi, MT
Canzian, F
Ljungberg, B
Tjonneland, A
Clavel-Chapelon, F
Bishop, DT
Teo, MTW
Knowles, MA
Guarrera, S
Polidoro, S
Ricceri, F
Sacerdote, C
Allione, A
Cancel-Tassin, G
Selinski, S
Hengstler, JG
Dietrich, H
Fletcher, T
Rudnai, P
Gurzau, E
Koppova, K
Bolick, SCE
Godfrey, A
Xu, ZL
Sanz-Velez, JI
Garcia-Prats, MD
Sanchez, M
Valdivia, G
Porru, S
Benhamou, S
Hoover, RN
Fraumeni, JF
Silverman, DT
Chanock, SJ
AF Rothman, Nathaniel
Garcia-Closas, Montserrat
Chatterjee, Nilanjan
Malats, Nuria
Wu, Xifeng
Figueroa, Jonine D.
Real, Francisco X.
Van den Berg, David
Matullo, Giuseppe
Baris, Dalsu
Thun, Michael
Kiemeney, Lambertus A.
Vineis, Paolo
De Vivo, Immaculata
Albanes, Demetrius
Purdue, Mark P.
Rafnar, Thorunn
Hildebrandt, Michelle A. T.
Kiltie, Anne E.
Cussenot, Olivier
Golka, Klaus
Kumar, Rajiv
Taylor, Jack A.
Mayordomo, Jose I.
Jacobs, Kevin B.
Kogevinas, Manolis
Hutchinson, Amy
Wang, Zhaoming
Fu, Yi-Ping
Prokunina-Olsson, Ludmila
Burdett, Laurie
Yeager, Meredith
Wheeler, William
Tardon, Adonina
Serra, Consol
Carrato, Alfredo
Garcia-Closas, Reina
Lloreta, Josep
Johnson, Alison
Schwenn, Molly
Karagas, Margaret R.
Schned, Alan
Andriole, Gerald, Jr.
Grubb, Robert, III
Black, Amanda
Jacobs, Eric J.
Diver, W. Ryan
Gapstur, Susan M.
Weinstein, Stephanie J.
Virtamo, Jarmo
Cortessis, Victoria K.
Gago-Dominguez, Manuela
Pike, Malcolm C.
Stern, Mariana C.
Yuan, Jian-Min
Hunter, David J.
McGrath, Monica
Dinney, Colin P.
Czerniak, Bogdan
Chen, Meng
Yang, Hushan
Vermeulen, Sita H.
Aben, Katja K.
Witjes, J. Alfred
Makkinje, Remco R.
Sulem, Patrick
Besenbacher, Soren
Stefansson, Kari
Riboli, Elio
Brennan, Paul
Panico, Salvatore
Navarro, Carmen
Allen, Naomi E.
Bueno-de-Mesquita, H. Bas
Trichopoulos, Dimitrios
Caporaso, Neil
Landi, Maria Teresa
Canzian, Federico
Ljungberg, Borje
Tjonneland, Anne
Clavel-Chapelon, Francoise
Bishop, David T.
Teo, Mark T. W.
Knowles, Margaret A.
Guarrera, Simonetta
Polidoro, Silvia
Ricceri, Fulvio
Sacerdote, Carlotta
Allione, Alessandra
Cancel-Tassin, Geraldine
Selinski, Silvia
Hengstler, Jan G.
Dietrich, Holger
Fletcher, Tony
Rudnai, Peter
Gurzau, Eugen
Koppova, Kvetoslava
Bolick, Sophia C. E.
Godfrey, Ashley
Xu, Zongli
Sanz-Velez, Jose I.
Garcia-Prats, Maria D.
Sanchez, Manuel
Valdivia, Gabriel
Porru, Stefano
Benhamou, Simone
Hoover, Robert N.
Fraumeni, Joseph F., Jr.
Silverman, Debra T.
Chanock, Stephen J.
TI A multi-stage genome-wide association study of bladder cancer identifies
multiple susceptibility loci
SO NATURE GENETICS
LA English
DT Article
ID CONFERS SUSCEPTIBILITY; UDP-GLUCURONOSYLTRANSFERASES; RECOMBINATION
HOTSPOTS; TELOMERASE MUTATIONS; PULMONARY-FIBROSIS; SEQUENCE VARIANT;
COMMON VARIANTS; CHROMOSOME 8Q24; DOWN-REGULATION; CELL-CARCINOMA
AB We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 x 10(-12)) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 x 10(-11)) on 19q12 maps to CCNE1 and rs11892031 (P = 1 x 10(-7)) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 x 10(-11)) and a tag SNP for NAT2 acetylation status (P = 4 x 10(-11)), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.
C1 [Rothman, Nathaniel; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Figueroa, Jonine D.; Baris, Dalsu; Albanes, Demetrius; Purdue, Mark P.; Fu, Yi-Ping; Prokunina-Olsson, Ludmila; Black, Amanda; Weinstein, Stephanie J.; Caporaso, Neil; Landi, Maria Teresa; Hoover, Robert N.; Fraumeni, Joseph F., Jr.; Silverman, Debra T.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Malats, Nuria; Real, Francisco X.] Spanish Natl Canc Res Ctr, Madrid, Spain.
[Wu, Xifeng; Hildebrandt, Michelle A. T.; Chen, Meng; Yang, Hushan] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Real, Francisco X.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.
[Van den Berg, David; Cortessis, Victoria K.; Gago-Dominguez, Manuela; Pike, Malcolm C.; Stern, Mariana C.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA.
[Matullo, Giuseppe] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy.
[Matullo, Giuseppe; Vineis, Paolo; Guarrera, Simonetta; Polidoro, Silvia; Ricceri, Fulvio; Sacerdote, Carlotta; Allione, Alessandra] Human Genet Fdn HuGeF, Turin, Italy.
[Thun, Michael; Jacobs, Eric J.; Diver, W. Ryan; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Kiemeney, Lambertus A.; Vermeulen, Sita H.; Aben, Katja K.] Radboud Univ Nijmegen Med Ctr, Dept Epidemiol Biostat & Hlth Technol Assessment, Nijmegen, Netherlands.
[Kiemeney, Lambertus A.] Comprehens Canc Ctr E, Nijmegen, Netherlands.
[Kiemeney, Lambertus A.; Witjes, J. Alfred] Radboud Univ Nijmegen Med Ctr, Dept Urol, Nijmegen, Netherlands.
[Vineis, Paolo; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, London, England.
[De Vivo, Immaculata] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Rafnar, Thorunn; Sulem, Patrick; Besenbacher, Soren; Stefansson, Kari] DeCODE Genet, Reykjavik, Iceland.
[Kiltie, Anne E.] Univ Oxford, Gray Inst Radiat Oncol & Biol, Oxford, England.
[Cussenot, Olivier] Tenon Hosp, AP HP, Dept Urol, Paris, France.
[Cussenot, Olivier; Cancel-Tassin, Geraldine] Ctr Rech Pathol Prostat, Paris, France.
[Golka, Klaus; Selinski, Silvia; Hengstler, Jan G.] Leibniz Res Ctr Working Environm & Human Factor, Dortmund, Germany.
[Kumar, Rajiv] German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany.
[Taylor, Jack A.; Bolick, Sophia C. E.; Godfrey, Ashley; Xu, Zongli] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Mayordomo, Jose I.; Sanchez, Manuel; Valdivia, Gabriel] Univ Zaragoza, Zaragoza, Spain.
[Jacobs, Kevin B.; Hutchinson, Amy; Wang, Zhaoming; Burdett, Laurie; Yeager, Meredith] SAIC Frederick Inc, Natl Canc Inst Frederick, Core Genotype Facil, Frederick, MD USA.
[Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Kogevinas, Manolis] Municipal Inst Med Res, Barcelona, Spain.
[Kogevinas, Manolis; Tardon, Adonina; Navarro, Carmen] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.
[Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, Greece.
[Wheeler, William] Informat Management Serv Inc, Rockville, MD USA.
[Tardon, Adonina] Univ Oviedo, Inst Univ Oncol, Oviedo, Spain.
[Carrato, Alfredo] Ramon & Cajal Univ Hosp, Madrid, Spain.
[Garcia-Closas, Reina] Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna, Spain.
[Lloreta, Josep] Univ Pompeu Fabra, Hosp Mar Inst Municipal Invest Med IMIM, Barcelona, Spain.
[Johnson, Alison] Vermont Canc Registry, Burlington, VT USA.
[Schwenn, Molly] Maine Canc Registry, Augusta, ME USA.
[Karagas, Margaret R.; Schned, Alan] Dartmouth Med Sch, Hanover, NH USA.
[Andriole, Gerald, Jr.; Grubb, Robert, III] Washington Univ, Sch Med, Dept Urol, St Louis, MO USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Helsinki, Finland.
[Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Yuan, Jian-Min] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA.
[Hunter, David J.; McGrath, Monica] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Dinney, Colin P.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
[Czerniak, Bogdan] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Vermeulen, Sita H.; Makkinje, Remco R.] Radboud Univ Nijmegen Med Ctr, Dept Human Genet, Nijmegen, Netherlands.
[Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Brennan, Paul] Int Agcy Res Canc, Lyon, France.
[Panico, Salvatore] Univ Naples Federico 2, Dept Clin & Expt Med, Naples, Italy.
[Navarro, Carmen] Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain.
[Allen, Naomi E.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany.
[Ljungberg, Borje] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden.
[Tjonneland, Anne] Inst Canc Epidemiol, Danish Canc Soc, Copenhagen, Denmark.
[Clavel-Chapelon, Francoise] Paris S Univ, Inst Gustave Roussy, Ctr Res Epidemiol & Populat Hlth, Villejuif, France.
[Bishop, David T.; Teo, Mark T. W.; Knowles, Margaret A.] Univ Leeds, St Jamess Univ Hosp, Leeds Inst Mol Med, Leeds, W Yorkshire, England.
[Sacerdote, Carlotta] Univ Turin, Canc Epidemiol Unit, Turin, Italy.
[Dietrich, Holger] Paul Gerhardt Fdn, Dept Urol, Wittenberg, Germany.
[Fletcher, Tony] Inst Hyg & Trop Med, London, England.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
[Gurzau, Eugen] Univ Babes Bolyai, Ctr Environm Hlth, R-3400 Cluj Napoca, Romania.
[Koppova, Kvetoslava] State Hlth Inst, Banska Bystrica, Slovakia.
[Sanz-Velez, Jose I.; Garcia-Prats, Maria D.] San Jorge Univ Hosp, Huesca, Spain.
[Porru, Stefano] Univ Brescia, Sect Occupat Med & Ind Hyg, Dept Expt & Appl Med, Brescia, Italy.
[Benhamou, Simone] CEPH, Fdn Jean Dausset, U946, INSERM, Paris, France.
[Benhamou, Simone] Inst Gustave Roussy, UMR8200, CNRS, Villejuif, France.
RP Garcia-Closas, M (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM montse.garciaclosas@icr.ac.uk
RI Purdue, Mark/C-9228-2016; Vermeulen, H.H.M./L-4716-2015; Aben,
Katja/G-9686-2016; Benhamou, Simone/K-6554-2015; Matullo,
Giuseppe/K-6383-2016; Panico, Salvatore/K-6506-2016; Kogevinas,
Manolis/C-3918-2017; Real, Francisco X/H-5275-2015; Albanes,
Demetrius/B-9749-2015; Garcia-Closas, Montserrat /F-3871-2015; Malats,
Nuria/H-7041-2015; Makkinje, Remco/Q-2406-2015; Mayordomo,
Jose/K-3453-2013; Hengstler, Jan/O-1415-2013; Witjes, Fred/N-9665-2013;
Kiemeney, Lambertus/D-3357-2009; Serra, C/E-6879-2014; Clavel-Chapelon,
Francoise/G-6733-2014; Lloreta, J/I-2112-2014
OI MATULLO, Giuseppe/0000-0003-0674-7757; Yuan,
Jian-Min/0000-0002-4620-3108; Sacerdote, Carlotta/0000-0002-8008-5096;
xu, zongli/0000-0002-9034-8902; Bishop, Tim/0000-0002-8752-8785; taylor,
jack/0000-0001-5303-6398; Besenbacher, Soren/0000-0003-1455-1738;
Cancel-Tassin, Geraldine/0000-0002-9583-6382; Purdue,
Mark/0000-0003-1177-3108; Aben, Katja/0000-0002-0214-2147; Panico,
Salvatore/0000-0002-5498-8312; Kumar, Rajiv/0000-0002-6093-0395; Kiltie,
Anne/0000-0001-7208-2912; Prokunina-Olsson, Ludmila/0000-0002-9622-2091;
Real, Francisco X/0000-0001-9501-498X; Allione,
Alessandra/0000-0001-9599-309X; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; Kiemeney,
Lambertus/0000-0002-2368-1326; Serra, C/0000-0001-8337-8356; Lloreta,
J/0000-0003-1644-9470
FU National Cancer Institute, US National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in part with federal funds from the
National Cancer Institute, US 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 52
TC 214
Z9 221
U1 1
U2 43
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 NOV
PY 2010
VL 42
IS 11
BP 978
EP U98
DI 10.1038/ng.687
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 671VW
UT WOS:000283540500015
PM 20972438
ER
PT J
AU Dinarello, C
Arend, W
Sims, J
Smith, D
Blumberg, H
O'Neill, L
Goldbach-Mansky, R
Pizarro, T
Hoffman, H
Bufler, P
Nold, M
Ghezzi, P
Mantovani, A
Garlanda, C
Boraschi, D
Rubartelli, A
Netea, M
van der Meer, J
Joosten, L
Mandrup-Poulsen, T
Donath, M
Lewis, E
Pfeilschifter, J
Martin, M
Kracht, M
Muehl, H
Novick, D
Lukic, M
Conti, B
Solinger, A
Peyman, K
van de Veerdonk, F
Gabel, C
AF Dinarello, Charles
Arend, William
Sims, John
Smith, Dirk
Blumberg, Hal
O'Neill, Luke
Goldbach-Mansky, Raphaela
Pizarro, Theresa
Hoffman, H.
Bufler, Philip
Nold, Marcel
Ghezzi, Pietro
Mantovani, Alberto
Garlanda, Cecilia
Boraschi, Diana
Rubartelli, Anna
Netea, Mihai
van der Meer, Jos
Joosten, Leo
Mandrup-Poulsen, Tom
Donath, Marc
Lewis, Eli
Pfeilschifter, Josef
Martin, Michael
Kracht, Michael
Muehl, H.
Novick, Daniela
Lukic, Miodrag
Conti, Bruno
Solinger, Alan
Peyman, Kelk
van de Veerdonk, Frank
Gabel, Chiristopher
TI IL-1 family nomenclature
SO NATURE IMMUNOLOGY
LA English
DT Letter
ID NF-KAPPA-B; INTERLEUKIN-1 FAMILY; MEMBERS; IDENTIFICATION
C1 [Dinarello, Charles] Univ Colorado Denver, Dept Med, Aurora, CO USA.
[Arend, William] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO USA.
[Blumberg, Hal] Novo Nordisk Inflammat Res Ctr, Dept Cellular Immunol, Seattle, WA USA.
[O'Neill, Luke] Trinity Coll Dublin, Dept Biochem, Dublin, Ireland.
[Goldbach-Mansky, Raphaela] Natl Inst Hlth, Natl Inst Arthrit, Translat Autoinflammatory Dis Sect, Bethesda, MD USA.
[Pizarro, Theresa] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.
[Hoffman, H.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Bufler, Philip] Univ Munich, Dept Pediat, Munich, Germany.
[Nold, Marcel] Monash Univ, Monash Inst Med Res, Melbourne, Australia.
[Ghezzi, Pietro] Brighton & Sussex Med Sch, Div Clin & Lab Investigat, Falmer, England.
[Mantovani, Alberto; Garlanda, Cecilia] Ist Clin Humanitas, Dept Inflammat, Milan, Italy.
[Boraschi, Diana] Inst Biomed Technol, Immunol Unit, Natl Res Council, Pisa, Italy.
[Rubartelli, Anna] Natl Inst Canc Res, Genoa, Italy.
[Netea, Mihai; van der Meer, Jos] Radboud Univ Nijmegen Med Ctr, Dept Med, Nijmegen, Netherlands.
[Joosten, Leo] Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol, NL-6525 ED Nijmegen, Netherlands.
[Mandrup-Poulsen, Tom] Steno Diabet Ctr, Copenhagen, Denmark.
[Donath, Marc] Univ Basel Hosp, Dept Diabet Endocrinol & Metab, CH-4031 Basel, Switzerland.
[Lewis, Eli] Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel.
[Pfeilschifter, Josef] Goethe Univ Frankfurt, Frankfurt, Germany.
[Martin, Michael] Justus Liebig Univ, Dept Biol & Chem, Giessen, Germany.
[Kracht, Michael] Justus Liebig Univ, Rudolf Buchheim Inst Pharmacol, Giessen, Germany.
[Muehl, H.] Univ Hosp Goethe Univ Frankfurt, Pharmazentrum Frankfurt, Frankfurt, Germany.
[Novick, Daniela] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
[Lukic, Miodrag] United Arab Emirates Univ, Dept Microbiol & Immunol, Al Ain, U Arab Emirates.
[Conti, Bruno] Scripps Res Inst, Dept Mol & Integrat Neurosci, La Jolla, CA 92037 USA.
[Solinger, Alan] XOMA, Berkeley, CA USA.
[Peyman, Kelk] Umea Univ, Umea, Sweden.
[van de Veerdonk, Frank] Radboud Univ Nijmegen Med Ctr, Nijmegen, Netherlands.
RP Dinarello, C (reprint author), Univ Colorado Denver, Dept Med, Aurora, CO USA.
RI LEWIS, ELI/F-1552-2012; van de Veerdonk, Frank/C-7256-2008; Netea,
Mihai/N-5155-2014; van der Meer, Jos/C-8521-2013; Garlanda,
Cecilia/K-4601-2016;
OI van de Veerdonk, Frank/0000-0002-1121-4894; van der Meer,
Jos/0000-0001-5120-3690; Garlanda, Cecilia/0000-0002-1510-7703; Kelk,
Peyman/0000-0003-1594-1738; Mantovani, Alberto/0000-0001-5578-236X;
Nold, Marcel/0000-0001-9682-4618; Ghezzi, Pietro/0000-0003-0911-8358
FU Intramural NIH HHS [ZIA AR041138-11]
NR 16
TC 105
Z9 119
U1 2
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD NOV
PY 2010
VL 11
IS 11
BP 973
EP 973
DI 10.1038/ni1110-973
PG 1
WC Immunology
SC Immunology
GA 666PI
UT WOS:000283127800002
PM 20959797
ER
PT J
AU Maecker, HT
McCoy, JP
AF Maecker, Holden T.
McCoy, J. Philip, Jr.
CA FOCIS Human Immunophenotyping Cons
TI A model for harmonizing flow cytometry in clinical trials
SO NATURE IMMUNOLOGY
LA English
DT Article
ID FICOLL-HYPAQUE SEPARATION; BLOOD MONONUCLEAR-CELLS; WHOLE-BLOOD;
T-CELLS; LYSIS TECHNIQUE; NORMAL ADULTS; ASSAYS; CRYOPRESERVATION;
ANTICOAGULANT; INFORMATION
C1 [Maecker, Holden T.] Stanford Univ, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA.
[McCoy, J. Philip, Jr.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Maecker, HT (reprint author), Stanford Univ, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA.
EM maecker@stanford.edu
OI Denny, Thomas/0000-0002-7364-8276
FU Intramural NIH HHS [ZIC HL005905-02, Z99 HL999999, ZIC HL005905-03, ZIC
HL005905-04]
NR 26
TC 55
Z9 57
U1 2
U2 10
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 NOV
PY 2010
VL 11
IS 11
BP 975
EP 978
DI 10.1038/ni1110-975
PG 4
WC Immunology
SC Immunology
GA 666PI
UT WOS:000283127800003
PM 20959798
ER
PT J
AU Unterholzner, L
Keating, SE
Baran, M
Horan, KA
Jensen, SB
Sharma, S
Sirois, CM
Jin, TC
Latz, E
Xiao, TS
Fitzgerald, KA
Paludan, SR
Bowie, AG
AF Unterholzner, Leonie
Keating, Sinead E.
Baran, Marcin
Horan, Kristy A.
Jensen, Soren B.
Sharma, Shruti
Sirois, Cherilyn M.
Jin, Tengchuan
Latz, Eicke
Xiao, T. Sam
Fitzgerald, Katherine A.
Paludan, Soren R.
Bowie, Andrew G.
TI IFI16 is an innate immune sensor for intracellular DNA
SO NATURE IMMUNOLOGY
LA English
DT Article
ID CYTOSOLIC DNA; CYTOPLASMIC DNA; I INTERFERONS; IFN-BETA; RECOGNITION;
PROTEIN; ACTIVATION; RNA; INFLAMMASOME; INDUCTION
AB The detection of intracellular microbial DNA is critical to appropriate innate immune responses; however, knowledge of how such DNA is sensed is limited. Here we identify IFI16, a PYHIN protein, as an intracellular DNA sensor that mediates the induction of interferon-beta (IFN-beta). IFI16 directly associated with IFN-beta-inducing viral DNA motifs. STING, a critical mediator of IFN-beta responses to DNA, was recruited to IFI16 after DNA stimulation. Lowering the expression of IFI16 or its mouse ortholog p204 by RNA-mediated interference inhibited gene induction and activation of the transcription factors IRF3 and NF-kappa B induced by DNA and herpes simplex virus type 1 (HSV-1). IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-beta induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).
C1 [Unterholzner, Leonie; Keating, Sinead E.; Baran, Marcin; Bowie, Andrew G.] Trinity Coll Dublin, Sch Biochem & Immunol, Dublin, Ireland.
[Horan, Kristy A.; Jensen, Soren B.; Paludan, Soren R.] Aarhus Univ, Dept Med Microbiol & Immunol, Aarhus, Denmark.
[Jensen, Soren B.; Sharma, Shruti; Sirois, Cherilyn M.; Latz, Eicke; Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA USA.
[Jin, Tengchuan; Xiao, T. Sam] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Latz, Eicke] Univ Bonn, Inst Clin Chem & Pharmacol, D-5300 Bonn, Germany.
RP Bowie, AG (reprint author), Trinity Coll Dublin, Sch Biochem & Immunol, Dublin, Ireland.
EM agbowie@tcd.ie
RI Xiao, Tsan/I-7616-2013; Xiao, Tsan/A-8590-2010; Jin,
Tengchuan/B-5883-2014; Latz, Eicke/H-3951-2014;
OI Xiao, Tsan/0000-0001-9688-475X; Sirois, Cherilyn M./0000-0002-5472-4288;
Unterholzner, Leonie/0000-0001-9824-692X; Jin,
Tengchuan/0000-0002-1395-188X; Latz, Eicke/0000-0003-1488-5666; Bowie,
Andrew/0000-0001-5316-4373
FU Science Foundation Ireland [07/IN1/B934]; Irish Health Research Board;
Danish Medical Research Council [09-072636]; Lundbeck Foundation
[R17-A1528, R34-A3855]; US National Institutes of Health [AI083713,
AI067497]; Faculty of Health Sciences, Aarhus
FX We thank C. Liu (New York University) for antibody to p204; S. Akira
(Osaka University) for Myd88-/-, Ticam1-/- and
Zbp1-/- mice; T. Taniguchi (University of Tokyo) for
Irf3-/- mice; M. Kelliher (University of Massachusetts
Medical School) for Tnfrsf1a-/- mice; T. Mak (University of
Toronto) for Tbk1-/- Tnfrsf1a-/- mice; G. Barber
(University of Miami) for Tmem173-/- femurs; D. Golenbock
(University of Massachusetts Medical School) for immortalized BMDMs
lacking MyD88 or TRIF; I. Julkunen (National Public Health Institute,
Finland) for Sendai virus; and S. Corr (Trinity College Dublin) for
Listeria monocytogenes DNA. Supported by Science Foundation Ireland
(07/IN1/B934 to L.U., S.E.K., M.B. and A.G.B.), the Irish Health
Research Board (S.E.K. and A.G.B.), the Danish Medical Research Council
(09-072636 to S.R.P.), the Lundbeck Foundation (R17-A1528 to S.R.P. and
R34-A3855 to K.A.H.), the US National Institutes of Health (AI083713 and
AI067497 to K.A.F.; Division of Intramural Research, National Institute
of Allergy and Infectious Diseases to T.S.X.) and the Faculty of Health
Sciences, Aarhus (S.B.J.).
NR 42
TC 571
Z9 599
U1 9
U2 71
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 NOV
PY 2010
VL 11
IS 11
BP 997
EP U42
DI 10.1038/ni.1932
PG 9
WC Immunology
SC Immunology
GA 666PI
UT WOS:000283127800009
PM 20890285
ER
PT J
AU Strober, W
AF Strober, Warren
TI Gut microbes: friends or fiends?
SO NATURE MEDICINE
LA English
DT Editorial Material
ID INFLAMMATORY BOWEL DISEASES; IMMUNE-SYSTEM; T-CELLS; MICROFLORA
C1 US Natl Inst Allergy & Infect Dis, Mucosal Immun Sect, Host Def Lab, Bethesda, MD USA.
RP Strober, W (reprint author), US Natl Inst Allergy & Infect Dis, Mucosal Immun Sect, Host Def Lab, Bethesda, MD USA.
EM wstrober@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000354-25]
NR 14
TC 11
Z9 12
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD NOV
PY 2010
VL 16
IS 11
BP 1195
EP 1197
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 675TV
UT WOS:000283860100023
PM 21052070
ER
PT J
AU De Keersmaecker, K
Real, PJ
Della Gatta, G
Palomero, T
Sulis, ML
Tosello, V
Van Vlierberghe, P
Barnes, K
Castillo, M
Sole, X
Hadler, M
Lenz, J
Aplan, PD
Kelliher, M
Kee, BL
Pandolfi, PP
Kappes, D
Gounari, F
Petrie, H
Van der Meulen, J
Speleman, F
Paietta, E
Racevskis, J
Wiernik, PH
Rowe, JM
Soulier, J
Avran, D
Cave, H
Dastugue, N
Raimondi, S
Meijerink, JPP
Cordon-Cardo, C
Califano, A
Ferrando, AA
AF De Keersmaecker, Kim
Real, Pedro J.
Della Gatta, Giusy
Palomero, Teresa
Luisa Sulis, Maria
Tosello, Valeria
Van Vlierberghe, Pieter
Barnes, Kelly
Castillo, Mireia
Sole, Xavier
Hadler, Michael
Lenz, Jack
Aplan, Peter D.
Kelliher, Michelle
Kee, Barbara L.
Pandolfi, Pier Paolo
Kappes, Dietmar
Gounari, Fotini
Petrie, Howard
Van der Meulen, Joni
Speleman, Frank
Paietta, Elisabeth
Racevskis, Janis
Wiernik, Peter H.
Rowe, Jacob M.
Soulier, Jean
Avran, David
Cave, Helene
Dastugue, Nicole
Raimondi, Susana
Meijerink, Jules P. P.
Cordon-Cardo, Carlos
Califano, Andrea
Ferrando, Adolfo A.
TI The TLX1 oncogene drives aneuploidy in T cell transformation
SO NATURE MEDICINE
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-EXPRESSION; TRANSGENIC MICE;
MUTATIONS; HOX11; SURVIVAL; BCL11B; NOTCH1; LYMPHOMAGENESIS; LYMPHOCYTES
AB The TLX1 oncogene (encoding the transcription factor T cell leukemia homeobox protein-1) has a major role in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). However, the specific mechanisms of T cell transformation downstream of TLX1 remain to be elucidated. Here we show that transgenic expression of human TLX1 in mice induces T-ALL with frequent deletions and mutations in Bcl11b (encoding B cell leukemia/lymphoma-11B) and identify the presence of recurrent mutations and deletions in BCL11B in 16% of human T-ALLs. Most notably, mouse TLX1 tumors were typically aneuploid and showed a marked defect in the activation of the mitotic checkpoint. Mechanistically, TLX1 directly downregulates the expression of CHEK1 (encoding CHK1 checkpoint homolog) and additional mitotic control genes and induces loss of the mitotic checkpoint in nontransformed preleukemic thymocytes. These results identify a previously unrecognized mechanism contributing to chromosomal missegregation and aneuploidy active at the earliest stages of tumor development in the pathogenesis of cancer.
C1 [De Keersmaecker, Kim; Real, Pedro J.; Della Gatta, Giusy; Palomero, Teresa; Luisa Sulis, Maria; Tosello, Valeria; Van Vlierberghe, Pieter; Barnes, Kelly; Hadler, Michael; Califano, Andrea; Ferrando, Adolfo A.] Columbia Univ, Inst Canc Genet, New York, NY 10027 USA.
[De Keersmaecker, Kim] VIB, Dept Mol & Dev Genet, Louvain, Belgium.
[De Keersmaecker, Kim] Katholieke Univ Leuven, Ctr Human Genet, Louvain, Belgium.
[Palomero, Teresa; Castillo, Mireia; Cordon-Cardo, Carlos; Ferrando, Adolfo A.] Columbia Univ, Dept Pathol, Med Ctr, New York, NY USA.
[Luisa Sulis, Maria; Ferrando, Adolfo A.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA.
[Sole, Xavier] Inst Invest Biomed Bellvitge, Biomarkers & Susceptibil Unit, Catalan Inst Oncol, Barcelona, Spain.
[Sole, Xavier] IDIBELL, Biomed Res Ctr Network Epidemiol & Publ Hlth, Catalan Inst Oncol, Barcelona, Spain.
[Lenz, Jack] Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA.
[Aplan, Peter D.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Kelliher, Michelle] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA USA.
[Kee, Barbara L.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
[Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Canc Ctr, Boston, MA USA.
[Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Canc Ctr, Boston, MA 02115 USA.
[Kappes, Dietmar] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Gounari, Fotini] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Petrie, Howard] Scripps Res Inst, Dept Canc Biol, Jupiter, FL USA.
[Van der Meulen, Joni; Speleman, Frank] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium.
[Paietta, Elisabeth; Racevskis, Janis; Wiernik, Peter H.] Montefiore Med Ctr, North Div, New York, NY USA.
[Paietta, Elisabeth; Racevskis, Janis; Wiernik, Peter H.] New York Med Coll, New York, NY USA.
[Rowe, Jacob M.] Technion Israel Inst Technol, Haifa, Israel.
[Soulier, Jean; Avran, David] Hop St Louis, AP HP, Hematol Lab, Paris, France.
[Soulier, Jean; Avran, David] Hop St Louis, INSERM, U944, Paris, France.
[Soulier, Jean; Avran, David] Univ Paris 07, Hop St Louis, Inst Univ Hematol, Paris, France.
[Cave, Helene] Univ Paris 07, Hop Robert Debre, AP HP, Dept Genet, Paris, France.
[Dastugue, Nicole] Hop Purpan, Hematol Lab, Toulouse, France.
[Raimondi, Susana] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Meijerink, Jules P. P.] Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Oncology Hematol, Rotterdam, Netherlands.
[Califano, Andrea] Columbia Univ, Joint Ctr Syst Biol, New York, NY USA.
[Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel.
RP Ferrando, AA (reprint author), Columbia Univ, Inst Canc Genet, New York, NY 10027 USA.
EM af2196@columbia.edu
RI Califano, Andrea/F-7239-2012; Van Vlierberghe, Pieter/G-8894-2013;
Castillo-Martin, Mireia/H-6152-2013; Real, Pedro/K-2994-2014; Aplan,
Peter/K-9064-2016; Ferrando, Adolfo /Q-7026-2016; Meijerink,
Jules/D-4393-2017;
OI De Keersmaecker, Kim/0000-0002-7420-9531; Van Vlierberghe,
Pieter/0000-0001-9063-7205; Real, Pedro/0000-0001-7968-5353; Meijerink,
Jules/0000-0002-6860-798X; Sole, Xavier/0000-0002-2197-3325; Tosello,
Valeria/0000-0001-9560-340X
FU New York Community Trust; US National Institutes of Health [R01CA120196,
R01CA129382, CA21765, U24 CA114737]; Eastern Cooperative Oncology Group
tumor bank; European Organization for Research and Treatment of Cancer
Children Leukemia Group; Leukemia & Lymphoma Society Scholar Award; US
National Institutes of Health; Fonds voor Wetenschappelijk
Onderzoek-Vlaanderen; Belgian American Educational Foundation; France
National Cancer Institute
FX This work was supported by a Blood Disease Research Project research
grant from The New York Community Trust (A.A.F.); the US National
Institutes of Health (grants R01CA120196 and R01CA129382 to A.A.F.;
CA21765 to S.R. and U24 CA114737 to E.P.), the Spanish Ministry of
Science and Innovation (fellowship EX-2006-0739 to P.J.R.), a
Canceropole Ile-de-France Research research grant (J.S.), the Eastern
Cooperative Oncology Group tumor bank and the European Organization for
Research and Treatment of Cancer Children Leukemia Group, the Leukemia &
Lymphoma Society Scholar Award (A.A.F.) and the Intramural Program of
the US National Institutes of Health (P.D.A.). K.D.K. is a postdoctoral
researcher funded by the Fonds voor Wetenschappelijk
Onderzoek-Vlaanderen and a recipient of a Belgian American Educational
Foundation fellowship. D.A. is recipient of a predoctoral fellowship
from the France National Cancer Institute. We are also grateful to T.
Ludwig for helpful discussions, to J.C. Zuniga-Pflucker (University of
Toronto) for the OP9-DL1 cells, to F. Gounari (University of Chicago)
for the pUC1017 vector and S. Cory (Walter and Eliza Hall Institute of
Medical Research) and H.G. Wendel (Memorial Sloan Kettering Cancer
Center) for the Vav-Bcl2 mouse line.
NR 35
TC 63
Z9 64
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD NOV
PY 2010
VL 16
IS 11
BP 1321
EP U65
DI 10.1038/nm.2246
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 675TV
UT WOS:000283860100045
PM 20972433
ER
PT J
AU Kummar, S
Chen, HX
Wright, J
Holbeck, S
Millin, MD
Tomaszewski, J
Zweibel, J
Collins, J
Doroshow, JH
AF Kummar, Shivanni
Chen, Helen X.
Wright, John
Holbeck, Susan
Millin, Myrtle Davis
Tomaszewski, Joseph
Zweibel, James
Collins, Jerry
Doroshow, James H.
TI Utilizing targeted cancer therapeutic agents in combination: novel
approaches and urgent requirements
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Article
ID RENAL-CELL CARCINOMA; METASTATIC COLORECTAL-CANCER; PHASE-II TRIAL;
SYNTHETIC LETHAL SCREEN; ADP-RIBOSE POLYMERASE; EARLY CLINICAL-TRIALS;
BREAST-CANCER; LUNG-CANCER; KINASE INHIBITOR; DRUG-DEVELOPMENT
AB The rapid development of new therapeutic agents that target specific molecular pathways involved in tumour cell proliferation provides an unprecedented opportunity to achieve a much higher degree of biochemical specificity than previously possible with traditional chemotherapeutic anticancer agents. However, the lack of specificity of these established chemotherapeutic drugs allowed a relatively straightforward approach to their use in combination therapies. Developing a paradigm for combining new, molecularly targeted agents, on the other hand, is substantially more complex. The abundance of molecular data makes it possible, at least in theory, to predict how such agents might interact across crucial growth control networks. Initial strategies to examine molecularly targeted agent combinations have produced a small number of successes in the clinic. However, for most of these combination strategies, both in preclinical models and in patients, it is not clear whether the agents being combined actually hit their targets to induce growth inhibition. Here, we consider the initial approach of the US National Cancer Institute (NCI) to the evaluation of combinations of molecularly targeted anticancer agents in patients and provide a description of several new approaches that the NCI has initiated to improve the effectiveness of combination-targeted therapy for cancer.
C1 [Kummar, Shivanni; Doroshow, James H.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Chen, Helen X.; Wright, John; Holbeck, Susan; Millin, Myrtle Davis; Tomaszewski, Joseph; Zweibel, James; Collins, Jerry; Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Doroshow, JH (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM doroshoj@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
FX The authors wish to express their appreciation to the members of the
National Cancer Institute's Cancer Therapy Evaluation Program who have
overseen the clinical trials described in this paper and the members of
the National Cancer Institute's Developmental Therapeutics Program who
have had an essential role in coordinating the initiatives outlined in
the paper. This work was supported by federal funds from the National
Cancer Institute, National Institutes of Health. The content of this
publication does not necessarily reflect the views or the policies of
the US Department of Health and Human Services nor does the mention of
trade names, commercial products or organizations imply endorsement by
the US government.
NR 90
TC 91
Z9 94
U1 2
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1776
EI 1474-1784
J9 NAT REV DRUG DISCOV
JI Nat. Rev. Drug Discov.
PD NOV
PY 2010
VL 9
IS 11
BP 843
EP 856
DI 10.1038/nrd3216
PG 14
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA 673II
UT WOS:000283652500023
PM 21031001
ER
PT J
AU Pierce, SK
Liu, WL
AF Pierce, Susan K.
Liu, Wanli
TI The tipping points in the initiation of B cell signalling: how small
changes make big differences
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID RESONANCE ENERGY-TRANSFER; RECEPTOR TYROSINE KINASES; SINGLE-MOLECULE
TRACKING; BASOPHIL LEUKEMIA-CELLS; RESPONSES IN-VIVO; ANTIGEN RECEPTOR;
PLASMA-MEMBRANE; SYNAPSE FORMATION; LIPID RAFTS; LYMPH-NODE
AB B cells are selected by the binding of antigen to clonally distributed B cell receptors (BCRs), triggering signalling cascades that result in B cell activation. With the recent application of high-resolution live-cell imaging, we are gaining an understanding of the events that initiate BCR signalling within seconds of its engagement with antigen. These observations are providing a molecular explanation for fundamental aspects of B cell responses, including antigen affinity discrimination and the value of class switching, as well as insights into the underlying causes of B cell tumorigenesis. Advances in our understanding of the earliest molecular events that follow antigen binding to the BCR may provide a general framework for the initiation of signalling in the adaptive immune system.
C1 [Pierce, Susan K.; Liu, Wanli] NIAID, NIH, Rockville, MD 20852 USA.
RP Pierce, SK (reprint author), NIAID, NIH, Rockville, MD 20852 USA.
EM spierce@niaid.nih.gov
RI liu, wanli/H-5690-2011
OI liu, wanli/0000-0003-2624-6802
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX We thank J. Brzostowski for expert comments on live-cell imaging
techniques. This work has been supported by the Intramural Research
Program of the National Institutes of Health, National Institute of
Allergy and Infectious Diseases.
NR 83
TC 75
Z9 76
U1 2
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD NOV
PY 2010
VL 10
IS 11
BP 767
EP 777
DI 10.1038/nri2853
PG 11
WC Immunology
SC Immunology
GA 670NM
UT WOS:000283431100013
PM 20935671
ER
PT J
AU Bluestone, JA
Auchincloss, H
Nepom, GT
Rotrosen, D
Clair, EWS
Turka, LA
AF Bluestone, Jeffrey A.
Auchincloss, Hugh
Nepom, Gerald T.
Rotrosen, Daniel
Clair, E. William St.
Turka, Laurence A.
TI TIMELINE The Immune Tolerance Network at 10 years: tolerance research at
the bedside
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Article
ID FACILITATED ALLERGEN BINDING; RENAL-TRANSPLANT TOLERANCE; REGULATORY
T-CELLS; IN-VIVO; MARROW-TRANSPLANTATION; MULTIPLE-SCLEROSIS; RUSH
IMMUNOTHERAPY; ACUTE REJECTION; COMBINED KIDNEY; CO-STIMULATION
AB Immune tolerance-inducing therapies reprogramme immune cells to eliminate pathogenic immune responses while preserving protective immunity. The Immune Tolerance Network (ITN), sponsored by the US National Institutes of Health, was established in 1999 to evaluate new tolerance-inducing therapies and carry out mechanistic studies using a unique interactive approach in partnership with industry, academia and foundations. Ten years later, the ITN has carried out approximately 36 clinical trials and tolerance studies examining innovative tolerogenic approaches in the settings of allergy, autoimmune diseases and organ transplantation. ITN investigators have published more than 80 original research papers based on this work. This Timeline article summarizes the progress and challenges of clinical research in the ITN.
C1 [Bluestone, Jeffrey A.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
[Bluestone, Jeffrey A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Auchincloss, Hugh; Rotrosen, Daniel] NIAID, Bethesda, MD 20817 USA.
[Nepom, Gerald T.] Benaroya Res Inst, Seattle, WA 98101 USA.
[Clair, E. William St.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Turka, Laurence A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Transplant Inst, Boston, MA 02115 USA.
RP Bluestone, JA (reprint author), Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
EM jeff.bluestone@ucsf.edu
FU NIAID; JDRF; FAI; NIDDK
FX We thank the many people inside the ITN, NIAID and Rho, as well as the
immunology community at large, for the hard work, support and creative
ideas that have helped the ITN to flourish. Special thanks to the ITN
funders - NIAID, JDRF, FAI and NIDDK - and to all the companies who have
worked with the ITN and its clinical investigators.
NR 45
TC 31
Z9 34
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD NOV
PY 2010
VL 10
IS 11
BP 797
EP 803
DI 10.1038/nri2869
PG 7
WC Immunology
SC Immunology
GA 670NM
UT WOS:000283431100016
PM 20972473
ER
PT J
AU Pepin, KM
Lass, S
Pulliam, JRC
Read, AF
Lloyd-Smith, JO
AF Pepin, Kim M.
Lass, Sandra
Pulliam, Juliet R. C.
Read, Andrew F.
Lloyd-Smith, James O.
TI Identifying genetic markers of adaptation for surveillance of viral host
jumps
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Review
ID INFLUENZA-A VIRUS; RESPIRATORY-SYNDROME-CORONAVIRUS; EMERGING
INFECTIOUS-DISEASES; VESICULAR STOMATITIS-VIRUS; EQUINE
ENCEPHALITIS-VIRUS; EXPERIMENTAL EVOLUTION; WITHIN-HOST; IN-VIVO;
MOLECULAR EPIDEMIOLOGY; ENVELOPE GLYCOPROTEIN
AB Adaptation is often thought to affect the likelihood that a virus will be able to successfully emerge in a new host species. If so, surveillance for genetic markers of adaptation could help to predict the risk of disease emergence. However, adaptation is difficult to distinguish conclusively from the other processes that generate genetic change. In this Review we survey the research on the host jumps of influenza A, severe acute respiratory syndrome-coronavirus, canine parvovirus and Venezuelan equine encephalitis virus to illustrate the insights that can arise from combining genetic surveillance with microbiological experimentation in the context of epidemiological data. We argue that using a multidisciplinary approach for surveillance will provide a better understanding of when adaptations are required for host jumps and thus when predictive genetic markers may be present.
C1 [Pepin, Kim M.] Penn State Univ, Dept Phys, University Pk, PA 16802 USA.
[Pulliam, Juliet R. C.; Read, Andrew F.; Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Pulliam, Juliet R. C.; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolut Biol, Los Angeles, CA 90095 USA.
[Read, Andrew F.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16827 USA.
[Read, Andrew F.] Penn State Univ, Ctr Infect Dis Dynam, Dept Entomol, University Pk, PA 16827 USA.
RP Pepin, KM (reprint author), Penn State Univ, Dept Phys, 104 Davey Lab, University Pk, PA 16802 USA.
EM kmp29@psu.edu
RI Pulliam, Juliet/A-6516-2008; Lloyd-Smith, James/K-4080-2012
OI Pulliam, Juliet/0000-0003-3314-8223; Lloyd-Smith,
James/0000-0001-7941-502X
FU Research and Policy for Infectious Diseases Dynamics (RAPIDD) of the
Science and Technology Directorate; Department of Homeland Security and
Fogarty International Center; National Institutes of Health; National
Science Foundation [0742373, DEB-0520468, EF-0928690]; De Logi Chair in
Biological Sciences
FX This work was supported by the Research and Policy for Infectious
Diseases Dynamics (RAPIDD) programme of the Science and Technology
Directorate, the Department of Homeland Security and Fogarty
International Center and the National Institutes of Health. K. M. P. was
also supported by National Science Foundation grant 0742373; S. L. was
supported by National Science Foundation grant DEB-0520468 to P. Hudson;
J.L.-S. was supported by National Science Foundation grant EF-0928690
and the De Logi Chair in Biological Sciences.
NR 117
TC 55
Z9 55
U1 3
U2 39
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 NOV
PY 2010
VL 8
IS 11
BP 802
EP 813
DI 10.1038/nrmicro2440
PG 12
WC Microbiology
SC Microbiology
GA 665RY
UT WOS:000283054400017
PM 20938453
ER
PT J
AU Wang, LW
Yang, JK
Kabaleeswaran, V
Rice, AJ
Cruz, AC
Park, AY
Yin, QA
Damko, E
Jang, SB
Raunser, S
Robinson, CV
Siegel, RM
Walz, T
Wu, H
AF Wang, Liwei
Yang, Jin Kuk
Kabaleeswaran, Venkataraman
Rice, Amanda J.
Cruz, Anthony C.
Park, Ah Young
Yin, Qian
Damko, Ermelinda
Jang, Se Bok
Raunser, Stefan
Robinson, Carol V.
Siegel, Richard M.
Walz, Thomas
Wu, Hao
TI The Fas-FADD death domain complex structure reveals the basis of DISC
assembly and disease mutations
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; MACROMOLECULAR ASSEMBLIES;
SIGNALING COMPLEX; CRYSTAL-STRUCTURE; APOPTOSIS; RECEPTOR; PROTEIN;
SUPERFAMILY; INHIBITION; MECHANISM
AB The death-inducing signaling complex (DISC) formed by the death receptor Fas, the adaptor protein FADD and caspase-8 mediates the extrinsic apoptotic program. Mutations in Fas that disrupt the DISC cause autoimmune lymphoproliferative syndrome (ALPS). Here we show that the Fas-FADD death domain (DD) complex forms an asymmetric oligomeric structure composed of 5-7 Fas DD and 5 FADD DD, whose interfaces harbor ALPS-associated mutations. Structure-based mutations disrupt the Fas-FADD interaction in vitro and in living cells; the severity of a mutation correlates with the number of occurrences of a particular interaction in the structure. The highly oligomeric structure explains the requirement for hexameric or membrane-bound FasL in Fas signaling. It also predicts strong dominant negative effects from Fas mutations, which are confirmed by signaling assays. The structure optimally positions the FADD death effector domain (DED) to interact with the caspase-8 DED for caspase recruitment and higher-order aggregation.
C1 [Wang, Liwei; Yang, Jin Kuk; Kabaleeswaran, Venkataraman; Yin, Qian; Damko, Ermelinda; Jang, Se Bok; Wu, Hao] Weill Cornell Med Coll, Dept Biochem, New York, NY USA.
[Yang, Jin Kuk] Soongsil Univ, Dept Chem, Seoul, South Korea.
[Rice, Amanda J.; Raunser, Stefan; Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[Cruz, Anthony C.; Siegel, Richard M.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Park, Ah Young; Robinson, Carol V.] Univ Oxford, Dept Chem, Oxford, England.
[Jang, Se Bok] Pusan Natl Univ, Dept Mol Biol, Pusan, South Korea.
[Walz, Thomas] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Wu, H (reprint author), Weill Cornell Med Coll, Dept Biochem, New York, NY USA.
EM haowu@med.cornell.edu
OI Siegel, Richard/0000-0001-5953-9893; Raunser, Stefan/0000-0001-9373-3016
FU US National Institutes of Health [R01-AI50872]; Korea Science and
Engineering Foundation (KOSEF); Long-term Overseas Dispatch Program for
Pusan National University's Tenure-track Faculty; Biotechnology and
Biological Sciences Research Council; Royal Society; Walters-Kundert
Trust; National Center for Research Resources at the US National
Institutes of Health [RR-15301]
FX We thank Y.C. Park for earlier work on this project and K. Rajashankar,
I. Kourinov and N. Sukumar for help with data collection. This work was
supported by US National Institutes of Health grant R01-AI50872 (H.W.),
the Post-doctoral Fellowship Program of Korea Science and Engineering
Foundation (KOSEF) (J.K.Y.), the 2008 Long-term Overseas Dispatch
Program for Pusan National University's Tenure-track Faculty (S.B.J.),
the Biotechnology and Biological Sciences Research Council (A.Y.P.), the
Royal Society (C.V.R.) and the Walters-Kundert Trust (C.V.R.).
Diffraction data collection was conducted at the Northeastern
Collaborative Access Team beam lines of the Advanced Photon Source at
Argonne National Laboratory, supported by award RR-15301 from the
National Center for Research Resources at the US National Institutes of
Health. S.R. was a fellow of the German Academy of Sciences Leopoldina
(BMBF-LPD 9901/8-163). T.W. is an investigator of the Howard Hughes
Medical Institute.
NR 43
TC 122
Z9 130
U1 3
U2 19
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 NOV
PY 2010
VL 17
IS 11
BP 1324
EP U176
DI 10.1038/nsmb.1920
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 674TQ
UT WOS:000283773200009
PM 20935634
ER
PT J
AU Klover, PJ
Muller, WJ
Robinson, GW
Pfeiffer, RM
Yamaji, D
Hennighausen, L
AF Klover, Peter J.
Muller, William J.
Robinson, Gertraud W.
Pfeiffer, Ruth M.
Yamaji, Daisuke
Hennighausen, Lothar
TI Loss of STAT1 from Mouse Mammary Epithelium Results in an Increased
Neu-Induced Tumor Burden
SO NEOPLASIA
LA English
DT Article
ID BREAST-CANCER; TARGETED DISRUPTION; I INTERFERON; IFN-ALPHA; IMMUNITY;
GENE; RADIATION; MELANOMA; INNATE; MODELS
AB Type I and type II classes of interferons (IFNs) signal through the JAK/STAT1 pathway and are known to be important in adaptive and innate immune responses and in protection against tumors. Although STAT1 is widely considered a tumor suppressor, it remains unclear, however, if this function occurs in tumor cells ( cell autonomous) or if STAT1 acts primarily through immune cells. Here, the question of whether STAT1 has a cell autonomous role in mammary tumor formation was addressed in a mouse model of ERBB2/neu-induced breast cancer in the absence and presence of STAT1. For this purpose, mice that carry floxed Stat1 alleles, which permit cell-specific removal of STAT1, were generated. To induce tumors only in mammary cells lacking STAT1, Stat1 floxed mice were crossed with transgenic mice that express cre recombinase and the neu oncogene under the mouse mammary tumor virus LTR (Stat1fl/fl NIC). Stat1 was effectively deleted in mammary epithelium of virgin Stat1fl/fl NIC females. Time-to-tumor onset was significantly shorter in Stat1fl/fl NIC females than in WT NIC ( Wilcoxon rank sum test, P = .02). The median time-to-tumor onset in the Stat1fl/fl NIC mice was 49.4 weeks, whereas it was 62.4 weeks in the WT NIC mice. These results suggest that STAT1 in mammary epithelial cells may play a role in suppressing tumorigenesis. The Stat1 floxed allele described in this study is also a unique resource to determine the cellular targets of IFNs and STAT1 action, which should aid our understanding and appreciation of these pathways.
C1 [Klover, Peter J.; Robinson, Gertraud W.; Yamaji, Daisuke; Hennighausen, Lothar] NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
[Muller, William J.] McGill Univ, Ctr Hlth, Dept Med, Montreal, PQ, Canada.
[Muller, William J.] McGill Univ, Ctr Hlth, Dept Biochem, Montreal, PQ, Canada.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, NIH, Rockville, MD USA.
RP Klover, PJ (reprint author), 8 Ctr Dr,Bldg 8,Room 107, Bethesda, MD 20817 USA.
EM peter_klover@yahoo.com
RI Pfeiffer, Ruth /F-4748-2011; Robinson, Gertraud/I-2136-2012
FU National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases; National Cancer Institute
FX This work was supported by the National Institutes of Health intramural
research programs of National Institute of Diabetes and Digestive and
Kidney Diseases and National Cancer Institute.
NR 20
TC 42
Z9 44
U1 0
U2 0
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
USA
SN 1522-8002
J9 NEOPLASIA
JI Neoplasia
PD NOV
PY 2010
VL 12
IS 11
BP 899
EP 905
DI 10.1593/neo.10716
PG 7
WC Oncology
SC Oncology
GA 693FB
UT WOS:000285208900005
PM 21076615
ER
PT J
AU Moustakas, A
Iwamoto, FM
Kreisl, TN
Sul, J
Kim, L
Butman, J
Albert, P
Fine, HA
AF Moustakas, Argirios
Iwamoto, Fabio M.
Kreisl, Teri N.
Sul, Joohee
Kim, Lyndon
Butman, John
Albert, Paul
Fine, Howard A.
TI PHASE II TRIAL OF ENZASTAURIN (ENZ) WITH BEVACIZUMAB (BV) IN ADULTS WITH
RECURRENT GLIOBLASTOMA (GEM)
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT Advances in Inflammatory Bowel Diseases Crohns and Colitis Foundations
National Clinical and Research Conference
CY DEC 09-12, 2010
CL Hollywood, FL
C1 [Moustakas, Argirios; Iwamoto, Fabio M.; Kreisl, Teri N.; Sul, Joohee; Butman, John; Albert, Paul; Fine, Howard A.] NCI, NIH, Bethesda, MD 20892 USA.
[Kim, Lyndon] UMass, Amherst, MA USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD NOV
PY 2010
VL 12
SU 4
BP 37
EP 37
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 691LX
UT WOS:000285082400160
ER
PT J
AU Inskip, PD
Hoover, RN
Devesa, SS
AF Inskip, Peter D.
Hoover, Robert N.
Devesa, Susan S.
TI Brain cancer incidence trends in relation to cellular telephone use in
the United States
SO NEURO-ONCOLOGY
LA English
DT Article
DE brain cancer; cellular telephones; epidemiology; SEER
ID CENTRAL-NERVOUS-SYSTEM; MOBILE PHONES; TUMOR-INCIDENCE; TIME TRENDS;
1900 MHZ; RATES; RISK
AB The use of cellular telephone has grown explosively during the past two decades, and there are now more than 279 million wireless subscribers in the United States. If cellular phone use causes brain cancer, as some suggest, the potential public health implications could be considerable. One might expect the effects of such a prevalent exposure to be reflected in general population incidence rates, unless the induction period is very long or confined to very long-term users. To address this issue, we examined temporal trends in brain cancer incidence rates in the United States, using data collected by the Surveillance, Epidemiology, and End Results (SEER) Program. Log-linear models were used to estimate the annual percent change in rates among whites. With the exception of the 20-29-year age group, the trends for 1992-2006 were downward or flat. Among those aged 20-29 years, there was a statistically significant increasing trend between 1992 and 2006 among females but not among males. The recent trend in 20-29-year-old women was driven by a rising incidence of frontal lobe cancers. No increases were apparent for temporal or parietal lobe cancers, or cancers of the cerebellum, which involve the parts of the brain that would be more highly exposed to radiofrequency radiation from cellular phones. Frontal lobe cancer rates also rose among 20-29-year-old males, but the increase began earlier than among females and before cell phone use was highly prevalent. Overall, these incidence data do not provide support to the view that cellular phone use causes brain cancer.
C1 [Inskip, Peter D.; Hoover, Robert N.; Devesa, Susan S.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Inskip, PD (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza S,Room 7052, Bethesda, MD 20892 USA.
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services
FX This research was supported by intramural funds from the National Cancer
Institute, National Institutes of Health, Department of Health and Human
Services.
NR 20
TC 43
Z9 45
U1 8
U2 55
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD NOV
PY 2010
VL 12
IS 11
BP 1147
EP 1151
DI 10.1093/neuonc/noq077
PG 5
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 673EU
UT WOS:000283642700007
PM 20639214
ER
PT J
AU Stranahan, AM
Lee, K
Becker, KG
Zhang, YQ
Maudsley, S
Martin, B
Cutler, RG
Mattson, MP
AF Stranahan, Alexis M.
Lee, Kim
Becker, Kevin G.
Zhang, Yonqing
Maudsley, Stuart
Martin, Bronwen
Cutler, Roy G.
Mattson, Mark P.
TI Hippocampal gene expression patterns underlying the enhancement of
memory by running in aged mice
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Wheel running; Hippocampus; Aging; Cognition; Gene expression
ID LONG-TERM POTENTIATION; RAT HIPPOCAMPUS; ENVIRONMENTAL ENRICHMENT;
SYNAPTIC PLASTICITY; NERVOUS-SYSTEM; NEUROGENESIS; EXERCISE; BRAIN;
PATHWAYS; PROTEIN
AB Physical activity preserves cognition in the aging brain, but the mechanisms remain obscure. In order to identify candidate genes and pathways responsible for the preservation of cognitive function by exercise, we trained mice that had been exposed to lifelong running or sedentary lifestyle for 16 months in the hippocampus-dependent water maze. After water maze training, we analyzed the expression of 24,000 genes in the hippocampus using Illumina bead microarray. Runners show greater activation of genes associated with synaptic plasticity and mitochondrial function, and also exhibit significant downregulation of genes associated with oxidative stress and lipid metabolism. Running also modified the effects of learning on the expression of genes involved in cell excitability, energy metabolism, and insulin, MAP kinase and Wnt signaling. These results suggest that the enhancement of cognitive function by lifelong exercise is associated with an altered transcriptional profile following learning. Published by Elsevier Inc.
C1 [Stranahan, Alexis M.; Lee, Kim; Martin, Bronwen; Cutler, Roy G.; Mattson, Mark P.] NIA, Cellular & Mol Neurosci Sect, Neurosci Lab, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Becker, Kevin G.; Zhang, Yonqing] NIA, Gene Express & Genom Unit, Res Resources Branch, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Maudsley, Stuart] NIA, Receptor Pharmacol Sect, Neurosci Lab, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Mattson, MP (reprint author), NIA, Cellular & Mol Neurosci Sect, Neurosci Lab, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM astrana1@jhu.edu; mattsonm@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012;
OI Becker, Kevin/0000-0002-6794-6656
FU National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institute on Aging. We would like to thank Xiangru Xu for
valuable discussions. The authors have no actual or potential conflicts
of interest.
NR 31
TC 60
Z9 61
U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD NOV
PY 2010
VL 31
IS 11
BP 1937
EP 1949
DI 10.1016/j.neurobiolaging.2008.10.016
PG 13
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 663SC
UT WOS:000282907800011
PM 19070401
ER
PT J
AU Cippitelli, A
Zook, M
Bell, L
Damadzic, R
Eskay, RL
Schwandt, M
Heilig, M
AF Cippitelli, Andrea
Zook, Michelle
Bell, Lauren
Damadzic, Ruslan
Eskay, Robert L.
Schwandt, Melanie
Heilig, Markus
TI Reversibility of object recognition but not spatial memory impairment
following binge-like alcohol exposure in rats
SO NEUROBIOLOGY OF LEARNING AND MEMORY
LA English
DT Article
DE Memory; Learning; Recognition; Hippocampus; Entorhinal
ID BRAIN-DAMAGE; ETHANOL-CONSUMPTION; NONSPATIAL CHANGES; ENTORHINAL
CORTEX; ADULT RATS; RETROHIPPOCAMPAL LESIONS; NEURONAL DEGENERATION;
COGNITIVE DEFICITS; PREFRONTAL CORTEX; HIPPOCAMPUS
AB Excessive alcohol use leads to neurodegeneration in several brain structures including the hippocampal dentate gyrus and the entorhinal cortex Cognitive deficits that result are among the most insidious and debilitating consequences of alcoholism The object exploration task (OET) provides a sensitive measurement of spatial memory impairment Induced by hippocampal and cortical damage In this study we examine whether the observed neurotoxicity produced by a 4-day binge ethanol treatment results in long-term memory impairment by observing the time course of reactions to spatial change (object configuration) and non-spatial change (object recognition) Wistar rats were assessed for their abilities to detect spatial configuration in the OFT at 1 week and 10 weeks following the ethanol treatment in which ethanol groups received 9-15 g/kg/day and achieved blood alcohol levels over 300 mg/dl At 1 week results indicated that the binge alcohol treatment produced impairment in both spatial memory and non-spatial object recognition performance Unlike the controls ethanol treated rats did not increase the duration or number of contacts with the displaced object in the spatial memory task nor did they increase the duration of contacts with the novel object in the object recognition task After 10 weeks spatial memory remained impaired in the ethanol treated rats but object recognition ability was recovered Our data suggest that episodes of binge like alcohol exposure result in long-term and possibly permanent impairments in memory for the configuration of objects during exploration whereas the ability to detect non-spatial changes is only temporarily affected Published by Elsevier Inc
C1 [Cippitelli, Andrea; Zook, Michelle; Bell, Lauren; Damadzic, Ruslan; Eskay, Robert L.; Schwandt, Melanie; Heilig, Markus] NIAAA, LCTS, NIH, Bethesda, MD 20892 USA.
RP Cippitelli, A (reprint author), NIAAA, LCTS, NIH, 10 Ctr Dr 1-5330, Bethesda, MD 20892 USA.
RI Schwandt, Melanie/L-9866-2016;
OI Heilig, Markus/0000-0003-2706-2482
NR 50
TC 17
Z9 17
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1074-7427
J9 NEUROBIOL LEARN MEM
JI Neurobiol. Learn. Mem.
PD NOV
PY 2010
VL 94
IS 4
BP 538
EP 546
DI 10.1016/j.nlm.2010.09.006
PG 9
WC Behavioral Sciences; Neurosciences; Psychology; Psychology,
Multidisciplinary
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 681GF
UT WOS:000284298700012
PM 20849966
ER
PT J
AU Gu, H
Salmeron, BJ
Ross, TJ
Geng, XJ
Zhan, W
Stein, EA
Yang, YH
AF Gu, Hong
Salmeron, Betty Jo
Ross, Thomas J.
Geng, Xiujuan
Zhan, Wang
Stein, Elliot A.
Yang, Yihong
TI Mesocorticolimbic circuits are impaired in chronic cocaine users as
demonstrated by resting-state functional connectivity
SO NEUROIMAGE
LA English
DT Article
ID DRUG-ADDICTION; CINGULATE CORTEX; MOTOR CORTEX; NEURAL BASIS; HUMAN
BRAIN; ABUSERS; NETWORKS; REWARD; MRI; THALAMUS
AB Preclinical models have consistently demonstrated the importance of the mesocorticolimbic (MCL) brain reward system in drug dependence, with critical molecular and cellular neuroadaptations identified within these structures following chronic cocaine administration Cocaine dependent individuals manifest alterations in reward functioning that may relate to changes induced by cocaine or to pre-existing differences related to vulnerability to addiction. The circuit level manifestations of these drug-induced plastic changes and predispositions to drug dependence are poorly understood in preclinical models and virtually unknown in human drug dependence Using whole-brain resting-state fMRI connectivity analysis with 'seed voxels' placed within individual nodes of the MCL system, we report network-specific functional connectivity strength decreases in cocaine users within distinct circuits of the system, including between ventral tegmental area (VIA) and a region encompassing thalamus/lentiform nucleus/nucleus accumbens, between amygdala and medial prefrontal cortex (mPFC). and between hippocampus and dorsal mPFC Further, regression analysis on regions showing significant functional connectivity decrease in chronic cocaine users revealed that the circuit strength between VTA and thalamus/lentiform nucleus/nucleus accumbens was negatively correlated with years of cocaine use This is the first evidence of circuit-related changes in human cocaine dependence and is consistent with the range of cognitive and behavioral disruptions seen in cocaine dependence. As potential circuit level biomarkers of cocaine dependence, these circuit alterations may be usefully applied in treatment development and monitoring treatment outcome Published by Elsevier Inc
C1 [Gu, Hong; Salmeron, Betty Jo; Ross, Thomas J.; Geng, Xiujuan; Zhan, Wang; Stein, Elliot A.; Yang, Yihong] Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA.
RP Yang, YH (reprint author), Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, 251 Bayview Blvd,Suite 200,Room 07A709, Baltimore, MD 21224 USA.
RI Ross, Thomas/B-7469-2008; Geng, Xiujuan/I-3852-2012; Salmeron, Betty
Jo/M-1793-2016
OI Ross, Thomas/0000-0002-7745-3572; Salmeron, Betty Jo/0000-0003-1699-9333
FU National Institute on Drug Abuse
FX Supported by the Intramural Research Program of the National Institute
on Drug Abuse
NR 68
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U1 1
U2 30
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 NOV 1
PY 2010
VL 53
IS 2
BP 593
EP 601
DI 10.1016/j.neuroimage.2010.06.066
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 648JB
UT WOS:000281688000023
PM 20603217
ER
PT J
AU Waltz, JA
Schweitzer, JB
Ross, TJ
Kurup, PK
Salmeron, BJ
Rose, EJ
Gold, JM
Stein, EA
AF Waltz, James A.
Schweitzer, Julie B.
Ross, Thomas J.
Kurup, Pradeep K.
Salmeron, Betty J.
Rose, Emma J.
Gold, James M.
Stein, Elliot A.
TI Abnormal Responses to Monetary Outcomes in Cortex, but not in the Basal
Ganglia, in Schizophrenia
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE schizophrenia; dopamine; reinforcement; basal ganglia; ventromedial
prefrontal cortex
ID STRIATAL REWARD PREDICTION; EVENT-RELATED FMRI; DECISION-MAKING;
NEGATIVE SYMPTOMS; NEURAL RESPONSE; FRONTAL-CORTEX; RATING-SCALE;
DYSFUNCTION; DISSOCIATION; ACTIVATION
AB Psychosis has been associated with aberrant brain activity concurrent with both the anticipation and integration of monetary outcomes. The extent to which abnormal reward-related neural signals can be observed in chronic, medicated patients with schizophrenia (SZ), however, is not clear. In an fMRI study involving 17 chronic outpatients with SZ and 17 matched controls, we used a monetary incentive delay (MID) task, in which different-colored shapes predicted gains, losses, or neutral outcomes. Subjects needed to respond to a target within a time window in order to receive the indicated gain or avoid the indicated loss. Group differences in blood-oxygen-level-dependent responses to cues and outcomes were assessed through voxel-wise whole-brain analyses and regions-of-interest analyses in the neostriatum and prefrontal cortex (PFC). Significant group by outcome valence interactions were observed in the medial and lateral PFC, lateral temporal cortex, and amygdalae, such that controls, but not patients, showed greater activation for gains, relative to losses. In the striatum, neural activity was modulated by outcome magnitude in both groups. Additionally, we found that ratings of negative symptoms in patients correlated with sensitivity to obtained losses in medial PFC, obtained gains in lateral PFC, and anticipated gains in left ventral striatum. Sensitivity to obtained gains in lateral PFC also correlated with positive symptom scores in patients. Our findings of systematic relationships between clinical symptoms and neural responses to stimuli associated with rewards and punishments offer promise that reward-related neural responses may provide sensitive probes of the effectiveness of treatments for negative symptoms. Neuropsychopharmacology (2010) 35, 2427-2439; doi: 10.1038/npp.2010.126; published online 18 August 2010
C1 [Waltz, James A.; Gold, James M.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21228 USA.
[Schweitzer, Julie B.] Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA 95817 USA.
[Ross, Thomas J.; Kurup, Pradeep K.; Salmeron, Betty J.; Rose, Emma J.; Stein, Elliot A.] Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD USA.
RP Waltz, JA (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, POB 21247, Baltimore, MD 21228 USA.
EM jwaltz@mprc.umaryland.edu
RI Ross, Thomas/B-7469-2008; Rose, Emma/A-9960-2010; Salmeron, Betty
Jo/M-1793-2016
OI Ross, Thomas/0000-0002-7745-3572; Rose, Emma/0000-0001-5365-4794;
Salmeron, Betty Jo/0000-0003-1699-9333
FU National Institutes of Mental Health [1 K12 RR023250-01, P30
MH068580-01, 1 R24 MH72647-01A1]; National Institute on Drug Abuse
FX This research was made possible by Grant Nos. 1 K12 RR023250-01, P30
MH068580-01, and 1 R24 MH72647-01A1 from the National Institutes of
Mental Health and the Intramural Research Program of the National
Institute on Drug Abuse. Sharon August and Kimberly Warren assisted with
screening and neuropsychological assessments. These data were presented,
in part, at the 38th annual meeting of the Society for Neuroscience, in
Washington, DC.; James M Gold receives royalty payments from sales of
the BACS (Brief Assessment of Cognition in Schizophrenia) battery (Keefe
et al, 2004). He has had consulting relationships with Merck
Pharmaceuticals, AstraZeneca Pharmaceuticals, Solvay Pharmaceuticals,
and GlaxoSmithKline. None of these relationships represent a conflict of
interest, regarding this work. All other authors declare that, except
for income received from their primary employer, no financial support or
compensation has been received from any individual or corporate entity
over the past 3 years for research or professional service and there are
no personal financial holdings that could be perceived as constituting a
potential conflict of interest.
NR 61
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U1 3
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD NOV
PY 2010
VL 35
IS 12
BP 2427
EP 2439
DI 10.1038/npp.2010.126
PG 13
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 664LA
UT WOS:000282960200012
PM 20720534
ER
PT J
AU Furey, ML
Khanna, A
Hoffman, EM
Drevets, WC
AF Furey, Maura L.
Khanna, Ashish
Hoffman, Elana M.
Drevets, Wayne C.
TI Scopolamine Produces Larger Antidepressant and Antianxiety Effects in
Women Than in Men
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE depression; gender; antidepressant; antimuscarinic; anticholinergic
ID LOW-DOSE PHYSOSTIGMINE; REM INDUCTION TEST; GENDER-DIFFERENCES;
AFFECTIVE-DISORDERS; MAJOR DEPRESSIVES; RECEPTOR-BINDING;
SEX-DIFFERENCES; RATING-SCALE; CHRM2 GENE; ACETYLCHOLINE
AB Some antidepressant agents generate differential benefit based on gender. Blocking cholinergic muscarinic receptors using scopolamine produces robust and rapid antidepressant effects in males and females combined. This study evaluated if males and females differ in the antidepressant response magnitude following scopolamine administration. A total of 52 male and female outpatients meeting criteria for recurrent major depressive or bipolar disorder participated in a double-blind, randomized, placebo-controlled, crossover clinical trial involving seven i.v. infusions of placebo or scopolamine (4 mu g/kg). Following a single-blind placebo lead-in, participants entered either a placebo-block/scopolamine-block or a scopolamine-block/placebo-block sequence. Each block included three sessions. Clinical ratings were acquired before each infusion and included the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A). A treatment group x block interaction (F = 21.0, p<0.001) was observed in MADRS scores across gender, and the reduction was significant by the evaluation following the first scopolamine administration (F = 8.4, p = 0.006). The treatment group x block interaction was also significant in males (F = 3.8, p = 0.043) and females (F = 35.6, p<0.001) separately. A block x gender interaction (F = 7.4, p = 0.009) indicated that the response magnitude was larger in women. The treatment x block interaction was significant for the HAM-A across gender (F = 12.0, p<0.001), and was significant for females (F = 24.9, p<0.001) but not for males (F = 1.3, p = 0.30). When comparing the baseline block to study end, the block x gender interaction (F = 12.6, p = 0.001) showed that the antianxiety response was greater in women. Men and women show a rapid antidepressant response following scopolamine, but the magnitude of response is larger in women than in men. Neuropsychopharmacology (2010) 35, 2479-2488; doi: 10.1038/npp.2010.131; published online 25 August 2010
C1 [Furey, Maura L.; Hoffman, Elana M.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Khanna, Ashish] American Univ, Caribbean Sch Med, Coral Gables, FL USA.
[Drevets, Wayne C.] Laureate Inst Brain Res, Tulsa, OK USA.
RP Furey, ML (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 15K N Dr,Bldg 15K,Room 115B, Bethesda, MD 20892 USA.
EM mfurey@mail.nih.gov
RI Furey, Maura/H-5273-2013
FU NIH; NIMH-DIRP
FX We thank Mark Opal and Summer Peck for technical support, Michele
Drevets and Joan Williams for patient recruitment and evaluation, David
Luckenbaugh for statistical advice, and Paul Carlson, Alan Mallinger,
Andy Speer, Carlos Zarate, Meena Vythilingam, and the 5SW Day Hospital
nursing staff for medical support. This research was supported by the
NIH NIMH-DIRP.
NR 55
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U1 2
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD NOV
PY 2010
VL 35
IS 12
BP 2479
EP 2488
DI 10.1038/npp.2010.131
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 664LA
UT WOS:000282960200016
PM 20736989
ER
PT J
AU Ikemoto, S
AF Ikemoto, Satoshi
TI Brain reward circuitry beyond the mesolimbic dopamine system: A
neurobiological theory
SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
LA English
DT Review
DE Motivation; Affective arousal; Conditioned place preference; Module;
Median and dorsal raphe nuclei; GABA; Glutamate; Seeking; Depression;
Mania; Addiction
ID VENTRAL TEGMENTAL AREA; MEDIAN RAPHE NUCLEUS; INTRACRANIAL
SELF-STIMULATION; PHASEOLUS-VULGARIS-LEUKOAGGLUTININ; HIPPOCAMPAL
THETA-RHYTHM; PHA-L ANALYSIS; CONDITIONED PLACE PREFERENCE; LATERAL
HYPOTHALAMIC AREA; FOS-LIKE IMMUNOREACTIVITY; WHEAT-GERM-AGGLUTININ
AB Reductionist attempts to dissect complex mechanisms into simpler elements are necessary, but not sufficient for understanding how biological properties like reward emerge out of neuronal activity. Recent studies on intracranial self-administration of neurochemicals (drugs) found that rats learn to self-administer various drugs into the mesolimbic dopamine structures the posterior ventral tegmental area, medial shell nucleus accumbens and medial olfactory tubercle. In addition, studies found roles of non-dopaminergic mechanisms of the supramammillary, rostromedial tegmental and midbrain raphe nuclei in reward.
To explain intracranial self-administration and related effects of various drug manipulations, I outlined a neurobiological theory claiming that there is an intrinsic central process that coordinates various selective functions (including perceptual, visceral, and reinforcement processes) into a global function of approach. Further, this coordinating process for approach arises from interactions between brain structures including those structures mentioned above and their closely linked regions: the medial prefrontal cortex, septal area, ventral pallidum, bed nucleus of stria terminalis, preoptic area, lateral hypothalamic areas, lateral habenula, periaqueductal gray, laterodorsal tegmental nucleus and parabrachical area. Published by Elsevier Ltd.
C1 NIDA, Behav Neurosci Res Branch, NIH, US Dept HHS, Baltimore, MD 21224 USA.
RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Res Branch, NIH, US Dept HHS, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM Satoshi.Ikemoto@nih.gov
OI Ikemoto, Satoshi/0000-0002-0732-7386
FU National Institute on Drug Abuse
FX The present work was supported by the Intramural Research Program of the
National Institute on Drug Abuse. I would like to thank Dr. Emily
Wentzell for editorial assistance and my group's members - Fiori
Vollrath-Smith, Sierra Webb, Drs. Tom Jhou and Mingliang Tang - for
comments on an earlier version of the manuscript. Tom also helped me on
the RMTg section.
NR 278
TC 135
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U1 5
U2 57
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0149-7634
J9 NEUROSCI BIOBEHAV R
JI Neurosci. Biobehav. Rev.
PD NOV
PY 2010
VL 35
IS 2
SI SI
BP 129
EP 150
DI 10.1016/j.neubiorev.2010.02.001
PG 22
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 681UG
UT WOS:000284344900002
PM 20149820
ER
PT J
AU Ghitza, UE
Zhai, HF
Wu, P
Airavaara, M
Shaham, Y
Lu, L
AF Ghitza, Udi E.
Zhai, Haifeng
Wu, Ping
Airavaara, Mikko
Shaham, Yavin
Lu, Lin
TI Role of BDNF and GDNF in drug reward and relapse: A review
SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
LA English
DT Review
DE Addiction; Alcohol; Cocaine; Craving; Drug self-administration;
Extinction; Heroin; Incubation; Mesocorticolimbic dopamine system;
Neuroadaptations; Relapse; Reinstatement
ID MESOLIMBIC DOPAMINE SYSTEM; VENTRAL TEGMENTAL AREA; CONDITIONED-PLACE
PREFERENCE; CORTICOTROPIN-RELEASING-FACTOR; COCAINE-SEEKING BEHAVIOR;
NEUROTROPHIC FACTOR EXPRESSION; PRIMING-INDUCED REINSTATEMENT;
LONG-LASTING POTENTIATION; STRESS-INDUCED RELAPSE; NECROSIS-FACTOR-ALPHA
AB Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) are neurotrophic factors that are critical for the growth, survival, and differentiation of developing neurons. These neurotrophic factors also play important roles in the survival and function of adult neurons, learning and memory, and synaptic plasticity. Since the mid-1990s, investigators have studied the role of BDNF and GDNF in the behavioral effects of abused drugs and in the neuroadaptations induced by repeated exposure to drugs in the mesocorticolimbic dopamine system. Here, we review rodent studies on the role of BDNF and GDNF in drug reward, as assessed in the drug self-administration and the conditioned place preference procedures, and in drug relapse, as assessed in extinction and reinstatement procedures. Our main conclusion is that whether BDNF or GDNF would facilitate or inhibit drug-taking behaviors depends on the drug type, the brain site, the addiction phase (initiation, maintenance, or abstinence/relapse), and the time interval between site-specific BDNF or GDNF injections and the reward- and relapse-related behavioral assessments. Published by Elsevier Ltd.
C1 [Airavaara, Mikko; Shaham, Yavin] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Zhai, Haifeng; Wu, Ping; Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Beijing 100871, Peoples R China.
[Ghitza, Udi E.] NIDA, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA.
RP Shaham, Y (reprint author), NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
EM yshaham@intra.nida.nih.gov; linlu@bjmu.edu.cn
RI shaham, yavin/G-1306-2014;
OI Airavaara, Mikko/0000-0002-2026-1609
FU National Basic Research Program of China [2009CB522004]; Natural Science
Foundation of China [30725016]; NIDA, NIH
FX This work was supported by the National Basic Research Program of China
(2009CB522004) and the Natural Science Foundation of China (No:
30725016) and the Intramural Program of NIDA, NIH.
NR 177
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U1 1
U2 26
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0149-7634
J9 NEUROSCI BIOBEHAV R
JI Neurosci. Biobehav. Rev.
PD NOV
PY 2010
VL 35
IS 2
SI SI
BP 157
EP 171
DI 10.1016/j.neubiorev.2009.11.009
PG 15
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 681UG
UT WOS:000284344900004
PM 19914287
ER
PT J
AU Heilig, M
Thorsell, A
Sommer, WH
Hansson, AC
Ramchandani, VA
George, DT
Hommer, D
Barr, CS
AF Heilig, Markus
Thorsell, Annika
Sommer, Wolfgang H.
Hansson, Anita C.
Ramchandani, Vijay A.
George, David T.
Hommer, Daniel
Barr, Christina S.
TI Translating the neuroscience of alcoholism into clinical treatments:
From blocking the buzz to curing the blues
SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
LA English
DT Review
DE Alcoholism; Reward; Opioids; Pharmacogenetics; Stress; Anxiety;
Amygdala; Corticotropin-releasing hormone; Substance P; Neurokinin
ID CORTICOTROPIN-RELEASING-FACTOR; OPIOID RECEPTOR GENE; ANXIETY-LIKE
BEHAVIOR; SINGLE-NUCLEOTIDE POLYMORPHISM; INTERMITTENT ETHANOL EXPOSURE;
WITHDRAWAL-INDUCED ANXIETY; SUBSTANCE-P RECEPTORS; NUCLEUS-ACCUMBENS;
DOPAMINE RELEASE; DEPENDENT RATS
AB Understanding the pathophysiology of addictive disorders is critical for development of new treatments. A major focus of addiction research has for a long time been on systems that mediate acute positively reinforcing effects of addictive drugs, most prominently the mesolimbic dopaminergic (DA) system and its connections. This research line has been successful in shedding light on the physiology of both natural and drug reward, but has not led to therapeutic breakthroughs. The role of classical reward systems is perhaps least clear in alcohol addiction. Here, recent work is summarized that points to some clinically important conclusions. First, important pharmacogenetic differences exist with regard to positively reinforcing effects of alcohol and the ability of this drug to activate classical reward pathways. This offers an opportunity for personalized treatment approaches in alcoholism. Second, brain stress and fear systems become pathologically activated in later stages of alcoholism and their activation is a major influence in escalation of alcohol intake, sensitization of stress responses, and susceptibility to relapse. These findings offer a new category of treatment mechanisms. Corticotropin-releasing hormone (CRH) signaling through CRH1 receptors is a major candidate target in this category, but recent data indicate that antagonists for substance P (SP) neurokinin 1 (NK1) receptors may have a similar potential. Published by Elsevier Ltd.
C1 [Heilig, Markus; Thorsell, Annika; Sommer, Wolfgang H.; Hansson, Anita C.; Ramchandani, Vijay A.; George, David T.; Hommer, Daniel; Barr, Christina S.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Sommer, Wolfgang H.; Hansson, Anita C.] Cent Inst Mental Hlth, Dept Psychopharmacol, D-6800 Mannheim, Germany.
RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,10-1E-5334, Bethesda, MD 20892 USA.
EM markus.heilig@mail.nih.gov
OI Heilig, Markus/0000-0003-2706-2482; Sommer,
Wolfgang/0000-0002-5903-6521; Thorsell, Annika/0000-0003-3535-3845
FU NIAAA
FX The research from the NIAAA Laboratory of Clinical and Translational
Studies reviewed here is supported by intramural NIAAA funding.
NR 143
TC 61
Z9 62
U1 3
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0149-7634
J9 NEUROSCI BIOBEHAV R
JI Neurosci. Biobehav. Rev.
PD NOV
PY 2010
VL 35
IS 2
SI SI
BP 334
EP 344
DI 10.1016/j.neubiorev.2009.11.018
PG 11
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 681UG
UT WOS:000284344900015
PM 19941895
ER
PT J
AU Church, MW
Wapner, RJ
Mele, LM
Johnson, F
Dudley, DJ
Spong, CY
Peaceman, AM
Moawad, AH
O'Sullivan, MJ
Miodovnik, M
AF Church, Michael W.
Wapner, Ronald J.
Mele, Lisa M.
Johnson, Francee
Dudley, Donald J.
Spong, Catherine Y.
Peaceman, Alan M.
Moawad, Atef H.
O'Sullivan, Mary J.
Miodovnik, Menachem
CA Eunice Kennedy Shriver Natl Inst C
TI Repeated courses of antenatal corticosteroids: Are there effects on the
infant's auditory brainstem responses?
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Article
DE Antenatal corticosteroid (AC); Auditory brainstem response (ABR);
Betamethasone; Brain development; Hearing; Premature birth
ID PRENATAL GLUCOCORTICOIDS; MATERNAL INJECTIONS; PREMATURE-INFANTS;
PRETERM DELIVERY; HEARING-LOSS; OUTCOMES; GROWTH; SHEEP; MATURATION;
SINGLE
AB Our objective was to assess the effects of repeated antenatal corticosteroid treatments on the neonatal auditory brainstem response (ABR), a sensitive measure of neonatal brain maturity and auditory function. To achieve this, we performed and blindly evaluated neonatal ABRs on a subset of infants delivering within a multicenter randomized placebo-controlled clinical trial comparing single versus repeated courses of antenatal corticosteroid treatments for women at 23-31 weeks gestation who remained at increased risk for preterm birth. The women were randomly assigned to either the single or the repeated antenatal corticosteroid treatment group. Women in the repeated antenatal corticosteroid group received weekly antenatal corticosteroid treatments until 34 weeks gestation or until they reached a study-determined limited number of courses, whereas women in the single antenatal corticosteroid group received an initial course of corticosteroid followed by weekly placebo injections. We performed ABR testing on their infants prior to discharge. The latencies of waves I, III and V and the peak-to-trough amplitudes of waves I and V were compared between those in the single (n = 27) and repeated antenatal corticosteroid treatment (n = 24) groups. The majority of repeated antenatal corticosteroid infants (20 of 24) were exposed to >= 4 antenatal corticosteroid treatments. Even though gestational age was similar between our subset of single and repeated antenatal corticosteroid treatment groups, infant birth weight and length and head circumference were significantly smaller in the repeated antenatal corticosteroid group (p<0.05). Despite these differences in birth sizes, there were no significant group differences in the ABR wave latencies or amplitudes. We concluded that our repeated antenatal corticosteroid treatments, in comparison to a single treatment, did not significantly benefit or harm the neonatal ABR despite significant effects on birth size. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Church, Michael W.] Wayne State Univ, Sch Med, Detroit, MI 48201 USA.
[Wapner, Ronald J.] Drexel Univ, Coll Med, Philadelphia, PA 19103 USA.
[Mele, Lisa M.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA.
[Johnson, Francee] Ohio State Univ, Columbus, OH 43210 USA.
[Dudley, Donald J.] Univ Utah, Salt Lake City, UT 84132 USA.
[Spong, Catherine Y.] NICHHD, Bethesda, MD 20892 USA.
[Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA.
[Moawad, Atef H.] Univ Chicago, Chicago, IL 60637 USA.
[O'Sullivan, Mary J.] Univ Miami, Miami, FL 33136 USA.
[Miodovnik, Menachem] Univ Cincinnati, Cincinnati, OH 45267 USA.
RP Church, MW (reprint author), CS Mott Ctr Human Growth & Dev, 275 E Hancock, Detroit, MI 48201 USA.
EM mchurch@med.wayne.edu
OI Peaceman, Alan/0000-0002-4515-4850; Berghella,
Vincenzo/0000-0003-2854-0239
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD27917, HD27905, HD27861, HD27915, HD34122, HD34208,
HD34136, HD40512, HD36801]
FX This study was funded by grants HD27917, HD27905, HD27861, HD27915,
HD34122, HD34208, HD34136, HD40512, and HD36801 from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development. There
were no conflicts of interest to report. Other participating members of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development Maternal-Fetal Medicine Units Network are as follows:;
Drexel University; M. DiVito, A. Sciscione, V. Berghella, P. Trauffer,
M. Pollock, M. Talucci, M. Goodman; Wayne State University; Y. Sorokin,
M. Dombrowski, G. Norman, A. Millinder, C. Sudz, D. Driscoll; George
Washington University, Biostatistics Center; E. Thom, F. Galbis-Reig, A.
Das, L. Leuchtenburg, D. Johnson; Ohio State University; J. Iams, M.
Landon, S. Meadows, P. Shubert; University of Utah; M. Varner, K.
Anderson, A. Guzman, A. Crowley, M. Fuller, S. Bohning
NR 41
TC 7
Z9 8
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD NOV-DEC
PY 2010
VL 32
IS 6
BP 605
EP 610
DI 10.1016/j.ntt.2010.05.006
PG 6
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 692BY
UT WOS:000285127700004
PM 20553856
ER
PT J
AU Kubben, N
Voncken, JW
Misteli, T
AF Kubben, Nard
Voncken, Jan Willem
Misteli, Tom
TI Mapping of protein- and chromatin-interactions at the nuclear lamina
SO NUCLEUS-AUSTIN
LA English
DT Review
DE laminopathies; lamin A; protein interactions; chromatin interactions;
mass spectrometry; oneSTrEP; immunoprecipitation; affinity purification;
chromatin immunoprecipitation; DamID
AB The nuclear envelope and the lamina define the nuclear periphery and are implicated in many nuclear processes including chromatin organization, transcription and DNA replication. Mutations in lamin A proteins, major components of the lamina, interfere with these functions and cause a set of phenotypically diverse diseases referred to as laminopathies. The phenotypic diversity of laminopathies is thought to be the result of alterations in specific protein-and chromatin interactions due to lamin A mutations. Systematic identification of lamin A-protein and -chromatin interactions will be critical to uncover the molecular etiology of laminopathies. Here we summarize and critically discuss recent technology to analyze lamina-protein and-chromatin interactions.
C1 [Kubben, Nard] Maastricht Univ, Med Ctr, Ctr Heart Failure Res, Maastricht, Netherlands.
[Kubben, Nard; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
[Voncken, Jan Willem] Maastricht Univ, Med Ctr, Dept Mol Genet, Maastricht, Netherlands.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM Mistelit@mail.nih.gov
FU Intramural NIH HHS [ZIA BC010309-11]
NR 78
TC 14
Z9 14
U1 1
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1949-1034
J9 NUCLEUS-AUSTIN
JI Nucleus-Austin
PD NOV-DEC
PY 2010
VL 1
IS 6
BP 460
EP 471
DI 10.4161/nucl.1.6.13513
PG 12
WC Cell Biology
SC Cell Biology
GA V28GG
UT WOS:000208668700002
PM 21327087
ER
PT J
AU Rafikova, ER
Melikov, K
Chernomordik, LV
AF Rafikova, Elvira R.
Melikov, Kamran
Chernomordik, Leonid V.
TI Cytosol-dependent membrane fusion in ER, nuclear envelope and nuclear
pore assembly Biological implications
SO NUCLEUS-AUSTIN
LA English
DT Article
DE nuclear envelope; endoplasmic reticulum; nuclear pore complex; membrane
fusion; Xenopus egg extract; liposome
AB Endoplasmic reticulum and nuclear envelope rearrangements after mitosis are often studied in the reconstitution system based on Xenopus egg extract. In our recent work we partially replaced the membrane vesicles in the reconstitution mix with protein-free liposomes to explore the relative contributions of cytosolic and transmembrane proteins. Here we discuss our finding that cytosolic proteins mediate fusion between membranes lacking functional transmembrane proteins and the role of membrane fusion in endoplasmic reticulum and nuclear envelope reorganization. Cytosol-dependent liposome fusion has allowed us to restore, without adding transmembrane nucleoporins, functionality of nuclear pores, their spatial distribution and chromatin decondensation in nuclei formed at insufficient amounts of membrane material and characterized by only partial decondensation of chromatin and lack of nuclear transport. Both the mechanisms and the biological implications of the discovered coupling between spatial distribution of nuclear pores, chromatin decondensation and nuclear transport are discussed.
C1 [Rafikova, Elvira R.] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA.
[Melikov, Kamran; Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD USA.
RP Chernomordik, LV (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
FX We thank Sergei Pourmal for critical reading of the manuscript. 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 (L.V.C.).
NR 41
TC 2
Z9 2
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1949-1034
J9 NUCLEUS-AUSTIN
JI Nucleus-Austin
PD NOV-DEC
PY 2010
VL 1
IS 6
BP 487
EP 491
DI 10.4161/nucl.1.6.13514
PG 5
WC Cell Biology
SC Cell Biology
GA V28GG
UT WOS:000208668700006
PM 21327091
ER
PT J
AU Kubben, N
Voncken, JW
Demmers, J
Calis, C
van Almen, G
Pinto, Y
Misteli, T
AF Kubben, Nard
Voncken, Jan Willem
Demmers, Jeroen
Calis, Chantal
van Almen, Geert
Pinto, Yigal
Misteli, Tom
TI Identification of differential protein interactors of lamin A and
progerin
SO NUCLEUS-AUSTIN
LA English
DT Article
DE laminopathies; lamin A; progerin; Hutchinson-Gilford progeria syndrome;
protein interactions; mass spectrometry; oneSTrEP pull-down
AB The nuclear lamina is an interconnected meshwork of intermediate filament proteins underlying the nuclear envelope. The lamina is an important regulator of nuclear structural integrity as well as nuclear processes, including transcription, DNA replication and chromatin remodeling. The major components of the lamina are A-and B-type lamins. Mutations in lamins impair lamina functions and cause a set of highly tissue-specific diseases collectively referred to as laminopathies. The phenotypic diversity amongst laminopathies is hypothesized to be caused by mutations affecting specific protein interactions, possibly in a tissue-specific manner. Current technologies to identify interaction partners of lamin A and its mutants are hampered by the insoluble nature of lamina components. To overcome the limitations of current technologies, we developed and applied a novel, unbiased approach to identify lamin A-interacting proteins. This approach involves expression of the high-affinity OneSTrEP-tag, precipitation of lamin-protein complexes after reversible protein cross-linking and subsequent protein identification by mass spectrometry. We used this approach to identify in mouse embryonic fibroblasts and cardiac myocyte NklTAg cell lines proteins that interact with lamin A and its mutant isoform progerin, which causes the premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS). We identified a total of 313 lamina-interacting proteins, including several novel lamin A interactors, and we characterize a set of 35 proteins which preferentially interact with lamin A or progerin.
C1 [Kubben, Nard; van Almen, Geert] Maastricht Univ, Cardiovasc Res Inst Maastricht, Ctr Heart Failure Res, Maastricht, Netherlands.
[Voncken, Jan Willem] Maastricht Univ, Dept Mol Genet, GROW Sch Oncol & Dev Biol, Maastricht, Netherlands.
[Calis, Chantal] Maastricht Univ, Dept Clin Genet, Maastricht, Netherlands.
[Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
[Demmers, Jeroen] Erasmus MC, Prote Ctr, Rotterdam, Netherlands.
[Pinto, Yigal] Med Ctr, Heart Failure Res Ctr, Amsterdam, Netherlands.
RP Pinto, Y (reprint author), Med Ctr, Heart Failure Res Ctr, Amsterdam, Netherlands.
EM Mistelit@mail.nih.gov
OI Demmers, Jeroen/0000-0002-8757-9611
FU National Institutes of Health (NIH), NCI, Center for Cancer Research;
Dutch Heart Foundation; ZonMW; EU-KP7
FX We thank Gunter Blobel, Brian Burke, Thomas Schwartz, Larry Gerace and
Peter Lloyd Jones for kindly sharing expression plasmids. Thijs Konsten
is thanked for his help in optimization of the OST pull-down assay. This
research was supported in part by the Intramural Research Program of the
National Institutes of Health (NIH), NCI, Center for Cancer Research,
grants from the Dutch Heart Foundation, ZonMW and the EU-KP7 grant
'Inheritance'.
NR 72
TC 33
Z9 34
U1 0
U2 5
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1949-1034
J9 NUCLEUS-AUSTIN
JI Nucleus-Austin
PD NOV-DEC
PY 2010
VL 1
IS 6
BP 513
EP 525
DI 10.4161/nucl.1.6.13512
PG 13
WC Cell Biology
SC Cell Biology
GA V28GG
UT WOS:000208668700010
PM 21327095
ER
PT J
AU Gardner, D
AF Gardner, Deborah
TI For Health Care Reform to Survive We Must Stick to the Facts
SO NURSING ECONOMICS
LA English
DT Editorial Material
C1 NIH, Off Org Dev, Ctr Clin, Bethesda, MD 20892 USA.
RP Gardner, D (reprint author), NIH, Off Org Dev, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
NR 9
TC 0
Z9 0
U1 0
U2 0
PU JANNETTI PUBLICATIONS, INC
PI PITMAN
PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA
SN 0746-1739
J9 NURS ECON
JI Nurs. Econ.
PD NOV-DEC
PY 2010
VL 28
IS 6
BP 401
EP +
PG 3
WC Nursing
SC Nursing
GA 704HH
UT WOS:000286041200006
PM 21291061
ER
PT J
AU Mitchell, SA
Fisher, CA
Hastings, CE
Silverman, LB
Wallen, GR
AF Mitchell, Sandra A.
Fisher, Cheryl A.
Hastings, Clare E.
Silverman, Leanne B.
Wallen, Gwenyth R.
TI A thematic analysis of theoretical models for translational science in
nursing: Mapping the field
SO NURSING OUTLOOK
LA English
DT Article
ID FOCUSED KNOWLEDGE TRANSLATION; CLINICAL-RESEARCH ENTERPRISE; RESEARCH
INITIATIVE QUERI; HEALTH-CARE-SYSTEMS; TOBACCO-DEPENDENCE;
SMOKING-CESSATION; PUBLIC-HEALTH; CANCER CONTROL; IMPLEMENTATION
FIDELITY; DISSEMINATION RESEARCH
AB The quantity and diversity of conceptual models in translational science may complicate rather than advance the use of theory. This paper offers a comparative thematic analysis of the models available to inform knowledge development, transfer, and utilization. Literature searches identified 47 models for knowledge translation. Four thematic areas emerged: (1) evidence-based practice and knowledge transformation processes, (2) strategic change to promote adoption of new knowledge, (3) knowledge exchange and synthesis for application and inquiry, and (4) designing and interpreting dissemination research. This analysis distinguishes the contributions made by leaders and researchers at each phase in the process of discovery, development, and service delivery. It also informs the selection of models to guide activities in knowledge translation. A flexible theoretical stance is essential to simultaneously develop new knowledge and accelerate the translation of that knowledge into practice behaviors and programs of care that support optimal patient outcomes.
C1 [Mitchell, Sandra A.] NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, Appl Res Program, Bethesda, MD 20892 USA.
[Mitchell, Sandra A.; Fisher, Cheryl A.; Hastings, Clare E.; Silverman, Leanne B.; Wallen, Gwenyth R.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Mitchell, SA (reprint author), NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, Appl Res Program, 6130 Execut Blvd,MSC 7344,EPN4020, Bethesda, MD 20892 USA.
EM mitchlis@mail.nih.gov
RI lyp, maggie/G-1471-2011
FU National Institutes of Health, Clinical Center, Nursing Research and
Translational Science, Nursing and Patient Care Services
FX We gratefully acknowledge Josanne Revoir, RN, MS, National Institutes of
Health Clinical Center for her assistance with development of figures.
This work was supported by the National Institutes of Health, Clinical
Center, Nursing Research and Translational Science, Nursing and Patient
Care Services.
NR 164
TC 27
Z9 28
U1 7
U2 42
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0029-6554
J9 NURS OUTLOOK
JI Nurs. Outlook
PD NOV-DEC
PY 2010
VL 58
IS 6
SI SI
BP 287
EP 300
DI 10.1016/j.outlook.2010.07.001
PG 14
WC Nursing
SC Nursing
GA 686XW
UT WOS:000284734100004
PM 21074646
ER
PT J
AU Bradley, DP
Johnson, LA
Zhang, ZM
Subar, AF
Troiano, RP
Schatzkin, A
Schoeller, DA
AF Bradley, David P.
Johnson, Lindsey A.
Zhang, Zhumin
Subar, Amy F.
Troiano, Richard P.
Schatzkin, Arthur
Schoeller, Dale A.
TI Effect of smoking status on total energy expenditure
SO NUTRITION & METABOLISM
LA English
DT Article
ID DOUBLY LABELED WATER; CIGARETTE-SMOKING; WEIGHT-GAIN; BODY-WEIGHT;
PHYSICAL-ACTIVITY; DIETARY-INTAKE; CALORIC-INTAKE; METABOLIC-RATE;
UNITED-STATES; SOCIAL-CLASS
AB Individuals who smoke generally have a lower body mass index (BMI) than nonsmokers. The relative roles of energy expenditure and energy intake in maintaining the lower BMI, however, remain controversial. We tested the hypothesis that current smokers have higher total energy expenditure than never smokers in 308 adults aged 40-69 years old of which 47 were current smokers. Energy expenditure was measured by doubly labeled water during a two week period in which the subjects lived at home and performed their normal activities. Smoking status was determined by questionnaire. There were no significant differences in mean BMI (mean +/- SD) between smokers and never smokers for either males (27.8+5.1 kg/m(2) vs. 27.5+4.0 kg/m(2)) or females (26.5+5.3 kg/m(2) vs. 28.1+6.6 kg/m(2)), although the difference in females was of similar magnitude to previous reports. Similarly, total energy expenditure of male smokers (3069+764 kcal/d) was not significantly different from that of never smokers (2854+468 kcal/d), and that of female smokers (2266+387 kcal/d) was not different from that of never smokers (2330+415 kcal/d). These findings did not change after adjustment for age, fat-free mass and self-reported physical activity. Using doubly labeled water, we found no evidence of increased energy expenditure among smokers, however, it should be noted that BMI differences in this cohort also did not differ by smoking status.
C1 [Johnson, Lindsey A.; Zhang, Zhumin; Schoeller, Dale A.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA.
[Bradley, David P.] Univ Wisconsin, Dept Endocrinol, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Johnson, Lindsey A.] Univ Wisconsin, Catering & Conf Serv, Madison, WI 53706 USA.
[Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
[Subar, Amy F.; Troiano, Richard P.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
RP Schoeller, DA (reprint author), Univ Wisconsin, Dept Nutr Sci, 1415 Linden Dr, Madison, WI 53706 USA.
EM dschoell@nutrisci.wisc.edu
OI Troiano, Richard/0000-0002-6807-989X
NR 43
TC 6
Z9 6
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-7075
J9 NUTR METAB
JI Nutr. Metab.
PD NOV 1
PY 2010
VL 7
AR 81
DI 10.1186/1743-7075-7-81
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 683MQ
UT WOS:000284480300001
PM 21040542
ER
PT J
AU Preis, SR
Massaro, JM
Robins, SJ
Hoffmann, U
Vasan, RS
Irlbeck, T
Meigs, JB
Sutherland, P
D'Agostino, RB
O'Donnell, CJ
Fox, CS
AF Preis, Sarah R.
Massaro, Joseph M.
Robins, Sander J.
Hoffmann, Udo
Vasan, Ramachandran S.
Irlbeck, Thomas
Meigs, James B.
Sutherland, Patrice
D'Agostino, Ralph B., Sr.
O'Donnell, Christopher J.
Fox, Caroline S.
TI Abdominal Subcutaneous and Visceral Adipose Tissue and Insulin
Resistance in the Framingham Heart Study
SO OBESITY
LA English
DT Article
ID FATTY-ACID-METABOLISM; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN;
PREMENOPAUSAL WOMEN; MUSCLE COMPOSITION; MEASUREMENT SITE; RISK-FACTORS;
OBESE MEN; SENSITIVITY; GLUCOSE
AB Insulin resistance is associated with central obesity and an increased risk of cardiovascular disease. Our objective is to examine the association between abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) and insulin resistance, to determine which fat depot is a stronger correlate of insulin resistance, and to assess whether there was an interaction between SAT, VAT, and age, sex, or BMI. Participants without diabetes from the Framingham Heart Study (FHS), who underwent multidetector computed tomography to assess SAT and VAT (n = 3,093; 48% women; mean age 50.4 years; mean BMI 27.6 kg/m(2)), were evaluated. Insulin resistance was measured using the homeostasis model and defined as HOMA(IR) >= 75th percentile. Logistic regression models, adjusted for age, sex, smoking, alcohol, menopausal status, and hormone replacement therapy use, were used to assess the association between fat measures and insulin resistance. The odds ratio (OR) for insulin resistance per standard deviation increase in SAT was 2.5 (95% confidence interval (CI): 2.2-2.7; P < 0.0001), whereas the OR for insulin resistance per standard deviation increase in VAT was 3.5 (95% CI: 3.1-3.9; P < 0.0001). Overall, VAT was a stronger correlate of insulin resistance than SAT (P < 0.0001 for SAT vs. VAT comparison). After adjustment for BMI, the OR of insulin resistance for VAT was 2.2 (95% CI: 1.9-2.5; P < 0.0001). We observed an interaction between VAT and BMI for insulin (P interaction = 0.0004), proinsulin (P interaction = 0.003), and HOMA(IR) (P interaction = 0.003), where VAT had a stronger association in obese individuals. In conclusion, SAT and VAT are both correlates of insulin resistance; however, VAT is a stronger correlate of insulin resistance than SAT.
C1 [Preis, Sarah R.; Robins, Sander J.; Vasan, Ramachandran S.; Sutherland, Patrice; D'Agostino, Ralph B., Sr.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Preis, Sarah R.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Ctr Populat Studies, NIH, Framingham, MA USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Robins, Sander J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
[Robins, Sander J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Irlbeck, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA.
[Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA.
[D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol & Metab, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
EM foxca@nhlbi.nih.gov
OI Preis, Sarah/0000-0002-9360-4166; Massaro, Joseph/0000-0002-2682-4812;
Ramachandran, Vasan/0000-0001-7357-5970
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]; NIDDK [K24 DK080140]; GlaxoSmithKline; Sanofi-Aventis;
[R01DK080739]
FX This study was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (N01-HC-25195). R. S. V. was
supported in part by R01DK080739. J.B.M. is supported by NIDDK K24
DK080140.; J.B.M. currently has research grants from GlaxoSmithKline and
Sanofi-Aventis, and has consulting agreements with Eli Lilly,
Interleukin Genetics, Kalypsys, and Outcomes Science. The other authors
declared no conflict of interest.
NR 32
TC 116
Z9 123
U1 1
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD NOV
PY 2010
VL 18
IS 11
BP 2191
EP 2198
DI 10.1038/oby.2010.59
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 671GE
UT WOS:000283487700022
PM 20339361
ER
PT J
AU Laughon, SK
Reddy, UM
Sun, LP
Zhang, J
AF Laughon, S. Katherine
Reddy, Uma M.
Sun, Liping
Zhang, Jun
TI Precursors for Late Preterm Birth in Singleton Gestations
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID NEAR-TERM INFANTS; UNITED-STATES; PREECLAMPSIA; HYPERTENSION; MORTALITY;
OUTCOMES
AB OBJECTIVE: To characterize precursors for late preterm birth in singletons and incidences of neonatal morbidities and perinatal mortality by gestational age and precursor.
METHODS: Using retrospective observational data, we compared 15,136 gestations born late preterm with 170,593 deliveries between 37 0/7 and 41 6/7 weeks. We defined the following categories of precursors for late preterm delivery: "spontaneous labor," "premature rupture of the membranes (preterm PROM)," "indicated" delivery, and "unknown." Incidences of neonatal morbidities were calculated according to category of precursor stratified by gestational age at delivery. Neonatal morbidities and mortality associated with potentially avoidable deliveries (eg, "soft" precursors or elective) were compared between late preterm births and neonates born at 37-40 weeks.
RESULTS: Late preterm birth comprised 7.8% of all births and 65.7% of preterm births. Percentages of precursors were 29.8% spontaneous labor, 32.3% preterm PROM, 31.8% "indicated" (obstetric, maternal, or fetal condition), and 6.1% unknown. Different precursors for delivery were associated with varying incidences of neonatal morbidity. One in 15 neonates delivered late preterm for "soft" or elective precursors, and neonatal morbidity and mortality were increased compared with delivery at or after 37 weeks for these same indications.
CONCLUSION: A significant number of late preterm births were potentially avoidable. Elective deliveries should be postponed until 39 weeks of gestation. (Obstet Gynecol 2010;116:1047-55)
C1 [Laughon, S. Katherine; Reddy, Uma M.; Sun, Liping; Zhang, Jun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Laughon, SK (reprint author), NICHD, Epidemiol Branch, NIH, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM laughonsk@mail.nih.gov
OI Grantz, Katherine/0000-0003-0276-8534
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health [HHSN267200603425C]
FX The data included in this article were obtained from the Consortium on
Safe Labor, which was supported by the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, through Contract No.
HHSN267200603425C.
NR 16
TC 37
Z9 42
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD NOV
PY 2010
VL 116
IS 5
BP 1047
EP 1055
DI 10.1097/AOG.0b013e3181f73f97
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 669EK
UT WOS:000283329000008
PM 20966688
ER
PT J
AU Reddy, UM
Laughon, SK
Sun, LP
Troendle, J
Willinger, M
Zhang, J
AF Reddy, Uma M.
Laughon, S. Katherine
Sun, Liping
Troendle, James
Willinger, Marian
Zhang, Jun
TI Prepregnancy Risk Factors for Antepartum Stillbirth in the United States
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID MATERNAL AGE; UNEXPLAINED STILLBIRTH; FETAL-DEATH; PREGNANCY; DELIVERY;
SMOKING; COHORT; WOMEN
AB OBJECTIVE: To identify possible prepregnancy risk factors for antepartum stillbirth and to determine whether these factors identify women at higher risk for term stillbirth.
METHODS: This retrospective cohort study of prepregnancy risk factors compared 712 singleton antepartum stillbirths with 174,097 singleton live births at or after 23 weeks of gestation. The risk of term antepartum stillbirth then was assessed in a subset of 155,629 singleton pregnancies.
RESULTS: In adjusted multivariable analyses, African-American race, Hispanic ethnicity, maternal age 35 years or older, nulliparity, prepregnancy body mass index (BMI) 30 or higher, preexisting diabetes, chronic hypertension, smoking, and alcohol use were independently associated with stillbirth. Prior cesarean delivery and history of preterm birth were associated with increased stillbirth risk in multiparous women. The risk of a term stillbirth for women who were white, 25-29 years old, normal weight, multiparous, no chronic hypertension, and no preexisting diabetes was 0.8 per 1,000. Term stillbirth risk increased with the following conditions: preexisting diabetes (3.1 per 1,000), chronic hypertension (1.7 per 1,000), African-American race (1.8 per 1,000), maternal age 35 years or older (1.3 per 1,000), BMI 30 or higher (1 per 1,000), and nulliparity (0.9 per 1,000).
CONCLUSION: There are multiple independent risk factors for antepartum stillbirth. However, the value of individual risk factors of race, parity, advanced maternal age (35-39 years old), and BMI to predict term stillbirth is poor. Our results do not support routine antenatal surveillance for any of these risk factors when present in isolation. (Obstet Gynecol 2010;116:1119-26)
C1 [Reddy, Uma M.; Laughon, S. Katherine; Sun, Liping; Troendle, James; Willinger, Marian; Zhang, Jun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Reddy, UM (reprint author), 6100 Execut Blvd,Room 4B03F, Bethesda, MD 20892 USA.
EM reddyu@mail.nih.gov
OI Grantz, Katherine/0000-0003-0276-8534
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health [HHSN267200603425C]
FX The data included in this article were obtained from the Consortium on
Safe Labor, which was supported by the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, through Contract No.
HHSN267200603425C.
NR 19
TC 46
Z9 49
U1 0
U2 2
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 NOV
PY 2010
VL 116
IS 5
BP 1119
EP 1126
DI 10.1097/AOG.0b013e3181f903f8
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 669EK
UT WOS:000283329000017
PM 20966697
ER
PT J
AU Signore, C
AF Signore, Caroline
TI No Time for Complacency: Labor Inductions, Cesarean Deliveries, and the
Definition of "Term" Reply
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Letter
C1 NICHHD, Bethesda, MD 20892 USA.
RP Signore, C (reprint author), NICHHD, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD NOV
PY 2010
VL 116
IS 5
BP 1219
EP 1219
DI 10.1097/AOG.0b013e3181f7399d
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 669EK
UT WOS:000283329000034
ER
PT J
AU Schiffman, M
Wentzensen, N
AF Schiffman, Mark
Wentzensen, Nicolas
TI From Human Papillomavirus to Cervical Cancer Reply
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Letter
C1 [Schiffman, Mark; Wentzensen, Nicolas] NCI, Rockville, MD USA.
RP Schiffman, M (reprint author), NCI, Rockville, MD USA.
NR 4
TC 0
Z9 0
U1 0
U2 2
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 NOV
PY 2010
VL 116
IS 5
BP 1221
EP 1222
DI 10.1097/AOG.0b013e3181fa7d13
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 669EK
UT WOS:000283329000039
ER
PT J
AU Peplonska, B
Stewart, P
Szeszenia-Dabrowska, N
Lissowska, J
Brinton, LA
Gromiec, JP
Brzeznicki, S
Yang, XHR
Sherman, M
Garcia-Closas, M
Blair, A
AF Peplonska, Beata
Stewart, Patricia
Szeszenia-Dabrowska, Neonila
Lissowska, Jolanta
Brinton, Louise A.
Gromiec, Jan Piotr
Brzeznicki, Slawomir
Yang, Xiaohong R.
Sherman, Mark
Garcia-Closas, Montserrat
Blair, Aaron
TI Occupational exposure to organic solvents and breast cancer in women
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID ESTROGEN-RECEPTOR; RISK-FACTORS; POPULATION; MORTALITY; CHEMICALS;
TISSUE; HYPOTHESIS; SHANGHAI; WORKERS; CYP2E1
AB Background Although studies in rodents suggest possible associations between exposure to organic solvents and breast cancer, the evidence in humans is limited.
Methods We evaluated job histories of 2383 incident breast cancer cases diagnosed during 2000-2003, and 2502 controls who participated in a large population-based case-control study in Poland. Industrial hygienists reviewed occupational histories and developed exposure metrics for total organic solvents and benzene. Unconditional logistic regression analyses estimated ORs and 95% CIs as the measure of association with breast cancer, controlling for breast cancer risk factors. Stratified analyses examined the potential modification by known breast cancer risk factors. Associations were also evaluated by oestrogen and progesterone receptor status and by other clinical characteristics of the tumours using polytomous regression analyses.
Results Women who ever worked at jobs with organic solvents exposure had a small, non-significant increase in breast cancer risk (OR=1.16; 95% CI 0.99 to 1.4). A significant association was present for oestrogen receptor- and progesterone receptor-negative tumours (OR 1.40; 95% CI 1.1 to 1.8), but there was no association with tumours with both positive receptors (OR 0.97; 95% CI 0.8 to 1.2 (p heterogeneity: 0.008)). We did not observe trends with increasing level of exposure. Known breast cancer risk factors did not modify the association between organic solvents and breast cancer risk. No association with breast cancer was found for benzene exposure (OR 1.00; 95% CI 0.8 to 1.3).
Conclusion Our study provides weak evidence for a possible association between occupational exposure to organic solvents as a class and breast cancer risk. The association might be limited to hormone receptor-negative tumours.
C1 [Peplonska, Beata; Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Dept Environm Epidemiol, PL-91348 Lodz, Poland.
[Stewart, Patricia; Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Div Canc Epidemiol & Prevent, Warsaw, Poland.
[Brinton, Louise A.; Yang, Xiaohong R.; Sherman, Mark; Garcia-Closas, Montserrat] NCI, Hormonal & Reprod Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Gromiec, Jan Piotr; Brzeznicki, Slawomir] Nofer Inst Occupat Med, Dept Chem Hazards, PL-91348 Lodz, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
RP Peplonska, B (reprint author), Nofer Inst Occupat Med, Dept Environm Epidemiol, Teresy 8 St, PL-91348 Lodz, Poland.
EM beatap@imp.lodz.pl
RI Brinton, Louise/G-7486-2015; BRZEZNICKI, SLAWOMIR/G-4762-2010;
Szeszenia-Dabrowska, Neonila/F-7190-2010; Peplonska, Beata/F-6004-2010;
Garcia-Closas, Montserrat /F-3871-2015
OI Brinton, Louise/0000-0003-3853-8562; Lissowska,
Jolanta/0000-0003-2695-5799; Garcia-Closas, Montserrat
/0000-0003-1033-2650
FU National Cancer Institute, National Institutes of Health [NCI
N01-CP-91013]
FX The study was supported by Intramural Funds of the National Cancer
Institute, National Institutes of Health (contract number: NCI
N01-CP-91013).
NR 36
TC 8
Z9 8
U1 2
U2 8
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 NOV
PY 2010
VL 67
IS 11
BP 722
EP 729
DI 10.1136/oem.2009.046557
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 667EM
UT WOS:000283175500002
PM 19819862
ER
PT J
AU Ehsanian, R
Brown, M
Lu, H
Yang, XP
Pattatheyil, A
Yan, B
Duggal, P
Chuang, R
Doondeea, J
Feller, S
Sudol, M
Chen, Z
Van Waes, C
AF Ehsanian, R.
Brown, M.
Lu, H.
Yang, X. P.
Pattatheyil, A.
Yan, B.
Duggal, P.
Chuang, R.
Doondeea, J.
Feller, S.
Sudol, M.
Chen, Z.
Van Waes, C.
TI YAP dysregulation by phosphorylation or Delta Np63-mediated gene
repression promotes proliferation, survival and migration in head and
neck cancer subsets
SO ONCOGENE
LA English
DT Article
DE YAP; p53; Delta Np63; p73; apoptosis; cancer
ID SQUAMOUS-CELL CARCINOMA; YES-ASSOCIATED PROTEIN; NF-KAPPA-B;
GROWTH-FACTOR-RECEPTOR; TUMOR-SUPPRESSOR; WW DOMAIN; PROANGIOGENIC
CYTOKINES; HIPPO PATHWAY; DNA-DAMAGE; ACTIVATION
AB Overexpression of the Yes-associated protein (YAP), and TP53 family members Delta Np63 and p73, have been independently detected in subsets of head and neck squamous cell carcinomas (HNSCCs). YAP may serve as a nuclear cofactor with Delta Np63 and p73, but the functional role of YAP and their potential relationship in HNSCCs are unknown. In this study, we show that in a subset of HNSCC lines and tumors, YAP expression is increased but localized in the cytoplasm in association with increased AKT and YAP phosphorylation, and with decreased expression of Delta Np63 and p73. In another subset, YAP expression is decreased but detectable in the nucleus in association with lower AKT and YAP phosphorylation, and with increased Delta Np63 and p73 expression. Inhibiting AKT decreased serine-127 phosphorylation and enhanced nuclear translocation of YAP. Delta Np63 bound to the YAP promoter and suppressed its expression. Transfection of a YAP-serine-127-alanine phosphoacceptor-site mutant or Delta Np63 knockdown significantly increased nuclear YAP and cell death. Conversely, YAP knockdown enhanced cell proliferation, survival, migration and cisplatin chemoresistance. Thus, YAP function as a tumor suppressor may alternatively be dysregulated by AKT phosphorylation at serine-127 and cytoplasmic sequestration, or by transcriptional repression by Delta Np63, in different subsets of HNSCC. AKT and/or Delta Np63 are potential targets for enhancing YAP-mediated apoptosis and chemosensitivity in HNSCCs. Oncogene (2010) 29, 6160-6171; doi:10.1038/onc.2010.339; published online 23 August 2010
C1 [Ehsanian, R.; Brown, M.; Lu, H.; Yang, X. P.; Pattatheyil, A.; Yan, B.; Duggal, P.; Chuang, R.; Chen, Z.; Van Waes, C.] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
[Ehsanian, R.] Howard Hughes Med Inst, Natl Inst Hlth Res Scholars Program, Bethesda, MD 20817 USA.
[Ehsanian, R.] NIH Oxford Univ Stanford Univ, Sch Med, Grad Partnership Program, NIH, Bethesda, MD USA.
[Brown, M.] NIH, NIH Pfizer Clin Res Training Program, Bethesda, MD USA.
[Doondeea, J.; Feller, S.] Univ Oxford, Weatherall Inst Mol Med, Oxford, England.
[Sudol, M.] Weis Ctr Res, Geisinger Clin, Lab Signal Transduct & Prote Profiling, Danville, PA 17822 USA.
[Sudol, M.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
RP Van Waes, C (reprint author), NIDCD, Head & Neck Surg Branch, NIH, 10-5D55,MSC 1419, Bethesda, MD 20892 USA.
EM vanwaesc@nidcd.nih.gov
FU NIDCD [Z1ADC-000073, Z1ADC-000074]; Head and Neck Cancer Charity;
Pennsylvania Department of Health
FX We thank Drs Tsutomu Oka, Maie St John and Ms Cindy Clark for their
critical review; Ning Yeh, Dr Liesl Nottingham, Dr Jay Friedman, Dr
Yansong Bian and Jonah Cohen for technical assistance; and Dr Paul
Albert for assistance with statistical analysis. This study was
supported by the NIDCD Intramural project Z1ADC-000073, Z1ADC-000074,
Head and Neck Cancer Charity Grant and the Breast Cancer Coalition Grant
from the Pennsylvania Department of Health.
NR 52
TC 30
Z9 33
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD NOV
PY 2010
VL 29
IS 46
BP 6160
EP 6171
DI 10.1038/onc.2010.339
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 681XD
UT WOS:000284356500008
PM 20729916
ER
PT J
AU Chew, EY
Kim, J
Sperduto, RD
Datiles, MB
Coleman, HR
Thompson, DJS
Milton, RC
Clayton, JA
Hubbard, LD
Danis, RP
Ferris, FL
AF Chew, Emily Y.
Kim, Jonghyeon
Sperduto, Robert D.
Datiles, Manuel B., III
Coleman, Hanna R.
Thompson, Darby J. S.
Milton, Roy C.
Clayton, Janine A.
Hubbard, Larry D.
Danis, Ronald P.
Ferris, Frederick L., III
TI Evaluation of the Age-Related Eye Disease Study Clinical Lens Grading
System AREDS Report No. 31
SO OPHTHALMOLOGY
LA English
DT Article
ID OPACITIES CLASSIFICATION-SYSTEM; II LOCS-II; WEIGHTED KAPPA; AGREEMENT;
RELIABILITY; COEFFICIENT
AB Purpose: To examine the grading (interrater) reliability of the Age-Related Eye Disease Study (AREDS) Clinical Lens Grading System (ARLNS).
Design: Evaluation of diagnostic test or technology.
Participants: One hundred fifty volunteers (284 eyes).
Methods: Participants with lens opacities of varying severity were independently graded at the slit lamp for cataract severity by 2 examiners (retinal or anterior segment specialists) using the ARLNS, which employs 3 standard photographs of increasing severity for classifying each of the 3 major types of opacity. Lens photographs were taken and graded at a reading center using the more detailed AREDS System for Classifying Cataracts from photographs.
Main Outcome Measures: The Pearson correlation, weighted-kappa, and limits-of-agreement statistics were used to assess the interrater agreement of the gradings.
Results: Examinations were performed on 284 lenses (150 participants). Tests of interrater reliability between pairs of clinicians showed substantial agreement between clinicians for cortical and posterior subcapsular opacities and moderate agreement for nuclear opacities. A similar pattern and strength of agreement was present when comparing scores of retinal versus anterior segment specialists. Interrater agreement between clinical and reading center gradings was not as great as inter-clinician agreement.
Conclusions: Interrater agreements were in the moderate to substantial range for the clinical assessment of lens opacities. Inherent differences in cataract classification systems that rely on slit lamp vs photographic assessments of lens opacities may explain some of the disagreement noted between slit lamp and photographic gradings. Given the interrater reliability statistics for clinicians and the simplicity of the grading procedure, ARLNS is presented for use in studies requiring a simple, inexpensive method for detecting the presence and severity of the major types of lens opacities. Financial
Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2010; 117: 2112-2119 (C) 2010 by the American Academy of Ophthalmology.
C1 [Chew, Emily Y.] EMMES Corp, AREDS Coordinating Ctr, Rockville, MD 20850 USA.
[Chew, Emily Y.; Datiles, Manuel B., III; Coleman, Hanna R.; Clayton, Janine A.; Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA.
[Hubbard, Larry D.; Danis, Ronald P.] Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI 53706 USA.
RP Chew, EY (reprint author), EMMES Corp, AREDS Coordinating Ctr, 401 N Washington St, Rockville, MD 20850 USA.
EM aredspub@emmes.com
OI Datiles, Manuel III B./0000-0003-4660-1664
FU National Eye Institute, National Institutes of Health, Department of
Health and Human Services, Bethesda, Maryland
FX Supported by contracts from the National Eye Institute, National
Institutes of Health, Department of Health and Human Services, Bethesda,
Maryland.
NR 18
TC 16
Z9 16
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2010
VL 117
IS 11
BP 2112
EP U299
DI 10.1016/j.ophtha.2010.02.033
PG 11
WC Ophthalmology
SC Ophthalmology
GA 668JI
UT WOS:000283264200012
PM 20561686
ER
PT J
AU Zhao, JL
Ellwein, LB
Cui, H
Ge, JA
Guan, HJ
Lv, JH
Ma, XZ
Yin, JL
Yin, ZQ
Yuan, YS
Liu, H
AF Zhao, Jialiang
Ellwein, Leon B.
Cui, Hao
Ge, Jian
Guan, Huaijin
Lv, Jianhua
Ma, Xianzhi
Yin, Jinglin
Yin, Zheng Qin
Yuan, Yuansheng
Liu, Hu
TI Prevalence and Outcomes of Cataract Surgery in Rural China The China
Nine-Province Survey
SO OPHTHALMOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; VISUAL-ACUITY; EYE SURVEY; SHUNYI COUNTY; DOUMEN
COUNTY; OLDER ADULTS; BLINDNESS; POPULATION; DISTRICT; VISION
AB Purpose: To investigate the prevalence and visual acuity (VA) outcomes of cataract surgery in rural populations throughout China.
Design: Population-based, cross-sectional study.
Participants: Forty-five thousand seven hundred forty-seven adults 50 years of age and older.
Methods: Geographically defined cluster sampling was used in randomly selecting a cross-section of residents from a representative rural county within each of 9 provinces in mainland China. Participants underwent VA measurements, refraction, and a slit-lamp examination at local examination sites; those with previous cataract surgery were queried as to the year and type of surgical facility. Surgical procedure and evidence of surgery complications were noted during the examination. The principal cause of visual impairment was identified for eyes with VA of 20/40 or worse.
Main Outcome Measures: Cataract surgery procedure, presenting and best-corrected distance VA, and causes of visual impairment.
Results: Of 50 395 enumerated eligible persons, 45 747 (90.8%) were examined and tested for VA. The overall prevalence of cataract surgery was 2.09%. Surgical coverage among those with VA worse than 20/200 in both eyes because of cataract was 35.7%. Unoperated cataract was associated with older age, female gender, lack of education, and geographic area (province). Among the 1174 cataract-operated eyes, 31.1% had presenting VA of 20/32 or better, 15.4% had presenting VA of 20/40 to 20/63, 30.0% had presenting VA worse than 20/63 to 20/200, and 23.5% had presenting VA worse than 20/200. With best correction, the percentages were 57.6%, 6.2%, 18.5%, and 17.7%, respectively. Posterior capsule opacification, refractive error, and retinal disorders were the main causes in cataract-operated eyes with VA worse than 20/63.
Conclusions: Two thirds of those with bilateral visual impairment or blindness because of cataract remain in need of sight-restoring surgery. Posterior capsule opacification and refractive error, both readily amenable to treatment, were common in cataract-operated eyes. Sustained government efforts to provide access to affordable modern cataract surgery with a greater emphasis on postoperative follow-up and the quality of VA outcomes are needed.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2010; 117: 2120-2128 (C) 2010 by the American Academy of Ophthalmology.
C1 [Zhao, Jialiang; Liu, Hu] Beijing Union Med Coll Hosp, Dept Ophthalmol, Beijing 100730, Peoples R China.
[Zhao, Jialiang; Liu, Hu] Chinese Acad Med Sci, Beijing 100037, Peoples R China.
[Ellwein, Leon B.] NEI, NIH, Bethesda, MD 20892 USA.
[Cui, Hao] Harbin Med Coll, Affiliated Hosp 1, Dept Ophthalmol, Harbin, Peoples R China.
[Ge, Jian] Sun Yat Sen Univ, Zhongshan Eye Ctr, Guangzhou 510275, Guangdong, Peoples R China.
[Guan, Huaijin] Nantong Univ, Affiliated Hosp, Dept Ophthalmol, Nantong, Peoples R China.
[Lv, Jianhua] Xingtai Eye Hosp, Xingtai, Hebei, Peoples R China.
[Ma, Xianzhi] Peoples Hosp Xinjiang, Dept Ophthalmol, Urumqi, Peoples R China.
[Yin, Jinglin] Peoples Hosp Jiangxi, Dept Ophthalmol, Nanchang, Peoples R China.
[Yin, Zheng Qin] Third Mil Med Univ, Southwest Hosp, Dept Ophthalmol, Chongqing, Peoples R China.
[Yuan, Yuansheng] Yunnan Med Coll, Attached Hosp 1, Dept Ophthalmol, Kunming, Peoples R China.
RP Zhao, JL (reprint author), Beijing Union Med Coll Hosp, Dept Ophthalmol, 1 Shuai Fu Yuan, Beijing 100730, Peoples R China.
EM zhaojialiang@medmail.com.cn
FU Chinese Ministry of Health, Beijing, China; World Health Organization,
Geneva, Switzerland (under National Institutes of Health [Bethesda,
Maryland] [N01-EY-2103]; Lions Clubs International Foundation, Oak
Brook, Illinois, USA
FX Supported by the Chinese Ministry of Health, Beijing, China; the World
Health Organization, Geneva, Switzerland (under National Institutes of
Health [Bethesda, Maryland] contract no.: N01-EY-2103); and the Lions
Clubs International Foundation, Oak Brook, Illinois, USA. The World
Health Organization participated in the design of the study.
NR 16
TC 35
Z9 44
U1 2
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2010
VL 117
IS 11
BP 2120
EP 2128
DI 10.1016/j.ophtha.2010.03.005
PG 9
WC Ophthalmology
SC Ophthalmology
GA 668JI
UT WOS:000283264200013
PM 20663565
ER
PT J
AU Jakubovics, NS
Kolenbrander, PE
AF Jakubovics, N. S.
Kolenbrander, P. E.
TI The road to ruin: the formation of disease-associated oral biofilms
SO ORAL DISEASES
LA English
DT Review
DE antigen I; II protein; autoinducer-2; biofilm matrix; coaggregation;
dental plaque; oral streptococcus
ID ANTIGEN-I/II FAMILY; AGGREGATIBACTER ACTINOBACILLUS
ACTINOMYCETEMCOMITANS; DENTAL PLAQUE BACTERIA; STREPTOCOCCUS-MUTANS;
PORPHYROMONAS-GINGIVALIS; FUSOBACTERIUM-NUCLEATUM;
ACTINOMYCES-NAESLUNDII; GENE-EXPRESSION; CELL-SURFACE;
VEILLONELLA-ATYPICA
AB The colonization of oral surfaces by micro-organisms occurs in a characteristic sequence of stages, each of which is potentially amenable to external intervention. The process begins with the adhesion of bacteria to host receptors on epithelial cells or in the salivary pellicle covering tooth surfaces. Interbacterial cell-cell binding interactions facilitate the attachment of new species and increase the diversity of the adherent microbial population. Microbial growth in oral biofilms is influenced by the exchange of chemical signals, metabolites and toxic products between neighbouring cells. Bacterial cells on tooth surfaces (dental plaque) produce extracellular polymers such as complex carbohydrates and nucleic acids. These large molecules form a protective matrix that contributes to the development of dental caries and, possibly, to periodontitis. The identification of key microbial factors underlying each step in the formation of oral biofilms will provide new opportunities for preventative or therapeutic measures aimed at controlling oral infectious diseases.
C1 [Jakubovics, N. S.] Newcastle Univ, Sch Dent Sci, Newcastle Upon Tyne NE2 4BW, Tyne & Wear, England.
[Kolenbrander, P. E.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Jakubovics, NS (reprint author), Newcastle Univ, Sch Dent Sci, Newcastle Upon Tyne NE2 4BW, Tyne & Wear, England.
EM nick.jakubovics@ncl.ac.uk
OI Jakubovics, Nicholas/0000-0001-6667-0515
NR 80
TC 59
Z9 60
U1 3
U2 37
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1354-523X
J9 ORAL DIS
JI Oral Dis.
PD NOV
PY 2010
VL 16
IS 8
BP 729
EP 739
DI 10.1111/j.1601-0825.2010.01701.x
PG 11
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 666EE
UT WOS:000283094500003
PM 20646235
ER
PT J
AU Vardanyan, M
Melemedjian, OK
Price, TJ
Ossipov, MH
Lai, J
Roberts, E
Boos, TL
Deschamps, JR
Jacobson, AE
Rice, KC
Porreca, F
AF Vardanyan, Marina
Melemedjian, Ohannes K.
Price, Theodore J.
Ossipov, Michael H.
Lai, Josephine
Roberts, Ed
Boos, Terrence L.
Deschamps, Jeffrey R.
Jacobson, Arthur E.
Rice, Kenner C.
Porreca, Frank
TI Reversal of pancreatitis-induced pain by an orally available, small
molecule interleukin-6 receptor antagonist
SO PAIN
LA English
DT Article
DE Pancreatitis; Pain; Mechanisms; Interleukin-6
ID PERIPHERAL-NERVE INJURY; RHEUMATOID-ARTHRITIS; CAPSAICIN RECEPTOR;
NEUROPATHIC PAIN; DOUBLE-BLIND; CHAN SU; IL-6; RATS; NEURONS; CANCER
AB Pancreatic pain resulting from chronic inflammation of the pancreas is often intractable and clinically difficult to manage with available analgesics reflecting the need for more effective therapies. The mechanisms underlying pancreatitis pain are not well understood. Here, the possibility that interleukin-6 (IL-6) may promote pancreatitis pain was investigated with TB-2-081 (3-O-formyl-20R,21-epoxyresibufogenin, EBRF), a small molecule IL-6 receptor antagonist that was semi-synthetically derived from natural sources. The potential activity and mechanism of TB-2-081 were investigated following the induction of persistent pancreatitis using dibutyltin dichloride (DBTC) in rats. TB-2-081 displaces the binding of IL-6 to the human recombinant soluble IL-6 receptor with apparent high affinity and inhibits IL-6 mediated cell growth. Systemic or oral, but not intrathecal, administration of TB-2-081 reversed DBTC-induced abdominal hypersensitivity in a dose-and time-dependent manner. IL-6 levels were significantly up-regulated in the dorsal root ganglia (DRG) of rats with pancreatitis on day 6 after DBTC injection. IL-6-enhanced capsaicin-evoked release of calcitonin gene-related peptide from cultured DRG neurons was blocked by TB-2-081. Our data demonstrate that TB-2-081 acts as a systemically available and orally active small molecule IL-6 receptor antagonist. TB-2-081 effectively reduces pancreatitis-induced pain through peripheral mechanisms that are likely due to (a) increased expression of IL-6 in the DRG and (b) IL-6-mediated sensitization of nociceptive neurons. The activity of TB-2-081 implicates an important role for IL-6 in sustaining pancreatitis pain. Strategies targeting IL-6 actions through small molecule antagonists may offer novel approaches to improve the therapy of chronic pancreatitis and other chronic pain states. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
C1 [Vardanyan, Marina; Melemedjian, Ohannes K.; Price, Theodore J.; Ossipov, Michael H.; Lai, Josephine; Porreca, Frank] Univ Arizona, Dept Pharmacol, Coll Med, Tucson, AZ 85724 USA.
[Roberts, Ed] Scripps Res Inst, La Jolla, CA 92037 USA.
[Boos, Terrence L.; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, Drug Design & Synth Sect, Chem Biol Res Branch, NIDA,NIH, Bethesda, MD 20892 USA.
[Deschamps, Jeffrey R.] USN, Struct Matter Lab, Res Lab, Washington, DC 20375 USA.
RP Porreca, F (reprint author), Univ Arizona, Dept Pharmacol, Coll Med, Tucson, AZ 85724 USA.
EM frankp@email.arizona.edu
RI Price, Theodore/A-5094-2010;
OI Deschamps, Jeffrey/0000-0001-5845-0010; Price,
Theodore/0000-0002-6971-6221
FU National Institute on Drug Abuse (NIDA) [Y1-DA6002]; National Institute
on Alcohol Abuse and Alcoholism; NIH [NS065926, DA023513]
FX The research of the Drug Design and Synthesis Section, CBRB, NIDA &
NIAAA, was supported by the NIH Intramural Research Programs of the
National Institute on Drug Abuse (NIDA) and the National Institute on
Alcohol Abuse and Alcoholism. We thank NIDA for support of the X-ray
crystallographic studies (NIDA Contract Y1-DA6002). This work was also
funded by NIH Grants NS065926 and DA023513.
NR 44
TC 20
Z9 22
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD NOV
PY 2010
VL 151
IS 2
BP 257
EP 265
DI 10.1016/j.pain.2010.05.022
PG 9
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 662QJ
UT WOS:000282826100009
PM 20599324
ER
PT J
AU Colloca, L
Petrovic, P
Wager, TD
Ingvar, M
Benedetti, F
AF Colloca, Luana
Petrovic, Predrag
Wager, Tor D.
Ingvar, Martin
Benedetti, Fabrizio
TI How the number of learning trials affects placebo and nocebo responses
SO PAIN
LA English
DT Article
DE Expectations; Conditioning; Pain; Somatosensorial perception; Placebo;
Nocebo
ID ANALGESIA; EXPECTANCY; ANTICIPATION; EXPECTATIONS; PERSONALITY;
EXPERIENCE; NETWORK; HUMANS; PAIN; SKIN
AB Conditioning procedures are used in many placebo studies because evidence suggests that conditioning-related placebo responses are usually more robust than those induced by verbal suggestions alone. However, it has not been shown whether there is a causal relation between the number of conditioning trials and the resistance to extinction of placebo and nocebo responses. Here we test the effects of either one or four sessions of conditioning on the modulation of both non-painful and painful stimuli delivered to the dorsum of the foot. Placebo and nocebo manipulations were obtained by pairing green or red light to a series of stimuli that were made lower or higher with respect to a yellow light associated with a series of control stimuli. Subjects were told that the lights would indicate a treatment that would reduce or increase non-painful and painful stimuli to the foot. They were randomly assigned to either Group 1 or 2. Group 1 underwent one session of conditioning and Group 2 received four sessions of conditioning. We found that one session of conditioning (Group 1) induced nocebo responses, but not placebo responses in no pain condition. After one session of conditioning, we observed both nocebo and placebo responses to painful stimulation. However, these effects extinguished over time. Conversely, four sessions of conditioning (Group 2) induced robust placebo and nocebo responses to both non-painful and painful stimuli that persisted over the entire experiment. These findings suggest that the strength of learning may be clinically important for producing long-lasting placebo effects. Published by Elsevier B.V. on behalf of International Association for the Study of Pain.
C1 [Colloca, Luana] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
[Colloca, Luana] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
[Colloca, Luana; Benedetti, Fabrizio] Univ Turin, Dept Neurosci, Sch Med, Turin, Italy.
[Colloca, Luana; Benedetti, Fabrizio] Natl Inst Neurosci, Turin, Italy.
[Petrovic, Predrag; Ingvar, Martin] Karolinska Inst, MR Res Ctr, Stockholm, Sweden.
[Petrovic, Predrag; Ingvar, Martin] Karolinska Inst, Osher Ctr, Dept Clin Neurosci, Stockholm, Sweden.
[Wager, Tor D.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.
RP Colloca, L (reprint author), NIH, Ctr Clin, Dept Bioeth, Bldg 10-1C118, Bethesda, MD 20892 USA.
EM luana.colloca@unito.it
OI Colloca, Luana/0000-0002-6503-4709; Ingvar, Martin/0000-0002-9041-5714
FU International Association for Study of Pain (IASP); Regione Piemonte;
Istituto San Paolo di Torino; Volkswagen Foundation
FX This research was supported by grants from the International Association
for Study of Pain (IASP) Collaborative Research Grant, from the Regione
Piemonte, from the Istituto San Paolo di Torino, and from the Volkswagen
Foundation.
NR 49
TC 77
Z9 79
U1 2
U2 39
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD NOV
PY 2010
VL 151
IS 2
BP 430
EP 439
DI 10.1016/j.pain.2010.08.007
PG 10
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 662QJ
UT WOS:000282826100027
PM 20817355
ER
PT J
AU Goldberg, ME
Schwartzman, RJ
Torjman, MC
Wainer, IW
AF Goldberg, Michael E.
Schwartzman, Robert J.
Torjman, Marc C.
Wainer, Irving W.
TI Ketamine Infusion Successful in Some Patients
SO PAIN PHYSICIAN
LA English
DT Letter
ID REGIONAL PAIN SYNDROME
C1 [Goldberg, Michael E.; Torjman, Marc C.] UMDNJ, Cooper Univ Hosp, Dept Anesthesiol, Newark, NJ USA.
[Schwartzman, Robert J.] Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19104 USA.
[Wainer, Irving W.] NIA, Clin Invest Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Goldberg, ME (reprint author), UMDNJ, Cooper Univ Hosp, Dept Anesthesiol, Newark, NJ USA.
EM goldberg-Mike@cooperhealth.edu
NR 7
TC 2
Z9 2
U1 0
U2 3
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD NOV-DEC
PY 2010
VL 13
IS 6
BP E371
EP E372
PG 2
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 857KV
UT WOS:000297718300004
PM 21102974
ER
PT J
AU Phipps, S
Buckholt, K
Fernandez, I
Wiener, L
Noll, R
AF Phipps, Sean
Buckholt, Kelli
Fernandez, Ialy
Wiener, Lori
Noll, Robert
TI PEDIATRIC ONCOLOGISTS' PRACTICES OF PRESCRIBING SELECTIVE SEROTONIN
REUPTAKE INHIBITORS (SSRI'S) FOR CHILDREN AND ADOLESCENTS WITH CANCER: A
MULTI-SITE STU
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Phipps, Sean; Buckholt, Kelli] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Fernandez, Ialy; Noll, Robert] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
[Wiener, Lori] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD NOV
PY 2010
VL 55
IS 5
BP 817
EP 818
PG 2
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 663SN
UT WOS:000282910200147
ER
PT J
AU Kovar, H
Mestdagh, P
Kauer, M
Ban, J
Bilke, S
Schwentner, R
Speleman, F
Meltzer, P
Vandesompele, J
AF Kovar, Heinrich
Mestdagh, Pieter
Kauer, Max
Ban, Jozef
Bilke, Sven
Schwentner, Raphaela
Speleman, Frank
Meltzer, Paul
Vandesompele, Jo
TI AN INTEGRATED GENOMICS APPROACH UNRAVELS A ROLE FOR MICRO-RNAS IN
EWS-FLI1 DRIVEN EWINGS SARCOMA PATHOGENESIS
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Kovar, Heinrich; Kauer, Max; Ban, Jozef; Schwentner, Raphaela] St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria.
[Mestdagh, Pieter; Speleman, Frank; Vandesompele, Jo] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium.
[Bilke, Sven; Meltzer, Paul] NCI, NIH, Genet Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD NOV
PY 2010
VL 55
IS 5
BP 875
EP 875
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 663SN
UT WOS:000282910200349
ER
PT J
AU Horowitz, L
Ballard, E
Teach, SJ
Bosk, A
Rosenstein, DL
Joshi, P
Dalton, ME
Pao, M
AF Horowitz, Lisa
Ballard, Elizabeth
Teach, Stephen J.
Bosk, Abigail
Rosenstein, Donald L.
Joshi, Paramjit
Dalton, Marc E.
Pao, Maryland
TI Feasibility of Screening Patients With Nonpsychiatric Complaints for
Suicide Risk in a Pediatric Emergency Department A Good Time to Talk?
SO PEDIATRIC EMERGENCY CARE
LA English
DT Article
DE suicide; screening; nonpsychiatric patients; feasibility
ID PUBLIC-HEALTH; MENTAL-HEALTH; UNITED-STATES; CLINICAL-TRIAL;
PRIMARY-CARE; BEHAVIOR; YOUTH; IMPLEMENTATION; ADOLESCENTS; CHILDHOOD
AB Objective: Screening children for suicide risk when they present to the emergency department (ED) with nonpsychiatric complaints could lead to better identification and treatment of high-risk youth. Before suicide screening protocols can be implemented for nonpsychiatric patients in pediatric EDs, it is essential to determine whether such efforts are feasible.
Methods: As part of an instrument validation study, ED patients (10-21 years old) with both psychiatric and nonpsychiatric presenting complaints were recruited to take part in suicide screening. Clinically significant suicidal thoughts, as measured by the Suicidal Ideation Questionnaire, and suicidal behaviors were assessed, as well as patient opinions about suicide screening. Recruitment rates for the study as well as impact on length of stay were assessed.
Results: Of the 266 patients and parents approached for the study, 159 (60%) agreed to participate. For patients entering the ED for nonpsychiatric reasons (n = 106), 5.7% (n = 6) reported previous suicidal behavior, and 5.7% (n = 6) reported clinically significant suicidal ideation. There were no significant differences for mean length of stay in the ED for nonpsychiatric patients with positive triggers and those who screened negative (means, 382 [SD, 198] and 393 [SD, 166] minutes, respectively; P = 0.80). Ninety-six percent of participants agreed that suicide screening should occur in the ED.
Conclusions: Suicide screening of nonpsychiatric patients in the ED is feasible in terms of acceptability to parents, prevalence of suicidal thoughts and behaviors, practicality to ED flow, and patient opinion. Future endeavors should address brief screening tools validated on nonpsychiatric populations.
C1 [Horowitz, Lisa; Ballard, Elizabeth; Bosk, Abigail; Pao, Maryland] NIMH, NIH, Bethesda, MD 20892 USA.
[Ballard, Elizabeth] Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA.
[Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA.
[Rosenstein, Donald L.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA.
[Joshi, Paramjit] Childrens Natl Med Ctr, Dept Psychiat, Washington, DC 20010 USA.
[Dalton, Marc E.] Psychiat Inst Washington DC, Court Urgent Care Clin, Washington, DC USA.
RP Horowitz, L (reprint author), NIMH, NIH, 10 CRC,Room 6-5362,10 Ctr Dr, Bethesda, MD 20892 USA.
EM horowitzl@mail.nih.gov
FU National Institutes of Health; National Institute of Mental Health
FX The research for this article was supported by the Intramural Research
Program of the National Institutes of Health and the National Institute
of Mental Health.
NR 39
TC 20
Z9 20
U1 2
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0749-5161
J9 PEDIATR EMERG CARE
JI Pediatr. Emerg. Care
PD NOV
PY 2010
VL 26
IS 11
BP 787
EP 792
DI 10.1097/PEC.0b013e3181fa8568
PG 6
WC Emergency Medicine; Pediatrics
SC Emergency Medicine; Pediatrics
GA 675NW
UT WOS:000283838400001
PM 20944511
ER
PT J
AU Perez, MA
Gordon, A
Sanchez, F
Narvaez, F
Gutierrez, G
Ortega, O
Nunez, A
Harris, E
Balmaseda, A
AF Angeles Perez, Maria
Gordon, Aubree
Sanchez, Felix
Narvaez, Federico
Gutierrez, Gamaliel
Ortega, Oscar
Nunez, Andrea
Harris, Eva
Balmaseda, Angel
TI SEVERE COINFECTIONS OF DENGUE AND PANDEMIC INFLUENZA A H1N1 VIRUSES
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE dengue; influenza; coinfection; Nicaragua; children
ID RISK-FACTORS; CHILDREN; ASTHMA; BURDEN
AB Here we report on 4 hospitalized patients with dengue-influenza virus coinfections. All patients were RT-PCR positive for dengue virus and pandemic influenza A H1N1. Clinical findings at presentation ranged from influenza-like illness to severe dengue. Clinical progression of the infections varied, but all developed dengue symptoms and had interstitial infiltrates. Three cases required intensive care management and 1 case was fatal.
C1 [Harris, Eva] Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccinol, Berkeley, CA 94720 USA.
[Angeles Perez, Maria; Sanchez, Felix; Narvaez, Federico] Minist Salud, Hosp Infantil Manuel de Jesus Rivera, Managua, Nicaragua.
[Gordon, Aubree] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Narvaez, Federico; Gutierrez, Gamaliel; Ortega, Oscar] Sustainable Sci Inst, Managua, Nicaragua.
[Nunez, Andrea; Balmaseda, Angel] Minist Salud, Dept Virol, Ctr Nacl Diagnost & Referencia, Managua, Nicaragua.
RP Harris, E (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccinol, 1 Barker Hall, Berkeley, CA 94720 USA.
EM eharris@berkeley.edu
OI Gordon, Aubree/0000-0002-9352-7877
FU Pediatric Dengue Vaccine Initiative [VE-1]; NIH [AI65359]; Fogarty
International Center
FX Supported by the Pediatric Dengue Vaccine Initiative grant VE-1 (to
E.H.), NIH grant AI65359 (to E.H.), and the Fogarty International
Center.
NR 10
TC 16
Z9 16
U1 0
U2 0
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 NOV
PY 2010
VL 29
IS 11
BP 1052
EP 1055
DI 10.1097/INF.0b013e3181e6c69b
PG 4
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 671HT
UT WOS:000283492400018
PM 20811315
ER
PT J
AU Boyd, H
Feenstra, B
Geller, F
Feingold, E
Ryckman, K
Shaffer, J
Laurie, C
Zhang, Q
Doheny, K
Pugh, E
Manolio, T
Marazita, M
Melbye, M
Murray, J
AF Boyd, H.
Feenstra, B.
Geller, F.
Feingold, E.
Ryckman, K.
Shaffer, J.
Laurie, C.
Zhang, Q.
Doheny, K.
Pugh, E.
Manolio, T.
Marazita, M.
Melbye, M.
Murray, J.
CA GENEVA Consortium
TI A GENOME-WIDE ASSOCIATION STUDY OF SPONTANEOUS PRETERM DELIVERY
SO PEDIATRIC RESEARCH
LA English
DT Meeting Abstract
C1 [Boyd, H.; Feenstra, B.; Geller, F.; Melbye, M.] Statens Serum Inst, DK-2300 Copenhagen, Denmark.
[Feingold, E.; Shaffer, J.; Marazita, M.] Univ Pittsburgh, Pittsburgh, PA USA.
[Ryckman, K.; Murray, J.] Univ Iowa, Iowa City, IA USA.
[Laurie, C.; Zhang, Q.] Univ Washington, Seattle, WA 98195 USA.
[Doheny, K.; Pugh, E.] Johns Hopkins Univ, Inst Med Genet, Baltimore, MD USA.
[Manolio, T.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0031-3998
J9 PEDIATR RES
JI Pediatr. Res.
PD NOV
PY 2010
VL 68
SU 1
MA 292
BP 150
EP 150
PG 1
WC Pediatrics
SC Pediatrics
GA V25LO
UT WOS:000208479700293
ER
PT J
AU Delaney-Black, V
Chiodo, LM
Hannigan, JH
Greenwald, MK
Janisse, J
Patterson, G
Huestis, MA
Ager, J
Sokol, RJ
AF Delaney-Black, Virginia
Chiodo, Lisa M.
Hannigan, John H.
Greenwald, Mark K.
Janisse, James
Patterson, Grace
Huestis, Marilyn A.
Ager, Joel
Sokol, Robert J.
TI Just Say "I Don't": Lack of Concordance Between Teen Report and
Biological Measures of Drug Use
SO PEDIATRICS
LA English
DT Article
DE cocaine; opiates; teen; drug use
ID HAIR ANALYSIS; SELF-REPORT; COCAINE USE; HOUSEHOLD SURVEY;
SUBSTANCE-ABUSE; CANNABIS USE; VALIDITY; URINE; TESTS; EXPOSURE
AB BACKGROUND: Prevalence estimates of illicit drug use by teens are typically generated from confidential or anonymous self-report. While data comparing teen self-report with biological measures are limited, adult studies identify varying degrees of under-reporting.
METHODS: Hair analyses for cocaine, opiates and marijuana were compared to confidential teen self-and parent-reported teen drug use in a longitudinal cohort of >400 high-risk urban teens and parents.
RESULTS: Both teens and parents substantially underreported recent teen cocaine and opiate use. However, compared with parents, teens were more likely to deny biomarker-verified cocaine use. Teen specimens (hair) were 52 times more likely to identify cocaine use compared with self-report. Parent hair analyses for cocaine and opiate use were 6.5 times and 5.5 times, respectively, more likely to indicate drug use than were parental self-report. The lack of concordance between self-report and bioassay occurred despite participant's knowledge that a "certificate of confidentiality" protected both teen and adult participants, and that the biological specimens would be tested for drugs.
CONCLUSIONS: These findings confirm prior reports of adult under-reporting of their own drug use while extending our understanding of teen's self-admitted drug use. The lack of concordance between teen self-or parent-reported teen drug use and biomarkers confirm our concerns that both teen-and parent-reported teen drug use is limited, at least for youth in high-risk urban settings. Methods of ascertainment other than self-or parent-report must be considered when health care providers, researchers and public health agencies attempt to estimate teen drug-use prevalence. Pediatrics 2010;126:887-893
C1 [Delaney-Black, Virginia; Patterson, Grace] Wayne State Univ, Carmen & Ann Adams Dept Pediat, Detroit, MI USA.
[Hannigan, John H.; Sokol, Robert J.] Wayne State Univ, Coll Nursing, Dept Obstet & Gynecol, Detroit, MI 48202 USA.
[Hannigan, John H.] Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA.
[Greenwald, Mark K.] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI USA.
[Janisse, James; Ager, Joel] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
[Hannigan, John H.] Wayne State Univ, Merrill Palmer Skillman Inst, Detroit, MI USA.
[Hannigan, John H.; Sokol, Robert J.] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Detroit, MI USA.
[Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA.
RP Delaney-Black, V (reprint author), Childrens Hosp Michigan, Carmen & Ann Adams Dept Pediat, 3901 Beaubien St, Detroit, MI 48201 USA.
EM vdelaney@med.wayne.edu
RI Chiodo, Lisa/G-1427-2015
OI Chiodo, Lisa/0000-0001-7052-3569
FU National Institutes of Health (NIH); National Institute of Drug Abuse
[R01-DA08524, R01-DA016373]
FX Funded by the National Institutes of Health (NIH).; This work was
supported by National Institute of Drug Abuse grants R01-DA08524 and
R01-DA016373.
NR 44
TC 36
Z9 36
U1 1
U2 7
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 NOV
PY 2010
VL 126
IS 5
BP 887
EP 893
DI 10.1542/peds.2009-3059
PG 7
WC Pediatrics
SC Pediatrics
GA 673GY
UT WOS:000283648700046
PM 20974792
ER
PT J
AU Avila, EM
Uzel, G
Hsu, A
Milner, JD
Turner, ML
Pittaluga, S
Freeman, AF
Holland, SM
AF Avila, Elizabeth Mannino
Uzel, Gulbu
Hsu, Amy
Milner, Joshua D.
Turner, Maria L.
Pittaluga, Stefania
Freeman, Alexandra F.
Holland, Steven M.
TI Highly Variable Clinical Phenotypes of Hypomorphic RAG1 Mutations
SO PEDIATRICS
LA English
DT Article
DE severe combined immunodeficiency; SCID; granuloma; Mycobacterium avium
complex; MAC; Omenn syndrome
ID SEVERE COMBINED IMMUNODEFICIENCY; OMENN-SYNDROME; DEFECTS; AUTOIMMUNITY;
CELLS; IMMUNITY; DISEASES; GAMMA
AB Hypomorphic mutations that lead to "leaky" severe combined immunodeficiency presentation with partial protein function are increasingly being identified. Mutations in recombination-activating genes (RAGs) 1 and 2 cause immunodeficiency and dysregulation ranging from severe combined immunodeficiency to Omenn syndrome to more mild immunodeficiencies. We report here the cases of 3 patients with hypomorphic RAG1 mutations with distinct presentations. One patient had granulomatous skin disease and disseminated nontuberculous mycobacteria; the second patient presented with predominantly autoimmune manifestations; and the third patient presented with relatively late onset of infections and had isolated T-cell lymphopenia. These disparate and atypical presentations of hypomorphic RAG1 mutations highlight the role of RAG1 in immune function and autoimmunity and expand the disease spectrum linked to these genes. Pediatrics 2010; 126: e1248-e1252
C1 [Avila, Elizabeth Mannino; Uzel, Gulbu; Hsu, Amy; Freeman, Alexandra F.; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Avila, Elizabeth Mannino] Duke Univ, Sch Med, Durham, NC USA.
[Avila, Elizabeth Mannino] NIAID, NIH, Pfizer Clin Res Training Program, Bethesda, MD 20892 USA.
[Milner, Joshua D.; Turner, Maria L.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Milner, Joshua D.; Turner, Maria L.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
[Pittaluga, Stefania] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Freeman, AF (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bldg 10,Room 11N234,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM freemaal@mail.nih.gov
FU National Institutes of Health (NIH); National Institute of Allergy and
Infectious Diseases; National Cancer Institute, National Institutes of
Health (NIH); Pfizer Inc
FX Funded by the National Institutes of Health (NIH).; This research was
supported by the Intramural Research Program of the National Institute
of Allergy and Infectious Diseases and National Cancer Institute,
National Institutes of Health (NIH). For Dr Avila, this research was
made possible through the Clinical Research Training Program, a
public-private partnership supported jointly by the NIH and Pfizer Inc
(via a grant to the Foundation for the National Institutes of Health
from Pfizer Inc).
NR 17
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Z9 29
U1 0
U2 1
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 NOV
PY 2010
VL 126
IS 5
BP E1248
EP E1252
DI 10.1542/peds.2009-3171
PG 5
WC Pediatrics
SC Pediatrics
GA 673GY
UT WOS:000283648700029
PM 20956421
ER
PT J
AU Carlo, WA
Goudar, SS
Jehan, I
Chomba, E
Tshefu, A
Garces, A
Parida, S
Althabe, F
McClure, EM
Derman, RJ
Goldenberg, RL
Bose, C
Hambidge, M
Panigrahi, P
Buekens, P
Chakraborty, H
Hartwell, TD
Moore, J
Wright, LL
AF Carlo, Waldemar A.
Goudar, Shivaprasad S.
Jehan, Imtiaz
Chomba, Elwyn
Tshefu, Antoinette
Garces, Ana
Parida, Sailajanandan
Althabe, Fernando
McClure, Elizabeth M.
Derman, Richard J.
Goldenberg, Robert L.
Bose, Carl
Hambidge, Michael
Panigrahi, Pinaki
Buekens, Pierre
Chakraborty, Hrishikesh
Hartwell, Tyler D.
Moore, Janet
Wright, Linda L.
CA First Breath Study Grp
TI High Mortality Rates for Very Low Birth Weight Infants in Developing
Countries Despite Training
SO PEDIATRICS
LA English
DT Article
DE neonatal mortality; perinatal mortality; stillbirth; developing
countries; health care systems; very low birth weight; prematurity
ID PERINATAL-MORTALITY; NEONATAL DEATHS; CARE; IMPACT; INTERVENTIONS;
STILLBIRTHS; HEALTH
AB OBJECTIVE: The goal was to determine the effect of training in newborn care and resuscitation on 7-day (early) neonatal mortality rates for very low birth weight (VLBW) infants. The study was designed to test the hypothesis that these training programs would reduce neonatal mortality rates for VLBW infants.
METHODS: Local instructors trained birth attendants from 96 rural communities in 6 developing countries in protocol and data collection, the World Health Organization Essential Newborn Care (ENC) course, and a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (NRP), by using a train-the-trainer model. To test the impact of ENC training, data on infants of 500 to 1499 g were collected by using a before/after, active baseline, controlled study design. A cluster-randomized, controlled trial design was used to test the impact of the NRP.
RESULTS: A total of 1096 VLBW (500-1499 g) infants were enrolled, and 98.5% of live-born infants were monitored to 7 days. All-cause, 7-day neonatal mortality, stillbirth, and perinatal mortality rates were not affected by ENC or NRP training.
CONCLUSIONS: Neither ENC nor NRP training of birth attendants decreased 7-day neonatal, stillbirth, or perinatal mortality rates for VLBW infants born at home or at first-level facilities. Encouragement of delivery in a facility where a higher level of care is available may be preferable when delivery of a VLBW infant is expected. Pediatrics 2010;126:e1072-e1080
C1 [Carlo, Waldemar A.] Univ Alabama Birmingham, Sch Med, Dept Pediat, Div Neonatol, Birmingham, AL 35249 USA.
[Carlo, Waldemar A.; Chomba, Elwyn] Ctr Infect Dis Res Zambia, Lusaka, Zambia.
[Goudar, Shivaprasad S.] Jawaharlal Nehru Med Coll, Dept Pediat, Belgaum, India.
[Jehan, Imtiaz] Aga Khan Univ, Sch Med, Dept Pediat, Karachi, Pakistan.
[Chomba, Elwyn] Univ Teaching Hosp, Dept Pediat & Child Hlth, Lusaka, Zambia.
[Tshefu, Antoinette] Kinshasa Sch Publ Hlth, Dept Publ Hlth, Kinshasa, Zaire.
[Garces, Ana] San Carlos Univ, Sch Med, Dept Pediat, Guatemala City, Guatemala.
[Parida, Sailajanandan] Sriramchandra Bhanja Med Coll, Dept Pediat, Cuttack, Orissa, India.
[Althabe, Fernando; Hartwell, Tyler D.; Moore, Janet] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
[McClure, Elizabeth M.; Chakraborty, Hrishikesh] RTI Int, Dept Stat & Epidemiol, Durham, NC USA.
[Derman, Richard J.] Univ Missouri, Sch Med, Dept Pediat, Kansas City, MO 64108 USA.
[Goldenberg, Robert L.] Drexel Univ, Dept Pediat, Coll Med, Philadelphia, PA 19104 USA.
[Bose, Carl] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA.
[Hambidge, Michael] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA.
[Panigrahi, Pinaki] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA.
[Buekens, Pierre] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70118 USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Res Mothers & Children, Bethesda, MD USA.
RP Carlo, WA (reprint author), Univ Alabama Birmingham, Sch Med, Dept Pediat, Div Neonatol, 176F Suite 9380,619 S 19th St, Birmingham, AL 35249 USA.
EM wcarlo@peds.uab.edu
OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development Global Network for Women's and Children's Health Research
[U01 HD040477, U01 HD043475, U01 HD043464, U01 HD040657, U01 HD042372,
U01 HD040607, U01 HD040636, U01 HD040574]; Bill and Melinda Gates
Foundation; National Institutes of Health (NIH)
FX This work was funded by the Eunice Kennedy Shriver National Institute of
Child Health and Human Development Global Network for Women's and
Children's Health Research (grants U01 HD040477, U01 HD043475, U01
HD043464, U01 HD040657, U01 HD042372, U01 HD040607, U01 HD040636, and
U01 HD040574) and the Bill and Melinda Gates Foundation. Eunice Kennedy
Shriver National Institute of Child Health and Human Development staff
members participated in the study design, study conduct, data
interpretation, and manuscript editing. Neither funding agency limited
the ability to complete the research as planned. The authors had full
control of the primary data.; Funded by the National Institutes of
Health (NIH).
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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 NOV
PY 2010
VL 126
IS 5
BP E1072
EP E1080
DI 10.1542/peds.2010-1183
PG 9
WC Pediatrics
SC Pediatrics
GA 673GY
UT WOS:000283648700010
PM 20937655
ER
PT J
AU Carlo, WA
McClure, EM
Chomba, E
Chakraborty, H
Hartwell, T
Harris, H
Lincetto, O
Wright, LL
AF Carlo, Waldemar A.
McClure, Elizabeth M.
Chomba, Elwyn
Chakraborty, Hrishikesh
Hartwell, Tyler
Harris, Hillary
Lincetto, Ornella
Wright, Linda L.
TI Newborn Care Training of Midwives and Neonatal and Perinatal Mortality
Rates in a Developing Country
SO PEDIATRICS
LA English
DT Article
DE neonatal mortality; perinatal mortality; developing countries; health
systems; effectiveness
ID CHILD SURVIVAL; SRI-LANKA; INTERVENTIONS; STRATEGIES; IMPACT; HOSPITALS;
PAKISTAN; HEALTH
AB OBJECTIVE: This study was designed to test the hypothesis that 2 training programs would reduce incrementally 7-day neonatal mortality rates for low-risk institutional deliveries.
METHODS: Using a train-the-trainer model, certified research midwives sequentially trained the midwives who performed deliveries in low-risk, first-level, urban, community health clinics in 2 cities in Zambia in the protocol and data collection, in the World Health Organization Essential Newborn Care (ENC) course (universal precautions and cleanliness, routine neonatal care, resuscitation, thermoregulation, breastfeeding, kangaroo care, care of small infants, and common illnesses), and in the American Academy of Pediatrics Neonatal Resuscitation Program (in-depth basic resuscitation). Data were collected during 3 periods, after implementation of each training course.
RESULTS: A total of 71 689 neonates were enrolled in the 3 study periods. All-cause, 7-day neonatal mortality rates decreased from 11.5 deaths per 1000 live births to 6.8 deaths per 1000 live births after ENC training (relative risk: 0.59 [95% confidence interval: 0.48-0.77]; P < .001), because of decreases in rates of deaths attributable to birth asphyxia and infection. Perinatal mortality rates but not stillbirth rates decreased. The 7-day neonatal mortality rate was decreased further after Neonatal Resuscitation Program training, after correction for loss to follow-up monitoring.
CONCLUSIONS: ENC training for midwives reduced 7-day neonatal mortality rates in low-risk clinics. Additional in-depth basic training in neonatal resuscitation may reduce mortality rates further. Pediatrics 2010;126:e1064-e1071
C1 [Carlo, Waldemar A.] Univ Alabama, Women & Infants Ctr 9380, Div Neonatol, Dept Pediat,Sch Med, Birmingham, AL 35233 USA.
[Carlo, Waldemar A.; Chomba, Elwyn] Ctr Infect Dis Res Zambia, Lusaka, Zambia.
[McClure, Elizabeth M.; Chakraborty, Hrishikesh; Hartwell, Tyler; Harris, Hillary] RTI Int, Dept Stat & Epidemiol, Durham, NC USA.
[Chomba, Elwyn] Univ Zambia, Univ Teaching Hosp, Dept Paediat & Child Hlth, Lusaka, Zambia.
[Lincetto, Ornella] World Hlth Org Country Off Hanoi, Dept Child & Adolescent Hlth, Hanoi, Vietnam.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Res Mothers & Children, Bethesda, MD 20892 USA.
RP Carlo, WA (reprint author), Univ Alabama, Women & Infants Ctr 9380, Div Neonatol, Dept Pediat,Sch Med, 1700 6th Ave S, Birmingham, AL 35233 USA.
EM wcarlo@peds.uab.edu
FU National Institutes of Health (NIH); Eunice Kennedy Shriver National
Institute of Child Health and Human Development Global Network for
Women's and Children's Health Research [HD43475, HD404636]; Bill and
Melinda Gates Foundation
FX Funded by the National Institutes of Health (NIH).; This work was funded
by the Eunice Kennedy Shriver National Institute of Child Health and
Human Development Global Network for Women's and Children's Health
Research (grants HD43475 and HD404636) and the Bill and Melinda Gates
Foundation.
NR 28
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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 NOV
PY 2010
VL 126
IS 5
BP E1064
EP E1071
DI 10.1542/peds.2009-3464
PG 8
WC Pediatrics
SC Pediatrics
GA 673GY
UT WOS:000283648700009
PM 20937659
ER
PT J
AU Chiu, CT
Chuang, DM
AF Chiu, Chi-Tso
Chuang, De-Maw
TI Molecular actions and therapeutic potential of lithium in preclinical
and clinical studies of CNS disorders
SO PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
DE Apoptosis; Brain-derived neurotrophic factor (BDNF); Glycogen synthase
kinase 3 (GSK-3); Lithium; Neurodegenerative diseases; Neuroprotection
ID GLYCOGEN-SYNTHASE KINASE-3; AMYOTROPHIC-LATERAL-SCLEROSIS;
FRAGILE-X-SYNDROME; ENDOTHELIAL GROWTH-FACTOR; EXPERIMENTAL AUTOIMMUNE
ENCEPHALOMYELITIS; TISSUE-PLASMINOGEN ACTIVATOR; CEREBELLAR GRANULE
NEURONS; CYCLIN-DEPENDENT KINASE-5; GLOBAL CEREBRAL-ISCHEMIA;
AGGREGATE-PRONE PROTEINS
AB Lithium has been used clinically to treat bipolar disorder for over half a century, and remains a fundamental pharmacological therapy for patients with this illness. Although lithium's therapeutic mechanisms are not fully understood, substantial in vitro and in vivo evidence suggests that it has neuroprotective/neurotrophic properties against various insults, and considerable clinical potential for the treatment of several neurodegenerative conditions. Evidence from pharmacological and gene manipulation studies support the notion that glycogen synthase kinase-3 inhibition and induction of brain-derived neurotrophic factor-mediated signaling are lithium's main mechanisms of action, leading to enhanced cell survival pathways and alteration of a wide variety of downstream effectors. By inhibiting N-methyl-D-aspartate receptor-mediated calcium influx, lithium also contributes to calcium homeostasis and suppresses calcium-dependent activation of pro-apoptotic signaling pathways. In addition, lithium decreases inositol 1,4,5-trisphosphate by inhibiting phosphoinositol phosphatases, a process recently identified as a novel mechanism for inducing autophagy. Through these mechanisms, therapeutic doses of lithium have been demonstrated to defend neuronal cells against diverse forms of death insults and to improve behavioral as well as cognitive deficits in various animal models of neurodegenerative diseases, including stroke, amyotrophic lateral sclerosis, fragile X syndrome, as well as Huntington's, Alzheimer's, and Parkinson's diseases, among others. Several clinical trials are also underway to assess the therapeutic effects of lithium for treating these disorders. This article reviews the most recent findings regarding the potential targets involved in lithium's neuroprotective effects, and the implication of these findings for the treatment of a variety of diseases. Published by Elsevier Inc.
C1 [Chiu, Chi-Tso; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bldg 10,Room 3D38,10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA.
EM chuang@mail.nih.gov
FU NIMH, NIH
FX This work was supported by the Intramural Research Program of the NIMH,
NIH. The authors thank Dr. Joshua Hunsberger, Peter Leeds, and Ioline
Henter of the Mood and Anxiety Disorder Program, NIMH, NIH, for critical
review and editorial assistance of this manuscript.
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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 NOV
PY 2010
VL 128
IS 2
BP 281
EP 304
DI 10.1016/j.pharmthera.2010.07.006
PG 24
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 670FP
UT WOS:000283406900003
PM 20705090
ER
PT J
AU Friedly, J
Standaert, C
Chan, L
AF Friedly, Janna
Standaert, Christopher
Chan, Leighton
TI Epidemiology of Spine Care: The Back Pain Dilemma
SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
LA English
DT Article
DE Low back pain; Epidemiology; Low back pain treatments; Low back pain
outcomes; Spine interventions
ID EPIDURAL STEROID INJECTIONS; LUMBAR RADICULAR PAIN; INTRADISCAL
ELECTROTHERMAL THERAPY; EVIDENCE-INFORMED MANAGEMENT; AMBULATORY SURGERY
CENTERS; UNITED-STATES; DOUBLE-BLIND; CONTROLLED-TRIAL; OLDER-ADULTS;
DEGENERATIVE SPONDYLOLISTHESIS
AB In this article the epidemiology of back pain and the use of a variety of treatments for back pain in the United States are reviewed The dilemma faced by medical providers caring for patients with low back pain is examined in the context of epidemiologic data Back pain is becoming increasingly common and a growing number of treatment options are being used with increasing frequency in clinical practice However, limited evidence exists to demonstrate the effectiveness of these treatments In addition, health-related quality of life for persons with back pain is not improving despite the availability and use of an expanding array of treatments This dilemma poses a difficult challenge for medical providers treating individual patients who suffer from back pain
C1 [Friedly, Janna] Univ Washington, Dept Rehabil Med, Seattle, WA 98104 USA.
[Standaert, Christopher] Univ Washington Sports & Spine Phys, Harborview Med Ctr, Seattle, WA 98104 USA.
[Chan, Leighton] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Friedly, J (reprint author), Univ Washington, Dept Rehabil Med, 325 9th Ave, Seattle, WA 98104 USA.
FU Intramural NIH HHS [ZIA CL060073-03]
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PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1047-9651
J9 PHYS MED REH CLIN N
JI Phys. Med. Rehabil. Clin. N. Am.
PD NOV
PY 2010
VL 21
IS 4
BP 659
EP +
DI 10.1016/j.pmr.2010.08.002
PG 20
WC Rehabilitation
SC Rehabilitation
GA 687PJ
UT WOS:000284790100003
PM 20977955
ER
PT J
AU Moreau, NG
Simpson, KN
Teefey, SA
Damiano, DL
AF Moreau, Noelle G.
Simpson, Kit N.
Teefey, Sharlene A.
Damiano, Diane L.
TI Muscle Architecture Predicts Maximum Strength and Is Related to Activity
Levels in Cerebral Palsy
SO PHYSICAL THERAPY
LA English
DT Article
ID CROSS-SECTIONAL AREA; MOTOR FUNCTION; LOWER-LIMB; CHILDREN; ADOLESCENTS;
THICKNESS; GASTROCNEMIUS; RELIABILITY; VALIDITY; MEN
AB Background. Muscle architecture is known to be predictive of muscle function. However, it is unknown whether this relationship is similar in children and adolescents with and without cerebral palsy (CP).
Objective. The objective of this study was to determine whether the architecture of the rectus femoris (RF) and vastus lateralis (VL) muscles was predictive of maximum voluntary knee extensor torque in children and adolescents with and without CP and whether these measures were related to activity and participation levels.
Design. A case-control design was used.
Methods. Eighteen participants with CP (mean age=12.0 years, SD=3.2) at Gross Motor Function Classification System (GMFCS) levels I through IV and 12 age-matched peers with typical development (mean age=12.3 years, SD=3.9) were evaluated. Muscle thickness, fascicle length, and fascicle angle of the RF and VL muscles were measured with 2-dimensional, B-mode ultrasound imaging. The activity and participation measures used for participants with CP were the Pediatric Outcomes Data Collection Instrument (PODCI) and the Activities Scale for Kids, Performance Version (ASKp).
Results. When age and GMFCS level were controlled for, VL muscle thickness was the best predictor of knee extensor isometric torque in the group with CP (R(2)=.85). This prediction was similar to the prediction from VL muscle thickness and age in participants with typical development (R(2)=.91). Rectus femoris muscle fascicle length was significantly correlated with the Sports and Physical Functioning Scale of the PODCI (rho=.49), and VL muscle fascicle angle was correlated with the Transfers and Basic Mobility Scale of the PODCI (r=.47) and with ASKp Locomotion subdomain (r=.50).
Limitations. A limitation of this study was the small sample size.
Conclusions. Ultrasound measures of VL muscle thickness, adjusted for age and GMFCS level, were highly predictive of maximum torque and have the potential to serve as surrogate measures of voluntary strength (force-generating capacity) in children and adolescents with and without CP.
C1 [Moreau, Noelle G.] Med Univ S Carolina, Dept Hlth Profess, Charleston, SC 29425 USA.
[Simpson, Kit N.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA.
[Teefey, Sharlene A.] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[Damiano, Diane L.] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Moreau, NG (reprint author), Med Univ S Carolina, Dept Hlth Profess, 77 President St,MSC 700, Charleston, SC 29425 USA.
EM moreau@musc.edu
RI Damiano, Diane/B-3338-2010
OI Damiano, Diane/0000-0002-2770-5356
FU PT, MPT; GE Healthcare; National Center for Medical Rehabilitation
Research/National Institutes of Health [T32HD007434-16]; Section on
Pediatrics of the American Physical Therapy Association; NIH Clinical
Center
FX The authors thank Chris Stanley for assistance with data collection and
processing and Dr Janice Brunstrom-Hernandez and Jennifer Miros, PT,
MPT, for their support and assistance with recruitment. They thank GE
Healthcare and Tania Gordley, Applications Specialist for GE Healthcare
Ultrasound, for their support and technical assistance with this
project.; Dr Moreau was a postdoctoral fellow in the Movement Science
Program at Washington University, St Louis, Missouri, when this study
was conducted and was supported by a National Center for Medical
Rehabilitation Research/National Institutes of Health grant
(T32HD007434-16). This project also was supported by a clinical research
grant from the Section on Pediatrics of the American Physical Therapy
Association. This research was supported, in part, by the Intramural
Research Program of the NIH Clinical Center.
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PU AMER PHYSICAL THERAPY ASSOC
PI ALEXANDRIA
PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA
SN 0031-9023
J9 PHYS THER
JI Phys. Ther.
PD NOV
PY 2010
VL 90
IS 11
BP 1619
EP 1630
DI 10.2522/ptj.20090377
PG 12
WC Orthopedics; Rehabilitation
SC Orthopedics; Rehabilitation
GA 673MC
UT WOS:000283666200007
PM 20847035
ER
PT J
AU Li, RHH
Churchill, GA
AF Li, Renhua H.
Churchill, Gary A.
TI Epistasis contributes to the genetic buffering of plasma HDL cholesterol
in mice
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE structural equation model
ID INBRED MOUSE STRAINS; ARTERY-DISEASE; ATHEROSCLEROSIS; LOCI; EXPRESSION;
CROSSES; LESIONS; DIET; ARCHITECTURE; METABOLISM
AB Li RH, Churchill GA. Epistasis contributes to the genetic buffering of plasma HDL cholesterol in mice. Physiol Genomics 42A: 228-234, 2010. First published September 21, 2010; doi: 10.1152/physiolgenomics.00044.2010.-Stressful environmental factors, such as a high-fat diet, can induce responses in the expression of genes that act to maintain physiological homeostasis. We observed variation in plasma concentrations of high-density lipoprotein (HDL) cholesterol across inbred mouse strains in response to high dietary fat intake. Several strains, including C57BL/6J, have stable levels of plasma HDL independent of diet, whereas other strains, including DBA2/J, show marked changes in plasma HDL. To explore this phenomenon further, we used publicly available data from a C57BL/6J x DBA/2J intercross to identify genetic factors that associate with HDL under high-fat diet conditions. Our analysis identified an epistatic interaction that plays a role in the buffering of HDL levels in C57BL/6J mice, and we have identified Arl4d as a candidate gene that mediates this effect. Structural modeling further elucidates the interaction of genetic factors that contribute to the robustness of HDL in response to high-fat diet in the C57BL/6J strain.
C1 [Li, Renhua H.] Natl Inst Digest Dis Diabet & Kidney Dis, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Li, Renhua H.; Churchill, Gary A.] Jackson Lab, Bar Harbor, ME 04609 USA.
RP Li, RHH (reprint author), Natl Inst Digest Dis Diabet & Kidney Dis, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM lir3@niddk.nih.gov
FU National Institute of General Medical Sciences [GM-070683, GM-076468]
FX This study was supported by National Institute of General Medical
Sciences Grants GM-070683 and GM-076468.
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U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD NOV
PY 2010
VL 42A
IS 4
BP 228
EP 234
DI 10.1152/physiolgenomics.00044.2010
PG 7
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA 686GP
UT WOS:000284685100002
PM 20858711
ER
PT J
AU Alvarenga, PH
Francischetti, IMB
Calvo, E
Sa-Nunes, A
Ribeiro, JMC
Andersen, JF
AF Alvarenga, Patricia H.
Francischetti, Ivo M. B.
Calvo, Eric
Sa-Nunes, Anderson
Ribeiro, Jose M. C.
Andersen, John F.
TI The Function and Three-Dimensional Structure of a Thromboxane
A(2)/Cysteinyl Leukotriene-Binding Protein from the Saliva of a Mosquito
Vector of the Malaria Parasite
SO PLOS BIOLOGY
LA English
DT Article
ID PLATELET COLLAGEN RECEPTORS; BLOOD-FEEDING ARTHROPODS;
RHODNIUS-PROLIXUS; HIGH-AFFINITY; HUMAN-SKIN; EICOSANOID MEDIATORS;
ANOPHELES-GAMBIAE; SMOOTH-MUSCLE; SHAPE CHANGE; SOFT TICKS
AB The highly expressed D7 protein family of mosquito saliva has previously been shown to act as an anti-inflammatory mediator by binding host biogenic amines and cysteinyl leukotrienes (CysLTs). In this study we demonstrate that AnSt-D7L1, a two-domain member of this group from Anopheles stephensi, retains the CysLT binding function seen in the homolog AeD7 from Aedes aegypti but has lost the ability to bind biogenic amines. Unlike any previously characterized members of the D7 family, AnSt-D7L1 has acquired the important function of binding thromboxane A(2) (TXA(2)) and its analogs with high affinity. When administered to tissue preparations, AnSt-D7L1 abrogated Leukotriene C-4 (LTC4)-induced contraction of guinea pig ileum and contraction of rat aorta by the TXA(2) analog U46619. The protein also inhibited platelet aggregation induced by both collagen and U46619 when administered to stirred platelets. The crystal structure of AnSt-D7L1 contains two OBP-like domains and has a structure similar to AeD(7). In AnSt-D7L1, the binding pocket of the C-terminal domain has been rearranged relative to AeD7, making the protein unable to bind biogenic amines. Structures of the ligand complexes show that CysLTs and TXA(2) analogs both bind in the same hydrophobic pocket of the N-terminal domain. The TXA(2) analog U46619 is stabilized by hydrogen bonding interactions of the omega-5 hydroxyl group with the phenolic hydroxyl group of Tyr 52. LTC4 and occupies a very similar position to LTE4 in the previously determined structure of its complex with AeD7. As yet, it is not known what, if any, new function has been acquired by the rearranged C-terminal domain. This article presents, to our knowledge, the first structural characterization of a protein from mosquito saliva that inhibits collagen mediated platelet activation.
C1 [Alvarenga, Patricia H.; Francischetti, Ivo M. B.; Calvo, Eric; Sa-Nunes, Anderson; Ribeiro, Jose M. C.; Andersen, John F.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Alvarenga, Patricia H.] Univ Fed Rural Rio de Janeiro, Lab Bioquim & Fisiol Artropodes, Dept Quim, Seropedica, Brazil.
[Sa-Nunes, Anderson] Univ Sao Paulo, Inst Ciencias Biomed, Lab Imunol Expt, Dept Imunol, BR-05508 Sao Paulo, Brazil.
RP Alvarenga, PH (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
EM jandersen@niaid.nih.gov
RI Sa-Nunes, Anderson/D-8667-2012;
OI Sa-Nunes, Anderson/0000-0002-1859-4973; Calvo, Eric/0000-0001-7880-2730;
Ribeiro, Jose/0000-0002-9107-0818
FU NIAID
FX This work was funded by the intramural research program of the NIAID.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 59
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Z9 24
U1 1
U2 6
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 NOV
PY 2010
VL 8
IS 11
AR e1000547
DI 10.1371/journal.pbio.1000547
PG 15
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 687ES
UT WOS:000284762300019
PM 21152418
ER
PT J
AU Colina, C
Palavicini, JP
Srikumar, D
Holmgren, M
Rosenthal, JJC
AF Colina, Claudia
Palavicini, Juan Pablo
Srikumar, Deepa
Holmgren, Miguel
Rosenthal, Joshua J. C.
TI Regulation of Na+/K+ ATPase Transport Velocity by RNA Editing
SO PLOS BIOLOGY
LA English
DT Article
ID NA/K PUMP CURRENT; VOLTAGE-DEPENDENCE; NERVOUS-SYSTEM; SODIUM-PUMP;
POTASSIUM CHANNELS; NA,K PUMP; DROSOPHILA; SUBUNIT; GIANT; NA+,K+-ATPASE
AB Because firing properties and metabolic rates vary widely, neurons require different transport rates from their Na+/K+ pumps in order to maintain ion homeostasis. In this study we show that Na+/K+ pump activity is tightly regulated by a novel process, RNA editing. Three codons within the squid Na+/K+ ATPase gene can be recoded at the RNA level, and the efficiency of conversion for each varies dramatically, and independently, between tissues. At one site, a highly conserved isoleucine in the seventh transmembrane span can be converted to a valine, a change that shifts the pump's intrinsic voltage dependence. Mechanistically, the removal of a single methyl group specifically targets the process of Na+ release to the extracellular solution, causing a higher turnover rate at the resting membrane potential.
C1 [Colina, Claudia; Palavicini, Juan Pablo; Rosenthal, Joshua J. C.] Univ Puerto Rico, Inst Neurobiol, San Juan, PR 00901 USA.
[Srikumar, Deepa; Holmgren, Miguel] Natl Inst Neurol Disorders & Stroke, Mol Neurophysiol Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD USA.
[Rosenthal, Joshua J. C.] Univ Puerto Rico, Dept Biochem, San Juan, PR 00936 USA.
RP Colina, C (reprint author), Univ Puerto Rico, Inst Neurobiol, Med Sci Campus, San Juan, PR 00901 USA.
EM holmgren@ninds.nih.gov; joshua.rosenthal@upr.edu
FU NSF [IBN-0344070, NIH 2 U54 NS039405-06, NIH 1 R01 NS064259]; National
Institutes of Health, National Institute of Neurological Disorders and
Stroke; RCMI [G12 RR 03051]; NCRR-AABRE [P20 RR16470]; NIH-SCORE
[S06GM08102]; University of Puerto Rico Biology Department; NSF-CREST
[0206200]
FX This work was directly supported by NSF IBN-0344070, NIH 2 U54
NS039405-06, NIH 1 R01 NS064259, and the Intramural Research Program of
the National Institutes of Health, National Institute of Neurological
Disorders and Stroke. Part of the work was conducted in the Molecular
Biology Core Facility at the Institute of Neurobiology that is supported
by RCMI grant #G12 RR 03051. DNA sequencing at the Sequencing and
Genotyping facility, University of Puerto Rico-Rio Piedras is supported
in part by NCRR-AABRE Grant #P20 RR16470, NIH-SCORE grant #S06GM08102,
University of Puerto Rico Biology Department, and NSF-CREST grant
#0206200. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 47
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U1 1
U2 8
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 NOV
PY 2010
VL 8
IS 11
AR e1000540
DI 10.1371/journal.pbio.1000540
PG 9
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 687ES
UT WOS:000284762300012
PM 21124885
ER
PT J
AU Shamir, L
Delaney, JD
Orlov, N
Eckley, DM
Goldberg, IG
AF Shamir, Lior
Delaney, John D.
Orlov, Nikita
Eckley, D. Mark
Goldberg, Ilya G.
TI Pattern Recognition Software and Techniques for Biological Image
Analysis
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID FLUORESCENCE-MICROSCOPE IMAGES; NONLINEAR DIMENSIONALITY REDUCTION;
GENE-EXPRESSION PATTERNS; QUANTITATIVE-ANALYSIS; BIOIMAGE INFORMATICS;
SUBCELLULAR STRUCTURES; FLY EMBRYOS; CELLS; SEGMENTATION; ENVIRONMENT
AB The increasing prevalence of automated image acquisition systems is enabling new types of microscopy experiments that generate large image datasets. However, there is a perceived lack of robust image analysis systems required to process these diverse datasets. Most automated image analysis systems are tailored for specific types of microscopy, contrast methods, probes, and even cell types. This imposes significant constraints on experimental design, limiting their application to the narrow set of imaging methods for which they were designed. One of the approaches to address these limitations is pattern recognition, which was originally developed for remote sensing, and is increasingly being applied to the biology domain. This approach relies on training a computer to recognize patterns in images rather than developing algorithms or tuning parameters for specific image processing tasks. The generality of this approach promises to enable data mining in extensive image repositories, and provide objective and quantitative imaging assays for routine use. Here, we provide a brief overview of the technologies behind pattern recognition and its use in computer vision for biological and biomedical imaging. We list available software tools that can be used by biologists and suggest practical experimental considerations to make the best use of pattern recognition techniques for imaging assays.
C1 [Shamir, Lior; Delaney, John D.; Orlov, Nikita; Eckley, D. Mark; Goldberg, Ilya G.] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
RP Shamir, L (reprint author), NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
EM igg@nih.gov
RI Goldberg, Ilya/H-5307-2011; Eckley, Mark/M-3526-2014
OI Goldberg, Ilya/0000-0001-8514-6110; Eckley, Mark/0000-0003-2296-5164
FU NIH, National Institute on Aging [Z01:AG000685-02]
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Institute on Aging (Z01:AG000685-02). The funders
had no role in the decision to publish or preparation of the manuscript.
NR 64
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Z9 56
U1 0
U2 25
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD NOV
PY 2010
VL 6
IS 11
AR e1000974
DI 10.1371/journal.pcbi.1000974
PG 10
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 684WH
UT WOS:000284585400001
PM 21124870
ER
PT J
AU Aksenova, A
Volkov, K
Maceluch, J
Pursell, ZF
Rogozin, IB
Kunkel, TA
Pavlov, YI
Johansson, E
AF Aksenova, Anna
Volkov, Kirill
Maceluch, Jaroslaw
Pursell, Zachary F.
Rogozin, Igor B.
Kunkel, Thomas A.
Pavlov, Youri I.
Johansson, Erik
TI Mismatch Repair-Independent Increase in Spontaneous Mutagenesis in Yeast
Lacking Non-Essential Subunits of DNA Polymerase epsilon
SO PLOS GENETICS
LA English
DT Article
ID EUKARYOTIC REPLICATION FORK; SACCHAROMYCES-CEREVISIAE; HOMONUCLEOTIDE
RUNS; MUTATION AVOIDANCE; GENOMIC DELETIONS; LIGATABLE NICK; S PHASE;
DELTA; FIDELITY; ZETA
AB Yeast DNA polymerase epsilon (Pol epsilon) is a highly accurate and processive enzyme that participates in nuclear DNA replication of the leading strand template. In addition to a large subunit (Pol2) harboring the polymerase and proofreading exonuclease active sites, Pol epsilon also has one essential subunit (Dpb2) and two smaller, non-essential subunits (Dpb3 and Dpb4) whose functions are not fully understood. To probe the functions of Dpb3 and Dpb4, here we investigate the consequences of their absence on the biochemical properties of Pol epsilon in vitro and on genome stability in vivo. The fidelity of DNA synthesis in vitro by purified Pol2/Dpb2, i.e. lacking Dpb3 and Dpb4, is comparable to the four-subunit Pol e holoenzyme. Nonetheless, deletion of DPB3 and DPB4 elevates spontaneous frameshift and base substitution rates in vivo, to the same extent as the loss of Pol epsilon proofreading activity in a pol2-4 strain. In contrast to pol2-4, however, the dpb3 Delta dpb4 Delta does not lead to a synergistic increase of mutation rates with defects in DNA mismatch repair. The increased mutation rate in dpb3 Delta dpb4 Delta strains is partly dependent on REV3, as well as the proofreading capacity of Pol delta. Finally, biochemical studies demonstrate that the absence of Dpb3 and Dpb4 destabilizes the interaction between Pol epsilon and the template DNA during processive DNA synthesis and during processive 3' to 5'exonucleolytic degradation of DNA. Collectively, these data suggest a model wherein Dpb3 and Dpb4 do not directly influence replication fidelity per se, but rather contribute to normal replication fork progression. In their absence, a defective replisome may more frequently leave gaps on the leading strand that are eventually filled by Pol zeta or Pol delta, in a post-replication process that generates errors not corrected by the DNA mismatch repair system.
C1 [Aksenova, Anna; Volkov, Kirill; Maceluch, Jaroslaw; Johansson, Erik] Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden.
[Pursell, Zachary F.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Pursell, Zachary F.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Rogozin, Igor B.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Pavlov, Youri I.] Univ Nebraska Med Ctr, Eppley Inst Res Canc, Dept Biochem & Mol Biol, Omaha, NE USA.
[Pavlov, Youri I.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA.
RP Aksenova, A (reprint author), Tufts Univ, Dept Biol, Medford, MA 02155 USA.
EM erik.johansson@medchem.umu.se
RI Aksenova, Anna/O-8309-2015
OI Aksenova, Anna/0000-0002-1601-1615
FU Swedish Research Council; Swedish Cancer Society; Smartafonden;
Samfundet Wenner-Grenska stiftelsen; Kempestiftelserna; Swedish Royal
Academy of Sciences; National Library of Medicine at National Institutes
of Health/DHHS; Division of Intramural Research of the National
Institutes of Health, National Institute of Environmental Health
Sciences [Z01 ES065070]; UNMC Cancer Center [2008 LB506 NE DHHS]; NCI [1
R01 CA129925-01A1, 5R01CA129925-03]
FX This work was in part supported by the Swedish Research Council (EJ),
Swedish Cancer Society (EJ), Smartafonden (EJ), Samfundet Wenner-Grenska
stiftelsen (EJ), Kempestiftelserna (EJ), The Swedish Royal Academy of
Sciences (EJ), the Intramural Research Program of the National Library
of Medicine at National Institutes of Health/DHHS (IBR), Project Z01
ES065070 (TAK) from the Division of Intramural Research of the National
Institutes of Health, National Institute of Environmental Health
Sciences, and the UNMC Cancer Center Pilot Grants 2008 LB506 NE DHHS
grant, NCI grant 1 R01 CA129925-01A1, and NCI grant 5R01CA129925-03
(YIP). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 70
TC 24
Z9 25
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD NOV
PY 2010
VL 6
IS 11
AR e1001209
DI 10.1371/journal.pgen.1001209
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 684WX
UT WOS:000284587100023
PM 21124948
ER
PT J
AU Pomerantz, MM
Shrestha, Y
Flavin, RJ
Regan, MM
Penney, KL
Mucci, LA
Stampfer, MJ
Hunter, DJ
Chanock, SJ
Schafer, EJ
Chan, JA
Tabernero, J
Baselga, J
Richardson, AL
Loda, M
Oh, WK
Kantoff, PW
Hahn, WC
Freedman, ML
AF Pomerantz, Mark M.
Shrestha, Yashaswi
Flavin, Richard J.
Regan, Meredith M.
Penney, Kathryn L.
Mucci, Lorelei A.
Stampfer, Meir J.
Hunter, David J.
Chanock, Stephen J.
Schafer, Eric J.
Chan, Jennifer A.
Tabernero, Josep
Baselga, Jose
Richardson, Andrea L.
Loda, Massimo
Oh, William K.
Kantoff, Philip W.
Hahn, William C.
Freedman, Matthew L.
TI Analysis of the 10q11 Cancer Risk Locus Implicates MSMB and NCOA4 in
Human Prostate Tumorigenesis
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; HUMAN GENE-EXPRESSION; FUNCTIONAL-ANALYSIS;
COLORECTAL-CANCER; SECRETORY PROTEIN; EPITHELIAL-CELLS; FAMILY-HISTORY;
NUDE MICE; MULTIPLE; SUSCEPTIBILITY
AB Genome-wide association studies (GWAS) have established a variant, rs10993994, on chromosome 10q11 as being associated with prostate cancer risk. Since the variant is located outside of a protein-coding region, the target genes driving tumorigenesis are not readily apparent. Two genes nearest to this variant, MSMB and NCOA4, are strong candidates for mediating the effects of rs109939934. In a cohort of 180 individuals, we demonstrate that the rs10993994 risk allele is associated with decreased expression of two MSMB isoforms in histologically normal and malignant prostate tissue. In addition, the risk allele is associated with increased expression of five NCOA4 isoforms in histologically normal prostate tissue only. No consistent association with either gene is observed in breast or colon tissue. In conjunction with these findings, suppression of MSMB expression or NCOA4 overexpression promotes anchorage-independent growth of prostate epithelial cells, but not growth of breast epithelial cells. These data suggest that germline variation at chromosome 10q11 contributes to prostate cancer risk by influencing expression of at least two genes. More broadly, the findings demonstrate that disease risk alleles may influence multiple genes, and associations between genotype and expression may only be observed in the context of specific tissue and disease states.
C1 [Pomerantz, Mark M.; Shrestha, Yashaswi; Schafer, Eric J.; Loda, Massimo; Kantoff, Philip W.; Hahn, William C.; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Pomerantz, Mark M.; Regan, Meredith M.; Mucci, Lorelei A.; Stampfer, Meir J.; Hunter, David J.; Richardson, Andrea L.; Loda, Massimo; Kantoff, Philip W.; Hahn, William C.] Harvard Univ, Sch Med, Boston, MA USA.
[Shrestha, Yashaswi; Schafer, Eric J.; Loda, Massimo; Hahn, William C.; Freedman, Matthew L.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Shrestha, Yashaswi; Schafer, Eric J.; Loda, Massimo; Hahn, William C.; Freedman, Matthew L.] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA.
[Flavin, Richard J.; Loda, Massimo] Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Penney, Kathryn L.; Mucci, Lorelei A.; Stampfer, Meir J.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Mucci, Lorelei A.; Stampfer, Meir J.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Stampfer, Meir J.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Chan, Jennifer A.] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB, Canada.
[Tabernero, Josep; Baselga, Jose] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain.
[Richardson, Andrea L.; Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Oh, William K.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
RP Pomerantz, MM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM freedman@broadinstitute.org
RI Oh, William/B-9163-2012
OI Oh, William/0000-0001-5113-8147
FU Howard Hughes Medical Institute; Doris Duke Clinical Scientist
Development Award; Claudia Adams Barr award; US National Institutes of
Health [R01 CA129435]; Mayer Foundation; H.L. Snyder Medical Foundation;
Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (National Cancer
Institute) [5P50CA90381]; Emerald Foundation, Inc.; William L.
Edwards-Prostate Cancer Foundation; Prostate Cancer Foundation; John
Snyder Medical Foundation
FX MLF is a Howard Hughes Medical Institute Physician-Scientist Early
Career Awardee (www.hhmi.org), a recipient of a 2006 Doris Duke Clinical
Scientist Development Award (www.ddcf.org), and a recipient of a 2009
Claudia Adams Barr award (www.dana-farber.org). This work was supported
by grants from the US National Institutes of Health (R01 CA129435 to
MLF), the Mayer Foundation (to MLF), the H.L. Snyder Medical Foundation
(to MLF), the Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE
(National Cancer Institute Grant No. 5P50CA90381), and the Emerald
Foundation, Inc. (to MLF). MMP is supported by the William L.
Edwards-Prostate Cancer Foundation Young Investigator Award
(www.prostatecancerfoundation.org). WCH receives support from the
Prostate Cancer Foundation and the John Snyder Medical Foundation
(snydermf.org). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 42
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Z9 40
U1 1
U2 6
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 NOV
PY 2010
VL 6
IS 11
AR e1001204
DI 10.1371/journal.pgen.1001204
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 684WX
UT WOS:000284587100018
PM 21085629
ER
PT J
AU Adar, SD
Klein, R
Klein, BEK
Szpiro, AA
Cotch, MF
Wong, TY
O'Neill, MS
Shrager, S
Barr, RG
Siscovick, DS
Daviglus, ML
Sampson, PD
Kaufman, JD
AF Adar, Sara D.
Klein, Ronald
Klein, Barbara E. K.
Szpiro, Adam A.
Cotch, Mary Frances
Wong, Tien Y.
O'Neill, Marie S.
Shrager, Sandi
Barr, R. Graham
Siscovick, David S.
Daviglus, Martha L.
Sampson, Paul D.
Kaufman, Joel D.
TI Air Pollution and the Microvasculature: A Cross-Sectional Assessment of
In Vivo Retinal Images in the Population-Based Multi-Ethnic Study of
Atherosclerosis (MESA)
SO PLOS MEDICINE
LA English
DT Article
ID DIESEL-EXHAUST INHALATION; ACUTE ARTERIAL VASOCONSTRICTION; PARTICULATE
MATTER EXPOSURE; CORONARY-HEART-DISEASE; LONG-TERM EXPOSURE;
CARDIOVASCULAR-DISEASE; VESSEL DIAMETERS; VASCULAR CALIBER;
MYOCARDIAL-INFARCTION; MACULAR DEGENERATION
AB Background: Long-and short-term exposures to air pollution, especially fine particulate matter (PM(2.5)), have been linked to cardiovascular morbidity and mortality. One hypothesized mechanism for these associations involves microvascular effects. Retinal photography provides a novel, in vivo approach to examine the association of air pollution with changes in the human microvasculature.
Methods and Findings: Chronic and acute associations between residential air pollution concentrations and retinal vessel diameters, expressed as central retinal arteriolar equivalents (CRAE) and central retinal venular equivalents (CRVE), were examined using digital retinal images taken in Multi-Ethnic Study of Atherosclerosis (MESA) participants between 2002 and 2003. Study participants (46 to 87 years of age) were without clinical cardiovascular disease at the baseline examination (2000-2002). Long-term outdoor concentrations of PM2.5 were estimated at each participant's home for the 2 years preceding the clinical exam using a spatio-temporal model. Short-term concentrations were assigned using outdoor measurements on the day preceding the clinical exam. Residential proximity to roadways was also used as an indicator of long-term traffic exposures. All associations were examined using linear regression models adjusted for subject-specific age, sex, race/ethnicity, education, income, smoking status, alcohol use, physical activity, body mass index, family history of cardiovascular disease, diabetes status, serum cholesterol, glucose, blood pressure, emphysema, C-reactive protein, medication use, and fellow vessel diameter. Short-term associations were further controlled for weather and seasonality. Among the 4,607 participants with complete data, CRAE were found to be narrower among persons residing in regions with increased long-and short-term levels of PM(2.5). These relationships were observed in a joint exposure model with -0.8 mm (95% confidence interval [CI]-1.1 to -0.5) and -0.4 mu m (95% CI -0.8 to 0.1) decreases in CRAE per interquartile increases in long-(3 mu g/m(3)) and short-term (9 mu g/m(3)) PM(2.5) levels, respectively. These reductions in CRAE are equivalent to 7-and 3-year increases in age in the same cohort. Similarly, living near a major road was also associated with a -0.7 mu m decrease (95% CI -1.4 to 0.1) in CRAE. Although the chronic association with CRAE was largely influenced by differences in exposure between cities, this relationship was generally robust to control for city-level covariates and no significant differences were observed between cities. Wider CRVE were associated with living in areas of higher PM(2.5) concentrations, but these findings were less robust and not supported by the presence of consistent acute associations with PM(2.5).
Conclusions: Residing in regions with higher air pollution concentrations and experiencing daily increases in air pollution were each associated with narrower retinal arteriolar diameters in older individuals. These findings support the hypothesis that important vascular phenomena are associated with small increases in short-term or long-term air pollution exposures, even at current exposure levels, and further corroborate reported associations between air pollution and the development and exacerbation of clinical cardiovascular disease.
C1 [Adar, Sara D.; Siscovick, David S.; Kaufman, Joel D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Adar, Sara D.; Kaufman, Joel D.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA.
[Adar, Sara D.; O'Neill, Marie S.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[Szpiro, Adam A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
[Wong, Tien Y.] Univ Melbourne, Dept Ophthalmol, Melbourne, Vic, Australia.
[Wong, Tien Y.; Shrager, Sandi] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore.
[O'Neill, Marie S.] Univ Michigan, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Barr, R. Graham] Columbia Univ Med Ctr, Dept Med, New York, NY USA.
[Barr, R. Graham] Columbia Univ Med Ctr, Dept Epidemiol, New York, NY USA.
[Siscovick, David S.; Kaufman, Joel D.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Daviglus, Martha L.] Northwestern Univ, Dept Prevent Med & Med, Chicago, IL 60611 USA.
[Sampson, Paul D.] Univ Washington, Dept Stat, Seattle, WA 98195 USA.
RP Adar, SD (reprint author), Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
EM sadar@umich.edu
RI Kaufman, Joel/B-5761-2008; Adar, Sara/L-2278-2016;
OI Kaufman, Joel/0000-0003-4174-9037; Adar, Sara/0000-0001-8383-485X;
Cotch, Mary Frances/0000-0002-2046-4350; Klein,
Ronald/0000-0002-4428-6237
FU Environmental Protection Agency [RD831697]; National Eye Institute
[EY000403]; National Heart, Lung, Blood Institute [HL69979, N01-HC-
95159, N01-HC-95165, N01-HC-95169]; National Institutes of Environmental
Health Sciences [K24ES013195, P50ES015915, P30ES07033, R01ES016932]
FX This work was supported by awards RD831697 from the Environmental
Protection Agency; EY000403 from the National Eye Institute; HL69979,
N01-HC- 95159 through N01-HC-95165, and N01-HC-95169 from the National
Heart, Lung, Blood Institute; and K24ES013195, P50ES015915, P30ES07033
and R01ES016932 from the National Institutes of Environmental Health
Sciences. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 52
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PI SAN FRANCISCO
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SN 1549-1277
J9 PLOS MED
JI PLos Med.
PD NOV
PY 2010
VL 7
IS 11
AR e1000372
DI 10.1371/journal.pmed.1000372
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 688BE
UT WOS:000284822600013
PM 21152417
ER
PT J
AU Baas, DC
Despriet, DD
Gorgels, TGMF
Bergeron-Sawitzke, J
Uitterlinden, AG
Hofman, A
van Duijn, CM
Merriam, JE
Smith, RT
Barile, GR
ten Brink, JB
Vingerling, JR
Klaver, CCW
Allikmets, R
Dean, M
Bergen, AAB
AF Baas, Dominique C.
Despriet, Dominiek D.
Gorgels, Theo G. M. F.
Bergeron-Sawitzke, Julie
Uitterlinden, Andre G.
Hofman, Albert
van Duijn, Cornelia M.
Merriam, Joanna E.
Smith, R. Theodore
Barile, Gaetano R.
ten Brink, Jacoline B.
Vingerling, Johannes R.
Klaver, Caroline C. W.
Allikmets, Rando
Dean, Michael
Bergen, Arthur A. B.
TI The ERCC6 Gene and Age-Related Macular Degeneration
SO PLOS ONE
LA English
DT Article
ID COMPLEMENT FACTOR-H; COCKAYNE-SYNDROME; OXIDATIVE STRESS; RISK; REPAIR;
POLYMORPHISM; MACULOPATHY; ROTTERDAM; VARIANT; DAMAGE
AB Background: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the developed countries and is caused by both environmental and genetic factors. A recent study (Tuo et al., PNAS) reported an association between AMD and a single nucleotide polymorphism (SNP) (rs3793784) in the ERCC6 (NM_000124) gene. The risk allele also increased ERCC6 expression. ERCC6 is involved in DNA repair and mutations in ERCC6 cause Cockayne syndrome (CS). Amongst others, photosensitivity and pigmentary retinopathy are hallmarks of CS.
Methodology/Principal Findings: Separate and combined data from three large AMD case-control studies and a prospective population-based study (The Rotterdam Study) were used to analyse the genetic association between ERCC6 and AMD (2682 AMD cases and 3152 controls). We also measured ERCC6 mRNA levels in retinal pigment epithelium (RPE) cells of healthy and early AMD affected human donor eyes. Rs3793784 conferred a small increase in risk for late AMD in the Dutch population (The Rotterdam and AMRO-NL study), but this was not replicated in two non-European studies (AREDS, Columbia University). In addition, the AMRO-NL study revealed no significant association for 9 other variants spanning ERCC6. Finally, we determined that ERCC6 expression in the human RPE did not depend on rs3793784 genotype, but, interestingly, on AMD status: Early AMD-affected donor eyes had a 50% lower ERCC6 expression than healthy donor eyes (P = 0.018).
Conclusions/Significance: Our meta-analysis of four Caucasian cohorts does not replicate the reported association between SNPs in ERCC6 and AMD. Nevertheless, our findings on ERCC6 expression in the RPE suggest that ERCC6 may be functionally involved in AMD. Combining our data with those of the literature, we hypothesize that the AMD-related reduced transcriptional activity of ERCC6 may be caused by diverse, small and heterogeneous genetic and/or environmental determinants.
C1 [Baas, Dominique C.; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; Bergen, Arthur A. B.] Royal Netherlands Acad Arts & Sci KNAW, Dept Clin & Mol Ophthalmogenet, Netherlands Inst Neurosci NIN, Amsterdam, Netherlands.
[Despriet, Dominiek D.; Uitterlinden, Andre G.; Hofman, Albert; van Duijn, Cornelia M.; Vingerling, Johannes R.; Klaver, Caroline C. W.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Bergeron-Sawitzke, Julie] SAIC Frederick, Basic Sci Program, Human Genet Sect, Frederick, MD USA.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Merriam, Joanna E.; Smith, R. Theodore; Barile, Gaetano R.; Allikmets, Rando] Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA.
[Merriam, Joanna E.; Smith, R. Theodore; Barile, Gaetano R.; Allikmets, Rando] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10027 USA.
[Dean, Michael] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA.
[Bergen, Arthur A. B.] Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands.
[Bergen, Arthur A. B.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands.
RP Baas, DC (reprint author), Royal Netherlands Acad Arts & Sci KNAW, Dept Clin & Mol Ophthalmogenet, Netherlands Inst Neurosci NIN, Amsterdam, Netherlands.
EM a.bergen@nin.knaw.nl
RI Dean, Michael/G-8172-2012; Bergen, Arthur/J-3637-2013;
OI Dean, Michael/0000-0003-2234-0631; smith, theodore/0000-0002-1693-943X
FU Merck & Co, Inc., NJ, USA; Nederlandse Vereniging ter Voorkoming van
Blindheid; Dutch Macula Foundation; LSBS; Oogfonds Nederland; de
Rotterdamse Vereniging Blindenbelangen; Netherlands Organization of
Scientific Research NWO Investments [175.010.2005.011, 911-03-012];
Research Institute for Diseases in the Elderly [014-93-015, RIDE2];
Netherlands Genomics Initiative (NGI)/Netherlands Organization for
Scientific Research (NWO) [050-060-810]; Erasmus Medical Center; Erasmus
University, Rotterdam; Netherlands Organization for the Health Research
and Development (ZonMw); Research Institute for Diseases in the Elderly
(RIDE),; Ministry for Health, Welfare and Sports; European Commission;
Municipality of Rotterdam; National Eye Institute [EY13435, EY017404];
Macula Vision Research Foundation; Kaplen Foundation; Wigdeon Point
Charitable Foundation; Research to Prevent Blindness, Inc.; Merck Co;
Ministry of Education, Culture and Science
FX This work was in part supported by an unrestricted research grant from
Merck & Co, Inc., NJ, USA and the Nederlandse Vereniging ter Voorkoming
van Blindheid, The Dutch Macula Foundation, the LSBS, the Oogfonds
Nederland, de Rotterdamse Vereniging Blindenbelangen (to A. A. B.). The
generation and management of GWAS genotype data for the Rotterdam Study
is supported by the Netherlands Organization of Scientific Research NWO
Investments (nr. 175.010.2005.011, 911-03-012). This study is funded by
the Research Institute for Diseases in the Elderly (014-93-015; RIDE2),
the Netherlands Genomics Initiative (NGI)/Netherlands Organization for
Scientific Research (NWO) project nr. 050-060-810, and funding from the
Erasmus Medical Center and Erasmus University, Rotterdam, 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 Columbia University study population is supported in part
by the grants from the National Eye Institute EY13435 and EY017404; the
Macula Vision Research Foundation; Kaplen Foundation; Wigdeon Point
Charitable Foundation and an unrestricted grant to the Department of
Ophthalmology, Columbia University, from Research to Prevent Blindness,
Inc. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.; The
funding of Merck & Co was an unrestricted grant to A. A. B. and did not,
in any way, interfere with the conception and/or design and/or outcome
and/or publication of this study. This does not alter the authors'
adherence to all the PLoS ONE policies on sharing data and materials.
NR 50
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PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 1
PY 2010
VL 5
IS 11
AR e13786
DI 10.1371/journal.pone.0013786
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 673FY
UT WOS:000283645700009
PM 21072178
ER
PT J
AU Das, SR
Puigbo, P
Hensley, SE
Hurt, DE
Bennink, JR
Yewdell, JW
AF Das, Suman R.
Puigbo, Pere
Hensley, Scott E.
Hurt, Darrell E.
Bennink, Jack R.
Yewdell, Jonathan W.
TI Glycosylation Focuses Sequence Variation in the Influenza A Virus H1
Hemagglutinin Globular Domain
SO PLOS PATHOGENS
LA English
DT Article
ID N-LINKED GLYCOSYLATION; HYDROXY AMINO-ACID; INTRACELLULAR-TRANSPORT;
RECEPTOR-BINDING; MEMBRANE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES;
ANTIGENIC STRUCTURE; SITES; GLYCANS; VIRULENCE
AB Antigenic drift in the influenza A virus hemagglutinin (HA) is responsible for seasonal reformulation of influenza vaccines. Here, we address an important and largely overlooked issue in antigenic drift: how does the number and location of glycosylation sites affect HA evolution in man? We analyzed the glycosylation status of all full-length H1 subtype HA sequences available in the NCBI influenza database. We devised the "flow index'' (FI), a simple algorithm that calculates the tendency for viruses to gain or lose consensus glycosylation sites. The FI predicts the predominance of glycosylation states among existing strains. Our analyses show that while the number of glycosylation sites in the HA globular domain does not influence the overall magnitude of variation in defined antigenic regions, variation focuses on those regions unshielded by glycosylation. This supports the conclusion that glycosylation generally shields HA from antibody-mediated neutralization, and implies that fitness costs in accommodating oligosaccharides limit virus escape via HA hyperglycosylation.
C1 [Das, Suman R.; Hensley, Scott E.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
[Puigbo, Pere] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Hurt, Darrell E.] NIAID, Computat Biol Bioinformat & Computat Biosci Branc, Bethesda, MD 20892 USA.
RP Das, SR (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
RI Puigbo, Pere/A-2214-2008; yewdell, jyewdell@nih.gov/A-1702-2012; Das,
Suman/C-8760-2009
FU Division of Intramural Research, National Institutes of Health
FX This work was supported by the Division of Intramural Research, 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 44
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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 NOV
PY 2010
VL 6
IS 11
AR e1001211
DI 10.1371/journal.ppat.1001211
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 684WP
UT WOS:000284586300044
PM 21124818
ER
PT J
AU Dobson, DE
Kamhawi, S
Lawyer, P
Turco, SJ
Beverley, SM
Sacks, DL
AF Dobson, Deborah E.
Kamhawi, Shaden
Lawyer, Phillip
Turco, Salvatore J.
Beverley, Stephen M.
Sacks, David L.
TI Leishmania major Survival in Selective Phlebotomus papatasi Sand Fly
Vector Requires a Specific SCG-Encoded Lipophosphoglycan Galactosylation
Pattern
SO PLOS PATHOGENS
LA English
DT Article
ID PROTOZOAN PARASITE LEISHMANIA; SECRETED ACID-PHOSPHATASE; SURFACE
LIPOPHOSPHOGLYCAN; RECOGNITION RECEPTORS; FLIES; DONOVANI; STAGE;
PROMASTIGOTES; MIDGUT; POLYMORPHISMS
AB Phlebotomine sand flies that transmit the protozoan parasite Leishmania differ greatly in their ability to support different parasite species or strains in the laboratory: while some show considerable selectivity, others are more permissive. In "selective'' sand flies, Leishmania binding and survival in the fly midgut typically depends upon the abundant promastigote surface adhesin lipophosphoglycan (LPG), which exhibits species-and strain-specific modifications of the dominant phosphoglycan (PG) repeat units. For the "selective'' fly Phlebotomus papatasi PpapJ, side chain galactosyl-modifications (scGal) of PG repeats play key roles in parasite binding. We probed the specificity and properties of this scGal-LPG PAMP (Pathogen Associated Molecular Pattern) through studies of natural isolates exhibiting a wide range of galactosylation patterns, and of a panel of isogenic L. major engineered to express similar scGal-LPG diversity by transfection of SCG-encoded beta 1,3-galactosyltransferases with different activities. Surprisingly, both 'poly-scGal' and 'null-scGal' lines survived poorly relative to PpapJ-sympatric L. major FV1 and other 'mono-scGal' lines. However, survival of all lines was equivalent in P. duboscql, which naturally transmit L. major strains bearing 'null-scGal'-LPG PAMPs. We then asked whether scGal-LPG-mediated interactions were sufficient for PpapJ midgut survival by engineering Leishmania donovani, which normally express unsubstituted LPG, to express a 'PpapJ-optimal' scGal-LPG PAMP. Unexpectedly, these "L. major FV1-cloaked'' L. donovani-SCG lines remained unable to survive within PpapJ flies. These studies establish that midgut survival of L. major in PpapJ flies is exquisitely sensitive to the scGal-LPG PAMP, requiring a specific 'mono-scGal' pattern. However, failure of 'mono-scGal' L. donovani-SCG lines to survive in selective PpapJ flies suggests a requirement for an additional, as yet unidentified L. major-specific parasite factor(s). The interplay of the LPG PAMP and additional factor(s) with sand fly midgut receptors may determine whether a given sand fly host is "selective'' or "permissive'', with important consequences to both disease transmission and the natural co-evolution of sand flies and Leishmania.
C1 [Dobson, Deborah E.; Beverley, Stephen M.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Kamhawi, Shaden; Lawyer, Phillip; Sacks, David L.] NIH, Parasit Dis Lab, Intracellular Parasite Biol Sect, Bethesda, MD 20892 USA.
[Turco, Salvatore J.] Univ Kentucky, Med Ctr, Dept Mol & Cellular Biochem, Lexington, KY USA.
RP Dobson, DE (reprint author), Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
EM dedobson@borcim.wustl.edu
OI Beverley, Stephen/0000-0001-5319-0811
FU US National Institutes of Health [AI31078, AI20941]
FX This work was supported by US National Institutes of Health grants
AI31078 (SMB, SJT) and AI20941 (DED, SMB, SJT). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 56
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PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD NOV
PY 2010
VL 6
IS 11
AR e1001185
DI 10.1371/journal.ppat.1001185
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 684WP
UT WOS:000284586300019
PM 21085609
ER
PT J
AU Gustchina, E
Li, M
Louis, JM
Anderson, DE
Lloyd, J
Frisch, C
Bewley, CA
Gustchina, A
Wlodawer, A
Clore, GM
AF Gustchina, Elena
Li, Mi
Louis, John M.
Anderson, D. Eric
Lloyd, John
Frisch, Christian
Bewley, Carole A.
Gustchina, Alla
Wlodawer, Alexander
Clore, G. Marius
TI Structural Basis of HIV-1 Neutralization by Affinity Matured Fabs
Directed against the Internal Trimeric Coiled-Coil of gp41
SO PLOS PATHOGENS
LA English
DT Article
ID HUMAN MONOCLONAL-ANTIBODY; TERMINAL HEPTAD REPEATS; MEDIATED
CELL-FUSION; POTENT INHIBITORS; MEMBRANE-FUSION; PHAGE LIBRARY; ENVELOPE
GLYCOPROTEIN; PEPTIDE INHIBITOR; MASS-SPECTROMETRY; ENTRY INHIBITION
AB The conserved internal trimeric coiled-coil of the N-heptad repeat (N-HR) of HIV-1 gp41 is transiently exposed during the fusion process by forming a pre-hairpin intermediate, thus representing an attractive target for the design of fusion inhibitors and neutralizing antibodies. In previous studies we reported a series of broadly neutralizing mini-antibodies derived from a synthetic naive human combinatorial antibody library by panning against a mimetic of the trimeric N-HR coiled coil, followed by affinity maturation using targeted diversification of the CDR-H2 loop. Here we report crystal structures of the N-HR mimetic 5-Helix with two Fabs that represent the extremes of this series: Fab 8066 is broadly neutralizing across a wide panel of B and C type HIV-1 viruses, whereas Fab 8062 is non-neutralizing. The crystal structures reveal important differences in the conformations of the CDR-H2 loops in the complexes that propagate into other regions of the antigen-antibody interface, and suggest that both neutralization properties and affinity for the target can be attributed, at least in part, to the differences in the interactions of the CDR-H2 loops with the antigen. Furthermore, modeling of the complex of an N-HR trimer with three Fabs suggests that the CDR-H2 loop may be involved in close intermolecular contacts between neighboring antibody molecules, and that such contacts may hinder the formation of complexes between the N-HR trimer and more than one antibody molecule depending on the conformation of the bound CDR-H2 loop which is defined by its interactions with antigen. Comparison with the crystal structure of the complex of 5-Helix with another neutralizing monoclonal antibody known as D5, derived using an entirely different antibody library and panning procedure, reveals remarkable convergence in the optimal sequence and conformation of the CDR-H2 loop.
C1 [Gustchina, Elena; Louis, John M.; Clore, G. Marius] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Li, Mi; Gustchina, Alla; Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21701 USA.
[Li, Mi] SAIC Frederick, Basic Res Program, Frederick, MD USA.
[Anderson, D. Eric; Lloyd, John] NIDDKD, Prote & Mass Spectrometry Facil, NIH, Bethesda, MD 20892 USA.
[Frisch, Christian] MorphoSys AG, AbD Serotec, Martinsried, Germany.
[Bewley, Carole A.] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Gustchina, E (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM gustchia@mail.nih.gov; wlodawer@nih.gov; mariusc@mail.nih.gov
RI Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
FU U.S. Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; NIDDK; National Cancer Institute, Center for
Cancer Research at the NIH; National Cancer Institute, NIH
[HHSN261200800001E]; Office of the Director of the NIH
FX We acknowledge the use of beamline 22-ID of the Southeast Regional
Collaborative Access Team (SER-CAT), located at the Advanced Photon
Source, Argonne National Laboratory. Use of the APS was supported by the
U.S. Department of Energy, Office of Science, Office of Basic Energy
Sciences, under Contract No. W-31-109-Eng-38. This project was supported
in part by the Intramural Research Programs of the NIDDK (to G. M. C.
and C. A. B.) and National Cancer Institute, Center for Cancer Research
(to A. W.) at the NIH, by the AIDS Targeted Antiviral Program of the
Office of the Director of the NIH (to G. M. C. and C. A. B.), and with
Federal funds from the National Cancer Institute, NIH, under Contract
No. HHSN261200800001E (M. L.). The content of this publication is solely
the responsibility of the authors and does not necessarily represent the
official views or policies of the Department of Health and Human
Services, nor does the mention of trade names, commercial products, or
organizations imply endorsement by the U. S. Government. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 52
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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 NOV
PY 2010
VL 6
IS 11
AR e1001182
DI 10.1371/journal.ppat.1001182
PG 19
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 684WP
UT WOS:000284586300016
PM 21085615
ER
PT J
AU Wang, YE
Park, A
Lake, M
Pentecost, M
Torres, B
Yun, TE
Wolf, MC
Holbrook, MR
Freiberg, AN
Lee, B
AF Wang, Yao E.
Park, Arnold
Lake, Michael
Pentecost, Mickey
Torres, Betsabe
Yun, Tatyana E.
Wolf, Mike C.
Holbrook, Michael R.
Freiberg, Alexander N.
Lee, Benhur
TI Ubiquitin-Regulated Nuclear-Cytoplasmic Trafficking of the Nipah Virus
Matrix Protein Is Important for Viral Budding
SO PLOS PATHOGENS
LA English
DT Article
ID PROTEASOME INHIBITOR BORTEZOMIB; PLASMA-MEMBRANE; TYPE-1 GAG; FUSION
PROTEINS; EXPORT SIGNALS; INFECTED-CELLS; SENDAI-VIRUS; V-PROTEIN;
IN-VIVO; PHASE-I
AB Paramyxoviruses are known to replicate in the cytoplasm and bud from the plasma membrane. Matrix is the major structural protein in paramyxoviruses that mediates viral assembly and budding. Curiously, the matrix proteins of a few paramyxoviruses have been found in the nucleus, although the biological function associated with this nuclear localization remains obscure. We report here that the nuclear-cytoplasmic trafficking of the Nipah virus matrix (NiV-M) protein and associated post-translational modification play a critical role in matrix-mediated virus budding. Nipah virus (NiV) is a highly pathogenic emerging paramyxovirus that causes fatal encephalitis in humans, and is classified as a Biosafety Level 4 (BSL4) pathogen. During live NiV infection, NiV-M was first detected in the nucleus at early stages of infection before subsequent localization to the cytoplasm and the plasma membrane. Mutations in the putative bipartite nuclear localization signal (NLS) and the leucine-rich nuclear export signal (NES) found in NiV-M impaired its nuclear-cytoplasmic trafficking and also abolished NiV-M budding. A highly conserved lysine residue in the NLS served dual functions: its positive charge was important for mediating nuclear import, and it was also a potential site for monoubiquitination which regulates nuclear export of the protein. Concordantly, overexpression of ubiquitin enhanced NiV-M budding whereas depletion of free ubiquitin in the cell (via proteasome inhibitors) resulted in nuclear retention of NiV-M and blocked viral budding. Live Nipah virus budding was exquisitely sensitive to proteasome inhibitors: bortezomib, an FDA-approved proteasome inhibitor for treating multiple myeloma, reduced viral titers with an IC(50) of 2.7 nM, which is 100-fold less than the peak plasma concentration that can be achieved in humans. This opens up the possibility of using an "off-the-shelf'' therapeutic against acute NiV infection.
C1 [Wang, Yao E.; Park, Arnold; Lake, Michael; Pentecost, Mickey; Torres, Betsabe; Wolf, Mike C.; Lee, Benhur] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90024 USA.
[Yun, Tatyana E.; Holbrook, Michael R.; Freiberg, Alexander N.] Univ Texas Med Branch, Dept Pathol, Galveston, TX USA.
[Holbrook, Michael R.] NIAID, Integrated Res Facil, NIH, Frederick, MD USA.
[Lee, Benhur] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA.
[Lee, Benhur] Univ Calif Los Angeles, UCLA AIDS Inst, Los Angeles, CA USA.
RP Wang, YE (reprint author), Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90024 USA.
EM bleebhl@ucla.edu
RI Lee, Benhur/A-8554-2016;
OI Lee, Benhur/0000-0003-0760-1709; Park, Arnold/0000-0001-8916-2230
FU Cellular and Molecular Biology Training grant [T32 GM007185]; UCLA
[AI07323]; NIH [U01 AI082100, R01 AI069317, U01 AI070495, GM055052];
National Science Foundation [HRD-0603239]; Pacific Southwest Regional
Center of Excellence for Biodefense & Emerging Infectious Diseases [U54
AI065359]; UCLA AIDS Institute; CFAR [P30 AI028697]; Burroughs Wellcome
Fund; Rockefeller Brothers Fund
FX This work was supported by the Cellular and Molecular Biology Training
grant (T32 GM007185) to A. P., the Molecular Pathogenesis Training Grant
and UCLA Warsaw Fellowship to M. C. W. (AI07323), and NIH grants to B.
L. (U01 AI070495, U01 AI082100, R01 AI069317), M. R. H. (U01 AI070495,
U01 AI082100) and A.N.F. (U01 AI070495, U01 AI082100). B. T. was
supported by a National Science Foundation grant (HRD-0603239) and the
Maximizing Student Diversity Program (NIH grant GM055052). We also
acknowledge support from the Pacific Southwest Regional Center of
Excellence for Biodefense & Emerging Infectious Diseases (U54 AI065359)
and the UCLA AIDS Institute and CFAR (P30 AI028697). B. L. also thanks
the Burroughs Wellcome Fund and the Rockefeller Brothers Fund for
providing initial unrestricted funds to explore new fields. 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 NOV
PY 2010
VL 6
IS 11
AR e1001186
DI 10.1371/journal.ppat.1001186
PG 17
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 684WP
UT WOS:000284586300020
PM 21085610
ER
PT J
AU Agalliu, I
Leanza, SM
Smith, L
Trent, JM
Carpten, JD
Bailey-Wilson, JE
Burk, RD
AF Agalliu, Ilir
Leanza, Suzanne M.
Smith, Lorie
Trent, Jeffrey M.
Carpten, John D.
Bailey-Wilson, Joan E.
Burk, Robert D.
TI Contribution of HPC1 (RNASEL) and HPCX Variants to Prostate Cancer in a
Founder Population
SO PROSTATE
LA English
DT Article
DE prostate cancer; genetic susceptibility; RNASEL; founder population;
HPCX
ID SUSCEPTIBILITY LOCUS HPCX; 2-5A-DEPENDENT RNASE; LINKAGE ANALYSIS; GENE;
FAMILIES; RISK; ASSOCIATION; HEREDITARY; MUTATION; METAANALYSIS
AB BACKGROUND. Prostate cancer is a genetically complex disease with locus and disease heterogeneity. The RNASEL gene and HPCX locus have been implicated in hereditary prostate cancer; however, their contributions to sporadic forms of this malignancy remain uncertain.
METHODS. Associations of prostate cancer with two variants in the RNASEL gene (a founder mutation, 471delAAAG, and a non-synonymous SNP, rs486907), and with five microsatellite markers in the HPCX locus, were examined in 979 cases and 1,251 controls of Ashkenazi Jewish descent. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models.
RESULTS. There was an inverse association between RNASEL rs486907 and prostate cancer in younger men (<65 years) and those with a first-degree relative with prostate cancer; men with AA genotype had ORs of 0.64 and 0.47 (both P < 0.05), respectively, in comparison to men with GG genotype. Within the HPCX region, there were positive associations for allele 135 of bG82i1.1 marker (OR = 1.77, P = 0.01) and allele 188 of DXS1205 (OR = 1.65, P = 0.02). In addition, allele 248 of marker D33 was inversely associated (OR = 0.65, P = 0.05) with Gleason score >= 7 tumors.
CONCLUSIONS. Results suggest that variants in RNASEL contribute to susceptibility to early onset and familial forms of prostate cancer, whereas HPCX variants are associated with prostate cancer risk and tumor aggressiveness. The observation that a mutation predicted to completely inactivate RNASEL protein was not associated with prostate cancer, but that a missense variant was associated, suggests that the effect is due to either partial inactivation of the protein, and/or acquisition of a new protein activity. Prostate 70: 1716-1727, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Leanza, Suzanne M.; Smith, Lorie; Burk, Robert D.] Albert Einstein Coll Med, Dept Pediat Genet, Bronx, NY 10461 USA.
[Agalliu, Ilir; Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Trent, Jeffrey M.] Translat Genom Res Inst TGen, Phoenix, AZ USA.
[Carpten, John D.; Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, Bethesda, MD 20892 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10467 USA.
RP Burk, RD (reprint author), Albert Einstein Coll Med, Dept Pediat Genet, 1300 Morris Pk Ave,Ullmann Bldg,Room 515, Bronx, NY 10461 USA.
EM robert.burk@einstein.yu.edu
OI Bailey-Wilson, Joan/0000-0002-9153-2920
FU US Army, Department of Defense [PC001076]; Albert Einstein College of
Medicine; National Human Genome Research Institute, National Institutes
of Health
FX We thank Stacey Fishman, Gloria Ho, Nicolas Schlecht, Victor Kamensky,
Mindy Ginsberg, Leonid Strizhevsky, Rochelle Demsky, Peggy Cottrel,
Betsy Vibert, Kit Tam, and Lydia Chiu for their help with study design
and data collection. We are grateful to all men who participated in this
study for their time, effort and collaboration. This project was
supported by the US Army, Department of Defense grant (PC001076), in
part by a translational-medicine grant from the Albert Einstein College
of Medicine and in part by the Intramural program of the National Human
Genome Research Institute, National Institutes of Health. Ilir Agalliu
was supported by university funds from the Albert Einstein College of
Medicine.
NR 51
TC 15
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 NOV 1
PY 2010
VL 70
IS 15
BP 1716
EP 1727
DI 10.1002/pros.21207
PG 12
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 672EO
UT WOS:000283566000012
PM 20564318
ER
PT J
AU Chun, PW
Lewis, MS
AF Chun, Paul W.
Lewis, Marc S.
TI Planck-Benzinger Thermal Work Function: Thermodynamic Characterization
of the Carboxy-Terminus of p53 Peptide Fragments
SO PROTEIN JOURNAL
LA English
DT Article
ID TUMOR-SUPPRESSOR P53; BIOLOGICAL-SYSTEMS; MOLECULAR SWITCH;
CRYSTAL-STRUCTURE; OLIGOMERIZATION DOMAIN; TETRAMERIZATION DOMAIN;
TRANSFORMING DOMAIN; RIBONUCLEASE-A; WATER-VAPOR; PROTEIN P53
AB The thermodynamic parameters for six p53 carboxy-terminus peptide fragments as determined by analytical ultracentrifugal analysis were compared over the experimental temperature range of 275-310 K to evaluate the Gibbs free energy change as a function of temperature, Delta G (o) (T), from 0 to 400 K using our general linear third-order fitting function, Delta G (o) (T) = alpha + beta T (2) + gamma T (3). Data obtained at the typical experimental temperature range are not sufficient to accurately describe the variations observed in the oligomerization of these p53 fragments. It is necessary to determine a number of thermodynamic parameters, all of which can be precisely assessed using this general third-order linear fitting function. These are the heat of reaction, innate temperature-invariant enthalpy, compensatory temperatures and the thermodynamic molecular switch occurring at the thermal set point. This methodology can be used to distinguish the characteristic structure and stability of p53 carboxy-terminal fragments or other p53 mutants. It should be used for the thermodynamic characterization of any interacting biological system.
C1 [Chun, Paul W.] Univ Florida, Dept Biochem & Mol Biol, Coll Med, Gainesville, FL 32610 USA.
[Lewis, Marc S.] NIH, Natl Ctr Res Resources, Biomed Engn & Instrumentat Program, Bethesda, MD 20892 USA.
RP Chun, PW (reprint author), Univ Florida, Dept Biochem & Mol Biol, Coll Med, Gainesville, FL 32610 USA.
EM pwchun@ufl.edu
NR 73
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1572-3887
J9 PROTEIN J
JI Protein J.
PD NOV
PY 2010
VL 29
IS 8
BP 617
EP 630
DI 10.1007/s10930-010-9286-9
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 685QY
UT WOS:000284644400011
PM 21086029
ER
PT J
AU Sayer, JM
Agniswamy, J
Weber, IT
Louis, JM
AF Sayer, Jane M.
Agniswamy, Johnson
Weber, Irene T.
Louis, John M.
TI Autocatalytic maturation, physical/chemical properties, and crystal
structure of Group N HIV-1 protease: Relevance to drug resistance
SO PROTEIN SCIENCE
LA English
DT Article
DE HIV/AIDS; retroviral protease; dimer dissociation; enzyme kinetics;
calorimetry; crystal structure; polyprotein processing
ID VIRUS TYPE-1 PROTEASE; ACTIVE-SITE; INHIBITOR; STABILITY; MONOMER;
POTENT; IDENTIFICATION; MUTATIONS; SEQUENCE; CAMEROON
AB The mature protease from Group N human immunodeficiency virus Type 1 (HIV-1) (PR1(N)) differs in 20 amino acids from the extensively studied Group M protease (PRIM) at positions corresponding to minor drug-resistance mutations (DRMs). The first crystal structure (1.09 angstrom resolution) of PR1(N) with the clinical inhibitor darunavir (DRV) reveals the same overall structure as PR1(M), but with a slightly larger inhibitor-binding cavity. Changes in the 10s loop and the flap hinge propagate to shift one flap away from the inhibitor, whereas L89F and substitutions in the 60s loop perturb inhibitor-binding residues 29-32. However, kinetic parameters of PR1(N) closely resemble those of PR1(M), and calorimetric results are consistent with similar binding affinities for DRV and two other clinical PIs, suggesting that minor DRMs coevolve to compensate for the detrimental effects of drug-specific major DRMs. A miniprecursor (TFR1-61-PR1(N)) comprising the transframe region (TFR) fused to the N-terminus of PR1(N) undergoes autocatalytic cleavage at the TFR/PR1(N) site concomitant with the appearance of catalytic activity characteristic of the dimeric, mature enzyme. This cleavage is inhibited at an equimolar ratio of precursor to DRV (similar to 6 mu M), which partially stabilizes the precursor dimer from a monomer. However, cleavage at L34/W35 within the TFR, which precedes the TFR1-61/PR1(N) cleavage at pH <= 5, is only partially inhibited. Favorable properties of PR1(N) relative to PR1(M) include its suitability for column fractionation by size under native conditions and >10-fold higher dimer dissociation constant (150 nM). Exploiting these properties may facilitate testing of potential dimerization inhibitors that perturb early precursor processing steps.
C1 [Sayer, Jane M.; Louis, John M.] NIDDK, NIH, LCP, DHHS, Bethesda, MD 20892 USA.
[Agniswamy, Johnson; Weber, Irene T.] Georgia State Univ, Dept Biol, Mol Basis Dis Program, Atlanta, GA 30303 USA.
RP Louis, JM (reprint author), NIDDK, NIH, LCP, DHHS, Bldg 5,Room B2-29, Bethesda, MD 20892 USA.
EM johnl@intra.niddk.nih.gov
FU NIH [GM062920]; NIDDK; Office of the Director, NIH; U. S. Department of
Energy, Office of Science, Office of Basic Energy Sciences
[W-31-109-Eng-38]
FX Grant sponsor: NIH; Grant number: GM062920; Grant sponsors: Intramural
Research Program of the NIDDK, Intramural AIDS-Targeted Antiviral
Program of the Office of the Director, NIH.; This research was authored,
in whole or in part, by National Institutes of Health staff. The authors
thank Annie Aniana for technical assistance and the staff at the
Southeast Regional-Collaborative Access Team (SER-CAT) at the Advanced
Photon Source, Argonne National Laboratory, for assistance during X-ray
data collection. Use of the Advanced Photon Source was supported by the
U. S. Department of Energy, Office of Science, Office of Basic Energy
Sciences, under Contract No. W-31-109-Eng-38. DRV, ATV, and SQV were
obtained through the NIH AIDS Research and Reference Reagent Program,
Division of AIDS, NIAID, NIH and DMP323 from DuPont Pharmaceuticals.
NR 54
TC 14
Z9 14
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
EI 1469-896X
J9 PROTEIN SCI
JI Protein Sci.
PD NOV
PY 2010
VL 19
IS 11
BP 2055
EP 2072
DI 10.1002/pro.486
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 674PG
UT WOS:000283759000004
PM 20737578
ER
PT J
AU Sun, P
Austin, BP
Tozser, J
Waugh, DS
AF Sun, Ping
Austin, Brian P.
Toezser, Jozsef
Waugh, David S.
TI Structural determinants of tobacco vein mottling virus protease
substrate specificity
SO PROTEIN SCIENCE
LA English
DT Article
DE tobacco vein mottling virus; tobacco etch virus; crystal structure;
protease
ID POLYPROTEIN CLEAVAGE SITE; ELECTRON-DENSITY MAPS; MACROMOLECULAR
STRUCTURES; NUCLEAR INCLUSION; ACTIVE-SITE; IN-VIVO; PURIFICATION;
EXPRESSION; NIA; PROTEINASES
AB Tobacco vein mottling virus (TVMV) is a member of the Potyviridae, one of the largest families of plant viruses. The TVMV genome is translated into a single large polyprotein that is subsequently processed by three virally encoded proteases. Seven of the nine cleavage events are carried out by the NIa protease. Its homolog from the tobacco etch virus (TEV) is a widely used reagent for the removal of affinity tags from recombinant proteins. Although TVMV protease is a close relative of TEV protease, they exhibit distinct sequence specificities. We report here the crystal structure of a catalytically inactive mutant TVMV protease (K65A/K67A/C151A) in complex with a canonical peptide substrate (Ac-RETVRFQSD) at 1.7-angstrom resolution. As observed in several crystal structures of TEV protease, the C-terminus (similar to 20 residues) of TVMV protease is disordered. Unexpectedly, although deleting the disordered residues from TEV protease reduces its catalytic activity by -10-fold, an analogous truncation mutant of TVMV protease is significantly more active. Comparison of the structures of TEV and TVMV protease in complex with their respective canonical substrate peptides reveals that the S3 and S4 pockets are mainly responsible for the differing substrate specificities. The structure of TVMV protease suggests that it is less tolerant of variation at the P1' position than TEV protease. This conjecture was confirmed experimentally by determining kinetic parameters k(cat) and K(m) for a series of oligopeptide substrates. Also, as predicted by the cocrystal structure, we confirm that substitutions in the P6 position are more readily tolerated by TVMV than TEV protease.
C1 [Sun, Ping; Austin, Brian P.; Waugh, David S.] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD USA.
[Toezser, Jozsef] Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, Debrecen, Hungary.
RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, POB B, Frederick, MD USA.
EM waughd@mail.nih.gov
RI Tozser, Jozsef/A-7840-2008;
OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729
FU NIH, National Cancer Institute, Center for Cancer Research; U.S.
Department of Energy, Office of Science, Office of Basic Energy Sciences
[W-31-109-Eng-38]
FX Grant sponsor: Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.; The authors thank Scott Cherry
and Kerri Penrose for technical assistance. X-ray diffraction data were
collected at the Southeast Regional Collaborative Access Team (SER-CAT)
22-ID beamline at the Advanced Photon Source, Argonne National
Laboratory. Supporting institutions may be found at
http://www.ser-cat.org/members.html. Use of the Advanced Photon Source
was supported by the U.S. Department of Energy, Office of Science,
Office of Basic Energy Sciences, under contract no. W-31-109-Eng-38.
This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 37
TC 10
Z9 11
U1 0
U2 11
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 NOV
PY 2010
VL 19
IS 11
BP 2240
EP 2251
DI 10.1002/pro.506
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 674PG
UT WOS:000283759000020
PM 20862670
ER
PT J
AU Ruge, H
Muller, SC
Braver, TS
AF Ruge, Hannes
Mueller, Sven C.
Braver, Todd S.
TI Brief Reports: Anticipating the consequences of action: An fMRI study of
intention-based task preparation
SO PSYCHOPHYSIOLOGY
LA English
DT Article
DE Action selection; Action effects; Attention; Cognitive control; Task
switching
ID MEDIAL FRONTAL-CORTEX; DORSOLATERAL PREFRONTAL CORTEX; COGNITIVE
CONTROL; FUNCTIONAL MRI; WILLED ACTION; MECHANISMS; ATTENTION;
SELECTION; AREAS; MAINTENANCE
AB A key component of task preparation may be to anticipate the consequences of task-appropriate actions. This task switching study examined whether such type of "intentional" preparatory control relies on the presentation of explicit action effects. Preparatory BOLD activation in a condition with task-specific motion effect feedback was compared to identical task conditions with accuracy feedback only. Switch-related activation was found selectively in the effect feedback condition in the middle mid-frontal gyrus and in the anterior intraparietal sulcus. Consistent with research on attentional control, the posterior superior parietal lobule exhibited switch-related preparatory activation irrespective of feedback type. To conclude, preparatory control can occur via complementary attentional and intentional neural mechanisms depending on whether meaningful task-specific action effects lead to the formation of explicit effect representations.
C1 [Ruge, Hannes] Tech Univ Dresden, Fak Math & Nat Wissensch, Fachrichtung Psychol, Neuroimaging Ctr, D-01062 Dresden, Germany.
[Ruge, Hannes] Tech Univ Dresden, Dept Psychol, Inst Gen Psychol Biopsychol & Methods Psychol, D-01062 Dresden, Germany.
[Mueller, Sven C.] NIMH, Sect Dev & Affect Neurosci, NIH, Bethesda, MD 20892 USA.
[Braver, Todd S.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA.
RP Ruge, H (reprint author), Tech Univ Dresden, Fak Math & Nat Wissensch, Fachrichtung Psychol, Neuroimaging Ctr, D-01062 Dresden, Germany.
EM ruge@psychologie.tu-dresden.de
RI Ruge, Hannes/K-4634-2015
OI Ruge, Hannes/0000-0001-9793-3859
FU NIMH NIH HHS [R01 MH066078, R01 MH066078-08]
NR 42
TC 9
Z9 9
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0048-5772
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD NOV
PY 2010
VL 47
IS 6
BP 1019
EP 1027
DI 10.1111/j.1469-8986.2010.01027.x
PG 9
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA 663HU
UT WOS:000282874800004
PM 20477978
ER
PT J
AU Beydoun, MA
Shroff, MR
Beydoun, HA
Zonderman, AB
AF Beydoun, May A.
Shroff, Monal R.
Beydoun, Hind A.
Zonderman, Alan B.
TI Serum Folate, Vitamin B-12, and Homocysteine and Their Association With
Depressive Symptoms Among U.S. Adults
SO PSYCHOSOMATIC MEDICINE
LA English
DT Article
DE depression; folate; vitamin B-12; homocysteine; adults
ID HEALTHY ELDERLY INDIVIDUALS; LATE-LIFE DEPRESSION; FOLIC-ACID; PLASMA
HOMOCYSTEINE; BRAIN ATROPHY; PSYCHIATRIC-DISORDERS; DIETARY-FOLATE;
UNITED-STATES; CELL FOLATE; RISK-FACTOR
AB To examine, in a nationally representative sample of U.S. adults, the associations of serum folate, vitamin B-12, and total homocysteine (tHcy) levels with depressive symptoms. Several nutritional and physiological factors have been linked to depression in adults, including low folate and vitamin B-12 and elevated tHcy levels. Methods: Data on U.S. adults (age, 20-85 years; n = 2524) from the National Health and Nutrition Examination Survey during the period 2005 to 2006 were used. Depressive symptoms were measured with the Patient Health Questionnaire (PHQ), and elevated symptoms were defined as a PHQ total score of Serum folate, vitamin B-12, and tHcy were mainly expressed as tertiles. Multiple ordinary least square (OLS), logistic, and zero-inflated Poisson regression models were conducted in the main analysis. Results: Overall, mean PHQ score was significantly higher among women compared with men. Elevated depressive symptoms (PHQ score of >= 10) were inversely associated with folate status, particularly among women (fully adjusted odds ratio [tertiles T(3), versus T(1)] = 0.37; 95% confidence interval, 0.17-0.86), but not significantly related to tHcy or vitamin B-12. No interaction was noted between the three exposures in affecting depressive symptoms. In older adults (50 years) and both sexes combined, tHcy was positively associated with elevated depressive symptoms (fully adjusted odds ratio [tertiles T(2) versus T,] = 3.01; 95% confidence interval, 1.01-9.03), although no significant dose-response relationship was found. Conclusions: Future interventions to improve mental health outcomes among U.S. adults should take into account dietary and other factors that would increase levels of serum folate.
C1 [Beydoun, May A.] NIA, NIH, Biomed Res Ctr, IRP, Baltimore, MD 21224 USA.
[Shroff, Monal R.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA.
[Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA.
RP Beydoun, MA (reprint author), NIA, NIH, Biomed Res Ctr, IRP, 251 Bayview Blvd,Suite 100,Room 04B118, Baltimore, MD 21224 USA.
EM baydounm@mail.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institute on Aging/National Institutes of Health/Intramural
Research Program
FX This research was supported entirely by the National Institute on Aging,
Intramural Research Program (National Institute on Aging/National
Institutes of Health/Intramural Research Program).
NR 72
TC 31
Z9 37
U1 3
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0033-3174
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD NOV-DEC
PY 2010
VL 72
IS 9
BP 862
EP 873
DI 10.1097/PSY.0b013e3181f61863
PG 12
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA 685ZA
UT WOS:000284665400005
PM 20841559
ER
PT J
AU Connerney, I
Sloan, RP
Shapiro, PA
Bagiella, E
Seckman, C
AF Connerney, Ingrid
Sloan, Richard P.
Shapiro, Peter A.
Bagiella, Emilia
Seckman, Charlotte
TI Depression Is Associated With Increased Mortality 10 Years After
Coronary Artery Bypass Surgery
SO PSYCHOSOMATIC MEDICINE
LA English
DT Article
DE depression; coronary bypass; mortality; Diagnostic Interview Schedule;
Beck Depression Inventory
ID ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED-CONTROLLED-TRIAL; RISK-FACTOR;
CARDIAC MORTALITY; HEART-DISEASE; GRAFT-SURGERY; SYMPTOMS; EVENTS;
METAANALYSIS; SURVIVAL
AB Objective: To determine if depression is independently associated with cardiac and all-cause mortality 10 years after coronary artery bypass graft (CABG) surgery. Although many studies have examined the relationship of depression and mortality in patients with myocardial infarction, there is less understanding of the relationship between depression and long-term mortality after CABG surgery. Methods: In a prospective study, we collected data on 309 patients hospitalized after CABG surgery. Before discharge, patients were assessed for depression using the Diagnostic Interview Schedule and the Beck Depression Inventory (BDI). Subsequently, mortality data were obtained from the National Center for Health Statistics and supplemented with phone interviews. Results: Sixty-three (20%) patients met modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder (MDD) and 87 (28%) had BDI scores of >= 10, indicating elevated depressive symptoms. Time-to-event or last follow-up phone contact ranged from 9 days to 11.5 years (median, 9.3 years). The overall mortality rate was 37.9% (117 of 309), with 20.1% (62 of 309) due to cardiac causes. Cox proportional hazard modeling showed that age (hazard ratio [HR], 1.04; p = .005), left ventricular ejection fraction (EF) (EF <0.35 [HR], 3.9;p < .001; EF, 0.35-0.49 [HR], 1.9; p = .03), and MDD (HR, 1.8; p = .04) were independent predictors of cardiac mortality. The BDI and the cognitive-affective symptoms subset of BDI symptoms were also predictors of cardiac mortality. Age, EF, and diabetes predicted all-cause mortality, but MDD did not. Conclusions: Depression, assessed both in structured interview and by BDI, was significantly associated with elevated cardiac mortality 10 years after CABG surgery.
C1 [Connerney, Ingrid] Univ Maryland, Med Ctr, Div Qual & Safety, Baltimore, MD 21201 USA.
[Sloan, Richard P.; Shapiro, Peter A.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Bagiella, Emilia] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Seckman, Charlotte] NIH, Bethesda, MD 20892 USA.
RP Connerney, I (reprint author), Univ Maryland, Med Ctr, Div Qual & Safety, 22 S Greene St,Box 316, Baltimore, MD 21201 USA.
EM iconnerney@umm.edu
FU University of Maryland Medical Center; Nathaniel Wharton Fund; National
Heart Lung and Blood Institute [R01 HL072057]
FX The work was supported, in part, by the University of Maryland Medical
Center (I.C.) and the Nathaniel Wharton Fund (IC., P.A.S.), as well as
Grant R01 HL072057 from the National Heart Lung and Blood Institute
(R.P.S.).
NR 39
TC 51
Z9 53
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0033-3174
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD NOV-DEC
PY 2010
VL 72
IS 9
BP 874
EP 881
DI 10.1097/PSY.0b013e3181f65fc1
PG 8
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA 685ZA
UT WOS:000284665400006
PM 20841558
ER
PT J
AU Riley, WT
Rothrock, N
Bruce, B
Christodolou, C
Cook, K
Hahn, EA
Cella, D
AF Riley, William T.
Rothrock, Nan
Bruce, Bonnie
Christodolou, Christopher
Cook, Karon
Hahn, Elizabeth A.
Cella, David
TI Patient-reported outcomes measurement information system (PROMIS) domain
names and definitions revisions: further evaluation of content validity
in IRT-derived item banks
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE Content validity; Conceptual framework; Domain definition; Item response
theory
AB Content validity of patient-reported outcomes (PROs) is evaluated primarily during item development, but subsequent psychometric analyses, particularly for item response theory (IRT)-derived scales, often result in considerable item pruning and potential loss of content. After selecting items for the PROMIS banks based on psychometric and content considerations, we invited external content expert reviews of the degree to which the initial domain names and definitions represented the calibrated item bank content.
A minimum of four content experts reviewed each item bank and recommended a domain name and definition based on item content. Domain names and definitions then were revealed to the experts who rated how well these names and definitions fit the bank content and provided recommendations for definition revisions.
These reviews indicated that the PROMIS domain names and definitions remained generally representative of bank content following item pruning, but modifications to two domain names and minor to moderate revisions of all domain definitions were needed to optimize fit with the item bank content.
This reevaluation of domain names and definitions following psychometric item pruning, although not previously documented in the literature, appears to be an important procedure for refining conceptual frameworks and further supporting content validity.
C1 [Riley, William T.] NHLBI, Bethesda, MD 20892 USA.
[Rothrock, Nan; Hahn, Elizabeth A.; Cella, David] Northwestern Univ, Chicago, IL 60611 USA.
[Bruce, Bonnie] Stanford Univ, Stanford, CA 94305 USA.
[Christodolou, Christopher] SUNY Stony Brook, Stony Brook, NY 11794 USA.
[Cook, Karon] Univ Washington, Seattle, WA 98195 USA.
RP Riley, WT (reprint author), NHLBI, 6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA.
EM wiriley@mail.nih.gov
FU Northwestern University, PI [U01AR52177]; Duke University, PI
[U01AR52186]; University of North Carolina, PI [U01AR52181]; University
of Pittsburgh, PI [U01AR52155]; Stanford University, PI [U01AR52158];
Stony Brook University, PI [U01AR52170]; University of Washington, PI
[U01AR52171]; NIH
FX The patient-reported outcomes measurement information system (PROMIS) is
a 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 have included Deborah Ader, PhD, Susan
Czajkowski, PhD, Lawrence Fine, MD, DrPH, Laura Lee Johnson, PhD, Louis
Quatrano, PhD, Bryce Reeve, PhD, William Riley, PhD, Susana
Serrate-Sztein, MD, and James Witter, MD, PhD. This manuscript was
reviewed by the PROMIS Publications Subcommittee prior to external peer
review. See the Web site at www.nihpromis.org for additional information
on the PROMIS cooperative group.
NR 18
TC 43
Z9 43
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
J9 QUAL LIFE RES
JI Qual. Life Res.
PD NOV
PY 2010
VL 19
IS 9
BP 1311
EP 1321
DI 10.1007/s11136-010-9694-5
PG 11
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 671KZ
UT WOS:000283506100008
PM 20593306
ER
PT J
AU Bhatti, P
Yong, LC
Doody, MM
Preston, DL
Kampa, DM
Ramsey, MJ
Ward, EM
Edwards, AA
Ron, E
Tucker, JD
Sigurdson, AJ
AF Bhatti, Parveen
Yong, Lee C.
Doody, Michele M.
Preston, Dale L.
Kampa, Diane M.
Ramsey, Marilyn J.
Ward, Elizabeth M.
Edwards, Alan A.
Ron, Elaine
Tucker, James D.
Sigurdson, Alice J.
TI Diagnostic X-ray examinations and increased chromosome translocations:
evidence from three studies
SO RADIATION AND ENVIRONMENTAL BIOPHYSICS
LA English
DT Article
ID RADIATION-INDUCED TRANSLOCATIONS; US RADIOLOGIC TECHNOLOGISTS; INCREASED
FREQUENCY; IONIZING-RADIATION; MEDICAL RADIATION; COMPUTED-TOMOGRAPHY;
CANCER-RISKS; EXPOSURE; CT; COHORT
AB Controversy regarding potential health risks from increased use of medical diagnostic radiologic examinations has come to public attention. We evaluated whether chromosome damage, specifically translocations, which are a potentially intermediate biomarker for cancer risk, was increased after exposure to diagnostic X-rays, with particular interest in the ionizing radiation dose-response below the level of approximately 50 mGy. Chromosome translocation frequency data from three separately conducted occupational studies of ionizing radiation were pooled together. Studies 1 and 2 included 79 and 150 medical radiologic technologists, respectively, and study 3 included 83 airline pilots and 50 university faculty members (total = 155 women and 207 men; mean age = 62 years, range 34-90). Information on personal history of radiographic examinations was collected from a detailed questionnaire. We computed a cumulative red bone marrow (RBM) dose score based on the numbers and types of X-ray examinations reported with 1 unit approximating 1 mGy. Poisson regression analyses were adjusted for age and laboratory method. Mean RBM dose scores were 49, 42, and 11 for Studies 1-3, respectively (overall mean = 33.5, range 0-303). Translocation frequencies significantly increased with increasing dose score (P < 0.001). Restricting the analysis to the lowest dose scores of under 50 did not materially change these results. We conclude that chromosome damage is associated with low levels of radiation exposure from diagnostic X-ray examinations, including dose scores of approximately 50 and lower, suggesting the possibility of long-term adverse health effects.
C1 [Bhatti, Parveen] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA USA.
[Bhatti, Parveen; Doody, Michele M.; Ron, Elaine; Sigurdson, Alice J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Yong, Lee C.] NIOSH, Cincinnati, OH 45226 USA.
[Preston, Dale L.] HiroSoft Int Corp, Seattle, WA USA.
[Kampa, Diane M.] Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN USA.
[Ramsey, Marilyn J.] Lawrence Livermore Natl Lab, Livermore, CA USA.
[Ward, Elizabeth M.] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA.
[Edwards, Alan A.] Hlth Protect Agcy, Radiat Protect Div, Didcot, Oxon, England.
[Tucker, James D.] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA.
RP Bhatti, P (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, POB 19024,M4-B874, Seattle, WA USA.
EM pbhatti@fhcrc.org
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute;
National Institute for Occupational Safety and Health; National Cancer
Institute [Y1CP802904]; US DOE by the Lawrence Livermore National
Laboratory [W-7405-ENG-48]
FX This research was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute
and in part by an interagency agreement between the National Institute
for Occupational Safety and Health and the National Cancer Institute
(contract Y1CP802904). Work was performed in part under the auspices of
the US DOE by the Lawrence Livermore National Laboratory under contract
no. W-7405-ENG-48. We thank the two anonymous reviewers for their
helpful comments on the manuscript.
NR 31
TC 14
Z9 15
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-634X
J9 RADIAT ENVIRON BIOPH
JI Radiat. Environ. Biophys.
PD NOV
PY 2010
VL 49
IS 4
BP 685
EP 692
DI 10.1007/s00411-010-0307-z
PG 8
WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine
& Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental
Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging
GA 671KS
UT WOS:000283504900015
PM 20602108
ER
PT J
AU Huff, J
Chan, P
Melnick, R
AF Huff, James
Chan, Po
Melnick, Ronald
TI Clarifying carcinogenicity of ethylbenzene
SO REGULATORY TOXICOLOGY AND PHARMACOLOGY
LA English
DT Editorial Material
DE Cancer bioassay; Carcinogenesis; Chemicals; Long-term study;
Occupational cancer; Primary prevention
ID INDUCED HEPATOCYTE PROLIFERATION; NATIONAL TOXICOLOGY PROGRAM; HUMAN
CANCER HAZARDS; MAJOR RISK FACTOR; CELL-PROLIFERATION; CHEMICAL
CARCINOGENESIS; LIVER CARCINOGENESIS; TUMOR-INDUCTION; TOXICITY;
MECHANISMS
AB Ethylbenzene has been evaluated for carcinogenic activity in Fischer rats and B6C3F1 mice exposed by inhalation (Chan et al., 1998; Chan, 1999) and in Sprague-Dawley rats after oral exposure (Maltoni et al., 1985,1997). Bioassay findings are summarized below to expand on those not stated clearly or completely in Saghir et al. (2010). Overall in these three studies animals exposed to ethylbenzene had increased tumors in rats for kidneys, testes, head (including rare neuroesthesioepitheliomas), and total malignant tumors, whilst in mice tumor incidences were increased in the lung and liver (Huff. 2002). Thus ethylbenzene was carcinogenic by two exposure routes to both sexes of two species of rodents, two strains of rats, and one strain of mice, causing collectively tumors in five different target organs and a composite of "total malignant" tumors. Published by Elsevier Inc.
C1 [Huff, James; Chan, Po; Melnick, Ronald] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Huff, J (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM huff1@niehs.nih.gov
NR 39
TC 2
Z9 2
U1 3
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0273-2300
EI 1096-0295
J9 REGUL TOXICOL PHARM
JI Regul. Toxicol. Pharmacol.
PD NOV
PY 2010
VL 58
IS 2
BP 167
EP 169
DI 10.1016/j.yrtph.2010.08.011
PG 3
WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology
SC Legal Medicine; Pharmacology & Pharmacy; Toxicology
GA 667OW
UT WOS:000283204400002
PM 20723573
ER
PT J
AU Dragomir, AD
Schroeder, JC
Connolly, A
Kupper, LL
Hill, MC
Olshan, AF
Baird, DD
AF Dragomir, Anca D.
Schroeder, Jane C.
Connolly, AnnaMarie
Kupper, Larry L.
Hill, Michael C.
Olshan, Andrew F.
Baird, Donna D.
TI Potential Risk Factors Associated With Subtypes of Uterine Leiomyomata
SO REPRODUCTIVE SCIENCES
LA English
DT Article
DE epidemiology; uterine leiomyomata subtypes; smoking; sonogram
ID BODY-SIZE; FIBROIDS; MYOMAS; WOMEN; SMOKING; UTERUS; HEALTH
AB Objective: To compare potential risk factors for uterine leiomyomata (UL) subtypes among premenopausal African American and Caucasian women. Methods: This cross-sectional study included 986 premenopausal women, aged 35 to 49 years old, from the National Institute of Environmental Health Sciences (NIEHS) Uterine Fibroid Study (UFS). Uterine leiomyomata were subtyped as submucosal, intramural/subserosal, and diffuse, based on ultrasound examinations. Results: For both ethnic groups, age, age at menarche, body mass index, and current physical activity had similar associations across the 3 UL subtypes. Inverse associations with pregnancies after age 24 appeared to be stronger for the submucosal subtype. Current smoking was associated only with diffuse UL (adjusted odds ratio [aOR] = 1.97, 95% CI: 1.11, 3.51 in African Americans, aOR = 3.00, 95% CI: 1.07, 8.38 in Caucasians). Conclusions: Although the 2 focal UL subtypes had similar risk factor profiles, the diffuse UL subtype appeared to have a distinctive risk profile with regard to current smoking. Further study of the diffuse heterogeneity seen with uterine ultrasound is needed.
C1 [Dragomir, Anca D.; Schroeder, Jane C.; Olshan, Andrew F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Connolly, AnnaMarie] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA.
[Kupper, Larry L.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Hill, Michael C.] George Washington Univ, Med Ctr, Dept Radiol, Washington, DC 20037 USA.
[Baird, Donna D.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Dragomir, AD (reprint author), POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA.
EM dragomir@email.unc.edu
RI Baird, Donna/D-5214-2017
OI Baird, Donna/0000-0002-5544-2653
FU NIH, National Institute of Environmental Health Sciences
FX The author(s) disclosed receipt of the following financial support for
the research and/or authorship of this article: the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences.
NR 22
TC 17
Z9 18
U1 0
U2 5
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 NOV
PY 2010
VL 17
IS 11
BP 1029
EP 1035
DI 10.1177/1933719110376979
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 662NV
UT WOS:000282815100008
PM 20693498
ER
PT J
AU Cooney, MA
Louis, GMB
Hediger, ML
Vexler, A
Kostyniak, PJ
AF Cooney, Maureen A.
Louis, Germaine M. Buck
Hediger, Mary L.
Vexler, Albert
Kostyniak, Paul J.
TI Organochlorine pesticides and endometriosis
SO REPRODUCTIVE TOXICOLOGY
LA English
DT Article
DE Endometriosis; Environment; Fecundity; Organochlorines; Pesticides;
Reproductive toxicant
ID HIGH PLASMA-CONCENTRATIONS; POLYCHLORINATED-BIPHENYLS; ITALIAN WOMEN;
SERUM-LEVELS; EXPOSURE; RISK
AB Limited study of persistent organochlorine pesticides (OCPs) and endometriosis has been conducted. One hundred women aged 18-40 years who were undergoing laparoscopy provided 20 cm(3) of blood for toxicologic analysis and surgeons completed operative reports regarding the presence of endometriosis. Gas chromatography with electron capture was used to quantify (ng/g serum) six OCPs. Logistic regression was utilized to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (Cl) for individual pesticides and groups based on chemical structure adjusting for current cigarette smoking and lipids. The highest tertile of aromatic fungicide was associated with a fivefold risk of endometriosis (aOR = 5.3: 95% CI, 1.2-23.6) compared to the lowest tertile. Similar results were found for t-nonachlor and HCB. These are the first such findings in a laproscopic cohort that suggest an association between OCP exposure and endometriosis. More prospective studies are necessary to ensure temporal ordering and confirm these findings. Published by Elsevier Inc.
C1 [Cooney, Maureen A.; Louis, Germaine M. Buck; Hediger, Mary L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
[Vexler, Albert] SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA.
[Kostyniak, Paul J.] SUNY Buffalo, Dept Pharmacol & Toxicol, Sch Med & Biomed Sci, Buffalo, NY 14214 USA.
RP Cooney, MA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Rm 7805, Rockville, MD 20852 USA.
EM cooneyma@mail.nih.gov; louisg@mail.nih.gov; hedigerm@mail.nih.gov;
avexler@buffalo.edu; pjkost@buffalo.edu
OI Buck Louis, Germaine/0000-0002-1774-4490
FU National Institute of Environmental Health Sciences [R01ES09044]; Eunice
Kennedy Shriver National Institute of Child Health & Human Development
FX This work was supported in part with grants from the National Institute
of Environmental Health Sciences (R01ES09044) and intramural resources
of the Eunice Kennedy Shriver National Institute of Child Health & Human
Development.
NR 32
TC 16
Z9 17
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0890-6238
J9 REPROD TOXICOL
JI Reprod. Toxicol.
PD NOV
PY 2010
VL 30
IS 3
BP 365
EP 369
DI 10.1016/j.reprotox.2010.05.011
PG 5
WC Reproductive Biology; Toxicology
SC Reproductive Biology; Toxicology
GA 654JT
UT WOS:000282165000003
PM 20580667
ER
PT J
AU Doerge, DR
Twaddle, NC
Churchwell, MI
Newbold, RR
Delclos, KB
AF Doerge, Daniel R.
Twaddle, Nathan C.
Churchwell, Mona I.
Newbold, Retha R.
Delclos, K. Barry
TI Lactational transfer of the soy isoflavone, genistein, in Sprague-Dawley
rats consuming dietary genistein (vol 21, pg 307, 2006)
SO REPRODUCTIVE TOXICOLOGY
LA English
DT Correction
C1 [Doerge, Daniel R.; Twaddle, Nathan C.; Churchwell, Mona I.; Delclos, K. Barry] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Newbold, Retha R.] NIEHS, Dev Endocrinol & Endocrine Disrupter Sect, Mol Toxicol Lab, NIH DHHS, Res Triangle Pk, NC 27709 USA.
RP Doerge, DR (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM daniel.doerge@fda.hhs.gov
NR 1
TC 0
Z9 0
U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0890-6238
J9 REPROD TOXICOL
JI Reprod. Toxicol.
PD NOV
PY 2010
VL 30
IS 3
BP 493
EP 493
DI 10.1016/j.reprotox.2010.06.005
PG 1
WC Reproductive Biology; Toxicology
SC Reproductive Biology; Toxicology
GA 654JT
UT WOS:000282165000022
ER
PT J
AU Nussenblatt, RB
Byrnes, G
Sen, HN
Yeh, S
Faia, L
Meyerle, C
Wroblewski, K
Li, ZQ
Liu, BY
Chew, E
Sherry, PR
Friedman, P
Gill, F
Ferris, F
AF Nussenblatt, Robert B.
Byrnes, Gordon
Sen, H. Nida
Yeh, Steven
Faia, Lisa
Meyerle, Catherine
Wroblewski, Keith
Li, Zhuqing
Liu, Baoying
Chew, Emily
Sherry, Patti R.
Friedman, Penelope
Gill, Fred
Ferris, Frederick, III
TI A RANDOMIZED PILOT STUDY OF SYSTEMIC IMMUNOSUPPRESSION IN THE TREATMENT
OF AGE-RELATED MACULAR DEGENERATION WITH CHOROIDAL NEOVASCULARIZATION
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE age-related macular degeneration; immunosuppression; T cell; choroidal
neovascularization
ID RAPAMYCIN; THERAPY; SUSCEPTIBILITY; INFLAMMATION; SIROLIMUS; UVEITIS;
VARIANT; ALPHA; CELLS; HTRA1
AB Background: Age-related macular degeneration remains the leading cause of irreversible blindness in the United States and the developed world. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) medications have become standard of care for the treatment of the wet form of the disease. Recent reports have demonstrated an association with various immune factors. We aimed to investigate the effect of immunosuppressive therapy in the clinical course of the wet form of the disease. We compared anti-VEGF therapy plus one of three systemic immunosuppressive therapies versus anti-VEGF therapy alone for recurrent choroidal neovascularization associated with age-related macular degeneration.
Methods: This was a pilot, Phase I/II, prospective, randomized, unmasked, single-center trial. Patients with subretinal exudation secondary to recurrent choroidal neovascularization associated with age-related macular degeneration were included in the study. Patients were randomized to 1 of 3 systemic arms immunosuppressive agents (daclizumab, rapamycin, or infliximab) for 6 months plus intraocular anti-VEGF therapy if indicated, compared with a group who received only anti-VEGF therapy if indicated.
Results: The number of anti-VEGF injections per group, visual acuity, retinal thickness, and safety measures were assessed in all groups. Thirteen patients were randomized; comparing anti-VEGF injections before and during the study, a decrease in the number of injections from 0.73 injections per month to 0.42 for daclizumab and from 0.67 to 0.34 for sirolimus was seen, while no apparent decrease was seen for either infliximab or observation. Visual acuities were maintained in all groups.
Conclusion: These preliminary data suggest that some immunosuppressive agents given systemically can alter the clinical course of the wet form of the disease and support the notion that more definitive clinical trials of immune mediation of age-related macular degeneration are indicated. RETINA 30:1579-1587, 2010
C1 [Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Byrnes, Gordon] Retina Grp Washington, Fairfax, VA USA.
[Wroblewski, Keith] Walter Reed Army Med Ctr, Dept Ophthalmol, Washington, DC USA.
[Gill, Fred] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N112,10 Ctr Dr, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov
FU National Eye Institute, National Institutes of Health, Bethesda,
Maryland
FX Supported by intramural funds of the National Eye Institute, National
Institutes of Health, Bethesda, Maryland.
NR 29
TC 38
Z9 39
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 NOV-DEC
PY 2010
VL 30
IS 10
BP 1579
EP 1587
DI 10.1097/IAE.0b013e3181e7978e
PG 9
WC Ophthalmology
SC Ophthalmology
GA 678HL
UT WOS:000284064600004
PM 20847709
ER
PT J
AU Geisbert, TW
Bausch, DG
Feldmann, H
AF Geisbert, Thomas W.
Bausch, Daniel G.
Feldmann, Heinz
TI Prospects for immunisation against Marburg and Ebola viruses
SO REVIEWS IN MEDICAL VIROLOGY
LA English
DT Review
ID ATTENUATED RECOMBINANT VACCINE; PROTECTS NONHUMAN-PRIMATES;
VESICULAR-STOMATITIS; HEMORRHAGIC-FEVER; GUINEA-PIGS; MOUSE MODEL;
NEUTRALIZING ANTIBODIES; POSTEXPOSURE PROTECTION; ADENOVIRUS VECTORS;
ALPHAVIRUS VECTORS
AB For more than 30 years the filoviruses, Marburg virus and Ebola virus, have been associated with periodic outbreaks of hemorrhagic fever that produce severe and often fatal disease. The filoviruses are endemic primarily in resource-poor regions in Central Africa and are also potential agents of bioterrorism. Although no vaccines or antiviral drugs for Marburg or Ebola are currently available, remarkable progress has been made over the last decade in developing candidate preventive vaccines against filoviruses in nonhuman primate models. Due to the generally remote locations of filovirus outbreaks, a single-injection vaccine is desirable. Among the prospective vaccines that have shown efficacy in nonhuman primate models of filoviral hemorrhagic fever, two candidates, one based on a replication-defective adenovirus serotype 5 and the other on a recombinant VSV (rVSV), were shown to provide complete protection to nonhuman primates when administered as a single injection. The rVSV-based vaccine has also shown utility when administered for postexposure prophylaxis against filovirus infections. A VSV-based Ebola vaccine was recently used to manage a potential laboratory exposure. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Geisbert, Thomas W.] Univ Texas Med Branch, Galveston Natl Lab1, Galveston, TX USA.
[Geisbert, Thomas W.] Univ Texas Med Branch, Dept Microbiol & Immunol2, Galveston, TX USA.
[Geisbert, Thomas W.] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
[Geisbert, Thomas W.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Bausch, Daniel G.] Tulane Sch Publ Hlth & Trop Med, Dept Trop Med, New Orleans, LA USA.
[Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.
RP Geisbert, TW (reprint author), Univ Texas Med Branch, Galveston Natl Lab1, 301 Univ Blvd, Galveston, TX USA.
EM twgeisbe@utmb.edu
FU Intramural NIH HHS [Z99 AI999999]
NR 89
TC 50
Z9 52
U1 1
U2 36
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1052-9276
J9 REV MED VIROL
JI Rev. Med. Virol.
PD NOV
PY 2010
VL 20
IS 6
BP 344
EP 357
DI 10.1002/rmv.661
PG 14
WC Virology
SC Virology
GA 677ZL
UT WOS:000284036600002
PM 20658513
ER
PT J
AU Rein, A
AF Rein, Alan
TI Nucleic acid chaperone activity of retroviral Gag proteins
SO RNA BIOLOGY
LA English
DT Article
DE retroviruses; Gag protein; RNA chaperone; HIV-1; protein-nucleic acid
interaction
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 NUCLEOCAPSID PROTEIN; MURINE
LEUKEMIA-VIRUS; PRIMER-BINDING-SITE; ROUS-SARCOMA-VIRUS; ASSEMBLY
IN-VITRO; REVERSE TRANSCRIPTION; TRANSFER-RNA; GENOMIC RNA; STRUCTURAL
BASIS
AB Retrovirus particles in which the Gag protein has not yet been cleaved by the viral protease are termed immature particles. The viral RNA within these particles shows clear evidence of the action of a nucleic acid chaperone (NAC): the genomic RNA is dimeric, and a cellular tRNA molecule is annealed, by its 3' 18 nucleotides, to a complementary stretch in the viral RNA, in preparation for priming reverse transcription in the next round of infection. It seems very likely that the NAC that has catalyzed dimerization and tRNA annealing is the NC domain of the Gag protein itself. However, neither the dimeric linkage nor the tRNA: viral RNA complex has the same structure as those in mature virus particles: thus the conformational effects of Gag within the particles are not equivalent to those of the free NC protein present in mature particles.
It is not known whether these dissimilarities reflect intrinsic differences in the NAC activities of Gag and NC, or limitations on Gag imposed by the structure of the immature particle. Analysis of the interactions of recombinant Gag proteins with nucleic acids is complicated by the fact that they result in assembly of virus-like particles. Nevertheless, the available data indicates that the affinity of Gag for nucleic acids can be considerably higher than that of free NC. This enhanced affinity may be due to contributions of the matrix domain, a positively charged region at the N-terminus of Gag; interactions of neighboring Gag molecules with each other may also increase the affinity due to cooperativity of the binding.
Recombinant HIV-1 Gag protein clearly exhibits NAC activity. In two well-studied experimental systems, Gag was more efficient than NC, as its NAC effects could be detected at a significantly lower molar ratio of protein to nucleotide than with NC. In one system, binding of nucleic acid by the matrix domain of Gag retarded the Gag-induced annealing of two RNAs; this effect could be ameliorated by the competitive binding of inositol hexakisphosphate to the matrix domain.
C1 Natl Canc Inst Frederick, HIV Drug Resistance Program, Frederick, MD USA.
RP Rein, A (reprint author), Natl Canc Inst Frederick, HIV Drug Resistance Program, Frederick, MD USA.
EM reina@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX I am grateful to Ioulia Rouzina, Judith Levin, Christopher Jones and
Karin Musier-Forsyth for many helpful discussions. This research was
supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 51
TC 18
Z9 18
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1547-6286
J9 RNA BIOL
JI RNA Biol.
PD NOV-DEC
PY 2010
VL 7
IS 6
SI SI
BP 700
EP 705
DI 10.4161/rna.7.6.13685
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736JN
UT WOS:000288490500008
PM 21045546
ER
PT J
AU Mirambeau, G
Lyonnais, S
Gorelick, RJ
AF Mirambeau, Gilles
Lyonnais, Sebastien
Gorelick, Robert J.
TI Features, processing states and heterologous protein interactions in the
modulation of the retroviral nucleocapsid protein function
SO RNA BIOLOGY
LA English
DT Article
DE capsid; HIV-1; nucleic acid chaperone; nucleocapsid protein; protease;
retrovirus; reverse transcription; zinc-finger
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACID-CHAPERONE ACTIVITY; MURINE
LEUKEMIA-VIRUS; REVERSE TRANSCRIPTION COMPLEXES; TYPE-1 GAG POLYPROTEIN;
ROUS-SARCOMA-VIRUS; HIV-1 GENOMIC RNA; ZINC-FINGER STRUCTURES; PRIMER
BINDING-SITE; IN-VITRO
AB Nucleocapsid (NC) is central to retroviral replication. Nucleic acid chaperoning is a key function for NC through the action of its conserved basic amino acids and zinc-finger structures. NC manipulates genomic RNA from its packaging in the producer cell to reverse transcription into the infected host cell. This chaperone function, in conjunction with NCs aggregating properties, is up-modulated by successive NC processing events, from the Gag precursor to the fully mature protein, resulting in the condensation of the nucleocapsid within the capsid shell. Reverse transcription also depends on NC processing, whereas this process provokes NC dissociation from double-stranded DNA, leading to a preintegration complex (PIC), competent for host chromosomal integration. In addition NC interacts with cellular proteins, some of which are involved in viral budding, and also with several viral proteins. All of these properties are reviewed here, focusing on HIV-1 as a paradigmatic reference and highlighting the plasticity of the nucleocapsid architecture.
C1 [Gorelick, Robert J.] NCI Frederick, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD USA.
[Mirambeau, Gilles; Lyonnais, Sebastien] Univ Barcelona, Hosp Clin IDIBAPS, Infectious Dis & AIDS Unit, Barcelona, Spain.
[Mirambeau, Gilles] Sorbonne Univ, Univ Paris 06, Fac Biol, Paris, France.
RP Gorelick, RJ (reprint author), NCI Frederick, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD USA.
EM gorelicr@mail.nih.gov
OI Lyonnais, Sebastien/0000-0002-3154-8568
FU Marie Curie Intra-European Fellowship [237738]; National Cancer
Institute, National Institutes of Health [N01-CO-12400,
HHSN261200800001E]
FX G.M. and S.L. are greatly indebted to Jose Maria Gatell and Laura Zamora
for their kind hosting and support at the Infectious Disease and AIDS
Unit. We wish to thank Sophie Brouillet, Joel Pothier (ABI, UPMC, Paris)
and Anne Voinet (MTI-Universite Paris Diderot, Paris) for the alignment
of HIV-1 NC sequences. We also wish to thank James A. Thomas
(NCI-Frederick) and Judith G. Levin (NICHD, NIH) for critical reading of
this manuscript. S.L. is funded by a Marie Curie Intra-European
Fellowship IEF No 237738. (R.J.G.) this project has been funded in whole
or in part with federal funds from the National Cancer Institute,
National Institutes of Health, under contracts N01-CO-12400 and
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 124
TC 35
Z9 35
U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1547-6286
EI 1555-8584
J9 RNA BIOL
JI RNA Biol.
PD NOV-DEC
PY 2010
VL 7
IS 6
SI SI
BP 724
EP 734
DI 10.4161/rna.7.6.13777
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736JN
UT WOS:000288490500011
PM 21045549
ER
PT J
AU Levin, JG
Mitra, M
Mascarenhas, A
Musier-Forsyth, K
AF Levin, Judith G.
Mitra, Mithun
Mascarenhas, Anjali
Musier-Forsyth, Karin
TI Role of HIV-1 nucleocapsid protein in HIV-1 reverse transcription
SO RNA BIOLOGY
LA English
DT Article
DE nucleocapsid protein; HIV-1; nucleic acid chaperone; reverse
transcription; Gag; zinc fingers; tRNA(3)(Lys); APOBEC3G; retroviruses
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACID-CHAPERONE ACTIVITY; STRAND
DNA-SYNTHESIS; TRANSFER-RNA SYNTHETASE; MURINE LEUKEMIA-VIRUS; PRIMER
BINDING-SITE; STRONG-STOP DNA; CENTRAL POLYPURINE TRACT; ZINC-FINGER
STRUCTURES; IN-VITRO SYNTHESIS
AB The HIV-1 nucleocapsid protein (NC) is a nucleic acid chaperone, which remodels nucleic acid structures so that the most thermodynamically stable conformations are formed. This activity is essential for virus replication and has a critical role in mediating highly specific and efficient reverse transcription. NC's function in this process depends upon three properties: (1) ability to aggregate nucleic acids; (2) moderate duplex destabilization activity; and (3) rapid on-off binding kinetics. Here, we present a detailed molecular analysis of the individual events that occur during viral DNA synthesis and show how NC's properties are important for almost every step in the pathway. Finally, we also review biological aspects of reverse transcription during infection and the interplay between NC, reverse transcriptase and human APOBEC3G, an HIV-1 restriction factor that inhibits reverse transcription and virus replication in the absence of the HIV-1 Vif protein.
C1 [Levin, Judith G.; Mitra, Mithun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, Program Genom Differentiat, NIH, Bethesda, MD USA.
[Mascarenhas, Anjali; Musier-Forsyth, Karin] Ohio State Univ, Ctr Retrovirus Res, Dept Chem, Columbus, OH 43210 USA.
[Mascarenhas, Anjali; Musier-Forsyth, Karin] Ohio State Univ, Ctr Retrovirus Res, Dept Biochem, Columbus, OH 43210 USA.
[Mascarenhas, Anjali; Musier-Forsyth, Karin] Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA.
RP Levin, JG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, Program Genom Differentiat, NIH, Bethesda, MD USA.
EM levinju@mail.nih.gov
RI Mitra, Mithun/A-2133-2015
FU NIH (Eunice Kennedy Shriver National Institute of Child Health and Human
Development); NIH [GM065056]
FX 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 NIH grant GM065056 [K.M.F.].
NR 256
TC 64
Z9 64
U1 2
U2 12
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1547-6286
EI 1555-8584
J9 RNA BIOL
JI RNA Biol.
PD NOV-DEC
PY 2010
VL 7
IS 6
SI SI
BP 754
EP 774
DI 10.4161/rna.7.6.14115
PG 21
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736JN
UT WOS:000288490500014
PM 21160280
ER
PT J
AU Cuthbert, BN
Insel, TR
AF Cuthbert, Bruce N.
Insel, Thomas R.
TI Toward New Approaches to Psychotic Disorders: The NIMH Research Domain
Criteria Project
SO SCHIZOPHRENIA BULLETIN
LA English
DT Editorial Material
ID KRAEPELINIAN DICHOTOMY; SCHIZOPHRENIA
C1 [Cuthbert, Bruce N.; Insel, Thomas R.] NIH, Bethesda, MD 20892 USA.
RP Cuthbert, BN (reprint author), NIH, 6001 Execut Blvd,MSC 9625, Bethesda, MD 20892 USA.
EM bcuthber@mail.nih.gov
NR 10
TC 144
Z9 145
U1 0
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD NOV
PY 2010
VL 36
IS 6
BP 1061
EP 1062
DI 10.1093/schbul/sbq108
PG 2
WC Psychiatry
SC Psychiatry
GA 673SR
UT WOS:000283683800001
PM 20929969
ER
PT J
AU Li, QZ
Zheng, G
Liu, AY
Li, ZH
Yu, K
AF Li QiZhai
Zheng Gang
Liu AiYi
Li ZhaoHai
Yu Kai
TI Approximating probabilities of correlated events
SO SCIENCE CHINA-MATHEMATICS
LA English
DT Article
DE case-control; group sequential test; genetic association studies; MAX;
parallelogram
ID GENOME-WIDE ASSOCIATION; CLINICAL-TRIALS; NUISANCE PARAMETER;
GENETIC-LINKAGE; TREND TESTS; RISK; STATISTICS; MAXIMUM; DESIGNS; CANCER
AB Efron (1997) considered several approximations of p-values for simultaneous hypothesis testing. An extension of his approaches is considered here to approximate various probabilities of correlated events. Compared with multiple-integrations, our proposed method, the parallelogram formulas, based on a one-dimensional integral, not only substantially reduces the computational complexity but also maintains good accuracy. Applications of the proposed method to genetic association studies and group sequential analysis are investigated in detail. Numerical results including real data analysis and simulation studies demonstrate that the proposed method performs well.
C1 [Li QiZhai] Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China.
[Li QiZhai; Li ZhaoHai; Yu Kai] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Zheng Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Liu AiYi] NICHHD, Biostat & Bioinformat Branch, Bethesda, MD 20892 USA.
[Li ZhaoHai] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
RP Li, QZ (reprint author), Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China.
EM liqz@amss.ac.cn; zhengg@mail.nih.gov; liua@mail.nih.gov; zli@gwu.edu;
yuka@mail.nih.gov
OI Liu, Aiyi/0000-0002-6618-5082
FU NIH [EY014478]; National Natural Science Foundation of China [10901155]
FX We would like to thank the editor and the reviewer for the insightful
comments. We thank Dr. Barry Graubard and Dr. B.J. Stone for their
valuable help. This research utilized the high-performance computational
capabilities of the Biowulf PC/Linux cluster at the National Institutes
of Health (NIH), Bethesda, Maryland, USA (http://biowulf.nih.gov). K Yu
and A Liu are supported by the Intramural Program of NIH; Q Li is
supported in part by National Natural Science Foundation of China (Grant
No.10901155); Z Li is supported in part by NIH (Grant No. EY014478).
NR 24
TC 1
Z9 1
U1 0
U2 0
PU SCIENCE PRESS
PI BEIJING
PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA
SN 1674-7283
J9 SCI CHINA MATH
JI Sci. China-Math.
PD NOV
PY 2010
VL 53
IS 11
BP 2937
EP 2948
DI 10.1007/s11425-010-4053-0
PG 12
WC Mathematics, Applied; Mathematics
SC Mathematics
GA 682EB
UT WOS:000284382200012
ER
PT J
AU Seeff, LB
Ghany, MG
AF Seeff, Leonard B.
Ghany, Marc G.
TI Management of Untreated and Nonresponder Patients with Chronic Hepatitis
C
SO SEMINARS IN LIVER DISEASE
LA English
DT Review
DE Chronic hepatitis C; peginterferon; ribavirin; sustained virologic
response; nonresponder; retreatment
ID SUSTAINED VIROLOGICAL RESPONSE; ALPHA-2B PLUS RIBAVIRIN; CHRONIC HCV
INFECTION; COMBINATION THERAPY; INTERFERON-ALPHA; VIRUS-INFECTION;
FOLLOW-UP; HEPATOCELLULAR-CARCINOMA; ALTERNATIVE MEDICINE; MAINTENANCE
THERAPY
AB Hepatitis C infection has evolved in the past quarter century from a newly recognized entity without a known pathogen (non-A, non-B hepatitis) to one of the world's most prevalent causes of liver disease, an important source for hepatocellular carcinoma, and the major indication for liver transplantation. It is caused by a virus with a complex replication cycle that occurs in multiple genotypes, of which the four most prevalent (1, 2, 3, and 4) exhibit differences in clinical behavior and responses to therapy. Chronic hepatitis C virus (HCV) in particular has evolved from a disease with no known treatment to one with several primary treatment options, none of which is uniformly effective, and a growing list of secondary treatment options for those who have failed to respond to, or relapsed after initial therapy. As treatment is often associated with significant side effects, it is now a disease that presents clinicians with multiple important decisions: whom to treat, when and with what to treat them initially, and how to manage patients who have failed during initial therapy to achieve a sustained virological response, the gold standard of effective therapy. This review examines each of these important decisions, presenting evidence to help guide clinicians in their choices. The decisions are addressed sequentially as they arise during the initial evaluation and subsequent treatment of a typical, newly recognized patient with chronic HCV, and the considerations facing the clinician when the patient has failed to achieve an SVR.
C1 [Seeff, Leonard B.] Hill Grp, Bethesda, MD 20817 USA.
[Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
RP Seeff, LB (reprint author), Hill Grp, 6903 Rockledge Dr,Suite 540, Bethesda, MD 20817 USA.
EM Mahler68@hotmail.com
NR 65
TC 4
Z9 6
U1 0
U2 0
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0272-8087
J9 SEMIN LIVER DIS
JI Semin. Liver Dis.
PD NOV
PY 2010
VL 30
IS 4
BP 348
EP 360
DI 10.1055/s-0030-1267536
PG 13
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 667UG
UT WOS:000283219900004
PM 20960375
ER
PT J
AU Coseo, S
Porras, C
Hildesheim, A
Rodriguez, AC
Schiffman, M
Herrero, R
Wacholder, S
Gonzalez, P
Wang, SS
Sherman, ME
Jimenez, S
Solomon, D
Bougelet, C
van Doorn, LJ
Quint, W
Safaeian, M
AF Coseo, Sarah
Porras, Carolina
Hildesheim, Allan
Cecilia Rodriguez, Ana
Schiffman, Mark
Herrero, Rolando
Wacholder, Sholom
Gonzalez, Paula
Wang, Sophia S.
Sherman, Mark E.
Jimenez, Silvia
Solomon, Diane
Bougelet, Catherine
van Doorn, Leen-Jan
Quint, Wim
Safaeian, Mahboobeh
CA Costa Rica HPV Vaccine Trial CVT
TI Seroprevalence and Correlates of Human Papillomavirus 16/18
Seropositivity Among Young Women in Costa Rica
SO SEXUALLY TRANSMITTED DISEASES
LA English
DT Article
ID VIRUS-LIKE PARTICLES; CERVICAL-CANCER; UNITED-STATES; VACCINE;
INFECTION; TYPE-16; HPV; PREVALENCE; POPULATION; TRIAL
AB Background: Serological indicators of human papillomavirus (HPV) infection are being used to differentiate HPV-naive from previously infected women in vaccine and epidemiologic/clinical studies. We investigated HPV16 and 18 seroepidemiology among young, unvaccinated women aged between 18 and 25.
Materials and Methods: We conducted a cross-sectional evaluation of the enrollment visit in the ongoing community-based HPV16/18 Costa Rica Vaccine Trial. Prevaccination serum immunoglobulin G (IgG) antibodies were measured against HPV16 and HPV18 by enzyme-linked immunosorbent assay; cervical samples were tested for HPV DNA using Hybrid Capture 2 and SPF(10)/LiPA(25). Seroprevalence and its correlates were evaluated using unconditional logistic regression.
Results: Among 5871 nonvirginal women, HPV16 and 18 seroprevalences were 30.8% and 28.1%, HPV16 and HPV18 DNA prevalences were 8.3% and 3.2%, respectively. About 37% of HPV16 DNA-positives and 42% of HPV18 DNA-positives were seronegative. Seroprevalence increased with time since sexual debut, whereas DNA prevalence did not. The correlates of HPV16 and/or 18 seropositivity were related to sexual behaviors, particularly higher number of lifetime sexual partners. There was no evidence of assay cross-reactivity as HPV16 seroprevalence was similar (approximately 34%) among women singly infected with genetically and nongenetically related species (alpha 9 and non-alpha 9); likewise, seropositivity to HPV18 was similar (approximately 30%) among women singly infected with alpha 7 and non-alpha 7 species.
Conclusions: The increasing seroprevalence observed with time since first sex suggests that HPV serology is a cumulative marker of HPV exposure. However, many DNA infected women were seronegative; thus, serology is an imperfect measure of past exposure to cervical HPV, at best. Additionally, we found no evidence of assay cross-reactivity.
C1 [Coseo, Sarah; Porras, Carolina; Hildesheim, Allan; Schiffman, Mark; Wacholder, Sholom; Wang, Sophia S.; Sherman, Mark E.; Safaeian, Mahboobeh] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Cecilia Rodriguez, Ana; Herrero, Rolando; Gonzalez, Paula; Jimenez, Silvia] Fundac INCIENSA, Proyecto Epidemiol Guanacaste, Liberia, Costa Rica.
[Solomon, Diane] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Bougelet, Catherine] GlaxoSmithKline Biol, Rixensart, Belgium.
[van Doorn, Leen-Jan; Quint, Wim] DDL Diagnost Lab, Voorburg, Netherlands.
RP Coseo, S (reprint author), Natl Canc Inst, NIH DHHS, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, 6120 Executive Blvd,EPS,Room 7079, Rockville, MD 20852 USA.
EM coseose@mail.nih.gov
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU NCI [N01-CP-11005]; GSK [FDA BB-IND 7920]; NIH Office of Research on
Women's Health
FX Supported by intramural NCI (N01-CP-11005) with support from the NIH
Office of Research on Women's Health and is conducted in agreement with
the Ministry of Health of Costa Rica. Vaccine was provided for our trial
by GSK Biologicals, under a clinical trials agreement with NCI. GSK also
provided support for aspects of the trial associated with the regulatory
submission needs of the company under FDA BB-IND 7920. NCI and Costa
Rican investigators make final editorial decisions on this presentation
and subsequent publications; GSK has the right to review/comment.
NR 29
TC 14
Z9 14
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-5717
J9 SEX TRANSM DIS
JI Sex. Transm. Dis.
PD NOV
PY 2010
VL 37
IS 11
BP 706
EP 714
DI 10.1097/OLQ.0b013e3181e1a2c5
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA 671FY
UT WOS:000283487100008
PM 20661178
ER
PT J
AU Miller, FG
Kallmes, DF
AF Miller, Franklin G.
Kallmes, David F.
TI The Case of Vertebroplasty Trials Promoting a Culture of Evidence-Based
Procedural Medicine
SO SPINE
LA English
DT Article
ID OSTEOPOROTIC VERTEBRAL FRACTURES; PERCUTANEOUS VERTEBROPLASTY;
RANDOMIZED-TRIAL
C1 [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
[Kallmes, David F.] Mayo Clin, Dept Radiol, Rochester, MN USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
NR 14
TC 11
Z9 11
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0362-2436
J9 SPINE
JI SPINE
PD NOV 1
PY 2010
VL 35
IS 23
BP 2023
EP 2026
DI 10.1097/BRS.0b013e3181ecd393
PG 4
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 671GX
UT WOS:000283490100018
PM 20938382
ER
PT J
AU Pistollato, F
Rampazzo, E
Persano, L
Abbadi, S
Frasson, C
Denaro, L
D'Avella, D
Panchision, DM
Della Puppa, A
Scienza, R
Basso, G
AF Pistollato, Francesca
Rampazzo, Elena
Persano, Luca
Abbadi, Sara
Frasson, Chiara
Denaro, Luca
D'Avella, Domenico
Panchision, David M.
Della Puppa, Alessandro
Scienza, Renato
Basso, Giuseppe
TI Interaction of Hypoxia-Inducible Factor-1 alpha and Notch Signaling
Regulates Medulloblastoma Precursor Proliferation and Fate
SO STEM CELLS
LA English
DT Article
DE Medulloblastoma; Cancer stem cells; Hypoxia; Notch1; Hypoxia-inducible
factor-1 alpha
ID CANCER STEM-CELLS; TUMOR-INITIATING CELLS; PROGENITOR CELLS; NEURON
PRECURSORS; VASCULAR NICHE; BRAIN-TUMORS; MOUSE MODEL; GROWTH;
EXPRESSION; GLIOBLASTOMA
AB Medulloblastoma (MDB) is the most common brain malignancy of childhood. It is currently thought that MDB arises from aberrantly functioning stem cells in the cerebellum that fail to maintain proper control of self-renewal. Additionally, it has been reported that MDB cells display higher endogenous Notch signaling activation, known to promote the survival and proliferation of neoplastic neural stem cells and to inhibit their differentiation. Although interaction between hypoxia-inducible factor-1 alpha (HIF-1 alpha) and Notch signaling is required to maintain normal neural precursors in an undifferentiated state, an interaction has not been identified in MDB. Here, we investigate whether hypoxia, through HIF-1 alpha stabilization, modulates Notch1 signaling in primary MDB-derived cells. Our results indicate that MDB-derived precursor cells require hypoxic conditions for in vitro expansion, whereas acute exposure to 20% oxygen induces tumor cell differentiation and death through inhibition of Notch signaling. Importantly, stimulating Notch1 activation with its ligand Dll4 under hypoxic conditions leads to expansion of MDB-derived CD133(+) and nestin(+) precursors, suggesting a regulatory effect on stem cells. In contrast, MDB cells undergo neuronal differentiation when treated with gamma-secretase inhibitor, which prevents Notch activation. These results suggest that hypoxia, by maintaining Notch1 in its active form, preserves MDB stem cell viability and expansion. STEM CELLS 2010;28:1918-1929
C1 [Pistollato, Francesca; Rampazzo, Elena; Persano, Luca; Abbadi, Sara; Frasson, Chiara; Basso, Giuseppe] Univ Padua, Dept Pediat, SSD Clin & Expt Hematol, I-35128 Padua, Italy.
[Denaro, Luca; D'Avella, Domenico; Della Puppa, Alessandro; Scienza, Renato] Univ Padua, Dept Neurosurg, I-35128 Padua, Italy.
[Panchision, David M.] NIMH, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA.
RP Persano, L (reprint author), Univ Padua, Dept Pediat, SSD Clin & Expt Hematol, Via Giustiniani 3, I-35128 Padua, Italy.
EM luca.persano@unipd.it
RI Persano, Luca/H-6416-2016;
OI Persano, Luca/0000-0002-0050-3666; BASSO, GIUSEPPE/0000-0002-2634-9302
FU Italian Association for the Fight against Neuroblastoma; Italian
Association AIRC
FX We thank Dr. Pier Giorgio Modena, from CRO, Aviano, Italy, for providing
MDB-derived cells and Prof. Felice Giangaspero, from University of "La
Sapienza" Rome, for providing a quote of MDB histological samples. We
are grateful to Dr. Stefano Indraccolo for lentiviral vectors production
and thank Dr. Andrea Zangrando for his help with image management. This
research was supported by funds from the Italian Association for the
Fight against Neuroblastoma (Pensiero Project) and the Italian
Association AIRC (Interregional pediatric project grant).
NR 64
TC 54
Z9 58
U1 1
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD NOV
PY 2010
VL 28
IS 11
BP 1918
EP 1929
DI 10.1002/stem.518
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 682IW
UT WOS:000284395900002
PM 20827750
ER
PT J
AU Matsuda, H
Shi, YB
AF Matsuda, Hiroki
Shi, Yun-Bo
TI An Essential and Evolutionarily Conserved Role of Protein Arginine
Methyltransferase 1 for Adult Intestinal Stem Cells During Postembryonic
Development
SO STEM CELLS
LA English
DT Article
DE Adult organ-specific stem cell; Histone arginine methyltransferase;
Transcriptional coactivator; Thyroid hormone receptor; Dedifferentiation
ID THYROID-HORMONE RECEPTOR; XENOPUS-LAEVIS; AMPHIBIAN METAMORPHOSIS;
TRANSCRIPTIONAL REGULATION; MEDIATED TRANSCRIPTION; LIMB REGENERATION;
GENE-EXPRESSION; EPITHELIUM; PROLIFERATION; RECRUITMENT
AB Organ-specific adult stem cells are critical for the homeo-stasis of adult organs and organ repair and regeneration. Unfortunately, it has been difficult to investigate the origins of these stem cells and the mechanisms of their development, especially in mammals. Intestinal remodeling during frog metamorphosis offers a unique opportunity for such studies. During the transition from an herbivorous tadpole to a carnivorous frog, the intestine is completely remodeled as the larval epithelial cells undergo apoptotic degeneration and are replaced by adult epithelial cells developed de novo. The entire metamorphic process is under the control of thyroid hormone, making it possible to control the development of the adult intestinal stem cells. Here, we show that the thyroid hormone receptor-coactivator protein arginine methyltransferase 1 (PRMT1) is upregulated in a small number of larval epithelial cells and that these cells dedifferentiate to become the adult stem cells. More importantly, transgenic overexpression of PRMT1 leads to increased adult stem cells in the intestine, and conversely, knocking down the expression of endogenous PRMT1 reduces the adult stem cell population. In addition, PRMT1 expression pattern during zebrafish and mouse development suggests that PRMT1 may play an evolutionally conserved role in the development of adult intestinal stem cells throughout vertebrates. These findings are not only important for the understanding of organ-specific adult stem cell development