FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Duggan, C
Risques, R
Alfano, C
Prunkard, D
Imayama, I
Holte, S
Baumgartner, K
Baumgartner, R
Bernstein, L
Ballard-Barbash, R
Rabinovitch, P
McTiernan, A
AF Duggan, Catherine
Risques, Rosana
Alfano, Catherine
Prunkard, Donna
Imayama, Ikuyo
Holte, Sarah
Baumgartner, Kathy
Baumgartner, Rick
Bernstein, Leslie
Ballard-Barbash, Rachel
Rabinovitch, Peter
McTiernan, Anne
TI Change in Peripheral Blood Leukocyte Telomere Length and Mortality in
Breast Cancer Survivors
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SHANGHAI WOMENS HEALTH; PERCEIVED STRESS; INCIDENT CANCER; LIFE-STYLE;
FOLLOW-UP; RISK; ASSOCIATION; DYSFUNCTION; SENESCENCE; CELLS
AB Background Progressive telomere shortening with cell division is a hallmark of aging. Short telomeres are associated with increased cancer risk, but there are conflicting reports about telomere length and mortality in breast cancer survivors.
Methods We measured peripheral blood leukocyte telomere length at two time points in women enrolled in a multiethnic, prospective cohort of stage I to stage IIIA breast cancer survivors diagnosed between 1995 and 1999 with a median follow-up of 11.2 years. We evaluated associations between telomere length measured at mean 6 (baseline; LTL0; n = 611) and 30 months (LTL30; n = 478) after diagnosis and the change between those time points (n = 478), with breast cancer-specific and all-cause mortality using Cox proportional hazards models adjusted for possible confounders. Statistical tests were two-sided.
Results There were 135 deaths, of which 74 were due to breast cancer. Neither baseline nor 30-month telomere length was associated with either all-cause or breast cancer-specific mortality (LTL0: hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.67 to 1.02; HR = 0.88; 95% CI = 0.67 to 1.15; LTL30: HR = 0.78, 95% CI = 0.59 to 1.05; HR = 0.86; 95% = CI = 0.58 to 1.26, respectively). However, participants whose telomeres shortened between baseline and 30 months were at a statistically significantly increased risk of breast cancer-specific (HR = 3.03; 95% CI = 1.11 to 8.18) and all-cause mortality (HR = 2.38; 95% CI = 1.28 to 4.39) compared with participants whose telomeres lengthened. When follow-up was censored at 5-years after diagnosis, LTL0 (HR = 0.66; 95% CI = 0.45 to 0.96), LTL30 (HR = 0.51; 95% CI = 0.29 to 0.92), and change in telomere length (HR = 3.45; 95% CI = 1.11 to 10.75) were statistically significantly associated with all-cause mortality.
Conclusions Telomere shortening was associated with increased risk of breast cancer-specific and all-cause mortality, suggesting that change in blood telomere length over time could be a biomarker of prognosis. Research on determinants of telomere length and change is needed.
C1 [Duggan, Catherine; Imayama, Ikuyo; Holte, Sarah; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Risques, Rosana; Prunkard, Donna; Rabinovitch, Peter] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[McTiernan, Anne] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Risques, Rosana; Prunkard, Donna; Rabinovitch, Peter; McTiernan, Anne] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
[Alfano, Catherine] NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA.
[Ballard-Barbash, Rachel] NCI, Appl Res Program, NIH, Bethesda, MD 20892 USA.
[Baumgartner, Kathy; Baumgartner, Rick] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Dept Canc Etiol, Duarte, CA 91010 USA.
RP Duggan, C (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1100 Fairview Ave N, Seattle, WA 98109 USA.
EM cduggan@fhcrc.org
RI Duggan, Catherine/F-9414-2015
OI Duggan, Catherine/0000-0001-7369-4021
FU National Cancer Institute at the National Institutes of Health
[N01-CN-75036-20, N01-CN-05228, N01-PC-67010, U54-CA116847, U54CA116848,
R25-CA94880, HHSN261200900581P]; National Institutes of Health
[M01-RR-00037]; University of New Mexico [NCRR M01-RR-0997]; National
Institute of Child Health and Human Development at the National
Institutes of Health [N01-HD-3-3175]; California Department of Health
Services [050Q-8709-S1528]
FX This work was supported by grants from the National Cancer Institute at
the National Institutes of Health (N01-CN-75036-20, N01-CN-05228,
N01-PC-67010, U54-CA116847, U54CA116848, R25-CA94880,
HHSN261200900581P); the National Institutes of Health (M01-RR-00037);
the University of New Mexico (NCRR M01-RR-0997); the National Institute
of Child Health and Human Development at the National Institutes of
Health (N01-HD-3-3175); and the California Department of Health Services
(050Q-8709-S1528).
NR 48
TC 10
Z9 10
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD APR
PY 2014
VL 106
IS 4
AR dju035
DI 10.1093/jnci/dju035
PG 10
WC Oncology
SC Oncology
GA AF4OA
UT WOS:000334691500018
PM 24627273
ER
PT J
AU Freidlin, B
Korn, EL
AF Freidlin, Boris
Korn, Edward L.
TI RE: A Model Too Far Response
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
ID LOCALIZED PROSTATE-CANCER; CONSERVATIVE MANAGEMENT; OUTCOMES
C1 [Freidlin, Boris; Korn, Edward L.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Freidlin, B (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
EM freidlinb@ctep.nci.nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD APR
PY 2014
VL 106
IS 4
AR dju059
DI 10.1093/jnci/dju059
PG 1
WC Oncology
SC Oncology
GA AF4OA
UT WOS:000334691500031
PM 24659792
ER
PT J
AU Park, SL
Fesinmeyer, MD
Timofeeva, M
Caberto, CP
Kocarnik, JM
Han, YH
Love, SA
Young, A
Dumitrescu, L
Lin, Y
Goodloe, R
Wilkens, LR
Hindorff, L
Fowke, JH
Carty, C
Buyske, S
Schumacher, FR
Butler, A
Dilks, H
Deelman, E
Cote, ML
Chen, W
Pande, M
Christiani, DC
Field, JK
Bickeboller, H
Risch, A
Heinrich, J
Brennan, P
Wang, YF
Eisen, T
Houlston, RS
Thun, M
Albanes, D
Caporaso, N
Peters, U
North, KE
Heiss, G
Crawford, DC
Bush, WS
Haiman, CA
Landi, MT
Hung, RJ
Kooperberg, C
Amos, CI
Le Marchand, L
Cheng, I
AF Park, S. Lani
Fesinmeyer, Megan D.
Timofeeva, Maria
Caberto, Christian P.
Kocarnik, Jonathan M.
Han, Younghun
Love, Shelly-Ann
Young, Alicia
Dumitrescu, Logan
Lin, Yi
Goodloe, Robert
Wilkens, Lynne R.
Hindorff, Lucia
Fowke, Jay H.
Carty, Cara
Buyske, Steven
Schumacher, Frederick R.
Butler, Anne
Dilks, Holli
Deelman, Ewa
Cote, Michele L.
Chen, Wei
Pande, Mala
Christiani, David C.
Field, John K.
Bickeboeller, Heike
Risch, Angela
Heinrich, Joachim
Brennan, Paul
Wang, Yufei
Eisen, Timothy
Houlston, Richard S.
Thun, Michael
Albanes, Demetrius
Caporaso, Neil
Peters, Ulrike
North, Kari E.
Heiss, Gerardo
Crawford, Dana C.
Bush, William S.
Haiman, Christopher A.
Landi, Maria Teresa
Hung, Rayjean J.
Kooperberg, Charles
Amos, Christopher I.
Le Marchand, Loic
Cheng, Iona
TI Pleiotropic Associations of Risk Variants Identified for Other Cancers
With Lung Cancer Risk: The PAGE and TRICL Consortia
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COMMON GENETIC-VARIATION; SUSCEPTIBILITY LOCI;
BREAST-CANCER; GENOTYPE DATA; METAANALYSIS; POPULATION; GLIOMA;
ADENOCARCINOMA; AGGREGATION
AB Background Genome-wide association studies have identified hundreds of genetic variants associated with specific cancers. A few of these risk regions have been associated with more than one cancer site; however, a systematic evaluation of the associations between risk variants for other cancers and lung cancer risk has yet to be performed.
Methods We included 18 023 patients with lung cancer and 60 543 control subjects from two consortia, Population Architecture using Genomics and Epidemiology (PAGE) and Transdisciplinary Research in Cancer of the Lung (TRICL). We examined 165 single-nucleotide polymorphisms (SNPs) that were previously associated with at least one of 16 non-lung cancer sites. Study-specific logistic regression results underwent meta-analysis, and associations were also examined by race/ethnicity, histological cell type, sex, and smoking status. A Bonferroni-corrected P value of 2.5 x 10(-5) was used to assign statistical significance.
Results The breast cancer SNP LSP1 rs3817198 was associated with an increased risk of lung cancer (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.05 to 1.14; P = 2.8 x 10(-6)). This association was strongest for women with adenocarcinoma (P = 1.2 x 10(-4)) and not statistically significant in men (P = .14) with this cell type (P-het by sex = .10). Two glioma risk variants, TERT rs2853676 and CDKN2BAS1 rs4977756, which are located in regions previously associated with lung cancer, were associated with increased risk of adenocarcinoma (OR = 1.16; 95% CI = 1.10 to 1.22; P = 1.1 x 10(-8)) and squamous cell carcinoma (OR = 1.13; CI = 1.07 to 1.19; P = 2.5 x 10(-5)), respectively.
Conclusions Our findings demonstrate a novel pleiotropic association between the breast cancer LSP1 risk region marked by variant rs3817198 and lung cancer risk.
C1 [Park, S. Lani; Schumacher, Frederick R.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Fesinmeyer, Megan D.; Kocarnik, Jonathan M.; Young, Alicia; Lin, Yi; Carty, Cara; Peters, Ulrike; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Timofeeva, Maria] Univ Edinburgh, Inst Genet & Mol Med, Colon Canc Genet Grp, Edinburgh, Midlothian, Scotland.
[Timofeeva, Maria] MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland.
[Caberto, Christian P.; Wilkens, Lynne R.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA.
[Han, Younghun; Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA.
[Love, Shelly-Ann; Butler, Anne; North, Kari E.; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Dumitrescu, Logan; Crawford, Dana C.; Bush, William S.] Vanderbilt Univ, Nashville, TN 37235 USA.
[Dumitrescu, Logan; Goodloe, Robert; Dilks, Holli; Crawford, Dana C.; Bush, William S.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37235 USA.
[Fowke, Jay H.] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Nashville, TN 37235 USA.
[Hindorff, Lucia] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA.
[Albanes, Demetrius; Caporaso, Neil; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Buyske, Steven] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA.
[Deelman, Ewa] Univ So Calif, Inst Informat Sci, Marina Del Rey, CA 90292 USA.
[Cote, Michele L.] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA.
[Chen, Wei; Pande, Mala] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Christiani, David C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Field, John K.] Univ Liverpool, Roy Castle Lung Canc Res Programme, Dept Mol & Clin Canc Med, Canc Res Ctr,Inst Translat Med, Liverpool L69 3BX, Merseyside, England.
[Bickeboeller, Heike] Univ Med Ctr Gottingen, Dept Genet Epidemiol, Gottingen, Germany.
[Risch, Angela] DKFZ German Canc Res Ctr, Heidelberg, Germany.
[Risch, Angela] Translat Lung Res Ctr Heidelberg, Heidelberg, Germany.
[Heinrich, Joachim] Helmholtz Zentrum Munchen, Inst Epidemiol 1, Munich, Germany.
[Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Wang, Yufei; Houlston, Richard S.] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
[Eisen, Timothy] Cambridge Univ Hlth Partners, Cambridge, England.
[Thun, Michael] Amer Canc Soc, Atlanta, GA 30329 USA.
[Hung, Rayjean J.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Cheng, Iona] Canc Prevent Inst Calif, Fremont, CA USA.
RP Park, SL (reprint author), USC Keck Sch Med, Dept Prevent Med, 1450 Biggy St,NRT 1509G, Los Angeles, CA 90033 USA.
EM sungship@med.usc.edu
RI Albanes, Demetrius/B-9749-2015; Hung, Rayjean/A-7439-2013; Risch,
Angela/H-2669-2013;
OI Risch, Angela/0000-0002-8026-5505; Bush, William/0000-0002-9729-6519;
Field, John/0000-0003-3951-6365; Buyske, Steven/0000-0001-8539-5416;
Houlston, Richard/0000-0002-5268-0242
FU Population Architecture Using Genomics and Epidemiology (PAGE) program -
National Human Genome Research Institute (NHGRI); NHGRI PAGE program
[U01HG004798-01, U01HG004802]; Johns Hopkins University from NHLBI
[N01-HV-48195]; Centers for Disease Control and Prevention (CDC);
Vanderbilt CTSA from NCATS/NIH [UL1 TR000445]; National Cancer Institute
[R37CA54281, R01 CA63, P01CA33619, U01CA136792, U01CA98758]; CALiCo
[U01HG004803]; EAGLE [U01HG004798]; MEC [U01HG004802]; WHI
[U01HG004790]; Coordinating Center [U01HG004801]; "Epidemiology of
putative genetic variants: The Women's Health Initiative" through the
NHGRI PAGE program [U01HG004790]; National Heart, Lung, and Blood
Institute, NIH, US Department of Health and Human Services
[HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; NCI
[R25CA94880, NO1-CN-25514]; Genetic Epidemiology of Causal Variants
Across the Life Course (CALiCo) program through the NHGRI PAGE program
[U01HG004803]; Atherosclerosis Risk in Communities Study - National
Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; NHGRI
[U01HG004402]; NIH [HHSN268200625226C, UL1RR025005, 5R01CA055769,
5R01CA127219, 5R01CA133996, 5R01CA121197, U19CA148127,
HHSN268200782096C, P50 CA70907, R01CA121197, R01 CA127219, U19 CA148127,
R01 CA55769, K07CA160753]; NIH Roadmap for Medical Research; National
Institute of Mental Health; Transdisciplinary Research in Cancer of the
Lung (TRICL) Study [U19-CA148127]; Canadian Cancer Society Research
Institute [020214]; Ontario Institute of Cancer; Cancer Care Ontario
Chair; Cancer Research UK [C1298/A8780, C1298/A8362]; NCRN; HEAL;
Sanofi-Aventis; Roy Castle Lung Cancer Foundation, UK; Deutsche
Krebshilfe [70-2919]; Helmholtz-DAAD fellowship [A/07/97379]; GSF -
German Federal Ministry of Education, Science, Research and Technology;
State of Bavaria; National Genome Research Network (NGFN); DFG [BI
576/2-1, BI 576/2-2]; Helmholtzgemeinschaft (HGF); Federal office for
Radiation Protection [BfS: STSch4454]; Central Europe; HUNT2/Tromso;
CARET genome; European Community; Central Europe study, Czech Republic;
European Regional Development Fund; State Budget of the Czech Republic
(RECAMO) [CZ.1.05/2.1.00/03.0101]; US National Cancer Institute, NIH
[R01 CA111703, UO1 CA63673]; Fred Hutchinson Cancer Research Center; US
National Cancer Institute [R01 CA092039]; FP7 grant [REGPOT 245536];
Estonian Government [SF0180142s08]; EU RDF; Estoinian Research
Infrastructure's Roadmap; University of Tartu (SP1GVARENG); IARC;
Intramural Research Program of NIH, NCI, Division of Cancer Epidemiology
and Genetics; US Public Health Service from the NCI [N01-CN-45165,
N01-RC-45035, N01-RC-37004]; Georgetown University [NO1-CN-25522];
Pacific Health Research Institute [NO1-CN-25515]; Henry Ford Health
System [NO1-CN-25512]; University of Minnesota [NO1-CN-25513];
Washington University [NO1-CN-25516]; University of Pittsburgh
[NO1-CN-25511]; University of Utah [NO1-CN-25524]; Marshfield Clinic
Research Foundation [NO1-CN-25518]; University of Alabama at Birmingham
[NO1-CN-75022]; Westat, Inc. [NO1-CN-25476]; University of California,
Los Angeles [NO1-CN-25404]; American Cancer Society; Johns Hopkins
University Center for Inherited Disease Research [HG-06-033-NCI-01,
RO1HL091172-01, U01HG004438]; CPRIT [RP100443]; NIH (National Cancer
Institute) [CA092824, CA090578, CA074386]; [R01HL087641];
[R01HL59367]; [R01HL086694]; [U01 HG004446]
FX PAGE; This work was supported by the Population Architecture Using
Genomics and Epidemiology (PAGE) program that is funded by the National
Human Genome Research Institute (NHGRI), supported by U01HG004803
(CALiCo), U01HG004798 (EAGLE), U01HG004802 (MEC), U01HG004790 (WHI), and
U01HG004801 (Coordinating Center), and their respective NHGRI ARRA
supplements. The contents of this paper are solely the responsibility of
the authors and do not necessarily represent the official views of the
National Institutes of Health (NIH). The complete list of PAGE members
can be found at http://www.pagestudy.org.; Epidemiologic Architecture
for Genes Linked to Environment (EAGLE) is funded through the NHGRI PAGE
program (U01HG004798-01 and its NHGRI ARRA supplement). Genotyping
services for select NHANES III SNPs presented here were also provided by
the Johns Hopkins University under federal contract number
(N01-HV-48195) from NHLBI. The study participants derive from the
National Health and Nutrition Examination Survey (NHANES), and these
studies are supported by the Centers for Disease Control and Prevention
(CDC). The findings and conclusions in this report are those of the
authors and do not necessarily represent the views of the CDC. The
dataset used for the analyses described was obtained from Vanderbilt
University Medical Center's BioVU, which is supported by institutional
funding and by the Vanderbilt CTSA grant UL1 TR000445 from NCATS/NIH.;
The Multiethnic Cohort study (MEC) characterization of epidemiological
architecture is funded through the NHGRI PAGE program (U01HG004802 and
its NHGRI ARRA supplement). The MEC study is funded through the National
Cancer Institute (R37CA54281, R01 CA63, P01CA33619, U01CA136792, and
U01CA98758).; Funding support for the "Epidemiology of putative genetic
variants: The Women's Health Initiative" study is provided through the
NHGRI PAGE program (U01HG004790 and its NHGRI ARRA supplement). The WHI
program is funded by the National Heart, Lung, and Blood Institute, NIH,
US Department of Health and Human Services through contracts
HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. JK is
supported by R25CA94880 from NCI. The authors thank the WHI
investigators and staff for their dedication, and the study participants
for making the program possible. A full listing of WHI investigators can
be found at:
http://www.whiscience.org/publications/WHI_investigators_shortlist.pdf.;
Funding support for the Genetic Epidemiology of Causal Variants Across
the Life Course (CALiCo) program was provided through the NHGRI PAGE
program (U01HG004803 and its NHGRI ARRA supplement). The following study
contributed to this manuscript and is funded by the following agencies:
the Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by National Heart, Lung, and Blood
Institute contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C),
R01HL087641, R01HL59367 and R01HL086694; NHGRI contract U01HG004402; and
NIH contract HHSN268200625226C. The authors thank the staff and
participants of the ARIC study for their important contributions.
Infrastructure was partly supported by Grant Number UL1RR025005, a
component of the NIH and NIH Roadmap for Medical Research. Assistance
with phenotype harmonization, SNP selection and annotation, data
cleaning, data management, integration and dissemination, and general
study coordination was provided by the PAGE Coordinating Center
(U01HG004801-01 and its NHGRI ARRA supplement). The National Institute
of Mental Health also contributes to the support for the Coordinating
Center.; TRICL; This work was supported by the Transdisciplinary
Research in Cancer of the Lung (TRICL) Study, U19-CA148127 on behalf of
the Genetic Associations and Mechanisms in Oncology (GAME-ON) Network.;
The SLRI study was supported by Canadian Cancer Society Research
Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario
Chair Award to RH The ICR study was supported by Cancer Research UK
(C1298/A8780 and C1298/A8362-Bobby Moore Fund for Cancer Research UK)
and NCRN, HEAL and Sanofi-Aventis. Additional funding was obtained from
NIH grants (5R01CA055769, 5R01CA127219, 5R01CA133996, and 5R01CA121197).
The Liverpool Lung Project (LLP) was supported by The Roy Castle Lung
Cancer Foundation, UK. The ICR and LLP studies made use of genotyping
data from the Wellcome Trust Case Control Consortium 2 (WTCCC2); a full
list of the investigators who contributed to the generation of the data
is available from www.wtccc.org.uk. Sample collection for the Heidelberg
lung cancer study was in part supported by a grant (70-2919) from the
Deutsche Krebshilfe. The work was additionally supported by a
Helmholtz-DAAD fellowship (A/07/97379 to MNT) and by the NIH
(U19CA148127). The KORA Surveys were financed by the GSF, which is
funded by the German Federal Ministry of Education, Science, Research
and Technology and the State of Bavaria. The LUng Cancer in the Young
study (LUCY) was funded in part by the National Genome Research Network
(NGFN), the DFG (BI 576/2-1; BI 576/2-2), the Helmholtzgemeinschaft
(HGF) and the Federal office for Radiation Protection (BfS: STSch4454).
Genotyping was performed in the Genome Analysis Center (GAC) of the
Helmholtz ZentrumMuenchen. Support for the Central Europe, HUNT2/Tromso
and CARET genome-wide studies was provided by Institut National du
Cancer, France. Support for the HUNT2/Tromso genome-wide study was also
provided by the European Community; (Integrated Project DNA repair,
LSHG-CT-2005-512113), the Norwegian Cancer Association and the
Functional Genomics Programme of Research Council of Norway. Support for
the Central Europe study, Czech Republic, was also provided by the
European Regional Development Fund and the State Budget of the Czech
Republic (RECAMO, CZ.1.05/2.1.00/03.0101). Support for the CARET
genomewide study was also provided by grants from the US National Cancer
Institute, NIH (R01 CA111703 and UO1 CA63673), and by funds from the
Fred Hutchinson Cancer Research Center. Additional funding for study
coordination, genotyping of replication studies and statistical analysis
was provided by the US National Cancer Institute (R01 CA092039). The
lung cancer GWAS from Estonia was partly supported by a FP7 grant
(REGPOT 245536), by the Estonian Government (SF0180142s08), by EU RDF in
the frame of Centre of Excellence in Genomics and Estoinian Research
Infrastructure's Roadmap and by University of Tartu (SP1GVARENG). The
work reported in this paper was partly undertaken during the tenure of a
Postdoctoral Fellowship from the IARC (for MNT). The Environment and
Genetics in Lung Cancer Etiology (EAGLE), the Alpha-Tocopherol,
Beta-Carotene Cancer Prevention Study (ATBC), and the Prostate, Lung,
Colon, Ovary Screening Trial (PLCO) studies and the genotyping of ATBC,
the; Cancer Prevention Study II Nutrition Cohort (CPS-II) and part of
PLCO were supported by the Intramural Research Program of NIH, NCI,
Division of Cancer Epidemiology and Genetics. ATBC was also supported by
US Public Health Service contracts (N01-CN-45165, N01-RC-45035 and
N01-RC-37004) from the NCI. PLCO was also supported by individual
contracts from the NCI to the University of Colorado Denver
(NO1-CN-25514), Georgetown University; (NO1-CN-25522), Pacific Health
Research Institute (NO1-CN-25515), Henry Ford Health System
(NO1-CN-25512), University of Minnesota (NO1-CN-25513), Washington
University; (NO1-CN-25516), University of Pittsburgh (NO1-CN-25511),
University of Utah (NO1-CN-25524), Marshfield Clinic Research Foundation
(NO1-CN-25518), University of Alabama at Birmingham (NO1-CN-75022,
Westat, Inc. NO1-CN-25476), University of California, Los Angeles
(NO1-CN-25404). The Cancer Prevention Study II Nutrition Cohort was
supported by the American Cancer Society. The NIH Genes, Environment and
Health Initiative (GEI) partly; funded DNA extraction and statistical
analyses (HG-06-033-NCI-01 and RO1HL091172-01), genotyping at the Johns
Hopkins University Center for Inherited Disease Research (U01HG004438
and NIH HHSN268200782096C) and study coordination at the GENEVA
Coordination Center (U01 HG004446) for EAGLE and part of PLCO studies.
Funding for the MD Anderson Cancer Study was provided by NIH grants (P50
CA70907, R01CA121197, R01 CA127219, U19 CA148127, R01 CA55769,
K07CA160753) and CPRIT grant (RP100443). Genotyping services were
provided by the Center for Inherited Disease Research (CIDR). CIDR is
funded through a federal contract from the NIH to The Johns Hopkins
University (HHSN268200782096C). The Harvard Lung Cancer Study was
supported by the NIH (National Cancer Institute) grants CA092824,
CA090578, CA074386.
NR 36
TC 6
Z9 7
U1 1
U2 12
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD APR
PY 2014
VL 106
IS 4
AR dju061
DI 10.1093/jnci/dju061
PG 8
WC Oncology
SC Oncology
GA AF4OA
UT WOS:000334691500032
PM 24681604
ER
PT J
AU Visser, M
Brychta, RJ
Chen, KY
Koster, A
AF Visser, Marjolein
Brychta, Robert J.
Chen, Kong Y.
Koster, Annemarie
TI Self-Reported Adherence to the Physical Activity Recommendation and
Determinants of Misperception in Older Adults
SO JOURNAL OF AGING AND PHYSICAL ACTIVITY
LA English
DT Article
DE accelerometry; physical activity questionnaire; overestimation
ID PUBLIC-HEALTH; US ADULTS; ACCELEROMETER; PEOPLE; QUESTIONNAIRE;
CALIBRATION; BEHAVIORS; PEDOMETER; VALIDITY; PROFILE
AB We aimed to compare self-reported adherence to the physical activity recommendation with accelerometry in older adults and to identify determinants of misperception. The sample included 138 adults age 65-75 yr old participating in the Longitudinal Aging Study Amsterdam. Participants completed a lifestyle questionnaire and wore an accelerometer for one week. More than half (56.8%) of the participants reported to adhere to the physical activity recommendation (in 5-min bouts), however, based on accelerometry, this percentage was only 24.6%. Of those who reported to adhere, 65.3% did not do so based on accelerometry. The misperceivers were older (p <.009), more often female (p =.007), had a poorer walking performance (p =.02), reported a lower social support (p =.04), and tended to have a lower self-efficacy (p =.09) compared with those who correctly perceived their adherence to the recommendation. These results suggest that misperception of adherence to the physical activity recommendation is highly prevalent among specific subgroups of older adults.
C1 [Visser, Marjolein] Vrije Univ Amsterdam, Amsterdam, Netherlands.
[Visser, Marjolein] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
[Brychta, Robert J.; Chen, Kong Y.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Koster, Annemarie] Maastricht Univ, Maastricht, Netherlands.
RP Visser, M (reprint author), Vrije Univ Amsterdam, Amsterdam, Netherlands.
RI Koster, Annemarie/E-7438-2010;
OI Chen, Kong/0000-0002-0306-1904
FU Dutch Ministry of Public Health, Welfare and Sports; NIH, National
Institute on Aging
FX The Longitudinal Aging Study Amsterdam is financially supported by the
Dutch Ministry of Public Health, Welfare and Sports. This study was
partly funded by the Intramural Research Program of the NIH, National
Institute on Aging.
NR 33
TC 7
Z9 7
U1 1
U2 8
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1063-8652
EI 1543-267X
J9 J AGING PHYS ACTIV
JI J. Aging Phys. Act.
PD APR
PY 2014
VL 22
IS 2
BP 226
EP 234
DI 10.1123/JAPA.2012-0219
PG 9
WC Geriatrics & Gerontology; Gerontology; Sport Sciences
SC Geriatrics & Gerontology; Sport Sciences
GA AF0HT
UT WOS:000334395600006
PM 23752449
ER
PT J
AU Ying, JF
Roche, JL
Bax, A
AF Ying, Jinfa
Roche, Julien
Bax, Ad
TI Homonuclear decoupling for enhancing resolution and sensitivity in NOE
and RDC measurements of peptides and proteins
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Diffusion anisotropy; IDP; Residual dipolar coupling; RDC; Weak
alignment; Liquid crystal; NOESY; Synuclein; Ubiquitin
ID MULTIDIMENSIONAL NMR EXPERIMENTS; LIQUID-CRYSTALLINE PHASE;
TWO-DIMENSIONAL NMR; DIPOLAR COUPLINGS; PULSE SEQUENCES; PROTON NMR;
SPECTROSCOPY; SPECTRA; ASSIGNMENT; ALIGNMENT
AB Application of band-selective homonuclear (BASH) H-1 decoupling pulses during acquisition of the 1H free induction decay is shown to be an efficient procedure for removal of scalar and residual dipolar couplings between amide and aliphatic protons. BASH decoupling can be applied in both dimensions of a homonuclear 20 NMR experiment and is particularly useful for enhancing spectral resolution in the H-N-H-alpha region of NOESY spectra of peptides and proteins, which contain important information on the backbone torsion angles. The method then also prevents generation of zero quantum and H-z(N)-H-z(alpha) terms, thereby facilitating analysis of intraresidue interactions. Application to the NOESY spectrum of a hexapeptide fragment of the intrinsically disordered protein alpha-synuclein highlights the considerable diffusion anisotropy present in linear peptides. Removal of residual dipolar couplings between H-N and aliphatic protons in weakly aligned proteins increases resolution in the H-1-N-15 HSQC region of the spectrum and allows measurement of RDCs in samples that are relatively strongly aligned. The approach is demonstrated for measurement of RDCs in protonated N-15/C-13-enriched ubiquitin, aligned in Pf1, yielding improved fitting to the ubiquitin structure. Published by Elsevier Inc.
C1 [Ying, Jinfa; Roche, Julien; Bax, Ad] Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM bax@nih.gov
RI Roche, Julien/O-3204-2013
OI Roche, Julien/0000-0003-3892-0200
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; National Institutes of Health (NIH);
Intramural AIDS-Targeted Antiviral Program of the Office of the
Director, NIH
FX This work was funded by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health (NIH) and the Intramural AIDS-Targeted Antiviral
Program of the Office of the Director, NIH.
NR 35
TC 49
Z9 49
U1 4
U2 44
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
EI 1096-0856
J9 J MAGN RESON
JI J. Magn. Reson.
PD APR
PY 2014
VL 241
SI SI
BP 97
EP 102
DI 10.1016/j.jmr.2013.11.006
PG 6
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA AF4AK
UT WOS:000334653600010
PM 24360766
ER
PT J
AU Choi, HJ
Shung, KK
AF Choi, Hojong
Shung, K. Kirk
TI Protection Circuits for Very High Frequency Ultrasound Systems
SO JOURNAL OF MEDICAL SYSTEMS
LA English
DT Article
DE Very high frequency; Ultrasonic transducers; Protection circuits; MOSFET
ID PREAMPLIFIER; TRANSDUCERS; DESIGN; FILMS
AB The purpose of protection circuits in ultrasound applications is to block noise signals from the transmitter from reaching the transducer and also to prevent unwanted high voltage signals from reaching the receiver. The protection circuit using a resistor and diode pair is widely used due to its simple architecture, however, it may not be suitable for very high frequency (VHF) ultrasound transducer applications (>100 MHz) because of its limited bandwidth. Therefore, a protection circuit using MOSFET devices with unique structure is proposed in this paper. The performance of the designed protection circuit was compared with that of other traditional protection schemes. The performance characteristics measured were the insertion loss (IL), total harmonic distortion (THD) and transient response time (TRT). The new protection scheme offers the lowest IL (-1.0 dB), THD (-69.8 dB) and TRT (78 ns) at 120 MHz. The pulse-echo response using a 120 MHz LiNbO3 transducer with each protection circuit was measured to validate the feasibility of the protection circuits in VHF ultrasound applications. The sensitivity and bandwidth of the transducer using the new protection circuit improved by 252.1 and 50.9%, respectively with respect to the protection circuit using a resistor and diode pair. These results demonstrated that the new protection circuit design minimizes the IL, THD and TRT for VHF ultrasound transducer applications.
C1 [Choi, Hojong; Shung, K. Kirk] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
[Choi, Hojong; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
RP Choi, HJ (reprint author), Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
EM hojongch@usc.edu
FU National Institutes of Health [P41-EB002182]
FX The authors thank Mr. Thomas Cummins for his editing contribution. This
research was supported by National Institutes of Health Grant #
P41-EB002182.
NR 15
TC 0
Z9 0
U1 0
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0148-5598
EI 1573-689X
J9 J MED SYST
JI J. Med. Syst.
PD APR
PY 2014
VL 38
IS 4
AR 34
DI 10.1007/s10916-014-0034-0
PG 6
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA AF1WB
UT WOS:000334503500008
PM 24682684
ER
PT J
AU Ellis, A
Wieseler, J
Favret, J
Johnson, KW
Rice, KC
Maier, SF
Falci, S
Watkins, LR
AF Ellis, Amanda
Wieseler, Julie
Favret, Jacob
Johnson, Kirk W.
Rice, Kenner C.
Maier, Steven F.
Falci, Scott
Watkins, Linda R.
TI Systemic Administration of Propentofylline, Ibudilast, and
(+)-Naltrexone Each Reverses Mechanical Allodynia in a Novel Rat Model
of Central Neuropathic Pain
SO JOURNAL OF PAIN
LA English
DT Article
DE Avulsion; toll-like receptor 4; D-naltrexone; glia; pain
ID SPINAL-CORD-INJURY; MIGRATION INHIBITORY FACTOR; PERIPHERAL-NERVE
INJURY; TRAUMATIC BRAIN-INJURY; EXPERIMENTAL AUTOIMMUNE
ENCEPHALOMYELITIS; CAMP-ELEVATING AGENTS; ROOT AVULSION; NEURONAL
HYPEREXCITABILITY; MICROGLIAL ACTIVATION; RECEPTOR 4
AB Central neuropathic pain (CNP) is a debilitating consequence of central nervous system damage for which current treatments are ineffective. To explore mechanisms underlying CNP, we developed a rat model involving T13/L1 dorsal root avulsion. The resultant dorsal horn damage creates bilateral below-level (L4-L6) mechanical allodynia. This allodynia, termed spinal neuropathic avulsion pain, occurs in the absence of confounding paralysis. To characterize this model, we undertook a series of studies aimed at defining whether spinal neuropathic avulsion pain could be reversed by any of 3 putative glial activation inhibitors, each with distinct mechanisms of action. Indeed, the phosphodiesterase inhibitor propentofylline, the macrophage migration inhibitory factor inhibitor ibudilast, and the toll-like receptor 4 antagonist (+)-naltrexone each reversed below-level allodynia bilaterally. Strikingly, none of these impacted spinal neuropathic avulsion pain upon first administration but required 1 to 2 weeks of daily administration before pain reversal was obtained. Given reversal of CNP by each of these glial modulatory agents, these results suggest that glia contribute to the maintenance of such pain and enduring release of macrophage migration inhibitory factor and endogenous agonists of toll-like receptor 4 is important for sustaining CNP. The markedly delayed efficacy of all 3 glial modulatory drugs may prove instructive for interpretation of apparent drug failures after shorter dosing regimens.
Perspective: CNP that develops after trauma is often described by patients as severe and intolerable. Unfortunately, current treatments are not effective. This work suggests that using pharmacologic treatments that target glial cells could be an effective clinical treatment for CNP. (C) 2014 by the American Pain Society. Published by Elsevier Inc. All rights reserved
C1 [Ellis, Amanda; Wieseler, Julie; Favret, Jacob; Maier, Steven F.; Watkins, Linda R.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.
[Johnson, Kirk W.] Medicinova, San Diego, CA USA.
[Rice, Kenner C.] NIDA, Chem Biol Res Branch, Rockville, MD USA.
[Rice, Kenner C.] NIAAA, NIH, Rockville, MD 20852 USA.
[Falci, Scott] Craig Hosp, Englewood, CO USA.
RP Ellis, A (reprint author), Univ Colorado, Dept Psychol & Neurosci, 345 UCB, Boulder, CO 80309 USA.
EM ellisal@colorado.edu
FU Craig Hospital; [DA024044]
FX Financial and material support was given by Craig Hospital and DA024044.
All animal work was done on the University of Colorado Boulder campus.
NR 89
TC 9
Z9 9
U1 1
U2 5
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD APR
PY 2014
VL 15
IS 4
BP 407
EP 421
DI 10.1016/j.jpain.2013.12.007
PG 15
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AF3YM
UT WOS:000334648600007
PM 24412802
ER
PT J
AU Lukkahatai, N
Patel, S
Gucek, M
Hsiao, CP
Saligan, LN
AF Lukkahatai, Nada
Patel, Sajni
Gucek, Marjan
Hsiao, Chao-Pin
Saligan, Leorey N.
TI Proteomic Serum Profile of Fatigued Men Receiving Localized External
Beam Radiation Therapy for Non-Metastatic Prostate Cancer
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Article
DE External beam radiation therapy; fatigue; prostate cancer; quantitative
proteomics; Western blot
ID BIOMARKER DISCOVERY; MASS-SPECTROMETRY; ALPHA-SYNUCLEIN; A-BETA; BREAST;
PATTERNS; DISEASE; PROTEIN; APOE; NEURODEGENERATION
AB Context. Fatigue is the most distressing side effect of radiation therapy, and its progression etiology is unknown.
Objectives. This study describes proteome changes from sera of fatigued men with non-metastatic prostate cancer receiving external beam radiation therapy (EBRT).
Methods. Fatigue scores, measured by the Functional Assessment of Chronic Illness Therapy-Fatigue, and serum were collected from 12 subjects at baseline (before EBRT) and at midpoint (Day 21) of EBRT. Depleted sera from both time points were analyzed using two-dimensional difference gel electrophoresis, and up/down regulated proteins were identified using liquid chromatography-tandem mass spectrometry. Western blot analyses confirmed the protein changes observed.
Results. Results showed that apolipoprotein (Apo) A1, ApoE, and transthyretin (TTR) consistently changed from baseline (Day 0) to midpoint (Day 21). The mean ApoE level of subjects with high change in fatigue (HF: n = 9) increased significantly from baseline to midpoint and were higher than in subjects with no change in fatigue. The mean ApoA1 level was higher in HF subjects at baseline and at midpoint than in no fatigue subjects at both time points. The mean TTR level of no fatigue subjects was higher at baseline and midpoint than in HF subjects.
Conclusion. These ApoE, ApoA1, and TTR results may assist in understanding pathways that can explain fatigue progression etiology in this clinical population. J Pain Symptom Manage 2014;47:748-756. Published by Elsevier Inc. on behalf of U. S. Cancer Pain Relief Committee.
C1 [Lukkahatai, Nada; Hsiao, Chao-Pin; Saligan, Leorey N.] NINR, Bethesda, MD 20892 USA.
[Patel, Sajni; Gucek, Marjan] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Lukkahatai, N (reprint author), NINR, 3 Ctr Dr,Bldg 3,Room 5E26, Bethesda, MD 20892 USA.
EM nada.lukkahatai@nih.gov
FU Intramural NIH HHS [Z99 NR999999]
NR 39
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0885-3924
EI 1873-6513
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD APR
PY 2014
VL 47
IS 4
BP 748
EP +
DI 10.1016/j.jpainsymman.2013.05.016
PG 13
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA AF3CC
UT WOS:000334588100014
PM 23916682
ER
PT J
AU Wilson, VK
Houston, DK
Kilpatrick, L
Lovato, J
Yaffe, K
Cauley, JA
Harris, TB
Simonsick, EM
Ayonayon, HN
Kritchevsky, SB
Sink, KM
AF Wilson, Valerie K.
Houston, Denise K.
Kilpatrick, Laurel
Lovato, James
Yaffe, Kristine
Cauley, Jane A.
Harris, Tamara B.
Simonsick, Eleanor M.
Ayonayon, Hilsa N.
Kritchevsky, Stephen B.
Sink, Kaycee M.
CA Hlth Aging Body Composition Study
TI Relationship Between 25-Hydroxyvitamin D and Cognitive Function in Older
Adults: The Health, Aging and Body Composition Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE memory; cognitive function; cognition; vitamin D
ID VITAMIN-D DEFICIENCY; D-RECEPTOR; ASSOCIATION; IMPAIRMENT; DECLINE;
METAANALYSIS; HIPPOCAMPUS; POPULATION; ALZHEIMER; DISEASE
AB Objectives
To examine the relationship between 25-hydroxyvitamin D (25(OH)D) levels and cognitive performance over time in older adults in the Health, Aging and Body Composition (Health ABC) Study.
Design
Prospective cohort study.
Setting
Community-dwelling participants in Pittsburgh, Pennsylvania, and Memphis, Tennessee.
Participants
Well-functioning adults aged 70 to 79 at baseline with serum 25(OH)D measured at the 12-month follow-up visit and cognitive function measured at baseline and 4-year follow-up visit (N=2,777).
Measurements
Vitamin D status was categorized as 25(OH)D levels of less than 20.0ng/mL, 20.0 to 29.9 ng/mL, or 30.0ng/mL or greater. Cognition was measured using the modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST). Linear regression models adjusting for multiple covariates, including age, education, sex, race, site, season, physical activity, and comorbidities, were used in the analysis.
Results
Sixty-eight percent of participants had 25(OH)D levels of less than 30.0ng/mL. Lower 25(OH)D levels were associated with lower baseline cognitive scores on the 3MS (adjusted mean 89.9, 95% confidence interval (CI)=89.4-90.4 for <20.0ng/mL; adjusted mean 90.8, 95% CI=90.4-91.3 for 20.0-29.9ng/mL; adjusted mean 90.6, 95% CI=90.2-91.1 for >= 30.0ng/mL; P trend=.02) and the DSST (adjusted mean 35.2, 95% CI=34.5-36.0 for <20.0ng/mL; adjusted mean 35.9, 95% CI=35.2-36.6 for 20.0-29.9ng/mL; adjusted mean 37.0, 95% CI=36.3-37.8 for >= 30.0ng/mL; P trend=.01).
Participants with low 25(OH)D levels had greater declines in 3MS scores over 4years than those with higher levels (least square mean change -1.0, 95% CI=-1.5 to -0.6 for <20.0ng/mL; least square mean change -0.8, 95% CI=-1.2 to -0.3 for 20.0-29.9ng/mL; least square mean change -0.2, 95% CI=-0.7 to 0.2 for >= 30.0ng/mL; P=.05). There was no significant difference in DSST decline according to 25(OH)D level.
Conclusion
Low 25(OH)D levels were associated with worse global cognitive function and greater decline over time according to the 3MS. Intervention trials are needed to determine whether vitamin D supplementation can reduce cognitive decline.
C1 [Wilson, Valerie K.; Houston, Denise K.; Kritchevsky, Stephen B.; Sink, Kaycee M.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA.
[Kilpatrick, Laurel] Univ Alabama Birmingham, Dept Internal Med, Birmingham, AL USA.
[Lovato, James] Wake Forest Sch Med, Dept Biostat, Winston Salem, NC USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Yaffe, Kristine; Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Harris, Tamara B.] NIA, Intramural Res Program, Bethesda, MD 20892 USA.
[Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
RP Wilson, VK (reprint author), Sticht Ctr Aging, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM vwilson@wakehealth.edu
RI Cauley, Jane/N-4836-2015
OI Cauley, Jane/0000-0003-0752-4408
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging (NIA); NIA [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01 AG028050, R01 AG029364]; National Institute of
Nursing Research [R01 NR012459]
FX Supported in part by the Intramural Research Program of the National
Institutes of Health, National Institute on Aging (NIA) and NIA
Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA Grants
R01 AG028050 and R01 AG029364; and National Institute of Nursing
Research Grant R01 NR012459.
NR 24
TC 12
Z9 12
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD APR
PY 2014
VL 62
IS 4
BP 636
EP 641
DI 10.1111/jgs.12765
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AE8YV
UT WOS:000334289900006
PM 24635412
ER
PT J
AU Schrack, JA
Knuth, ND
Simonsick, EM
Ferrucci, L
AF Schrack, Jennifer A.
Knuth, Nicolas D.
Simonsick, Eleanor M.
Ferrucci, Luigi
TI "IDEAL" Aging Is Associated with Lower Resting Metabolic Rate: The
Baltimore Longitudinal Study of Aging
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE comorbidities; resting metabolic rate; aging
ID ENERGY-EXPENDITURE; INDIRECT CALORIMETRY; OXIDATIVE STRESS; MORTALITY;
ADOLESCENTS; EXERCISE; HUMANS; WOMEN; AGE
AB Objectives
To assess the associations among age, health status, and resting metabolic rate (RMR) in a large population of older adults.
Design
Cross-sectional analysis.
Setting
Community-dwelling volunteers from the Baltimore Longitudinal Study of Aging (BLSA).
Participants
Persons aged 40 to 96 (mean 68.2 +/- 11.0) who underwent a comprehensive physical examination, cognitive assessment, RMR testing, body composition assessment, and physical function testing during a 3-day clinic visit (N=420).
Measurements
Participants were assigned to Insight into the Determination of Exceptional Aging and Longevity (IDEAL) or non-IDEAL categories based on health status. IDEAL participants were defined according to the absence of physical and cognitive impairments, chronic conditions and comorbidities, and blood profile abnormalities. A three-stage linear regression model was used to assess the relationship between RMR and age, using IDEAL classification as a predictor and adjusting for sex and body composition.
Results
Resting metabolic rate averaged 1,512.4 +/- 442.9kcal/d and was lower with older age (beta=-8.55, P<.001). After adjusting for age, sex, and body composition, RMR was 109.6kcal/d lower in IDEAL than non-IDEAL participants (P<.005).
Conclusion
Individuals who are fully functional and free of major medical conditions have lower RMR than those with disease and functional impairments. These findings suggest that health status plays a role in energy use and regulation independent of age and body composition and that elevated RMR may be a global biomarker of poor health in older persons.
C1 [Schrack, Jennifer A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Schrack, Jennifer A.; Simonsick, Eleanor M.; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Knuth, Nicolas D.] Towson Univ, Dept Kinesiol, Towson, MD USA.
RP Schrack, JA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, 615 N Wolfe St,E6137, Baltimore, MD 21205 USA.
EM jschrack@jhsph.edu
FU Intramural Research Program of the NIH, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging. Data for these analyses were obtained
from the Baltimore Longitudinal Study of Aging, a study performed by the
National Institute on Aging.
NR 29
TC 12
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U1 5
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD APR
PY 2014
VL 62
IS 4
BP 667
EP 672
DI 10.1111/jgs.12740
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AE8YV
UT WOS:000334289900010
PM 24635835
ER
PT J
AU Thambisetty, M
Ferrucci, L
AF Thambisetty, Madhav
Ferrucci, Luigi
TI Soluble Interleukin-6 Receptor Levels and Risk of Dementia: One More
Signpost on a Long Road Ahead
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Editorial Material
ID PLASMA CLUSTERIN CONCENTRATION; GENOME-WIDE ASSOCIATION;
ALZHEIMERS-DISEASE; ALPHA-SECRETASE; IDENTIFIES VARIANTS; SIGNALING
PROTEINS; BRAIN; NEUROGENESIS; MARKERS; ADAM10
C1 [Thambisetty, Madhav] NIA, Clin & Translat Neurosci Unit, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
RP Thambisetty, M (reprint author), NIA, Clin & Translat Neurosci Unit, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA.
FU Intramural NIH HHS [ZIA AG000200-01]
NR 35
TC 3
Z9 3
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD APR
PY 2014
VL 62
IS 4
BP 772
EP 774
DI 10.1111/jgs.12737
PG 3
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AE8YV
UT WOS:000334289900027
PM 24731027
ER
PT J
AU Clark, C
AF Clark, Cindy
TI Expert Internet Searching, 4th edition
SO LEARNED PUBLISHING
LA English
DT Book Review
C1 [Clark, Cindy] NIH, NIH Lib, Off Res Serv, Bethesda, MD 20892 USA.
RP Clark, C (reprint author), NIH, NIH Lib, Off Res Serv, Bethesda, MD 20892 USA.
EM clarkc@ors.od.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 6
PU ASSOC LEARNED PROFESSIONAL SOC PUBL
PI W SUSSEX
PA SOUTH HOUSE, THE STREET WORTHING, W SUSSEX BN13 3UU, ENGLAND
SN 0953-1513
EI 1741-4857
J9 LEARN PUBL
JI Learn. Publ.
PD APR
PY 2014
VL 27
IS 2
BP 157
EP 158
DI 10.1087/20140211
PG 2
WC Information Science & Library Science
SC Information Science & Library Science
GA AF2VA
UT WOS:000334569400011
ER
PT J
AU Zhang, M
Luo, Z
Liu, H
Croce, C
Burke, TR
Bottaro, DP
AF Zhang, M.
Luo, Z.
Liu, H.
Croce, C. M.
Burke, T. R., Jr.
Bottaro, D. P.
TI Synergistic anti-leukemic activity of imatinib in combination with a
small molecule Grb2 SH2 domain binding antagonist
SO LEUKEMIA
LA English
DT Letter
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; MICRORNA
EXPRESSION; TRANSFORMATION; INHIBITION; CELL
C1 [Zhang, M.; Luo, Z.; Liu, H.; Croce, C. M.; Burke, T. R., Jr.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Burke, T. R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Bottaro, D. P.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Zhang, M (reprint author), Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
EM manchao.zhang@osumc.edu; don.bottaro@nih.gov
RI Burke, Terrence/N-2601-2014;
OI Bottaro, Donald/0000-0002-5057-5334
FU Intramural NIH HHS; NCI NIH HHS [Z01 BC011123-01]
NR 15
TC 0
Z9 0
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
EI 1476-5551
J9 LEUKEMIA
JI Leukemia
PD APR
PY 2014
VL 28
IS 4
BP 948
EP 951
DI 10.1038/leu.2013.323
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA AE9SU
UT WOS:000334350900029
PM 24172825
ER
PT J
AU Shukla, S
Chufan, EE
Singh, S
Skoumbourdis, AP
Kapoor, K
Boxer, MB
Duveau, DY
Thomas, CJ
Talele, TT
Ambudkar, SV
AF Shukla, S.
Chufan, E. E.
Singh, S.
Skoumbourdis, A. P.
Kapoor, K.
Boxer, M. B.
Duveau, D. Y.
Thomas, C. J.
Talele, T. T.
Ambudkar, S. V.
TI Elucidation of the structural basis of interaction of the BCR-ABL kinase
inhibitor, nilotinib (Tasigna) with the human ABC drug transporter
P-glycoprotein
SO LEUKEMIA
LA English
DT Letter
ID MULTIDRUG-RESISTANCE; TYROSINE KINASE; SIMULTANEOUS BINDING; ATP
BINDING; MODULATORS; REVEALS; PUMP
C1 [Shukla, S.; Chufan, E. E.; Kapoor, K.; Ambudkar, S. V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Singh, S.; Talele, T. T.] St Johns Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Queens, NY USA.
[Skoumbourdis, A. P.; Boxer, M. B.; Duveau, D. Y.; Thomas, C. J.] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD USA.
RP Shukla, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM ambudkar@helix.nih.gov
FU Intramural NIH HHS [Z99 CA999999, Z01 BC010030-13]
NR 16
TC 4
Z9 4
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
EI 1476-5551
J9 LEUKEMIA
JI Leukemia
PD APR
PY 2014
VL 28
IS 4
BP 961
EP 964
DI 10.1038/leu.2014.21
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA AE9SU
UT WOS:000334350900033
PM 24418991
ER
PT J
AU Asman, AJ
Bryan, FW
Smith, SA
Reich, DS
Landman, BA
AF Asman, Andrew J.
Bryan, Frederick W.
Smith, Seth A.
Reich, Daniel S.
Landman, Bennett A.
TI Groupwise multi-atlas segmentation of the spinal cord's internal
structure
SO MEDICAL IMAGE ANALYSIS
LA English
DT Article
DE Cervical spinal cord segmentation; Groupwise registration; Multi-atlas
segmentation; Spinal cord internal structure
ID SPATIALLY VARYING PERFORMANCE; MAGNETIC-RESONANCE IMAGES; LABEL FUSION;
AFFINE REGISTRATION; MRI SEGMENTATION; BRAIN IMAGES; IN-VIVO; 3 TESLA;
SCLEROSIS; ALGORITHM
AB The spinal cord is an essential and vulnerable component of the central nervous system. Differentiating and localizing the spinal cord internal structure (i.e., gray matter vs. white matter) is critical for assessment of therapeutic impacts and determining prognosis of relevant conditions. Fortunately, new magnetic resonance imaging (MRI) sequences enable clinical study of the in vivo spinal cord's internal structure. Yet, low contrast-to-noise ratio, artifacts, and imaging distortions have limited the applicability of tissue segmentation techniques pioneered elsewhere in the central nervous system. Additionally, due to the inter-subject variability exhibited on cervical MRI, typical deformable volumetric registrations perform poorly, limiting the applicability of a typical multi-atlas segmentation framework. Thus, to date, no automated algorithms have been presented for the spinal cord's internal structure. Herein, we present a novel slice-based groupwise registration framework for robustly segmenting cervical spinal cord MRI. Specifically, we provide a method for (1) pre-aligning the slice-based atlases into a groupwise-consistent space, (2) constructing a model of spinal cord variability, (3) projecting the target slice into the low-dimensional space using a model-specific registration cost function, and (4) estimating robust segmentation susing geodesically appropriate atlas information. Moreover, the proposed framework provides a natural mechanism for performing atlas selection and initializing the free model parameters in an informed manner. In a cross-validation experiment using 67 MR volumes of the cervical spinal cord, we demonstrate sub-millimetric accuracy, significant quantitative and qualitative improvement over comparable multi-atlas frameworks, and provide insight into the sensitivity of the associated model parameters. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Asman, Andrew J.; Bryan, Frederick W.; Smith, Seth A.; Landman, Bennett A.] Vanderbilt Univ, Nashville, TN 37235 USA.
[Smith, Seth A.; Landman, Bennett A.] Vanderbilt Univ, Inst Imaging Sci, Nashville, TN 37235 USA.
[Reich, Daniel S.] NIH, Translat Neuroradiol Unit, Bethesda, MD USA.
RP Asman, AJ (reprint author), Vanderbilt Univ EECS, 2301 Vanderbilt Pl,POB 351679 Stn B, Nashville, TN 37235 USA.
EM andrew.j.asman@vanderbilt.edu
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU NIH [1R21NS064534, NIH 1R03EB012461, NIH 2R01EB006136, NIH R01EB006193,
NIH 1T32EB014841]; NIH/NINDS Intramural Research Program; National
Multiple Sclerosis Society (Peter Calabresi)
FX This research was supported by in part by NIH 1R21NS064534, NIH
1R03EB012461, NIH 2R01EB006136, NIH R01EB006193, NIH 1T32EB014841, the
NIH/NINDS Intramural Research Program, and the National Multiple
Sclerosis Society (Peter Calabresi). The authors are grateful to
Zhoubing Xu for the provided manual labels.
NR 73
TC 21
Z9 21
U1 0
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1361-8415
EI 1361-8423
J9 MED IMAGE ANAL
JI Med. Image Anal.
PD APR
PY 2014
VL 18
IS 3
BP 460
EP 471
DI 10.1016/j.media.2014.01.003
PG 12
WC Computer Science, Artificial Intelligence; Computer Science,
Interdisciplinary Applications; Engineering, Biomedical; Radiology,
Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical
Imaging
GA AG0JH
UT WOS:000335101300003
PM 24556080
ER
PT J
AU Liu, YX
Sadowski, SM
Weisbrod, AB
Kebebew, E
Summers, RM
Yao, JH
AF Liu, Yixun
Sadowski, Samira M.
Weisbrod, Allison B.
Kebebew, Electron
Summers, Ronald M.
Yao, Jianhua
TI Patient specific tumor growth prediction using multimodal images
SO MEDICAL IMAGE ANALYSIS
LA English
DT Article
DE Tumor growth modeling; Multimodal images; Intracellular Volume Fraction;
Metabolic rate
ID METABOLIC-RATE; CANCER-CELLS; MR-IMAGES; MODEL; REGISTRATION;
DEFORMATION; DIFFUSION
AB Personalized tumor growth model is valuable in tumor staging and therapy planning. In this paper, we present a patient specific tumor growth model based on longitudinal multimodal imaging data including dual-phase CT and FDG-PET. The proposed Reaction-Advection-Diffusion model is capable of integrating cancerous cell proliferation, infiltration, metabolic rate and extracellular matrix biomechanical response. To bridge the model with multimodal imaging data, we introduce Intracellular Volume Fraction (ICVF) measured from dual-phase CT and Standardized Uptake Value (SUV) measured from FDG-PET into the model. The patient specific model parameters are estimated by fitting the model to the observation, which leads to an inverse problem formalized as a coupled Partial Differential Equations (PDE)-constrained optimization problem. The optimality system is derived and solved by the Finite Difference Method. The model was evaluated by comparing the predicted tumors with the observed tumors in terms of average surface distance (ASD), root mean square difference (RMSD) of the ICVF map, average ICVF difference (AICVFD) of tumor surface and tumor relative volume difference (RVD) on six patients with pathologically confirmed pancreatic neuroendocrine tumors. The ASD between the predicted tumor and the reference tumor was 2.4 +/- 0.5 mm, the RMSD was 4.3 +/- 0.4%, the AICVFD was 2.6 +/- 0.6%, and the RVD was 7.7 +/- 1.3%. Published by Elsevier B.V.
C1 [Liu, Yixun; Summers, Ronald M.; Yao, Jianhua] NIH, Clin Image Proc Serv, Bethesda, MD 20892 USA.
[Sadowski, Samira M.; Weisbrod, Allison B.; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Yao, JH (reprint author), NIH, Radiol & Imaging Sci Clin Ctr, 10 Ctr Dr,Bldg 10,Rm 1C515, Bethesda, MD 20892 USA.
EM JYao@cc.nih.gov
FU National Institutes of Health (NIH) Intramural program
FX Funded by the National Institutes of Health (NIH) Intramural program.
NR 21
TC 9
Z9 9
U1 1
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1361-8415
EI 1361-8423
J9 MED IMAGE ANAL
JI Med. Image Anal.
PD APR
PY 2014
VL 18
IS 3
BP 555
EP 566
DI 10.1016/j.media.2014.02.005
PG 12
WC Computer Science, Artificial Intelligence; Computer Science,
Interdisciplinary Applications; Engineering, Biomedical; Radiology,
Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical
Imaging
GA AG0JH
UT WOS:000335101300010
PM 24607911
ER
PT J
AU Garriock, RJ
Mikawa, T
Yamaguchi, TP
AF Garriock, Robert J.
Mikawa, Takashi
Yamaguchi, Terry P.
TI Isolation and culture of mouse proepicardium using serum-free conditions
SO METHODS
LA English
DT Article
DE Proepicardium; Stem cells; Cardiovascular; Progenitor cell culture;
Mouse
ID GROWTH-FACTOR; PROGENITORS CONTRIBUTE; EPICARDIAL PROGENITORS;
PERICARDIAL MESODERM; HEART DEVELOPMENT; CORONARY VESSEL; CHICK-EMBRYO;
CELLS; EXPRESSION; LINEAGE
AB The proepicardium (PE) is an embryonic tissue that gives rise to multipotent vascular progenitors. Most notably the PE gives rise to the epicardium, cardiac fibroblasts, myocardium, and coronary vessels including both vascular smooth muscle and vascular endothelium. Much attention has been given to epicardial-derived cells that show the capacity to differentiate into a wide variety of vascular progenitors including cardiomyocytes. However, it is the PE itself that possesses the greatest potential as a source of multipotent vascular progenitors. We show here a simple method to manually isolate mouse PE at the ninth day of mouse embryonic development and culture highly pure PE tissue in serum-free conditions. This PE culture method allows for the ex vivo analysis of specific growth factors on PE and epicardial development with greater efficiency and precision than existing epicardial culture methods. Published by Elsevier Inc.
C1 [Garriock, Robert J.; Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 20701 USA.
[Mikawa, Takashi] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
RP Yamaguchi, TP (reprint author), NCI, NIH, Bldg 539,Room 218, Frederick, MD 20701 USA.
EM yamagute@mail.nih.gov
FU Intramural NIH HHS [ZIA BC010345-13]
NR 34
TC 6
Z9 6
U1 1
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD APR 1
PY 2014
VL 66
IS 3
BP 365
EP 369
DI 10.1016/j.ymeth.2013.06.030
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AF8SC
UT WOS:000334984900002
PM 23816793
ER
PT J
AU Arroyo, JO
Andrecka, J
Spillane, KM
Billington, N
Takagi, Y
Sellers, JR
Kukura, P
AF Arroyo, J. Ortega
Andrecka, J.
Spillane, K. M.
Billington, N.
Takagi, Y.
Sellers, J. R.
Kukura, P.
TI Label-Free, All-Optical Detection, Imaging, and Tracking of a Single
Protein
SO NANO LETTERS
LA English
DT Article
DE Single molecule detection; label-free; biosensing; myosin 5a;
interferometric scattering microscopy
ID HAND-OVER-HAND; MYOSIN-V; ROOM-TEMPERATURE; MOLECULES; ABSORPTION;
LOCALIZATION; MICROSCOPY; NANOPARTICLES; PROCESSIVITY; SENSITIVITY
AB Optical detection of individual proteins requires fluorescent labeling. Cavity and plasmonic methodologies enhance single molecule signatures in the absence of any labels but have struggled to demonstrate routine and quantitative single protein detection. Here, we used interferometric scattering microscopy not only to detect but also to image and nanometrically track the motion of single myosin 5a heavy meromyosin molecules without the use of labels or any nanoscopic amplification. Together with the simple experimental arrangement, an intrinsic independence from strong electronic transition dipoles and a detection limit of <60 kDa, our approach paves the way toward nonresonant, label-free sensing and imaging of nanoscopic objects down to the single protein level.
C1 [Arroyo, J. Ortega; Andrecka, J.; Spillane, K. M.; Kukura, P.] Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, Oxford OX1 3QZ, England.
[Billington, N.; Takagi, Y.; Sellers, J. R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
RP Kukura, P (reprint author), Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, S Parks Rd, Oxford OX1 3QZ, England.
EM philipp.kukura@chem.ox.ac.uk
OI Kukura, Philipp/0000-0003-0136-7704
FU John Fell Fund; EPSRC [EP/H003541]; ERC; National Institute of
Biomedical Imaging and Bioengineering, National Institutes of Health
[FEB013960]; CONACyT [213546]; Marie Curie Fellowship [330215]; National
Heart, Lung, and Blood Institute, National Institutes of Health [ZIA
HL004229]; Electron Microscopy Core Facility of the NHLBI
FX P.K. is supported by the John Fell Fund, a career acceleration
fellowship by the EPSRC (EP/H003541) and an ERC starting grant
(NanoScope). K.S. was supported by a fellowship from the National
Institute of Biomedical Imaging and Bioengineering, National Institutes
of Health (FEB013960). J.O.A was supported by a scholarship from CONACyT
to pursue his doctoral work (scholar: 213546). J.A. was supported by a
Marie Curie Fellowship (330215). J.R.S. was supported by the intramural
funds from the National Heart, Lung, and Blood Institute, National
Institutes of Health (ZIA HL004229). The authors thank the Electron
Microscopy Core Facility of the NHLBI for support and the use of
facilities.
NR 29
TC 24
Z9 25
U1 6
U2 38
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1530-6984
EI 1530-6992
J9 NANO LETT
JI Nano Lett.
PD APR
PY 2014
VL 14
IS 4
BP 2065
EP 2070
DI 10.1021/nl500234t
PG 6
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA AF2WE
UT WOS:000334572400059
ER
PT J
AU Resnik, DB
AF Resnik, David B.
TI The morality of patents on preimplantation genetic diagnosis
SO NATURE BIOTECHNOLOGY
LA English
DT Letter
C1 Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA.
RP Resnik, DB (reprint author), Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
NR 13
TC 0
Z9 0
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
EI 1546-1696
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD APR
PY 2014
VL 32
IS 4
BP 319
EP 320
DI 10.1038/nbt.2865
PG 3
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA AE9PT
UT WOS:000334340800011
PM 24714476
ER
PT J
AU Cooke, SL
Shlien, A
Marshall, J
Pipinikas, CP
Martincorena, I
Tubio, JMC
Li, Y
Menzies, A
Mudie, L
Ramakrishna, M
Yates, L
Davies, H
Bolli, N
Bignell, GR
Tarpey, PS
Behjati, S
Nik-Zainal, S
Papaemmanuil, E
Teixeira, VH
Raine, K
O'Meara, S
Dodoran, MS
Teague, JW
Butler, AP
Iacobuzio-Donahue, C
Santarius, T
Grundy, RG
Malkin, D
Greaves, M
Munshi, N
Flanagan, AM
Bowtell, D
Martin, S
Larsimont, D
Reis-Filho, JS
Boussioutas, A
Taylor, JA
Hayes, DN
Janes, SM
Futreal, PA
Stratton, MR
McDermott, U
Campbell, PJ
AF Cooke, Susanna L.
Shlien, Adam
Marshall, John
Pipinikas, Christodoulos P.
Martincorena, Inigo
Tubio, Jose M. C.
Li, Yilong
Menzies, Andrew
Mudie, Laura
Ramakrishna, Manasa
Yates, Lucy
Davies, Helen
Bolli, Niccolo
Bignell, Graham R.
Tarpey, Patrick S.
Behjati, Sam
Nik-Zainal, Serena
Papaemmanuil, Elli
Teixeira, Vitor H.
Raine, Keiran
O'Meara, Sarah
Dodoran, Maryam S.
Teague, Jon W.
Butler, Adam P.
Iacobuzio-Donahue, Christine
Santarius, Thomas
Grundy, Richard G.
Malkin, David
Greaves, Mel
Munshi, Nikhil
Flanagan, Adrienne M.
Bowtell, David
Martin, Sancha
Larsimont, Denis
Reis-Filho, Jorge S.
Boussioutas, Alex
Taylor, Jack A.
Hayes, D. Neil
Janes, Sam M.
Futreal, P. Andrew
Stratton, Michael R.
McDermott, Ultan
Campbell, Peter J.
CA ICGC Breast Cancer Grp
TI Processed pseudogenes acquired somatically during cancer development
SO NATURE COMMUNICATIONS
LA English
DT Article
ID CELL LUNG CANCERS; 21 BREAST CANCERS; L1 RETROTRANSPOSITION; MUTATIONAL
PROCESSES; GENE-EXPRESSION; HUMAN BRAIN; A549 CELLS; REARRANGEMENT;
LANDSCAPE; GENOMES
AB Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target- site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 50 truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context.
C1 [Cooke, Susanna L.; Shlien, Adam; Marshall, John; Martincorena, Inigo; Tubio, Jose M. C.; Li, Yilong; Menzies, Andrew; Mudie, Laura; Ramakrishna, Manasa; Yates, Lucy; Davies, Helen; Bolli, Niccolo; Bignell, Graham R.; Tarpey, Patrick S.; Behjati, Sam; Nik-Zainal, Serena; Papaemmanuil, Elli; Raine, Keiran; O'Meara, Sarah; Dodoran, Maryam S.; Teague, Jon W.; Butler, Adam P.; Martin, Sancha; Futreal, P. Andrew; Stratton, Michael R.; McDermott, Ultan; ICGC Breast Cancer Grp] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, Cambs, England.
[Pipinikas, Christodoulos P.; Teixeira, Vitor H.; Janes, Sam M.] UCL, Lungs Living Res Ctr, Rayne Inst, London WC1E 6JF, England.
[Bolli, Niccolo; Behjati, Sam] Univ Cambridge, Cambridge CB2 0XY, England.
[Iacobuzio-Donahue, Christine] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Iacobuzio-Donahue, Christine] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA.
[Santarius, Thomas; McDermott, Ultan; Campbell, Peter J.] Addenbrookes NHS Fdn Trust, Cambridge CB2 0QQ, England.
[Grundy, Richard G.] Univ Nottingham, Childrens Brain Tumour Res Ctr, Nottingham NG7 2UH, England.
[Malkin, David] Univ Toronto, Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada.
[Greaves, Mel] Inst Canc Res, Sutton SM2 5NG, Surrey, England.
[Munshi, Nikhil] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Flanagan, Adrienne M.] Royal Natl Orthopaed Hosp, Stanmore HA7 4LP, Middx, England.
[Bowtell, David] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia.
[Larsimont, Denis] Inst Jules Bordet, Dept Pathol, B-1000 Brussels, Belgium.
[Reis-Filho, Jorge S.; Campbell, Peter J.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Boussioutas, Alex] Univ Melbourne, Royal Melbourne Hosp, Dept Gastroenterol, Parkville, Vic 3050, Australia.
[Taylor, Jack A.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27713 USA.
[Hayes, D. Neil] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
RP Campbell, PJ (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Genome Campus, Hinxton CB10 1SA, Cambs, England.
EM pc8@sanger.ac.uk
RI Sweep, C.G.J./H-8096-2014; Stunnenberg, Hendrik/D-6875-2012; Simpson,
Peter/F-1225-2010; Tubio, Jose/H-5076-2015; Bowtell, David/H-1007-2016;
Span, Paul/G-4710-2012; Bolli, Niccolo/D-4057-2011;
OI Simpson, Peter/0000-0002-4816-8289; Tubio, Jose/0000-0003-3540-2459;
Bowtell, David/0000-0001-9089-7525; Span, Paul/0000-0002-1930-6638;
Bolli, Niccolo/0000-0002-1018-5139; chin,
suet-feung/0000-0001-5697-1082; Purdie, Colin/0000-0002-1258-4010;
Ehinger, Anna/0000-0001-9225-7396; McDermott, Ultan/0000-0001-9032-4700;
Desmedt, Christine/0000-0002-5223-5579; Martin,
Sancha/0000-0001-6213-5259; taylor, jack/0000-0001-5303-6398;
Boussioutas, Alex/0000-0002-8109-6897
FU Health Innovation Challenge Fund; Wellcome Trust [077012/Z/05/Z]; Kay
Kendall Leukaemia Fund; Wellcome Trust Senior Clinical Research
Fellowships; National Research Council Canada; EMBO fellowship; Cancer
Research UK Clinician Scientist Fellowship; Academy of Medical Sciences;
Lady Tata Memorial Trust; European Community's Seventh Framework
Programme [242006]; Intramural Research Program of the NIH; National
Institute of Environmental Health Sciences; UCL/UCLH NIHR Biomedical
Centre; Skeletal Cancer Action Trust; Rosetrees Trust
FX This work was supported by the Health Innovation Challenge Fund, the
Wellcome Trust (grant reference 077012/Z/05/Z), and the Kay Kendall
Leukaemia Fund. P. J. C. and S. M. J. are personally funded through
Wellcome Trust Senior Clinical Research Fellowships. A. S. is funded by
the H. L. Holmes Award from the National Research Council Canada and an
EMBO fellowship. UAM is personally supported by a Cancer Research UK
Clinician Scientist Fellowship. NB was supported by a starter grant from
the Academy of Medical Sciences and from Lady Tata Memorial Trust. The
breast cancer sequencing was supported by the BASIS project. The BASIS
project is a European research project funded by the European
Community's Seventh Framework Programme (FP7/2010-2014) under the grant
agreement number 242006. This research was supported in part by the
Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences. We also acknowledge support for the
sample banking and processing from UCL/UCLH NIHR Biomedical Centre, the
Skeletal Cancer Action Trust (SCAT), especially Miss Dina Halai, and the
Rosetrees Trust.
NR 42
TC 19
Z9 19
U1 1
U2 14
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 APR
PY 2014
VL 5
AR 3644
DI 10.1038/ncomms4644
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG2BV
UT WOS:000335221300001
PM 24714652
ER
PT J
AU Hill, JH
Chen, Z
Xu, H
AF Hill, Jahda H.
Chen, Zhe
Xu, Hong
TI Selective propagation of functional mitochondrial DNA during oogenesis
restricts the transmission of a deleterious mitochondrial variant
SO NATURE GENETICS
LA English
DT Article
ID BALBIANI BODY; CYST FORMATION; DROSOPHILA; HETEROPLASMY; INHERITANCE;
MEDICINE; OOCYTES; FUSOME
AB Although mitochondrial DNA (mtDNA) is prone to mutation and few mtDNA repair mechanisms exist(1), crippling mitochondrial mutations are exceedingly rare(2). Recent studies have demonstrated strong purifying selection in the mouse female germline(3,4). However, the mechanisms underlying positive selection of healthy mitochondria remain to be elucidated. We visualized mtDNA replication during Drosophila melanogaster oogenesis, finding that mtDNA replication commenced before oocyte determination during the late germarium stage and was dependent on mitochondrial fitness. We isolated a temperature- sensitive lethal mtDNA allele, mt:CoIT300I, which resulted in reduced mtDNA replication in the germarium at the restrictive temperature. Additionally, the frequency of the mt:CoIT300I allele in heteroplasmic flies was decreased, both during oogenesis and over multiple generations, at the restrictive temperature. Furthermore, we determined that selection against mt:CoIT300I overlaps with the timing of selective replication of mtDNA in the germarium. These findings establish a previously uncharacterized developmental mechanism for the selective amplification of wild-type mtDNA, which may be evolutionarily conserved to limit the transmission of deleterious mutations.
C1 [Hill, Jahda H.; Chen, Zhe; Xu, Hong] NHLBI, Mol Genet Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Xu, H (reprint author), NHLBI, Mol Genet Lab, US Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA.
EM xuh5@nhlbi.nih.gov
RI Chen, Zhe/E-4278-2015; Chen, Zhe/H-1417-2016; Xu, Hong/H-9997-2016
OI Chen, Zhe/0000-0002-8209-0999; Xu, Hong/0000-0003-1049-1184
FU National, Heart, Lung, and Blood Institute (NHLBI)
FX We are indebted to P. O'Farrell, in whose laboratory the
mt:CoIT300I fly was isolated. We thank R. Balaban, T. Finkel,
A. Michelson, H. Parthasarathy, N. Rusan and R. Youle for comments on
the manuscript; P. O'Farrell and A. Spradling for their insightful
discussions; P. Hwang for technical assistance; the Spradling laboratory
(Carnegie Institute) and the Bloomington and Vienna stock centers for
Drosophila stocks; Genetic Services, Inc., for embryo injection; and the
Developmental Studies Hybridoma Bank for antibodies. This work was
supported by the National, Heart, Lung, and Blood Institute (NHLBI)
Intramural Program.
NR 26
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Z9 35
U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD APR
PY 2014
VL 46
IS 4
BP 389
EP +
DI 10.1038/ng.2920
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA AF1YP
UT WOS:000334510100017
PM 24614072
ER
PT J
AU Wang, CL
Zhan, XW
Bragg-Gresham, J
Kang, HM
Stambolian, D
Chew, EY
Branham, KE
Heckenlively, J
Fulton, R
Wilson, RK
Mardis, ER
Lin, XH
Swaroop, A
Zollner, S
Abecasis, GR
AF Wang, Chaolong
Zhan, Xiaowei
Bragg-Gresham, Jennifer
Kang, Hyun Min
Stambolian, Dwight
Chew, Emily Y.
Branham, Kari E.
Heckenlively, John
Fulton, Robert
Wilson, Richard K.
Mardis, Elaine R.
Lin, Xihong
Swaroop, Anand
Zoellner, Sebastian
Abecasis, Goncalo R.
CA FUSION Study
TI Ancestry estimation and control of population stratification for
sequence-based association studies
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COPY-NUMBER VARIATION; MACULAR DEGENERATION;
GENETIC-VARIATION; STRUCTURED POPULATIONS; CANDIDATE GENES; COMPLEX
TRAITS; RARE VARIANTS; LARGE-SCALE; DISEASE
AB Estimating individual ancestry is important in genetic association studies where population structure leads to false positive signals, although assigning ancestry remains challenging with targeted sequence data. We propose a new method for the accurate estimation of individual genetic ancestry, based on direct analysis of off-target sequence reads, and implement our method in the publicly available LASER software. We validate the method using simulated and empirical data and show that the method can accurately infer worldwide continental ancestry when used with sequencing data sets with whole-genome shotgun coverage as low as 0.001x. For estimates of fine-scale ancestry within Europe, the method performs well with coverage of 0.1x. On an even finer scale, the method improves discrimination between exome-sequenced study participants originating from different provinces within Finland. Finally, we show that our method can be used to improve case-control matching in genetic association studies and to reduce the risk of spurious findings due to population structure.
C1 [Wang, Chaolong; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Wang, Chaolong; Zhan, Xiaowei; Bragg-Gresham, Jennifer; Kang, Hyun Min; Zoellner, Sebastian; Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Stambolian, Dwight] Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Chew, Emily Y.] NEI, Div Epidemiol & Clin Res, Bethesda, MD USA.
[Branham, Kari E.; Heckenlively, John] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol, Ann Arbor, MI 48105 USA.
[Fulton, Robert; Wilson, Richard K.; Mardis, Elaine R.] Washington Univ, Sch Med, Genome Inst, St Louis, MO USA.
[Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD USA.
[Zoellner, Sebastian] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA.
RP Wang, CL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
EM chaolong@umich.edu; goncalo@umich.edu
OI Swaroop, Anand/0000-0002-1975-1141
FU Howard Hughes Medical Institute International Student Research
Fellowship; US National Institutes of Health [DK062370, HG000376,
HG005552, HG006513, EY022005, HG007022, HG005855, HG003079, CA076404,
CA134294]; National Eye Institute Intramural Research Program
FX We thank investigators from the FUSION study and the GoT2D Sequencing
Project for generously sharing whole-genome and deep exome sequence data
for 941 individuals before publication and the D2D, Finrisk 2002, Health
2000, Action LADA and Saviatipale studies for providing some of the
FUSIONsequenced DNA. We thank J.Z. Li for his assistance with the HGDP
data set, H. Stringham and A. Locke for assistance with the FUSION data
set and M. Brooks for organizing the macular degeneration samples. C.W.
acknowledges funding support from a Howard Hughes Medical Institute
International Student Research Fellowship. This study is supported by
the US National Institutes of Health (DK062370, HG000376, HG005552,
HG006513, EY022005, HG007022, HG005855, HG003079, CA076404 and CA134294)
and by the National Eye Institute Intramural Research Program.
NR 52
TC 14
Z9 14
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD APR
PY 2014
VL 46
IS 4
BP 409
EP +
DI 10.1038/ng.2924
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA AF1YP
UT WOS:000334510100021
PM 24633160
ER
PT J
AU LaFave, MC
Varshney, GK
Gildea, DE
Wolfsberg, TG
Baxevanis, AD
Burgess, SM
AF LaFave, Matthew C.
Varshney, Gaurav K.
Gildea, Derek E.
Wolfsberg, Tyra G.
Baxevanis, Andreas D.
Burgess, Shawn M.
TI MLV integration site selection is driven by strong enhancers and active
promoters
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID LEUKEMIA-VIRUS INTEGRATION; DNASE HYPERSENSITIVE SITES; TRANSCRIPTION
START SITES; HUMAN GENOME; GENE-THERAPY; CHROMATIN STATE; RETROVIRUSES;
SEQUENCES; ELEMENTS; BROWSER
AB Retroviruses integrate into the host genome in patterns specific to each virus. Understanding the causes of these patterns can provide insight into viral integration mechanisms, pathology and genome evolution, and is critical to the development of safe gene therapy vectors. We generated murine leukemia virus integrations in human HepG2 and K562 cells and subjected them to second-generation sequencing, using a DNA barcoding technique that allowed us to quantify independent integration events. We characterized > 3 700 000 unique integration events in two ENCODE-characterized cell lines. We find that integrations were most highly enriched in a subset of strong enhancers and active promoters. In both cell types, approximately half the integrations were found in < 2% of the genome, demonstrating genomic influences even narrower than previously believed. The integration pattern of murine leukemia virus appears to be largely driven by regions that have high enrichment for multiple marks of active chromatin; the combination of histone marks present was sufficient to explain why some strong enhancers were more prone to integration than others. The approach we used is applicable to analyzing the integration pattern of any exogenous element and could be a valuable preclinical screen to evaluate the safety of gene therapy vectors.
C1 [LaFave, Matthew C.; Varshney, Gaurav K.; Gildea, Derek E.; Wolfsberg, Tyra G.; Baxevanis, Andreas D.; Burgess, Shawn M.] NHGRI, Div Intramural Res, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Burgess, SM (reprint author), NHGRI, Div Intramural Res, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
EM burgess@mail.nih.gov
RI Varshney, Gaurav/L-5261-2014;
OI Burgess, Shawn/0000-0003-1147-0596; LaFave, Matthew/0000-0001-9165-041X;
Varshney, Gaurav K./0000-0002-0429-1904
FU National Human Genome Research Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health.
Funding open access charge: Intramural Research Program of the National
Human Genome Research Institute, National Institutes of Health.
NR 45
TC 36
Z9 36
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD APR
PY 2014
VL 42
IS 7
BP 4257
EP 4269
DI 10.1093/nar/gkt1399
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AF5NV
UT WOS:000334761100021
PM 24464997
ER
PT J
AU Yun, WJ
Kim, YW
Kang, Y
Lee, J
Dean, A
Kim, A
AF Yun, Won Ju
Kim, Yea Woon
Kang, Yujin
Lee, Jungbae
Dean, Ann
Kim, AeRi
TI The hematopoietic regulator TAL1 is required for chromatin looping
between the beta-globin LCR and human gamma-globin genes to activate
transcription
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID LOCUS-CONTROL REGION; ERYTHROID-DIFFERENTIATION; FACTOR GATA-1;
QUANTITATIVE-ANALYSIS; CELLS; COMPLEXES; SCL; EXPRESSION; BINDING; NF-E2
AB TAL1 is a key hematopoietic transcription factor that binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. The complex mediates long-range interaction between the beta-globin locus control region (LCR) and active globin genes, and although TAL1 is one of the two DNA-binding complex members, its role is unclear. To explore the role of TAL1 in transcription activation of the human gamma-globin genes, we reduced the expression of TAL1 in erythroid K562 cells using lentiviral short hairpin RNA, compromising its association in the beta-globin locus. In the TAL1 knockdown cells, the gamma-globin transcription was reduced to 35% and chromatin looping of the (G)gamma-globin gene with the LCR was disrupted with decreased occupancy of the complex member Ldb1 and LMO2 in the locus. However, GATA-1 binding, DNase I hypersensitive site formation and several histone modifications were largely maintained across the beta-globin locus. In addition, overexpression of TAL1 increased the gamma-globin transcription and increased interaction frequency between the (G)gamma-globin gene and LCR. These results indicate that TAL1 plays a critical role in chromatin loop formation between the gamma-globin genes and LCR, which is a critical step for the transcription of the gamma-globin genes.
C1 [Yun, Won Ju; Kim, Yea Woon; Kang, Yujin; Lee, Jungbae; Kim, AeRi] Pusan Natl Univ, Coll Nat Sci, Dept Mol Biol, Pusan 609735, South Korea.
[Dean, Ann] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Kim, A (reprint author), Pusan Natl Univ, Coll Nat Sci, Dept Mol Biol, Pusan 609735, South Korea.
EM kimaeri@pusan.ac.kr
FU National Research Foundation of Korea - Korean Government MEST
[NRF-2011-013-C00045, NRF-2012R1A1B5001946]; National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health [DK075033]
FX National Research Foundation of Korea Grant funded by the Korean
Government MEST, Basic Research Promotion Fund (to A. K.)
[NRF-2011-013-C00045] [NRF-2012R1A1B5001946] and the Intramural Program
of the National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health (to A. D.) [DK075033]. Funding for open
access charge: [NRF-2012R1A1B5001946].
NR 48
TC 19
Z9 19
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD APR
PY 2014
VL 42
IS 7
BP 4283
EP 4293
DI 10.1093/nar/gku072
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AF5NV
UT WOS:000334761100023
PM 24470145
ER
PT J
AU Hu, JB
Lei, Y
Wong, WK
Liu, SQ
Lee, KC
He, XJ
You, WX
Zhou, R
Guo, JT
Chen, XF
Peng, XL
Sun, H
Huang, H
Zhao, H
Feng, B
AF Hu, Jiabiao
Lei, Yong
Wong, Wing-Ki
Liu, Senquan
Lee, Kai-Chuen
He, Xiangjun
You, Wenxing
Zhou, Rui
Guo, Jun-Tao
Chen, Xiongfong
Peng, Xianlu
Sun, Hao
Huang, He
Zhao, Hui
Feng, Bo
TI Direct activation of human and mouse Oct4 genes using engineered TALE
and Cas9 transcription factors
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PLURIPOTENT STEM-CELLS; SOMATIC-CELLS; HUMAN GENOME; EXPRESSION; DNA;
CRISPR; EFFECTORS; SYSTEM; PROTEINS; DOMAIN
AB The newly developed transcription activator-like effector protein (TALE) and clustered regularly interspaced short palindromic repeats/Cas9 transcription factors (TF) offered a powerful and precise approach for modulating gene expression. In this article, we systematically investigated the potential of these new tools in activating the stringently silenced pluripotency gene Oct4 (Pou5f1) in mouse and human somatic cells. First, with a number of TALEs and sgRNAs targeting various regions in the mouse and human Oct4 promoters, we found that the most efficient TALE-VP64s bound around -120 to -80 bp, while highly effective sgRNAs targeted from -147 to -89-bp upstream of the transcription start sites to induce high activity of luciferase reporters. In addition, we observed significant transcriptional synergy when multiple TFs were applied simultaneously. Although individual TFs exhibited marginal activity to up-regulate endogenous gene expression, optimized combinations of TALE-VP64s could enhance endogenous Oct4 transcription up to 30-fold in mouse NIH3T3 cells and 20-fold in human HEK293T cells. More importantly, the enhancement of OCT4 transcription ultimately generated OCT4 proteins. Furthermore, examination of different epigenetic modifiers showed that histone acetyltransferase p300 could enhance both TALE-VP64 and sgRNA/dCas9-VP64 induced transcription of endogenous OCT4. Taken together, our study suggested that engineered TALE-TF and dCas9-TF are useful tools for modulating gene expression in mammalian cells.
C1 [Hu, Jiabiao; Lei, Yong; Wong, Wing-Ki; Liu, Senquan; Lee, Kai-Chuen; He, Xiangjun; You, Wenxing; Zhou, Rui; Zhao, Hui; Feng, Bo] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Key Lab Regenerat Med,Minist Educ, Hong Kong, Hong Kong, Peoples R China.
[Hu, Jiabiao; Lee, Kai-Chuen; He, Xiangjun; You, Wenxing; Zhao, Hui; Feng, Bo] CUHK Shenzhen Res Inst, SBS Core Lab, Shenzhen, Peoples R China.
[Liu, Senquan; Huang, He] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Bone Marrow Transplantat Ctr, Hangzhou 310003, Zhejiang, Peoples R China.
[Guo, Jun-Tao] Univ N Carolina, Dept Bioinformat & Genom, Charlotte, NC 28223 USA.
[Chen, Xiongfong] NCI, Adv Biomed Comp Ctr, NIH, Frederick, MD 21702 USA.
[Peng, Xianlu; Sun, Hao] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Shatin, Hong Kong, Peoples R China.
[Peng, Xianlu; Sun, Hao] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Chem Pathol, Hong Kong, Hong Kong, Peoples R China.
RP Feng, B (reprint author), Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Key Lab Regenerat Med,Minist Educ, Hong Kong, Hong Kong, Peoples R China.
EM fengbo@cuhk.edu.hk
RI Zhao, Hui/B-8429-2016; Feng, Bo/D-7831-2014;
OI sun, hao/0000-0002-5547-9501
FU Research Grants Council of Hong Kong [CUHK 464411, CUHK 478812, HKUST
T13-607/12R]; National Natural Science Foundation of China [NSFC
31171433]; Shenzhen Basic Research Funding [JC201104220293A]; National
Science Foundation, USA [DBI0844749]
FX Research Grants Council of Hong Kong [CUHK 464411 to B. F; CUHK 478812
to B. F.; HKUST T13-607/12R to Y.I.]; National Natural Science
Foundation of China [NSFC 31171433 to B. F. (in part)]; Shenzhen Basic
Research Funding [JC201104220293A to B. F. (in part)]; National Science
Foundation, USA [DBI0844749 to J.G. (in part)]. Funding for open access
charges: Research Grants Council of Hong Kong.
NR 61
TC 46
Z9 49
U1 1
U2 42
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD APR
PY 2014
VL 42
IS 7
BP 4375
EP 4390
DI 10.1093/nar/gku109
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AF5NV
UT WOS:000334761100030
PM 24500196
ER
PT J
AU Das, BB
Huang, SYN
Murai, J
Rehman, I
Ame, JC
Sengupta, S
Das, SK
Majumdar, P
Zhang, HL
Biard, D
Majumder, HK
Schreiber, V
Pommier, Y
AF Das, Benu Brata
Huang, Shar-yin N.
Murai, Junko
Rehman, Ishita
Ame, Jean-Christophe
Sengupta, Souvik
Das, Subhendu K.
Majumdar, Papiya
Zhang, Hongliang
Biard, Denis
Majumder, Hemanta K.
Schreiber, Valerie
Pommier, Yves
TI PARP1-TDP1 coupling for the repair of topoisomerase I-induced DNA damage
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID STRAND BREAK REPAIR; SPINOCEREBELLAR ATAXIA; POLY(ADP-RIBOSE)
POLYMERASE; HOMOLOGOUS RECOMBINATION; PHOSPHODIESTERASE TDP1; AXONAL
NEUROPATHY-1; COVALENT COMPLEXES; VERTEBRATE CELLS; PARP INHIBITION;
PATHWAYS
AB Poly(ADP-ribose) polymerases (PARP) attach poly(ADP-ribose) (PAR) chains to various proteins including themselves and chromatin. Topoisomerase I (Top1) regulates DNA supercoiling and is the target of camptothecin and indenoisoquinoline anticancer drugs, as it forms Top1 cleavage complexes (Top1cc) that are trapped by the drugs. Endogenous and carcinogenic DNA lesions can also trap Top1cc. Tyrosyl-DNA phosphodiesterase 1 (TDP1), a key repair enzyme for trapped Top1cc, hydrolyzes the phosphodiester bond between the DNA 3'-end and the Top1 tyrosyl moiety. Alternative repair pathways for Top1cc involve endonuclease cleavage. However, it is unknown what determines the choice between TDP1 and the endonuclease repair pathways. Here we show that PARP1 plays a critical role in this process. By generating TDP1 and PARP1 double-knockout lymphoma chicken DT40 cells, we demonstrate that TDP1 and PARP1 are epistatic for the repair of Top1cc. The N-terminal domain of TDP1 directly binds the C-terminal domain of PARP1, and TDP1 is PARylated by PARP1. PARylation stabilizes TDP1 together with SUMOylation of TDP1. TDP1 PARylation enhances its recruitment to DNA damage sites without interfering with TDP1 catalytic activity. TDP1-PARP1 complexes, in turn recruit X-ray repair cross-complementing protein 1 (XRCC1). This work identifies PARP1 as a key component driving the repair of trapped Top1cc by TDP1.
C1 [Das, Benu Brata; Huang, Shar-yin N.; Murai, Junko; Zhang, Hongliang; Pommier, Yves] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Das, Benu Brata; Huang, Shar-yin N.; Murai, Junko; Zhang, Hongliang; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Das, Benu Brata; Rehman, Ishita; Sengupta, Souvik; Das, Subhendu K.; Majumdar, Papiya] Indian Assoc Cultivat Sci, Mol Biol Lab, Kolkata 700032, India.
[Ame, Jean-Christophe; Schreiber, Valerie] Univ Strasbourg, UMR7242, CNRS, Lab Excellence Medalis,ESBS, F-67412 Illkirch Graffenstaden, France.
[Biard, Denis] CEA DSV IMETI SEPIA, BP6, F-92265 Fontenay Aux Roses, France.
[Majumder, Hemanta K.] Indian Inst Chem Biol, Mol Parasitol Lab, Kolkata 700032, India.
RP Pommier, Y (reprint author), NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
EM pommier@nih.gov
RI Schreiber, Valerie/M-5007-2016;
OI Schreiber, Valerie/0000-0003-0507-639X; Sengupta,
Souvik/0000-0001-7452-979X; BIARD, Denis Serge
Francois/0000-0001-9697-4392
FU NCI Intramural Program, Center for Cancer Research, National Cancer
Institute, NIH [Z01 BC 006161]; Wellcome Trust/India alliance
intermediate fellowship [IA/I/13/1/500888]; IACS startup fund,
Department of science and technology, Government of India; CNRS;
University of Strasbourg; Ligue contre le Cancer (comites du Bas-Rhin et
du Haut-Rhin); Labex Medalis [11LABX065]
FX The NCI Intramural Program, Center for Cancer Research, National Cancer
Institute, NIH, supported this work (Z01 BC 006161). The BBD team is
supported by Wellcome Trust/India alliance intermediate fellowship
(Award# IA/I/13/1/500888) and IACS startup fund, Department of science
and technology, Government of India. VS team is Equipe Labellisee Ligue
contre le Cancer and is supported by CNRS, University of Strasbourg,
Ligue contre le Cancer (comites du Bas-Rhin et du Haut-Rhin) and Labex
Medalis (11LABX065). Funding for open access charge: The NCI Intramural
Program, Center for Cancer Research, National Cancer Institute, NIH.
NR 68
TC 37
Z9 38
U1 1
U2 13
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD APR
PY 2014
VL 42
IS 7
BP 4435
EP 4449
DI 10.1093/nar/gku088
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AF5NV
UT WOS:000334761100035
PM 24493735
ER
PT J
AU Li, JF
Kannan, M
Trivett, AL
Liao, HL
Wu, XL
Akagi, K
Symer, DE
AF Li, Jingfeng
Kannan, Manoj
Trivett, Anna L.
Liao, Hongling
Wu, Xiaolin
Akagi, Keiko
Symer, David E.
TI An antisense promoter in mouse L1 retrotransposon open reading frame-1
initiates expression of diverse fusion transcripts and limits
retrotransposition
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID SMALL INTERFERING RNAS; TRANSPOSABLE ELEMENTS; HUMAN GENOME; STRUCTURAL
VARIATION; CHAPERONE ACTIVITY; SOMATIC MOSAICISM; MAMMALIAN-CELLS; DNA
METHYLATION; GENE-EXPRESSION; BETA-LACTAMASE
AB Between 6 and 30% of human and mouse transcripts are initiated from transposable elements. However, the promoters driving such transcriptional activity are mostly unknown. We experimentally characterized an antisense (AS) promoter in mouse L1 retrotransposons for the first time, oriented antiparallel to the coding strand of L1 open reading frame-1. We found that AS transcription is mediated by RNA polymerase II. Rapid amplification of cDNA ends cloning mapped transcription start sites adjacent to the AS promoter. We identified > 100 novel fusion transcripts, of which many were conserved across divergent mouse lineages, suggesting conservation of potential functions. To evaluate whether AS L1 transcription could regulate L1 retrotransposition, we replaced portions of native open reading frame-1 in donor elements by synonymously recoded sequences. The resulting L1 elements lacked AS promoter activity and retrotransposed more frequently than endogenous L1s. Overexpression of AS L1 transcripts also reduced L1 retrotransposition. This suppression of retrotransposition was largely independent of Dicer. Our experiments shed new light on how AS fusion transcripts are initiated from endogenous L1 elements across the mouse genome. Such AS transcription can contribute substantially both to natural transcriptional variation and to endogenous regulation of L1 retrotransposition.
C1 [Li, Jingfeng; Akagi, Keiko; Symer, David E.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Li, Jingfeng; Kannan, Manoj; Trivett, Anna L.; Symer, David E.] NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Liao, Hongling; Wu, Xiaolin] SAIC Frederick Inc, Lab Mol Technol, Adv Technol Program, Frederick, MD 21702 USA.
[Akagi, Keiko] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Symer, David E.] Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA.
[Symer, David E.] Ohio State Univ, Columbus, OH 43210 USA.
RP Symer, DE (reprint author), Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
EM david.symer@osumc.edu
FU Intramural Research Program, Center for Cancer Research, National Cancer
Institute (NIH); National Cancer Institute, NIH [N01-CO-12400]; Ohio
State University Comprehensive Cancer Center
FX Funded by the Intramural Research Program, Center for Cancer Research,
National Cancer Institute (NIH); federal funds from the National Cancer
Institute, NIH to SAIC-Frederick [contract N01-CO-12400]; and Ohio State
University Comprehensive Cancer Center. Funding for open access charge:
Ohio State University Comprehensive Cancer Center.
NR 87
TC 14
Z9 14
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD APR
PY 2014
VL 42
IS 7
BP 4546
EP 4562
DI 10.1093/nar/gku091
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AF5NV
UT WOS:000334761100043
PM 24493738
ER
PT J
AU Fojo, AT
Bates, SE
AF Fojo, Antonio Tito
Bates, Susan E.
TI Clinical Trial Results: A Clinical Trial Bazaar!
SO ONCOLOGIST
LA English
DT Editorial Material
C1 [Fojo, Antonio Tito; Bates, Susan E.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Fojo, AT (reprint author), NCI, Ctr Canc Res, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM fojot@mail.nih.gov
NR 8
TC 0
Z9 0
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PD APR
PY 2014
VL 19
IS 4
BP 313
EP 314
DI 10.1634/theoncologist.2014-0091
PG 2
WC Oncology
SC Oncology
GA AF0JY
UT WOS:000334401300001
PM 24668329
ER
PT J
AU Liu, XC
LoRusso, P
Mita, M
Piha-Paul, S
Hong, DS
Fu, SQ
McQuinn, L
Asatiani, E
Doyle, LA
Chen, HX
Hess, KR
Kurzrock, R
Naing, A
AF Liu, Xiaochun
LoRusso, Patricia
Mita, Monica
Piha-Paul, Sarina
Hong, David S.
Fu, Siqing
McQuinn, Lacey
Asatiani, Ekaterine
Doyle, Lawrence A.
Chen, Helen X.
Hess, Kenneth R.
Kurzrock, Razelle
Naing, Aung
TI Incidence of Mucositis in Patients Treated With Temsirolimus-Based
Regimens and Correlation to Treatment Response
SO ONCOLOGIST
LA English
DT Editorial Material
ID MTOR INHIBITOR TEMSIROLIMUS; RENAL-CELL CARCINOMA; CANCER-PATIENTS;
CCI-779; TUMORS; TRIAL
C1 [Liu, Xiaochun; Piha-Paul, Sarina; Hong, David S.; Fu, Siqing; McQuinn, Lacey; Naing, Aung] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA.
[LoRusso, Patricia] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI USA.
[Mita, Monica] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Asatiani, Ekaterine] Merck Serono SA, Geneva, Switzerland.
[Doyle, Lawrence A.; Chen, Helen X.] NCI, Canc Therapy Evaluat Program, NIH, Rockville, MD USA.
[Hess, Kenneth R.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Kurzrock, Razelle] Univ Calif San Diego, Moores Canc Ctr, Div Hematol Oncol, La Jolla, CA 92093 USA.
RP Liu, XC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA.
FU NCATS NIH HHS [UL1 TR000371]; NCI NIH HHS [R21CA13763301A1, U01
CA062461, U01 CA062487, U01CA62461, U01CA62487, P30 CA016672]
NR 13
TC 2
Z9 2
U1 0
U2 1
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PD APR
PY 2014
VL 19
IS 4
BP 426
EP 428
DI 10.1634/theoncologist.2013-0231
PG 3
WC Oncology
SC Oncology
GA AF0JY
UT WOS:000334401300021
PM 24668327
ER
PT J
AU Lembersky, BC
Rastogi, P
AF Lembersky, Barry C.
Rastogi, Priya
TI COMMENTARY ON THE BROWN-GLABERMAN/DAYAO/ROYCE ARTICLE: HER2 Targeting in
Early Breast Cancer: More Options and More Questions
SO ONCOLOGY-NEW YORK
LA English
DT Editorial Material
ID ADJUVANT CHEMOTHERAPY; TRASTUZUMAB; PERTUZUMAB; SAFETY
C1 [Lembersky, Barry C.; Rastogi, Priya] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA.
[Lembersky, Barry C.; Rastogi, Priya] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
RP Lembersky, BC (reprint author), Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA.
FU NCI NIH HHS [U10 CA012027, U10 CA037377, U10 CA069651, U10 CA069974, U10
CA180822, U10 CA180868, U10-CA-37377]
NR 10
TC 0
Z9 0
U1 0
U2 0
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD APR
PY 2014
VL 28
IS 4
BP 293
EP 294
PG 2
WC Oncology
SC Oncology
GA AF5CO
UT WOS:000334731800004
PM 24839799
ER
PT J
AU Dunleavy, K
Wilson, WH
AF Dunleavy, Kieron
Wilson, Wyndham H.
TI Appropriate Management of Molecular Subtypes of Diffuse Large B-Cell
Lymphoma
SO ONCOLOGY-NEW YORK
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; DOSE-ADJUSTED EPOCH; RITUXIMAB PLUS
CYCLOPHOSPHAMIDE; RANDOMIZED CONTROLLED-TRIAL; 3-WEEKLY CHOP
CHEMOTHERAPY; GERMINAL-CENTER; ELDERLY-PATIENTS; PHASE-II; AGGRESSIVE
LYMPHOMAS; ANTITUMOR-ACTIVITY
AB In recent years, we have made huge strides in our understanding of the molecular complexity of diffuse large B-cell lymphoma (DLBCL). New technologies, such as gene expression profiling, RNA interference screening, and DNA sequencing, have identified several new signaling pathways and therapeutic targets for drug development. While we once considered DLBCL to be a single disease entity, recent insights have helped identify the existence of at least three distinct molecular diseases: a germinal center B-cell-like subtype, an activated B-cell-like subtype, and a primary mediastinal B-cell lymphoma subtype. All three subtypes originate from different stages of B-cell differentiation and are characterized by distinct mechanisms of oncogenic activation. This classification of DLBCL has laid the foundation for the development of new agents and novel strategies that target individual subtypes.
C1 [Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Lymphoid Malignancies Branch, Bethesda, MD 20892 USA.
RP Dunleavy, K (reprint author), NCI, Lymphoid Malignancies Branch, Bethesda, MD 20892 USA.
NR 74
TC 8
Z9 8
U1 0
U2 4
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD APR
PY 2014
VL 28
IS 4
BP 326
EP 334
PG 9
WC Oncology
SC Oncology
GA AF5CO
UT WOS:000334731800012
PM 24839807
ER
PT J
AU Louis, GMB
AF Louis, Germaine M. Buck
TI Persistent environmental pollutants and couple fecundity: an overview
SO REPRODUCTION
LA English
DT Article; Proceedings Paper
CT 7th Copenhagen Workshop on Endocrine Disrupters
CY MAY 28-31, 2013
CL Copenhagen, DENMARK
ID POLYCYSTIC-OVARY-SYNDROME; BISPHENOL-A CONCENTRATIONS; SEMEN QUALITY;
REGIONAL DIFFERENCES; PERFLUORINATED COMPOUNDS; REPRODUCTIVE FUNCTION;
PROSPECTIVE COHORT; PREGNANCY; TIME; WOMEN
AB Speculation has arisen that human fecundity may be declining, possibly a function of exposure to persistent environmental chemicals that resist degradation resulting in various pathways for human exposure. In contrast to considerable animal evidence suggesting adverse effects of such chemicals on reproduction, limited human research has been undertaken. To date, available data stem largely from ten unique study cohorts that have quantified individual chemical exposures in relation to time-to-pregnancy (TTP), which is a measure of couple fecundity. Diminished fecundability odds ratios indicative of longer TTP were observed in all but two studies, although not all findings achieved statistical significance. Persistent chemicals associated with reduced couple fecundity as measured by a longer TTP included beta HCH, cadmium, lead, mercury, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, TCCD dioxin, and select polybrominated diethers, polychlorinated biphenyls, and perfluorochemicals. Important methodologic limitations need to be considered in weighing the evidence: i) reliance on pregnant women, which may exclude women with the highest exposures if related to the inability to conceive; ii) retrospectively reported TTP, which may be associated with bidirectional reporting errors; and iii) limited attention to male partners or couples' exposures. While current evidence is not inconsistent with animal evidence, concerted efforts to address lingering data gaps should include novel strategies for recruiting couples, the longitudinal measurement of TTP, and the continued enrollment of couples across successive pregnancies. This latter strategy will provide a more complete understanding of the toxicokinetics of chemicals during sensitive windows and their implications for fecundity and its related impairments.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM louisg@mail.nih.gov
OI Buck Louis, Germaine/0000-0002-1774-4490
NR 60
TC 4
Z9 4
U1 0
U2 15
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1470-1626
J9 REPRODUCTION
JI Reproduction
PD APR
PY 2014
VL 147
IS 4
SI SI
BP R97
EP R104
DI 10.1530/REP-13-0472
PG 8
WC Developmental Biology; Reproductive Biology
SC Developmental Biology; Reproductive Biology
GA AE8YA
UT WOS:000334287700003
ER
PT J
AU Wendler, D
AF Wendler, David
TI Should protections for research with humans who cannot consent apply to
research with nonhuman primates?
SO THEORETICAL MEDICINE AND BIOETHICS
LA English
DT Article
DE Nonhuman primates; Clinical research; Risks; Informed consent; Assent
AB Research studies and interventions sometimes offer potential benefits to subjects that compensate for the risks they face. Other studies and interventions, which I refer to as "nonbeneficial" research, do not offer subjects a compensating potential for benefit. These studies and interventions have the potential to exploit subjects for the benefit of others, a concern that is especially acute when investigators enroll individuals who are unable to give informed consent. US regulations for research with human subjects attempt to address this concern by mandating strict protections for nonbeneficial research with subjects who cannot consent. Typically, humans who cannot consent, such as children, may be enrolled in nonbeneficial research only when it poses low risks and has the potential to gather information of sufficient value to justify the risks, an appropriate surrogate gives permission on the individual's behalf and the individual agrees (assents). In contrast, US regulations for nonbeneficial research with nonhuman primates do not include these protections, even though it too involves subjects who cannot consent and who face risks for the benefit of others. Is this difference in regulatory protections justified? Or does the principle of fairness-treat like cases alike-imply that regulations for nonbeneficial research with nonhuman primates should include protections similar to those that apply to nonbeneficial research with humans who cannot consent?.
C1 NIH Clin Ctr, Dept Bioeth, Bethesda, MD 20892 USA.
RP Wendler, D (reprint author), NIH Clin Ctr, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM dwendler@nih.gov
NR 15
TC 3
Z9 3
U1 1
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1386-7415
EI 1573-1200
J9 THEOR MED BIOETH
JI Theor. Med. Bioeth.
PD APR
PY 2014
VL 35
IS 2
SI SI
BP 157
EP 173
DI 10.1007/s11017-014-9285-5
PG 17
WC Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Social Issues; Biomedical Social
Sciences
GA AF0UR
UT WOS:000334430100007
PM 24647873
ER
PT J
AU Zhang, LS
Gaskins, K
Yu, ZY
Xiong, Y
Merino, MJ
Kebebew, E
AF Zhang, Lisa
Gaskins, Kelli
Yu, Zhiya
Xiong, Yin
Merino, Maria J.
Kebebew, Electron
TI An In Vivo Mouse Model of Metastatic Human Thyroid Cancer
SO THYROID
LA English
DT Article
ID CARCINOMA; GROWTH; CELLS; MICE; PROGRESSION; MODULATION; RECEPTOR;
THERAPY; KINASE; VITRO
AB Background: Mouse models of metastatic human cancers are important tools in preclinical studies for testing new systematic therapies and studying effectors of cancer metastasis. The major drawbacks of current mouse models for metastatic thyroid cancer are that they have low metastasis rates and do not allow in vivo tumor detection. Here, we report and characterize an in vivo detectable metastasis mouse model of human thyroid cancer using multiple thyroid cancer cell lines.
Methods: Human anaplastic thyroid cancer cell lines 8505C, C-643, SW-1736, and THJ-16T; follicular thyroid cancer cell lines FTC-133, FTC-236, and FTC-238; and Hurthle cell carcinoma cell line XTC-1 were transfected with a linearized pGL4.51[luc2/CMV/Neo] vector or transduced with lentivirus containing Luc2-eGFP reporter genes. The stably transfected cells were injected intravenously into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice. Tumors were detected with an in vivo imaging system-Xenogen IVIS. Vemurafenib, a BRAF inhibitor, was used to treat lung metastases generated from 8505C-Luc2 cells with a BRAF(V600E) mutation to test the accuracy of the model to evaluate response to therapy.
Results: Intravenous injection of as few as 30,000 8505C-Luc2 cells produced lung metastases in 100% of the injected mice, and many of these mice also developed bone metastases at a later stage of the disease. Similarly, metastatic tumors also developed in all mice injected with C-643-Luc2, THJ-16T-Luc2, FTC-133-Luc2, FTC-236-Luc2, FTC-238-Luc2, and XTC-1-Luc2 cells. The metastases were easily detectable in vivo, and tumor progression could be dynamically and accurately followed and correlated with the actual tumor burden. Furthermore, disease progression could be easily controlled by adjusting the number of injected cells. The in vivo treatment of 8505C xenograft lung metastases with vemurafenib dramatically reduced the growth and signal intensity with good correlation with actual tumor burden.
Conclusions: Herein we report an in vivo detectable mouse model of metastatic human thyroid cancer that is reliable and reproducible. It will serve as a useful tool in the preclinical testing of alternative systematic therapies for metastatic thyroid cancer, and for functional studies of thyroid cancer tumor biology in vivo.
C1 [Zhang, Lisa; Gaskins, Kelli; Xiong, Yin; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Yu, Zhiya] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, 10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
FU Intramural Research Program, Center for Cancer Research, National Cancer
Institute, National Institutes of Health
FX We thank Dr. Bih-Rong Wei (NCI/NIH) and Dr. Yaroslav Teper (NCI/NIH) for
technical help. This research was supported by the Intramural Research
Program, Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 25
TC 14
Z9 14
U1 1
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD APR 1
PY 2014
VL 24
IS 4
BP 695
EP 704
DI 10.1089/thy.2013.0149
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AE6NN
UT WOS:000334110700011
PM 24262022
ER
PT J
AU Perrine, CG
Cogswell, ME
Swanson, CA
Sullivan, KM
Chen, TC
Carriquiry, AL
Dodd, KW
Caldwell, KL
Wang, CY
AF Perrine, Cria G.
Cogswell, Mary E.
Swanson, Christine A.
Sullivan, Kevin M.
Chen, Te-Ching
Carriquiry, Alicia L.
Dodd, Kevin W.
Caldwell, Kathleen L.
Wang, Chia-Yih
TI Comparison of Population Iodine Estimates from 24-Hour Urine and
Timed-Spot Urine Samples
SO THYROID
LA English
DT Article
ID UNITED-STATES; CREATININE CONCENTRATIONS; IODINE/CREATININE RATIO;
EXCRETION; NUTRITION; SODIUM; ADULTS; DEFICIENCY; ADJUSTMENT; POTASSIUM
AB Background: Median urine iodine concentration (UIC; mu g/L) in spot urine samples is recommended for monitoring population iodine status. Other common measures are iodine:creatinine ratio (I/Cr; mu g/g) and estimated 24-hour urine iodine excretion (UIE; I/Crxpredicted 24-hour Cr; mu g/day). Despite different units, these measures are often used interchangeably, and it is unclear how they compare with the reference standard 24-hour UIE.
Methods: Volunteers aged 18-39 years collected all their urine samples for 24 hours (n=400). Voids from morning, afternoon, evening, overnight, and a composite 24-hour sample were analyzed for iodine. We calculated median observed 24-hour UIE and 24-hour UIC, and spot UIC, I/Cr, and two measures of estimated UIE calculated using predicted 24-hour Cr from published estimates by Kesteloot and Joosens (varies by age and sex) and published equations by Mage et al. (varies by age, sex, race, and anthropometric measures). We examined mean differences and relative difference across iodine excretion levels using Bland-Altman plots.
Results: Median 24-hour UIE was 173.6 mu g/day and 24-hour UIC was 144.8 mu g/L. From timed-spot urine samples, estimates were: UIC 147.3-156.2 mu g/L; I/Cr 103.6-114.3 mu g/g, estimated 24-hour UIE (Kesteloot and Joosens) 145.7-163.3 mu g/day; and estimated 24-hour UIE (Mage) 176.5-187.7 mu g/day. Iodine measures did not vary consistently by timing of spot urine collection. Compared with observed 24-hour UIE, on average, estimated (Mage) 24-hour UIE was not significantly different, while estimated 24-hour UIE (Kesteloot and Joosens) was significantly different for some ethnicity/sex groups. Compared with 24-hour UIC, on average, spot UIC did not differ.
Conclusions: Estimates of UIC, I/Cr, and estimated 24-hour UIE (I/Crxpredicted 24-hour Cr) from spot urine samples should not be used interchangeably. Estimated 24-hour UIE, where predicted 24-hour Cr varies by age, sex, ethnicity, and anthropometric measures and was calculated with prediction equations using data from the sample, was more comparable to observed 24-hour UIE than when predicted 24-hour Cr was from published estimates from a different population. However, currently no cutoffs exist to interpret population estimated 24-hour UIE values.
C1 [Perrine, Cria G.; Dodd, Kevin W.] Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, Atlanta, GA 30333 USA.
[Cogswell, Mary E.] Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Atlanta, GA 30333 USA.
[Chen, Te-Ching; Wang, Chia-Yih] Ctr Dis Control & Prevent, Div Hlth & Nutr Examinat Surveys, Atlanta, GA 30333 USA.
[Caldwell, Kathleen L.] Ctr Dis Control & Prevent, Div Sci Lab, Atlanta, GA 30333 USA.
[Swanson, Christine A.] NCI, Off Dietary Supplements, NIH, Bethesda, MD 20892 USA.
[Dodd, Kevin W.] NCI, NIH, Bethesda, MD 20892 USA.
[Sullivan, Kevin M.] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA.
[Carriquiry, Alicia L.] Iowa State Univ, Dept Stat, Ames, IA USA.
RP Perrine, CG (reprint author), Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, 1600 Clifton Rd, Atlanta, GA 30333 USA.
EM cperrine@cdc.gov
FU NIDDK NIH HHS [T32 DK007734]
NR 32
TC 11
Z9 12
U1 0
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD APR 1
PY 2014
VL 24
IS 4
BP 748
EP 757
DI 10.1089/thy.2013.0404
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AE6NN
UT WOS:000334110700017
PM 24308769
ER
PT J
AU Fisher, V
Khuu, H
David-OCampo, V
Byrne, K
Pavletic, S
Bishop, M
Fowler, DH
Barrett, AJ
Stroncek, DF
AF Fisher, Virginia
Khuu, Hanh
David-OCampo, Virginia
Byrne, Karen
Pavletic, Steven
Bishop, Michael
Fowler, Daniel H.
Barrett, A. John
Stroncek, David F.
TI Analysis of the recovery of cryopreserved and thawed CD34+and CD3+cells
collected for hematopoietic transplantation
SO TRANSFUSION
LA English
DT Article
ID 5-PERCENT DIMETHYL-SULFOXIDE; LONG-TERM CRYOPRESERVATION; BLOOD
PROGENITOR CELLS; STEM-CELLS; IN-VITRO; STORAGE; TEMPERATURE; VIABILITY;
-80-DEGREES-C; APHERESIS
AB BackgroundCryopreservation is often used to store cellular therapies, but little is known about how well CD3+ or CD34+ cells tolerate this process.
Study Design and MethodsViable CD34+ cell recoveries were analyzed from related and unrelated donor granulocyte-colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell (PBSC) products and viable CD3+ cell recoveries from G-CSF-mobilized and nonmobilized apheresis products from related and unrelated donors. All products were cryopreserved with 5% dimethyl sulfoxide and 6% pentastarch using a controlled-rate freezer and were stored in liquid nitrogen. Related donor products were cryopreserved immediately after collection and unrelated donor products greater than 12 hours postcollection.
ResultsThe postthaw recovery of CD34+ cells from related donor PBSCs was high (n=86; 97.523.1%) and there was no difference in postthaw CD34+ cell recovery from unrelated donor PBSCs (n=14; 98.8 +/- 37.2%; p=0.863). In related donor lymphocyte products the postthaw CD3+ cell recovery (n=48; 90.7 +/- 21.4%) was greater than that of unrelated donor products (n=14; 66.6 +/- 35.8%; p=0.00251). All unrelated donor lymphocyte products were from G-CSF-mobilized products, while most related donor lymphocyte products were from nonmobilized products. A comparison of the CD3+ cell recovery from related donor G-CSF-mobilized products (n=19; 85.0 +/- 29.2%) with that of unrelated donor products found no significant difference (p=0.137).
ConclusionsThe postthaw recovery of CD34+ cells was high in both related and unrelated donor products, but the recovery of CD3+ cells in unrelated donor G-CSF-mobilized products was lower. G-CSF-mobilized unrelated donor products may contain fewer CD3+ cells than non-G-CSF-exposed products upon thaw and, when indicated, cell doses should be monitored.
C1 [Fisher, Virginia; Khuu, Hanh; David-OCampo, Virginia; Byrne, Karen; Stroncek, David F.] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Pavletic, Steven; Bishop, Michael; Fowler, Daniel H.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Stroncek, DF (reprint author), NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, 10 Ctr Drive MSC-1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA.
EM dstroncek@cc.nih.gov
FU Intramural Research Programs of the Clinical Center, NCI; NHLBI, NIH
FX This work was supported by the Intramural Research Programs of the
Clinical Center, NCI and NHLBI, NIH.
NR 23
TC 2
Z9 2
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD APR
PY 2014
VL 54
IS 4
BP 1088
EP 1092
DI 10.1111/trf.12428
PG 5
WC Hematology
SC Hematology
GA AE7DF
UT WOS:000334156200019
PM 24117879
ER
PT J
AU Kuzembayeva, M
Dilley, K
Sardo, L
Hu, WS
AF Kuzembayeva, Malika
Dilley, Kari
Sardo, Luca
Hu, Wei-Shau
TI Life of psi: How full-length HIV-1 RNAs become packaged genomes in the
viral particles
SO VIROLOGY
LA English
DT Review
DE HIV-1; Retrovirus; RNA transcription and processing; Full-length RNA;
RNA export; Rev; RRE; RNA dimerization; RNA packaging; Gag; Virus
assembly
ID HUMAN-IMMUNODEFICIENCY-VIRUS; REV-RESPONSE ELEMENT; MURINE
LEUKEMIA-VIRUS; CONSTITUTIVE TRANSPORT ELEMENT; TYPE-1 GAG POLYPROTEIN;
NUCLEAR-PORE COMPLEX; MAJOR SPLICE DONOR; MESSENGER-RNA;
GENE-EXPRESSION; NUCLEOCAPSID PROTEIN
AB As a member of the retrovirus family, HIV-1 packages its RNA genome into particles and replicates through a DNA intermediate that integrates into the host cellular genome. The multiple genes encoded by HIV-1 are expressed from the same promoter and their expression is regulated by splicing and ribosomal frameshift The full-length HIV-1 RNA plays a central role in viral replication as it serves as the genome in the progeny virus and is used as the template for Gag and GagPol translation. In this review, we summarize findings that contribute to our current understanding of how full-length RNA is expressed and transported, cis- and transacting elements important for RNA packaging, the locations and timing of RNA:RNA and RNA:Gag interactions, and the processes required for this RNA to be packaged into viral particles. Published by Elsevier Inc.
C1 [Kuzembayeva, Malika; Dilley, Kari; Sardo, Luca; Hu, Wei-Shau] NCI, Viral Recombinat Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Hu, WS (reprint author), NCI, Viral Recombinat Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM Wei-Shau.Hu@nih.gov
FU Intramural Research Program of the Center for Cancer Research, NCI;
Intramural AIDS Targeted Antiviral Program, NIH
FX We thank Vinay K Pathak for insightful discussions and suggestions; Olga
Nikolaitchik, Krista Delviks-Frankenberry, and Yang Liu for critical
reading of the manuscript This work was funded by the Intramural
Research Program of the Center for Cancer Research, NCI and the
Intramural AIDS Targeted Antiviral Program, NIH. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government
NR 158
TC 30
Z9 30
U1 4
U2 18
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD APR
PY 2014
VL 454
BP 362
EP 370
DI 10.1016/j.virol.2014.01.019
PG 9
WC Virology
SC Virology
GA AF4AY
UT WOS:000334655000037
PM 24530126
ER
PT J
AU Bonzo, JA
Brocker, C
Jiang, CT
Wang, RH
Deng, CX
Gonzalez, FJ
AF Bonzo, Jessica A.
Brocker, Chad
Jiang, Changtao
Wang, Rui-Hong
Deng, Chu-Xia
Gonzalez, Frank J.
TI Hepatic sirtuin 1 is dispensable for fibrate- induced peroxisome
proliferator-activated receptor-alpha function in vivo
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE peroxisome proliferator-activated receptor-alpha; sirtuin 1; fibrates
ID HIGH-FAT DIET; PPAR-ALPHA; METABOLISM; MICE; EXPRESSION; DAMAGE;
TUMORIGENESIS; STEATOSIS; DELETION; NAD(+)
AB Peroxisome proliferator-activated receptor-alpha (PPAR alpha) mediates metabolic remodeling, resulting in enhanced mitochondrial and peroxisomal beta-oxidation of fatty acids. In addition to the physiological stimuli of fasting and high-fat diet, PPAR alpha is activated by the fibrate class of drugs for the treatment of dyslipidemia. Sirtuin 1 (SIRT1), an important regulator of energy homeostasis, was downregulated in fibrate-treated wild-type mice, suggesting PPAR alpha regulation of Sirt1 gene expression. The impact of SIRT1 loss on PPAR alpha functionality in vivo was assessed in hepato-cyte-specific knockout mice that lack the deacetylase domain of SIRT1 (Sirt1(triangle Liv)). Knockout mice were treated with fibrates or fasted for 24 h to activate PPAR alpha. Basal expression of the PPAR alpha target genes Cyp4a10 and Cyp4a14 was reduced in Sirt1(triangle Liv) mice compared with wild-type mice. However, no difference was observed between wild-type and Sirt1(triangle Liv) mice in either fasting-or fibrate-mediated induction of PPAR alpha target genes. Similar to the initial results, there was no difference in fibrate-activated PPAR alpha gene induction. To assess the relationship between SIRT1 and PPAR alpha in a pathophysiological setting, Sirt1(triangle Liv) mice were maintained on a high-fat diet for 14 wk, followed by fibrate treatment. Sirt1(triangle Liv) mice exhibited increased body mass compared with control mice. In the context of a high-fat diet, Sirt1(triangle Liv) mice did not respond to the cholesterol-lowering effects of the fibrate treatment. However, there were no significant differences in PPAR alpha target gene expression. These results suggest that, in vivo, SIRT1 deacetylase activity does not significantly impact induced PPAR alpha activity.
C1 [Bonzo, Jessica A.; Brocker, Chad; Jiang, Changtao; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wang, Rui-Hong; Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, CCR, NIH, Bldg 37,Rm 3106,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
RI deng, chuxia/N-6713-2016
FU National Cancer Institute; National Institute of Diabetes and Digestive
and Kidney Diseases; Postdoctoral Research Associate program through the
National Institute of General Medical Sciences
FX This work was funded by the intramural research program at the National
Cancer Institute (J. A. Bonzo, C. Brocker, C. Jiang, and F. J. Gonzalez)
and the National Institute of Diabetes and Digestive and Kidney Diseases
(R. -H. Wang and C. -X. Deng). J. A. Bonzo and C. Brocker were
additionally supported by the Postdoctoral Research Associate program
through the National Institute of General Medical Sciences.
NR 38
TC 4
Z9 4
U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
EI 1522-1555
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD APR
PY 2014
VL 306
IS 7
BP E824
EP E837
DI 10.1152/ajpendo.00175.2013
PG 14
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA AE9TX
UT WOS:000334354300012
PM 24496310
ER
PT J
AU Kistemaker, LEM
Bos, ST
Mudde, WM
Hylkema, MN
Hiemstra, PS
Wess, J
Meurs, H
Kerstjens, HAM
Gosens, R
AF Kistemaker, Loes E. M.
Bos, Sophie T.
Mudde, Willemieke M.
Hylkema, Machteld N.
Hiemstra, Pieter S.
Wess, Juergen
Meurs, Herman
Kerstjens, Huib A. M.
Gosens, Reinoud
TI Muscarinic M-3 Receptors Contribute to Allergen-Induced Airway
Remodeling in Mice
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE airway pharmacology; anticholinergics; asthma; nonneuronal acetylcholine
ID NONNEURONAL CHOLINERGIC SYSTEM; HUMAN LUNG FIBROBLAST; SMOOTH-MUSCLE;
TIOTROPIUM BROMIDE; ACETYLCHOLINE-RECEPTOR; MEDIATE STIMULATION;
UNCONTROLLED ASTHMA; GROWTH-FACTOR; INFLAMMATION; BRONCHOCONSTRICTION
AB Asthma is a chronic obstructive airway disease, characterized by inflammation and remodeling. Acetylcholine contributes to symptoms by inducing bronchoconstriction via the muscarinic M-3 receptor. Recent evidence suggests that bronchoconstriction can regulate airway remodeling, and therefore implies a role for the muscarinic M-3 receptor. The objective of this work was to study the contribution of the muscarinic M-3 receptor to allergen-induced remodeling using muscarinic M-3 receptor subtype-deficient (M3R-/-) mice. Wild-type (WT), M1R-/-, and M2R-/- mice were used as controls. C57Bl/ 6 mice were sensitized and challenged with ovalbumin (twice weekly for 4 wk). Control animals were challenged with saline. Allergen exposure induced goblet cell metaplasia, airway smooth muscle thickening (1.7-fold), pulmonary vascular smooth muscle remodeling (1.5-fold), and deposition of collagen I (1.7-fold) and fibronectin (1.6-fold) in the airway wall ofWT mice. These effects were absent or markedly lower inM(3)R(-/-) mice (30-100%), whereas M1R-/- and M2R-/- mice responded similarly to WT mice. In addition, airway smooth muscle and pulmonary vascular smooth muscle mass were 35-40% lower in saline-challenged M3R-/- 2 mice compared with WT mice. Interestingly, allergen-induced airway inflammation, assessed as infiltrated eosinophils and T helper type 2 cytokine expression, was similar or even enhanced in M3R-/- mice. Our data indicate that acetylcholine contributes to allergen-induced remodeling and smooth muscle mass via the muscarinic M-3 receptor, and not via M-1 or M-2 receptors. No stimulatory role for muscarinic M-3 receptors in allergic inflammation was observed, suggesting that the role of acetylcholine in remodeling is independent of the allergic inflammatory response, and may involve bronchoconstriction.
C1 [Kistemaker, Loes E. M.; Bos, Sophie T.; Mudde, Willemieke M.; Meurs, Herman; Gosens, Reinoud] Univ Groningen, Dept Mol Pharmacol, NL-9713 AV Groningen, Netherlands.
[Hylkema, Machteld N.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9713 AV Groningen, Netherlands.
[Hiemstra, Pieter S.] Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands.
[Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Kerstjens, Huib A. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Resp Med, NL-9713 AV Groningen, Netherlands.
[Kistemaker, Loes E. M.; Bos, Sophie T.; Mudde, Willemieke M.; Hylkema, Machteld N.; Meurs, Herman; Kerstjens, Huib A. M.; Gosens, Reinoud] Univ Groningen, Univ Med Ctr Groningen, Groningen Res Inst Asthma & COPD, NL-9713 AV Groningen, Netherlands.
RP Kistemaker, LEM (reprint author), Univ Groningen, Dept Mol Pharmacol, A Deusinglaan 1, NL-9713 AV Groningen, Netherlands.
EM l.e.m.kistemaker@rug.nl
FU Netherlands Lung Foundation grant [3.2.08.014]
FX This work was supported by Netherlands Lung Foundation grant 3.2.08.014.
NR 42
TC 15
Z9 18
U1 0
U2 9
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1044-1549
EI 1535-4989
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD APR
PY 2014
VL 50
IS 4
BP 690
EP 698
DI 10.1165/rcmb.2013-0220OC
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA AF0KW
UT WOS:000334403900004
PM 24156289
ER
PT J
AU Li, Y
Wang, N
Zhang, M
Ito, Y
Zhang, HY
Wang, YR
Guo, X
Hu, P
AF Li, Yang
Wang, Nan
Zhang, Min
Ito, Yoichiro
Zhang, Hongyang
Wang, Yuerong
Guo, Xin
Hu, Ping
TI Development of a Method to Extract and Purify Target Compounds from
Medicinal Plants in a Single Step: Online Hyphenation of Expanded Bed
Adsorption Chromatography and Countercurrent Chromatography
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID SALVIA-MILTIORRHIZA BUNGE; PREPARATIVE ISOLATION; ACID B; SEPARATION;
LIQUID; PURIFICATION
AB Pure compounds extracted and purified from natural sources are crucial to lead discovery and drug screening. This study presents a novel two-dimensional hyphenation of expanded bed adsorption chromatography (EBAC) and high-speed countercurrent chromatography (HSCCC) for extraction and purification of target compounds from medicinal plants in a single step. The EBAC and HSCCC were hyphenated via a six-port injection valve as an interface. Fractionation of ingredients of Salvia miltiorrhiza and Rhizoma coptidis was performed on the hyphenated system to verify its efficacy. Two compounds were harvested from Salvia miltiorrhiza, one was 52.9 mg of salvianolic acid B with an over 95% purity and the other was 2.1 mg of rosmarinic acid with a 74% purity. Another two components were purified from Rhizoma coptidis, one was 4.6 mg of coptisine with a 98% purity and one was 4.1 mg of berberine with a 82% purity. The processing time was nearly 50% that of the multistep method. The results indicate that the present method is a rapid and green way to harvest targets from medicinal plants in a single step.
C1 [Li, Yang; Wang, Nan; Zhang, Hongyang; Wang, Yuerong; Guo, Xin; Hu, Ping] E China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai 200237, Peoples R China.
[Zhang, Min] E China Univ Sci & Technol, Sch Pharm, Modern Engn Ctr Tradit Chinese Med, Shanghai 200237, Peoples R China.
[Zhang, Min; Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Zhang, M (reprint author), E China Univ Sci & Technol, Sch Pharm, Modern Engn Ctr Tradit Chinese Med, Shanghai 200237, Peoples R China.
EM zhangm@ecust.edu.cn; huping@ecust.edu.cn
FU National Natural Science Foundation of China [81273481, 21006023];
Fundamental Research Funds from the Central Universities; National
Science and Technology Major Project for Significant New Drugs
Development [2013ZX09507005]
FX This research was financially supported by the National Natural Science
Foundation of China (No. 81273481 and 21006023), the Fundamental
Research Funds from the Central Universities, and National Science and
Technology Major Project for Significant New Drugs Development (No.
2013ZX09507005).
NR 20
TC 10
Z9 10
U1 5
U2 67
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
EI 1520-6882
J9 ANAL CHEM
JI Anal. Chem.
PD APR 1
PY 2014
VL 86
IS 7
BP 3373
EP 3379
DI 10.1021/ac4035955
PG 7
WC Chemistry, Analytical
SC Chemistry
GA AE2AV
UT WOS:000333776600019
PM 24588208
ER
PT J
AU Miller, FG
AF Miller, Franklin G.
TI Heart Donation Without the Dead Donor Rule
SO ANNALS OF THORACIC SURGERY
LA English
DT Article; Proceedings Paper
CT 49th Annual Meeting of the Society-of-Thoracic-Surgeons
CY JAN 26-30, 2013
CL Los Angeles, CA
SP Soc Thorac Surg
ID LIFE-SUSTAINING TREATMENT; CARDIAC DEATH; WITHDRAWAL; TIME
C1 [Miller, Franklin G.] NIH, Dept Biophys, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Ctr Clin, Dept Bioeth, Bldg 10,Rm 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
FU Intramural NIH HHS
NR 8
TC 3
Z9 3
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
EI 1552-6259
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD APR
PY 2014
VL 97
IS 4
BP 1133
EP 1134
DI 10.1016/j.athoracsur.2014.01.007
PG 2
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA AE2NQ
UT WOS:000333810300013
PM 24694403
ER
PT J
AU Cheung, RCF
Wong, JH
Pan, WL
Chan, YS
Yin, CM
Dan, XL
Wang, HX
Fang, EF
Lam, SK
Ngai, PHK
Xia, LX
Liu, F
Ye, XY
Zhang, GQ
Liu, QH
Sha, O
Lin, P
Ki, C
Bekhit, AA
Bekhit, AE
Wan, DCC
Ye, XJ
Xia, J
Ng, TB
AF Cheung, Randy Chi Fai
Wong, Jack Ho
Pan, Wen Liang
Chan, Yau Sang
Yin, Cui Ming
Dan, Xiu Li
Wang, He Xiang
Fang, Evandro Fei
Lam, Sze Kwan
Ngai, Patrick Hung Kui
Xia, Li Xin
Liu, Fang
Ye, Xiu Yun
Zhang, Guo Qing
Liu, Qing Hong
Sha, Ou
Lin, Peng
Ki, Chan
Bekhit, Adnan A.
Bekhit, Alaa El-Din
Wan, David Chi Cheong
Ye, Xiu Juan
Xia, Jiang
Ng, Tzi Bun
TI Antifungal and antiviral products of marine organisms
SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
LA English
DT Review
DE Antifungal; Antiviral; Products; Marine; organisms
ID PENICILLIUM-PURPUROGENUM JS03-21; NECROSIS VIRUS IPNV; IN-VITRO;
TRITERPENE GLYCOSIDES; NATURAL-PRODUCTS; CANDIDA-ALBICANS;
DRUG-RESISTANCE; PLANT DEFENSINS; STREPTOMYCES SP; NS3 HELICASE
AB Marine organisms including bacteria, fungi, algae, sponges, echinoderms, mollusks, and cephalochordates produce a variety of products with antifungal activity including bacterial chitinases, lipopeptides, and lactones; fungal (-)-sclerotiorin and peptaibols, purpurides B and C, berkedrimane B and purpuride; algal gambieric acids A and B, phlorotannins; 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy)phenol, spongistatin 1, eurysterols A and B, nortetillapyrone, bromotyrosine alkaloids, bis-indole alkaloid, ageloxime B and (-)-ageloxime D, haliscosamine, hamigeran G, hippolachnin A from sponges; echinoderm triterpene glycosides and alkene sulfates; molluscan kahalalide F and a 1485-Da peptide with a sequence SRSELIVHQR; and cepalochordate chitotriosidase and a 5026.9-Da antifungal peptide. The antiviral compounds from marine organisms include bacterial polysaccharide and furan-2-yl acetate; fungal macrolide, purpurester A, purpurquinone B, isoindolone derivatives, alterporriol Q, tetrahydroaltersolanol C and asperterrestide A, algal diterpenes, xylogalactofucan, alginic acid, glycolipid sulfoquinovosyldiacylglycerol, sulfated polysaccharide p-KG03, meroditerpenoids, methyl ester derivative of vatomaric acid, lectins, polysaccharides, tannins, cnidarian zoanthoxanthin alkaloids, norditerpenoid and capilloquinol; crustacean antilipopolysaccharide factors, molluscan hemocyanin; echinoderm triterpenoid glycosides; tunicate didemnin B, tamandarins A and B and; tilapia hepcidin 1-5 (TH 1-5), seabream SauMx1, SauMx2, and SauMx3, and orange-spotted grouper beta-defensin. Although the mechanisms of antifungal and antiviral activities of only some of the aforementioned compounds have been elucidated, the possibility to use those known to have distinctly different mechanisms, good bioavailability, and minimal toxicity in combination therapy remains to be investigated. It is also worthwhile to test the marine antimicrobials for possible synergism with existing drugs. The prospects of employing them in clinical practice are promising in view of the wealth of these compounds from marine organisms. The compounds may also be used in agriculture and the food industry.
C1 [Cheung, Randy Chi Fai; Wong, Jack Ho; Pan, Wen Liang; Chan, Yau Sang; Yin, Cui Ming; Dan, Xiu Li; Wan, David Chi Cheong; Ng, Tzi Bun] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
[Wang, He Xiang; Liu, Qing Hong] China Agr Univ, State Key Lab Agrobiotechnol, Beijing 100094, Peoples R China.
[Wang, He Xiang; Liu, Qing Hong] China Agr Univ, Dept Microbiol, Beijing 100094, Peoples R China.
[Fang, Evandro Fei] NIA, NIH, Baltimore, MD 21224 USA.
[Lam, Sze Kwan] Univ Hong Kong, Dept Med, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China.
[Ngai, Patrick Hung Kui] Chinese Univ Hong Kong, Fac Sci, Sch Life Sci, Hong Kong, Hong Kong, Peoples R China.
[Xia, Li Xin; Sha, Ou] Shengzhen Univ, Sch Med, State Key Lab Resp Dis Allergy, Shenzhen, Peoples R China.
[Liu, Fang] Nankai Univ, Dept Microbiol, Tianjin 300071, Peoples R China.
[Ye, Xiu Yun] Fuzhou Univ, Natl Engn Lab High Efficiency Enzyme Express, Fuzhou 350002, Fujian, Peoples R China.
[Ye, Xiu Yun] Fuzhou Univ, Coll Biol Sci & Technol, Fuzhou 350002, Fujian, Peoples R China.
[Zhang, Guo Qing] China Agr Univ, Coll Biosci & Biotechnol, Beijing 100094, Peoples R China.
[Lin, Peng] Novartis, China Resources Pharmaceut, Shanghai, Peoples R China.
[Ki, Chan] Univ Hong Kong, Prince Philip Dent Hosp, Fac Dent, Biomed & Tissue Engn Res Grp, Hong Kong, Hong Kong, Peoples R China.
[Bekhit, Adnan A.] Univ Alexandria, Fac Pharm, Alexandria 21521, Egypt.
[Bekhit, Alaa El-Din] Univ Otago, Dept Food Sci, Dunedin, New Zealand.
[Ye, Xiu Juan] Fujian Agr & Forestry Univ, Inst Plant Virol, Key Lab Plant Virol Fujian Prov, Fuzhou 350002, Fujian, Peoples R China.
[Ye, Xiu Juan] Fujian Agr & Forestry Univ, Minist Educ, Key Lab Biopesticide & Chem Biol, Fuzhou 350002, Fujian, Peoples R China.
[Xia, Jiang] Chinese Univ Hong Kong, Fac Sci, Dept Chem, Hong Kong, Hong Kong, Peoples R China.
RP Wong, JH (reprint author), Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
EM jack1993@yahoo.com; xiujuanye2004@gmail.com; jiangxia@cuhk.edu.hk;
b021770@mailserv.cuhk.edu.hk
RI Wan, David/H-3335-2014
FU RFCID research grant from Food and Health Bureau, The Government of Hong
Kong Special Administrative Region [10090812]; National Natural Science
Foundation of China [81201270, 81273275]
FX We gratefully acknowledge the award of an RFCID research grant (no.
10090812) from Food and Health Bureau, The Government of Hong Kong
Special Administrative Region, and grants from National Natural Science
Foundation of China (nos. 81201270 and 81273275).
NR 124
TC 18
Z9 20
U1 12
U2 181
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0175-7598
EI 1432-0614
J9 APPL MICROBIOL BIOT
JI Appl. Microbiol. Biotechnol.
PD APR
PY 2014
VL 98
IS 8
BP 3475
EP 3494
DI 10.1007/s00253-014-5575-0
PG 20
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA AE7IO
UT WOS:000334171100009
PM 24562325
ER
PT J
AU Joshi, S
Savani, BN
Chow, EJ
Gilleece, MH
Halter, J
Jacobsohn, DA
Pidala, J
Quinn, GP
Cahn, JY
Jakubowski, AA
Kamani, NR
Lazarus, HM
Rizzo, JD
Schouten, HC
Socie, G
Stratton, P
Sorror, ML
Warwick, AB
Wingard, JR
Loren, AW
Majhail, NS
AF Joshi, S.
Savani, B. N.
Chow, E. J.
Gilleece, M. H.
Halter, J.
Jacobsohn, D. A.
Pidala, J.
Quinn, G. P.
Cahn, J-Y
Jakubowski, A. A.
Kamani, N. R.
Lazarus, H. M.
Rizzo, J. D.
Schouten, H. C.
Socie, G.
Stratton, P.
Sorror, M. L.
Warwick, A. B.
Wingard, J. R.
Loren, A. W.
Majhail, N. S.
TI Clinical guide to fertility preservation in hematopoietic cell
transplant recipients
SO BONE MARROW TRANSPLANTATION
LA English
DT Review
DE hematopoietic cell transplantation; autologous; allogeneic; fertility
preservation; pregnancy; assisted reproduction
ID BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; CRYOPRESERVED
OVARIAN TISSUE; LONG-TERM SURVIVORS; CHILDHOOD-CANCER SURVIVOR; IN-VITRO
FERTILIZATION; QUALITY-OF-LIFE; BREAST-CANCER; FEMALE-PATIENTS;
LEYDIG-CELL
AB With broadening indications, more options for hematopoietic cell transplantation (HCT) and improvement in survival, the number of long-term HCT survivors is expected to increase steadily. Infertility is a frequent problem that long-term HCT survivors and their partners face and it can negatively impact on the quality of life. The most optimal time to address fertility issues is before the onset of therapy for the underlying disease; however, fertility preservation should also be addressed before HCT in all children and patients of reproductive age, with referral to a reproductive specialist for patients interested in fertility preservation. In vitro fertilization (IVF) and embryo cryopreservation, oocyte cryopreservation and ovarian tissue banking are acceptable methods for fertility preservation in adult women/pubertal females. Sperm banking is the preferred method for adult men/pubertal males. Frequent barriers to fertility preservation in HCT recipients may include the perception of lack of time to preserve fertility given an urgency to move ahead with transplant, lack of patient-physician discussion because of several factors (for example, time constraints, lack of knowledge), inadequate access to reproductive specialists, and costs and lack of insurance coverage for fertility preservation. There is a need to raise awareness in the medical community about fertility preservation in HCT recipients.
C1 [Joshi, S.] Nationwide Childrens Hosp, Columbus, OH USA.
[Savani, B. N.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Chow, E. J.; Sorror, M. L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Gilleece, M. H.] St James Univ Hosp, Dept Haematol, Leeds, W Yorkshire, England.
[Halter, J.] Univ Basel Hosp, Div Hematol, Basel, Switzerland.
[Jacobsohn, D. A.] Childrens Natl Med Ctr, Div Blood & Marrow Transplantat, Washington, DC 20010 USA.
[Pidala, J.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Quinn, G. P.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Hlth Outcomes & Behav, Tampa, FL 33682 USA.
[Cahn, J-Y] Univ Hosp, Dept Hematol, Grenoble, France.
[Jakubowski, A. A.] Mem Sloan Kettering Canc Ctr, Div Hematol Oncol, New York, NY 10021 USA.
[Kamani, N. R.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA.
[Lazarus, H. M.] Univ Hosp Cleveland, Case Med Ctr, Seidman Canc Ctr, Cleveland, OH 44106 USA.
[Rizzo, J. D.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI USA.
[Schouten, H. C.] Univ Hosp Maastricht, Maastricht, Netherlands.
[Socie, G.] Hop St Louis, Paris, France.
[Stratton, P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hlt, Bethesda, MD USA.
[Warwick, A. B.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD USA.
[Wingard, J. R.] Univ Florida, Shands HealthCare, Gainesville, FL USA.
[Loren, A. W.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Majhail, N. S.] Natl Marrow Donor Program, Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN 55413 USA.
RP Majhail, NS (reprint author), Natl Marrow Donor Program, Ctr Int Blood & Marrow Transplant Res, 3001 Broadway St NE,Suite 100, Minneapolis, MN 55413 USA.
EM nmajhail@nmdp.org
RI Cahn, Jean-Yves/M-6493-2014
FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and
Blood Institute (NHLBI; National Institute of Allergy and Infectious
Diseases (NIAID); NHLBI and NCI [5U01HL069294]
FX The CIBMTR is supported by Public Health Service Grant/Cooperative
Agreement U24-CA76518 from the National Cancer Institute (NCI), the
National Heart, Lung and Blood Institute (NHLBI) and the National
Institute of Allergy and Infectious Diseases (NIAID); a
Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract
HHSH234200637015C with Health Resources and Services Administration
(HRSA/DHHS); two Grants N00014-06-1-0704 and N00014-08-1-0058 from the
Office of Naval Research; and grants from Allos, Inc., Amgen, Inc.,
Angioblast, anonymous donation to the Medical College of Wisconsin,
Ariad, Be the Match Foundation, Blue Cross and Blue Shield Association,
Buchanan Family Foundation, CaridianBCT, Celgene Corporation, CellGenix,
GmbH, Children's Leukemia Research Association, Fresenius-Biotech North
America, Inc., Gamida Cell Teva Joint Venture Ltd., Genentech, Inc.,
Genzyme Corporation, GlaxoSmithKline, HistoGenetics, Inc., Kiadis
Pharma, The Leukemia & Lymphoma Society, The Medical College of
Wisconsin, Merck & Co, Inc., Millennium: The Takeda Oncology Co.,
Milliman USA, Inc., Miltenyi Biotec, Inc., National Marrow Donor
Program, Optum Healthcare Solutions, Inc., Osiris Therapeutics, Inc.,
Otsuka America Pharmaceutical, Inc., RemedyMD, Sanofi, Seattle Genetics,
Sigma-Tau Pharmaceuticals, Soligenix, Inc., StemCyte, A Global Cord
Blood Therapeutics Co., Stemsoft Software, Inc., Swedish Orphan
Biovitrum, Tarix Pharmaceuticals, Teva Neuroscience, Inc., THERAKOS,
Inc. and Wellpoint, Inc. P Stratton is supported by the Intramural
Program of the National Institutes of Child Health and Human
Development.
NR 105
TC 15
Z9 15
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD APR
PY 2014
VL 49
IS 4
BP 477
EP 484
DI 10.1038/bmt.2013.211
PG 8
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA AF1VB
UT WOS:000334500900002
PM 24419521
ER
PT J
AU Inamoto, Y
Jagasia, M
Wood, WA
Pidala, J
Palmer, J
Khera, N
Weisdorf, D
Carpenter, PA
Flowers, MED
Jacobsohn, D
Martin, PJ
Lee, SJ
Pavletic, SZ
AF Inamoto, Y.
Jagasia, M.
Wood, W. A.
Pidala, J.
Palmer, J.
Khera, N.
Weisdorf, D.
Carpenter, P. A.
Flowers, M. E. D.
Jacobsohn, D.
Martin, P. J.
Lee, S. J.
Pavletic, S. Z.
CA Chronic GVHD Consortium
TI Investigator feedback about the 2005 NIH diagnostic and scoring criteria
for chronic GVHD
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE allogeneic hematopoietic cell transplantation; chronic GVHD; consensus;
controversy; National Institutes of Health
ID VERSUS-HOST-DISEASE; CONSENSUS DEVELOPMENT PROJECT; WORKING
GROUP-REPORT; CLINICAL-TRIALS; ACTIVITY INDEX; SEVERITY;
TRANSPLANTATION; VALIDATION; CONSORTIUM; SURVIVAL
AB The 2005 National Institutes of Health (NIH) consensus criteria for chronic GVHD have set standards for reporting. Many questions, however, have arisen regarding their implementation and utilization. To identify perceived areas of controversy, we conducted an international survey on diagnosis and scoring of chronic GVHD. Agreement was observed for 50-83% of the 72 questions in 7 topic areas. There was agreement on the need for modifying criteria in six situations: two or more distinctive manifestations should be enough to diagnose chronic GVHD; symptoms that are not due to chronic GVHD should be scored differently; active disease and fixed deficits should be distinguished; a minimum threshold body surface area of hidebound skin involvement should be required for a skin score of 3; asymptomatic oral lichenoid changes should be considered a score 1; and lung biopsy should be unnecessary to diagnose chronic GVHD in a patient with bronchiolitis obliterans as the only manifestation. The survey also identified 26 points of controversy. Whenever possible, studies should be conducted to confirm the appropriateness of any revisions. In cases where data are not available, clarification of the NIH recommendations by consensus is necessary. This survey should inform future research in the field and revisions of the current consensus criteria.
C1 [Inamoto, Y.; Carpenter, P. A.; Flowers, M. E. D.; Martin, P. J.; Lee, S. J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
[Jagasia, M.] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplant Program, Nashville, TN USA.
[Wood, W. A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Pidala, J.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Palmer, J.] Med Coll Wisconsin, Div Hematol Oncol, Milwaukee, WI 53226 USA.
[Khera, N.] Mayo Clin Arizona, Div Hematol Oncol, Scottsdale, AZ USA.
[Weisdorf, D.] Univ Minnesota, Med Ctr, Blood & Marrow Transplant Program, Minneapolis, MN 55455 USA.
[Jacobsohn, D.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Div Blood & Marrow Transplantat, Washington, DC 20010 USA.
[Pavletic, S. Z.] NCI, Bethesda, MD 20892 USA.
RP Inamoto, Y (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D5-290, Seattle, WA 98109 USA.
EM yinamoto@fhcrc.org
OI Wood, William/0000-0001-7439-2543
FU National Institutes of Health (NIH) [CA118953, CA163438]; The Chronic
GVHD Consortium [U54 CA163438]; NIH Rare Diseases Clinical Research
Network (RDCRN), supported through collaboration between the NIH Office
of Rare Diseases Research (ORDR) at the National Center for Advancing
Translational Science (NCATS); National Cancer Institute; Fred
Hutchinson Cancer Research Center
FX We thank all participants in the web survey for their valuable time and
opinions. This work was supported by grants CA118953 and CA163438 from
the National Institutes of Health (NIH). The Chronic GVHD Consortium
(U54 CA163438) is a part of the NIH Rare Diseases Clinical Research
Network (RDCRN), supported through collaboration between the NIH Office
of Rare Diseases Research (ORDR) at the National Center for Advancing
Translational Science (NCATS), the National Cancer Institute, and the
Fred Hutchinson Cancer Research Center. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 33
TC 8
Z9 8
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD APR
PY 2014
VL 49
IS 4
BP 532
EP 538
DI 10.1038/bmt.2013.225
PG 7
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA AF1VB
UT WOS:000334500900011
PM 24464142
ER
PT J
AU Williams, KM
Hnatiuk, O
Mitchell, SA
Baird, K
Gadalla, SM
Steinberg, SM
Shelhamer, J
Carpenter, A
Avila, D
Taylor, T
Grkovic, L
Pulanic, D
Comis, LE
Blacklock-Schuver, B
Gress, RE
Pavletic, SZ
AF Williams, K. M.
Hnatiuk, O.
Mitchell, S. A.
Baird, K.
Gadalla, S. M.
Steinberg, S. M.
Shelhamer, J.
Carpenter, A.
Avila, D.
Taylor, T.
Grkovic, L.
Pulanic, D.
Comis, L. E.
Blacklock-Schuver, B.
Gress, R. E.
Pavletic, S. Z.
TI NHANES III equations enhance early detection and mortality prediction of
bronchiolitis obliterans syndrome after hematopoietic SCT
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE bronchiolitis obliterans syndrome; pulmonary function equation;
hematopoietic SCT; chronic GVHD
ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; CONSENSUS DEVELOPMENT
PROJECT; BONE-MARROW-TRANSPLANTATION; WORKING GROUP-REPORT; CHRONIC
GVHD; PULMONARY COMPLICATIONS; NUTRITION EXAMINATION; LABORATORY
MARKERS; REFERENCE VALUES
AB Bronchiolitis obliterans syndrome (BOS) is a serious complication of chronic GVHD (cGVHD) following HSCT (hematopoietic SCT). The clinical diagnosis of BOS is based on pulmonary function test (PFT) abnormalities including: FEV1<75% predicted and obstructive FEV1/VC ratio, calculated using reference equations. We sought to determine if the frequency of clinical diagnoses and severity of BOS would be altered by using the recommended NHANES III vs older equations (Morris/Goldman/Bates, MGB) in 166 cGVHD patients, median age 48 (range: 12-67). We found that NHANES III equations significantly increased the prevalence of BOS, with an additional 11% (18/166) meeting diagnostic criteria by revealing low FEV1 (<75%) (P<0.0001), and six additional patients by obstructive ratio (vs MBG). Collectively, this led to an increase of BOS incidence from 17 (29/166) to 29% (41/166). For patients with severe BOS, (FEV1<35%), NHANES III equations correctly predicted death 71.4% vs 50% using MGB. In conclusion, the use of NHANES III equations markedly increases the proportion of cases meeting diagnostic criteria for BOS and improves prediction of survival.
C1 [Williams, K. M.; Carpenter, A.; Avila, D.; Taylor, T.; Blacklock-Schuver, B.; Gress, R. E.; Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Williams, K. M.] George Washington Univ, Childrens Natl Med Ctr, Med Ctr, Ctr Canc & Blood Disorders,Div Blood & Marrow Tra, Washington, DC 20010 USA.
[Hnatiuk, O.] Raymond G Murphy VA Med Ctr, Pulm Crit Care & Sleep Med Serv, Albuquerque, NM USA.
[Mitchell, S. A.] NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, NIH, Bethesda, MD 20892 USA.
[Baird, K.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Gadalla, S. M.] NCI, DCEG, Clin Genet Branch, Bethesda, MD 20892 USA.
[Steinberg, S. M.] NCI, Biostat & Data Management Sect, OCD, CCR,NIH, Bethesda, MD 20892 USA.
[Shelhamer, J.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Grkovic, L.; Pulanic, D.] Clin Hosp, Ctr Zagreb, Dept Internal Med, Div Hematol, Zagreb, Croatia.
[Comis, L. E.] NIH, Bethesda, MD 20892 USA.
RP Williams, KM (reprint author), George Washington Univ, Childrens Natl Med Ctr, Med Ctr, Ctr Canc & Blood Disorders,Div Blood & Marrow Tra, 111 Michigan Ave,NW, Washington, DC 20010 USA.
EM williaki@mail.nih.gov
FU National Institutes of Health intramural funds
FX We acknowledge Dr David Jacobsohn for his thorough review of this
manuscript. National Institutes of Health intramural funds supported
this research.
NR 37
TC 3
Z9 3
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD APR
PY 2014
VL 49
IS 4
BP 561
EP 566
DI 10.1038/bmt.2013.222
PG 6
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA AF1VB
UT WOS:000334500900015
PM 24419526
ER
PT J
AU Miyano, Y
Tahara, S
Sakata, I
Sakai, T
Abe, H
Kimura, S
Kurotani, R
AF Miyano, Yuki
Tahara, Shigeyuki
Sakata, Ichiro
Sakai, Takafumi
Abe, Hiroyuki
Kimura, Shioko
Kurotani, Reiko
TI Regulation of LH/FSH expression by secretoglobin 3A2 in the mouse
pituitary gland
SO CELL AND TISSUE RESEARCH
LA English
DT Article
DE SCGB3A2; Nkx2-1; C/EBP; LH/FSH; Pituitary
ID BINDING-PROTEIN-ALPHA; UTEROGLOBIN-RELATED PROTEIN-1; LUNG
MORPHOGENESIS; GENE-EXPRESSION; TRANSCRIPTION FACTOR; HOMEODOMAIN;
TTF-1; FETAL; EMBRYOS; T/EBP
AB Secretoglobin (SCGB) 3A2 was originally identified as a downstream target for the homeodomain transcription factor NKX2-1 in the lung. NKX2-1 plays a role in the genesis and expression of genes in the thyroid, lung and ventral forebrain; Nkx2-1-null mice have no thyroid and pituitary and severely hypoplastic lungs and hypothalamus. To demonstrate whether SCGB3A2 plays any role in pituitary hormone production, NKX2-1 and SCGB3A2 expression in the mouse pituitary gland was examined by immunohistochemical analysis and RT-PCR. NKX2-1 was localized in the posterior pituitary lobe, whereas SCGB3A2 was observed in both anterior and posterior lobes as shown by immunohistochemistry and RT-PCR. Expression of CCAAT-enhancer binding proteins (C/EBPs), which regulate mouse Scgb3a2 transcription, was also examined by RT-PCR. C/EBP beta, gamma, delta and zeta were expressed in the adult mouse pituitary gland. SCGB3A2 was expressed in the anterior and posterior lobes from postnatal days 1 and 5, respectively and the areas where SCGB3A2 expression was found coincided with the area where FSH-secreting cells were found. Double-staining for SCGB3A2 and pituitary hormones revealed that SCGB3A2 was mainly localized in gonadotrophs in 49 % of FSH-secreting cells and 47 % of LH-secreting cells. In addition, SCGB3A2 dramatically inhibited LH and FSH mRNA expression in rat pituitary primary cell cultures. These results suggest that SCGB3A2 regulates FSH/LH production in the anterior pituitary lobe and that transcription factors other than NKX2-1 may regulate SCGB3A2 expression.
C1 [Miyano, Yuki; Abe, Hiroyuki; Kurotani, Reiko] Yamagata Univ, Fac Engn, Yonezawa, Yamagata 9928510, Japan.
[Tahara, Shigeyuki] Nippon Med Sch, Dept Neurosurg, Tokyo 1138603, Japan.
[Sakata, Ichiro; Sakai, Takafumi] Saitama Univ, Grad Sch Sci & Engn, Div Life Sci, Area Regulatory Biol, Saitama 3388570, Japan.
[Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Kurotani, R (reprint author), Yamagata Univ, Fac Engn, Yonezawa, Yamagata 9928510, Japan.
EM kurotanir@yz.yamagata-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology-Japan
FX We thank Ms. Sayaka Komino (Yamagata University) and Dr. Ken Fujiwara
(Jichi Medical University) for technical support and advice. This study
was supported by a Grant-in-Aid for Young Scientists (C) and by the
Dissemination of Tenure Tracking System Program of Ministry of
Education, Culture, Sports, Science and Technology-Japan.
NR 26
TC 0
Z9 0
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0302-766X
EI 1432-0878
J9 CELL TISSUE RES
JI Cell Tissue Res.
PD APR
PY 2014
VL 356
IS 1
BP 253
EP 260
DI 10.1007/s00441-014-1794-z
PG 8
WC Cell Biology
SC Cell Biology
GA AE7JY
UT WOS:000334175100023
PM 24514953
ER
PT J
AU Grosz, M
Kolter, J
Paprotka, K
Winkler, AC
Schafer, D
Chatterjee, SS
Geiger, T
Wolz, C
Ohlsen, K
Otto, M
Rudel, T
Sinha, B
Fraunholz, M
AF Grosz, Magdalena
Kolter, Julia
Paprotka, Kerstin
Winkler, Ann-Cathrin
Schaefer, Daniel
Chatterjee, Som Subra
Geiger, Tobias
Wolz, Christiane
Ohlsen, Knut
Otto, Michael
Rudel, Thomas
Sinha, Bhanu
Fraunholz, Martin
TI Cytoplasmic replication of Staphylococcus aureus upon phagosomal escape
triggered by phenol-soluble modulin alpha
SO CELLULAR MICROBIOLOGY
LA English
DT Article
ID FIBRONECTIN-BINDING PROTEINS; CULTURED ENDOTHELIAL-CELLS;
LISTERIA-MONOCYTOGENES; EPITHELIAL-CELLS; DELTA-HEMOLYSIN; VIRULENCE
DETERMINANTS; FRANCISELLA-TULARENSIS; HUMAN KERATINOCYTES; HUMAN
MACROPHAGES; MEDIATE ESCAPE
AB Staphylococcus aureus is a Gram-positive human pathogen that is readily internalized by professional phagocytes such as macrophages and neutrophils but also by non-professional phagocytes such as epithelial or endothelial cells. Intracellular bacteria have been proposed to play a role in evasion of the innate immune system and may also lead to dissemination within migrating phagocytes. Further, S.aureus efficiently lyses host cells with a battery of cytolytic toxins. Recently, phenol-soluble modulins (PSM) have been identified to comprise a genus-specific family of cytolytic peptides. Of these the PSM peptides have been implicated in killing polymorphonuclear leucocytes after phagocytosis. We questioned if the peptides were active in destroying endosomal membranes to avoid lysosomal killing of the pathogen and monitored integrity of infected host cell endosomes by measuring the acidity of the intracellular bacterial microenvironment via flow cytometry and by a reporter recruitment technique. Isogenic mutants of the methicillin-resistant S.aureus (MRSA) strains USA300 LAC, USA400 MW2 as well as the strongly cytolytic methicillin-sensitive strain 6850 were compared with their respective wild type strains. In all three genetic backgrounds, PSM mutants were unable to escape from phagosomes in non-professional (293, HeLa, EAhy.926) and professional phagocytes (THP-1), whereas mutants in PSM and -toxin as well as -toxin, phosphatidyl inositol-dependent phospholipase C and Panton Valentine leucotoxin escaped with efficiencies of the parental strains. S.aureus replicated intracellularly only in presence of a functional PSM operon thereby illustrating that bacteria grow in the host cell cytoplasm upon phagosomal escape.
C1 [Grosz, Magdalena; Kolter, Julia; Paprotka, Kerstin; Winkler, Ann-Cathrin; Rudel, Thomas; Fraunholz, Martin] Univ Wurzburg, Dept Microbiol, Bioctr, D-97074 Wurzburg, Germany.
[Grosz, Magdalena; Schaefer, Daniel; Sinha, Bhanu] Inst Hyg & Med Microbiol, D-97080 Wurzburg, Germany.
[Chatterjee, Som Subra; Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, Pathogen Mol Genet Sect, NIH, Bethesda, MD 20892 USA.
[Geiger, Tobias; Wolz, Christiane] Inst Med Microbiol & Hyg, D-72076 Tubingen, Germany.
[Ohlsen, Knut] Univ Wurzburg, Inst Mol Infect Biol, D-97080 Wurzburg, Germany.
[Sinha, Bhanu] Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol & Infect Prevent, Groningen, Netherlands.
RP Fraunholz, M (reprint author), Univ Wurzburg, Dept Microbiol, Bioctr, D-97074 Wurzburg, Germany.
EM martin.fraunholz@uni-wuerzburg.de
OI Fraunholz, Martin/0000-0002-4581-6244
FU German Science Foundation (DFG) [TRR34, FR1504/2-1]; National Institute
of Allergy and Infectious Diseases (NIAID), US National Institutes of
Health; NIAID/NIH [HHSN272200700055C]
FX We thank the German Science Foundation (DFG; http://www.dfg.de) for
funding this project within the Transregional Research Collaborative
TRR34, project C6 (M. G., B. S.), B1 (C. W., T. G.), C11 (A.-C. W., T.
R.) and within FR1504/2-1 (M. F.) and the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases (NIAID), US
National Institutes of Health (http://www.nih.gov; M.O.). We are
grateful to Barbara Conrad and Heidi Linss for excellent technical
assistance, Christiane Goerke and Bernhard Krismer (Tubingen, Germany)
for kindly supplying strain 6850 pCG33 and pBASE6, respectively, and
Andreas Demuth for critically reading the manuscript. The alpha-toxin
mutant (NE1354) was obtained through the Network on Antimicrobial
Resistance in Staphylococcus aureus (NARSA) Program supported under
NIAID/NIH Contract No. HHSN272200700055C. The authors declare no
conflict of interests.
NR 94
TC 38
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U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-5814
EI 1462-5822
J9 CELL MICROBIOL
JI Cell Microbiol.
PD APR
PY 2014
VL 16
IS 4
BP 451
EP 465
DI 10.1111/cmi.12233
PG 15
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA AD0UR
UT WOS:000332950100001
PM 24164701
ER
PT J
AU Panackal, AA
Williamson, PR
AF Panackal, Anil A.
Williamson, Peter R.
TI The Promise of Immunogenomics at the Bedside: Genetic Risk of Intra-
Abdominal Candidiasis*
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE antifungal; Candida; cytokines; immunogenetics; invasive candidiasis
ID INVASIVE CANDIDIASIS; POLYMORPHISM; DIAGNOSIS; CULTURE; HUMANS
C1 [Panackal, Anil A.; Williamson, Peter R.] NIAID, Translat Mycol Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Panackal, AA (reprint author), NIAID, Translat Mycol Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 AI999999]
NR 15
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD APR
PY 2014
VL 42
IS 4
BP 1019
EP 1020
DI 10.1097/CCM.0000000000000252
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA AC9FL
UT WOS:000332839700068
PM 24633117
ER
PT J
AU Liu, WH
Ralston, E
AF Liu, Wenhua
Ralston, Evelyn
TI A new directionality tool for assessing microtubule pattern alterations
SO CYTOSKELETON
LA English
DT Article
DE texture correlation; muscle fiber; directionality; Duchenne muscular
dystrophy; microtubule; gray-level co-occurrence matrices
ID GOLGI-COMPLEX; TEXTURAL FEATURES; SKELETAL-MUSCLE; MYOGENIC CELLS;
ORGANIZATION; CYTOSKELETON; DIFFERENTIATION; DYSTROPHIN; RETRIEVAL;
FIBERS
AB The cytoskeleton (microtubules, actin and intermediate filaments) has a cell type-specific spatial organization that is essential and reflects cell health. We are interested in understanding how changes in the organization of microtubules contribute to muscle diseases such as Duchenne muscular dystrophy (DMD). The grid-like immunofluorescence microtubule pattern of fast-twitch muscle fibers lends itself well to visual assessment. The more complicated pattern of other fibers does not. Furthermore, visual assessment is not quantitative. Therefore we have developed a robust software program for detecting and quantitating microtubule directionality. Such a tool was necessary because existing methods focus mainly on local image features and are not well suited for microtubules. Our tool, texture detection technique (TeDT), is based on the Haralick texture method and takes into account both local and global features with more weight on the latter. The results are expressed in a graphic form responsive to subtle variations in microtubule distribution, while a numerical score allows quantitation of directionality. Furthermore, the results are not affected by imaging conditions or post-imaging procedures. TeDT successfully assesses test images and microtubules in fast-twitch fibers of wild-type and mdx mice (a model for DMD); TeDT also identifies and quantitates microtubule directionality in slow-twitch fibers, in the fibers of young animals, and in other mouse models which could not be assessed visually. TeDT might also contribute to directionality assessments of other cytoskeletal components. Published 2014 Wiley Periodicals Inc. This article is a US government work and, as such, is in the public domain in the United States of America.
C1 [Liu, Wenhua; Ralston, Evelyn] NIAMSD, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA.
RP Liu, WH (reprint author), NIAMSD, Light Imaging Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM liuw5@mail.nih.gov
FU Intramural Program of National Institute of Arthritis and
Musculoskeletal and Skin Diseases
FX The authors thank Jim Ervasti (University of Minnesota) for the mouse
muscle samples, provided in the context of a previous collaboration,
Kristien J.M. Zaal, Sarah Oddoux, Aster Kenea and Andrew Milgroom from
the Light Imaging Section for sample images, critical reading of the
manuscript, and many stimulating discussions. This work was supported by
the Intramural Program of National Institute of Arthritis and
Musculoskeletal and Skin Diseases.
NR 32
TC 3
Z9 3
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1949-3584
EI 1949-3592
J9 CYTOSKELETON
JI Cytoskeleton
PD APR
PY 2014
VL 71
IS 4
BP 230
EP 240
DI 10.1002/cm.21166
PG 11
WC Cell Biology
SC Cell Biology
GA AE9WM
UT WOS:000334362200002
PM 24497496
ER
PT J
AU Pedersen, LC
Birnbaum, LS
Gosavi, RA
Knudsen, GA
AF Pedersen, Lars C.
Birnbaum, Linda S.
Gosavi, Rajendrakumar A.
Knudsen, Gabriel A.
TI Crystallographic Analysis and Mimicking of Estradiol Binding: Pedersen
et al. Respond
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Letter
ID BROMINATED FLAME RETARDANTS; ESTROGEN SULFOTRANSFERASE; METABOLITES;
MECHANISM; CELLS
C1 [Pedersen, Lars C.; Gosavi, Rajendrakumar A.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Birnbaum, Linda S.; Knudsen, Gabriel A.] NCI, Lab Toxicol & Toxicokinet, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
RP Pedersen, LC (reprint author), NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
EM pederse2@niehs.nih.gov
RI Knudsen, Gabriel/G-3706-2013
OI Knudsen, Gabriel/0000-0002-7208-6451
NR 9
TC 0
Z9 0
U1 0
U2 3
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD APR
PY 2014
VL 122
IS 4
BP A91
EP A92
DI 10.1289/ehp.1307987R
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA AE5ZY
UT WOS:000334069100005
PM 24691124
ER
PT J
AU Verner, MA
Andersen, ME
Clewell, HJ
Longnecker, MP
AF Verner, Marc-Andre
Andersen, Melvin E.
Clewell, Harvey J., III
Longnecker, Matthew P.
TI Prenatal PCB-153 Exposure and Decreased Birth Weight: Verner et al.
Respond
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Letter
C1 [Verner, Marc-Andre] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Verner, Marc-Andre] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Andersen, Melvin E.; Clewell, Harvey J., III] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA.
[Longnecker, Matthew P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Verner, MA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
EM marcandre.verner@channing.harvard.edu
OI Longnecker, Matthew/0000-0001-6073-5322; Verner,
Marc-Andre/0000-0002-1935-8913
NR 4
TC 0
Z9 0
U1 0
U2 4
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD APR
PY 2014
VL 122
IS 4
BP A89
EP A90
DI 10.1289/ehp.1307796R
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA AE5ZY
UT WOS:000334069100003
PM 24691074
ER
PT J
AU Burkart, KM
Manichaikul, A
Wilk, JB
Ahmed, FS
Burke, GL
Enright, P
Hansel, NN
Haynes, D
Heckbert, SR
Hoffman, EA
Kaufman, JD
Kurai, J
Loehr, L
London, SJ
Meng, Y
O'Connor, GT
Oelsner, E
Petrini, M
Pottinger, TD
Powell, CA
Redline, S
Rotter, JI
Smith, LJ
Artigas, MS
Tobin, MD
Tsai, MY
Watson, K
White, W
Young, TR
Rich, SS
Barr, RG
AF Burkart, Kristin M.
Manichaikul, Ani
Wilk, Jemma B.
Ahmed, Firas S.
Burke, Gregory L.
Enright, Paul
Hansel, Nadia N.
Haynes, Demondes
Heckbert, Susan R.
Hoffman, Eric A.
Kaufman, Joel D.
Kurai, Jun
Loehr, Laura
London, Stephanie J.
Meng, Yang
O'Connor, George T.
Oelsner, Elizabeth
Petrini, Marcy
Pottinger, Tess D.
Powell, Charles A.
Redline, Susan
Rotter, Jerome I.
Smith, Lewis J.
Artigas, Maria Soler
Tobin, Martin D.
Tsai, Michael Y.
Watson, Karol
White, Wendy
Young, Taylor R.
Rich, Stephen S.
Barr, R. Graham
TI APOM and high-density lipoprotein cholesterol are associated with lung
function and per cent emphysema
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; GENOME-WIDE ASSOCIATION; AIR-FLOW
OBSTRUCTION; ENDOTHELIAL GROWTH-FACTOR; SUBTILISIN/KEXIN TYPE 9;
CORONARY-HEART-DISEASE; APOLIPOPROTEIN-M; MONOCLONAL-ANTIBODY; MESA
LUNG; SUBCLINICAL ATHEROSCLEROSIS
AB Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD.
We assessed the association of lung function with 2100 genes selected for cardiovascular diseases among 20 077 European-Americans and 6900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with per cent emphysema and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and per cent emphysema.
We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3 x 10(-6)) and a second (rs707974) in the combined European-American and African-American analysis (p =1.38 x 10(-7)). Both single-nucleotide polyrnorphisms (SNPs) flank the gene for apolipoprotein M (APOM), a component of high-density lipoprotein (HDL) cholesterol. Both were replicated in an independent cohort. SNPs in a second gene related to apolipoprotein M and HDL, PCSK9, were associated with FEV1/FVC ratio among African-Americans. rs707974 was associated with per cent emphysema among European-Americans and African-Americans and APOM expression was related to FEV1/FVC ratio and per cent emphysema. Higher HDL levels were associated with lower FEVi/FVC ratio and greater per cent emphysema.
These findings suggest a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.
C1 [Burkart, Kristin M.; Ahmed, Firas S.; Oelsner, Elizabeth; Pottinger, Tess D.; Barr, R. Graham] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA.
[Manichaikul, Ani; Rich, Stephen S.] Univ Virginia, Sch Med, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
[Wilk, Jemma B.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Wilk, Jemma B.; Redline, Susan] Harvard Univ, Sch Med, Boston, MA USA.
[Ahmed, Firas S.] Columbia Univ Coll Phys & Surg, Dept Radiol, New York, NY 10032 USA.
[Burke, Gregory L.] Wake Forest Sch Med, Dept Publ Hlth Sci, Winston Salem, NC USA.
[Enright, Paul] Univ Arizona, Dept Med, Tucson, AZ USA.
[Hansel, Nadia N.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Haynes, Demondes; Petrini, Marcy] Univ Mississippi, Dept Med, Jackson, MS 39216 USA.
[Heckbert, Susan R.; Kaufman, Joel D.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Hoffman, Eric A.] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA.
[Kaufman, Joel D.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA.
[Kaufman, Joel D.] Univ Washington, Dept Med, Seattle, WA USA.
[Kaufman, Joel D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Kurai, Jun; Powell, Charles A.] Mt Sinai Hosp, Dept Med, New York, NY 10029 USA.
[Loehr, Laura] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[London, Stephanie J.] Natl Inst Hlth & Human Serv, Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
[Meng, Yang] Broad Inst MIT & Harvard, Cambridge, MA USA.
[O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA.
[O'Connor, George T.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Redline, Susan] Brigham & Womens Hosp, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Smith, Lewis J.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Artigas, Maria Soler; Tobin, Martin D.] Univ Leicester, Dept Hlth Sci, Genet Epidemiol Grp, Leicester, Leics, England.
[Tobin, Martin D.] Glenfield Hosp, Leicester Resp Biomed Res Unit, Natl Inst Hlth Res, Leicester, Leics, England.
[Tsai, Michael Y.] Univ Minnesota, Dept Lab Med Pathol, Minneapolis, MN USA.
[Watson, Karol] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[White, Wendy] Tougaloo Coll, Jackson Heart Study, Tougaloo, MS USA.
[Young, Taylor R.] MIT, Broad Inst, Cambridge, MA 02139 USA.
[Young, Taylor R.] Harvard Univ, Cambridge, MA 02138 USA.
[Barr, R. Graham] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
RP Barr, RG (reprint author), Columbia Univ, Med Ctr, 630 West 168th St,PH 9 East Room 105, New York, NY 10032 USA.
EM rgb9@columbia.edu
RI Kaufman, Joel/B-5761-2008; Soler Artigas, Maria/L-6529-2013;
OI Kaufman, Joel/0000-0003-4174-9037; Soler Artigas,
Maria/0000-0002-3213-1107; Smith, Lewis J/0000-0002-4728-1562;
Pottinger, Tess/0000-0003-0647-5712; POWELL,
CHARLES/0000-0003-3509-891X; London, Stephanie/0000-0003-4911-5290
FU National Institutes of Health (NIH)/National Heart, Lung, and Blood
Institute (NHLBI) [RC1-HL100543, R01-HL077612, R01-HL093081];
NIH/National Human Genome Research Institute [U01HG004402]; NIH
[HHSN268200625226C, N01-HC-55015, N01-HC-55016, N01-HC-55021,
N01-HC-55019, N01-HC-55020, N01-HC-55017, N01-HC-55018, UL1RR025005];
NIH Roadmap for Medical Research; Broad Institute [N01-HC-65226];
Coronary Artery Risk Development in Young Adults (CARDIA) [N01-HC-48047,
N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095, N01-HC-45204,
N01-HC-45205, N01-HC-05187, N01-HC-45134, N01-HC-95100]; Cleveland
Family Study (CFS) [RO1 HL46380-01-16]; NHLBI [N01-HC-85239,
N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083,
N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103,
N01-HC-75150, N01-HC-45133, N01 HC-55222, U01 HL080295, AG-023629,
AG-15928, AG-20098, AG-027058]; Environmental Protection Agency (EPA)
[RD831697]; Medical Research Council [G0902313]; National Institute for
Health Research; Division of Intramural Research, National Institute of
Environmental Health Sciences, NIH; Department of Health and Human
Services; [N01-HC-25195]; [N01-HC-95170]; [N01-HC-95171];
[N01-HC-95172]; [N01-HC-95159]; [N01-HC-95160]; [N01-HC-95161];
[N01-HC-95162]; [N01-HC-95163]; [N01-HC-95164]; [N01-HC-95165];
[N01-HC-95166]; [N01-HC-95167]; [N01-HC-95168]; [N01-HC-95169];
[RR-024156]; [R01-HL-071051]; [R01-HL-071205]; [R01-HL-071250];
[R01-HL-071251]; [R01-HL-071252]; [R01-HL-071258]; [R01-HL-071259];
[HHSN268201100005C]; [HHSN268201100006C]; [HHSN268201100007C];
[HHSN268201100008C]; [HHSN268201100009C]; [HHSN268201100010C];
[HHSN268201100011C]; [HHSN268201100012C]; [R01HL087641];
[R01HL59367]; [R01HL086694]
FX National Institutes of Health (NIH)/National Heart, Lung, and Blood
Institute (NHLBI) grants RC1-HL100543, R01-HL077612 and R01-HL093081, in
addition to the following. Atherosclerosis Risk in Communities:
HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367,
R01HL086694, NIH/National Human Genome Research Institute contract
U01HG004402, NIH contract HHSN268200625226C, N01-HC-55015, N01-HC-55016,
N01-HC-55021, N01-HC-55019, N01-HC-55020, N01-HC-55017 and N01-HC-55018,
and UL1RR025005, a component of the NIH and NIH Roadmap for Medical
Research; Broad Institute: N01-HC-65226; Coronary Artery Risk
Development in Young Adults (CARDIA): N01-HC-48047, N01-HC-48048,
N01-HC-48049, N01-HC-48050, N01-HC-95095, N01-HC-45204, N01-HC-45205,
N01-HC-05187, N01-HC-45134 and N01-HC-95100; Cleveland Family Study
(CFS): RO1 HL46380-01-16; Cardiovascular Health Study (CHS): CHS
research was supported by NHLBI contracts N01-HC-85239, N01-HC-85079,
N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084,
N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01-HC-75150,
N01-HC-45133, N01 HC-55222, U01 HL080295, AG-023629, AG-15928, AG-20098
and AG-027058 with additional contribution from National Institute of
Neurological Diseases and the National Institute on Aging; Framingham
Heart Study (FHS): N01-HC-25195; Jackson Heart Study (JHS):
N01-HC-95170, N01-HC-95171 and N01-HC-95172; Multi-Ethnic Study of
Atherosclerosis (MESA): N01-HC-95159, N01-HC-95160, N01-HC-95161,
N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166,
N01-HC-95167, N01-HC-95168, N01-HC-95169, R01-HL093081, RR-024156,
R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251,
R01-HL-071252, R01-HL-071258, R01-HL-071259 and Environmental Protection
Agency (EPA) grant RD831697; SpiroMeta: M.D. Tobin holds a Medical
Research Council Senior Clinical Fellowship (G0902313) and research
undertaken by M.D. Tobin was part-funded by the National Institute for
Health Research. S.J. London is supported by the Division of Intramural
Research, National Institute of Environmental Health Sciences, NIH and
the Department of Health and Human Services.
NR 99
TC 10
Z9 10
U1 0
U2 7
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD APR
PY 2014
VL 43
IS 4
BP 1003
EP 1017
DI 10.1183/09031936.00147612
PG 15
WC Respiratory System
SC Respiratory System
GA AE8OT
UT WOS:000334261900015
PM 23900982
ER
PT J
AU Kouprina, N
Tomilin, AN
Masumoto, H
Earnshaw, WC
Larionov, V
AF Kouprina, Natalay
Tomilin, Alexey N.
Masumoto, Hiroshi
Earnshaw, William C.
Larionov, Vladimir
TI Human artificial chromosomebased gene delivery vectors for biomedicine
and biotechnology
SO EXPERT OPINION ON DRUG DELIVERY
LA English
DT Review
DE gene delivery vector; gene expression; gene therapy; human artificial
chromosomes insulators; TAR cloning
ID PLURIPOTENT STEM-CELLS; TRANSFORMATION-ASSOCIATED RECOMBINATION; YEAST
SACCHAROMYCES-CEREVISIAE; MICROCELL-MEDIATED TRANSFER; HUMAN
Y-CHROMOSOME; CONDITIONAL CENTROMERE; TRANSGENE EXPRESSION; COMPLEX
GENOMES; HOMOLOGOUS RECOMBINATION; FUNCTIONAL GENOMICS
AB Introduction: Human artificial chromosomes (HACs) have several advantages over viruses as gene delivery vectors, including stable episomal maintenance in a single copy and the ability to carry large gene inserts.
Areas covered: In this review, we summarise recent work on gene transfer into mammalian cells using the HACs. HACs allow therapeutic transgenes to be expressed in target cells under conditions that recapitulate the physiological regulation of endogenous loci.
Expert opinion: Based on the published data, the HAC vectors have a great potential for gene therapy, regenerative medicine, screening of anticancer drugs and biotechnology.
C1 [Kouprina, Natalay; Larionov, Vladimir] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
[Tomilin, Alexey N.] Russian Acad Sci, Inst Cytol, St Petersburg 194064, Russia.
[Masumoto, Hiroshi] Kazusa DNA Res Inst, Dept Human Genome Res, Lab Cell Engn, Kisarazu, Chiba 2920818, Japan.
[Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
RP Kouprina, N (reprint author), NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
EM kouprinn@mail.nih.gov
RI Tomilin, Alexey/C-3361-2014
OI Tomilin, Alexey/0000-0002-1137-7167
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research, USA; Wellcome Trust [073915]; Ministry of
Education, Culture, Sports, Science and Technology of Japan; Kazusa DNA
Research Institute Foundation; Goskontrakt [02.512.11.2085]; Russian
Academy of Sciences Molecular and Cellular Biology; Presidium of the
Russian Academy of Sciences
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research, USA (N.K., V.L.),
the Wellcome Trust of which WC Earnshaw is a Principal Research Fellow
(grant number 073915), the Grand-in-Aid for Scientific Research from
Ministry of Education, Culture, Sports, Science and Technology of Japan
(H.M.), the Kazusa DNA Research Institute Foundation, by Goskontrakt
02.512.11.2085 (A.V.T.) and by the program of the Russian Academy of
Sciences Molecular and Cellular Biology. AN Tomilin was also supported
by the Program of the Presidium of the Russian Academy of Sciences
"Molecular and Cellular Biology".
NR 132
TC 24
Z9 25
U1 3
U2 31
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1742-5247
EI 1744-7593
J9 EXPERT OPIN DRUG DEL
JI Expert Opin. Drug Deliv.
PD APR
PY 2014
VL 11
IS 4
BP 517
EP 535
DI 10.1517/17425247.2014.882314
PG 19
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AE8NP
UT WOS:000334258900006
PM 24479793
ER
PT J
AU Fortner, RT
Oh, H
Daugherty, SE
Xu, X
Hankinson, SE
Ziegler, RG
Eliassen, AH
AF Fortner, Renee T.
Oh, Hannah
Daugherty, Sarah E.
Xu, Xia
Hankinson, Susan E.
Ziegler, Regina G.
Eliassen, A. Heather
TI Analgesic Use and Patterns of Estrogen Metabolism in Premenopausal Women
SO HORMONES & CANCER
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CHROMATOGRAPHY-MASS SPECTROMETRY;
15 URINARY ESTROGENS; SERVICES-TASK-FORCE; BREAST-CANCER RISK;
COLORECTAL-CANCER; PRIMARY PREVENTION; ENZYME-INHIBITORS; NURSES HEALTH;
ASPIRIN
AB Analgesic use has been hypothesized to reduce the risk of some cancers, with inverse associations between analgesics and colon cancer, and suggestive inverse associations for breast cancer. Estrogen metabolites (EM) have genotoxic and estrogenic potential; genotoxicity may differ by hydroxylation pathway. Analgesic use may impact patterns of estrogen metabolism; effects of analgesics on disease risk could be mediated through these patterns. We conducted a cross-sectional study among 603 premenopausal women in the Nurses' Health Study II. Frequency of aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen use was reported via questionnaire; average frequency in 1997 and 1999 was calculated. Women provided urine samples between 1996 and 1999, collected during the mid-luteal phase of the menstrual cycle. Urinary EM were quantified using high-performance liquid chromatography-tandem mass spectrometry. We observed no association between analgesic use and estradiol, estrone, or specific pathways of estrogen metabolism. Women reporting more frequent aspirin use had lower methylated 2-catechols (e.g., 2-hydroxyestrone-3-methyl ether, 2+ days/week vs. non-use: 0.95 vs. 1.21 pmol/mg creatinine; p (difference) = 0.01, p (trend) = 0.07). Non-aspirin NSAID use was positively associated with 17-epiestriol (4+ days/week vs. non-use: 2.48 vs. 1.52 pmol/mg creatinine; p (difference) = 0.01, p (trend) = 0.11). Acetaminophen use was positively associated with total EM (2+ days/week vs. non-use: 236 vs. 198 pmol/mg creatinine; p (difference) = 0.02, p (trend) = 0.11), 2-hydroxyestrone-3-methyl ether (1.6 vs. 1.1 pmol/mg creatinine; p (difference) < 0.01, p (trend) = 0.02), and 16 alpha-hydroxyestrone (17 vs. 12 pmol/mg creatinine; p (difference) = 0.01, p (trend) = 0.05). This study provides the first assessment of analgesic use and patterns of estrogen metabolism in women. While we observed some associations between analgesics and individual EM, no clear patterns emerged.
C1 [Fortner, Renee T.; Oh, Hannah; Hankinson, Susan E.; Eliassen, A. Heather] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Fortner, Renee T.; Oh, Hannah; Hankinson, Susan E.; Eliassen, A. Heather] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Fortner, Renee T.; Oh, Hannah; Hankinson, Susan E.; Eliassen, A. Heather] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Daugherty, Sarah E.; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Xu, Xia] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Hankinson, Susan E.] Univ Massachusetts, Amherst, MA 01003 USA.
RP Eliassen, AH (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA.
EM heather.eliassen@channing.harvard.edu
OI Fortner, Renee/0000-0002-1426-8505; Oh, Hannah/0000-0002-8368-3032
FU National Cancer Institute [UM1 CA176726, CA67262, CA50385,
HHSN261200800001E]; Intramural Research Program of the Division of
Cancer Epidemiology and Genetics of the National Cancer Institute; [T32
CA09001]
FX This study was supported by infrastructure grant UM1 CA176726 and
research grants CA67262 and CA50385 from the National Cancer Institute
and the Intramural Research Program of the Division of Cancer
Epidemiology and Genetics of the National Cancer Institute, and with
federal funds of the National Cancer Institute awarded under contract
HHSN261200800001E to SAIC-Frederick. RT Fortner and H Oh are supported
in part by T32 CA09001. The content of this publication does not
necessarily reflect the views or policies of the US Department of Health
and Human Services nor does mention of trade names, commercial products,
or organizations that imply endorsement by the US government.
NR 28
TC 3
Z9 3
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1868-8497
EI 1868-8500
J9 HORM CANCER-US
JI Horm. Cancer
PD APR
PY 2014
VL 5
IS 2
BP 104
EP 112
DI 10.1007/s12672-013-0167-5
PG 9
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA AE8TE
UT WOS:000334274100005
PM 24407556
ER
PT J
AU Candotti, F
AF Candotti, Fabio
TI Gene transfer into hematopoietic stem cells as treatment for primary
immunodeficiency diseases
SO INTERNATIONAL JOURNAL OF HEMATOLOGY
LA English
DT Article
DE Gene therapy; Clinical trials; Severe combined immunodeficiency; Chronic
granulomatous disease; Wiskott-Aldrich syndrome
ID WISKOTT-ALDRICH-SYNDROME; CHRONIC GRANULOMATOUS-DISEASE; LEUKOCYTE
ADHESION DEFICIENCY; ADENOSINE-DEAMINASE DEFICIENCY; FUNCTIONAL LYMPHOID
RECONSTITUTION; INACTIVATING LENTIVIRAL VECTOR; X-LINKED
AGAMMAGLOBULINEMIA; CD40 LIGAND DEFICIENCY; HUMAN T-CELLS; MURINE MODEL
AB Gene transfer into the hematopoietic stem cell has shown curative potential for a variety of hematological disorders. Primary immunodeficiency diseases have led to the way in this field of gene therapy as an example and a model. Clinical results from the past 15 years have shown that significant improvement and even cure can be achieved for diseases such as X-linked severe combined immunodeficiency, adenosine deaminase deficiency, chronic granulomatous disease and Wiskott-Aldrich syndrome. Unfortunately, with the initial clear clinical benefits, the first serious complications of gene therapy have also occurred. In a significant number of patients treated using vectors based on murine gamma-retroviruses and carrying powerful viral enhancer elements, insertional oncogenesis events have resulted in acute leukemias that, in some cases, have had fatal outcomes. These serious adverse events have sparked a revision of the assessment of risks and benefits of integrating gene transfer for hematological diseases and prompted the development and application of new generations of viral vectors with recognized superior safety characteristics. This review summarizes the clinical experience of gene therapy for primary immunodeficiencies and discusses the likely avenues of progress in the future development of this expanding field of clinical investigations.
C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Candotti, F (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Bld 49,Rm 3A04, Bethesda, MD 20892 USA.
EM fabio@nhgri.nih.gov
NR 120
TC 9
Z9 9
U1 5
U2 9
PU SPRINGER JAPAN KK
PI TOKYO
PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065,
JAPAN
SN 0925-5710
EI 1865-3774
J9 INT J HEMATOL
JI Int. J. Hematol.
PD APR
PY 2014
VL 99
IS 4
BP 383
EP 392
DI 10.1007/s12185-014-1524-z
PG 10
WC Hematology
SC Hematology
GA AF1AK
UT WOS:000334446400006
PM 24488786
ER
PT J
AU Thumanu, K
Sangrajrang, S
Khuhaprema, T
Kalalak, A
Tanthanuch, W
Pongpiachan, S
Heraud, P
AF Thumanu, Kanjana
Sangrajrang, Suleeporn
Khuhaprema, Thiravud
Kalalak, Anant
Tanthanuch, Waraporn
Pongpiachan, Siwatt
Heraud, Philip
TI Diagnosis of liver cancer from blood sera using FTIR microspectroscopy:
a preliminary study
SO JOURNAL OF BIOPHOTONICS
LA English
DT Article
DE hepatocellular carcinoma (HCC); liver cirrhosis; FTIR microspectroscopy;
blood serum
ID HEPATOCELLULAR-CARCINOMA; FUNCTION TESTS; SURVIVAL; ALBUMIN; MARKERS
AB FTIR microspectroscopy was applied for studying macromolecular changes in human serum samples from patients with healthy livers, and those diagnosed with liver cirrhosis or hepatocellular carcinoma (HCC). Our study demonstrated that the serum samples from HCC and cirrhotic patients could readily be discriminated from those from healthy controls based on macromolecular differences related to their lipid and protein structure. Spectral changes appeared to indicate that the secondary structure of protein from HCC sample groups contained a more distinctive -sheet structure and a lower lipid content compared to samples from the healthy and cirrhosis group. This was correlated with measurements of large decreases in albumin levels in serum from diseased patients. We argue that this technique shows potential as a simple, rapid, inexpensive, and non-subjective methodology for the screening patients suspected of liver disease. ((c) 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
C1 [Thumanu, Kanjana; Tanthanuch, Waraporn] Synchrotron Light Res Inst Publ Org, Muang 30000, Nakhonratchasim, Thailand.
[Sangrajrang, Suleeporn; Khuhaprema, Thiravud; Kalalak, Anant] Natl Canc Res Inst Thailand, Bangkok 10400, Thailand.
[Pongpiachan, Siwatt] NIDA, NIDA Ctr Res & Dev Disaster Prevent & Management, Sch Social & Environm Dev, Bangkok 10240, Thailand.
[Heraud, Philip] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic 3800, Australia.
[Heraud, Philip] Monash Univ, Ctr Biospect, Clayton, Vic 3800, Australia.
RP Heraud, P (reprint author), Monash Univ, Dept Anat & Dev Biol, Clayton, Vic 3800, Australia.
EM phil.heraud@monash.edu
NR 28
TC 6
Z9 6
U1 1
U2 10
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1864-063X
EI 1864-0648
J9 J BIOPHOTONICS
JI J. Biophotonics
PD APR
PY 2014
VL 7
IS 3-4
BP 222
EP 231
DI 10.1002/jbio.201300183
PG 10
WC Biochemical Research Methods; Biophysics; Optics
SC Biochemistry & Molecular Biology; Biophysics; Optics
GA AE4RV
UT WOS:000333971600008
PM 24639420
ER
PT J
AU Yan, L
Liu, WX
Zhang, HH
Liu, C
Shang, YL
Ye, YH
Zhang, XD
Li, W
AF Yan, Long
Liu, Weixiao
Zhang, Huihui
Liu, Chao
Shang, Yongliang
Ye, Yihong
Zhang, Xiaodong
Li, Wei
TI Ube2g2-gp78-mediated HERP polyubiquitylation is involved in ER stress
recovery
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE HERP; ER Stress recovery; Ubiquitin-proteasome system; Ube2g2-gp78;
Trade-off
ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; EVOLUTIONARY
TRADE-OFFS; UBIQUITIN-LIGASE; CONJUGATING ENZYME; BETA-PROTEIN; CUE
DOMAIN; DEGRADATION; MECHANISMS; PATHWAY
AB A large number of studies have focused on how individual organisms respond to a stress condition, but little attention has been paid to the stress recovery process, such as the endoplasmic reticulum (ER) stress recovery. Homocysteine-induced ER protein (HERP) was originally identified as a chaperone-like protein that is strongly induced upon ER stress. Here we show that, after ER stress induction, HERP is rapidly degraded by Ube2g2-gp78-mediated ubiquitylation and proteasomal degradation. The polyubiquitylation of HERP in vitro depends on a physical interaction between the CUE domain of gp78 and the ubiquitin-like (UBL) domain of HERP, which is essential for HERP degradation in vivo during ER stress recovery. We further show that although HERP promotes cell survival under ER stress, high levels of HERP expression reduce cell viability under oxidative stress conditions, suggesting that HERP plays a dual role in cellular stress adaptation. Together, these results establish the ubiquitin-proteasome-mediated degradation of HERP as a novel mechanism that fine-tunes the stress tolerance capacity of the cell.
C1 [Yan, Long; Liu, Weixiao; Liu, Chao; Shang, Yongliang; Li, Wei] Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China.
[Zhang, Huihui; Zhang, Xiaodong] Wuhan Univ, Coll Life Sci, Wuhan 430072, Hubei, Peoples R China.
[Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Li, W (reprint author), Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China.
EM zhangxd@whu.edu.cn; leways@ioz.ac.cn
FU National Natural Science Foundation of China [30970603]; Knowledge
Innovation Program [KSCX2-YW-N-071]; Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases; One
Hundred Talents Program of the Chinese Academy of Sciences
FX This work was supported by the National Natural Science Foundation of
China [grant number 30970603 to W. L.]; the Knowledge Innovation Program
[grant number KSCX2-YW-N-071 to W. L.]; the Intramural Research Program
of the National Institute of Diabetes and Digestive and Kidney Diseases
(to Y.Y.); and the One Hundred Talents Program of the Chinese Academy of
Sciences. Deposited in PMC for release after 12 months.
NR 52
TC 8
Z9 9
U1 0
U2 6
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD APR 1
PY 2014
VL 127
IS 7
BP 1417
EP 1427
DI 10.1242/jcs.135293
PG 11
WC Cell Biology
SC Cell Biology
GA AE3UY
UT WOS:000333905100006
PM 24496447
ER
PT J
AU Fang, F
Wasserman, SM
Torres-Vazquez, J
Weinstein, B
Cao, F
Li, ZJ
Wilson, KD
Yue, W
Wu, JC
Xie, XY
Pei, XT
AF Fang, Fang
Wasserman, Scott M.
Torres-Vazquez, Jesus
Weinstein, Brant
Cao, Feng
Li, Zongjin
Wilson, Kitchener D.
Yue, Wen
Wu, Joseph C.
Xie, Xiaoyan
Pei, Xuetao
TI The role of Hath6, a newly identified shear-stress-responsive
transcription factor, in endothelial cell differentiation and function
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Hath6; Endothelial differentiation; Human embryonic stem cells
ID EMBRYONIC STEM-CELLS; NITRIC-OXIDE SYNTHASE; GENE-EXPRESSION; IN-VITRO;
PHYLOGENETIC ANALYSIS; MOLECULAR-MECHANISMS; PROFILE; FORCES; MATH6;
VASCULOGENESIS
AB The key regulators of endothelial differentiation that is induced by shear stress are mostly unclear. Human atonal homolog 6 (Hath6 or ATOH8) is an endothelial-selective and shear-stress-responsive transcription factor. In this study, we sought to elucidate the role of Hath6 in the endothelial specification of embryonic stem cells. In a stepwise human embryonic stem cell to endothelial cell (hESC-EC) induction system, Hath6 mRNA was upregulated synchronously with endothelial determination. Subsequently, gain-of-function and loss-of-function studies of Hath6 were performed using the hESC-EC induction model and endothelial cell lines. The overexpression of Hath6, which mimics shear stress treatment, resulted in an increased CD45(-)CD31(+)KDR(+) population, a higher tubular-structure-formation capacity and increased endothelial-specific gene expression. By contrast, the knockdown of Hath6 mRNA markedly decreased endothelial differentiation. Hath6 also facilitated the maturation of endothelial cells in terms of endothelial gene expression, tubular-structure formation and cell migration. We further demonstrated that the gene encoding eNOS is a direct target of Hath6 through a reporter system assay and western blot analysis, and that the inhibition of eNOS diminishes hESC-EC differentiation. These results suggest that eNOS plays a key role in linking Hath6 to the endothelial phenotype. Further in situ hybridization studies in zebrafish and mouse embryos indicated that homologs of Hath6 are involved in vasculogenesis and angiogenesis. This study provides the first confirmation of the positive impact of Hath6 on human embryonic endothelial differentiation and function. Moreover, we present a potential signaling pathway through which shear stress stimulates endothelial differentiation.
C1 [Fang, Fang; Yue, Wen; Xie, Xiaoyan; Pei, Xuetao] Beijing Inst Transfus Med, Stem Cells & Regenerat Med Lab, Beijing, Peoples R China.
[Wasserman, Scott M.] Amgen Inc, Newbury Pk, CA 91320 USA.
[Torres-Vazquez, Jesus; Weinstein, Brant] NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
[Cao, Feng; Li, Zongjin; Wilson, Kitchener D.; Wu, Joseph C.] Stanford Univ, Div Cardiol, Dept Med, Stanford, CA 94305 USA.
[Wu, Joseph C.; Xie, Xiaoyan] Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
RP Xie, XY (reprint author), Beijing Inst Transfus Med, Stem Cells & Regenerat Med Lab, Beijing, Peoples R China.
EM alpha131313@gmail.com; peixt@nic.bmi.ac.cn
RI Li, Zongjin/G-3118-2010; Wilson, Kitchener/A-7146-2016
OI Li, Zongjin/0000-0002-4603-3743;
FU National High Technology Research and Development Program of China
[2011AA020109, 2012AA020503]; National Nature Science Foundation of
China [31071303]; National Institutes of Health [K08HL076191,
U01HL107393]
FX This work was supported by National High Technology Research and
Development Program of China [grant number 2011AA020109 to X. P.,
2012AA020503 to X. X.]; National Nature Science Foundation of China
[grant number 31071303]; and National Institutes of Health [grant number
K08HL076191 to S. M. W., U01HL107393 to J. C. W.]. S. M. W. is an
employee of Amgen, Inc. S. M. W. declares that he has no competing
financial interest in this study. Deposited in PMC for release after 12
months.
NR 40
TC 10
Z9 11
U1 1
U2 11
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD APR 1
PY 2014
VL 127
IS 7
BP 1428
EP 1440
DI 10.1242/jcs.136358
PG 13
WC Cell Biology
SC Cell Biology
GA AE3UY
UT WOS:000333905100007
PM 24463812
ER
PT J
AU Ludtmann, MHR
Otto, GP
Schilde, C
Chen, ZH
Allan, CY
Brace, S
Beesley, PW
Kimmel, AR
Fisher, P
Killick, R
Williams, RSB
AF Ludtmann, Marthe H. R.
Otto, Grant P.
Schilde, Christina
Chen, Zhi-Hui
Allan, Claire Y.
Brace, Selina
Beesley, Philip W.
Kimmel, Alan R.
Fisher, Paul
Killick, Richard
Williams, Robin S. B.
TI An ancestral non-proteolytic role for presenilin proteins in
multicellular development of the social amoeba Dictyostelium discoideum
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Dictyostelium; gamma-secretase; Presenilin
ID GAMMA-SECRETASE ACTIVITY; ALZHEIMERS-DISEASE; BETA-CATENIN;
ENDOPLASMIC-RETICULUM; LINKED MUTATIONS; VALPROIC ACID; COMPLEX; CELL;
ACTIVATION; CHEMOTAXIS
AB Mutations in either of two presenilin genes can cause familial Alzheimer's disease. Presenilins have both proteolysis-dependent functions, as components of the gamma-secretase complex, and proteolysis-independent functions in signalling. In this study, we investigate a conserved function of human presenilins in the development of the simple model organism Dictyostelium discoideum. We show that the block in Dictyostelium development caused by the ablation of both Dictyostelium presenilins is rescued by the expression of human presenilin 1, restoring the terminal differentiation of multiple cell types. This developmental role is independent of proteolytic activity, because the mutation of both catalytic aspartates does not affect presenilin ability to rescue development, and the ablation of nicastrin, a gamma-secretase component that is crucial for proteolytic activity, does not block development. The role of presenilins during Dictyostelium development is therefore independent of their proteolytic activity. However, presenilin loss in Dictyostelium results in elevated cyclic AMP (cAMP) levels and enhanced stimulation-induced calcium release, suggesting that presenilins regulate these intracellular signalling pathways. Our data suggest that presenilin proteins perform an ancient non-proteolytic role in regulating intracellular signalling and development, and that Dictyostelium is a useful model for analysing human presenilin function.
C1 [Ludtmann, Marthe H. R.; Otto, Grant P.; Beesley, Philip W.; Williams, Robin S. B.] Royal Holloway Univ London, Sch Biol Sci, Ctr Biomed Sci, Egham TW20 0EX, Surrey, England.
[Schilde, Christina; Chen, Zhi-Hui] Univ Dundee, Sch Life Sci, Dundee DD1 5EH, Scotland.
[Allan, Claire Y.; Fisher, Paul] La Trobe Univ, Fac Sci Technol & Engn, Bundoora, Vic 3086, Australia.
[Brace, Selina] Royal Holloway Univ London, Sch Biol Sci, Ctr Ecol & Evolut, Egham TW20 0EX, Surrey, England.
[Kimmel, Alan R.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Killick, Richard] Kings Coll London, Inst Psychiat, London SE5 8AF, England.
RP Williams, RSB (reprint author), Royal Holloway Univ London, Sch Biol Sci, Ctr Biomed Sci, Egham TW20 0EX, Surrey, England.
EM robin.williams@rhul.ac.uk
RI Ludtmann, Marthe/A-1446-2013; Williams, Robin/G-6807-2011;
OI Ludtmann, Marthe/0000-0003-1051-6425; Killick,
Richard/0000-0002-8815-3436
FU Alzheimer's Society UK; Intramural Research Programs of the National
Institutes of Health; National Institute of Diabetes and Digestive and
Kidney Diseases; Alzheimer's Research UK; Central Research Fund; Helen
Shackleton travel scholarship; Dr Hadwen Trust (DHT)
FX This work was supported by the Alzheimer's Society UK (R.K.); by the
Intramural Research Programs of the National Institutes of Health; and
the National Institute of Diabetes and Digestive and Kidney Diseases
(A.R.K.); and by an Alzheimer's Research UK PhD studentship to
R.S.B.W.M.H.R.L. received a Central Research Fund and Helen Shackleton
travel scholarship. G.P.O. is funded by the Dr Hadwen Trust (DHT).
Deposited in PMC for release after 12 months.
NR 60
TC 5
Z9 6
U1 0
U2 7
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD APR 1
PY 2014
VL 127
IS 7
BP 1576
EP 1584
DI 10.1242/jcs.140939
PG 9
WC Cell Biology
SC Cell Biology
GA AE3UY
UT WOS:000333905100019
PM 24463814
ER
PT J
AU Prasad, V
Ho, N
AF Prasad, Vinay
Ho, Nancy
TI Why do we continue to adopt medical practices based on pathophysiology
alone when we should be insisting on clinical trials?
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Editorial Material
ID RANDOMIZED-TRIAL; STATIN USE; VERTEBROPLASTY; FRACTURES; PREVENTION
C1 [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Ho, Nancy] Univ Maryland, Med Ctr, Dept Med, Div Gastroenterol, Baltimore, MD 21201 USA.
RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,10-12N226, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov
NR 24
TC 6
Z9 6
U1 0
U2 2
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 APR
PY 2014
VL 67
IS 4
BP 361
EP 363
DI 10.1016/j.jclinepi.2013.11.009
PG 3
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA AE8MQ
UT WOS:000334256400002
PM 24581292
ER
PT J
AU Iacono, D
Resnick, SM
O'Brien, R
Zonderman, AB
An, Y
Pletnikova, O
Rudow, G
Crain, B
Troncoso, JC
AF Iacono, Diego
Resnick, Susan M.
O'Brien, Richard
Zonderman, Alan B.
An, Yang
Pletnikova, Olga
Rudow, Gay
Crain, Barbara
Troncoso, Juan C.
TI Mild Cognitive Impairment and Asymptomatic Alzheimer Disease Subjects:
Equivalent beta-Amyloid and Tau Loads With Divergent Cognitive Outcomes
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Alzheimer disease; Immunoreactivity; Neuronal hypertrophy; Preserved
cognition; Soluble -amyloid; Tau
ID NEUROPATHOLOGIC ASSESSMENT; IN-VIVO; DEMENTIA; RESERVE; HYPERTROPHY;
ASSOCIATION; RESILIENCE; ACTIVATION; PATHOLOGY; LESSONS
AB Older adults with intact cognition before death and substantial Alzheimer disease (AD) lesions at autopsy have been termed asymptomatic AD subjects (ASYMAD). We previously reported hypertrophy of neuronal cell bodies, nuclei, and nucleoli in the CA1 of the hippocampus (CA1), anterior cingulate gyrus, posterior cingulate gyrus, and primary visual cortex of ASYMAD versus age-matched Control and mild cognitive impairment (MCI) subjects. However, it was unclear whether the neuronal hypertrophy could be attributed to differences in the severity of AD pathology. Here, we performed quantitative analyses of the severity of -amyloid (A) and phosphorylated tau (tau) loads in the brains of ASYMAD, Control, MCI, and AD subjects (n = 15 per group) from the Baltimore Longitudinal Study of Aging. Tissue sections from CA1, anterior cingulate gyrus, posterior cingulate gyrus, and primary visual cortex were immunostained for A and tau; the respective loads were assessed using unbiased stereology by measuring the fractional areas of immunoreactivity for each protein in each region. The ASYMAD and MCI groups did not differ in A and tau loads. These data confirm that ASYMAD and MCI subjects have comparable loads of insoluble A and tau in regions vulnerable to AD pathology despite divergent cognitive outcomes. These findings imply that cognitive impairment in AD may be caused or modulated by factors other than insoluble forms of A and tau.
C1 [Iacono, Diego; Pletnikova, Olga; Rudow, Gay; Crain, Barbara; Troncoso, Juan C.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[O'Brien, Richard; Troncoso, Juan C.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Resnick, Susan M.; Zonderman, Alan B.; An, Yang] NIA, Lab Personal & Cognit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Iacono, Diego] Biomed Res Inst New Jersey, Cedar Knolls, NJ 07927 USA.
RP Iacono, D (reprint author), Biomed Res Inst New Jersey, 140 East Hanover Ave, Cedar Knolls, NJ 07927 USA.
EM diego.iacono@atlantichealth.org
FU JHU Alzheimer's Disease Research Center (National Institutes of Health)
[AG 05146]; Burroughs Wellcome Fund for Translational Research;
Intramural Research Program of the National Institute on Aging, National
institutes of Health; UNICO Foundation
FX This work was supported by grants from the JHU Alzheimer's Disease
Research Center (National Institutes of Health Grant AG 05146); the
Burroughs Wellcome Fund for Translational Research; the Intramural
Research Program of the National Institute on Aging, National institutes
of Health; and the UNICO Foundation.
NR 41
TC 11
Z9 11
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
EI 1554-6578
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD APR
PY 2014
VL 73
IS 4
BP 295
EP 304
DI 10.1097/NEN.0000000000000052
PG 10
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AD7UA
UT WOS:000333471100002
PM 24607960
ER
PT J
AU Zhu, M
Allard, JS
Zhang, YQ
Perez, E
Spangler, EL
Becker, KG
Rapp, PR
AF Zhu, Min
Allard, Joanne S.
Zhang, Yongqing
Perez, Evelyn
Spangler, Edward L.
Becker, Kevin G.
Rapp, Peter R.
TI Age-Related Brain Expression and Regulation of the Chemokine CCL4/MIP-1
beta in APP/PS1 Double-Transgenic Mice
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Alzheimer disease; ATF3; CCL4; MIP-1; Epigenetics; Neuroinflammation
ID ACTIVATING TRANSCRIPTION FACTOR-3; HUMAN-IMMUNODEFICIENCY-VIRUS;
MACROPHAGE INFLAMMATORY PROTEIN-1-BETA; AMYLOID PRECURSOR PROTEIN;
ALZHEIMERS-DISEASE; MOUSE MODEL; ATF3 REPRESSES; MESSENGER-RNA; C-JUN;
STRESS
AB The detrimental effect of activation of the chemokine CCL4/MIP-1 on neuronal integrity in patients with HIV-associated dementia has directed attention to the potential role of CCL4 expression and regulation in Alzheimer disease. Here, we show that CCL4 mRNA and protein are overexpressed in the brains of APP(swe)/PS1(E9) (APP/PS1) double-transgenic mice, a model of cerebral amyloid deposition; expression was minimal in brains from nontransgenic littermates or single-mutant controls. Increased levels of CCL4 mRNA and protein directly correlated with the age-related progression of cerebral amyloid- (A) levels in APP/PS1 mice. We also found significantly increased expression of activating transcription factor 3 (ATF3), which was positively correlated with age-related A deposition and CCL4 in the brains of APP/PS1 mice. Results from chromatin immunoprecipitation-quantitative polymerase chain reaction confirmed that ATF3 binds to the promoter region of the CCL4 gene, consistent with a potential role in regulating CCL4 transcription. Finally, elevated ATF3 mRNA expression in APP/PS1 brains was associated with hypomethylation of the ATF3 gene promoter region. These observations prompt the testable hypothesis for future study that CCL4 overexpression, regulated in part by hypomethylation of the ATF3 gene, may contribute to neuropathologic progression associated with amyloid deposition in Alzheimer disease.
C1 [Zhu, Min; Perez, Evelyn; Spangler, Edward L.; Rapp, Peter R.] NIA, Neurocognit Aging Sect, NIH, Intramural Res Program,Biomed Res Ctr, Baltimore, MD 21224 USA.
[Zhang, Yongqing; Becker, Kevin G.] NIA, Gene Express & Genom Unit, NIH, Intramural Res Program,Biomed Res Ctr, Baltimore, MD 21224 USA.
[Allard, Joanne S.] Howard Univ, Coll Med, Dept Physiol & Biophys, Washington, DC 20059 USA.
RP Rapp, PR (reprint author), NIA, Neurocognit Aging Sect, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM rappp@mail.nih.gov
FU Intramural Research Progam of the National Institute on Aging, National
Institutes of Health
FX This work was supported by the Intramural Research Progam of the
National Institute on Aging, National Institutes of Health.
NR 55
TC 3
Z9 3
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
EI 1554-6578
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD APR
PY 2014
VL 73
IS 4
BP 362
EP 374
DI 10.1097/NEN.0000000000000060
PG 13
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AD7UA
UT WOS:000333471100008
PM 24607962
ER
PT J
AU Taylor, KG
Peterson, KE
AF Taylor, Katherine G.
Peterson, Karin E.
TI Innate immune response to La Crosse virus infection
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Review
DE La Crosse; Encephalitis; Innate; SARM1; Interferon
ID WEST-NILE-VIRUS; CENTRAL-NERVOUS-SYSTEM; HUMAN MXA PROTEIN; CALIFORNIA
ENCEPHALITIS; AEDES-TRISERIATUS; NEGATIVE REGULATOR; INTERFERON SYSTEM;
BETA INTERFERON; NORTH-CAROLINA; LACROSSE VIRUS
AB Viral encephalitis represents a significant, and costly, public health threat particularly for high-risk pediatric populations. An emerging mosquito-borne pathogen endemic to the United States, La Crosse virus (LACV) is one of the most common causes of viral encephalitis in children in the United States. However, no licensed therapeutics or vaccines currently exist for treatment. Hampering development efforts, the host response to LACV and its role in disease pathogenesis has only recently been examined. In this review, we discuss the current understanding of innate immune response in the context of viral pathogenesis and host susceptibility to LACV. In addition, we address the need for a clearer understanding of the early host-virus interactions in LACV infections as it relates to viral pathogenesis in the central nervous system.
C1 [Taylor, Katherine G.; Peterson, Karin E.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Taylor, KG (reprint author), NIAID, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM katherine.taylor@nih.gov
RI Peterson, Karin/D-1492-2016
OI Peterson, Karin/0000-0003-4177-7249
NR 58
TC 7
Z9 7
U1 2
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
EI 1538-2443
J9 J NEUROVIROL
JI J. Neurovirol.
PD APR
PY 2014
VL 20
IS 2
SI SI
BP 150
EP 156
DI 10.1007/s13365-013-0186-6
PG 7
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA AE7RL
UT WOS:000334196300006
PM 23846288
ER
PT J
AU Maggio, M
Lauretani, F
De Vita, F
Butto, V
Cattabiani, C
Masoni, S
Sutti, E
Bondi, G
Dall'Aglio, E
Bandinelli, S
Corsonello, A
Abbatecola, AM
Lattanzio, F
Ferrucci, L
Ceda, GP
AF Maggio, M.
Lauretani, F.
De Vita, F.
Butto, V.
Cattabiani, C.
Masoni, S.
Sutti, E.
Bondi, G.
Dall'Aglio, E.
Bandinelli, S.
Corsonello, A.
Abbatecola, A. M.
Lattanzio, F.
Ferrucci, L.
Ceda, G. P.
TI Relationship between use of proton pump inhibitors and IGF system in
older subjects
SO JOURNAL OF NUTRITION HEALTH & AGING
LA English
DT Article
DE Proton pump inhibitors; IGF-1; older subjects
ID GROWTH-FACTOR-I; RISK; INCHIANTI
AB to investigate the effects of proton pump inhibitors (PPIs) on the insulin-like-growth factor 1(IGF-1) system in the elderly.
cross-sectional.
InCHIANTI study.
938 older subjects (536 women, 402 men, mean age 75.7 +/- 7.4 years).
complete data on age, sex, BMI, liver function, medications, dietary intake, IGF-1, IGF-binding protein-1 and -3 (IGFBP-1, IGFBP-3).
Participants were categorized by PPI use, identifying 903 PPI non users and 35 users. After adjusting for age, male PPI users (107.0 +/- 69.6 vs 127.1 +/- 55.8, p < 0.001) and female PPI users (87.6 +/- 29.1 vs 107.6 +/- 52.3, p=0.03) had lower IGF-1 levels than non-users. IGFBP-1 levels were similar in the two groups in both sexes. In whole population, after adjustment for age and sex, PPI users had lower IGF-1 levels 81.9 [61.1-113.8] than nonusers 110 [77.8-148.6], p=0.02. After further adjustment for BMI, albumin, liver function, C-reactive protein, Interleukin-6, number of medications, ACE-inhibitors use, caloric intake, protein intake, physical activity, glycemia, and IGFBP-1, the use of PPIs remained significantly and negatively associated with IGF-1 levels (beta +/- SE=-19.60 +/- 9.83, p=0.045).
Use of PPIs was independently and negatively associated with IGF-1 levels.
C1 [Maggio, M.; De Vita, F.; Butto, V.; Cattabiani, C.; Masoni, S.; Sutti, E.; Bondi, G.; Dall'Aglio, E.; Ceda, G. P.] Univ Parma, Dept Clin & Expt Med, Sect Geriatr, I-43100 Parma, Italy.
[Lauretani, F.; Ceda, G. P.] Univ Hosp Parma, Geriatr Rehabil Dept, Parma, Italy.
[Bandinelli, S.] Azienda Sanitaria Firenze, Florence, Italy.
[Corsonello, A.] INRCA, Unit Geriatr Pharmacoepidemiol, Cosenza, Italy.
[Abbatecola, A. M.; Lattanzio, F.] INRCA Ancona, Ancona, Italy.
[Ferrucci, L.] NIA, NIH, Baltimore, MD 21224 USA.
RP Maggio, M (reprint author), Dept Clin & Expt Med, Food Sci Unit, Geriatr Clin, Via gramsci 14, I-43100 Parma, Italy.
EM marcellomaggio2001@yahoo.it
RI Lauretani, Fulvio/K-5115-2016;
OI Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian
Paolo/0000-0002-9648-8295
FU Italian Ministry of Health [ICS 110.1/RS97.71, RF-2010-2312659]; US
National Institute on Aging [N01-AG-916413, N01-AG-821336, 263 MD 9164
13, 263 MD 821336]; Emilia Romagna Region
FX The InCHIANTI Study was supported as a "targeted project" (ICS
110.1/RS97.71) by the Italian Ministry of Health and in part by the US
National Institute on Aging (Contracts N01-AG-916413 and N01-AG-821336),
and by the Intramural Research Program of the US National Institute on
Aging (Contracts 263 MD 9164 13 and 263 MD 821336) and by grant
RF-2010-2312659 from the Italian Ministry of Health and Emilia Romagna
Region. None of the sponsoring institutions interfered with the
collection, analysis, presentation, or interpretation of the data
reported here. We thank Fabrizio Ablondi, Maurizio Conca and Pietro
Schianchi for their technical supports
NR 15
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER FRANCE
PI PARIS
PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE
SN 1279-7707
EI 1760-4788
J9 J NUTR HEALTH AGING
JI J. Nutr. Health Aging
PD APR
PY 2014
VL 18
IS 4
BP 420
EP 423
DI 10.1007/s12603-013-0430-z
PG 4
WC Geriatrics & Gerontology; Nutrition & Dietetics
SC Geriatrics & Gerontology; Nutrition & Dietetics
GA AF0KH
UT WOS:000334402200012
PM 24676324
ER
PT J
AU Darbari, D
Quinn, M
Seamon, C
Wallen, G
Belfer, I
Taylor, J
AF Darbari, D.
Quinn, M.
Seamon, C.
Wallen, G.
Belfer, I.
Taylor, J.
TI Experimental pain phenotyping in adults with sickle cell anemia and
normal volunteers
SO JOURNAL OF PAIN
LA English
DT Meeting Abstract
C1 [Darbari, D.; Quinn, M.; Seamon, C.; Wallen, G.; Belfer, I.; Taylor, J.] NHLBI, Genom Med Sect, Hematol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD APR
PY 2014
VL 15
IS 4
SU 1
MA 183
BP S21
EP S21
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AF3YN
UT WOS:000334648700084
ER
PT J
AU Heiss, J
Iadarola, M
Cantor, F
Oughourli, A
Smith, R
Mannes, A
AF Heiss, J.
Iadarola, M.
Cantor, F.
Oughourli, A.
Smith, R.
Mannes, A.
TI A Phase I study of the intrathecal administration of resiniferatoxin for
treating severe refractory pain associated with advanced cancer
SO JOURNAL OF PAIN
LA English
DT Meeting Abstract
C1 NIDCR, NINDS, Bethesda, MD USA.
NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 3
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD APR
PY 2014
VL 15
IS 4
SU 1
MA 364
BP S67
EP S67
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AF3YN
UT WOS:000334648700264
ER
PT J
AU Lukkahatai, N
Walitt, B
Alves, G
Saligan, L
AF Lukkahatai, N.
Walitt, B.
Alves, G.
Saligan, L.
TI Categorizing Fibromyalgia patients by symptom experience
SO JOURNAL OF PAIN
LA English
DT Meeting Abstract
C1 [Lukkahatai, N.; Walitt, B.; Alves, G.; Saligan, L.] NINR, Gaithersburg, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD APR
PY 2014
VL 15
IS 4
SU 1
MA 157
BP S15
EP S15
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AF3YN
UT WOS:000334648700058
ER
PT J
AU Oguhebe, A
Darbari, D
Quinn, M
Belfer, I
Okoye, N
Arroyo, J
Taylor, J
AF Oguhebe, A.
Darbari, D.
Quinn, M.
Belfer, I.
Okoye, N.
Arroyo, J.
Taylor, J.
TI Pain catastrophizing in children and adults with sickle cell disease
SO JOURNAL OF PAIN
LA English
DT Meeting Abstract
C1 [Oguhebe, A.; Darbari, D.; Quinn, M.; Belfer, I.; Okoye, N.; Arroyo, J.; Taylor, J.] NHLBI, Genom Med Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD APR
PY 2014
VL 15
IS 4
SU 1
MA 174
BP S19
EP S19
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AF3YN
UT WOS:000334648700075
ER
PT J
AU Batton, B
Li, L
Newman, NS
Das, A
Watterberg, KL
Yoder, BA
Faix, RG
Laughon, MM
Stoll, BJ
Higgins, RD
Walsh, MC
AF Batton, B.
Li, L.
Newman, N. S.
Das, A.
Watterberg, K. L.
Yoder, B. A.
Faix, R. G.
Laughon, M. M.
Stoll, B. J.
Higgins, R. D.
Walsh, M. C.
CA Eunice Kennedy Shriver Natl Inst C
Human Dev Neonatal Res Network
TI Evolving blood pressure dynamics for extremely preterm infants
SO JOURNAL OF PERINATOLOGY
LA English
DT Article
DE antihypotensive therapy; fluid bolus; dopamine
ID BIRTH-WEIGHT INFANTS; 1ST 7 DAYS; HYPOTENSION; DOPAMINE; HYDROCORTISONE;
MORBIDITY; LIFE
AB OBJECTIVE: To examine changes in arterial blood pressure (ABP) after birth in extremely preterm infants.
STUDY DESIGN: Prospective observational study of infants 23(0/7) to 26(6/7) weeks gestational age (GA). Antihypotensive therapy use and ABP measurements were recorded for the first 24 h.
RESULT: A cohort of 367 infants had 18 709 ABP measurements recorded. ABP decreased for the first 3 h, reached a nadir at 4 to 5 h and then increased at an average rate of 0.2mmHg h(-1). The rise in ABP from hour 4 to 24 was similar for untreated infants (n = 164) and infants given any antihypotensive therapy (n = 203), a fluid bolus (n = 135) or dopamine (n = 92). GA-specific trends were similar. ABP tended to be lower as GA decreased, but varied widely at each GA.
CONCLUSION: ABP increased spontaneously over the first 24 postnatal hours for extremely preterm infants. The rate of rise in ABP did not change with antihypotensive therapy.
C1 [Batton, B.; Newman, N. S.; Walsh, M. C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Div Neonatol, Cleveland, OH 44106 USA.
[Batton, B.] So Illinois Univ, Sch Med, Dept Pediat, Springfield, IL 62794 USA.
[Li, L.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Das, A.] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Watterberg, K. L.] Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Yoder, B. A.; Faix, R. G.] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA.
[Laughon, M. M.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA.
[Stoll, B. J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Stoll, B. J.] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Higgins, R. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Batton, B (reprint author), So Illinois Univ, Sch Med, Dept Pediat, Div Neonatol, POB 19676, Springfield, IL 62794 USA.
EM bbatton@siumed.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD); Best Pharmaceuticals for
Children Act
FX The National Institutes of Health and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD)
provided grant support, including funding from the Best Pharmaceuticals
for Children Act, for the Neonatal Research Network's Early Blood
Pressure Observational Study.
NR 21
TC 10
Z9 11
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0743-8346
EI 1476-5543
J9 J PERINATOL
JI J. Perinatol.
PD APR
PY 2014
VL 34
IS 4
BP 301
EP 305
DI 10.1038/jp.2014.6
PG 5
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA AE2PA
UT WOS:000333814200011
PM 24503912
ER
PT J
AU Kennedy, KA
Wrage, LA
Higgins, RD
Finer, NN
Carlo, WA
Walsh, MC
Laptook, AR
Faix, RG
Yoder, BA
Schibler, K
Gantz, MG
Das, A
Newman, NS
Phelps, DL
AF Kennedy, K. A.
Wrage, L. A.
Higgins, R. D.
Finer, N. N.
Carlo, W. A.
Walsh, M. C.
Laptook, A. R.
Faix, R. G.
Yoder, B. A.
Schibler, K.
Gantz, M. G.
Das, A.
Newman, N. S.
Phelps, D. L.
CA Eunice Kennedy Shriver Natl Inst C
Human Dev Neonatal Res Network
TI Evaluating retinopathy of prematurity screening guidelines for 24-to
27-week gestational age infants
SO JOURNAL OF PERINATOLOGY
LA English
DT Article
DE extremely premature infant; retinopathy of prematurity; screening
ID EXTREMELY PRETERM INFANTS; NATURAL-HISTORY; CRITERIA; LESS
AB OBJECTIVE: To determine whether current retinopathy of prematurity (ROP) screening guidelines adequately identify treatable ROP in a contemporary cohort of extremely low gestation infants.
STUDY DESIGN: Data from the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial were used. Inborn infants of 24 (0)/(7) to 27 (6)/(7) weeks gestational age (GA) with consent before delivery were enrolled in 2005 to 2009. Severe ROP (type 1 ROP or treatment with laser, cryotherapy or bevacizumab) or death was the primary outcome for the randomized trial. Examinations followed the then current AAP (American Academy of Pediatrics) screening recommendations, beginning by 31 to 33 weeks postmenstrual age (PMA).
RESULT: One thousand three hundred and sixteen infants were enrolled in the trial. Nine hundred and ninety-seven of the 1121 who survived to first eye exam had final ROP outcome determined. One hundred and thirty-seven (14% of 997) met criteria for severe ROP and 128 (93%) of those had sufficient data (without missing or delayed exams) to determine age of onset of severe ROP. PMA at onset was 32.1 to 53.1 weeks. In this referral center cohort, 1.4% (14/997) developed severe ROP after discharge.
CONCLUSION: Our contemporary data support the 2013 AAP screening guidelines for ROP for infants of 24 (0)/(7) to 27 (6)/(7) weeks GA. Some infants do not meet treatment criteria until after discharge home. Post-discharge follow-up of infants who are still at risk for severe ROP is crucial for timely detection and treatment.
C1 [Kennedy, K. A.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
[Wrage, L. A.; Gantz, M. G.] RTI Int, Biostat & Epidemiol Div, Res Triangle Pk, NC USA.
[Higgins, R. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Finer, N. N.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA.
[Carlo, W. A.] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA.
[Walsh, M. C.; Newman, N. S.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Laptook, A. R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Faix, R. G.; Yoder, B. A.] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA.
[Schibler, K.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA.
[Schibler, K.] Univ Cincinnati, Cincinnati, OH USA.
[Das, A.] RTI Int, Biostat & Epidemiol Div, Rockville, MD USA.
[Phelps, D. L.] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA.
RP Kennedy, KA (reprint author), UT Houston Med Sch, 6431 Fannin,Suite 2-106, Houston, TX 77030 USA.
EM Kathleen.A.Kennedy@uth.tmc.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD); National Heart, Lung, and
Blood Institute (NHLBI)
FX The National Institutes of Health, the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), and the
National Heart, Lung, and Blood Institute (NHLBI) provided grant support
for the Neonatal Research Network's SUPPORT trial.
NR 26
TC 1
Z9 1
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0743-8346
EI 1476-5543
J9 J PERINATOL
JI J. Perinatol.
PD APR
PY 2014
VL 34
IS 4
BP 311
EP 318
DI 10.1038/jp.2014.12
PG 8
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA AE2PA
UT WOS:000333814200013
PM 24503911
ER
PT J
AU Iacoviello, BM
Wu, G
Abend, R
Murrough, JW
Feder, A
Fruchter, E
Levinstein, Y
Wald, I
Bailey, CR
Pine, DS
Neumeister, A
Bar-Haim, Y
Charney, DS
AF Iacoviello, Brian M.
Wu, Gang
Abend, Rany
Murrough, James W.
Feder, Adriana
Fruchter, Eyal
Levinstein, Yoav
Wald, Ilan
Bailey, Christopher R.
Pine, Daniel S.
Neumeister, Alexander
Bar-Haim, Yair
Charney, Dennis S.
TI Attention Bias Variability and Symptoms of Posttraumatic Stress Disorder
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article
ID REACTION-TIME VARIABILITY; ANXIETY DISORDERS; THREAT; PTSD; DEPRESSION;
SUPPRESSION; CHILDREN; SCALE
AB Cognitive theories implicate information-processing biases in the etiology of anxiety disorders. Results of attention-bias studies in posttraumatic stress disorder (PTSD) have been inconsistent, suggesting biases towards and away from threat. Within-subject variability of attention biases in posttraumatic patients may be a useful marker for attentional control impairment and the development of posttrauma symptoms. This study reports 2 experiments investigating threat-related attention biases, mood and anxiety symptoms, and attention-bias variability following trauma. Experiment 1 included 3 groups in a cross-sectional design: (a) PTSD, (b) trauma-exposed without PTSD, and (c) healthy controls with no trauma or Axis I diagnoses. Greater attention-bias variability was found in the PTSD group compared to the other 2 groups (eta p2=.23); attention-bias variability was significantly and positively correlated (r = .37) with PTSD symptoms. Experiment 2 evaluated combat-exposed and nonexposed soldiers before and during deployment. Attention-bias variability did not differentiate groups before deployment, but did differentiate groups during deployment (eta p2=.16); increased variability was observed in groups with acute posttraumatic stress symptoms and acute depression symptoms only. Attention-bias variability could be a useful marker for attentional impairment related to threat cues associated with mood and anxiety symptoms after trauma exposure.
C1 [Iacoviello, Brian M.; Wu, Gang; Murrough, James W.; Feder, Adriana; Bailey, Christopher R.; Charney, Dennis S.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA.
[Abend, Rany; Wald, Ilan; Bar-Haim, Yair] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel.
[Fruchter, Eyal; Levinstein, Yoav] Israel Def Forces, Dept Mental Hlth, Med Corps, Tel Hashomer, Israel.
[Pine, Daniel S.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
[Neumeister, Alexander] NYU, Sch Med, Dept Psychiat, New York, NY USA.
[Bar-Haim, Yair] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel.
RP Iacoviello, BM (reprint author), One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA.
EM brian.iacoviello@mssm.edu
RI Murrough, James/J-7129-2013
OI Murrough, James/0000-0001-6286-1242
FU NIMH NIH HHS [K23 MH094707, K23 MH099223]
NR 30
TC 24
Z9 24
U1 6
U2 28
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-9867
EI 1573-6598
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD APR
PY 2014
VL 27
IS 2
BP 232
EP 239
DI 10.1002/jts.21899
PG 8
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA AF2II
UT WOS:000334535400015
PM 24604631
ER
PT J
AU Murphy, TP
Cooper, CJ
Cutlip, DE
Matsumoto, A
Jamerson, K
Rundback, J
Rosenfield, KA
Henrich, W
Shapiro, J
Massaro, J
Yen, CH
Burtch, H
Thum, C
Reid, D
Dworkin, L
AF Murphy, Timothy P.
Cooper, Christopher J.
Cutlip, Donald E.
Matsumoto, Alan
Jamerson, Kenneth
Rundback, John
Rosenfield, Kenneth A.
Henrich, William
Shapiro, Joseph
Massaro, Joseph
Yen, Chen-Hsing
Burtch, Holly
Thum, Claudia
Reid, Diane
Dworkin, Lance
TI Roll-in Experience from the Cardiovascular Outcomes with Renal
Atherosclerotic Lesions (CORAL) Study
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID ARTERY STENOSIS; RANDOMIZED-TRIAL; MEDICAL THERAPY; BLOOD-PRESSURE;
ANGIOPLASTY; REVASCULARIZATION; HYPERTENSION; PREVENTION
AB Purpose: To describe the experience and results from the roll-in phase of the Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) study.
Materials and Methods: The CORAL roll-in database was used to describe the baseline characteristics of the patients in the roll-in cohort, all of whom underwent renal artery stent placement; to evaluate CORAL site performance; to compare estimates of lesion (stenosis) severity made by site interventionalists with the central CORAL angiographic core laboratory readings; and to report outcomes after renal artery stent placement. During the roll-in phase, 239 patients (mean age, 70.2 y +/- 9.0; 49% male) underwent renal artery stent procedures. Angiographic core laboratory analysis of renal arteriograms was done, and participants were followed at 1 month and 9 months.
Results: Major angiographic complications were identified in 28 (13%) subjects. Kidney function remained unchanged at the short (2-4 weeks) follow-up interval. Improvement in systolic blood pressure with use of distal embolic protection devices (n = 161) did not show any clinical benefit over nonuse of such devices (n = 78) in this small series. At 9 months, there were significantly More endpoints reported by site in subjects with bilateral renal artery stenosis (P = .01) and prior history of stroke (P = .03).
Conclusions: In the roll-in phase of the CORAL study, a significant number of angiographic complications were identified. No effect was seen on estimated glomerular filtration rate after renal artery stent placement, but systolic blood pressure decreased significantly.
C1 [Murphy, Timothy P.] Rhode Isl Hosp, Vasc Dis Res Ctr, Providence, RI 02903 USA.
[Dworkin, Lance] Rhode Isl Hosp, Div Nephrol, Providence, RI 02903 USA.
[Cooper, Christopher J.; Burtch, Holly] Univ Toledo, Div Cardiol, Toledo, OH 43606 USA.
[Cutlip, Donald E.] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA USA.
[Cutlip, Donald E.; Massaro, Joseph; Yen, Chen-Hsing; Thum, Claudia] Harvard Clin Res Inst, Boston, MA USA.
[Rosenfield, Kenneth A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Massaro, Joseph] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Matsumoto, Alan] Univ Virginia, Dept Radiol, Charlottesville, VA USA.
[Jamerson, Kenneth] Univ Michigan, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Rundback, John] Holy Name Med Ctr, Intervent Inst, Teaneck, NJ USA.
[Henrich, William] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Shapiro, Joseph] Marshall Univ, Joan C Edwards Sch Med, Huntington, WV USA.
[Reid, Diane] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Murphy, TP (reprint author), Rhode Isl Hosp, Vasc Dis Res Ctr, Gerry 337,593 Eddy St, Providence, RI 02903 USA.
EM tmurphy@lifespan.org
FU National Heart, Lung and Blood Institute of the National Institutes of
Health [U01HL071556, U01HL072734, U01HL072735, U01HL072736,
U01HL072737]; Cordis/JohnsonJohnson; Pfizer, Inc.; Abbott Vascular;
Otsuka America; AstraZeneca; Pfizer; Medtronic; Cook, Inc.
FX Research reported in this article was supported by the National Heart,
Lung and Blood Institute of the National Institutes of Health under
Award Numbers U01HL071556, U01HL072734, U01HL072735, U01HL072736, and
U01HL072737. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institutes of Health. Drug for this study was provided by AstraZeneca
(Wilmington, Delaware), device support was provided by
Cordis/Johnson&Johnson (Bridgewater, New Jersey), and supplemental
financial support was granted by both Cordis/Johnson&Johnson and Pfizer,
Inc.; T.P.M. receives research support from Abbott Vascular,
Cordis/Johnson&Johnson, and Otsuka America. C.J.C. receives research
support from Cordis/Johnson&Johnson, AstraZeneca, and Pfizer. D.E.C. is
a consultant for St. Jude Medical. A.M. receives research, support from
Medtronic and Cook, Inc., and is on the scientific advisory board for
Boston Scientific. K.A.R. is on the scientific advisory board for Abbott
Vascular and Complete Conference Management, receives honoraria from
Covidien and royalty payments from Cordis/Johnson&Johnson, and is on the
board of VIVA Physicians. None of the other authors have identified a
conflict of interest.
NR 12
TC 5
Z9 5
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
EI 1535-7732
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD APR
PY 2014
VL 25
IS 4
BP 511
EP 520
DI 10.1016/j.jvir.2013.09.018
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA AE3HR
UT WOS:000333868100002
PM 24325931
ER
PT J
AU Hall, JA
Salgado, R
Lively, T
Sweep, F
Schuh, A
AF Hall, Jacqueline Anne
Salgado, Roberto
Lively, Tracy
Sweep, Fred
Schuh, Anna
TI A risk-management approach for effective integration of biomarkers in
clinical trials: perspectives of an NCI, NCRI, and EORTC working group
SO LANCET ONCOLOGY
LA English
DT Article
ID EXTERNAL QUALITY ASSESSMENT; OMICS-BASED PREDICTORS; BREAST-CANCER;
MOLECULAR PATHOLOGY; DRUG DEVELOPMENT; MINDACT TRIAL; RECOMMENDATIONS;
ASSAYS; LEUKEMIA; TEMOZOLOMIDE
AB Clinical cancer research today often includes testing the value of biomarkers to direct treatment and for drug development. However, the practical challenges of integration of molecular information into clinical trial protocols are increasingly appreciated. Inherent difficulties include evidence gaps in available biomarker data, a paucity of robust assay methods, and the design of appropriate studies within the constraints of feasible trial operations, and finite resources. Scalable and proportionate approaches are needed to systematically cope with these challenges. Therefore, we assembled international experts from three clinical trials organisations to identify the common challenges and common solutions. We present a practical risk-assessment framework allowing targeting of scarce resources to crucial issues coupled with a library of useful resources and a simple actionable checklist of recommendations. We hope that these practical methods will be useful for running biomarker-driven trials and ultimately help to develop biomarkers that are ready for integration in routine practice.
C1 [Hall, Jacqueline Anne] European Org Res Treatment Canc, Brussels, Belgium.
[Salgado, Roberto] Inst Jules Bordet, Breast Canc Translat Res Lab, B-1000 Brussels, Belgium.
[Salgado, Roberto] GasthuisZusters Antwerp, Dept Pathol, Antwerp, Belgium.
[Lively, Tracy] US Natl Canc Inst, Div Canc Treatment & Diag, Canc Diag Programme, Rockville, MD USA.
[Sweep, Fred] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, NL-6525 ED Nijmegen, Netherlands.
[Schuh, Anna] Churchill Hosp, Oxford Canc & Haematol Ctr, Oxford OX3 7LJ, England.
RP Hall, JA (reprint author), VIB Vzw, Rijvisschestr 120, B-9052 Zwijnaarde, Belgium.
EM jacqueline.a.hall@gmail.com
RI Sweep, C.G.J./H-8096-2014
FU UK Department of Health's National Institute for Health Research (NIHR)
Biomedical Research Centres funding scheme; EORTC Charitable Trust
FX JAH, RS, and FS are part of the EORTC PathoBiology group, and AS is part
of the NCRI Biomarker and Imaging Clinical Studies Group. The authors
thank the Oxford Partnership Comprehensive Biomedical Research Centre,
with funding from the UK Department of Health's National Institute for
Health Research (NIHR) Biomedical Research Centres funding scheme and
the EORTC Charitable Trust for funding support; Margaret M Cavenagh
(NCI, USA) for expert editorial assistance; and Han van Krieken from the
European Society of Pathology for review and helpful discussions. The
views expressed in this publication are those of the authors, and not
necessarily those of the US Department of Health and Human Services, nor
can they be considered policy of the NCI, NCRI, or EORTC.
NR 73
TC 11
Z9 11
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD APR
PY 2014
VL 15
IS 4
BP E184
EP E193
PG 10
WC Oncology
SC Oncology
GA AE9CN
UT WOS:000334301900021
PM 24694642
ER
PT J
AU Lee, SO
Jin, UH
Kang, JH
Kim, SB
Guthrie, AS
Sreevalsan, S
Lee, JS
Safe, S
AF Lee, Syng-Ook
Jin, Un-Ho
Kang, Jeong Han
Kim, Sang Bae
Guthrie, Aaron S.
Sreevalsan, Sandeep
Lee, Ju-Seog
Safe, Stephen
TI The Orphan Nuclear Receptor NR4A1 (Nur77) Regulates Oxidative and
Endoplasmic Reticulum Stress in Pancreatic Cancer Cells
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID NGFI-B; APOPTOSIS; PROTEIN; THIOREDOXIN; EXPRESSION; NURR1; GENE; TR3;
HETERODIMERIZATION; PATHWAY
AB NR4A1 (Nur77, TR3) is an orphan nuclear receptor that is overexpressed in pancreatic cancer and exhibits pro-oncogenic activity. RNA interference of NR4A1 expression in Panc-1 cells induced apoptosis and subsequent proteomic analysis revealed the induction of several markers of endoplasmic reticulum stress, including glucose-related protein 78 (GRP78), CCAAT/enhancer-binding protein-homologous protein (CHOP), and activating transcription factor-4 (ATF-4). Treatment of pancreatic cancer cells with the NR4A1 antagonist 1,1-bis(3'-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) gave similar results. Moreover, both NR4A1 knockdown and DIM-C-pPhOH induced reactive oxygen species (ROS), and induction of ROS and endoplasmic reticulum stress by these agents was attenuated after cotreatment with antioxidants. Manipulation of NR4A1 expression coupled with gene expression profiling identified a number of ROS metabolism transcripts regulated by NR4A1. Knockdown of one of these transcripts, thioredoxin domain containing 5 (TXNDC5), recapitulated the elevated ROS and endoplasmic reticulum stress; thus, demonstrating that NR4A1 regulates levels of endoplasmic reticulum stress and ROS in pancreatic cancer cells to facilitate cell proliferation and survival. Finally, inactivation of NR4A1 by knockdown or DIM-C-pPhOH decreased TXNDC5, resulting in activation of the ROS/endoplasmic reticulum stress and proapoptotic pathways.
Implications: The NR4A1 receptor is pro-oncogenic, regulates the ROS/endoplasmic reticulum stress pathways, and inactivation of the receptor represents a novel pathway for inducing cell death in pancreatic cancer. (C) 2014 AACR.
C1 [Lee, Syng-Ook; Jin, Un-Ho; Safe, Stephen] Texas A&M Univ, Hlth Sci Ctr, Inst Biosci & Technol, College Stn, TX USA.
[Kim, Sang Bae; Lee, Ju-Seog] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, College Stn, TX USA.
[Guthrie, Aaron S.] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA.
[Sreevalsan, Sandeep; Safe, Stephen] Texas A&M Univ, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA.
[Kang, Jeong Han] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Lee, Syng-Ook] Keimyung Univ, Dept Food Sci & Technol, Taegu, South Korea.
RP Safe, S (reprint author), Texas A&M Univ, Dept Vet Physiol & Pharmacol, 4466 TAMU,Vet Res Bldg 410, College Stn, TX 77843 USA.
EM ssafe@cvm.tamu.edu
FU National Institutes of Health [R01-CA124998]; Texas AgriLife Research
FX This work is funded by the National Institutes of Health (R01-CA124998)
and Texas AgriLife Research.
NR 46
TC 20
Z9 21
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
EI 1557-3125
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD APR
PY 2014
VL 12
IS 4
BP 527
EP 538
DI 10.1158/1541-7786.MCR-13-0567
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AF3AN
UT WOS:000334583900006
PM 24515801
ER
PT J
AU Yao, PL
Morales, JL
Zhu, B
Kang, BH
Gonzalez, FJ
Peters, JM
AF Yao, Pei-Li
Morales, Jose L.
Zhu, Bokai
Kang, Boo-Hyon
Gonzalez, Frank J.
Peters, Jeffrey M.
TI Activation of Peroxisome Proliferator-Activated Receptor-beta/delta
(PPAR-beta/delta) Inhibits Human Breast Cancer Cell Line Tumorigenicity
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID HUMAN HACAT KERATINOCYTES; EXPRESSION PATTERNS; RETINOIC ACID; DELTA;
DIFFERENTIATION; CARCINOGENESIS; MICE; PROGRESSION; CARCINOMAS; AGONISTS
AB The effect of activation and overexpression of the nuclear receptor PPAR-beta/delta in human MDA-MB-231 (estrogen receptor-negative; ER-) and MCF7 (estrogen-receptor-positive; ER dagger) breast cancer cell lines was examined. Target gene induction by ligand activation of PPAR-beta/delta was increased by overexpression of PPAR beta/delta compared with controls. Overexpression of PPAR-beta/delta caused a decrease in cell proliferation in MCF7 and MDA-MB-231 cells Compared with controls, whereas ligand activation of PPAR-beta/delta further inhibited proliferation of MCF7 but not MDA-MB-231 cells. Overexpression and/or ligand activation of PPAR-beta/delta in MDA-MB-231 or MCF7 cells had no effect on experimental apoptosis. Decreased clonogenicity was observed in both MDA-MB-231 and MCF7 overexpressing PPAR-beta/delta in response to ligand activation of PPAR-beta/delta as compared with controls. Ectopic xenografts developed from MDA-MB-231 and MCF7 cells overexpressing PPAR-beta/delta were significantly smaller, and ligand activation of PPAR-beta/delta caused an even greater reduction in tumor volume as compared with controls. Interestingly, the decrease in MDA-MB-231 tumor size after overexpressing PPAR-beta/delta and ligand activation of PPAR-beta/delta correlated with increased necrosis. These data show that ligand activation and/or overexpression of PPAR-beta/delta in two human breast cancer cell lines inhibits relative breast cancer tumorigenicity and provide further support for the development of ligands for PPAR-beta/delta to specifically inhibit breast carcinogenesis. These new cell-based models will be invaluable tools for delineating the role of PPAR-beta/delta in breast cancer and evaluating the effects of PPAR-beta/delta agonists. Mol Cancer Ther; 13(4); 1008-17. (C)2014 AACR.
C1 [Yao, Pei-Li; Morales, Jose L.; Zhu, Bokai; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Yao, Pei-Li; Morales, Jose L.; Zhu, Bokai; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Kang, Boo-Hyon] Chemon, Nonclin Res Inst, Yongin, Gyeonggi Do, South Korea.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
RP Yao, PL (reprint author), Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
EM pxy11@psu.edu
FU NIH [CA124533, CA141029, CA140369, AA018863]; National Cancer Institute
Intramural Research Program [ZIABC005561, ZIABC005562, ZIABC005708]
FX This work was supported by NIH (CA124533, CA141029, CA140369, AA018863;
to J.M. Peters) and the National Cancer Institute Intramural Research
Program (ZIABC005561, ZIABC005562, ZIABC005708; to F.J. Gonzalez).
NR 33
TC 15
Z9 15
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD APR
PY 2014
VL 13
IS 4
BP 1008
EP 1017
DI 10.1158/1535-7163.MCT-13-0836
PG 10
WC Oncology
SC Oncology
GA AE9QE
UT WOS:000334342300022
PM 24464939
ER
PT J
AU Christianson, JC
Ye, YH
AF Christianson, John C.
Ye, Yihong
TI Cleaning up in the endoplasmic reticulum: ubiquitin in charge
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Review
ID ER-ASSOCIATED DEGRADATION; PROTEIN-QUALITY-CONTROL; TRANSMEMBRANE
CONDUCTANCE REGULATOR; INTEGRAL MEMBRANE-PROTEINS; I HEAVY-CHAINS;
AAA-ATPASE; POLYUBIQUITIN CHAINS; RETRO-TRANSLOCATION; CUE DOMAIN;
SUBSTRATE RETROTRANSLOCATION
AB The eukaryotic endoplasmic reticulum (ER) maintains protein homeostasis by eliminating unwanted proteins through the evolutionarily conserved ER-associated degradation (ERAD) pathway. During ERAD, maturation-defective and surplus polypeptides are evicted from the ER lumen and/or lipid bilayer through the process of retrotranslocation and ultimately degraded by the proteasome. An integral facet of the ERAD mechanism is the ubiquitin system, composed of the ubiquitin modifier and the factors for assembling, processing and binding ubiquitin chains on conjugated substrates. Beyond simply marking polypeptides for degradation, the ubiquitin system is functionally intertwined with retrotranslocation machinery to transport polypeptides across the ER membrane.
C1 [Christianson, John C.] Univ Oxford, Ludwig Inst Canc Res, Oxford, England.
[Ye, Yihong] Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD USA.
RP Christianson, JC (reprint author), Univ Oxford, Ludwig Inst Canc Res, Oxford, England.
EM john.christianson@ludwig.ox.ac.uk; yihongy@mail.nih.gov
FU NIDDK; US National Institutes of Health; J.C.C; Cancer Research and the
UK Medical Research Council
FX We thank J. Schulz, E. Fenech, K. Bryon-Dodd (University of Oxford) and
J. Olzmann (University of California, Berkeley) for critical reading of
the manuscript. Research in the laboratory of Y.Y. is supported by the
intramural research program of the NIDDK, US National Institutes of
Health. J.C.C. is supported by funding from the Ludwig Institute for
Cancer Research and the UK Medical Research Council.
NR 131
TC 78
Z9 78
U1 3
U2 29
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
EI 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD APR
PY 2014
VL 21
IS 4
BP 325
EP 335
DI 10.1038/nsmb.2793
PG 11
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA AE9SH
UT WOS:000334349000008
PM 24699081
ER
PT J
AU Bonnemann, CG
Wang, CH
Quijano-Roy, S
Deconinck, N
Bertini, E
Ferreiro, A
Muntoni, F
Sewry, C
Beeroud, C
Mathews, KD
Moore, SA
Bellini, J
Rutkowski, A
North, KN
AF Boennemann, Carsten G.
Wang, Ching H.
Quijano-Roy, Susana
Deconinck, Nicolas
Bertini, Enrico
Ferreiro, Ana
Muntoni, Francesco
Sewry, Caroline
Beroud, Christophe
Mathews, Katherine D.
Moore, Steven A.
Bellini, Jonathan
Rutkowski, Anne
North, Kathryn N.
CA Int Stand Care Comm Congenital Mus
TI Diagnostic approach to the congenital muscular dystrophies
SO NEUROMUSCULAR DISORDERS
LA English
DT Article
DE Congenital muscular dystrophy; Collagen VI; Laminin alpha2;
Alpha-dystroglycan; SEPN1; Lamin A/C; RYR1; Diagnostic guideline
ID WALKER-WARBURG-SYNDROME; VI-RELATED MYOPATHIES; LAMININ ALPHA-2 CHAIN;
MITOCHONDRIAL STRUCTURAL ABNORMALITIES; VARIABLE CLINICAL PHENOTYPE;
FIBER-TYPE DISPROPORTION; FUKUTIN GENE-MUTATIONS; SELENOPROTEIN-N GENE;
RIGID SPINE SYNDROME; COLLAGEN-VI
AB Congenital muscular dystrophies (CMDs) are early onset disorders of muscle with histological features suggesting a dystrophic process. The congenital muscular dystrophies as a group encompass great clinical and genetic heterogeneity so that achieving an accurate genetic diagnosis has become increasingly challenging, even in the age of next generation sequencing. In this document we review the diagnostic features, differential diagnostic considerations and available diagnostic tools for the various CMD subtypes and provide a systematic guide to the use of these resources for achieving an accurate molecular diagnosis. An International Committee on the Standard of Care for Congenital Muscular Dystrophies composed of experts on various aspects relevant to the CMDs performed a review of the available literature as well as of the unpublished expertise represented by the members of the committee and their contacts. This process was refined by two rounds of online surveys and followed by a three-day meeting at which the conclusions were presented and further refined. The combined consensus summarized in this document allows the physician to recognize the presence of a CMD in a child with weakness based on history, clinical examination, muscle biopsy results, and imaging. It will be helpful in suspecting a specific CMD subtype in order to prioritize testing to arrive at a final genetic diagnosis. (C) 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
C1 [Boennemann, Carsten G.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Wang, Ching H.] Driscoll Childrens Hosp, Corpus Christi, TX USA.
[Quijano-Roy, Susana] Hop Raymond Poincare, Garches, France.
[Quijano-Roy, Susana] UFR Sci Sante Simone Veil UVSQ, Paris, France.
[Deconinck, Nicolas] Hop Univ Enfants Reine Fabiola, Brussels, Belgium.
[Deconinck, Nicolas] Ghent Univ Hosp, Ghent, Belgium.
[Bertini, Enrico] Bambino Gesu Childrens Res Hosp, Rome, Italy.
[Ferreiro, Ana] UPMC, INSERM, UMR787, Paris, France.
[Ferreiro, Ana] Grp Hosp Pitie Salpetriere, Reference Ctr Neuromuscular Disorders, F-75634 Paris, France.
[Muntoni, Francesco; Sewry, Caroline] UCL Inst Child Hlth, Dubowitz Neuromuscular Ctr, London, England.
[Beroud, Christophe] INSERM, U827, Genet Mol Lab, Montpellier, France.
[Mathews, Katherine D.; Moore, Steven A.] Univ Iowa, Iowa City, IA USA.
[Bellini, Jonathan] Stanford Univ, Sch Med, Stanford, CA USA.
[Rutkowski, Anne] Kaiser SCPMB, Los Angeles, CA USA.
[North, Kathryn N.] Murdoch Childrens Res Inst, Melbourne, Australia.
RP Bonnemann, CG (reprint author), Natl Inst Neurol Disorders & Stroke, Neuromuscular & Neurogenet Disorders Childhood Se, NIH, 35 Convent Dr,Bldg 35,Room 2A-116, Bethesda, MD 20892 USA.
EM carsten.bonnemann@nih.gov
RI BEROUD, Christophe/A-8381-2008; Ferreiro, Ana/F-5371-2011; North,
Kathryn/K-6476-2012; Kirschner, Janbernd/H-7418-2016
OI BEROUD, Christophe/0000-0003-2986-8738; Sejersen,
Thomas/0000-0001-5961-7097; North, Kathryn/0000-0003-0841-8009;
Kirschner, Janbernd/0000-0003-1618-7386
FU CureCMD group; TREAT-NMD group; AFM - Association Francaise contre les
Myopathies; Telethon, Italy; Wellstone Muscular Dystrophy Cooperative
Research Center [U54-NS053672]; MDA Special Grant for the preceding
Congenital Muscular Dystrophy Workshop held in July at the University of
Iowa; National Specialist Commissioning team; NINDS intramural funds;
[1R13AR056530-01]
FX This project is supported by grants from the following groups: CureCMD
(www.curecmd.org), TREAT-NMD (www.treat-nmd.edu), AFM - Association
Francaise contre les Myopathies (www.afm-france.org/), and Telethon,
Italy (www.telethon.it), and U54-NS053672 Wellstone Muscular Dystrophy
Cooperative Research Center Grant, 1R13AR056530-01, and MDA Special
Grant for the preceding Congenital Muscular Dystrophy Workshop held in
July 2008 at the University of Iowa. The support of the. National
Specialist Commissioning team to F. Muntoni and of NINDS intramural
funds to C. Bonnemann is also gratefully acknowledged.
NR 145
TC 57
Z9 58
U1 2
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
EI 1873-2364
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD APR
PY 2014
VL 24
IS 4
BP 289
EP 311
DI 10.1016/j.nmd.2013.12.011
PG 23
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AE6VD
UT WOS:000334135200001
PM 24581957
ER
PT J
AU Yi, X
Long, L
Yang, CZ
Lu, YY
Cheng, ML
AF Yi, Xu
Long, Li
Yang, Chunzhang
Lu, Yingying
Cheng, Mingliang
TI Maotai Ameliorates Diethylnitrosamine-Initiated Hepatocellular Carcinoma
Formation in Mice
SO PLOS ONE
LA English
DT Article
ID GLUTAMATE-CYSTEINE LIGASE; HEPATITIS-C VIRUS; OXIDATIVE STRESS;
DIAGNOSTIC-VALUE; LIVER FIBROSIS; GLYPICAN-3 EXPRESSION;
ALCOHOL-CONSUMPTION; 2-RELATED FACTOR-2; GENE-EXPRESSION;
METALLOTHIONEIN
AB Consumption of alcohol is closely related to liver disease, such as hepatic fibrosis or even hepatocellular carcinoma (HCC). However, epidemiological and experimental studies indicated that consumption of Maotai, one of the famous liquors in China, exhibits no significant correlation with hepatic fibrosis or cirrhosis as other beverage sources do. This study detected the relationship of Maotai consumption and HCC development in a diethylnitrosamine (DEN)-initiated HCC animal model. DEN was given to mice at a dose of 100 mg/kg, ip, and 50 mg/kg, ip in the following week. Mice were simultaneously given Maotai or an equal amount of ethanol (53%, 5 ml/kg/day, 5days/week for up to 35weeks). At 3-week and 35-week of the experiment, serum and livers were collected for biochemical and histopathological examination of liver injury and incidence of HCC. Real-time RT-PCR, immunohistochemistry and Western blotting were used to examine the expression of metallothionein-1/2 (MT-1/2), NF-E2-related factor 2 (Nrf2), glutamate-cysteine ligase catalytic subunit (GCLC) and modified subunit (GCLM). We identified tissue damage and dysfunction of liver in ethanol + DEN-treated mice, whereas the extent of injury was reduced in Maotai+ DEN-treated mice. Significant Glypican-3(GPC3) expression and precancerous injury or HCC were seen in approximately 50% of mice with ethanol+ DEN, but barely be seen in Maotai + DEN-treated mice. A higher expression of MT-1/2, Nrf2 and GCLC could be seen in Maotai + DEN-treated mice. Thus, Maotai liquor ameliorates the formation of DEN-induced HCC in mice, and the protection mechanism is possibly related with the activation of anti-oxidation factors, such as MTs, Nrf2 and GCLC.
C1 [Yi, Xu; Long, Li; Cheng, Mingliang] Guiyang Med Coll Hosp, Guiyang, Guizhou, Peoples R China.
[Yang, Chunzhang] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Lu, Yingying] Beijing 302 Hosp, Ctr Therapeut Res Hepatocellular Carcinoma, Beijing, Peoples R China.
RP Cheng, ML (reprint author), Guiyang Med Coll Hosp, Guiyang, Guizhou, Peoples R China.
EM mlcheng@yeah.net
FU project 973, Department of Science and Technology, Government of China
[2011CB512114]
FX Supported by a grant from the project 973, Department of Science and
Technology, Government of China (2011CB512114). The funder had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 54
TC 4
Z9 5
U1 6
U2 41
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 1
PY 2014
VL 9
IS 4
AR e93599
DI 10.1371/journal.pone.0093599
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE6KM
UT WOS:000334101100110
PM 24690765
ER
PT J
AU Belcher, AM
Volkow, ND
Moeller, FG
Ferre, S
AF Belcher, Annabelle M.
Volkow, Nora D.
Moeller, F. Gerard
Ferre, Sergi
TI Personality traits and vulnerability or resilience to substance use
disorders
SO TRENDS IN COGNITIVE SCIENCES
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; MENTAL-DISORDERS; INDIVIDUAL-DIFFERENCES;
POSITIVE EMOTIONALITY; RECEPTOR AVAILABILITY; RESPONSE-INHIBITION;
COGNITIVE CONTROL; DECISION-MAKING; BLINK RATES; DOPAMINE
AB Clear evidence supports a genetic basis for substance use disorders (SUD). Yet, the search to identify individual gene contributions to SUD has been unsuccessful. Here, we argue for the study of endophenotypes within the frame of individual differences, and identify three high-order personality traits that are tied to specific brain systems and genes, and that offer a tractable approach to studying SUD. These personality traits, and the genes that moderate them, interact dynamically with the environment and with the drugs themselves to determine ultimately an individual's vulnerability or resilience to developing SUD.
C1 [Belcher, Annabelle M.; Ferre, Sergi] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Volkow, Nora D.] NIDA, NIH, Bethesda, MD 20892 USA.
[Moeller, F. Gerard] Virginia Commonwealth Univ, Sch Med, Dept Psychiat, Richmond, VA 23219 USA.
[Moeller, F. Gerard] Virginia Commonwealth Univ, Sch Med, Dept Pharmacol & Toxicol, Richmond, VA 23219 USA.
RP Ferre, S (reprint author), NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM sferre@intra.nida.nih.gov
RI Ferre, Sergi/K-6115-2014
OI Ferre, Sergi/0000-0002-1747-1779
FU NIDA Intramural Research Program
FX Supported by the NIDA Intramural Research Program.
NR 78
TC 20
Z9 20
U1 3
U2 26
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1364-6613
J9 TRENDS COGN SCI
JI TRENDS COGN. SCI.
PD APR
PY 2014
VL 18
IS 4
BP 211
EP 217
DI 10.1016/j.tics.2014.01.010
PG 7
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA AE6UA
UT WOS:000334132200010
PM 24612993
ER
PT J
AU Bukreyev, AA
Chandran, K
Dolnik, O
Dye, JM
Ebihara, H
Leroy, EM
Muhlberger, E
Netesov, SV
Patterson, JL
Paweska, JT
Saphire, EO
Smither, SJ
Takada, A
Towner, JS
Volchkov, VE
Warren, TK
Kuhn, JH
AF Bukreyev, Alexander A.
Chandran, Kartik
Dolnik, Olga
Dye, John M.
Ebihara, Hideki
Leroy, Eric M.
Muehlberger, Elke
Netesov, Sergey V.
Patterson, Jean L.
Paweska, Janusz T.
Saphire, Erica Ollmann
Smither, Sophie J.
Takada, Ayato
Towner, Jonathan S.
Volchkov, Viktor E.
Warren, Travis K.
Kuhn, Jens H.
TI Discussions and decisions of the 2012-2014 International Committee on
Taxonomy of Viruses (ICTV) Filoviridae Study Group, January 2012-June
2013
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID FAMILY FILOVIRIDAE; STANDARDIZED NOMENCLATURE; SPECIES LEVEL;
CLASSIFICATION; FILOVIRUSES; VARIANTS; PROPOSAL; NAMES
AB The International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group prepares proposals on the classification and nomenclature of filoviruses to reflect current knowledge or to correct disagreements with the International Code of Virus Classification and Nomenclature (ICVCN). In recent years, filovirus taxonomy has been corrected and updated, but parts of it remain controversial, and several topics remain to be debated. This article summarizes the decisions and discussion of the currently acting ICTV Filoviridae Study Group since its inauguration in January 2012.
C1 [Bukreyev, Alexander A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Bukreyev, Alexander A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA.
[Chandran, Kartik] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
[Dolnik, Olga] Univ Marburg, Inst Virol, D-35032 Marburg, Germany.
[Dye, John M.; Warren, Travis K.] US Army Med Res Inst Infect Dis, Frederick, MD USA.
[Ebihara, Hideki] NIAID, Rocky Mt Labs, Integrated Res Facil, NIH, Hamilton, MT 59840 USA.
[Leroy, Eric M.] IRD, Ctr Int Rech Med Franceville, Franceville, Gabon.
[Muehlberger, Elke] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
[Muehlberger, Elke] Boston Univ, Sch Med, Natl Emerging Infect Dis Lab, Boston, MA 02118 USA.
[Netesov, Sergey V.] Novosibirsk State Univ, Novosibirsk 630090, Novosibirsk Obl, Russia.
[Patterson, Jean L.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX USA.
[Paweska, Janusz T.] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Ctr Emerging & Zoonot Dis, Johannesburg, Gauteng, South Africa.
[Saphire, Erica Ollmann] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Saphire, Erica Ollmann] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Smither, Sophie J.] DSTL, Dept Biomed Sci, Salisbury, Wilts, England.
[Takada, Ayato] Hokkaido Univ, Div Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido, Japan.
[Towner, Jonathan S.] Ctr Dis Control & Prevent, Viral Special Pathogens Branch, Div High Consequence Pathogens Pathol, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA.
[Volchkov, Viktor E.] Univ Lyon, UCB Lyon 1, Ecole Normale Super Lyon, INSERM,U758,Lab Filovirus, Lyon, France.
[Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, Frederick, MD 21702 USA.
RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA.
EM kuhnjens@mail.nih.gov
RI Volchkov, Viktor/M-7846-2014; Kuhn, Jens H./B-7615-2011; Netesov,
Sergey/A-3751-2013; LEROY, Eric/I-4347-2016
OI Volchkov, Viktor/0000-0001-7896-8706; Kuhn, Jens H./0000-0002-7800-6045;
Netesov, Sergey/0000-0002-7786-2464; LEROY, Eric/0000-0003-0022-0890
FU NIAID [HHSN272200700016I]
FX The content of this publication does not necessarily reflect the views
or policies of the US Department of the Army, the US Department of
Defense or the US Department of Health and Human Services or of the
institutions and companies affiliated with the authors. JHK performed
this work as an employee of Tunnell Consulting, Inc., a subcontractor to
Battelle Memorial Institute under its prime contract with NIAID, under
Contract No. HHSN272200700016I.
NR 17
TC 25
Z9 28
U1 0
U2 11
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0304-8608
EI 1432-8798
J9 ARCH VIROL
JI Arch. Virol.
PD APR
PY 2014
VL 159
IS 4
BP 821
EP 830
DI 10.1007/s00705-013-1846-9
PG 10
WC Virology
SC Virology
GA AE5UQ
UT WOS:000334055200025
PM 24122154
ER
PT J
AU Webster, BR
Scott, I
Traba, J
Han, K
Sack, MN
AF Webster, Bradley R.
Scott, Iain
Traba, Javier
Han, Kim
Sack, Michael N.
TI Regulation of autophagy and mitophagy by nutrient availability and
acetylation
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Review
DE Acetylation; Sirt3; GCN5L1; Mitophagy; Autophagy
ID MITOCHONDRIAL PROTEIN ACETYLATION; LIFE-SPAN EXTENSION;
STARVATION-INDUCED AUTOPHAGY; FATTY-ACID OXIDATION; CALORIE RESTRICTION;
LYSINE ACETYLATION; SACCHAROMYCES-CEREVISIAE; PARKINSONS-DISEASE; MOUSE
MODEL; SIRT3-MEDIATED DEACETYLATION
AB Normal cellular function is dependent on a number of highly regulated homeostatic mechanisms, which act in concert to maintain conditions suitable for life. During periods of nutritional deficit, cells initiate a number of recycling programs which break down complex intracellular structures, thus allowing them to utilize the energy stored within. These recycling systems, broadly named "autophagy", enable the cell to maintain the flow of nutritional substrates until they can be replenished from external sources. Recent research has shown that a number of regulatory components of the autophagy program are controlled by lysine acetylation. Lysine acetylation is a reversible post-translational modification that can alter the activity of enzymes in a number of cellular compartments. Strikingly, the main substrate for this modification is a product of cellular energy metabolism: acetyl-CoA. This suggests a direct and intricate link between fuel metabolites and the systems which regulate nutritional homeostasis. In this review, we examine how acetylation regulates the systems that control cellular autophagy, and how global protein acetylation status may act as a trigger for recycling of cellular components in a nutrient-dependent fashion. In particular, we focus on how acetylation may control the degradation and turnover of mitochondria, the major source of fuel-derived acetyl-CoA. Published by Elsevier B.V.
C1 [Webster, Bradley R.; Scott, Iain; Traba, Javier; Han, Kim; Sack, Michael N.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
RP Sack, MN (reprint author), Bld 10 CRC,Room 5-3150,10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA.
EM sackm@nih.gov
FU Division of Intramural Research of the National Heart Lung and Blood
Institute of the NIH
FX This study was supported by the Division of Intramural Research of the
National Heart Lung and Blood Institute of the NIH.
NR 138
TC 12
Z9 12
U1 2
U2 33
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1388-1981
EI 0006-3002
J9 BBA-MOL CELL BIOL L
JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids
PD APR
PY 2014
VL 1841
IS 4
BP 525
EP 534
DI 10.1016/j.bbalip.2014.02.001
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA AE3CD
UT WOS:000333853600006
PM 24525425
ER
PT J
AU Vuong, H
Stephens, RM
Volfovsky, N
AF Vuong, Hue
Stephens, Robert M.
Volfovsky, Natalia
TI AVIA: an interactive web-server for annotation, visualization and impact
analysis of genomic variations
SO BIOINFORMATICS
LA English
DT Article
ID GENETIC-VARIANTS; DATABASE
AB Motivation: The plethora of information that emerges from largescale genome characterization studies has triggered the development of computational frameworks and tools for efficient analysis, interpretation and visualization of genomic data. Functional annotation of genomic variations and the ability to visualize the data in the context of whole genome and/or multiple genomes has remained a challenging task. We have developed an interactive web-based tool, AVIA (Annotation, Visualization and Impact Analysis), to explore and interpret large sets of genomic variations (single nucleotide variations and insertion/deletions) and to help guide and summarize genomic experiments. The annotation, summary plots and tables are packaged and can be downloaded by the user from the email link provided.
C1 [Vuong, Hue; Stephens, Robert M.; Volfovsky, Natalia] SAIC Frederick Inc, ABCC, Informat Syst Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Vuong, H (reprint author), SAIC Frederick Inc, ABCC, Informat Syst Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM vuonghm@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX National Cancer Institute, National Institutes of Health, under contract
[HHSN261200800001E].
NR 15
TC 2
Z9 2
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD APR 1
PY 2014
VL 30
IS 7
BP 1013
EP 1014
DI 10.1093/bioinformatics/btt655
PG 2
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA AE6DC
UT WOS:000334078300020
PM 24215028
ER
PT J
AU Sarkar, SK
Bumb, A
Wu, XF
Sochacki, KA
Kellman, P
Brechbiel, MW
Neuman, KC
AF Sarkar, Susanta K.
Bumb, Ambika
Wu, Xufeng
Sochacki, Kem A.
Kellman, Peter
Brechbiel, Martin W.
Neuman, Keir C.
TI Wide-field in vivo background free imaging by selective magnetic
modulation of nanodiamond fluorescence
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID REAL-TIME; DIAMOND; MULTICOLOR; STABILITY
AB The sensitivity and resolution of fluorescence-based imaging in vivo is often limited by autofluorescence and other background noise. To overcome these limitations, we have developed a wide-field background-free imaging technique based on magnetic modulation of fluorescent nanodiamond emission. Fluorescent nanodiamonds are bright, photo-stable, biocompatible nanoparticles that are promising probes for a wide range of in vitro and in vivo imaging applications. Our readily applied background-free imaging technique improves the signal-to-background ratio for in vivo imaging up to 100-fold. This technique has the potential to significantly improve and extend fluorescent nanodiamond imaging capabilities on diverse fluorescence imaging platforms. (C) 2014 Optical Society of America
C1 [Sarkar, Susanta K.; Bumb, Ambika; Sochacki, Kem A.; Neuman, Keir C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Wu, Xufeng] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
[Kellman, Peter] NHLBI, NIH, Bethesda, MD 20892 USA.
[Brechbiel, Martin W.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Sarkar, SK (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM neumankc@mail.nih.gov
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
FU National Heart, Lung, and Blood Institute; National Cancer Institute,
Center for Cancer Research, National Institutes of Health
FX The authors thank the National Cancer Institute's Molecular Imaging
Program for allowing access to their Maestro imaging system. This work
was supported by the Intramural Research Programs of the National Heart,
Lung, and Blood Institute and the National Cancer Institute, Center for
Cancer Research, National Institutes of Health. We are indebted to
Gopalakrishnan Balasubramanian and John Silver for helpful discussions
and we thank John Silver, Tamara Litwin and Maria Mills for comments on
the manuscript.
NR 34
TC 19
Z9 19
U1 2
U2 44
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD APR 1
PY 2014
VL 5
IS 4
BP 1190
EP 1202
DI 10.1364/BOE.5.001190
PG 13
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA AE6DB
UT WOS:000334078100018
PM 24761300
ER
PT J
AU Greenwald, P
Stoner, G
Colburn, N
Lippman, SM
AF Greenwald, Peter
Stoner, Gary
Colburn, Nancy
Lippman, Scott M.
TI John A. Milner: In Memoriam (1947-2013)
SO CANCER PREVENTION RESEARCH
LA English
DT Biographical-Item
C1 [Greenwald, Peter] NCI, NIH, Bethesda, MD 20892 USA.
[Stoner, Gary] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Colburn, Nancy] NCI, Canc Res Ctr, Frederick Natl Lab, Frederick, MD 21701 USA.
[Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
RP Greenwald, P (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD APR
PY 2014
VL 7
IS 4
BP 373
EP 374
DI 10.1158/1940-6207.CAPR-14-0060
PG 2
WC Oncology
SC Oncology
GA AE5VK
UT WOS:000334057200001
PM 24695271
ER
PT J
AU Braganza, MZ
de Gonzalez, AB
Schonfeld, SJ
Wentzensen, N
Brenner, AV
Kitahara, CM
AF Braganza, Melissa Z.
de Gonzalez, Amy Berrington
Schonfeld, Sara J.
Wentzensen, Nicolas
Brenner, Alina V.
Kitahara, Cari M.
TI Benign Breast and Gynecologic Conditions, Reproductive and Hormonal
Factors, and Risk of Thyroid Cancer
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID EPITHELIAL OVARIAN-CANCER; LIFETIME OVULATORY CYCLES; POSTMENOPAUSAL
WOMEN; UTERINE FIBROIDS; UNITED-STATES; ENDOMETRIAL CANCER; CUMULATIVE
NUMBER; MENSTRUAL CYCLES; POOLED ANALYSIS; SEX-HORMONES
AB The higher incidence of thyroid cancer in women compared with men suggests an influence of sex steroid hormones in the etiology of this malignancy. We investigated a comprehensive set of potential indicators of lifetime sex steroid hormone exposure in relation to thyroid cancer risk. Using data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which enrolled 70,047 women, 50 to 78 years old, we prospectively examined associations of self-reported history of benign breast and gynecologic conditions, reproductive factors, and exogenous sex hormone use with thyroid cancer risk. Multivariable-adjusted HRs and 95% confidence intervals (CI) were calculated in models using age as the time metric. During follow-up (median, 11 years), 127 women were diagnosed with first primary thyroid cancer. Older age at natural menopause (>= 55 vs. < 50 years; HR, 2.24; 95% CI, 1.20-4.18), greater estimated lifetime number of ovulatory cycles (>= 490 vs. < 415 cycles; HR, 2.40; 95% CI, 1.33-4.30), greater number of live births (>= 5 vs. 1-2; HR, 1.72; 95% CI, 1.05-2.82), and history of uterine fibroids (HR, 1.72; 95% CI, 1.18-2.50) were associated with an increased risk of thyroid cancer. Earlier age at menarche, greater number of reproductive years, history of a tubal ligation, and history of ovarian cysts were nonsignificantly associated with increased thyroid cancer risk. No associations were observed for oral contraceptive use, menopausal hormone therapy, or history of benign breast disease or endometriosis. In general, we found that factors reflecting a greater length of exposure to endogenous hormones, particularly during the reproductive years, were associated with risk of postmenopausal thyroid cancer.(c) 2014 AACR.
C1 [Braganza, Melissa Z.; de Gonzalez, Amy Berrington; Wentzensen, Nicolas; Brenner, Alina V.; Kitahara, Cari M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Schonfeld, Sara J.] Int Agcy Res Canc, Sect Environm & Radiat, F-69372 Lyon, France.
RP Braganza, MZ (reprint author), NCI, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM melissa.braganza@nih.gov
RI Kitahara, Cari/R-8267-2016
FU Intramural Research Program of the National Cancer Institute, NIH
FX This work was supported in part by the Intramural Research Program of
the National Cancer Institute, NIH.
NR 49
TC 10
Z9 10
U1 1
U2 12
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD APR
PY 2014
VL 7
IS 4
BP 418
EP 425
DI 10.1158/1940-6207.CAPR-13-0367
PG 8
WC Oncology
SC Oncology
GA AE5VK
UT WOS:000334057200007
PM 24449056
ER
PT J
AU Ardiani, A
Gameiro, SR
Palena, C
Hamilton, DH
Kwilas, A
King, TH
Schlom, J
Hodge, JW
AF Ardiani, Andressa
Gameiro, Sofia R.
Palena, Claudia
Hamilton, Duane H.
Kwilas, Anna
King, Thomas H.
Schlom, Jeffrey
Hodge, James W.
TI Vaccine-Mediated Immunotherapy Directed against a Transcription Factor
Driving the Metastatic Process
SO CANCER RESEARCH
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; BREAST-CANCER; PROSTATE-CANCER;
E-CADHERIN; COMBINATION THERAPY; COLORECTAL-CANCER; PROMOTES INVASION;
TUMOR PROGRESSION; TWIST EXPRESSION; FACTOR BRACHYURY
AB Numerous reports have now demonstrated that the epithelial-to-mesenchymal transition (EMT) process is involved in solid tumor progression, metastasis, and drug resistance. Several transcription factors have been implicated as drivers of EMT and metastatic progression, including Twist. Overexpression of Twist has been shown to be associated with poor prognosis and drug resistance for many carcinomas and other tumor types. The role of Twist in experimental cancer metastases has been principally studied in the 4T1 mammary tumor model, where silencing of Twist in vitro has been shown to greatly reduce in vivo metastatic spread. Transcription factors such as Twist are generally believed to be "undruggable" because of their nuclear location and lack of a specific groove for tight binding of a small molecule inhibitor. An alternative approach to drug therapy targeting transcription factors driving the metastatic process is T-cell-mediated immunotherapy. A therapeutic vaccine platform that has been previously characterized consists of heat-killed recombinant Saccharomyces cerevisiae (yeast) capable of expressing tumor-associated antigen protein. We report here the construction and characterization of a recombinant yeast expressing the entire Twist protein, which is capable of inducing both CD8(+) and CD4(+) Twist-specific T-cell responses in vivo. Vaccination of mice reduced the size of primary transplanted 4T1 tumors and had an even greater antitumor effect on lung metastases of the same mice, which was dependent on Twist-specific CD8(+) T cells. These studies provide the rationale for vaccine-induced T-cell-mediated therapy of transcription factors involved in driving the metastatic process. (C)2014 AACR.
C1 [Ardiani, Andressa; Gameiro, Sofia R.; Palena, Claudia; Hamilton, Duane H.; Kwilas, Anna; Schlom, Jeffrey; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[King, Thomas H.] GlobeImmune Inc, Louisville, CO USA.
RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA.
EM js141c@nih.gov
RI Hodge, James/D-5518-2015
OI Hodge, James/0000-0001-5282-3154
FU Intramural Research Program of the Center for Cancer Research;
Cooperative Research and Development Agreement (CRADA); GlobeImmune,
Inc.; National Cancer Institute, NIH
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, NIH, and through
a Cooperative Research and Development Agreement (CRADA) with
GlobeImmune, Inc.
NR 50
TC 9
Z9 9
U1 0
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 1
PY 2014
VL 74
IS 7
BP 1945
EP 1957
DI 10.1158/0008-5472.CAN-13-2045
PG 13
WC Oncology
SC Oncology
GA AE3TL
UT WOS:000333900500008
PM 24520078
ER
PT J
AU Ohnuki, H
Jiang, K
Wang, DR
Salvucci, O
Kwak, H
Sanchez-Martin, D
Maric, D
Tosato, G
AF Ohnuki, Hidetaka
Jiang, Kan
Wang, Dunrui
Salvucci, Ombretta
Kwak, Hyeongil
Sanchez-Martin, David
Maric, Dragan
Tosato, Giovanna
TI Tumor-Infiltrating Myeloid Cells Activate DII4/Notch/TGF-beta Signaling
to Drive Malignant Progression
SO CANCER RESEARCH
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; TRANSCRIPTION FACTOR GFI-1; TGF-BETA;
BREAST-CANCER; C-MYC; NOTCH; MICROENVIRONMENT; DIFFERENTIATION;
ANGIOGENESIS; METASTASIS
AB Myeloid cells that orchestrate malignant progression in the tumor microenvironment offer targets for a generalized strategy to attack solid tumors. Through an analysis of tumor microenvironments, we explored an experimental model of lung cancer that uncovered a network of DII4/Notch/TGF-beta 1 signals that links myeloid cells to cancer progression. Myeloid cells attracted to the tumor microenvironment by the tumor-derived cytokines CCL2 and M-CSF expressed increased levels of the Notch ligand DII4, thereby activating Notch signaling in the tumor cells and amplifying tumor-intrinsic Notch activation. Heightened DII4/Notch signaling in tumor cells magnified TGF-beta-induced pSMAD2/3 signaling and was required to sustain TGF-beta-induced tumor cell growth. Conversely, Notch blockade reduced TGF-beta signaling and limited lung carcinoma tumor progression. Corroborating these findings, by interrogating RNAseq results from tumor and adjacent normal tissue in clinical specimens of human head and neck squamous carcinoma, we found evidence that TGF-beta/Notch crosstalk contributed to progression. In summary, the myeloid cell-carcinoma signaling network we describe uncovers novel mechanistic links between the tumor microenvironment and tumor growth, highlighting new opportunities to target tumors where this network is active. (C)2014 AACR.
C1 [Ohnuki, Hidetaka; Jiang, Kan; Salvucci, Ombretta; Kwak, Hyeongil; Sanchez-Martin, David; Tosato, Giovanna] NCI, Cellular Oncol Lab, CCR, NIH, Bethesda, MD 20892 USA.
[Maric, Dragan] Natl Inst Neurol Disorders & Stroke, Dept Intramural Res, Bethesda, MD USA.
[Wang, Dunrui] W2Motif LLC, San Diego, CA USA.
RP Tosato, G (reprint author), NCI, Cellular Oncol Lab, CCR, NIH, Bldg 37,Room 4124,37 Convent Dr, Bethesda, MD 20892 USA.
EM Tosatog@mail.nih.gov
RI Ohnuki, Hidetaka/E-1877-2012; Sanchez-Martin, David/C-9927-2013
OI Ohnuki, Hidetaka/0000-0001-8951-3264; Sanchez-Martin,
David/0000-0002-2712-4762
FU Intramural Research Program of CCR/NCI/NIH; NINDS/NIH; JSPS [S2207]
FX The work was supported by the Intramural Research Program of CCR/NCI/NIH
and NINDS/NIH; H. Ohnuki was supported in part by Grant-in-Aid for
Scientific Research (S2207), JSPS.
NR 50
TC 14
Z9 14
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 1
PY 2014
VL 74
IS 7
BP 2038
EP 2049
DI 10.1158/0008-5472.CAN-13-3118
PG 12
WC Oncology
SC Oncology
GA AE3TL
UT WOS:000333900500016
PM 24520074
ER
PT J
AU Horska, A
Nidecker, A
Intrapiromkul, J
Tannazi, F
Ardekani, S
Brant, LJ
Wharam, M
Mahone, EM
AF Horska, Alena
Nidecker, Anna
Intrapiromkul, Jarunee
Tannazi, Firouzeh
Ardekani, Siamak
Brant, Larry J.
Wharam, Moody, Jr.
Mahone, E. Mark
TI Diffusion tensor imaging of deep gray matter in children treated for
brain malignancies
SO CHILDS NERVOUS SYSTEM
LA English
DT Article
DE Radiation therapy; Children; Brain; Basal ganglia; Hippocampus;
Diffusion tensor imaging
ID WHITE-MATTER; CRANIAL RADIATION; CHILDHOOD-CANCER; GREY-MATTER;
MEDULLOBLASTOMA; MATURATION; NETWORK; PERFORMANCE; SURVIVORS; THERAPY
AB Previous DTI studies reported microstructural changes in white matter of patients receiving treatment for brain malignancies. The primary aim of this prospective pilot longitudinal study was to examine if DTI can detect microstructural changes in deep gray matter (as evaluated by the apparent diffusion coefficient, ADC) between pediatric patients treated with cranial radiation therapy and typically developing healthy children. The relationship between ADC and neurobehavioral performance was also examined.
ADC was measured at 1.5 T in the caudate, putamen, globus pallidus, thalamus, and hippocampus in nine patients (mean age 11.8 years) and nine age-matched healthy controls. The study was designed with four visits: baseline, 6-month, 15-month, and 27-month follow-ups.
Patients had 24 % higher overall mean ADC in the hippocampus compared with controls (p = 0.003). Post hoc analyses revealed significantly elevated ADC at baseline (p = 0.003) and at the 27-month follow-up (p = 0.006). Nevertheless, patients performed normally on a verbal memory test considered to be a hippocampus-related function. Relative to controls, patients' performance on the tests of the visual-spatial working memory decreased over time (group by visit, p = 0.036). Both patients and controls showed a decline in motor speed with increasing ADC in the globus pallidus and putamen.
Childhood brain malignancies and their treatment may affect gray matter microstructure as measured by water diffusion. Significant findings in the hippocampus but not other regions suggest that differences in tissue sensitivity to disease- and treatment-related injury among gray matter regions may exist. ADC in basal ganglia may be associated with motor performance.
C1 [Horska, Alena; Nidecker, Anna; Intrapiromkul, Jarunee; Tannazi, Firouzeh] Johns Hopkins Univ, Div Neuroradiol, Russell H Morgan Dept Radiol & Radiol Sci, Sch Med, Baltimore, MD 21287 USA.
[Ardekani, Siamak] Johns Hopkins Univ, Ctr Imaging Sci, Baltimore, MD 21218 USA.
[Brant, Larry J.] NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Wharam, Moody, Jr.] Johns Hopkins Univ, Dept Radiat Oncol & Mol Radiat Sci, Sch Med, Baltimore, MD 21231 USA.
[Mahone, E. Mark] Kennedy Krieger Inst, Dept Neuropsychol, Baltimore, MD 21231 USA.
RP Horska, A (reprint author), Johns Hopkins Univ, Div Neuroradiol, Russell H Morgan Dept Radiol & Radiol Sci, Sch Med, 600 N Wolfe St, Baltimore, MD 21287 USA.
EM ahorska@jhmi.edu
FU National Institutes of Health [R01 NS042851, P30HD024061-16]; Johns
Hopkins University School of Medicine Institute for Clinical and
Translational Research, National Institutes of Health/National Center
for Research Resources Clinical and Translational Sciences Awards
Program [UL1-RR025005]; Intellectual and Developmental Disabilities
Research Center, Imaging Core, National Institute of Child Health and
Human Development [P30HD024061]
FX The study was supported by the National Institutes of Health R01
NS042851; P30HD024061-16; Johns Hopkins University School of Medicine
Institute for Clinical and Translational Research, National Institutes
of Health/National Center for Research Resources Clinical and
Translational Sciences Awards Program, UL1-RR025005; Intellectual and
Developmental Disabilities Research Center, Imaging Core, P30HD024061,
National Institute of Child Health and Human Development.
NR 29
TC 2
Z9 2
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0256-7040
EI 1433-0350
J9 CHILD NERV SYST
JI Childs Nerv. Syst.
PD APR
PY 2014
VL 30
IS 4
BP 631
EP 638
DI 10.1007/s00381-013-2315-1
PG 8
WC Clinical Neurology; Pediatrics; Surgery
SC Neurosciences & Neurology; Pediatrics; Surgery
GA AE5UT
UT WOS:000334055500012
PM 24264381
ER
PT J
AU Tan, PZ
Lee, KH
Dahl, RE
Nelson, EE
Stroud, LJ
Siegle, GJ
Morgan, JK
Silk, JS
AF Tan, Patricia Z.
Lee, Kyung Hwa
Dahl, Ronald E.
Nelson, Eric E.
Stroud, Laura J.
Siegle, Greg J.
Morgan, Judith K.
Silk, Jennifer S.
TI Associations between maternal negative affect and adolescent's neural
response to peer evaluation
SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE
LA English
DT Article
DE Parenting; Adolescents; Peer evaluation; Reward; Amygdala; Subgenual
anterior cingulate cortex
ID FALSE DISCOVERY RATE; ANTERIOR CINGULATE CORTEX; MAJOR DEPRESSIVE
DISORDER; INTEROCEPTIVE AWARENESS; CHILD INTERACTIONS; PREFRONTAL
CORTEX; SOCIAL EVALUATION; ANGER REGULATION; BRAIN STRUCTURE; POSITIVE
AFFECT
AB Parenting is often implicated as a potential source of individual differences in youths' emotional information processing. The present study examined whether parental affect is related to an important aspect of adolescent emotional development, response to peer evaluation. Specifically, we examined relations between maternal negative affect, observed during parent-adolescent discussion of an adolescent-nominated concern with which s/he wants parental support, and adolescent neural responses to peer evaluation in 40 emotionally healthy and depressed adolescents. We focused on a network of ventral brain regions involved in affective processing of social information: the amygdala, anterior insula, nucleus accumbens, and subgenual anterior cingulate, as well as the ventrolateral prefrontal cortex. Maternal negative affect was not associated with adolescent neural response to peer rejection. However, longer durations of maternal negative affect were associated with decreased responsivity to peer acceptance in the amygdala, left anterior insula, subgenual anterior cingulate, and left nucleus accumbens. These findings provide some of the first evidence that maternal negative affect is associated with adolescents' neural processing of social rewards. Findings also suggest that maternal negative affect could contribute to alterations in affective processing, specifically, dampening the saliency and/or reward of peer interactions during adolescence. (C) 2014 The Authors. Published by Elsevier Ltd. All rights reserved.
C1 [Tan, Patricia Z.; Lee, Kyung Hwa; Siegle, Greg J.; Morgan, Judith K.; Silk, Jennifer S.] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA.
[Dahl, Ronald E.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Nelson, Eric E.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA.
[Stroud, Laura J.] Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI USA.
RP Tan, PZ (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, 3811 Ohara St, Pittsburgh, PA 15213 USA.
EM tanpz@upmc.edu
OI Nelson, Eric/0000-0002-3376-2453; Silk, Jennifer/0000-0002-8638-4337
FU National Institute of Drug Abuse [R21DA024144]; Clinical and
Translational Science Institute at the University of Pittsburgh
(NIH/NCRR/CTSA) [UL1 RR024153]; National Institute of Mental Health
intramural research program
FX This research was supported by National Institute of Drug Abuse grant
R21DA024144 (Jennifer S. Silk/Ronald E. Dahl, PI's), the Clinical and
Translational Science Institute at the University of Pittsburgh
(NIH/NCRR/CTSA Grant UL1 RR024153), and the National Institute of Mental
Health intramural research program.
NR 70
TC 8
Z9 8
U1 5
U2 14
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1878-9293
EI 1878-9307
J9 DEV COGN NEUROS-NETH
JI Dev. Cogn. Neurosci.
PD APR
PY 2014
VL 8
BP 28
EP 39
DI 10.1016/j.dcn.2014.01.006
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA AE5HW
UT WOS:000334019400004
PM 24613174
ER
PT J
AU Ernst, M
Plate, RC
Carlisi, CO
Gorodetsky, E
Goldman, D
Pine, DS
AF Ernst, Monique
Plate, Rista C.
Carlisi, Christina O.
Gorodetsky, Elena
Goldman, David
Pine, Daniel S.
TI Loss aversion and 5HTT gene variants in adolescent anxiety
SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE
LA English
DT Article
DE Risk-taking; Microeconomics; Lambda; Impulsivity; Development;
Risk-avoidance
ID SEROTONIN TRANSPORTER GENE; DEFICIT HYPERACTIVITY DISORDER;
OBSESSIVE-COMPULSIVE DISORDER; PROMOTER REGION POLYMORPHISM; SOCIAL
ANXIETY; RISK-TAKING; REGULATORY REGION; MENTAL-DISORDERS;
DECISION-MAKING; PROSPECT-THEORY
AB Loss aversion, a well-documented behavioral phenomenon, characterizes decisions under risk in adult populations. As such, loss aversion may provide a reliable measure of risky behavior. Surprisingly, little is known about loss aversion in adolescents, a group who manifests risk-taking behavior, or in anxiety disorders, which are associated with risk avoidance. Finally, loss aversion is expected to be modulated by genotype, particularly the serotonin transporter (SERT) gene variant, based on its role in anxiety and impulsivity. This genetic modulation may also differ between anxious and healthy adolescents, given their distinct propensities for risk taking. The present work examines the modulation of loss aversion, an index of risk-taking, and reaction-time to decision, an index of impulsivity, by the serotonin-transporter-gene-linked polymorphisms (5HTTLPR) in healthy and clinically anxious adolescents. Findings show that loss aversion (1) does manifest in adolescents, (2) does not differ between healthy and clinically anxious participants, and (3), when stratified by SERT genotype, identifies a subset of anxious adolescents who are high SERT-expressers, and show excessively low loss-aversion and high impulsivity. This last finding may serve as preliminary evidence for 5HTTLPR as a risk factor for the development of comorbid disorders associated with risk-taking and impulsivity in clinically anxious adolescents. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
C1 [Ernst, Monique; Carlisi, Christina O.; Gorodetsky, Elena; Pine, Daniel S.] NIMH, Bethesda, MD 20817 USA.
[Plate, Rista C.; Gorodetsky, Elena] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA.
[Gorodetsky, Elena; Goldman, David] NIAAA, NIH, Bethesda, MD USA.
RP Ernst, M (reprint author), NIMH, Bldg 15-K,Room 110,MSC 2670, Bethesda, MD 20817 USA.
EM ernstm@mail.nih.gov
RI Goldman, David/F-9772-2010;
OI Goldman, David/0000-0002-1724-5405; Carlisi,
Christina/0000-0002-0942-8586
FU Intramural NIH HHS [Z99 MH999999]
NR 40
TC 4
Z9 5
U1 0
U2 10
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1878-9293
EI 1878-9307
J9 DEV COGN NEUROS-NETH
JI Dev. Cogn. Neurosci.
PD APR
PY 2014
VL 8
BP 77
EP 85
DI 10.1016/j.dcn.2013.10.002
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA AE5HW
UT WOS:000334019400008
PM 24280015
ER
PT J
AU Thomas, LA
Brotman, MA
Bones, BL
Chen, G
Rosen, BH
Pine, DS
Leibenluft, E
AF Thomas, Laura A.
Brotman, Melissa A.
Bones, Brian L.
Chen, Gang
Rosen, Brooke H.
Pine, Daniel S.
Leibenluft, Ellen
TI Neural circuitry of masked emotional face processing in youth with
bipolar disorder, severe mood dysregulation, and healthy volunteers
SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE
LA English
DT Article
DE Bipolar disorder; Adolescence; Mood disorder; Functional neuroimaging;
Backwards masking; Affective priming
ID POSTTRAUMATIC-STRESS-DISORDER; FACIAL EXPRESSIONS; AMYGDALA RESPONSE;
PREFRONTAL CORTEX; CLINICAL DEPRESSION; LABELING DEFICITS;
BACKWARD-MASKING; FUNCTIONAL MRI; VISUAL-CORTEX; ANGRY FACES
AB Youth with bipolar disorder (BD) and those with severe, non-episodic irritability (severe mood dysregulation, SMD) show face-emotion labeling deficits. These groups differ from healthy volunteers (HV) in neural responses to emotional faces. It is unknown whether awareness is required to elicit these differences. We compared activation in BD (N = 20), SMD (N = 18), and HV (N = 22) during "Aware" and "Non-aware" priming of shapes by emotional faces. Subjects rated how much they liked the shape. In aware, a face ( angry, fearful, happy, neutral, blank oval) appeared (187 ms) before the shape. In non-aware, a face appeared (17 ms), followed by a mask (170 ms), and shape. A Diagnosis-by-Awareness-by-Emotion ANOVA was not significant. There were significant Diagnosis-by-Awareness-interactions in occipital regions. BD and SMD showed increased activity for non-aware vs. aware; HV showed the reverse pattern. When subjects viewed angry or neutral faces, there were Emotion-by-Diagnosis interactions in face-emotion processing regions, including the L precentral gyrus, R posterior cingulate, R superior temporal gyrus, R middle occipital gyrus, and L medial frontal gyrus. Regardless of awareness, BD and SMD differ in activation patterns from HV and each other in multiple brain regions, suggesting that BD and SMD are distinct developmental mood disorders. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
C1 [Thomas, Laura A.; Brotman, Melissa A.; Bones, Brian L.; Rosen, Brooke H.; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Emot & Dev Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Thomas, Laura A.] NIDA, Off Director, Bethesda, MD 20892 USA.
[Chen, Gang] NIMH, Sci & Stat Comp Core, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Thomas, LA (reprint author), 9000 Rockville Pike MSC 2670,Bldg 15K,Rm 204, Bethesda, MD 20892 USA.
EM tlaura@mail.nih.gov
RI Brotman, Melissa/H-7409-2013;
OI Thomas, Laura/0000-0002-4106-1358
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health
FX Funding for this study was provided exclusively by the Intramural
Research Program of the National Institute of Mental Health, National
Institutes of Health. We would like to thank the staff of the Emotion
and Development Branch at NIMH and the children and families for their
participation.
NR 78
TC 11
Z9 11
U1 4
U2 10
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1878-9293
EI 1878-9307
J9 DEV COGN NEUROS-NETH
JI Dev. Cogn. Neurosci.
PD APR
PY 2014
VL 8
BP 110
EP 120
DI 10.1016/j.dcn.2013.09.007
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA AE5HW
UT WOS:000334019400013
PM 24239048
ER
PT J
AU Ambale-Venkatesh, B
Armstrong, AC
Liu, CY
Donekal, S
Yoneyama, K
Wu, CO
Gomes, AS
Hundley, G
Bluemke, DA
Lima, JA
AF Ambale-Venkatesh, Bharath
Armstrong, Anderson C.
Liu, Chia-Ying
Donekal, Sirisha
Yoneyama, Kihei
Wu, Colin O.
Gomes, Antoinette S.
Hundley, GregoryW.
Bluemke, David A.
Lima, Joao A.
TI Diastolic function assessed from tagged MRI predicts heart failure and
atrial fibrillation over an 8-year follow-up period: themulti-ethnic
study of atherosclerosis
SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
LA English
DT Article
DE Heart failure; Atrial; Fibrillation; Diastole; Magnetic resonance
imaging
ID LEFT-VENTRICULAR MASS; INCIDENT CARDIOVASCULAR EVENTS;
ISCHEMIC-MYOCARDIUM; MAGNETIC-RESONANCE; RISK SCORE; DYSFUNCTION;
RELAXATION; STRAIN; INDIVIDUALS; CONTRACTION
AB Objectives The strain relaxation index (SRI), a novel diastolic functional parameter derived from tagged magnetic resonance imaging (MRI), is used to assess myocardial deformation during left ventricular relaxation. We investigated whether diastolic function indexed by SRI predicts heart failure (HF) and atrial fibrillation (AF) over an 8-year follow-up.
Methods As a part of the multi-ethnic study of atherosclerosis, 1544 participants free of known cardiovascular disease (CVD) underwent tagged MRI in 2000-02. Harmonic phase analysis was used to compute circumferential strain. Standard parameters, early diastolic strain rate (EDSR) and the peak torsion recoil rate were calculated. An SRI was calculated as difference between post-systolic and systolic times of the strain peaks, divided by the EDSR peak. It was normalized by the total interval of relaxation. Over an 8-year follow-up period, we defined AF (n = 57) or HF (n = 36) as combined (n 80) end-points. Cox regression assessed the ability of SRI to predict events adjusted for risk factors and markers of subclinical disease. Integrated discrimination index (IDI) and net reclassification index (NRI) of SRI, compared with conventional indices, were also assessed.
Results The hazard ratio for SRI remained significant for the combined HF and AF end-points as well as for HF alone after adjustment. For the combined end-point, IDI was 1.5% (P < 0.05) and NRI was 11.4% ( P < 0.05) for SRI. Finally, SRI was more robust than all other existing cardiovascular magnetic resonance diastolic functional parameters.
Conclusion SRI predicts HF and AF over an 8-year follow-up period in a large population free of known CVD, independent of established risk factors and markers of subclinical CVD.
C1 [Ambale-Venkatesh, Bharath; Liu, Chia-Ying] Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21287 USA.
[Armstrong, Anderson C.; Donekal, Sirisha; Yoneyama, Kihei; Lima, Joao A.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD 21287 USA.
[Armstrong, Anderson C.] Univ Fed Valedo, Sao Francisco, PE, Brazil.
[Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Gomes, Antoinette S.] Univ Calif Los Angeles, Sch Med, Dept Radiol, Los Angeles, CA 90024 USA.
[Hundley, GregoryW.] Wake Forest Univ Hlth Sci, Dept Cardiol, Winston Salem, NC USA.
[Bluemke, David A.] NIH, Bethesda, MD 20892 USA.
RP Lima, JA (reprint author), Johns Hopkins Univ, Div Cardiol, 600 N Wolfe St,Blalock 524D1, Baltimore, MD 21287 USA.
EM jlima@jhmi.edu
RI Armstrong, Anderson/G-8407-2012; Ambale Venkatesh, Bharath/F-4941-2016;
OI Armstrong, Anderson/0000-0003-3161-8922; Ambale Venkatesh,
Bharath/0000-0002-2330-2373; Bluemke, David/0000-0002-8323-8086
FU NIDDK NIH HHS [P30 DK079637]
NR 38
TC 8
Z9 8
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2047-2404
EI 2047-2412
J9 EUR HEART J-CARD IMG
JI Eur. Heart J.-Cardiovasc. Imaging
PD APR
PY 2014
VL 15
IS 4
BP 442
EP 449
DI 10.1093/ehjci/jet189
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AE6QE
UT WOS:000334117800014
PM 24145457
ER
PT J
AU Lussier, MP
Gu, XL
Lu, W
Roche, KW
AF Lussier, Marc P.
Gu, Xinglong
Lu, Wei
Roche, Katherine W.
TI Casein kinase 2 phosphorylates GluA1 and regulates its surface
expression
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE AMPAR; synapse; glutamate; CK2; trafficking
ID SYNAPTIC NMDA RECEPTORS; DEPENDENT PROTEIN-KINASE; METABOTROPIC
GLUTAMATE RECEPTORS; POSTSYNAPTIC DENSITY PROTEIN; LONG-TERM
POTENTIATION; AMPA RECEPTORS; GLUR1 SUBUNIT; PARKINSONS-DISEASE;
PLASTICITY; TRAFFICKING
AB Controlling the density of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at synapses is essential for regulating the strength of excitatory neurotransmission. In particular, the phosphorylation of AMPARs is important for defining both synaptic expression and intracellular routing of receptors. Phosphorylation is a post-translational modification known to regulate many cellular events and the C-termini of glutamate receptors are important targets. Recently, the first intracellular loop1 region of the GluA1 subunit of AMPARs was reported to regulate synaptic targeting through phosphorylation of S567 by Ca2+/calmodulin-dependent protein kinase II (CaMKII). Intriguingly, the loop1 region of all four AMPAR subunits contains many putative phosphorylation sites (S/T/Y), leaving the possibility that other kinases may regulate AMPAR surface expression via phosphorylation of the loop regions. To explore this hypothesis, we used in vitro phosphorylation assays with a small panel of purified kinases and found that casein kinase 2 (CK2) phosphorylates the GluA1 and GluA2 loop1 regions, but not GluA3 or GluA4. Interestingly, when we reduced the endogenous expression of CK2 using a specific short hairpin RNA against the regulatory subunit CK2 beta, we detected a reduction of GluA1 surface expression, whereas GluA2 was unchanged. Furthermore, we identified S579 of GluA1 as a substrate of CK2, and the expression of GluA1 phosphodeficient mutants in hippocampal neurons displayed reduced surface expression. Therefore, our study identifies CK2 as a regulator of GluA1 surface expression by phosphorylating the intracellular loop1 region.
C1 [Lussier, Marc P.; Roche, Katherine W.] NINDS, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
[Gu, Xinglong; Lu, Wei] NINDS, Synapse & Neural Circuit Res Unit, NIH, Bethesda, MD 20892 USA.
RP Roche, KW (reprint author), NINDS, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
EM rochek@ninds.nih.gov
RI gu, xinglong/A-3054-2011;
OI gu, xinglong/0000-0002-0437-5606; Roche, Katherine/0000-0001-7282-6539
FU NINDS Intramural Research Program
FX We thank John D. Badger II for technical assistance, the NINDS DNA
sequencing facility and Rolf Sprengel for providing us with the GluA1
knockout mouse line. The NINDS Intramural Research Program (to W. L. and
K. W. R.) supported this research and all the authors declare no
conflict of interest. All the authors contributed to the experimental
design, interpretation and analysis of data. M. P. L. and X. G.
performed experiments. M. P. L. and K. W. R. wrote the manuscript.
NR 52
TC 4
Z9 4
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
EI 1460-9568
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD APR
PY 2014
VL 39
IS 7
SI SI
BP 1148
EP 1158
DI 10.1111/ejn.12494
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA AE3PE
UT WOS:000333887600010
PM 24712994
ER
PT J
AU Maegawa, S
Gough, SM
Watanabe-Okochi, N
Lu, Y
Zhang, NX
Castoro, RJ
Estecio, MRH
Jelinek, J
Liang, SD
Kitamura, T
Aplan, PD
Issa, JPJ
AF Maegawa, Shinji
Gough, Sheryl M.
Watanabe-Okochi, Naoko
Lu, Yue
Zhang, Nianxiang
Castoro, Ryan J.
Estecio, Marcos R. H.
Jelinek, Jaroslav
Liang, Shoudan
Kitamura, Toshio
Aplan, Peter D.
Issa, Jean-Pierre J.
TI Age-related epigenetic drift in the pathogenesis of MDS and AML
SO GENOME RESEARCH
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CPG ISLAND METHYLATION; ACUTE
MYELOID-LEUKEMIA; DEPENDENT DNA METHYLATION; EMBRYONIC STEM-CELLS;
MYELODYSPLASTIC SYNDROMES; ULCERATIVE-COLITIS; DEVELOPMENTAL REGULATORS;
COLORECTAL-CANCER; PROGNOSTIC IMPACT
AB The myelodysplastic syndrome (MDS) is a clonal hematologic disorder that frequently evolves to acute myeloid leukemia (AML). Its pathogenesis remains unclear, but mutations in epigenetic modifiers are common and the disease often responds to DNA methylation inhibitors. We analyzed DNA methylation in the bone marrow and spleen in two mouse models of MDS/AML, the NUP98-HOXD13 (NHD13) mouse and the RUNX1 mutant mouse model. Methylation array analysis showed an average of 512/3445 (14.9%) genes hypermethylated in NHD13 MDS, and 331 (9.6%) genes hypermethylated in RUNX1 MDS. Thirty-two percent of genes in common between the two models (2/3 NHD13 mice and 2/3 RUNX1 mice) were also hypermethylated in at least two of 19 human MDS samples. Detailed analysis of 41 genes in mice showed progressive drift in DNA methylation from young to old normal bone marrow and spleen; to MDS, where we detected accelerated age-related methylation; and finally to AML, which markedly extends DNA methylation abnormalities. Most of these genes showed similar patterns in human MDS and AML. Repeat element hypomethylation was rare in MDS but marked the transition to AML in some cases. Our data show consistency in patterns of aberrant DNA methylation in human and mouse MDS and suggest that epigenetically, MDS displays an accelerated aging phenotype.
C1 [Maegawa, Shinji; Jelinek, Jaroslav; Issa, Jean-Pierre J.] Temple Univ, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA.
[Maegawa, Shinji; Lu, Yue; Castoro, Ryan J.; Estecio, Marcos R. H.; Jelinek, Jaroslav; Issa, Jean-Pierre J.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
[Gough, Sheryl M.; Aplan, Peter D.] Natl Canc Inst, Ctr Canc Res, Genet Branch, NIH, Bethesda, MD 20889 USA.
[Watanabe-Okochi, Naoko; Kitamura, Toshio] Univ Tokyo, Inst Med Sci, Div Cellular Therapy, Adv Clin Res Ctr, Tokyo 1088639, Japan.
[Watanabe-Okochi, Naoko] Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Tokyo 1088639, Japan.
[Zhang, Nianxiang; Liang, Shoudan] Univ Texas MD Anderson Canc Ctr, Dept Biostat & Computat Biol, Houston, TX 77030 USA.
[Estecio, Marcos R. H.] Univ Texas MD Anderson Canc Ctr, Dept Mol Carcinogenesis, Houston, TX 77030 USA.
RP Maegawa, S (reprint author), Temple Univ, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA.
EM shinji.maegawa@temple.edu
RI Aplan, Peter/K-9064-2016;
OI Castoro, Ryan/0000-0002-3242-3775
FU National Institutes of Health [CA100632, CA158112, CA108631]; Ellison
Medical Foundation
FX This work was supported by National Institutes of Health grants
CA100632, CA158112, and CA108631 and by a grant from the Ellison Medical
Foundation. J-P.J.I. is an American Cancer Society Clinical Research
professor supported by a generous gift from the F.M. Kirby Foundation.
NR 85
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Z9 23
U1 1
U2 12
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
EI 1549-5469
J9 GENOME RES
JI Genome Res.
PD APR
PY 2014
VL 24
IS 4
BP 580
EP 591
DI 10.1101/gr.157529.113
PG 12
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA AE5UU
UT WOS:000334055600005
PM 24414704
ER
PT J
AU Bakker, JL
Thirthagiri, E
van Mil, SE
Adank, MA
Ikeda, H
Verheul, HMW
Meijers-Heijboer, H
de Winter, JP
Sharan, SK
Waisfisz, Q
AF Bakker, Janine L.
Thirthagiri, Eswary
van Mil, Saskia E.
Adank, Muriel A.
Ikeda, Hideyuki
Verheul, Henk M. W.
Meijers-Heijboer, Hanne
de Winter, Johan P.
Sharan, Shyam K.
Waisfisz, Quinten
TI A Novel Splice Site Mutation in the Noncoding Region of BRCA2:
Implications for Fanconi Anemia and Familial Breast Cancer Diagnostics
SO HUMAN MUTATION
LA English
DT Article
DE Fanconi anemia; BRCA2; familial breast cancer; aberrant splicing
ID BIALLELIC MUTATIONS; PALB2; ASSAY
AB Fanconi anemia (FA) is a rare recessive disorder with chromosomal instability, congenital abnormalities, and a high cancer risk. The breast cancer susceptibility gene BRCA2 (FANCD1) is one of the 16 genes involved in this recessive disease. We have identified a novel mutation of the splice donor site of intron 1 in the noncoding region of BRCA2 in a Japanese FA family. This mutation may account for the FA phenotype in a patient originally reported to have biallelic mutations in BRCA2. Subsequent functional studies revealed that one of the mutations, K2729N, was a neutral change. As reported here, a more careful analysis resulted in the identification of a novel splice site mutation. Functional analysis using a mouse embryonic stem cell-based assay revealed that it causes aberrant splicing, reduced transcript levels and hypersensitivity to DNA damaging agents, suggesting that it is likely to be pathogenic. Although similar pathogenic variants in the noncoding region of BRCA1 and 2 were not identified in a cohort of 752 familial breast cancer cases, we still think this finding is relevant for mutation analysis in Hereditary Breast and Ovarian Cancer Syndrome families in a diagnostic setting.
C1 [Bakker, Janine L.; van Mil, Saskia E.; Adank, Muriel A.; Meijers-Heijboer, Hanne; de Winter, Johan P.; Waisfisz, Quinten] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, NL-1081 BT Amsterdam, Netherlands.
[Thirthagiri, Eswary; Sharan, Shyam K.] NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21701 USA.
[Ikeda, Hideyuki] Rumoi City Hosp, Dept Surg Pathol, Rumoi, Japan.
[Verheul, Henk M. W.] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, NL-1081 BT Amsterdam, Netherlands.
RP Waisfisz, Q (reprint author), Vrije Univ Amsterdam, Med Ctr, Sect Oncogenet, Van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands.
EM q.waisfisz@vumc.nl
FU Center for Cancer Research Intramural Program; National Cancer
Institute; National Institutes of Health of the U.S. Department of
Health and Human Services; Netherlands Organisation for Scientific
Research (NWO) [91756341]
FX Contract grant sponsors: Center for Cancer Research Intramural Program;
National Cancer Institute; National Institutes of Health of the U.S.
Department of Health and Human Services; The Netherlands Organisation
for Scientific Research (NWO) (91756341).
NR 14
TC 3
Z9 3
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
EI 1098-1004
J9 HUM MUTAT
JI Hum. Mutat.
PD APR
PY 2014
VL 35
IS 4
BP 442
EP 446
DI 10.1002/humu.22505
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA AC8UG
UT WOS:000332810000005
PM 24395671
ER
PT J
AU Lam, MPY
Wang, D
Lau, E
Liem, DA
Kim, AK
Ng, DCM
Liang, XB
Bleakley, BJ
Liu, CG
Tabaraki, JD
Cadeiras, M
Wang, YB
Deng, MC
Ping, PP
AF Lam, Maggie P. Y.
Wang, Ding
Lau, Edward
Liem, David A.
Kim, Allen K.
Ng, Dominic C. M.
Liang, Xiangbo
Bleakley, Brian J.
Liu, Chenguang
Tabaraki, Jason D.
Cadeiras, Martin
Wang, Yibin
Deng, Mario C.
Ping, Peipei
TI Protein kinetic signatures of the remodeling heart following
isoproterenol stimulation
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID MITOCHONDRIAL OXIDATIVE STRESS; CARDIAC-HYPERTROPHY; DYNAMICS; FAILURE;
EXPRESSION; TURNOVER; MICE; GENE; CARDIOMYOPATHY; DYSFUNCTION
AB Protein temporal dynamics play a critical role in time-dimensional pathophysiological processes, including the gradual cardiac remodeling that occurs in early-stage heart failure. Methods for quantitative assessments of protein kinetics are lacking, and despite knowledge gained from single-protein studies, integrative views of the coordinated behavior of multiple proteins in cardiac remodeling are scarce. Here, we developed a workflow that integrates deuterium oxide ((H2O)-H-2) labeling, high-resolution mass spectrometry (MS), and custom computational methods to systematically interrogate in vivo protein turnover. Using this workflow, we characterized the in vivo turnover kinetics of 2,964 proteins in a mouse model of beta-adrenergic-induced cardiac remodeling. The data provided a quantitative and longitudinal view of cardiac remodeling at the molecular level, revealing widespread kinetic regulations in calcium signaling, metabolism, proteostasis, and mitochondrial dynamics. We translated the workflow to human studies, creating a reference dataset of 496 plasma protein turnover rates from 4 healthy adults. The approach is applicable to short, minimal label enrichment and can be performed on as little as a single biopsy, thereby overcoming critical obstacles to clinical investigations. The protein turnover quantitation experiments and computational workflow described here should be widely applicable to large-scale biomolecular investigations of human disease mechanisms with a temporal perspective.
C1 [Lam, Maggie P. Y.; Wang, Ding; Lau, Edward; Liem, David A.; Kim, Allen K.; Ng, Dominic C. M.; Liang, Xiangbo; Bleakley, Brian J.; Liu, Chenguang; Ping, Peipei] Univ Calif Los Angeles, NHLBI Prote Ctr, Los Angeles, CA 90095 USA.
[Lam, Maggie P. Y.; Wang, Ding; Lau, Edward; Liem, David A.; Kim, Allen K.; Ng, Dominic C. M.; Liang, Xiangbo; Bleakley, Brian J.; Liu, Chenguang; Tabaraki, Jason D.; Wang, Yibin; Ping, Peipei] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90095 USA.
[Cadeiras, Martin; Wang, Yibin; Deng, Mario C.; Ping, Peipei] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA.
[Wang, Yibin] Univ Calif Los Angeles, Dept Anesthesiol, Los Angeles, CA 90095 USA.
RP Ping, PP (reprint author), Univ Calif Los Angeles, 675 Charles E Young Dr,MRL Bldg 1-619, Los Angeles, CA 90095 USA.
EM magelpy@ucla.edu; pping@mednet.ucla.edu
OI Lau, Edward/0000-0001-9083-5922; Wang, Yibin/0000-0003-0852-0767;
Bleakley, Brian/0000-0002-9930-2169; Ping, Peipei/0000-0003-3583-3881;
Wang, Ding/0000-0001-8236-8551
FU NIH awards [HL-R37-63901, HHSN268201000035C]; T.C. Laubisch endowment at
UCLA; American Heart Association fellowships [13POST14700031,
12PRE11610024]
FX This work was supported by NIH awards HL-R37-63901 and
HHSN268201000035C; the T.C. Laubisch endowment at UCLA (to P. Ping); and
by American Heart Association fellowships 13POST14700031 (to Maggie P.Y.
Lam) and 12PRE11610024 (to Edward Lau).
NR 50
TC 18
Z9 18
U1 0
U2 8
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD APR
PY 2014
VL 124
IS 4
BP 1734
EP 1744
DI 10.1172/JCI73787
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AE1IQ
UT WOS:000333723400033
PM 24614109
ER
PT J
AU Bonsignori, M
Wiehe, K
Grimm, SK
Lynch, R
Yang, G
Kozink, DM
Perrin, F
Cooper, AJ
Hwang, KK
Chen, X
Liu, MF
McKee, K
Parks, RJ
Eudailey, J
Wang, MY
Clowse, M
Criscione-Schreiber, LG
Moody, MA
Ackerman, ME
Boyd, SD
Gao, F
Kelsoe, G
Verkoczy, L
Tomaras, GD
Liao, HX
Kepler, TB
Montefiori, DC
Mascola, JR
Haynes, BF
AF Bonsignori, Mattia
Wiehe, Kevin
Grimm, Sebastian K.
Lynch, Rebecca
Yang, Guang
Kozink, Daniel M.
Perrin, Florence
Cooper, Abby J.
Hwang, Kwan-Ki
Chen, Xi
Liu, Mengfei
McKee, Krisha
Parks, Robert J.
Eudailey, Joshua
Wang, Minyue
Clowse, Megan
Criscione-Schreiber, Lisa G.
Moody, M. Anthony
Ackerman, Margaret E.
Boyd, Scott D.
Gao, Feng
Kelsoe, Garnett
Verkoczy, Laurent
Tomaras, Georgia D.
Liao, Hua-Xin
Kepler, Thomas B.
Montefiori, David C.
Mascola, John R.
Haynes, Barton F.
TI An autoreactive antibody from an SLE/HIV-1 individual broadly
neutralizes HIV-1
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4 BINDING-SITE;
SYSTEMIC-LUPUS-ERYTHEMATOSUS; HUMAN MONOCLONAL-ANTIBODIES; CLASS SWITCH
RECOMBINATION; PROXIMAL EXTERNAL REGION; B-CELL RESPONSES;
CONFORMATIONAL EPITOPE; HIV-1-INFECTED INDIVIDUALS; POTENT
NEUTRALIZATION
AB Broadly HIV-1-neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated that HIV-1-infected individuals with autoimmune disease and defective immune tolerance mechanisms may produce BnAbs more readily than those without autoimmune diseases. In this study, we identified an HIV-1-infected individual with SLE who exhibited controlled viral load (<5,000 copies/ml) in the absence of controlling HLA phenotypes and developed plasma HIV-1 neutralization. breadth. We collected memory B cells from this individual and isolated a BnAb, CH98, that targets the CD4 binding site (CD4bs) of HIV-1 envelope glycoprotein 120 (gp120). CH98 bound to human antigens including dsDNA, which is specifically associated with SLE. Anti-dsDNA reactivity was also present in the patient's plasma. CH98 had a mutation frequency of 25% and 15% nt somatic mutations in the heavy and light chain variable domains, respectively, a long HCDR3, and a deletion in the light chain CDR1. The occurrence of anti-dsDNA reactivity by a HIV-1 CD4bs BnAb in an individual with SLE raises the possibility that some BnAbs and SLE-associated autoantibodies arise from similar pools of B cells.
C1 [Bonsignori, Mattia; Wiehe, Kevin; Kozink, Daniel M.; Perrin, Florence; Cooper, Abby J.; Hwang, Kwan-Ki; Chen, Xi; Parks, Robert J.; Eudailey, Joshua; Wang, Minyue; Moody, M. Anthony; Gao, Feng; Kelsoe, Garnett; Verkoczy, Laurent; Tomaras, Georgia D.; Liao, Hua-Xin; Montefiori, David C.; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA.
[Bonsignori, Mattia; Wiehe, Kevin; Kozink, Daniel M.; Perrin, Florence; Cooper, Abby J.; Hwang, Kwan-Ki; Chen, Xi; Parks, Robert J.; Clowse, Megan; Criscione-Schreiber, Lisa G.; Gao, Feng; Verkoczy, Laurent; Liao, Hua-Xin; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Grimm, Sebastian K.; Ackerman, Margaret E.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA.
[Lynch, Rebecca; McKee, Krisha; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Yang, Guang; Kelsoe, Garnett; Tomaras, Georgia D.; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA.
[Liu, Mengfei] Duke Univ, Sch Med, Durham, NC 27710 USA.
[Moody, M. Anthony] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA.
[Boyd, Scott D.] Stanford Univ, Dept Pathol, Palo Alto, CA 94304 USA.
[Verkoczy, Laurent] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Tomaras, Georgia D.; Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Kepler, Thomas B.] Boston Univ, Dept Microbiol, Boston, MA 02215 USA.
RP Bonsignori, M (reprint author), Duke Univ, Med Ctr, Duke Human Vaccine Inst, 2 Genome Court,MSRB II,Room 4013,Duke Box 103020, Durham, NC 27710 USA.
EM mattia.bonsignori@duke.edu
RI Tomaras, Georgia/J-5041-2016
FU NIH, NIAID, Center for HIV/AIDS Vaccine Immunology [AI067854]; Center
for HIV/AIDS Vaccine Immunology-Immunogen Discovery [AI100645]
FX We thank Krissey Lloyd, Christina Scholarchuk, Julie Blinn, Andrew
Foulger, Fangping Cai, Miroslawa Bilska, Morgan Gilman, and Rekha
Bhaskarabhatla for excellent technical support; and Kelly A. Soderberg,
Megan McCormick, Jennifer Kirchherr, Celia C. LaBranche, and Janet
Mueller for project and/or regulatory management and coordination. We
thank the NISC Comparative Sequencing Program of the NIH Intramural
Sequencing Center, National Human Genome Research Institute, for 454
pyrosequencing. This study was supported by grants from NIH, NIAID,
Center for HIV/AIDS Vaccine Immunology (AI067854), and Center for
HIV/AIDS Vaccine Immunology-Immunogen Discovery (AI100645).
NR 67
TC 29
Z9 30
U1 0
U2 4
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD APR
PY 2014
VL 124
IS 4
BP 1835
EP 1843
DI 10.1172/JCI73441
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AE1IQ
UT WOS:000333723400041
PM 24614107
ER
PT J
AU Grady, KL
Naftel, D
Stevenson, L
Dew, MA
Weidner, G
Pagani, FD
Kirklin, JK
Myers, S
Baldwin, T
Young, J
AF Grady, Kathleen L.
Naftel, David
Stevenson, Lynne
Dew, Mary Amanda
Weidner, Gerdi
Pagani, Francis D.
Kirklin, James K.
Myers, Susan
Baldwin, Timothy
Young, James
TI Overall quality of life improves to similar levels after mechanical
circulatory support regardless of severity of heart failure before
implantation
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Article
DE mechanical circulatory support; health-related quality of life; heart
failure; INTERMACS; continuous-flow pump
ID VENTRICULAR ASSIST DEVICE; INTERMACS ANNUAL-REPORT; DESTINATION THERAPY;
HEALTH-STATUS; EQ-5D; OUTCOMES; SURVIVAL; IMPACT
AB BACKGROUND: The severity of pre-implantation heart failure may affect post-implantation health-related quality of life (HRQOL). The purpose of our study was to examine differences in HRQOL from before mechanical circulatory support (MCS) through 1 year after surgery by Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) patient profiles.
METHODS: Data from 1,559 adults with advanced heart failure who received primary continuous-flow pumps between June 23, 2006, and March 31, 2010, and were enrolled in INTERMACS were analyzed. IARQOL data were collected using the EQ-5D-3L survey before implantation and at 3, 6, and 12 months after implantation. Statistical analyses included chi-square and t-tests, using all available data for each time period. Paired t-tests and sensitivity analyses were also conducted.
RESULTS: HRQOL was poor before MCS implantation among patients with INTERMACS profiles 1 to 7 and significantly improved after MCS implantation for all profiles. Stratified by INTERMACS profile, problems within each of the 5 dimensions of HRQOL (i.e., mobility, self-care, usual activities, pain, and anxiety/depression) generally decreased from before to after implantation. By 6 months after implantation, patients with all INTERMACS profiles reported similar frequencies of problems for all HRQOL dimensions. Paired t-tests and sensitivity analyses supported almost all of our findings.
CONCLUSIONS: HRQOL is poor among advanced heart failure patients with INTERMACS profiles 1 to 7 before MCS implantation and improves to similar levels for patients who remained on MCS 1 year after surgery. Patients have problems in HRQOL dimensions before and after MCS; however, the frequency of reporting problems decreases for all dimensions within most profiles across time. (C) 2014 International Society for Heart and Lung Tiansplantation. All rights reserved.
C1 [Grady, Kathleen L.] Northwestern Univ, Div Cardiac Surg, Dept Surg, Chicago, IL 60611 USA.
[Naftel, David; Kirklin, James K.; Myers, Susan] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA.
[Stevenson, Lynne] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Dew, Mary Amanda] Univ Pittsburgh, Sch Med, Dept Epidemiol, Pittsburgh, PA USA.
[Dew, Mary Amanda] Univ Pittsburgh, Sch Med, Dept Biostat, Pittsburgh, PA USA.
[Dew, Mary Amanda] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Dew, Mary Amanda] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Weidner, Gerdi] San Francisco State Univ, Dept Biol, San Francisco, CA 94132 USA.
[Pagani, Francis D.] Univ Michigan, Ctr Circulatory Support, Ann Arbor, MI 48109 USA.
[Baldwin, Timothy] NHLBI, Bethesda, MD 20892 USA.
[Young, James] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
RP Grady, KL (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Heart Failure, Bluhm Cardiovasc Inst,Div Cardiac Surg, 201 E Huron St,Galter Pavil 11-140, Chicago, IL 60611 USA.
EM kgrady@nmh.org
FU Alexander-von-Humboldt Foundation; American Heart Association
FX K.L.G. is PI on an American Heart Association grant-in-aid. G.W. was
supported by grants from the Alexander-von-Humboldt Foundation.
NR 28
TC 20
Z9 20
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD APR
PY 2014
VL 33
IS 4
BP 412
EP 421
DI 10.1016/j.healun.2013.10.017
PG 10
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA AE3HB
UT WOS:000333866500013
PM 24360203
ER
PT J
AU Chuang, ML
Gona, P
Hautvast, GLTF
Salton, CJ
Breeuwer, M
O'Donnell, CJ
Manning, WJ
AF Chuang, Michael L.
Gona, Philimon
Hautvast, Gilion L. T. F.
Salton, Carol J.
Breeuwer, Marcel
O'Donnell, Christopher J.
Manning, Warren J.
TI CMR Reference Values for Left Ventricular Volumes, Mass, and Ejection
Fraction Using Computer-Aided Analysis: The Framingham Heart Study
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE left ventricle; reference values; automated border detection; magnetic
resonance imaging; epidemiology; aging
ID CARDIOVASCULAR MAGNETIC-RESONANCE; CINE-MR-IMAGES; STUDY OFFSPRING
COHORT; AUTOMATIC SEGMENTATION; VALIDATION; PARAMETERS; QUANTIFICATION;
ATRIAL; AGE
AB PurposeTo determine sex-specific reference values for left ventricular (LV) volumes, mass, and ejection fraction (EF) in healthy adults using computer-aided analysis and to examine the effect of age on LV parameters.
Materials and MethodsWe examined data from 1494 members of the Framingham Heart Study Offspring cohort, obtained using short-axis stack cine SSFP CMR, identified a healthy reference group (without cardiovascular disease, hypertension, or LV wall motion abnormality) and determined sex-specific upper 95th percentile thresholds for LV volumes and mass, and lower 5th percentile thresholds for EF using computer-assisted border detection. In secondary analyses, we stratified participants by age-decade and tested for linear trend across age groups.
ResultsThe reference group comprised 685 adults (423F; 61 9 years). Men had greater LV volumes and mass, before and after indexation to common measures of body size (all P = 0.001). Women had greater EF (73 +/- 6 versus 71 +/- 6%; P = 0.0002). LV volumes decreased with greater age in both sexes, even after indexation. Indexed LV mass did not vary with age. LV EF and concentricity increased with greater age in both sexes.
ConclusionWe present CMR-derived LV reference values. There are significant age and sex differences in LV volumes, EF, and geometry, whereas mass differs between sexes but not age groups. J. Magn. Reson. Imaging 2014;39:895-900. (c) 2013 Wiley Periodicals, Inc.
C1 [Chuang, Michael L.; Gona, Philimon; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Chuang, Michael L.; Salton, Carol J.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA.
[Gona, Philimon] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Biostat & Hlth Serv Res, Worcester, MA USA.
[Hautvast, Gilion L. T. F.; Breeuwer, Marcel] Philips Heathcare, Imaging Syst, Best, Netherlands.
[Breeuwer, Marcel] Eindhoven Univ Technol, NL-5600 MB Eindhoven, Netherlands.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[O'Donnell, Christopher J.; Manning, Warren J.] Harvard Univ, Sch Med, Boston, MA USA.
[Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA.
RP Chuang, ML (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM mlc48104@gmail.com
FU National Institutes of Health [RO1 AG17509, N01-HC-38038]; Philips
Healthcare, The Netherlands
FX Contract grant sponsor: National Institutes of Health; Contract grant
numbers: RO1 AG17509, N01-HC-38038; Contract grant sponsor: Philips
Healthcare, The Netherlands.
NR 24
TC 14
Z9 14
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD APR
PY 2014
VL 39
IS 4
BP 895
EP 900
DI 10.1002/jmri.24239
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AD2BQ
UT WOS:000333038300017
PM 24123369
ER
PT J
AU Neelavalli, J
Jella, PK
Krishnamurthy, U
Buch, S
Haacke, EM
Yeo, L
Mody, S
Katkuri, Y
Bahado-Singh, R
Hassan, SS
Romero, R
Thomason, ME
AF Neelavalli, Jaladhar
Jella, Pavan Kumar
Krishnamurthy, Uday
Buch, Sagar
Haacke, E. Mark
Yeo, Lami
Mody, Swati
Katkuri, Yashwanth
Bahado-Singh, Ray
Hassan, Sonia S.
Romero, Roberto
Thomason, Moriah E.
TI Measuring Venous Blood Oxygenation in Fetal Brain Using
Susceptibility-Weighted Imaging
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE susceptibility-weighted imaging; SWI; fetal; brain; oxygen saturation;
susceptometry
ID MAGNETIC-FIELD INHOMOGENEITY; PERINATAL ISCHEMIC-STROKE; RISK-FACTORS;
MR SUSCEPTOMETRY; NEWBORN-INFANTS; CEREBRAL-PALSY; SATURATION;
METABOLISM; OUTCOMES; INJURY
AB PurposeTo evaluate fetal cerebral venous blood oxygenation, Y-v, using principles of MR susceptometry.
Materials and MethodsA cohort of 19 pregnant subjects, with a mean gestational age of 31.6 4.7 weeks were imaged using a modified susceptibility-weighted imaging (SWI) sequence. Data quality was first assessed for feasibility of oxygen saturation measurement, and data from five subjects (mean std gestational age of 33.7 +/- 3.6 weeks) were then chosen for further quantitative analysis. SWI phase in the superior sagittal sinus was used to evaluate oxygen saturation using the principles of MR susceptometry. Systematic error in the measured Y-v values was studied through simulations.
ResultsSimulations showed that the systematic error in Y-v depended upon the assumed angle of the vessel, , relative to the main magnetic field and the error in that vessel angle . For the typical vessel angle of = 30 degrees encountered in the fetal data analyzed, a as large as +/- 20 degrees led to an absolute error, Y-v, of less than 11%. The measured mean oxygen saturation across the five fetuses was 66% +/- 9.4%. This average cerebral venous blood oxygenation value is in close agreement with values in the published literature.
ConclusionWe have reported the first in vivo measurement of human fetal cerebral venous oxygen saturation using MRI. J. Magn. Reson. Imaging 2014;39:998-1006. (c) 2013 Wiley Periodicals, Inc.
C1 [Neelavalli, Jaladhar; Jella, Pavan Kumar; Krishnamurthy, Uday; Haacke, E. Mark; Katkuri, Yashwanth] Wayne State Univ, Dept Radiol, Detroit, MI USA.
[Buch, Sagar] McMaster Univ, Sch Biomed Engn, Hamilton, ON, Canada.
[Yeo, Lami; Bahado-Singh, Ray; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Yeo, Lami; Hassan, Sonia S.; Romero, Roberto; Thomason, Moriah E.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Yeo, Lami; Hassan, Sonia S.; Romero, Roberto; Thomason, Moriah E.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Mody, Swati] Childrens Hosp Michigan, Dept Pediat Imaging, Detroit, MI 48201 USA.
[Thomason, Moriah E.] Wayne State Univ, Dept Pediat, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI 48202 USA.
RP Neelavalli, J (reprint author), Univ Hlth Ctr, 4201 St Antoine 5E-12, Detroit, MI 48201 USA.
EM jneelava@med.wayne.edu
RI NEELAVALLI, JALADHAR/C-6904-2014
FU NHLBI [1R42HL1 12580-01A1]
FX Contract grant sponsor: NHLBI; Contract grant number: 1R42HL1
12580-01A1.
NR 64
TC 4
Z9 6
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD APR
PY 2014
VL 39
IS 4
BP 998
EP 1006
DI 10.1002/jmri.24245
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AD2BQ
UT WOS:000333038300030
PM 24783243
ER
PT J
AU Hart, RG
Pearce, LA
Bakheet, MF
Benavente, OR
Conwit, RA
McClure, LA
Talbert, RL
Anderson, DC
AF Hart, Robert G.
Pearce, Lesly A.
Bakheet, Majid F.
Benavente, Oscar R.
Conwit, Robin A.
McClure, Leslie A.
Talbert, Robert L.
Anderson, David C.
TI Predictors of Stroke Recurrence in Patients with Recent Lacunar Stroke
and Response to Interventions According to Risk Status: Secondary
Prevention of Small Subcortical Strokes Trial
SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
LA English
DT Article
DE Lacunar infarct; cerebral small-vessel disease; prognosis; recurrent
stroke
ID LONG-TERM PROGNOSIS; INFARCTION; SPS3; POPULATION; SURVIVAL; SUBTYPES
AB Background: Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high versus low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status. Methods: Multivariable analyses of 3020 participants with recent magnetic resonance imaging-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes. Results: Prior symptomatic lacunar stroke or transient ischemic attack (TIA) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.6, 2.9), diabetes (HR 2.0, 95% CI 1.5, 2.5), black race (HR 1.7, 95% CI 1.3, 2.3), and male sex (HR 1.5, 95% CI 1.1, 1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3% per year (95% CI 3.4, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1% per year (95% CI 2.6, 3.9) in those with more than 1 of the other 3 risk factors (27% of the cohort), and 1.3% per year (95% CI 1.0, 1.7) in those with 0-1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status. Conclusions: In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, black race, and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk.
C1 [Hart, Robert G.] McMaster Univ, Dept Med Neurol, Hamilton, ON L8L 2X2, Canada.
[Bakheet, Majid F.] Taiba Univ, Dept Neurol, Medina, Saudi Arabia.
[Benavente, Oscar R.] Univ British Columbia, Dept Neurol, Vancouver, BC V5Z 1M9, Canada.
[Conwit, Robin A.] NINDS, Rockville, MD USA.
[McClure, Leslie A.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
[Talbert, Robert L.] Univ Texas Austin, Dept Clin Pharm, Austin, TX 78712 USA.
[Anderson, David C.] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA.
RP Hart, RG (reprint author), McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Dept Med Neurol, DBCVSRI C4-118,237 Barton St East, Hamilton, ON L8L 2X2, Canada.
EM robert.hart@phri.ca
RI McClure, Leslie/P-2929-2015
FU National Institute of Neurological Disorders and Stroke [U01
NS38529-04A1]
FX National Institute of Neurological Disorders and Stroke (U01
NS38529-04A1).
NR 22
TC 6
Z9 8
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1052-3057
EI 1532-8511
J9 J STROKE CEREBROVASC
JI J. Stroke Cerebrovasc. Dis.
PD APR
PY 2014
VL 23
IS 4
BP 618
EP 624
DI 10.1016/j.jstrokecerebrovasdis.2013.05.021
PG 7
WC Neurosciences; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA AE2OV
UT WOS:000333813700011
PM 23800503
ER
PT J
AU Kim, C
Chapman, RS
Hu, W
He, XZ
Hosgood, HD
Liu, LZ
Lai, H
Chen, W
Silverman, DT
Vermeulen, R
Tian, LW
Bassig, B
Shen, M
Zhang, YW
Ma, SG
Rothman, N
Lan, Q
AF Kim, Christopher
Chapman, Robert S.
Hu, Wei
He, Xingzhou
Hosgood, H. Dean
Liu, Larry Z.
Lai, Hong
Chen, Wei
Silverman, Debra T.
Vermeulen, Roel
Tian, Linwei
Bassig, Bryan
Shen, Min
Zhang, Yawei
Ma, Shuangge
Rothman, Nathaniel
Lan, Qing
TI Smoky coal, tobacco smoking, and lung cancer risk in Xuanwei, China
SO LUNG CANCER
LA English
DT Article
DE Coal; Tobacco; Lung cancer; Indoor air pollution; China; Global health;
Epidemiology
ID POLYCYCLIC AROMATIC-HYDROCARBONS; INDOOR AIR-POLLUTION; HOUSEHOLD STOVE
IMPROVEMENT; CURRENT PROGRESS; WEI; MORTALITY; EXPOSURE; COMBUSTION;
CIGARETTES; CIGARS
AB Objectives: Lung cancer rates in Xuanwei are the highest in China. In-home use of smoky coal has been associated with lung cancer risk, and the association of smoking and lung cancer risk strengthened after stove improvement. Here, we explored the differential association of tobacco use and lung cancer risk by the intensity, duration, and type of coal used.
Materials and methods: We conducted a population-based case-control study of 260 male lung cancer cases and 260 age-matched male controls. Odds ratios (OR) and 95% confidence interval (CI) for tobacco use was calculated by conditional logistic regression.
Results: Use of smoky coal was significantly associated with an increased risk of lung cancer, and tobacco use was weakly and non-significantly associated with lung cancer risk. When the association was assessed by coal use, the cigarette-lung cancer risk association was null in hazardous coal users and elevated in less hazardous smoky coal users and non-smoky coal users. The risk of lung cancer per cigarette per day decreased as annual use of coal increased (>0-3 tons: OR: 1.09; 95% CI: 1.03-1.17; >3 tons: OR: 0.99; 95% CI: 0.95-1.03). Among more hazardous coal users, attenuation occured at even low levels of usage (>0-3 tons: OR: 1.02; 95% Cl: 0.91-1.14; >3 tons: OR: 0.94; 95% CI: 0.97-1.03).
Conclusion: We found evidence that smoky coal attenuated the tobacco and lung cancer risk association in males that lived in Xuanwei, particularly among users of hazardous coal where even low levels of smoky coal attenuated the association. Our results suggest that the adverse effects of tobacco may become more apparent as China's population continues to switch to cleaner fuels for the home, underscoring the urgent need for smoking cessation in China and elsewhere. Published by Elsevier Ireland Ltd.
C1 [Kim, Christopher; Hu, Wei; Hosgood, H. Dean; Silverman, Debra T.; Bassig, Bryan; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Chapman, Robert S.] Chulalongkorn Univ, Coll Publ Hlth Sci, Bangkok 10330, Thailand.
[He, Xingzhou] Chinese Ctr Dis Control & Prevent, Inst Environm Hlth & Engn, Beijing 102206, Peoples R China.
[Liu, Larry Z.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
[Lai, Hong] Johns Hopkins Univ, Dept Radiol & Ophthalmol, Wilmer Eye Inst, Baltimore, MD 21287 USA.
[Chen, Wei] Forest Labs Inc, Jersey City, NJ 07311 USA.
[Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment, Utrecht, Netherlands.
[Tian, Linwei] Chinese Univ Hong Kong, Sch Publ Hlth & Primary Care, Hong Kong, Hong Kong, Peoples R China.
[Kim, Christopher; Bassig, Bryan; Zhang, Yawei; Ma, Shuangge] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
[Shen, Min] Interfaith Med Ctr, Brooklyn, NY 11213 USA.
[Hosgood, H. Dean] Albert Einstein Coll Med, Bronx, NY 10461 USA.
RP Kim, C (reprint author), 9609 Med Ctr Dr,MSC 9771, Bethesda, MD 20892 USA.
EM Christopher.kim@nih.gov
RI Tian, Linwei/A-9736-2009; Vermeulen, Roel/F-8037-2011
OI Tian, Linwei/0000-0002-4739-1534; Vermeulen, Roel/0000-0003-4082-8163
FU NIH intramural research program and NCI training grant [T32-CA105666]
FX This work was supported by NIH intramural research program and NCI
training grant T32-CA105666.
NR 24
TC 15
Z9 16
U1 2
U2 33
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
EI 1872-8332
J9 LUNG CANCER
JI Lung Cancer
PD APR
PY 2014
VL 84
IS 1
BP 31
EP 35
DI 10.1016/j.lungcan.2014.01.004
PG 5
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA AE3ED
UT WOS:000333858900005
PM 24506909
ER
PT J
AU Kellman, P
Herzka, DA
Hansen, MS
AF Kellman, Peter
Herzka, Daniel A.
Hansen, Michael Schacht
TI Adiabatic Inversion Pulses for Myocardial T1 Mapping
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE MRI; adiabatic inversion; T1 mapping; MOLLI
ID CARDIOVASCULAR MAGNETIC-RESONANCE; RECOVERY MOLLI; HEART;
QUANTIFICATION; VALIDATION; FIBROSIS; HUMANS; NMR
AB PurposeTo evaluate the error in T1 estimates using inversion-recovery-based T1 mapping due to imperfect inversion and to perform a systematic study of adiabatic inversion pulse designs in order to maximize inversion efficiency for values of transverse relaxation (T2) in the myocardium subject to a peak power constraint.
MethodsThe inversion factor for hyperbolic secant and tangent/hyperbolic tangent adiabatic full passage waveforms was calculated using Bloch equations. A brute-force search was conducted for design parameters: pulse duration, frequency range, shape parameters, and peak amplitude. A design was selected that maximized the inversion factor over a specified range of amplitude and off-resonance and validated using phantom measurements. Empirical correction for imperfect inversion was performed.
ResultsThe tangent/hyperbolic tangent adiabatic pulse was found to outperform hyperbolic secant designs and achieve an inversion factor of 0.96 within 150 Hz over 25% amplitude range with 14.7 mu T peak amplitude. T1 mapping errors of the selected design due to imperfect inversion was approximate to 4% and could be corrected to <1%.
ConclusionsNonideal inversion leads to significant errors in inversion-recovery-based T1 mapping. The inversion efficiency of adiabatic pulses is sensitive to transverse relaxation. The tangent/hyperbolic tangent design achieved the best performance subject to the peak amplitude constraint. Magn Reson Med 71:1428-1434, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Kellman, Peter; Hansen, Michael Schacht] NHLBI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Herzka, Daniel A.] Johns Hopkins Sch Med, Dept Biomed Engn, Baltimore, MD USA.
RP Kellman, P (reprint author), NHLBI, NIH, Room B1D416,Bldg 10,10 Ctr Dr,MSC 1061, Bethesda, MD 20892 USA.
EM kellman@nih.gov
RI Hansen, Michael/J-5391-2015;
OI Hansen, Michael/0000-0002-8087-8731; Herzka, Daniel/0000-0002-9400-7814
FU NIH/NHLBI
FX Grant sponsor: NIH/NHLBI Intramural Research Program.
NR 26
TC 22
Z9 22
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD APR
PY 2014
VL 71
IS 4
BP 1428
EP 1434
DI 10.1002/mrm.24793
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AD2CL
UT WOS:000333040500009
PM 23722695
ER
PT J
AU Roescher, N
Vosters, JL
Alsaleh, G
Dreyfus, P
Jacques, S
Chiocchia, G
Sibilia, J
Tak, PP
Chiorini, JA
Mariette, X
Gottenberg, JE
AF Roescher, N.
Vosters, J. L.
Alsaleh, G.
Dreyfus, P.
Jacques, S.
Chiocchia, G.
Sibilia, J.
Tak, P. P.
Chiorini, J. A.
Mariette, X.
Gottenberg, Jacques-Eric
TI Targeting the Splicing of mRNA in Autoimmune Diseases: BAFF Inhibition
in Sjogren's Syndrome as a Proof of Concept
SO MOLECULAR THERAPY
LA English
DT Article
ID NONOBESE DIABETIC MICE; GLAND EPITHELIAL-CELLS; SALIVARY-GLAND; ABERRANT
EXPRESSION; MUSCULAR-DYSTROPHY; DELTA-BAFF; OPEN-LABEL; B-CELLS; MOUSE;
PATHWAYS
AB BAFF (B-cell-activating factor of the tumor necrosis factor family), a pivotal cytokine for B-cell activation, is overexpressed by salivary gland (SG) epithelial cells in primary Sjogren's syndrome (pSS) Delta BAFF, a physiological inhibitor of BAFF, is a minor alternative splice variant of BAFF. A U7 RNA was reengineered to deliver antisense sequences targeting BAFF splice regions. A major decrease of BAFF messenger RNA (mRNA) and protein secretion, concomitantly with the increase of Delta BAFF mRNA, was observed in vitro. In vivo, SG retrograd instillation of nonobese diabetic mice by the modified U7 cloned into an adeno-associated virus vector significantly decreased BAFF protein expression and lymphocytic infiltrates and improved salivary flow. This study offers a rationale for localized therapeutic BAFF inhibition in pSS and represents a proof of concept of the interest of exon skipping in autoimmune diseases.
C1 [Roescher, N.; Vosters, J. L.; Tak, P. P.] Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, Netherlands.
[Roescher, N.; Vosters, J. L.; Chiorini, J. A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
[Alsaleh, G.; Sibilia, J.; Gottenberg, Jacques-Eric] Univ Strasbourg, Fac Med, INSERM UMR S 1109, Strasbourg, France.
[Alsaleh, G.; Sibilia, J.; Gottenberg, Jacques-Eric] Hop Univ Strasbourg, Hop Hautepierre, Serv Rhumatol, Ctr Rech Immunol & Hematol, Strasbourg, France.
[Dreyfus, P.] UPMC Um76, Inserm U974, CNRS UMR7215, Inst Myol, Paris, France.
[Jacques, S.; Chiocchia, G.] Univ Paris 05, Inserm, U1016, Paris, France.
[Jacques, S.; Chiocchia, G.] Univ Paris 05, Inst Cochin, CNRS, UMR8104, Paris, France.
[Mariette, X.] Univ Paris 11, INSERM U1012, AP HP, Hop Univ Paris Sud, Le Kremlin Bicetre, France.
RP Gottenberg, JE (reprint author), Univ Strasbourg, INSERM UMR S 1109, F-67000 Strasbourg, France.
EM jacques-eric.gottenberg@chru-strasbourg.fr
RI chiocchia, gilles/F-6287-2013
OI chiocchia, gilles/0000-0001-9973-0940
NR 29
TC 7
Z9 7
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD APR
PY 2014
VL 22
IS 4
BP 821
EP 827
DI 10.1038/mt.2013.275
PG 7
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AE5WX
UT WOS:000334061100015
PM 24304965
ER
PT J
AU Sansbury, B
Dasgupta, A
Guthrie, L
Ward, M
AF Sansbury, Brittany
Dasgupta, Abhijit
Guthrie, Lori
Ward, Michael
TI Time perspective and medication adherence among individuals with
hypertension or diabetes mellitus
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Medication adherence; Time perspective; Patient education
ID BREAST-CANCER PATIENTS; TREATMENT PERCEPTIONS; HEALTH; INTERVENTIONS;
METAANALYSIS; BELIEFS; DISEASE; MODEL; NONADHERENCE; PREDICTOR
AB Objective: The study determined if time perspective was associated with medication adherence among people with hypertension and diabetes.
Methods: Using the Health Beliefs Model, we used path analysis to test direct and indirect effects of time perspective and health beliefs on adherence among 178 people who participated in a community-based survey near Washington, D.C. We measured three time perspectives (future, present fatalistic, and present hedonistic) with the Zimbardo Time Perspective Inventory and medication adherence by self-report.
Results: The total model demonstrated a good fit (RMSEA = 0.17, 90% CI [0.10, 0.28], p = 0.003; comparative fit index = 0.91). Future time perspective and age showed direct effects on increased medication adherence; an increase by a single unit in future time perspective was associated with a 0.32 standard deviation increase in reported adherence. There were no significant indirect effects of time perspective with reported medication adherence through health beliefs.
Conclusion: The findings provide the first evidence that time perspective plays an under-recognized role as a psychological motivator in medication adherence.
Practice implications: Patient counseling for medication adherence may be enhanced if clinicians incorporate consideration of the patient's time perspective. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Sansbury, Brittany] Univ Memphis, Inst Disabil, Memphis, TN 38152 USA.
[Sansbury, Brittany; Dasgupta, Abhijit; Guthrie, Lori; Ward, Michael] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Sansbury, B (reprint author), Univ Memphis, Inst Disabil, Ball Hall 100, Memphis, TN 38152 USA.
EM bssnsbry@memphis.edu
FU Intramural Research Program, National Institute of Arthritis;
Musculoskeletal and Skin Diseases, National Institutes of Health
FX The study was supported by the Intramural Research Program, National
Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institutes of Health.
NR 52
TC 4
Z9 6
U1 1
U2 12
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD APR
PY 2014
VL 95
IS 1
BP 104
EP 110
DI 10.1016/j.pec.2013.12.016
PG 7
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA AE6GJ
UT WOS:000334088300012
PM 24480361
ER
PT J
AU Wada, T
Haddad, MR
Yi, L
Murakami, T
Sasaki, A
Shimbo, H
Kodama, H
Osaka, H
Kaler, SG
AF Wada, Takahito
Haddad, Marie Reine
Yi, Ling
Murakami, Tomomi
Sasaki, Akiko
Shimbo, Hiroko
Kodama, Hiroko
Osaka, Hitoshi
Kaler, Stephen G.
TI A Novel Two-Nucleotide Deletion in the ATP7A Gene Associated With
Delayed Infantile Onset of Menkes Disease
SO PEDIATRIC NEUROLOGY
LA English
DT Article
DE Menkes disease; ATP7A; translation reinitiation; premature termination
codon
ID OCCIPITAL HORN SYNDROME; CANDIDATE GENE; MUTATIONS; PROTEIN; ENCODES
AB BACKGROUND: Determining the relationship between clinical phenotype and genotype in genetic diseases is important in clinical practice. In general, frameshift mutations are expected to produce premature termination codons, leading to production of mutant transcripts destined for degradation by nonsense-mediated decay. In X-linked recessive diseases, male patients with frameshift mutations typically have a severe or even lethal phenotype. PATIENT: We report a case of a 17-month-old boy with Menkes disease (NIM #309400), an X-linked recessive copper metabolism disorder caused by mutations in the ATP7A copper transporter gene. He exhibited an unexpectedly late onset and experienced milder symptoms. STUDY AND RESULT: His genomic DNA showed a de novo two-nucleotide deletion in exon 4 of ATP7A, predicting a translational frameshift and premature stop codon, and a classic severe phenotype. Characterization of his ATP7A mRNA showed no abnormal splicing. CONCLUSION: We speculate that translation reinitiation could occur downstream to the premature termination codon and produce a partially functional ATP7A protein. Study of the child's fibroblasts found no evidence of translation reinitiation; however, the possibility remains that this phenomenon occurred in neural tissues and influenced the clinical phenotype.
C1 [Wada, Takahito; Murakami, Tomomi; Sasaki, Akiko; Shimbo, Hiroko; Osaka, Hitoshi] Kanagawa Childrens Med Ctr, Dept Pediat Neurol, Yokohama, Kanagawa, Japan.
[Haddad, Marie Reine; Yi, Ling; Kaler, Stephen G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD USA.
[Kodama, Hiroko] Teikyo Heisei Univ, Fac Hlth & Med Sci, Dept Hlth & Dietet, Tokyo, Japan.
RP Wada, T (reprint author), Kyoto Grad Sch Med, Dept Med Eth & Med Genet, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan.
EM takahito.wada0001@me.com
FU Ministry of Health, Labour and Welfare [H22-nanchi-ippan-114]; Kanagawa
Pediatric Medical Fund; Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
FX This work was supported by research grants from the Ministry of Health,
Labour and Welfare (H22-nanchi-ippan-114; T.W. and H.O.), Kanagawa
Pediatric Medical Fund (T.W.), and the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (M.R.H., E.Y.C., S.G.K.).
NR 13
TC 1
Z9 1
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0887-8994
EI 1873-5150
J9 PEDIATR NEUROL
JI Pediatr. Neurol.
PD APR
PY 2014
VL 50
IS 4
BP 417
EP 420
DI 10.1016/j.pediatrneurol.2014.01.005
PG 4
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA AE3GY
UT WOS:000333866200029
PM 24630286
ER
PT J
AU Williams, SK
Johns, JM
AF Williams, S. K.
Johns, J. M.
TI Prenatal and gestational cocaine exposure: Effects on the oxytocin
system and social behavior with implications for addiction
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Review
DE Prenatal cocaine; Oxytocin; Maternal behavior; Aggression; Addiction;
Social behavior
ID SPRAGUE-DAWLEY RATS; MEDIAL PREOPTIC AREA;
CORTICOTROPIN-RELEASING-FACTOR; MATERNAL AGGRESSIVE-BEHAVIOR;
PITUITARY-ADRENAL AXIS; ADULT RATS; LACTATING RAT; DOPAMINE
INTERACTIONS; RECEPTOR-BINDING; SUBSTANCE-ABUSE
AB Drug abuse during pregnancy is a major public health concern, with negative consequences throughout development. Prenatal cocaine exposure (PCE) in rats produces social behavior deficits with corresponding changes in neuroendocrine and monoaminergic signaling. The relevance of parental care in social behavior maturity cannot be ignored, and gestational exposure to cocaine severely disrupts parental care, thus impacting the early environment of the offspring. Oxytocin (Oxt) is critical in regulating social behaviors and central levels are disrupted following acute and chronic cocaine (CC) treatment in postpartum rat dams, coincident with deficits in maternal care. We will discuss studies aimed to determine the relative contribution of PCE and CC-induced deficits in maternal care to social behaviors and Oxt signaling across development. PCE results in decreased social (including parental) behaviors in adolescence and adulthood. PCE is also associated with increased aggression in adults. Rearing by CC-exposed mothers synergistically increases the behavioral effects of PCE. Rearing by CC-exposed mothers, but not PCE, disrupts Oxt levels and mRNA in regions relevant to social behavior, but does not affect receptors in postpartum adult offspring. Preliminary work indicates that PCE/CC rearing has dynamic effects on Oxt levels and receptors in neonatal rat pups, suggesting very early regulation of Oxt signaling. This work highlights how the interactive role of Oxt signaling and behavioral context throughout development can be derailed by drug abuse during pregnancy. The relevance of disrupted Oxt to intergenerational transmission of addiction is briefly discussed. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Williams, S. K.] NIMH, Sect Neural Gene Express, Bethesda, MD 20892 USA.
[Johns, J. M.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Johns, J. M.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA.
[Johns, J. M.] Univ N Carolina, Curriculum Neurobiol, Chapel Hill, NC USA.
RP Williams, SK (reprint author), 49 Convent Dr, Bethesda, MD 20892 USA.
EM williamssk@mail.nih.gov
FU NIDA [P01DA022446, 1R01 DA13362, 1R01 DA13282]
FX We would like to thank the many collaborators who contributed to the
work discussed in this review. This work was financially supported by
NIDA P01DA022446 (awarded to JMJ), NIDA 1R01 DA13362 (awarded to JMJ),
and NIDA 1R01 DA13282 (awarded to JMJ).
NR 178
TC 5
Z9 6
U1 1
U2 32
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0091-3057
J9 PHARMACOL BIOCHEM BE
JI Pharmacol. Biochem. Behav.
PD APR
PY 2014
VL 119
SI SI
BP 10
EP 21
DI 10.1016/j.pbb.2013.07.004
PG 12
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA AE5DU
UT WOS:000334008800003
PM 23880214
ER
PT J
AU Milaneschi, Y
Sutin, AR
Terracciano, A
Canepa, M
Gravenstein, KS
Egan, JM
Vogelzangs, N
Guralnik, JM
Bandinelli, S
Penninx, BWJH
Ferrucci, L
AF Milaneschi, Yuri
Sutin, Angelina R.
Terracciano, Antonio
Canepa, Marco
Gravenstein, Kristofer S.
Egan, Josephine M.
Vogelzangs, Nicole
Guralnik, Jack M.
Bandinelli, Stefania
Penninx, Brenda W. J. H.
Ferrucci, Luigi
TI The association between leptin and depressive symptoms is modulated by
abdominal adiposity
SO PSYCHONEUROENDOCRINOLOGY
LA English
DT Article
DE Leptin; Depression; Abdominal adiposity; Obesity; Aging
ID C-REACTIVE PROTEIN; PLASMA LEPTIN; SERUM LEPTIN; BODY-FAT; OBESITY;
RESISTANCE; LINKING; WOMEN; IL-1; SCHIZOPHRENIA
AB Background: Evidence for a role of leptin in depression is limited and conflicting. Inconclusive findings may be explained by the complex effect of obesity on leptin signaling. In particular, both hyperleptinemia due to leptin resistance in obese persons as well as low leptin in lean persons can imply that low leptin biological signaling is associated with an increased risk of significant depressive symptoms. We tested whether the relationship between leptin and depressive symptoms is modulated by abdominal adiposity in two population-based studies.
Methods: Data were from 851 participants (65-94 years) of the InCHIANTI Study and 1064 (26-93 years) of the Baltimore Longitudinal Study of Aging (BLSA). Plasma concentrations of leptin, waist circumference and depressive symptoms via the Center for Epidemiological Studies-Depression scale (CES-D) were assessed. In longitudinal InCHIANTI analyses onset of depressed mood (CES-D >= 20) was evaluated over a 9-year follow-up.
Results: In pooled cross-sectional analyses the interaction between leptin and waist circumference was significantly associated with CES-D scores ((log)leptin-by-waist interaction p = 0.01). Also in longitudinal analyses, the (log)leptin-by-waist interaction term significantly (p = 0.04) predicted depressed mood onset over time; depressed mood risk was especially increased for high levels of both leptin and waist circumference.
Conclusions: The present findings suggest that low leptin signaling rather than low leptin concentration is a risk factor for depression. Future studies should develop proxy measures of leptin signaling by combining information on abdominal adiposity and leptin level to be used for clinical and research applications. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Milaneschi, Yuri; Vogelzangs, Nicole; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, GGZ InGeest, Dept Psychiat, NL-1081 HL Amsterdam, Netherlands.
[Milaneschi, Yuri; Vogelzangs, Nicole; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, GGZ InGeest, EMGO Inst Hlth & Care Res, NL-1081 HL Amsterdam, Netherlands.
[Milaneschi, Yuri; Gravenstein, Kristofer S.; Egan, Josephine M.; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Sutin, Angelina R.] Florida State Univ, Coll Med, Dept Med Human & Social Sci, Tallahassee, FL 32306 USA.
[Sutin, Angelina R.] NIA, Lab Populat Sci, Baltimore, MD 21224 USA.
[Terracciano, Antonio] Florida State Univ, Coll Med, Dept Geriatr, Tallahassee, FL 32306 USA.
[Canepa, Marco] NIA, Cardiovasc Sci Lab, Human Cardiovasc Studies Unit, Baltimore, MD 21224 USA.
[Canepa, Marco] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy.
[Egan, Josephine M.] NIA, Clin Invest Lab, Baltimore, MD 21224 USA.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy.
RP Milaneschi, Y (reprint author), Vrije Univ Amsterdam Med Ctr, GGZ InGeest, Dept Psychiat, AJ Ernststr 1187, NL-1081 HL Amsterdam, Netherlands.
EM y.milaneschi@ggzingeest.nl
FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute
on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111,
N01-AG-5-0002]; Intramural research program of the National Institute on
Aging, National Institutes of Health
FX The InCHIANTI study baseline (1998-2000) was supported as a "targeted
project" (ICS110.1/RF97.71) by the Italian Ministry of Health and in
part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and
263 MD 821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the
U.S. National Institute on Aging (Contracts: N.1-AG-1-1 and
N.1-AG-1-2111); the InCHIANTI Follow-ups 2 and 3 studies (2004-2010)
were financed by the U.S. National Institute on Aging (Contract:
N01-AG-5-0002);supported in part by the Intramural research program of
the National Institute on Aging, National Institutes of Health. The BLSA
is supported by the Intramural research program of the National
Institute on Aging, National Institutes of Health.
NR 49
TC 14
Z9 15
U1 2
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4530
J9 PSYCHONEUROENDOCRINO
JI Psychoneuroendocrinology
PD APR
PY 2014
VL 42
BP 1
EP 10
DI 10.1016/j.psyneuen.2013.12.015
PG 10
WC Endocrinology & Metabolism; Neurosciences; Psychiatry
SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry
GA AE5AM
UT WOS:000334000200001
PM 24636496
ER
PT J
AU Hughes, S
Jaremka, LM
Alfano, CM
Glaser, R
Povoski, SP
Lipari, AM
Agnese, DM
Farrar, WB
Yee, LD
Carson, WE
Malarkey, WB
Kiecolt-Glaser, JK
AF Hughes, Spenser
Jaremka, Lisa M.
Alfano, Catherine M.
Glaser, Ronald
Povoski, Stephen P.
Lipari, Adele M.
Agnese, Doreen M.
Farrar, William B.
Yee, Lisa D.
Carson, William E., III
Malarkey, William B.
Kiecolt-Glaser, Janice K.
TI Social support predicts inflammation, pain, and depressive symptoms:
Longitudinal relationships among breast cancer survivors
SO PSYCHONEUROENDOCRINOLOGY
LA English
DT Article
DE Social support; Pain; Depressive symptoms; Cancer survivors;
Inflammation; IL-6
ID QUALITY-OF-LIFE; RHEUMATOID-ARTHRITIS; OVARIAN-CANCER; OLDER-ADULTS;
INTERLEUKIN-6; WOMEN; HEALTH; ANXIETY; IMMUNE; DIAGNOSIS
AB Objective: Pain and depressive symptoms are commonly experienced by cancer survivors. Lower social support is linked to a variety of negative mental and physical health outcomes among survivors. Immune dysregulation may be one mechanism linking low social support to the development of pain and depressive symptoms over time. Accordingly, the goal of the present study was to examine the relationships among survivors' social support, pain, depressive symptoms, and inflammation.
Methods: Breast cancer survivors (N = 164, stages 0-IIIA) completed two study visits, one before any cancer treatment and the other 6 months after the completion of surgery, radiation, or chemotherapy, whichever came last. Women completed self-report questionnaires assessing social support, pain, and depressive symptoms, and provided a blood sample at both visits.
Results: Survivors with lower social support prior to treatment experienced higher levels of pain and depressive symptoms over time than their more socially supported counterparts. Furthermore, women with lower pretreatment social support had higher levels of IL-6 over time, and these elevations in IL-6 predicted marginally larger increases in depressive symptoms.
Conclusions: The results of this study suggest that social support at the time of diagnosis predicts the post-treatment development of pain, depressive symptoms, and inflammation. Consequently, early interventions targeting survivors' social networks could improve quality of life during survivorship. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Hughes, Spenser; Jaremka, Lisa M.; Glaser, Ronald; Malarkey, William B.; Kiecolt-Glaser, Janice K.] Ohio State Univ, Coll Med, Inst Behav Med Res, Columbus, OH 43210 USA.
[Hughes, Spenser; Kiecolt-Glaser, Janice K.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
[Alfano, Catherine M.] NCI, Bethesda, MD 20892 USA.
[Glaser, Ronald] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Coll Med, Columbus, OH 43210 USA.
[Glaser, Ronald; Malarkey, William B.] Ohio State Univ, Dept Internal Med, Coll Med, Columbus, OH 43210 USA.
[Kiecolt-Glaser, Janice K.] Ohio State Univ, Dept Psychiat, Coll Med, Columbus, OH 43210 USA.
[Glaser, Ronald; Povoski, Stephen P.; Lipari, Adele M.; Agnese, Doreen M.; Farrar, William B.; Yee, Lisa D.; Carson, William E., III; Malarkey, William B.; Kiecolt-Glaser, Janice K.] Ohio State Univ, Ctr Comprehens Canc, Coll Med, Columbus, OH 43210 USA.
[Povoski, Stephen P.; Lipari, Adele M.; Agnese, Doreen M.; Farrar, William B.; Yee, Lisa D.; Carson, William E., III] Ohio State Univ, Dept Surg, Coll Med, Columbus, OH 43210 USA.
RP Hughes, S (reprint author), Ohio State Univ, Coll Med, Inst Behav Med Res, 460 Med Ctr Dr, Columbus, OH 43210 USA.
EM Spenser.Hughes@osumc.edu
RI Kiecolt-Glaser, Janice/A-3236-2009; Carson, William/E-2846-2011;
Povoski, Stephen/E-3887-2011; Agnese, Doreen/I-1351-2012
OI Kiecolt-Glaser, Janice/0000-0003-4900-9578;
FU NIH [CA131029, UL1TR000090, CA016058, K05 CA172296]; American Cancer
Society Postdoctoral Fellowship [121911-PF-12-040-01-CPPB]; Pelotonia
Postdoctoral Fellowship from the Ohio State University Comprehensive
Cancer Center
FX Work on this project was supported by NIH grants CA131029, UL1TR000090,
CA016058 and K05 CA172296, American Cancer Society Postdoctoral
Fellowship Grant 121911-PF-12-040-01-CPPB, and a Pelotonia Postdoctoral
Fellowship from the Ohio State University Comprehensive Cancer Center.
NR 53
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Z9 15
U1 5
U2 29
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4530
J9 PSYCHONEUROENDOCRINO
JI Psychoneuroendocrinology
PD APR
PY 2014
VL 42
BP 38
EP 44
DI 10.1016/j.psyneuen.2013.12.016
PG 7
WC Endocrinology & Metabolism; Neurosciences; Psychiatry
SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry
GA AE5AM
UT WOS:000334000200004
PM 24636499
ER
PT J
AU Dettmer, AM
Novak, MA
Meyer, JS
Suomi, SJ
AF Dettmer, A. M.
Novak, M. A.
Meyer, J. S.
Suomi, S. J.
TI Population density-dependent hair cortisol concentrations in rhesus
monkeys (Macaca mulatta)
SO PSYCHONEUROENDOCRINOLOGY
LA English
DT Article
DE Cortisol; Stress; Chronic; Population density; Rhesus monkey
ID FEMALE CYNOMOLGUS MONKEYS; INFECTIOUS-DISEASES; NONHUMAN-PRIMATES;
RELOCATION STRESS; PLASMA-CORTISOL; CROWDING STRESS; DOMINANCE RANK; HPA
AXIS; BEHAVIOR; GROWTH
AB Population density is known to influence acute measures of hypothalamic-pituitary-adrenal (HPA) axis activity in a variety of species, including fish, deer, birds, and humans. However, the effects of population density on levels of chronic stress are unknown. Given the fact that exposure to chronically elevated levels of circulating glucocorticoids results in a host of health disparities in animals and humans alike, it is important to understand how population density may impact chronic stress. We assessed hair cortisol concentrations (HCCs), which are reliable indicators of chronic HPA axis activity, in rhesus monkeys (Macaca mulatto) to determine the influence of population density on these values. In Experiment 1, we compared HCCs of monkeys living in high-density (HD; 1 monkey/0.87 m(2)) and low-density (LD; 1 monkey/63.37 m(2)) environments (N = 236 hair samples) and found that HD monkeys exhibited higher hair cortisol across all age categories (infant, juvenile, young adult, adult, and aged) except infancy and aged (F-(5) = 4.240, p = 0.001), for which differences were nearly significant. HD monkeys also received more severe fight wounds than LD monkeys (chi(2) = 26.053, p < 0.001), though no effects of dominance status emerged. In Experiment 2, we examined how HCCs change with fluctuating population levels across 5 years in the adult LD monkeys (N = 155 hair samples) and found that increased population density was significantly positively correlated with HCCs in this semi-naturalistic population (r((s)) = 0.975, p = 0.005). These are the first findings to demonstrate that increased population density is associated with increased chronic, endogenous glucocorticoid exposure in a nonhuman primate species. We discuss the implications of these findings with respect to laboratory research, population ecology, and human epidemiology. (C) Published by Elsevier Ltd.
C1 [Dettmer, A. M.; Suomi, S. J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Poolesville, MD 20837 USA.
[Novak, M. A.; Meyer, J. S.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA.
RP Dettmer, AM (reprint author), 16701 Elmer Sch Rd, Poolesville, MD 20837 USA.
EM dettmera@mail.nih.gov
OI Meyer, Jerrold/0000-0002-8382-7075
FU Division of Intramural Research, National Institute of Child Health Et
Human Development, NIH; NIH [RR11122, OD011180]
FX This research was supported by funds from the Division of Intramural
Research, National Institute of Child Health & Human Development, NIH,
and by NIH Grants RR11122 and OD011180 to M.A.N. Neither the NIH nor the
NICHD had any further role in study design; in the collection, analysis
and interpretation of data; in the writing of the report; and in the
decision to submit the paper for publication.
NR 74
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U1 6
U2 37
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4530
J9 PSYCHONEUROENDOCRINO
JI Psychoneuroendocrinology
PD APR
PY 2014
VL 42
BP 59
EP 67
DI 10.1016/j.psyneuen.2014.01.002
PG 9
WC Endocrinology & Metabolism; Neurosciences; Psychiatry
SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry
GA AE5AM
UT WOS:000334000200007
PM 24636502
ER
PT J
AU Fix, BV
O'Connor, RJ
Vogl, L
Smith, D
Bansal-Travers, M
Conway, KP
Ambrose, B
Yang, L
Hyland, A
AF Fix, Brian V.
O'Connor, Richard J.
Vogl, Lisa
Smith, Danielle
Bansal-Travers, Maansi
Conway, Kevin P.
Ambrose, Bridget
Yang, Ling
Hyland, Andrew
TI Patterns and correlates of polytobacco use in the United States over a
decade: NSDUH 2002-2011
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Polytobacco use; Tobacco; Cigarettes; Smokeless tobacco; Cigars; Tobacco
use trends
ID SMOKELESS TOBACCO; CIGARETTE-SMOKING; MALE-ADOLESCENTS; YOUNG-ADULTS;
PRODUCTS; SMOKERS; SNUS; POPULATION; PREVALENCE; ALCOHOL
AB Background: Few studies have examined the patterns and correlates of polytobacco use among a large, nationally representative population over an extended period of time.
Methods: This study examined 10 years of data from the National Survey on Drug Use and Health (NSDUH) to establish time trends and correlates for exclusive and mixed use of cigarettes, smokeless tobacco (SLT), cigars, and pipes.
Results: Results show that rates of polytobacco use were essentially unchanged from 2002 to 2011 (8.7% to 7.4%), though some product combinations, including cigarettes and SLT, cigars and SLT, and use of more than two products have increased. In tobacco users under age 26, the proportion of polytobacco use increased, even as overall tobacco use declined. The factors associated with polytobacco use among tobacco users included sex, income, education, risk taking/seeking behaviors, and outward indicators of 'risk-liability'.
Conclusions: Findings provide a snapshot of trends of single and polytobacco product use as well as trends in combinations of product use. Longitudinal studies are needed to examine the sequence of individual patterns of tobacco product use and to identify whether polytobacco use results in greater nicotine dependence, increased exposure to harmful and potentially harmful constituents and/or greater risk of tobacco related disease. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Fix, Brian V.; O'Connor, Richard J.; Vogl, Lisa; Smith, Danielle; Bansal-Travers, Maansi; Hyland, Andrew] Roswell Pk Canc Inst, Dept Hlth Behav, Buffalo, NY 14263 USA.
[Conway, Kevin P.] NIDA, NIH, Bethesda, MD 20892 USA.
[Ambrose, Bridget; Yang, Ling] US FDA, Ctr Tobacco Prod, Rockville, MD 20850 USA.
RP Fix, BV (reprint author), Roswell Pk Canc Inst, Dept Hlth Behav, Elm & Carlton St, Buffalo, NY 14263 USA.
EM brian.fix@roswellpark.org
RI O'Connor, Richard/A-6961-2009;
OI Conway, Kevin/0000-0002-7638-339X
FU National Institute on Drug Abuse; National Institutes of Health; Food
and Drug Administration; Department of Health and Human Services
[HHSN271201100027C]
FX This project has been funded in whole or in part with Federal funds from
the National Institute on Drug Abuse, the National Institutes of Health,
and the Food and Drug Administration, the Department of Health and Human
Services, under Contract No. HHSN271201100027C. Funders had no further
role in study design; in the collection, analysis, and interpretation of
data; in the writing of the report; or in the decision to submit the
paper for publication.
NR 30
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U1 2
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
EI 1873-6327
J9 ADDICT BEHAV
JI Addict. Behav.
PD APR
PY 2014
VL 39
IS 4
BP 768
EP 781
DI 10.1016/j.addbeh.2013.12.015
PG 14
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA AD8JF
UT WOS:000333511600004
PM 24457900
ER
PT J
AU Cohn, AM
Cobb, C
Hagman, BT
Cameron, A
Ehlke, S
Mitchell, JN
AF Cohn, Amy M.
Cobb, Caroline
Hagman, Brett T.
Cameron, Amy
Ehlke, Sarah
Mitchell, Jessica N.
TI Implicit alcohol cognitions in risky drinking nicotine users with and
without co-morbid major depressive disorder
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Implicit attitudes; Alcohol use; Drinking; Nicotine use; Depression;
Comorbidity
ID COMORBIDITY SURVEY REPLICATION; DSM-IV DISORDERS; TOBACCO DEPENDENCE;
SMOKING-CESSATION; ASSOCIATION TEST; NEGATIVE AFFECT; RESTRAINT
INVENTORY; ADDICTIVE DISORDERS; YOUNG ADULTHOOD; MENTAL-ILLNESS
AB Objective: Alcohol consumption, nicotine use, and major depressive disorder (MDD) are highly co-morbid. The negative reinforcement model of addiction would suggest that smokers may consume alcohol to relieve negative affective symptoms, such as those associated with MDD and withdrawal from nicotine. Over time, these behaviors may become so strongly paired together that they automatically activate a desire to use alcohol, even in the absence of conscious or deliberate intention. This study examined implicit alcohol cognitions in 146 risky drinking nicotine users (n = 83) and non-users (n = 63), to help uncover cognitive mechanisms that link drinking, nicotine use, and depression together. We proposed that nicotine users with a history of MDD would have stronger implicit motivations to drink than non-nicotine users without MDD.
Method: Participants were assessed on lifetime MDD (n = 84) or no MDD (n = 62), and then completed an Implicit Association Task designed to test the strength of associations between alcohol pictures and "approach" words. Results: Regression analyses showed that implicit alcohol-approach attitudes were stronger among risky drinking nicotine users than non-users. Alcohol-approach motivations were also stronger among risky drinking nicotine users compared to non-users with a history of MOD; nicotine use was unrelated to implicit alcohol cognitions for risky drinkers without MDD.
Conclusions: Implicit cognitive processes may be targeted in behavioral and pharmacological treatments in risky drinking nicotine users, particularly those with depression comorbidity. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Cohn, Amy M.; Cobb, Caroline] Schroeder Inst Tobacco Res & Policy Studies, Washington, DC 20036 USA.
[Hagman, Brett T.] NIAAA, Bethesda, MD USA.
[Cameron, Amy] Clark Univ, Dept Psychol, Worcester, MA 01610 USA.
[Ehlke, Sarah] Univ N Carolina, Dept Psychol, Wilmington, NC 28401 USA.
[Mitchell, Jessica N.] Univ S Florida, Dept Criminol, Tampa, FL 33620 USA.
RP Cohn, AM (reprint author), Schroeder Inst Tobacco Res & Policy Studies, 1724 Massachusetts Ave NW, Washington, DC 20036 USA.
EM acohn@legacyforhealth.org; ccobb@legacyforhealth.org;
brett.hagman@nih.gov; acameron@Clarku.edu; sehlke@usf.edu;
jmitche6@usf.edu
OI Cameron, Amy/0000-0003-2747-8365
FU NIAAA [T32 AA07569]; NIDA [P30DA028807]
FX This research was supported in part by NIAAA grant T32 AA07569 and NIDA
grant P30DA028807. The content is solely the responsibility of the
author(s). NIAAA, NIDA, or the NIH had no role in the study design,
collection, analysis or interpretation of the data, writing the
manuscript, or the decision to submit the paper for publication.
NR 51
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Z9 3
U1 3
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
EI 1873-6327
J9 ADDICT BEHAV
JI Addict. Behav.
PD APR
PY 2014
VL 39
IS 4
BP 797
EP 802
DI 10.1016/j.addbeh.2013.12.012
PG 6
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA AD8JF
UT WOS:000333511600008
PM 24531633
ER
PT J
AU Haley, DF
Lucas, J
Golin, CE
Wang, J
Hughes, JP
Emel, L
El-Sadr, W
Frew, PM
Justman, J
Adimora, AA
Watson, CC
Mannheimer, S
Rompalo, A
Soto-Torres, L
Tims-Cook, Z
Carter, Y
Hodder, SL
AF Haley, Danielle F.
Lucas, Jonathan
Golin, Carol E.
Wang, Jing
Hughes, James P.
Emel, Lynda
El-Sadr, Wafaa
Frew, Paula M.
Justman, Jessica
Adimora, Adaora A.
Watson, Christopher Chauncey
Mannheimer, Sharon
Rompalo, Anne
Soto-Torres, Lydia
Tims-Cook, Zandraetta
Carter, Yvonne
Hodder, Sally L.
CA HPTN 064 Study Team
TI Retention Strategies and Factors Associated with Missed Visits Among Low
Income Women at Increased Risk of HIV Acquisition in the US (HPTN 064)
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID HEALTH-SERVICES UTILIZATION; ANDERSEN BEHAVIORAL-MODEL; VACCINE EFFICACY
TRIALS; UNITED-STATES; CLINICAL-TRIALS; VULNERABLE POPULATIONS;
PARTICIPATION; PREVENTION; INFECTION; GENDER
AB Women at high-risk for HIV acquisition often face challenges that hinder their retention in HIV prevention trials. These same challenges may contribute to missed clinical care visits among HIV-infected women. This article, informed by the Gelberg-Andersen Behavioral Model for Vulnerable Populations, identifies factors associated with missed study visits and describes the multifaceted retention strategies used by study sites. HPTN 064 was a multisite, longitudinal HIV seroincidence study in 10 US communities. Eligible women were aged 18-44 years, resided in a census tract/zipcode with high poverty and HIV prevalence, and self-reported >= 1 personal or sex partner behavior related to HIV acquisition. Multivariate analyses of predisposing (e.g., substance use) and enabling (e.g., unmet health care needs) characteristics, and study attributes (i.e., recruitment venue, time of enrollment) identified factors associated with missed study visits. Retention strategies included: community engagement; interpersonal relationship building; reduction of external barriers; staff capacity building; and external tracing. Visit completion was 93% and 94% at 6 and 12 months. Unstable housing and later date of enrollment were associated with increased likelihood of missed study visits. Black race, recruitment from an outdoor venue, and financial responsibility for children were associated with greater likelihood of attendance. Multifaceted retention strategies may reduce missed study visits. Knowledge of factors associated with missed visits may help to focus efforts.
C1 [Haley, Danielle F.; Lucas, Jonathan] FHI 360, Durham, NC USA.
[Haley, Danielle F.; Frew, Paula M.] Rollins Sch Publ Hlth, Atlanta, GA USA.
[Golin, Carol E.; Adimora, Adaora A.; Carter, Yvonne] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Golin, Carol E.; Adimora, Adaora A.; Carter, Yvonne] Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Wang, Jing; Hughes, James P.; Emel, Lynda] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Hughes, James P.] Univ Washington, Seattle, WA 98195 USA.
[El-Sadr, Wafaa; Justman, Jessica; Mannheimer, Sharon] ICAP Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Frew, Paula M.] Emory Univ, Sch Med, Div Infect Dis, Dept Med, Atlanta, GA 30322 USA.
[Watson, Christopher Chauncey] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
[Mannheimer, Sharon] Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, New York, NY 10032 USA.
[Rompalo, Anne] Johns Hopkins Sch Med, Baltimore, MD USA.
[Soto-Torres, Lydia] NIAID, NIH, Bethesda, MD 20892 USA.
[Tims-Cook, Zandraetta] Ctr AIDS Res, Atlanta, GA USA.
[Hodder, Sally L.] Rutgers, New Jersey Med Sch, Newark, NJ USA.
RP Haley, DF (reprint author), Emory Univ, Dept Behav Sci & Hlth Educ, Rollins Sch Publ Hlth, 1518 Clifton Rd NE,Room 430, Atlanta, GA 30322 USA.
EM dfhaley@emory.edu
OI Frew, Paula/0000-0002-3078-9124
FU National Institute of Allergy and Infectious Diseases, National
Institute on Drug Abuse, and National Institute of Mental Health [UM1
AI068619, U01-AI068613, UM1-AI068613]; Centers for Innovative Research
to Control AIDS, Mailman School of Public Health, Columbia University
[5U1A1069466]; University of North Carolina Clinical Trials Unit
[AI069423]; University of North Carolina Clinical Trials Research Center
of the Clinical and Translational Science Award [RR 025747]; University
of North Carolina Center for AIDS Research [AI050410]; Emory University
HIV/AIDS Clinical Trials Unit [5UO1AI069418]; Center for AIDS Research
[P30 AI050409]; Clinical and Translational Science Award [UL1 RR025008];
Terry Beirn Community Programs for Clinical Research on AIDS Clinical
Trials Unit [5 UM1 AI069503-07]; Johns Hopkins Adult AIDS Clinical Trial
Unit [AI069465]; Johns Hopkins Clinical and Translational Science Award
[UL1 RR 25005]
FX Funding: Grant support provided by the National Institute of Allergy and
Infectious Diseases, National Institute on Drug Abuse, and National
Institute of Mental Health [UM1 AI068619, U01-AI068613, and
UM1-AI068613]; Centers for Innovative Research to Control AIDS, Mailman
School of Public Health, Columbia University [5U1A1069466]; University
of North Carolina Clinical Trials Unit [AI069423]; University of North
Carolina Clinical Trials Research Center of the Clinical and
Translational Science Award [RR 025747]; University of North Carolina
Center for AIDS Research [AI050410]; Emory University HIV/AIDS Clinical
Trials Unit [5UO1AI069418], Center for AIDS Research [P30 AI050409], and
Clinical and Translational Science Award [UL1 RR025008]; The Terry Beirn
Community Programs for Clinical Research on AIDS Clinical Trials Unit [5
UM1 AI069503-07], and; The Johns Hopkins Adult AIDS Clinical Trial Unit
[AI069465] and The Johns Hopkins Clinical and Translational Science
Award [UL1 RR 25005].
NR 49
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Z9 10
U1 1
U2 11
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
EI 1557-7449
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD APR 1
PY 2014
VL 28
IS 4
BP 206
EP 217
DI 10.1089/apc.2013.0366
PG 12
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA AE1WY
UT WOS:000333764700007
PM 24697160
ER
PT J
AU Parikh, CR
Butrymowicz, I
Yu, A
Chinchilli, VM
Park, M
Hsu, CY
Reeves, WB
Devarajan, P
Kimmel, PL
Siew, ED
Liu, KD
AF Parikh, Chirag R.
Butrymowicz, Isabel
Yu, Angela
Chinchilli, Vernon M.
Park, Meyeon
Hsu, Chi-yuan
Reeves, W. Brian
Devarajan, Prasad
Kimmel, Paul L.
Siew, Edward D.
Liu, Kathleen D.
CA ASSESS-AKI Study Investigators
TI Urine Stability Studies for Novel Biomarkers of Acute Kidney Injury
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Proteins; storage; handling; concordance; urine biomarker; acute kidney
injury (AKI); acute renal failure (ARF); protein stability; biospecimen
handling
ID GELATINASE-ASSOCIATED LIPOCALIN; ACUTE-RENAL-FAILURE; SERUM CYSTATIN-C;
CARDIAC-SURGERY; MOLECULE-1 KIM-1; PREDICTS; NGAL
AB Background: The study of novel urinary biomarkers of acute kidney injury has expanded exponentially. Effective interpretation of data and meaningful comparisons between studies require awareness of factors that can adversely affect measurement. We examined how variations in short-term storage and processing might affect the measurement of urine biomarkers.
Study Design: Cross-sectional prospective.
Setting & Participants: Hospitalized patients from 2 sites: Yale New Haven Hospital (n = 50) and University of California, San Francisco Medical Center (n = 36).
Predictors: We tested the impact of 3 urine processing conditions on these biomarkers: (1) centrifugation and storage at 4 degrees C for 48 hours before freezing at 280 degrees C, (2) centrifugation and storage at 25 degrees C for 48 hours before freezing at 280 degrees C, and (3) uncentrifuged samples immediately frozen at 280 degrees C.
Outcomes: Urine concentrations of = biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), and cystatin C.
Measurements: We measured urine biomarkers by established enzyme-linked immunosorbent assay methods. Biomarker values were log-transformed, and agreement with a reference standard of immediate centrifugation and storage at 280 degrees C was compared using concordance correlation coefficients (CCCs).
Results: Neither storing samples at 4 degrees C for 48 hours nor centrifugation had a significant effect on measured levels, with CCCs higher than 0.9 for all biomarkers tested. For samples stored at 25 degrees C for 48 hours, excellent CCC values (>0.9) also were noted between the test sample and the reference standard for NGAL, cystatin C, L-FABP and KIM-1. However, the CCC for IL-18 between samples stored at 25 degrees C for 48 hours and the reference standard was 0.81 (95% CI, 0.66-0.96).
Limitations: No comparisons to fresh, unfrozen samples; no evaluation of the effect of protease inhibitors.
Conclusions: All candidate markers tested using the specified assays showed high stability with both short-term storage at 4 degrees C and without centrifugation prior to freezing. For optimal fidelity, urine for IL-18 measurement should not be stored at 25 degrees C before long-term storage or analysis. (C) 2014 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Parikh, Chirag R.; Butrymowicz, Isabel; Yu, Angela] Yale Univ, Sch Med, Sect Nephrol, Dept Med, New Haven, CT 06510 USA.
[Parikh, Chirag R.; Butrymowicz, Isabel; Yu, Angela] Yale Univ, Sch Med, Program Appl Translat Res, New Haven, CT 06510 USA.
[Chinchilli, Vernon M.] Penn State Coll Med, Dept Publ Hlth Sci, Hershey, PA USA.
[Park, Meyeon; Hsu, Chi-yuan; Liu, Kathleen D.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA.
[Hsu, Chi-yuan] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Reeves, W. Brian] Penn State Coll Med, Dept Med, Div Nephrol, Hershey, PA USA.
[Devarajan, Prasad] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Kimmel, Paul L.] Natl Inst Diabet & Digest & Kidney Dis, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA.
[Siew, Edward D.] Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol & Hypertens, Nashville, TN USA.
RP Parikh, CR (reprint author), Yale Univ, Sch Med, Program Appl Translat Res, 60 Temple St,6th Fl,Ste 6C, New Haven, CT 06510 USA.
EM chirag.parikh@yale.edu
FU NIDDK of the National Institutes of Health (NIH) [U01-DK082223,
U01-DK082185, U01DK082192, U01DK082183]; US Department of Health and
Human Services; National Center for Research Resources; National Center
for Advancing Translational Sciences, NIH, through University of
California, San Francisco-Clinical and Translational Science Institute
[UL1 RR024131]; [K24 DK92291]; [5K23DK088964-02]
FX This study was supported by the supplemental American Recovery and
Reinvestment Act funds and research grants U01-DK082223, U01-DK082185,
U01DK082192, and U01DK082183 from the NIDDK of the National Institutes
of Health (NIH), US Department of Health and Human Services. This
publication was also supported by the National Center for Research
Resources and the National Center for Advancing Translational Sciences,
NIH, through University of California, San Francisco-Clinical and
Translational Science Institute grant UL1 RR024131. Drs Hsu and Siew are
additionally supported by grants K24 DK92291 and 5K23DK088964-02,
respectively. The opinions expressed in this article are the authors'
own and do not reflect the view of the NIH, the Department of Health and
Human Services, or the United States government.
NR 24
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U1 0
U2 13
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
EI 1523-6838
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD APR
PY 2014
VL 63
IS 4
BP 567
EP 572
DI 10.1053/j.ajkd.2013.09.013
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA AD7GB
UT WOS:000333429500009
PM 24200462
ER
PT J
AU Tan, WH
Bird, LM
Thibert, RL
Williams, CA
AF Tan, Wen-Hann
Bird, Lynne M.
Thibert, Ronald L.
Williams, Charles A.
TI If Not Angelman, What Is It? A Review of Angelman- like Syndromes
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE Angelman syndrome; differential diagnoses; Phelan-McDermid syndrome;
MBD5 deficiency; KANSL1 deficiency; Pitt-Hopkins syndrome; Christianson
syndrome; Mowat-Wilson syndrome; Kleefstra syndrome; HERC2 deficiency;
Adenylosuccinase lyase deficiency; ADSL deficiency; Rett syndrome; CDKL5
syndrome; FOXG1 syndrome; MECP2 duplication; MEF2C syndrome; ATRX
ID PITT-HOPKINS-SYNDROME; ADENYLOSUCCINATE LYASE DEFICIENCY; SEVERE
MENTAL-RETARDATION; MOWAT-WILSON-SYNDROME; 17Q21.31 MICRODELETION
SYNDROME; MECP2 DUPLICATION SYNDROME; AUTISM SPECTRUM DISORDER; 22Q13
DELETION SYNDROME; OF-THE-LITERATURE; BEHAVIORAL-PHENOTYPE
AB Angelman syndrome (AS) is caused by a lack of expression of the maternally inherited UBE3A gene in the brain. However, about 10% of individuals with a clinical diagnosis of AS do not have an identifiable molecular defect. It is likely that most of those individuals have an AS-like syndrome that is clinically and molecularly distinct from AS. These AS-like syndromes can be broadly classified into chromosomal microdeletion and microduplication syndromes, and single-gene disorders. The microdeletion/microduplication syndromes are now easily identified by chromosomal microarray analysis and include Phelan-McDermid syndrome (chromosome 22q13.3 deletion), MBD5 haploinsufficiency syndrome (chromosome 2q23.1 deletion), and KANSL1 haploinsufficiency syndrome (chromosome 17q21.31 deletion). The single-gene disorders include Pitt-Hopkins syndrome (TCF4), Christianson syndrome (SLC9A6), Mowat-Wilson syndrome (ZEB2), Kleefstra syndrome (EHMT1), and Rett (MECP2) syndrome. They also include disorders due to mutations in HERC2, adenylosuccinase lyase (ADSL), CDKL5, FOXG1, MECP2 (duplications), MEF2C, and ATRX. Although many of these single-gene disorders can be caused by chromosomal microdeletions resulting in haploinsufficiency of the critical gene, the individual disorders are often caused by intragenic mutations that cannot be detected by chromosomal microarray analysis. We provide an overview of the clinical features of these syndromes, comparing and contrasting them with AS, in the hope that it will help guide clinicians in the diagnostic work-up of individuals with AS-like syndromes. (c) 2014 Wiley Periodicals, Inc.
C1 [Williams, Charles A.] Univ Florida, Coll Med, Raymond C Philips Unit, Div Genet & Metab, 1600 SW Archer Rd,M-351,POB 100296, Gainesville, FL 32610 USA.
[Tan, Wen-Hann; Bird, Lynne M.] NIH, Rare Dis Clin Res Network, Angelman Rett & Prader Willi Syndromes Consortium, Birmingham, AL USA.
[Tan, Wen-Hann] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Tan, Wen-Hann; Thibert, Ronald L.] Harvard Univ, Sch Med, Boston, MA USA.
[Bird, Lynne M.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA.
[Bird, Lynne M.] Rady Childrens Hosp San Diego, Div Genet Dysmorphol, San Diego, CA USA.
[Thibert, Ronald L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Williams, CA (reprint author), Univ Florida, Coll Med, Raymond C Philips Unit, Div Genet & Metab, 1600 SW Archer Rd,M-351,POB 100296, Gainesville, FL 32610 USA.
EM willicx@peds.ufl.edu
FU National Center for Research Resources (NCRR) [NIH U54 RR019478];
National Institute of Child Health and Human Development [NIH U54
HD061222]; NIH Office of Rare Diseases Research (ORDR); Angelman
Syndrome Foundation - Western Area Chapter; Food and Drug Administration
(FDA) Office of Orphan Products Development [R01 FD003523-01A2]
FX Grant sponsor: National Center for Research Resources (NCRR); Grant
number: NIH U54 RR019478; Grant sponsor: National Institute of Child
Health and Human Development; Grant number: NIH U54 HD061222; Grant
sponsor: NIH Office of Rare Diseases Research (ORDR); Grant sponsor:
Angelman Syndrome Foundation - Western Area Chapter; Grant sponsor: Food
and Drug Administration (FDA) Office of Orphan Products Development;
Grant number: R01 FD003523-01A2.
NR 90
TC 17
Z9 19
U1 2
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD APR
PY 2014
VL 164
IS 4
BP 975
EP 992
DI 10.1002/ajmg.a.36416
PG 18
WC Genetics & Heredity
SC Genetics & Heredity
GA AD4CL
UT WOS:000333193800040
PM 24779060
ER
PT J
AU Fornetti, J
Jindal, S
Middleton, KA
Borges, VF
Schedin, P
AF Fornetti, Jaime
Jindal, Sonali
Middleton, Kara A.
Borges, Virginia F.
Schedin, Pepper
TI Physiological COX-2 Expression in Breast Epithelium Associates with
COX-2 Levels in Ductal Carcinoma in Situ and Invasive Breast Cancer in
Young Women
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID DISEASE-FREE SURVIVAL; CYCLOOXYGENASE-2 EXPRESSION; PROGNOSTIC-FACTOR;
MAMMARY-GLAND; RISK; AGE; ASPIRIN; RECURRENCE; RAT; TUMORIGENESIS
AB Cyclooxygenase-2 (COX-2) overexpression is implicated in increased risk and poorer outcomes in breast cancer in young women. We investigated COX-2 regulation in normal premenopausal breast tissue and its relationship to malignancy in young women. Quantitative COX-2 immunohistochemistry was performed on adjacent normal and breast cancer tissues from 96 premenopausal women with known clinical reproductive histories, and on rat mammary glands with distinct ovarian hormone exposures. COX-2 expression in the normal breast epithelium varied more than 40-fold between women and was associated with COX-2 expression levels in ductal carcinoma in situ and invasive cancer. Normal breast COX-2 expression was independent of known breast cancer prognostic indicators, including tumor stage and clinical subtype, indicating that factors regulating physiological COX-2 expression may be the primary drivers of COX-2 expression in breast cancer. Ovarian hormones, particularly at pregnancy levels, were identified as modulators of COX-2 in normal mammary epithelium. However, serial breast biopsy analysis in nonpregnant premenopausal women suggested relatively stable baseline levels of COX-2 expression, which persisted independent of menstrual cycling. These data provide impetus to investigate how baseline COX-2 expression is regulated in premenopausal breast tissue because COX-2 Levels in normal breast epithelium may prove to be an indicator of breast cancer risk in young women, and predict the chemopreventive and therapeutic efficacy of COX-2 inhibitors in this population.
C1 [Fornetti, Jaime; Jindal, Sonali; Borges, Virginia F.; Schedin, Pepper] Univ Colorado, Div Med Oncol, Ctr Canc, Aurora, CO 80045 USA.
[Fornetti, Jaime; Schedin, Pepper] Univ Colorado, Dept Med, Ctr Canc, Reprod Sci Program, Aurora, CO 80045 USA.
[Fornetti, Jaime; Jindal, Sonali; Borges, Virginia F.; Schedin, Pepper] Univ Colorado, Ctr Canc, Young Womens Breast Canc Translat Program, Aurora, CO 80045 USA.
[Middleton, Kara A.] NIA, Genet Lab, Baltimore, MD 21224 USA.
[Schedin, Pepper] AMC Canc Res Fdn, Denver, CO USA.
RP Schedin, P (reprint author), Univ Colorado, Div Med Oncol, Anschutz Med Campus,MS 8117,RC1 South 401K, Aurora, CO 80045 USA.
EM pepper.schedin@ucdenver.edu
OI jindal, sonali/0000-0002-3911-6815
FU Tissue Biobanking and Processing Shared Resource of Colorado's
NIH/National Cancer Institute Cancer Center [P30 CA046934]; Department
of Defense grants [BC104000, BC10400P1]; Department of Defense
Predoctoral Traineeship Award [BC093130]; Cancer Center grant [P30
CA016056-27]; Avon Foundation; Men for the Cure Foundation; Grohne
Family Foundation; Glass Family Foundation
FX Supported by a grant from the Tissue Biobanking and Processing Shared
Resource of Colorado's NIH/National Cancer Institute Cancer Center (P30
CA046934), Department of Defense grants (BC104000 and BC10400P1 to P.S.
and V.F.B.), a Department of Defense Predoctoral Traineeship Award
(BC093130 to J.F.), a Cancer Center grant (P30 CA016056-27), and by the
Avon, Men for the Cure, Grohne Family, and Glass Family Foundations.
NR 45
TC 14
Z9 15
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD APR
PY 2014
VL 184
IS 4
BP 1219
EP 1229
DI 10.1016/j.ajpath.2013.12.026
PG 11
WC Pathology
SC Pathology
GA AD8XI
UT WOS:000333548600031
PM 24518566
ER
PT J
AU Kiley, J
Gibbons, G
AF Kiley, James
Gibbons, Gary
TI Developing a Research Agenda for Primary Prevention of Chronic Lung
Diseases-An NHLBI Perspective
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
C1 [Kiley, James; Gibbons, Gary] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Kiley, J (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 5
Z9 5
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD APR 1
PY 2014
VL 189
IS 7
BP 762
EP 763
PG 3
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA AD9DS
UT WOS:000333565600003
PM 24684354
ER
PT J
AU Zelner, JL
Murray, MB
Becerra, MC
Galea, J
Lecca, L
Calderon, R
Yataco, R
Contreras, C
Zhang, ZB
Grenfell, BT
Cohen, T
AF Zelner, Jonathan L.
Murray, Megan B.
Becerra, Mercedes C.
Galea, Jerome
Lecca, Leonid
Calderon, Roger
Yataco, Rosa
Contreras, Carmen
Zhang, Zibiao
Grenfell, Bryan T.
Cohen, Ted
TI Bacillus Calmette-Guerin and Isoniazid Preventive Therapy Protect
Contacts of Patients with Tuberculosis
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE tuberculosis; isoniazid preventive therapy; bacillus Calmette-Guerin
vaccination; household intervention
ID BCG VACCINE; METAANALYSIS
AB Rationale: Individuals living with patients with tuberculosis (TB) are at elevated risk of infection and disease, with children at greatest risk. The World Health Organization recommends isoniazid preventive therapy (IPT) for HIV-positive contacts and those younger than 5 years. Despite these recommendations, household-level IPT programs are rarely implemented in high TB burden settings. Evidence is scarce about the age-specific efficacy of interventions, such as IPT and bacillus Calmette-Gu erin (BCG) vaccination for preventing TB disease among exposed contacts.
Objectives: We estimate the age-specific efficacy of IPT and BCG for preventing TB disease using data from a large observational prospective cohort study of household contacts of patients with TB in Lima, Peru.
Methods: We identified all adults (> 15 yr) with incident pulmonary TB (index cases) diagnosed at 106 public health centers in Lima from September 2009 to August 2012. Among 14,041 household contacts (of 3,446 index cases) assessed for infection and disease during the yearlong follow-up period, we identified 462 additional TB cases. We estimate risk ratios (RR) for pulmonary TB associated with BCG, IPT, and latent TB infection.
Measurements and Main Results: BCG confers protection against coprevalent and incident TB among HIV-negative children younger than 10 years (RR, 0.35; 95% confidence interval, 0.19-0.66). IPT confers protection against incident TB among HIV-negative contacts younger than 30 years (RR, 0.33; 95% confidence interval, 0.20-0.54). Risk of incident TB associated with latent TB infection is greatest for children younger than 5 years and decreases with age.
Conclusions: These findings support the use of IPT in older children and young-adult household contacts, in addition to children younger than 5 years.
C1 [Zelner, Jonathan L.; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Zelner, Jonathan L.; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Murray, Megan B.; Becerra, Mercedes C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA.
[Murray, Megan B.; Cohen, Ted] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Becerra, Mercedes C.; Galea, Jerome; Lecca, Leonid; Calderon, Roger; Yataco, Rosa; Contreras, Carmen] Partners Hlth, Boston, MA USA.
[Zhang, Zibiao; Cohen, Ted] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA.
RP Zelner, JL (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, 106A Guyot Hall, Princeton, NJ 08544 USA.
EM jzelner@princeton.edu
FU National Institutes of Health [U19 A1076217]; RAPIDD program of the
Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; Bill and
Melinda Gates Foundation; Science and Technology Directorate, US
Department of Homeland Security [HSHQDC-12-C-00058]
FX Supported by National Institutes of Health (NIH/NIAID grant U19 A1076217
to M.B.M., M.C.B., J.G., L.L., R.C., R.Y., C.C., Z.Z., and T.C.); the
RAPIDD program of the Science and Technology Directorate, Department of
Homeland Security (J.L.Z. and B.T.G.); the Fogarty International Center,
National Institutes of Health (J.L.Z. and B.T.G.); the Bill and Melinda
Gates Foundation (B.T.G.); and the Science and Technology Directorate,
US Department of Homeland Security (Contract # HSHQDC-12-C-00058 to B.
T. G.).
NR 18
TC 7
Z9 7
U1 1
U2 7
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD APR 1
PY 2014
VL 189
IS 7
BP 853
EP 859
DI 10.1164/rccm.201310-1896OC
PG 7
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA AD9DS
UT WOS:000333565600015
PM 24592878
ER
PT J
AU Hartung, DM
Zarin, DA
Guise, JM
McDonagh, M
Paynter, R
Helfand, M
AF Hartung, Daniel M.
Zarin, Deborah A.
Guise, Jeanne-Marie
McDonagh, Marian
Paynter, Robin
Helfand, Mark
TI Reporting Discrepancies Between the ClinicalTrials.gov Results Database
and Peer-Reviewed Publications
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIALS; BONE MORPHOGENETIC PROTEIN-2;
CLINICAL-TRIALS; OUTCOMES; DISSEMINATION; ISSUES
AB Background: ClinicalTrials.gov requires reporting of result summaries for many drug and device trials.
Purpose: To evaluate the consistency of reporting of trials that are registered in the ClinicalTrials.gov results database and published in the literature.
Data Sources: ClinicalTrials.gov results database and matched publications identified through ClinicalTrials.gov and a manual search of 2 electronic databases.
Study Selection: 10% random sample of phase 3 or 4 trials with results in the ClinicalTrials.gov results database, completed before 1 January 2009, with 2 or more groups.
Data Extraction: One reviewer extracted data about trial design and results from the results database and matching publications. A subsample was independently verified.
Data Synthesis: Of 110 trials with results, most were industry-sponsored, parallel-design drug studies. The most common inconsistency was the number of secondary outcome measures reported (80%). Sixteen trials (15%) reported the primary outcome description inconsistently, and 22 (20%) reported the primary outcome value inconsistently. Thirty-eight trials inconsistently reported the number of individuals with a serious adverse event (SAE); of these, 33 (87%) reported more SAEs in ClinicalTrials.gov. Among the 84 trials that reported SAEs in ClinicalTrials.gov, 11 publications did not mention SAEs, 5 reported them as zero or not occurring, and 21 reported a different number of SAEs. Among 29 trials that reported deaths in ClinicalTrials.gov, 28% differed from the matched publication.
Limitation: Small sample that included earliest results posted to the database.
Conclusion: Reporting discrepancies between the ClinicalTrials.gov results database and matching publications are common. Which source contains the more accurate account of results is unclear, although ClinicalTrials.gov may provide a more comprehensive description of adverse events than the publication.
C1 Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
Portland VA Med Ctr, Portland, OR USA.
Natl Lib Med, Bethesda, MD USA.
RP Hartung, DM (reprint author), Oregon Hlth & Sci Univ, Coll Pharm, Oregon State Univ, 3303 SW Bond Ave,CH12C, Portland, OR 97239 USA.
EM hartungd@ohsu.edu
OI Paynter, Robin/0000-0002-6969-4261
FU National Library of Medicine [HHSN 276-2009-00128P]; Agency for
Healthcare Research and Quality [K12HS019456]; Agency for Healthcare
Research and Quality career development award [K12 HS019456]; intramural
research program of the National Library of Medicine
FX By contract HHSN 276-2009-00128P from the National Library of Medicine
and grant K12HS019456 from the Agency for Healthcare Research and
Quality. Dr. Hartung received support from an Agency for Healthcare
Research and Quality career development award (K12 HS019456). Dr. Zarin
was funded by the intramural research program of the National Library of
Medicine.
NR 18
TC 40
Z9 40
U1 0
U2 10
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD APR 1
PY 2014
VL 160
IS 7
BP 477
EP +
DI 10.7326/M13-0480
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA AE6IL
UT WOS:000334093800005
PM 24687070
ER
PT J
AU Wright, JT
Fine, LJ
Lackland, DT
Ogedegbe, G
Himmelfarb, CRD
AF Wright, Jackson T., Jr.
Fine, Lawrence J.
Lackland, Daniel T.
Ogedegbe, Gbenga
Himmelfarb, Cheryl R. Dennison
TI Evidence Supporting a Systolic Blood Pressure Goal of Less Than 150 mm
Hg in Patients Aged 60 Years or Older: The Minority View
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID HYPERTENSION; STROKE; METAANALYSIS; PREVENTION; MANAGEMENT; REDUCTION;
MORTALITY; TRIALS; ADULTS
C1 Case Western Reserve Univ, Cleveland, OH 44106 USA.
NHLBI, Bethesda, MD 20892 USA.
Med Univ S Carolina, Charleston, SC 29425 USA.
NYU, Sch Med, New York, NY USA.
Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA.
RP Wright, JT (reprint author), Univ Hosp Case Med Ctr, Bolwell Suite 2200,11100 Euclid Ave, Cleveland, OH 44106 USA.
EM Jackson.Wright@case.edu
NR 22
TC 130
Z9 130
U1 0
U2 9
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD APR 1
PY 2014
VL 160
IS 7
BP 499
EP +
DI 10.7326/M13-2981
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA AE6IL
UT WOS:000334093800008
PM 24424788
ER
PT J
AU Stavrakis, AI
Niska, JA
Shahbazian, JH
Loftin, AH
Ramos, RI
Billi, F
Francis, KP
Otto, M
Bernthal, NM
Uslan, DZ
Miller, LS
AF Stavrakis, Alexandra I.
Niska, Jared A.
Shahbazian, Jonathan H.
Loftin, Amanda H.
Ramos, Romela Irene
Billi, Fabrizio
Francis, Kevin P.
Otto, Michael
Bernthal, Nicholas M.
Uslan, Daniel Z.
Miller, Lloyd S.
TI Combination Prophylactic Therapy with Rifampin Increases Efficacy
against an Experimental Staphylococcus epidermidis Subcutaneous
Implant-Related Infection
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID ELECTRONIC DEVICE INFECTIONS; CLINICAL-PRACTICE GUIDELINES; IN-VIVO;
ANTIBIOTIC-PROPHYLAXIS; PERMANENT PACEMAKER; MURINE MODEL;
CARDIOVERTER-DEFIBRILLATORS; TUBERCULOSIS TREATMENT; TELAVANCIN TD-6424;
AUREUS INFECTIONS
AB The incidence of infections related to cardiac devices (such as permanent pacemakers) has been increasing out of proportion to implantation rates. As management of device infections typically requires explantation of the device, optimal prophylactic strategies are needed. Cefazolin and vancomycin are widely used as single agents for surgical prophylaxis against cardiac device-related infections. However, combination antibiotic prophylaxis may further reduce infectious complications. To model a localized subcutaneous implant-related infection, a bioluminescent strain of Staphylococcus epidermidis was inoculated onto a medical-procedure-grade titanium disc, which was placed into a subcutaneous pocket in the backs of mice. In vivo bioluminescence imaging, quantification of ex vivo CFU from the capsules and implants, variable-pressure scanning electron microscopy (VP-SEM), and neutrophil enhanced green fluorescent protein (EGFP) fluorescence in LysEGFP mice were employed to monitor the infection. This model was used to evaluate the efficacies of low- and high-dose cefazolin (50 and 200 mg/kg of body weight) and vancomycin (10 and 110 mg/kg) intravenous prophylaxis with or without rifampin (25 mg/kg). High-dose cefazolin and high-dose vancomycin treatment resulted in almost complete bacterial clearance, whereas both low-dose cefazolin and low-dose vancomycin reduced the in vivo and ex vivo bacterial burden only moderately. The addition of rifampin to low-dose cefazolin and vancomycin was highly effective in further reducing the CFU harvested from the implants. However, vancomycin-rifampin was more effective than cefazolin-rifampin in further reducing the CFU harvested from the surrounding tissue capsules. Future studies in humans will be required to determine whether the addition of rifampin has improved efficacy in preventing device-related infections in clinical practice.
C1 [Stavrakis, Alexandra I.; Niska, Jared A.; Loftin, Amanda H.; Billi, Fabrizio; Bernthal, Nicholas M.] Univ Calif Los Angeles, Orthopaed Hosp, Res Ctr, Dept Orthopaed Surg, Los Angeles, CA USA.
[Ramos, Romela Irene] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Los Angeles, CA 90095 USA.
[Uslan, Daniel Z.] Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USA.
[Shahbazian, Jonathan H.; Miller, Lloyd S.] Johns Hopkins Univ, Sch Med, Dept Dermatol, Baltimore, MD 21205 USA.
[Francis, Kevin P.] PerkinElmer Inc, Hopkinton, MA USA.
[Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
RP Uslan, DZ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USA.
EM duslan@mednet.ucla.edu; lloydmiller@jhmi.edu
OI Miller, Lloyd/0000-0002-8332-2210; Otto, Michael/0000-0002-2222-4115
FU Medtronic, Inc.; CRDM (Cardiac Rhythm Disease Management) External
Research Program; H & H Lee Surgical Resident Research Scholars Program;
Intramural Program of the National Institute of Allergy and Infectious
Diseases (NIAID); National Institutes of Health [R24-CA92865, R01
HS021188, R01-AI078910]
FX This work was supported by the Medtronic, Inc., CRDM (Cardiac Rhythm
Disease Management) External Research Program (to D.Z.U. and L.S.M.), an
H & H Lee Surgical Resident Research Scholars Program (to A.I.S. and
J.A.N.), the Intramural Program of the National Institute of Allergy and
Infectious Diseases (NIAID), the National Institutes of Health (to M.
O.), and National Institutes of Health grants R24-CA92865 (to the UCLA
Small Animal Imaging Resource Program), R01 HS021188 (to D.Z.U.), and
R01-AI078910 (to L.S.M.).
NR 67
TC 3
Z9 3
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD APR
PY 2014
VL 58
IS 4
BP 2377
EP 2386
DI 10.1128/AAC.01943-13
PG 10
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA AD9SU
UT WOS:000333605600067
PM 24514089
ER
PT J
AU Koh, C
Liang, TJ
AF Koh, Christopher
Liang, T. Jake
TI What is the future of ribavirin therapy for hepatitis C?
SO ANTIVIRAL RESEARCH
LA English
DT Editorial Material
DE Hepatitis C virus; Ribavirin; Chronic hepatitis C; Direct-acting
antivirals; Antiviral therapy
ID GENOTYPE 1 INFECTION; TREATMENT-NAIVE PATIENTS; SOFOSBUVIR PLUS
RIBAVIRIN; VIRUS-INFECTION; DOUBLE-BLIND; COMBINATION THERAPY;
VIROLOGICAL RESPONSE; ANTIVIRAL THERAPY; TREATMENT OPTIONS;
INTERFERON-ALPHA
AB With the introduction of direct-acting antiviral (DAA) therapy against hepatitis C virus (HCV) infection, the field is rapidly evolving towards interferon-free regimens with high sustained virologic response (SVR) rates. The ultimate goal of therapy in chronic HCV infection should include an easily dosed all-oral regimen that is highly effective, inexpensive, pan-genotypic, safe and tolerable, with minimal to no resistance. Various investigational DAA regimens are currently under evaluation with and without ribavirin (Rbv). With the projected arrival of improved therapies over the next 5 years, the future role of Rbv comes into question. Despite being plagued by the lack of understanding of its mechanism of action and significant side effects such as anemia, Rbv has been a part of the standard-of-care therapies in chronic HCV infection for more than 10 years. As we look towards the future HCV therapy, Rbv may still have utility in the care of patients infected with HCV because of its low cost and potentially added value in combination with other DAAs. This article forms part of a symposium in Antiviral Research on "Hepatitis C: next steps toward global eradication." Published by Elsevier B.V.
C1 [Koh, Christopher; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Koh, C (reprint author), NIDDK, Liver Dis Branch, NIH, Bldg 10,Room 9B16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA.
EM Christopher.Koh@nih.gov; JakeL@bdg10.niddk.nih.gov
FU Intramural NIH HHS
NR 68
TC 16
Z9 16
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
EI 1872-9096
J9 ANTIVIR RES
JI Antiviral Res.
PD APR
PY 2014
VL 104
BP 34
EP 39
DI 10.1016/j.antiviral.2014.01.005
PG 6
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA AE1KY
UT WOS:000333729400005
PM 24468277
ER
PT J
AU Yazdany, J
Feldman, CH
Liu, J
Ward, MM
Fischer, MA
Costenbader, KH
AF Yazdany, Jinoos
Feldman, Candace H.
Liu, Jun
Ward, Michael M.
Fischer, Michael A.
Costenbader, Karen H.
TI Quality of Care for Incident Lupus Nephritis Among Medicaid
Beneficiaries in the United States
SO ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID STAGE RENAL-DISEASE; 3 ETHNIC-GROUPS; SOCIOECONOMIC-STATUS;
ERYTHEMATOSUS; COHORT; HYDROXYCHLOROQUINE; US; MANAGEMENT; RISK;
RECOMMENDATIONS
AB ObjectiveWe investigated the quality of care and factors associated with variations in care among a national cohort of Medicaid enrollees with incident lupus nephritis.
MethodsUsing Medicaid Analytic eXtract files from 47 US states and the District of Columbia for 2000-2006, we identified a cohort of individuals with incident lupus nephritis. We assessed performance on 3 measures of health care quality: receipt of immunosuppressive, renal-protective antihypertensive, and antimalarial medications. We examined performance on these measures over 1 year and applied multivariable logistic regression models to understand whether sociodemographic, geographic, or health care access factors were associated with higher performance on quality measures.
ResultsWe identified 1,711 Medicaid enrollees with incident lupus nephritis. Performance on quality measures was low at 90 days (21.9% for immunosuppressive therapy, 44.0% for renal protection, and 36.4% for antimalarials) but increased by 1 year (33.7%, 56.4%, and 45.8%, respectively). Younger individuals, African Americans, and Hispanics were more likely to receive immunosuppressive therapy and hydroxychloroquine. Younger individuals were less likely to receive renal-protective antihypertensive medications. We found significant geographic variation in performance, with patients in the Northeast receiving higher quality of care compared to other regions. Poor access to health care, as assessed by having a greater number of treat-and-release emergency department visits compared to ambulatory encounters, was associated with lower receipt of recommended treatment.
ConclusionThese nationwide data suggest low overall quality of care and potential delays in care for Medicaid enrollees with incident lupus nephritis. Significant regional differences also suggest room for quality improvement.
C1 [Yazdany, Jinoos] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Feldman, Candace H.; Liu, Jun; Fischer, Michael A.; Costenbader, Karen H.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Yazdany, J (reprint author), Univ Calif San Francisco, Div Rheumatol, Box 0920, San Francisco, CA 94143 USA.
EM jinoos.yazdany@ucsf.edu
FU Rosalind Russell Medical Research Center for Arthritis; National
Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH; NIH
[K23-AR-060259, R01-AR-057327]; Biogen Idec; Genzyme
FX Supported by the Rosalind Russell Medical Research Center for Arthritis,
and in part by the Intramural Research Program, National Institute of
Arthritis and Musculoskeletal and Skin Diseases, NIH. Dr. Yazdany's work
was supported by the NIH (grant K23-AR-060259). Dr. Costenbader's work
was supported by the NIH (grant R01-AR-057327).; Dr. Costenbader has
received consultant fees, speaking fees, and/or honoraria (less than
$10,000 each) from Biogen Idec and Genzyme.
NR 33
TC 10
Z9 10
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2151-464X
EI 2151-4658
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD APR
PY 2014
VL 66
IS 4
BP 617
EP 624
DI 10.1002/acr.22182
PG 8
WC Rheumatology
SC Rheumatology
GA AD6OK
UT WOS:000333380400015
PM 24124011
ER
PT J
AU Huber, AM
Lovell, DJ
Pilkington, CA
Rennebohm, RM
Rider, LG
AF Huber, Adam M.
Lovell, Daniel J.
Pilkington, Clarissa A.
Rennebohm, Robert M.
Rider, Lisa G.
TI Confusion concerning multiple versions of the Childhood Myositis
Assessment Scale
SO ARTHRITIS CARE & RESEARCH
LA English
DT Letter
ID IDIOPATHIC INFLAMMATORY MYOPATHIES; JUVENILE DERMATOMYOSITIS;
DISEASE-ACTIVITY; MUSCLE FUNCTION; CORE SET; VALIDATION
C1 [Huber, Adam M.] IWK Hlth Ctr, Halifax, NS, Canada.
[Huber, Adam M.] Dalhousie Univ, Halifax, NS, Canada.
[Lovell, Daniel J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Pilkington, Clarissa A.] Great Ormond St Hosp Sick Children, London, England.
[Pilkington, Clarissa A.] UCL, London, England.
[Rennebohm, Robert M.] Cleveland Clin, Cleveland, OH 44106 USA.
[Rider, Lisa G.] NIEHS, NIH, US Dept HHS, Bethesda, MD USA.
RP Huber, AM (reprint author), IWK Hlth Ctr, Halifax, NS, Canada.
OI Rider, Lisa/0000-0002-6912-2458
NR 6
TC 1
Z9 1
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2151-464X
EI 2151-4658
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD APR
PY 2014
VL 66
IS 4
BP 648
EP 648
DI 10.1002/acr.22239
PG 1
WC Rheumatology
SC Rheumatology
GA AD6OK
UT WOS:000333380400021
PM 24285368
ER
PT J
AU Mahler, M
Miller, FW
Fritzler, MJ
AF Mahler, Michael
Miller, Frederick W.
Fritzler, Marvin J.
TI Idiopathic inflammatory myopathies and the anti-synthetase syndrome: A
comprehensive review
SO AUTOIMMUNITY REVIEWS
LA English
DT Review
DE Autoantibodies; Myositis; Immunoassay; Jo-1; Synthetase
ID TRANSFER-RNA-SYNTHETASE; SYSTEMIC AUTOIMMUNE-DISEASES; LINE BLOT ASSAY;
ANTISYNTHETASE SYNDROME; POSITIVE PATIENTS; POLYMYOSITIS;
AUTOANTIBODIES; DERMATOMYOSITIS; MYOSITIS; PHENOTYPES
AB Autoantibodies are a hallmark in the diagnosis of many systemic autoimmune rheumatic diseases (SARD) including idiopathic inflammatory myopathies (IIM). Based on their specificity, autoantibodies in IIM are grouped into myositis specific (MSA) and myositis associated autoantibodies (MAA). Among the MSA, autoantibodies against aminoacyl-tRNA synthetases (ARS) represent the most common antibodies and can be detected in 25-35% of patients. The presence of ARS and other autoantibodies has become a key feature for classification and diagnosis of IIM and is increasingly used to define clinically distinguishable IIM subsets. For example, anti-ARS autoantibodies are the key features of what has become known as anti-synthetase syndrome (aSS), characterized by multiple organ involvement, primarily interstitial lung disease, often accompanied by myositis, non-erosive arthritis, Raynaud's phenomenon, fever, and "mechanic's hands". Autoantibodies directed to eight different ARS have been described: Jo-1 (histidyl), PL-7 (threonyl), PL-12 (alanyl), OJ (isoleucyl), EJ (glycyl), KS (asparaginyl), Zo (phenylalanyl) and Ha (tyrosyl). Each anti-ARS antibody seems to define a distinctive clinical phenotype. Although several research methods and commercial tests are available, routine testing for anti-ARS autoantibodies (other than anti-Jo-l/histidyl-tRNA synthetase) is not widely available, sometimes leading to delays in diagnosis and poor disease outcomes. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Mahler, Michael] INOVA Diagnost Inc, San Diego, CA USA.
[Miller, Frederick W.] NIEHS, NIH, DHHS, Bethesda, MD USA.
[Fritzler, Marvin J.] Univ Calgary, Dept Med, Calgary, AB T2N 4N1, Canada.
RP Fritzler, MJ (reprint author), Univ Calgary, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.
EM fritzler@ucalgary.ca
OI Miller, Frederick/0000-0003-2831-9593
FU Intramural Research Program of the NIH; National Institute of
Environmental Health Sciences
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences. We
thank Drs. Ejaz Shamim and Mark Gourley for the useful critical comments
on the manuscript, and Dr. Minoru Satoh for supplying Fig. 1B and C.
NR 41
TC 43
Z9 46
U1 2
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-9972
EI 1873-0183
J9 AUTOIMMUN REV
JI Autoimmun. Rev.
PD APR-MAY
PY 2014
VL 13
IS 4-5
SI SI
BP 367
EP 371
DI 10.1016/j.autrev.2014.01.022
PG 5
WC Immunology
SC Immunology
GA AE2AM
UT WOS:000333775700007
PM 24424190
ER
PT J
AU Barodka, VM
Nagababu, E
Mohanty, JG
Nyhan, D
Berkowitz, DE
Rifkind, JM
Strouse, JJ
AF Barodka, Viachaslau M.
Nagababu, Enika
Mohanty, Joy G.
Nyhan, Daniel
Berkowitz, Dan E.
Rifkind, Joseph M.
Strouse, John J.
TI New insights provided by a comparison of impaired deformability with
erythrocyte oxidative stress for sickle cell disease
SO BLOOD CELLS MOLECULES AND DISEASES
LA English
DT Article
DE Sickle cell disease; Erythrocytes; Hemoglobin; Heme degradation;
Fluorescence; Deformability
ID RED-BLOOD-CELLS; HEME DEGRADATION-PRODUCTS; HYDROGEN-PEROXIDE;
HEMOLYTIC-ANEMIAS; FETAL-HEMOGLOBIN; MEMBRANE; AUTOXIDATION; TRANSPORT;
POLYMERIZATION; DEHYDRATION
AB Sickle cell disease (SCD) is associated with increase in oxidative stress and irreversible membrane changes that originates from the instability and polymerization of deoxygenated hemoglobin S (HbS). The relationship between erythrocyte membrane changes as assessed by a decrease in deformability and oxidative stress as assessed by an increase in heme degradation was investigated. The erythrocyte deformability and heme degradation for 27 subjects with SCD and 7 with sickle trait were compared with normal healthy adults. Changes in both deformability and heme degradation increased in the order of control to trait to non-crisis SCD to crisis SCD resulting in a very significantly negative correlation between deformability and heme degradation. However, a quantitative analysis of the changes in deformability and heme degradation for these different groups of subjects indicated that sickle trait had a much smaller effect on deformability than on heme degradation, while crisis affects deformability to a greater extent than heme degradation. These findings provide insights into the relative contributions of erythrocyte oxidative stress and membrane damage during the progression of SCD providing a better understanding of the pathophysiology of SCD. Published by Elsevier Inc.
C1 [Barodka, Viachaslau M.; Nyhan, Daniel; Berkowitz, Dan E.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol Crit Care Med, Baltimore, MD USA.
[Strouse, John J.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Nagababu, Enika; Mohanty, Joy G.; Rifkind, Joseph M.] NIA, Mol Dynam Sect, Baltimore, MD 21224 USA.
RP Rifkind, JM (reprint author), NIA, Mol Dynam Sect, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM rifkindj@mail.nih.gov
FU National Institutes of Health [5R01 HL105296]; Doris Duke Charitable
Foundation; Intramural Research Program of National Institute of Aging
FX Supported in part by grants from National Institutes of Health, NIH 5R01
HL105296 to (DEB) and the Doris Duke Charitable Foundation (JJS) and
from the Intramural Research Program of National Institute of Aging.
NR 38
TC 10
Z9 10
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 1079-9796
EI 1096-0961
J9 BLOOD CELL MOL DIS
JI Blood Cells Mol. Dis.
PD APR
PY 2014
VL 52
IS 4
BP 230
EP 235
DI 10.1016/j.bcmd.2013.10.004
PG 6
WC Hematology
SC Hematology
GA AD5VP
UT WOS:000333321600015
PM 24246527
ER
PT J
AU Keysers, C
Meffert, H
Gazzola, V
AF Keysers, Christian
Meffert, Harma
Gazzola, Valeria
TI Reply: Spontaneous versus deliberate vicarious representations:
different routes to empathy in psychopathy and autism
SO BRAIN
LA English
DT Letter
ID NEURAL RESPONSES; RECOGNITION; OTHERS; PAIN; EXPERIENCE; DISGUST;
CORTEX; COMMON; BRAIN; MOTOR
C1 [Keysers, Christian; Gazzola, Valeria] Netherlands Inst Neurosci, KNAW, Social Brain Lab, NL-1105 BA Amsterdam, Netherlands.
[Keysers, Christian; Gazzola, Valeria] Univ Groningen, Univ Med Ctr Groningen, Dept Neurosci, NL-9700 AB Groningen, Netherlands.
[Meffert, Harma] NIMH, Sect Affect & Cognit Neurosci, NIH, Bethesda, MD USA.
RP Keysers, C (reprint author), Netherlands Inst Neurosci, Meibergdreef 47, NL-1105 BA Amsterdam, Netherlands.
EM C.keysers@nin.knaw.nl
OI Gazzola, Valeria/0000-0003-0324-0619; Keysers,
Christian/0000-0002-2845-5467
FU European Research Council [312511]; Intramural NIH HHS; NIMH NIH HHS
[1-ZIA-MH002860-08]
NR 30
TC 8
Z9 8
U1 0
U2 19
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD APR
PY 2014
VL 137
AR e273
DI 10.1093/brain/awt376
PN 4
PG 4
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AD4ZM
UT WOS:000333260900009
PM 24501095
ER
PT J
AU Lumelsky, N
AF Lumelsky, Nadya
TI Small Molecules Convert Fibroblasts into Islet-like Cells Avoiding
Pluripotent State
SO CELL METABOLISM
LA English
DT Editorial Material
ID DEFINED FACTORS; STEM-CELLS
C1 Natl Inst Dent & Craniofacial Res, Tissue Engn & Regenerat Med Res Program, Integrat Biol & Infect Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Lumelsky, N (reprint author), Natl Inst Dent & Craniofacial Res, Tissue Engn & Regenerat Med Res Program, Integrat Biol & Infect Dis Branch, NIH, 6701 Democracy Blvd, Bethesda, MD 20892 USA.
EM nadyal@nidcr.nih.gov
NR 9
TC 2
Z9 2
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD APR 1
PY 2014
VL 19
IS 4
BP 551
EP 552
DI 10.1016/j.cmet.2014.03.019
PG 2
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA AE1TA
UT WOS:000333751600002
PM 24703689
ER
PT J
AU Tan, MJ
Peng, C
Anderson, KA
Chhoy, P
Xie, ZY
Dai, LZ
Park, J
Chen, Y
Huang, H
Zhang, Y
Ro, J
Wagner, GR
Green, MF
Madsen, AS
Schmiesing, J
Peterson, BS
Xu, GF
Ilkayeva, OR
Muehlbauer, MJ
Braulke, T
Muhlhausen, C
Backos, DS
Olsen, CA
McGuire, PJ
Pletcher, SD
Lombard, DB
Hirschey, MD
Zhao, YM
AF Tan, Minjia
Peng, Chao
Anderson, Kristin A.
Chhoy, Peter
Xie, Zhongyu
Dai, Lunzhi
Park, Jeongsoon
Chen, Yue
Huang, He
Zhang, Yi
Ro, Jennifer
Wagner, Gregory R.
Green, Michelle F.
Madsen, Andreas S.
Schmiesing, Jessica
Peterson, Brett S.
Xu, Guofeng
Ilkayeva, Olga R.
Muehlbauer, Michael J.
Braulke, Thomas
Muehlhausen, Chris
Backos, Donald S.
Olsen, Christian A.
McGuire, Peter J.
Pletcher, Scott D.
Lombard, David B.
Hirschey, Matthew D.
Zhao, Yingming
TI Lysine Glutarylation Is a Protein Posttranslational Modification
Regulated by SIRT5
SO CELL METABOLISM
LA English
DT Article
ID CARBAMOYL-PHOSPHATE SYNTHETASE; ACETYL-COENZYME-A; HISTONE ACETYLATION;
MOUSE MODEL; SUCCINYLATION; ENZYME; IDENTIFICATION; TRANSCRIPTION;
BIOSYNTHESIS; DEACETYLASES
AB We report the identification and characterization of a five-carbon protein posttranslational modification (PTM) called lysine glutarylation (K-glu). This protein modification was detected by immunoblot and mass spectrometry (MS), and then comprehensively validated by chemical and biochemical methods. We demonstrated that the previously annotated deacetylase, sirtuin 5 (SIRT5), is a lysine deglutarylase. Proteome-wide analysis identified 683 Kglu sites in 191 proteins and showed that Kglu is highly enriched on metabolic enzymes and mitochondrial proteins. We validated carbamoyl phosphate synthase 1 (CPS1), the rate-limiting enzyme in urea cycle, as a glutarylated protein and demonstrated that CPS1 is targeted by SIRT5 for deglutarylation. We further showed that glutarylation suppresses CPS1 enzymatic activity in cell lines, mice, and a model of glutaric acidemia type I disease, the last of which has elevated glutaric acid and glutaryl-CoA. This study expands the landscape of lysine acyl modifications and increases our understanding of the deacylase SIRT5.
C1 [Tan, Minjia; Zhang, Yi; Zhao, Yingming] Chinese Acad Sci, Shanghai Inst Mat Med, Chem Prote Ctr, Shanghai 201203, Peoples R China.
[Tan, Minjia; Zhang, Yi; Zhao, Yingming] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China.
[Peng, Chao; Xie, Zhongyu; Dai, Lunzhi; Chen, Yue; Huang, He; Xu, Guofeng; Zhao, Yingming] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA.
[Anderson, Kristin A.; Chhoy, Peter; Wagner, Gregory R.; Green, Michelle F.; Peterson, Brett S.; Ilkayeva, Olga R.; Muehlbauer, Michael J.; Hirschey, Matthew D.] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27704 USA.
[Park, Jeongsoon; Lombard, David B.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Park, Jeongsoon; Lombard, David B.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA.
[Ro, Jennifer; Pletcher, Scott D.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Ro, Jennifer; Pletcher, Scott D.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA.
[Madsen, Andreas S.; Olsen, Christian A.] Tech Univ Denmark, Dept Chem, DK-2800 Lyngby, Denmark.
[Schmiesing, Jessica; Braulke, Thomas; Muehlhausen, Chris] Univ Med Ctr Hamburg Eppendorf, Childrens Hosp, Dept Biochem, D-20246 Hamburg, Germany.
[Backos, Donald S.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Computat Chem & Biol Core Facil, Aurora, CO 80045 USA.
[McGuire, Peter J.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Hirschey, MD (reprint author), Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27704 USA.
EM matthew.hirschey@duke.edu; yingming.zhao@uchicago.edu
OI Madsen, Andreas Stahl/0000-0001-7283-2090; Backos,
Donald/0000-0001-6735-6210
FU NIH [GM105933, CA160036, RR020839, GM101171, CA177925, AG000114]; Nancy
and Leonard Florsheim Family Fund; National Science and Technology Major
Project of the Ministry of Science and Technology of China
[2012ZX09301001-007]; Natural Science Foundation of China [31370814];
Shanghai Pujiang Program [13PJ1410300]; American Heart Association
[12SDG8840004, 12IRG9010008]; Edward Mallinckrodt Jr. Foundation;
Ellison Medical Foundation; National Institutes of Health [AA022146,
AG045351]; Duke O'Brien Center for Kidney Research [5P30DK096493-02];
NCI [CA059365-19]; Danish Independent Research Council-Technology and
Production Sciences (Sapere Aude grant) [12-132328]; Danish Independent
Research Council-Natural Sciences (Steno grant) [10-080907]; Villum
Foundation; Carlsberg Foundation; German Research Foundation (Deutsche
Forschungsgemeinschaft) [MU1778/3-1]; NIH/NIGMS [5T32GM007105-40]
FX We thank Leonard Guarente for the mouse SIRT5 antibody; we are grateful
to Dr. Gozde Colak for critically reading this manuscript; we thank
Ailan Guo and Cell Signaling Technology for helpful discussions. This
work was supported by NIH grants GM105933, CA160036, and RR020839 (to
Y.Z.); and GM101171 and CA177925 (to D. B. L.). Y.Z. is also supported
by the Nancy and Leonard Florsheim Family Fund. M. T. is supported by
the National Science and Technology Major Project of the Ministry of
Science and Technology of China (2012ZX09301001-007), Natural Science
Foundation of China (31370814), and Shanghai Pujiang Program
(13PJ1410300). M. D. H. and his laboratory are supported by the American
Heart Association grants 12SDG8840004 and 12IRG9010008, The Edward
Mallinckrodt Jr. Foundation, The Ellison Medical Foundation, the
National Institutes of Health (AA022146 and AG045351), and the Duke
O'Brien Center for Kidney Research (5P30DK096493-02); M. F. G. is
supported by a postdoctoral fellowship from the NIH and NCI training
grant to Duke University (CA059365-19). P. C. is supported by an
NIH/NIGMS training grant to Duke University Pharmacological Sciences
Training Program (5T32GM007105-40). J.S.P. was supported by NIH training
grant (AG000114). C.A.O. and his laboratory are supported by the Danish
Independent Research Council-Technology and Production Sciences (Sapere
Aude grant number 12-132328; A. S. M.), the Danish Independent Research
Council-Natural Sciences (Steno grant number 10-080907), the Villum
Foundation, and the Carlsberg Foundation. C.A.O. is a Lundbeck
Foundation Fellow. C. M. and J.S. are supported by the German Research
Foundation (Deutsche Forschungsgemeinschaft grant MU1778/3-1). This work
utilized the resources of the Drosophila Aging Core of the Nathan Shock
Center of Excellence in the Biology of Aging (NIA, P30-AG-013283). Y.Z.
is a shareholder and a member of the scientific advisory board of PTM
BioLabs, Co., Ltd. (Chicago).
NR 45
TC 120
Z9 129
U1 12
U2 57
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD APR 1
PY 2014
VL 19
IS 4
BP 605
EP 617
DI 10.1016/j.cmet.2014.03.014
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA AE1TA
UT WOS:000333751600008
PM 24703693
ER
PT J
AU Li, RF
Grimm, SA
Chrysovergis, K
Kosak, J
Wang, XY
Du, Y
Burkholder, A
Janardhan, K
Mav, D
Shah, R
Eling, TE
Wade, PA
AF Li, Ruifang
Grimm, Sara A.
Chrysovergis, Kaliopi
Kosak, Justin
Wang, Xingya
Du, Ying
Burkholder, Adam
Janardhan, Kyathanahalli
Mav, Deepak
Shah, Ruchir
Eling, Thomas E.
Wade, Paul A.
TI Obesity, Rather Than Diet, Drives Epigenomic Alterations in Colonic
Epithelium Resembling Cancer Progression
SO CELL METABOLISM
LA English
DT Article
ID TRANSCRIPTION FACTOR CDX2; COLORECTAL-CANCER; CHROMATIN INTERACTIONS;
INTESTINAL NEOPLASIA; DIFFERENTIATION; TUMORIGENESIS; METAANALYSIS;
LANDSCAPE; PHENOTYPE; IDENTITY
AB While obesity represents one of several risk factors for colorectal cancer in humans, the mechanistic underpinnings of this association remain unresolved. Environmental stimuli, including diet, can alter the epigenetic landscape of DNA cis-regulatory elements affecting gene expression and phenotype. Here, we explored the impact of diet and obesity on gene expression and the enhancer landscape in murine colonic epithelium. Obesity led to the accumulation of histone modifications associated with active enhancers at genomic loci downstream of signaling pathways integral to the initiation and progression of colon cancer. Meanwhile, colon-specific enhancers lost the same histone mark, poising cells for loss of differentiation. These alterations reflect a transcriptional program with many features shared with the program driving colon cancer progression. The interrogation of enhancer alterations by diet in colonic epithelium provides insights into the biology underlying high-fat diet and obesity as risk factors for colon cancer.
C1 [Li, Ruifang; Chrysovergis, Kaliopi; Kosak, Justin; Wang, Xingya; Eling, Thomas E.; Wade, Paul A.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
[Grimm, Sara A.; Du, Ying; Burkholder, Adam] NIEHS, Res Triangle Pk, NC 27709 USA.
[Janardhan, Kyathanahalli] ILS Inc, Res Triangle Pk, NC 27709 USA.
[Janardhan, Kyathanahalli] DNTP, Res Triangle Pk, NC 27709 USA.
[Mav, Deepak; Shah, Ruchir] SRA Int Inc, Durham, NC 27709 USA.
RP Wade, PA (reprint author), NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
EM wadep2@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [ZO1ES101965]
FX We thank Kevin Gerrish and the NIEHS microarray facility for their
assistance in microarray processing, the NIEHS pathology core for
technical assistance with immunohistochemistry, the NIEHS Epigenomics
Core for next-generation sequencing support, and the NIEHS viral vector
core facility for helping with virus packaging. We express gratitude to
Dr. Scott Bultman for many useful suggestions and vigorous discussion
throughout the course of this work. This research was supported (in
part) by the Intramural Research Program of the NIH, National Institute
of Environmental Health Sciences (project number ZO1ES101965 to P.A.W.).
NR 37
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U1 1
U2 19
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD APR 1
PY 2014
VL 19
IS 4
BP 702
EP 711
DI 10.1016/j.cmet.2014.03.012
PG 10
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA AE1TA
UT WOS:000333751600016
PM 24703701
ER
PT J
AU Whitaker, MJ
Debono, M
Huatan, H
Merke, DP
Arlt, W
Ross, RJ
AF Whitaker, Martin J.
Debono, Miguel
Huatan, Hiep
Merke, Deborah P.
Arlt, Wiebke
Ross, Richard J.
TI An oral multiparticulate, modified- release, hydrocortisone replacement
therapy that provides physiological cortisol exposure
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID CONGENITAL ADRENAL-HYPERPLASIA; ADDISONS-DISEASE; PREMATURE MORTALITY;
HEALTH-STATUS; INSUFFICIENCY; PLASMA; SERUM; INFUSION; PATTERN; COHORT
AB Objective It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified-release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multiparticulate technology.
Design and Measurements Screening by in vitro dissolution profiles, pharmacokinetic (PK) testing in dexamethasone-suppressed dogs and humans, and comparison with a reference population.
Setting Field laboratories and clinical research facility.
Results Formulations were generated using an enteric (delayed release) design configuration with an extended (sustained release) dissolution profile. In vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained-release functionality. PK characterization of DIURF-006 showed that, despite absence of a sustained-release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n=16) receiving a twice-daily toothbrush' regimen (20mg at 23:00h and 10mg at 07:00h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706h*nmol/l, Geomean C-max 665 vs 594nmol/l and Median T-max 8 center dot 5h vs clock time 08:12h for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89%, and cortisol levels increased linearly with doses between 5 and 30mg.
Conclusion A multiparticulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a toothbrush' regimen provides physiological cortisol exposure.
C1 [Whitaker, Martin J.; Huatan, Hiep] Diurnal Ltd, Cardiff, S Glam, Wales.
[Debono, Miguel; Ross, Richard J.] Univ Sheffield, Acad Unit Diabet Endocrinol & Reprod, Sheffield S10 2RX, S Yorkshire, England.
[Merke, Deborah P.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Arlt, Wiebke] Univ Birmingham, Ctr Endocrinol Diabet & Metab, Sch Clin & Expt Med, Birmingham, W Midlands, England.
RP Ross, RJ (reprint author), Univ Sheffield, Sch Med, Sheffield S10 2RX, S Yorkshire, England.
EM r.j.ross@sheffield.ac.uk
RI Arlt, Wiebke/B-6310-2009
OI Arlt, Wiebke/0000-0001-5106-9719
FU National Institutes of Health (NIH), Bethesda, US; Medical Research
Council UK [G0900567]; NIH; Diurnal Ltd.
FX This research was supported in part by the Intramural Research Program
at the National Institutes of Health (NIH), Bethesda, US. W.A. receives
grant support from the Medical Research Council UK (Program Grant
G0900567). Richard Ross and Martin Whitaker are Directors of Diurnal
Ltd, and Hiep Huatan and Wiebke Arlt are consultants to Diurnal Ltd, and
Deborah Merke has a CRADA agreement through the NIH with Diurnal Ltd.
NR 25
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U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
EI 1365-2265
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD APR
PY 2014
VL 80
IS 4
BP 554
EP 561
DI 10.1111/cen.12316
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AC3BW
UT WOS:000332391000012
PM 23980724
ER
PT J
AU Bhanushali, MJ
Gustafson, T
Powell, S
Conwit, RA
Wolinsky, JS
Cutter, GR
Lublin, FD
Cofield, SS
AF Bhanushali, Minal J.
Gustafson, Tarah
Powell, Steve
Conwit, Robin A.
Wolinsky, Jerry S.
Cutter, Gary R.
Lublin, Fred D.
Cofield, Stacey S.
TI Recruitment of participants to a multiple sclerosis trial: The CombiRx
experience
SO CLINICAL TRIALS
LA English
DT Article
ID CLINICAL-TRIALS; RETENTION
AB Background and purpose
Participant recruitment is central to all clinical trials. Any delay in recruitment affects the completion and ultimate success of the trial. We report our experience with patient screening and randomization in CombiRx, which may inform the design of other trials. CombiRx was a multicenter, phase III, double-blind, randomized clinical trial comparing the combined use of interferon beta-1a and glatiramer acetate to either agent alone in patients with relapsing-remitting multiple sclerosis (RRMS). This trial was launched in January 2005 in 69 centers in the United States and Canada under a co-operative agreement with the National Institute of Neurological Disorders and Stroke (NINDS). The goal was to recruit 1000 patients over 1.5 years after a 6-month start-up period. Instead, the investigators required 4.25 years to enroll 1008 patients.
Methods
During this trial, we assessed the effectiveness of various recruitment strategies, utility of rescreening prior screen failures, and potential factors and strategies used in study conduct, research, and infrastructure, all of which affected recruitment of participants and ultimately time to completion of CombiRx. We particularly were interested in the variability in time to site initiation between academic centers and private practice sites.
Results
Physicians who were directly involved in the medical care of patients with RRMS were the primary source of patients recruited to CombiRx. A flexible study design that allowed for rescreening of the initial screen failures after a period of time was useful due to the relapsing/remitting course of the disease. Academic centers took longer to implement the trial than the private practice centers, but once sites were approved for enrollment, there was no important difference in the number of participants enrolled.
Limitations
The CombiRx trial was conducted during a period when multiple new medications were being tested, thus affecting the pace of recruitment and limiting ability to generalize our experiences. However, the lessons we learned about process are relevant.
Conclusion
Participants can be enrolled successfully in a clinical trial for RRMS, but factors affecting the time to achieve the requirements needed to start screening can be unpredictable and problematic. Prospective planning by the sponsors and investigators, use of central institutional review boards (IRBs), master trial agreements and secure remote desktop access to the trial database may expedite trial implementation and participant recruitment. A good scientific research question with flexible study design and active involvement of the clinicians are important factors driving recruitment. Clinical trials can be implemented successfully both in private practices and at academic centers, a consideration when selecting sites.
C1 [Bhanushali, Minal J.; Conwit, Robin A.] NINDS, NIH, Rockville, MD USA.
[Gustafson, Tarah; Lublin, Fred D.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY USA.
[Powell, Steve; Cutter, Gary R.; Cofield, Stacey S.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA.
[Wolinsky, Jerry S.] Univ Texas Med Sch Houston, Dept Neurol, Houston, TX USA.
RP Cofield, SS (reprint author), Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Ryals Publ Hlth Bldg,410C,1665 Univ Blvd, Birmingham, AL 35294 USA.
EM SCofield@uab.edu
FU National Institutes of Health (NIH); National Institute of Neurological
Disorders and Stroke (NINDS) [U01 NS045719]; NINDS NIH Intramural
Program for the Biomarker MS ancillary study; National Multiple
Sclerosis Society for the Contrast Sensitivity ancillary project
FX The study was funded by the National Institutes of Health (NIH) and the
National Institute of Neurological Disorders and Stroke (NINDS), U01
NS045719, with medications and matched placebos provided by Biogen Idec
and Teva Pharmaceuticals. Design, analysis, and decision to publish
results are the responsibility of the CCC, SDMC, MRI-AC. Additional
funding was provided by the NINDS NIH Intramural Program for the
Biomarker MS ancillary study and the National Multiple Sclerosis Society
for the Contrast Sensitivity ancillary project.
NR 9
TC 1
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U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
EI 1740-7753
J9 CLIN TRIALS
JI Clin. Trials
PD APR
PY 2014
VL 11
IS 2
BP 159
EP 166
DI 10.1177/1740774513517184
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AE0HT
UT WOS:000333645300003
PM 24686106
ER
PT J
AU Wang, JHY
Sheppard, VB
Liang, WC
Ma, GX
Maxwell, AE
AF Wang, Judy Huei-yu
Sheppard, Vanessa B.
Liang, Wenchi
Ma, Grace X.
Maxwell, Annette E.
TI Recruiting Chinese Americans into cancer screening intervention trials:
Strategies and outcomes
SO CLINICAL TRIALS
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIALS; UNDERREPRESENTED
POPULATIONS; ASIAN-AMERICANS; BREAST-CANCER; WOMEN; MINORITIES; LESSONS;
IMMIGRANTS; PREVENTION
AB Background
Cancer is the leading cause of death among Asian Americans. While Asian Americans are the fastest growing minority population in the United States, they are underrepresented in cancer research and report poor adherence to cancer screening guidelines.
Purpose
This study utilized data from two large randomized intervention trials to evaluate strategies to recruit first-generation Chinese American immigrants from community settings and Chinese American physician practices. Findings will inform effective strategies for promoting Asian American participation in cancer control research.
Methods
Chinese Americans who were non-adherent to annual mammography screening guidelines (Study 1 with 664 immigrant women > 40 years of age) and to colorectal cancer screening guidelines (Study 2 with 455 immigrants > 50 years of age) were enrolled from the greater Washington DC, New York City (NYC), and Philadelphia (PA) areas. Both studies trained bilingual staff to enroll Chinese-speaking participants with the aid of linguistically appropriate fliers and brochures to obtain consent. Study 1 adopted community approaches and worked with community organizations to enroll participants. Study 2 randomly selected potential participants through 24 Chinese American primary-care physician offices, and mailed letters from physicians to enroll patients, followed by telephone calls from research staff. The success of recruitment approaches was assessed by yield rates based on number of participants approached, ineligible, and consented.
Results
Most participants (70%) of Study 1 were enrolled through in-person community approaches (e.g., Chinese schools, stores, health fairs, and personal networks). The final yield of specific venues differed widely (6% to 100%) due to various proportions of ineligible subjects (2%-64%) and refusals (0%-92%). The Study 2 recruitment approach (physician letter followed by telephone calls) had different outcomes in two geographic areas, partially due to differences in demographic characteristics in the DC and NYC/PA areas. The community approaches enrolled more recent immigrants and uninsured Chinese Americans than the physician and telephone call approach (p < .001). Enrollment cost is provided to inform future research studies.
Limitations
Our recruitment outcomes might not be generalizable to all Chinese Americans or other Asian American populations because they may vary by study protocols (e.g., length of trials), target populations (i.e., eligibility criteria), and available resources.
Conclusions
Use of multiple culturally relevant strategies (e.g., building trusting relationships through face-to-face enrollment, use of bilingual and bicultural staff, use of a physician letter, and employing linguistically appropriate materials) was crucial for successfully recruiting a large number of Chinese Americans in community and clinical settings. Our data demonstrate that substantial effort is required for recruitment; studies need to budget for this effort to ensure the inclusion of Asian Americans in health research.
C1 [Wang, Judy Huei-yu] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
[Wang, Judy Huei-yu] Georgetown Univ, Canc Prevent & Control Program, Lombardi Comprehens Canc Ctr, Med Ctr, Washington, DC 20007 USA.
[Sheppard, Vanessa B.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
[Sheppard, Vanessa B.] Georgetown Univ, Med Ctr, Breast Canc Program, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Liang, Wenchi] NIH, Ctr Sci Review, Bethesda, MD 20892 USA.
[Ma, Grace X.] Temple Univ, Dept Publ Hlth, Philadelphia, PA 19122 USA.
[Ma, Grace X.] Temple Univ, Ctr Asian Hlth, Philadelphia, PA 19122 USA.
[Maxwell, Annette E.] Univ Calif Los Angeles, Ctr Canc Prevent & Control Res, Fielding Sch Publ Hlth, Los Angeles, CA USA.
[Maxwell, Annette E.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
RP Wang, JHY (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, 3300 Whitehaven St,NW,Suite 4100, Washington, DC 20007 USA.
EM jw235@georgetown.edu
FU American Cancer Society Mentored Research Grant [MRSGT-05-104-01-CPPB];
Susan G. Komen for the Cure [POP0504327]; National Cancer Institute
(NCI) [R03 CA117552]; NCI [R01 CA121023, U54 CA153513]
FX The first study was supported by the American Cancer Society Mentored
Research Grant (MRSGT-05-104-01-CPPB), Susan G. Komen for the Cure
(POP0504327), and National Cancer Institute (NCI, R03 CA117552) to Judy
Huei-yu Wang. The second study was supported by NCI R01 CA121023 to
Wenchi Liang and Judy Huei-yu Wang and U54 CA153513 to Grace X Ma. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the funding agencies.
NR 42
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U1 0
U2 7
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
EI 1740-7753
J9 CLIN TRIALS
JI Clin. Trials
PD APR
PY 2014
VL 11
IS 2
BP 167
EP 177
DI 10.1177/1740774513518849
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AE0HT
UT WOS:000333645300004
PM 24567288
ER
PT J
AU Walsh, K
Elliott, JC
Shmulewitz, D
Aharonovich, E
Strous, R
Frisch, A
Weizman, A
Spivak, B
Grant, BF
Hasin, D
AF Walsh, Kate
Elliott, Jennifer C.
Shmulewitz, Dvora
Aharonovich, Efrat
Strous, Rael
Frisch, Amos
Weizman, Abraham
Spivak, Baruch
Grant, Bridget F.
Hasin, Deborah
TI Trauma exposure, posttraumatic stress disorder and risk for alcohol,
nicotine, and marijuana dependence in Israel
SO COMPREHENSIVE PSYCHIATRY
LA English
DT Article
ID NATIONAL EPIDEMIOLOGIC SURVEY; INTERVIEW SCHEDULE AUDADIS;
GENERAL-POPULATION SAMPLE; PSYCHIATRIC DIAGNOSTIC MODULES; RECENT
RUSSIAN IMMIGRANTS; OKLAHOMA-CITY; UNITED-STATES; SUBSTANCE USE; DRUG
MODULES; MENTAL-DISORDERS
AB Background: Substance dependence is more common among trauma-exposed individuals; however, most studies suggest that Posttraumatic Stress Disorder (PTSD) accounts for the link between trauma exposure (TB) and substance dependence.
Objectives: This study examined associations between TE and substance dependence (alcohol, nicotine, and marijuana), and whether PTSD accounted for this association.
Method: 1317 Jewish Israeli household residents completed in-person structured interviews assessing TB, PTSD, and substance (alcohol, nicotine, marijuana) dependence between 2007 and 2009. Regression analyses examined associations among TE, PTSD, and substance dependence.
Results: In the full sample, mean number of traumatic events was 2.7 (sd = 2.2), with 83.7% experiencing at least one event In the full sample, mean number of PTSD symptoms was 2.5 (sd = 3.4), with 13.5% meeting PTSD diagnostic criteria. Prevalence of alcohol dependence was 13.4%; nicotine dependence 52.8%; and marijuana dependence 12.1%. Number of traumatic events was associated with increased odds of alcohol (OR = 1.3; 95% CI = 1.2-1.4) and nicotine (OR = 1.2; 95% CI = 1.1-1.3) dependence. Similarly, any traumatic event exposure was associated with increased odds of alcohol (OR = 3.1; 95% CI = 1.6-6.0) and nicotine (OR = 1.9; 95% CI = 1.2-2.9) dependence. PTSD symptoms were associated with increased odds of alcohol (OR = 1.2; 95% CI = 1.1-1.3), nicotine (OR = 1.1; 95% CI = 1.1-1.2), and marijuana (OR = 1.1; 95% CI = 1.04-1.2) dependence; similarly, a PTSD diagnosis was associated with increased odds of alcohol (OR = 3.4; 95% CI = 2.1-5.5), nicotine (OR = 2.2; 95% CI = 1.4-3.4), and marijuana (OR = 2.6; 95% CI = 1.2-5.9) dependence. PTSD symptoms accounted for a sizeable proportion of the TB effect on alcohol (46%) and nicotine dependence (31%).
Conclusion: Individuals with more traumatic events had heightened risk for alcohol and nicotine dependence, and PTSD symptoms partially accounted for this risk. However, marijuana dependence was only significantly related to PTSD symptoms. Clinicians and researchers should separately assess different types of dependence among trauma-exposed individuals both with and without PTSD symptoms. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Walsh, Kate; Elliott, Jennifer C.; Hasin, Deborah] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Shmulewitz, Dvora; Aharonovich, Efrat; Hasin, Deborah] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY 10032 USA.
[Shmulewitz, Dvora; Aharonovich, Efrat; Hasin, Deborah] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Strous, Rael; Frisch, Amos; Weizman, Abraham; Spivak, Baruch] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Frisch, Amos; Weizman, Abraham] Felsenstein Med Res Ctr, IL-49100 Petah Tiqwa, Israel.
[Weizman, Abraham] Geha Mental Hlth Ctr, Res Unit, IL-49100 Petah Tiqwa, Israel.
[Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Rockville, MD 20852 USA.
RP Hasin, D (reprint author), Columbia Univ, Med Ctr, Dept Psychiat, 1051 Riverside Dr 123, New York, NY 10032 USA.
EM dsh2@columbia.edu
FU National Institutes of Health [R01AA013654, K05AA014223, T32DA031099,
K23DA016743]; New York State Psychiatric Institute
FX This research was funded by National Institutes of Health grants
R01AA013654, K05AA014223, T32DA031099 (Walsh, Elliott), K23DA016743
(Aharonovich), and the New York State Psychiatric Institute (Hasin).
None of the authors or researchers has any connection with the tobacco,
alcohol, pharmaceutical or gaming industries or anybody substantially
funded by one of these organizations. We would like to acknowledge the
helpful analytical advice of Melanie M. Wall, Ph.D., and consultations
of Rachel Bar-Hamburger, Ph.D., Rina Meyer and Zalman Shoval in
collecting the data in Israel.
NR 47
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U1 1
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0010-440X
EI 1532-8384
J9 COMPR PSYCHIAT
JI Compr. Psychiat.
PD APR
PY 2014
VL 55
IS 3
BP 621
EP 630
DI 10.1016/j.comppsych.2013.11.016
PG 10
WC Psychiatry
SC Psychiatry
GA AE0NA
UT WOS:000333661800030
PM 24387979
ER
PT J
AU Ricordi, C
Hering, B
Bridges, N
Eggerman, T
Naji, A
Posseit, A
Stock, P
Kaufman, D
Larsen, CP
Turgeon, N
Oberholzer, J
Barbaro, B
Korsgren, O
Markmann, J
Alejandro, R
Rickels, MR
Senior, PA
Luo, X
Zhang, X
Bellin, M
Lei, J
Clarke, W
Hunsicker, L
Goldstein, J
Czarniecki, C
Priore, A
Green, N
Shapiro, A
AF Ricordi, C.
Hering, B.
Bridges, N.
Eggerman, T.
Naji, A.
Posseit, A.
Stock, P.
Kaufman, D.
Larsen, C. P.
Turgeon, N.
Oberholzer, J.
Barbaro, B.
Korsgren, O.
Markmann, J.
Alejandro, R.
Rickels, M. R.
Senior, P. A.
Luo, X.
Zhang, X.
Bellin, M.
Lei, J.
Clarke, W.
Hunsicker, L.
Goldstein, J.
Czarniecki, C.
Priore, A.
Green, N.
Shapiro, A.
TI COMPLETION OF THE FIRST FDA PHASE 3 MULTICENTER TRIAL OF ISLET
TRANSPLANTATION IN TYPE 1 DIABETES BY THE NIH CIT CONSORTIUM
SO CYTOTHERAPY
LA English
DT Meeting Abstract
C1 [Ricordi, C.; Hering, B.; Bridges, N.; Eggerman, T.; Naji, A.; Posseit, A.; Stock, P.; Kaufman, D.; Larsen, C. P.; Turgeon, N.; Oberholzer, J.; Barbaro, B.; Korsgren, O.; Markmann, J.; Alejandro, R.; Rickels, M. R.; Senior, P. A.; Luo, X.; Zhang, X.; Bellin, M.; Lei, J.; Clarke, W.; Hunsicker, L.; Goldstein, J.; Czarniecki, C.; Priore, A.; Green, N.; Shapiro, A.] NIH, Clin Islet Transplantat Consortium, Bethesda, MD 20892 USA.
[Ricordi, C.; Alejandro, R.] Univ Miami, Diabet Res Inst, Miami, FL USA.
[Ricordi, C.; Alejandro, R.] Univ Miami, Cell Transplant Ctr, Miami, FL USA.
[Bridges, N.; Goldstein, J.; Czarniecki, C.; Priore, A.] NIAID, NIH, Bethesda, MD 20892 USA.
[Eggerman, T.; Green, N.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Clarke, W.; Hunsicker, L.] Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA.
[Hering, B.; Bellin, M.] Univ Minnesota, Minneapolis, MN USA.
[Senior, P. A.; Shapiro, A.] Univ Alberta, Edmonton, AB, Canada.
[Larsen, C. P.; Turgeon, N.] Emory Univ, Atlanta, GA 30322 USA.
[Kaufman, D.] Univ Wisconsin, Madison, WI USA.
[Naji, A.; Rickels, M. R.] Univ Penn, Philadelphia, PA 19104 USA.
[Markmann, J.; Lei, J.] Harvard Univ, MGH, Boston, MA 02115 USA.
[Korsgren, O.] Uppsala Univ, Uppsala, Sweden.
[Oberholzer, J.; Barbaro, B.] Univ Illinois, Chicago, IL USA.
[Posseit, A.; Stock, P.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Luo, X.; Zhang, X.] Northwestern Univ, Chicago, IL 60611 USA.
NR 0
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U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD APR
PY 2014
VL 16
IS 4
SU S
MA 22
BP S14
EP S14
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA AD7IT
UT WOS:000333438100024
ER
PT J
AU Tebebi, P
Burks, S
Nguyen, B
Kim, S
Frank, JA
AF Tebebi, P.
Burks, S.
Nguyen, B.
Kim, S.
Frank, J. A.
TI CYCLO-OXYGENASE OR TNF ALPHA INHIBITORS INTERFERES WITH THE ENHANCED
MESENCHYMAL STEM CELL HOMING INDUCED BY PULSED FOCUSED ULTRASOUND:
IMPLICATION FOR REGENERATIVE MEDICINE
SO CYTOTHERAPY
LA English
DT Meeting Abstract
C1 [Tebebi, P.; Burks, S.; Nguyen, B.; Kim, S.; Frank, J. A.] NIH, Frank Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD APR
PY 2014
VL 16
IS 4
SU S
MA 307
BP S88
EP S88
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA AD7IT
UT WOS:000333438100294
ER
PT J
AU Sullivan, SD
Jablonski, KA
Florez, JC
Dabelea, D
Franks, PW
Dagogo-Jack, S
Kim, C
Knowler, WC
Christophi, CA
Ratner, R
AF Sullivan, Shannon D.
Jablonski, Kathleen A.
Florez, Jose C.
Dabelea, Dana
Franks, Paul W.
Dagogo-Jack, Sam
Kim, Catherine
Knowler, William C.
Christophi, Costas A.
Ratner, Robert
CA Diabet Prevention Program Res Grp
TI Genetic Risk of Progression to Type 2 Diabetes and Response to Intensive
Lifestyle or Metformin in Prediabetic Women With and Without a History
of Gestational Diabetes Mellitus
SO DIABETES CARE
LA English
DT Article
ID PREVENTION PROGRAM; COHORT
AB OBJECTIVE
The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births.
RESEARCH DESIGN AND METHODS
We asked if genetic variability could account for these differences by comparing beta-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM.
RESULTS
beta-Cell function was reduced in women with GDM. The GRS was positively associated with a history of GDM; however, the GRS did not predict progression to diabetes or modulate response to intervention.
CONCLUSIONS
These data suggest that a diabetes-associated GRS is associated with development of GDM and may characterize women at risk for development of diabetes due to beta-cell dysfunction.
C1 [Sullivan, Shannon D.] MedStar Washington Hosp Ctr, Dept Med, Endocrine Div, Washington, DC USA.
[Jablonski, Kathleen A.; Christophi, Costas A.] George Washington Univ, Biostat Ctr, Rockville, MD USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Dabelea, Dana] Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA.
[Franks, Paul W.] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit,Diabet Ctr, Malmo, Sweden.
[Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Dagogo-Jack, Sam] Univ Tennessee, Hlth Sci Ctr, Div Endocrinol Diabet & Metab, Memphis, TN USA.
[Kim, Catherine] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
[Kim, Catherine] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Knowler, William C.] NIDDK, Phoenix, AZ USA.
[Ratner, Robert] Amer Diabet Assoc, Alexandria, VA USA.
RP Sullivan, SD (reprint author), MedStar Washington Hosp Ctr, Dept Med, Endocrine Div, Washington, DC USA.
EM dppmail@bsc.gwu.edu
OI Franks, Paul/0000-0002-0520-7604
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
of the National Institutes of Health [U01-DK-048489]; NIDDK
[R01-DK-072041]; Indian Health Service; Office of Research on Minority
Health; Eunice Kennedy Shriver National Institute of Child Health and
Human Development; National Institute on Aging; Centers for Disease
Control and Prevention; Office of Research on Women's Health; American
Diabetes Association; Novo Nordisk; Swedish Research Council; Swedish
Heart-Lung Foundation; Swedish Diabetes Association; AstraZeneca;
Bristol-Myers Squibb; Boehringer Ingelheim
FX The National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) of the National Institutes of Health provided funding to the
clinical centers and the coordinating center for the design and conduct
of the study and the collection, management, analysis, and
interpretation of the data (U01-DK-048489). The Southwestern American
Indian Centers were supported directly by the NIDDK and the Indian
Health Service. The General Clinical Research Center Program, National
Center for Research Resources, supported data collection at many of the
clinical centers. Funding for data collection and participant support
was also provided by the Office of Research on Minority Health, the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, the National Institute on Aging, the Centers for Disease
Control and Prevention, the Office of Research on Women's Health, and
the American Diabetes Association. This research was also supported, in
part, by the intramural research program of the NIDDK. Genotyping for
this project was supported by NIDDK R01-DK-072041 to J.C.F. and K.A.J.;
Bristol-Myers Squibb and Parke-Davis provided the medication. LifeScan,
Health o meter, Hoechst Marion Roussel, Merck-Medco Managed Care, Merck,
Nike Sports Marketing, Slim-Fast, and Quaker Oats Co. donated materials,
equipment, or medicines for concomitant conditions. McKesson Corp.,
Matthews Media Group, and the Henry M. Jackson Foundation provided
support services under subcontract with the coordinating center. P.W.F.
was supported by grants from Novo Nordisk, the Swedish Research Council,
the Swedish Heart-Lung Foundation, and the Swedish Diabetes Association.
J.C.F. has received consulting honoraria from Eli Lilly and Company and
Pfizer. S.D.-J. has received research grants from AstraZeneca,
Bristol-Myers Squibb, Novo Nordisk, and Boehringer Ingelheim (all under
contracts with his employer) and has received honoraria for serving as a
consultant for Merck, Santarus, Amylin Pharmaceuticals, and Novo
Nordisk. No other potential conflicts of interest relevant to this
article were reported.
NR 9
TC 3
Z9 3
U1 0
U2 11
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD APR
PY 2014
VL 37
IS 4
BP 909
EP 911
DI 10.2337/dc13-0700
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AD7BB
UT WOS:000333414700018
PM 24271189
ER
PT J
AU Muniyappa, R
Brown, RJ
Mari, A
Joseph, J
Warren, MA
Cochran, EK
Skarulis, MC
Gorden, P
AF Muniyappa, Ranganath
Brown, Rebecca J.
Mari, Andrea
Joseph, Jalaja
Warren, Mary A.
Cochran, Elaine K.
Skarulis, Monica C.
Gorden, Phillip
TI Effects of Leptin Replacement Therapy on Pancreatic beta-Cell Function
in Patients With Lipodystrophy
SO DIABETES CARE
LA English
DT Article
ID CONGENITAL GENERALIZED LIPODYSTROPHY; INSULIN-SECRETION; POSTMORTEM
FINDINGS; GLUCOSE-TOLERANCE; OB/OB MICE; ISLETS; SENSITIVITY;
RESISTANCE; HYPERINSULINEMIA; MECHANISMS
AB OBJECTIVE
Leptin administration is known to directly modulate pancreatic beta-cell function in leptin-deficient rodent models. However, human studies examining the effects of leptin administration on beta-cell function are lacking. In this study, we examined the effects (16-20 weeks) of leptin replacement on beta-cell function in patients with lipodystrophy.
RESEARCH DESIGN AND METHODS
In a prospective, open-label, currently ongoing study, we studied the effects of leptin replacement on beta-cell function in 13 patients with congenital or acquired lipodystrophy. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution from plasma glucose and C-peptide levels measured during oral glucose tolerance tests (OGTTs) performed at baseline and after 16-20 weeks of leptin replacement. beta-Cell glucose sensitivity and rate sensitivity were assessed by mathematical modeling of OGTT.
RESULTS
There was a significant decrease in triglycerides, free fatty acids, and glycosylated hemoglobin levels (A1C) after leptin therapy. Patients with lipodystrophy have high fasting and glucose-stimulated ISR. However, leptin therapy had no significant effect on fasting ISR, total insulin secretion during OGTT, beta-cell glucose sensitivity, rate sensitivity, or insulin clearance.
CONCLUSIONS
In contrast to the suppressive effects of leptin on beta-cell function in rodents, 16-20-week treatment with leptin in lipodystrophy patients did not significantly affect insulin secretion or beta-cell function in leptin-deficient individuals with lipodystrophy.
C1 [Muniyappa, Ranganath; Brown, Rebecca J.; Joseph, Jalaja; Warren, Mary A.; Cochran, Elaine K.; Skarulis, Monica C.; Gorden, Phillip] NIDDKD, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Mari, Andrea] CNR, Inst Biomed Engn, Padua, Italy.
RP Gorden, P (reprint author), NIDDKD, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
EM phillipg@intra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 31
TC 9
Z9 11
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD APR
PY 2014
VL 37
IS 4
BP 1101
EP 1107
DI 10.2337/dc13-2040
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AD7BB
UT WOS:000333414700043
PM 24496806
ER
PT J
AU Ciol, MA
Rasch, EK
Hoffman, JM
Huynh, M
Chan, L
AF Ciol, Marcia A.
Rasch, Elizabeth K.
Hoffman, Jeanne M.
Huynh, Minh
Chan, Leighton
TI Transitions in mobility, ADLs, and IADLs among working-age Medicare
beneficiaries
SO DISABILITY AND HEALTH JOURNAL
LA English
DT Article
DE Disabled persons; Limitation of activity; Mobility limitations;
Government programs
ID DISABILITY; CARE; LIMITATIONS; POPULATION; SERVICES; COSTS
AB Background: Disability is a dynamic process where functional status may change over time. Examination of the Medicare population suggests that, for those over age 65, disability status will fluctuate in 30% of beneficiaries each year. Less is known about those under age 65. The dynamic nature of disability is of relevance since it has important implications for social policies related to disability.
Objectives: To: 1) describe the characteristics of Medicare beneficiaries eligible due to disability; and 2) estimate the proportion of individuals with transitions in functional status over a one-year period stratified by baseline characteristics and diagnostic subgroups.
Methods: We used the Medicare Current Beneficiary Survey from 1995 to 2005 to examine transitions in mobility and daily activities among individuals who were eligible for Medicare coverage due to disability.
Results: From the standpoint of function in mobility and daily activities, the working-age Medicare population with disability is fairly stable. While 75%-90% of our sample reported no disability or stable disability from one year to the next, depending on the condition and disability metric, as many as 13-14% of individuals showed improvement or decline in their functional status.
Conclusions: In the working-age population with disability, a small percentage of individuals will improve or worsen from one year to the next. Since these transitions are associated with a variety of individual characteristics including health conditions, further research applied to larger samples is required to refine policy relevant models that might inform decisions related to ongoing eligibility for disability programs. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Ciol, Marcia A.; Hoffman, Jeanne M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Rasch, Elizabeth K.; Huynh, Minh; Chan, Leighton] NIH, Ctr Clin, Dept Rehabil Med, Bethesda, MD USA.
RP Ciol, MA (reprint author), Univ Washington, Dept Rehabil Med, 1959 NE Pacific St,UW Box 356490, Seattle, WA 98195 USA.
EM marciac@uw.edu
FU National Institutes of Health, Clinical Research Center
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, Clinical Research Center.
NR 17
TC 1
Z9 1
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-6574
EI 1876-7583
J9 DISABIL HEALTH J
JI Disabil. Health J.
PD APR
PY 2014
VL 7
IS 2
BP 206
EP 215
DI 10.1016/j.dhjo.2013.10.007
PG 10
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health; Rehabilitation
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Rehabilitation
GA AD7FM
UT WOS:000333427800011
PM 24680050
ER
PT J
AU Dibrova, DV
Galperin, MY
Mulkidjanian, AY
AF Dibrova, Daria V.
Galperin, Michael Y.
Mulkidjanian, Armen Y.
TI Phylogenomic reconstruction of archaeal fatty acid metabolism
SO ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID CYTOCHROME BC COMPLEXES; BETA-OXIDATION CYCLE; HALOBACTERIUM-CUTIRUBRUM;
PYROCOCCUS-FURIOSUS; MAXIMUM-LIKELIHOOD; HALOPHILIC ARCHAEA; ORTHOLOGOUS
GENES; ESCHERICHIA-COLI; PROTEIN FAMILIES; COG DATABASE
AB While certain archaea appear to synthesize and/or metabolize fatty acids, the respective pathways still remain obscure. By analysing the genomic distribution of the key lipid-related enzymes, we were able to identify the likely components of the archaeal pathway of fatty acid metabolism, namely, a combination of the enzymes of bacterial-type beta-oxidation of fatty acids [acyl-coenzyme A (CoA) dehydrogenase, enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase] with paralogs of the archaeal acetyl-CoA C-acetyltransferase, an enzyme of the mevalonate biosynthesis pathway. These three beta-oxidation enzymes working in the reverse direction could potentially catalyse biosynthesis of fatty acids, with paralogs of acetyl-CoA C-acetyltransferase performing addition of C-2 fragments. The presence in archaea of the genes for energy-transducing membrane enzyme complexes, such as cytochrome bc complex, cytochrome c oxidase and diverse rhodopsins, was found to correlate with the presence of the proposed system of fatty acid biosynthesis. We speculate that because these membrane complexes functionally depend on fatty acid chains, their genes could have been acquired via lateral gene transfer from bacteria only by those archaea that already possessed a system of fatty acid biosynthesis. The proposed pathway of archaeal fatty acid metabolism operates in extreme conditions and therefore might be of interest in the context of biofuel production and other industrial applications.
C1 [Dibrova, Daria V.; Mulkidjanian, Armen Y.] Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany.
[Dibrova, Daria V.; Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, Sch Bioengn & Bioinformat, Moscow, Russia.
[Dibrova, Daria V.] Moscow MV Lomonosov State Univ, Inst Mitoengn, Moscow, Russia.
[Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow, Russia.
[Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Mulkidjanian, AY (reprint author), Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany.
EM amulkid@uos.de
RI Mulkidjanian, Armen/J-8086-2013
OI Mulkidjanian, Armen/0000-0001-5844-3064
FU Deutsche Forschungsgemeinschaft [DFG-Mu-1285/1-10, DFG-436-RUS
113/963/0-1]; Russian Government [02.740.11.5228]; Deutscher
Akademischer Austausch Dienst (Ostpartnerschaften-Program); COST Action
of the EU [CM0902]; NIH Intramural Research Program at the National
Library of Medicine
FX We thank Drs. Kira S. Makarova, Yuri I. Wolf and Eugene V. Koonin for
their interest in this work and many helpful suggestions and Dr.
Jonathan Lombard for useful discussion. This study was supported by
grants from the Deutsche Forschungsgemeinschaft (DFG-Mu-1285/1-10,
DFG-436-RUS 113/963/0-1), the Russian Government (No 02.740.11.5228),
the Deutscher Akademischer Austausch Dienst
(Ostpartnerschaften-Program), and the COST Action CM0902 of the EU
(A.Y.M.) and the NIH Intramural Research Program at the National Library
of Medicine (M.Y.G.).
NR 73
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U1 3
U2 31
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-2912
EI 1462-2920
J9 ENVIRON MICROBIOL
JI Environ. Microbiol.
PD APR
PY 2014
VL 16
IS 4
SI SI
BP 907
EP 918
DI 10.1111/1462-2920.12359
PG 12
WC Microbiology
SC Microbiology
GA AE1FH
UT WOS:000333713300001
PM 24818264
ER
PT J
AU Morris, JC
Ramlogan-Steel, CA
Yu, P
Black, BA
Mannan, P
Allison, JP
Waldmann, TA
Steel, JC
AF Morris, J. C.
Ramlogan-Steel, C. A.
Yu, P.
Black, B. A.
Mannan, P.
Allison, J. P.
Waldmann, T. A.
Steel, J. C.
TI Vaccination with tumor cells expressing IL-15 and IL-15R alpha inhibits
murine breast and prostate cancer
SO GENE THERAPY
LA English
DT Article
ID RESPONSES IN-VIVO; IMMUNE-RESPONSES; NATURAL-KILLER; INTERLEUKIN-15;
RECEPTOR; ADENOCARCINOMA; PROLIFERATION; CARCINOMA; MICE; INDUCTION
AB A number of antitumor vaccines have recently shown promise in upregulating immune responses against tumor antigens and improving patient survival. In this study, we examine the effectiveness of vaccination using interleukin (IL)-15-expressing tumor cells and also examine their ability to upregulate immune responses to tumor antigens. We demonstrated that the coexpression of IL-15 with its receptor, IL-15R alpha, increased the cell-surface expression and secretion of IL-15. We show that a gene transfer approach using recombinant adenovirus to express IL-15 and IL-15R alpha in murine TRAMP-C2 prostate or TS/A breast tumors induced antitumor immune responses. From this, we developed a vaccine platform, consisting of TRAMP-C2 prostate cancer cells or TS/A breast cancer cells coexpressing IL-15 and IL-15R alpha that inhibited tumor formation when mice were challenged with tumor. Inhibition of tumor growth led to improved survival when compared with animals receiving cells expressing IL-15 alone or unmodified tumor cells. Animals vaccinated with tumor cells coexpressing IL-15 and IL-15Ra showed greater tumor infiltration with CD8(+) T and natural killer (NK) cells, as well as increased antitumor CD8(+) T-cell responses. Vaccination with IL-15/IL-15R alpha-modified TS/A breast cancer cells provided a survival advantage to mice challenged with unrelated murine TUBO breast cancer cells, indicating the potential for allogeneic IL-15/IL-15R alpha-expressing vaccines.
C1 [Morris, J. C.; Ramlogan-Steel, C. A.; Black, B. A.; Steel, J. C.] Univ Cincinnati, Dept Internal Med, Div Hematol Oncol, Cincinnati, OH USA.
[Morris, J. C.; Yu, P.; Mannan, P.; Waldmann, T. A.; Steel, J. C.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Allison, J. P.] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA.
[Steel, J. C.] Univ Queensland, Sch Med, Brisbane, Qld, Australia.
RP Steel, JC (reprint author), Univ Queensland, Sch Med, Greenslopes Private Hosp, Adm Bldg,Newdegate St, Greenslopes, Qld 4120, Australia.
EM j.steel2@uq.edu.au
RI Steel, Jason/D-1805-2013
OI Steel, Jason/0000-0003-3608-7542
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health, Bethesda, MD, USA; University of Cincinnati Cancer
Institute; Lcs Foundation, Cincinnati, OH, USA
FX This work was supported in part by the Intramural Research Program of
the National Cancer Institute, National Institutes of Health, Bethesda,
MD, USA, the University of Cincinnati Cancer Institute, and a grant from
the Lcs Foundation, Cincinnati, OH, USA.
NR 41
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Z9 8
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
EI 1476-5462
J9 GENE THER
JI Gene Ther.
PD APR
PY 2014
VL 21
IS 4
BP 393
EP 401
DI 10.1038/gt.2014.10
PG 9
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Research & Experimental Medicine
GA AE2BI
UT WOS:000333777900007
PM 24572789
ER
PT J
AU Graves, KD
Sinicrope, PS
Esplen, MJ
Peterson, SK
Patten, CA
Lowery, J
Sinicrope, FA
Nigon, SK
Borgen, J
Gorin, SS
Keogh, LA
Lindor, NM
AF Graves, Kristi D.
Sinicrope, Pamela S.
Esplen, Mary Jane
Peterson, Susan K.
Patten, Christi A.
Lowery, Jan
Sinicrope, Frank A.
Nigon, Sandra K.
Borgen, Joyce
Gorin, Sherri Sheinfeld
Keogh, Louise A.
Lindor, Noralane M.
CA Colon Canc Family Registry
TI Communication of genetic test results to family and health-care
providers following disclosure of research results
SO GENETICS IN MEDICINE
LA English
DT Article
DE communication; gene test disclosure; Lynch syndrome; research; telephone
genetic education
ID NONPOLYPOSIS COLORECTAL-CANCER; RANDOMIZED CONTROLLED-TRIAL; MUTATION
CARRIERS; LYNCH SYNDROME; COLON-CANCER; RISK; VALIDATION; GENOMICS;
SCALE; INTERVENTION
AB Purpose: Few studies have examined methods to promote communication following the return of DNA mismatch repair genetic tea results obtained during research. The purpose of the present study was to evaluate a telephone protocol for returning research results of DNA mismatch repair gene testing to identify Lynch syndrome.
Methods: We invited individuals with known DNA mismatch repair mutations in their family, who were enrolled in the Colon Cancer Family Registry at the Mayo Clinic, to participate in this study. Participants completed surveys before and 6 months after DNA mismatch repair test result disclosure.
Results: Among 107 participants, 79% opted to learn their DNA mismatch repair test results; of these, 44(41%) carried DNA mismatch repair mutations. After disclosure, 54% reported screening for any type Of cancer. Among carriers, >74% reported communicating results to family; communication was predicted by baseline confidence in coping with the genetic test result (Z = 1.97; P = 0.04). Result; disclosure to a physician was predicted by greater perceived cancer risk (Z = 2.08; P = .0.03) and greater intention to share results with family (Z = 3.07; P = 0.002).
Conclusion: Research versus clinically based gene disclosure presents challenges. A telephone disclosure process, for the return of research-based results among Lynch syndrome families led to high rates of result uptake and participant communication of results to providers and family members.
C1 [Graves, Kristi D.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA.
[Sinicrope, Pamela S.; Nigon, Sandra K.; Borgen, Joyce] Mayo Clin, Coll Med, Dept Med Genet, Rochester, MN USA.
[Esplen, Mary Jane] Univ Toronto, Dept Psychiat, Univ Hlth Network, Toronto, ON, Canada.
[Peterson, Susan K.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA.
[Lowery, Jan] Univ Colorado, Dept Epidemiol, Colorado Sch Hlth, Aurora, CO USA.
[Gorin, Sherri Sheinfeld] NCI, SAIC, Rockville, MD USA.
[Gorin, Sherri Sheinfeld] NYPAC, New York, NY USA.
[Keogh, Louise A.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia.
[Lindor, Noralane M.] Mayo Clin Arizona, Dept Hlth Sci Res, Scottsdale, AZ USA.
[Patten, Christi A.] Mayo Clin, Coll Med, Dept Psychiat & Psychol, Rochester, MN USA.
[Sinicrope, Frank A.] Mayo Clin, Coll Med, Dept Oncol, Rochester, MN USA.
[Sinicrope, Frank A.] Mayo Clin, Coll Med, Dept Gastroenterol, Rochester, MN USA.
RP Graves, KD (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA.
EM kdg9@georgetown.edu
RI keogh, Louise/D-4667-2015
OI keogh, Louise/0000-0003-2963-6451
FU National Cancer Institute, National Institutes of Health, under RFA
[CA-95-011]; NCI [CAK07131172-5, P30CA051008]
FX This work was supported by the National Cancer Institute, National
Institutes of Health, under RFA #CA-95-011 and through cooperative
agreements with the members of the Colon Cancer Family Registry and
principal investigators. This work was further supported by NCI
CAK07131172-5 (K.D.G.) and NCI P30CA051008. Portions of this work were
presented at the 32nd Annual Meeting and Scientific Sessions of the
Society of Behavioral Medicine, Washington, DC, April 2011. We thank the
Colon Cancer Family Registry participants for their involvement in the
study.
NR 38
TC 4
Z9 4
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD APR
PY 2014
VL 16
IS 4
BP 294
EP 301
DI 10.1038/gim.2013.137
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA AE2BZ
UT WOS:000333779600003
PM 24091800
ER
PT J
AU Goris, A
van Setten, J
Diekstra, F
Ripke, S
Patsopoulos, NA
Sawcer, SJ
van Es, M
Andersen, PM
Melki, J
Meininger, V
Hardiman, O
Landers, JE
Brown, RH
Shatunov, A
Leigh, N
Al-Chalabi, A
Shaw, CE
Traynor, BJ
Chio, A
Restagno, G
Mora, G
Ophoff, RA
Oksenberg, JR
Van Damme, P
Compston, A
Robberecht, W
Dubois, B
van den Berg, LH
De Jager, PL
Veldink, JH
Bakker, PIW
AF Goris, An
van Setten, Jessica
Diekstra, Frank
Ripke, Stephan
Patsopoulos, Nikolaos A.
Sawcer, Stephen J.
van Es, Michael
Andersen, Peter M.
Melki, Judith
Meininger, Vincent
Hardiman, Orla
Landers, John E.
Brown, Robert H., Jr.
Shatunov, Aleksey
Leigh, Nigel
Al-Chalabi, Ammar
Shaw, Christopher E.
Traynor, Bryan J.
Chio, Adriano
Restagno, Gabriella
Mora, Gabriele
Ophoff, Roel A.
Oksenberg, Jorge R.
Van Damme, Philip
Compston, Alastair
Robberecht, Wim
Dubois, Benedicte
van den Berg, Leonard H.
De Jager, Philip L.
Veldink, Jan H.
de Bakker, Paul I. W.
CA Int Multiple Sclerosis Genetics Co
Australia New Zealand MS Genetic C
TI No evidence for shared genetic basis of common variants in multiple
sclerosis and amyotrophic lateral sclerosis
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; HEXANUCLEOTIDE REPEAT;
AUTOIMMUNE; NEURODEGENERATION; INFLAMMATION; METAANALYSIS; STATISTICS;
ACTIVATION; MECHANISMS
AB Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within individuals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control individuals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS.
C1 [Goris, An; Dubois, Benedicte] Katholieke Univ Leuven, Lab Neuroimmunol, B-3000 Louvain, Belgium.
[Goris, An; Van Damme, Philip; Robberecht, Wim; Dubois, Benedicte] Katholieke Univ Leuven, LIND, B-3000 Louvain, Belgium.
[van Setten, Jessica; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[Diekstra, Frank; van Es, Michael; van den Berg, Leonard H.; Veldink, Jan H.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands.
[Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Ripke, Stephan] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Patsopoulos, Nikolaos A.; de Bakker, Paul I. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA.
[Patsopoulos, Nikolaos A.; De Jager, Philip L.; de Bakker, Paul I. W.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Patsopoulos, Nikolaos A.; De Jager, Philip L.] Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA.
[Sawcer, Stephen J.; Compston, Alastair] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 0QQ, England.
[Andersen, Peter M.] Umea Univ, Dept Clin Neurosci, SE-90185 Umea, Sweden.
[Melki, Judith] Univ Paris, Bicetre Hosp, Dept Neuropediat, F-94275 Paris, France.
[Meininger, Vincent] Univ Paris 06, Hop La Salpetriere, Dept Neurol, F-75013 Paris, France.
[Hardiman, Orla] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland.
[Hardiman, Orla] Univ Dublin Trinity Coll, Dept Neurol, Dublin 2, Ireland.
[Landers, John E.; Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA.
[Landers, John E.; Brown, Robert H., Jr.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.
[Shatunov, Aleksey; Leigh, Nigel; Al-Chalabi, Ammar; Shaw, Christopher E.] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, London SE5 8AF, England.
[Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Chio, Adriano] Univ Turin, Azienda Osped Citta Salute & Sci, Dept Neurosci, I-10126 Turin, Italy.
[Restagno, Gabriella] Azienda Osped Citta Salute & Sci, Dept Lab Med, I-10126 Turin, Italy.
[Mora, Gabriele] Sci Inst Milan, Fdn Salvatore Maugeri, I-20138 Milan, Italy.
[Ophoff, Roel A.] UMC, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands.
[Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA.
[Oksenberg, Jorge R.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Oksenberg, Jorge R.] Univ Calif San Francisco, Sch Med, Inst Human Genet, San Francisco, CA 94143 USA.
[Van Damme, Philip; Robberecht, Wim; Dubois, Benedicte] Katholieke Univ Leuven Hosp, Dept Neurol, Louvain, Belgium.
[Van Damme, Philip; Robberecht, Wim] Katholieke Univ Leuven, Lab Neurobiol Expt Neurol, B-3000 Louvain, Belgium.
[Van Damme, Philip; Robberecht, Wim] VIB, VRC, Louvain, Belgium.
[De Jager, Philip L.; de Bakker, Paul I. W.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands.
RP Goris, A (reprint author), Katholieke Univ Leuven, Sect Expt Neurol, Lab Neuroimmunol, Herestr 49 Bus 1022, B-3000 Louvain, Belgium.
EM an.goris@med.kuleuven.be
RI Van Damme, Philip/A-6464-2009; D'Alfonso, Sandra/K-7295-2014; de Bakker,
Paul/B-8730-2009; MOSCATO, PABLO/G-7668-2013; Goris, An/F-2943-2010;
Zipp, Frauke/C-9968-2015;
OI Hardiman, Orla/0000-0003-2610-1291; Van Damme,
Philip/0000-0001-6384-0611; D'Alfonso, Sandra/0000-0002-3983-9925; de
Bakker, Paul/0000-0001-7735-7858; Goris, An/0000-0002-1276-6682; Zipp,
Frauke/0000-0002-1231-1928; Field, Judith/0000-0002-7089-0999; Chio,
Adriano/0000-0001-9579-5341; Saarela, Janna/0000-0002-0853-6219;
Butzkueven, Helmut/0000-0003-3940-8727
FU Belgian Charcot Foundation; Wetenschappelijk Onderzoek Multiple Sclerose
(WOMS); Belgian Neurological Society (BNS); Research Fund KU Leuven
[OT/11/087]; National Multiple Sclerosis Society [FG 1938-A-1]; National
Institutes of Health [R01 NSO49477]; National Institutes of
Health/National Institute of Neurological Disorders and Stroke [R01
NS073873]; National Institute for Health Research (NIHR) Dementia
Biomedical Research Unit at South London; Maudsley NHS Foundation Trust
and King's College London; Belgian Federal Science Policy Office
[P6/43]; University of Leuven [GOA 11/014]; E von Behring Chair for
Neuromuscular and Neurodegenerative Disorders; Thierry Latran
Foundation; VIDI Award from the Netherlands Organization for Scientific
Research (NWO) [016.126.354]; Association pour la Recherche sur la SLA;
Association Roseau SLA Ile de France; ALS Therapy Alliance; Angel Fund;
Pierre L. de Bourgknecht ALS Research Foundation; Al-Athel ALS Research
Foundation; ALS Family Charitable Foundation; National Institute of
Neurological Disorders and Stroke [NS050557]; Muscular Dystrophy
Association (USA); Health Research Board of Ireland; Irish Neurological
Association; Irish Motor Neuron Disease Research Foundation; Italian
Ministry of Health [RF-PIE-2007-63565, RF-2010-2309849]; Regione
Piemonte [2004-A317]; Fondazione Vialli c Mauro per la SLA Onlus
[obiettivo 7]; Federazione Italiana Giuoco Calcio (FIGC); Prinses
Beatrix Fonds (Kersten Foundation); VSB fonds; Netherlands ALS
Foundation; Adessium Foundation; Netherlands Organization of Scientific
Research NWO Investments [175.010.2005.011, 911-03-012]; Research
Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics
Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO)
[050-060-810]; European Community's Health Seventh Framework Programme
[259867]; Swedish Brain Research Foundation; WIllstens Research
Foundation; Swedish Medical Society; Bjorklund Foundation; Swedish
Association for the Neurologically Disabled; US National Institutes of
Health (NIH), National Institute on Aging [Z01-AG000949-02]; National
Institute of Neurological Disorders and Stroke (NINDS)
FX A.G. is supported by the Belgian Charcot Foundation. A.G. and B.D. are
supported by Wetenschappelijk Onderzoek Multiple Sclerose (WOMS), the
Belgian Neurological Society (BNS) and the Research Fund KU Leuven
(OT/11/087). Computational resources used in this work were provided by
the Hercules Foundation and the Flemish Government department EWI. This
investigation was supported in part by a postdoctoral fellowship from
the National Multiple Sclerosis Society to N.A.P. (FG 1938-A-1) and by
National Institutes of Health funding to the International Multiple
Sclerosis Genetics Consortium (R01 NSO49477). J.E,L, received funding
from the National Institutes of Health/National Institute of
Neurological Disorders and Stroke (R01 NS073873). A.A.C. receives salary
support from the National Institute for Health Research (NIHR) Dementia
Biomedical Research Unit at South London and Maudsley NHS Foundation
Trust and King's College London. The views expressed are those of the
author and not necessarily those of the NHS, the NIHR or the Department
of Health, P,V,D, and B.D. are clinical investigators of the Research
Foundation Flanders (FWO-Vlaanderen), B,D, is supported by TEVA PHARMA
NEDERLAND BV. W.R. is supported by Interuniversity Attraction Poles
(IUAP) program P6/43 of the Belgian Federal Science Policy Office, the
University of Leuven (GOA 11/014 and Methusalem) and the E von Behring
Chair for Neuromuscular and Neurodegenerative Disorders. J.V. is
supported by the Thierry Latran Foundation. P.I.W.d.B. is the recipient
of a VIDI Award from the Netherlands Organization for Scientific
Research (NWO project 016.126.354). For the ALS GWA study, we thank all
patients and healthy volunteers who participated in the project; general
practitioners and pharmacists, In France, this study was funded by the
Association pour la Recherche sur la SLA; and the Association Roseau SLA
Ile de France, Support was also provided by the ALS Therapy Alliance;
Project ALS; the Angel Fund; the Pierre L. de Bourgknecht ALS Research
Foundation; the Al-Athel ALS Research Foundation; the ALS Family
Charitable Foundation and the National Institute of Neurological
Disorders and Stroke (NS050557). The Irish ALS study was funded by The
Muscular Dystrophy Association (USA); The Health Research Board of
Ireland; The Irish Neurological Association Travel Award and The Irish
Motor Neuron Disease Research Foundation. The ALS Study in Italy was
funded by the Italian Ministry of Health (RF-PIE-2007-63565 and
RF-2010-2309849); Regione Piemonte (2004-A317); the Fondazione Vialli c
Mauro per la SLA Onlus (obiettivo 7) and the Federazione Italiana Giuoco
Calcio (FIGC). The ALS study in the Netherlands was supported by the
Prinses Beatrix Fonds (Kersten Foundation); VSB fonds; the Netherlands
ALS Foundation and J.R. van Dijk; the Adessium Foundation to L.v.d.B.;
the Netherlands Organization of Scientific Research NWO Investments
(grant numbers 175.010.2005.011, 911-03-012): the Research Institute for
Diseases in the Elderly (014-93-015; RIDE) and the Netherlands Genomics
Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO)
(project number 050-060-810).; In addition, the research leading to
these results has received funding from the European Community's Health
Seventh Framework Programme (FP7/2007-2013) (grant agreement number
259867), In Sweden, the ALS study was supported by the Swedish Brain
Research Foundation; the WIllstens Research Foundation; the Swedish
Medical Society; the Bjorklund Foundation for ALS Research and the
Swedish Association for the Neurologically Disabled to P.A. For the ALS
UK study, we thank the Motor Neurone Disease Association of Great
Britain and Ireland, the Medical Research Council (UK), the Wellcome
Trust and the Psychiatry Research Trust (Tim Perkins Fund and Charcot
Fund). This work was supported in part by the Intramural Research
Programs of the US National Institutes of Health (NIH), National
Institute on Aging (Z01-AG000949-02) and National Institute of
Neurological Disorders and Stroke (NINDS), Members of the International
Multiple Sclerosis Genetics Consortium (IMSGC) and the Australia and New
Zealand MS Genetics Consortium (ANZGenc) are listed in the supplementary
file.
NR 43
TC 5
Z9 5
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD APR 1
PY 2014
VL 23
IS 7
BP 1916
EP 1922
DI 10.1093/hmg/ddt574
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AD5CA
UT WOS:000333267900020
PM 24234648
ER
PT J
AU Milne, RL
Herranz, J
Michailidou, K
Dennis, J
Tyrer, JP
Zamora, MP
Arias-Perez, JI
Gonzalez-Neira, A
Pita, G
Alonso, MR
Wang, Q
Bolla, MK
Czene, K
Eriksson, M
Humphreys, K
Darabi, H
Li, JM
Anton-Culver, H
Neuhausen, SL
Ziogas, A
Clarke, CA
Hopper, JL
Dite, GS
Apicella, C
Southey, MC
Chenevix-Trench, G
Swerdlow, A
Ashworth, A
Orr, N
Schoemaker, M
Jakubowska, A
Lubinski, J
Jaworska-Bieniek, K
Durda, K
Andrulism, IL
Knight, JA
Glendon, G
Mulligan, AM
Bojesen, SE
Nordestgaard, BG
Flyger, H
Nevanlinna, HL
Muranen, TA
Aittomaki, K
Blomqvist, C
Chang-Claude, J
Rudolph, A
Seibold, P
Flesch-Janys, D
Wang, XS
Olson, JE
Vachon, C
Purrington, K
Winqvist, R
Pylkas, K
Jukkola-Vuorinen, A
Grip, M
Dunning, AM
Shah, M
Guenel, P
Truong, T
Sanchez, M
Mulot, C
Brenner, H
Dieffenbach, AK
Arndt, V
Stegmaier, C
Lindblom, A
Margolin, S
Hooning, MJ
Hollestelle, A
Collee, JM
Jager, A
Cox, A
Brock, IW
Reed, MWR
Devilee, P
Tollenaar, RAEM
Seynaeve, C
Haiman, CA
Henderson, BE
Schumacher, F
Le Marchand, L
Simard, J
Dumont, M
Soucy, P
Dork, T
Bogdanova, NV
Hamann, U
Forsti, A
Rudiger, T
Ulmer, HU
Fasching, PA
Haberle, L
Ekici, AB
Beckmann, MW
Fletcher, O
Johnson, N
Silva, IDS
Peto, J
Radice, P
Peterlongo, P
Peissel, B
Mariani, P
Giles, GG
Severi, G
Baglietto, L
Sawyer, E
Tomlinson, I
Kerin, M
Miller, N
Marme, F
Burwinkei, B
Mannermaa, A
Kataja, V
Kosma, VM
Hartikainen, JM
Lambrechts, D
Yesilyurt, BT
Floris, G
Leunen, K
Alnaes, GG
Kristensen, V
Borresen-Dale, AL
Garcia-Closas, M
Chanock, SJ
Lissowska, J
Figueroa, JD
Schmidt, MK
Broeks, A
Verhoef, S
Rutgers, EJ
Brauch, H
Bruning, T
Ko, YD
Couch, FJ
Toland, AE
Yannoukakos, D
Pharoah, PDP
Hall, P
Benitez, J
Malats, N
Easton, DF
AF Milne, Roger L.
Herranz, Jesus
Michailidou, Kyriaki
Dennis, Joe
Tyrer, Jonathan P.
Zamora, M. Pilar
Arias-Perez, Jose Ignacio
Gonzalez-Neira, Anna
Pita, Guillermo
Alonso, M. Rosario
Wang, Qin
Bolla, Manjeet K.
Czene, Kamila
Eriksson, Mikael
Humphreys, Keith
Darabi, Hatef
Li, Jingmei
Anton-Culver, Hoda
Neuhausen, Susan L.
Ziogas, Argyrios
Clarke, Christina A.
Hopper, John L.
Dite, Gillian S.
Apicella, Carmel
Southey, Melissa C.
Chenevix-Trench, Georgia
Swerdlow, Anthony
Ashworth, Alan
Orr, Nicholas
Schoemaker, Minouk
Jakubowska, Anna
Lubinski, Jan
Jaworska-Bieniek, Katarzyna
Durda, Katarzyna
Andrulism, Irene L.
Knight, Julia A.
Glendon, Gord
Mulligan, Anna Marie
Bojesen, Stig E.
Nordestgaard, Borge G.
Flyger, Henrik
Nevanlinna, He Li
Muranen, Taru A.
Aittomaki, Kristiina
Blomqvist, Carl
Chang-Claude, Jenny
Rudolph, Anja
Seibold, Petra
Flesch-Janys, Dieter
Wang, Xianshu
Olson, Janet E.
Vachon, Celine
Purrington, Kristen
Winqvist, Robert
Pylkas, Katri
Jukkola-Vuorinen, Arja
Grip, Mervi
Dunning, Alison M.
Shah, Mitul
Guenel, Pascal
Truong, Therese
Sanchez, Marie
Mulot, Claire
Brenner, Hermann
Dieffenbach, Aida Karina
Arndt, Volker
Stegmaier, Christa
Lindblom, Annika
Margolin, Sara
Hooning, Maartje J.
Hollestelle, Antoinette
Collee, J. Margriet
Jager, Agnes
Cox, Angela
Brock, Ian W.
Reed, Malcolm W. R.
Devilee, Peter
Tollenaar, Robert A. E. M.
Seynaeve, Caroline
Haiman, Christopher A.
Henderson, Brian E.
Schumacher, Fredrick
Le Marchand, Loic
Simard, Jacques
Dumont, Martine
Soucy, Penny
Doerk, Thilo
Bogdanova, Natalia V.
Hamann, Ute
Foersti, Asia
Ruediger, Thomas
Ulmer, Hans-Ulrich
Fasching, Peter A.
Haeberle, Lothar
Ekici, Arif B.
Beckmann, Matthias W.
Fletcher, Olivia
Johnson, Nichola
Silva, Isabel dos Santos
Peto, Julian
Radice, Paolo
Peterlongo, Paolo
Peissel, Bernard
Mariani, Paolo
Giles, Graham G.
Severi, Gianluca
Baglietto, Laura
Sawyer, Elinor
Tomlinson, Ian
Kerin, Michael
Miller, Nicola
Marme, Federik
Burwinkei, Barbara
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M.
Lambrechts, Diether
Yesilyurt, Betul T.
Floris, Giuseppe
Leunen, Karin
Alnaes, Grethe Grenaker
Kristensen, Vessela
Borresen-Dale, Anne-Lise
Garcia-Closas, Montserrat
Chanock, Stephen J.
Lissowska, Jolanta
Figueroa, Jonine D.
Schmidt, Marjanka K.
Broeks, Annegien
Verhoef, Senno
Rutgers, Emiel J.
Brauch, Hiltrud
Bruening, Thomas
Ko, Yon-Dschun
Couch, Fergus J.
Toland, Amanda E.
Yannoukakos, Drakoulis
Pharoah, Paul D. P.
Hall, Per
Benitez, Javier
Malats, Nuria
Easton, Douglas F.
CA Kcon Fab Investigators
Australian Ovarian Canc Study Grp
Genica Network
TNBCC
TI A large-scale assessment of two-way SNP interactions in breast cancer
susceptibility using 46 450 cases and 42 461 controls from the breast
cancer association consortium
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GENETIC SUSCEPTIBILITY; CONFER SUSCEPTIBILITY;
COMMON VARIANTS; IDENTIFIES 2; RISK; LOCI; EPISTASIS; ERAP1; ALLELES
AB Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70 917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46 450 breast cancer cases and 42 461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P < 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P < 10(-4)) were selected for more careful assessment by logistic regression. Under the first approach, 3277 SNPs were preselected, but an evaluation of all possible two-SNP combinations (1 d.f.) identified no interactions at P < 10(-8). Results from the second analytic approach were consistent with those from the first (P > 10(-10)). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome.
C1 [Milne, Roger L.; Herranz, Jesus; Benitez, Javier; Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet, Madrid, Spain.
[Gonzalez-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genotyping CEGEN Unit, Madrid, Spain.
[Milne, Roger L.; Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura] Univ Melbourne, Ctr Epidemiol & Biostatist, Sch Populat Hlth, Melbourne, Vic, Australia.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
[Milne, Roger L.; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura] Canc Epidemiol Ctr, Canc Council Victoria, Melbourne, Vic, Australia.
[Herranz, Jesus] IMDEA Food Inst, Biostatist Unit, Madrid, Spain.
[Michailidou, Kyriaki; Dennis, Joe; Wang, Qin; Bolla, Manjeet K.; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
[Tyrer, Jonathan P.; Dunning, Alison M.; Shah, Mitul; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England.
[Zamora, M. Pilar] Hosp Univ La Paz, Med Oncol Serv, Madrid, Spain.
[Arias-Perez, Jose Ignacio] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain.
[Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostatist, Stockholm, Sweden.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
[Li, Jingmei] Genome Inst Singapore, Div Human Genet, Singapore, Singapore.
[Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA.
[Clarke, Christina A.] Canc Prevent Inst Calif, Fremont, CA USA.
[Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
[Kcon Fab Investigators; Australian Ovarian Canc Study Grp] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Swerdlow, Anthony; Schoemaker, Minouk; Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
[Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Garcia-Closas, Montserrat] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England.
[Ashworth, Alan; Orr, Nicholas; Fletcher, Olivia; Johnson, Nichola; Garcia-Closas, Montserrat] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Ashworth, Alan] Inst Canc Res, Div Mol Pathol, London SW3 6JB, England.
[Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
[Jaworska-Bieniek, Katarzyna] Med Univ Warsaw, Postgrad Sch Mol Med, Warsaw, Poland.
[Andrulism, Irene L.; Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Andrulism, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Knight, Julia A.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Glendon, Gord] Ontario Canc Genet Network, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.
[Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada.
[Bojesen, Stig E.; Nordestgaard, Borge G.] Univ Copenhagen, Copenhagen Gen Populat Study, Copenhagen, Denmark.
[Bojesen, Stig E.; Nordestgaard, Borge G.] Univ Copenhagen, Dept Clin Biochem, Copenhagen, Denmark.
[Flyger, Henrik] Univ Copenhagen, Dept Breast Surg, Herlev Univ Hosp, Copenhagen, Denmark.
[Nevanlinna, He Li; Muranen, Taru A.] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland.
[Nevanlinna, He Li; Muranen, Taru A.] Univ Helsinki, Cent Hosp, Helsinki, Finland.
[Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland.
[Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland.
[Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Mulot, Claire; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Foersti, Asia] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany.
[Burwinkei, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Dept Canc Epidemiol, Clin Canc Registry, Hamburg, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany.
[Wang, Xianshu; Couch, Fergus J.; TNBCC] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Olson, Janet E.; Vachon, Celine; Purrington, Kristen] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Lab Canc Genet & Tumor Biol, Dept Clin Chem & Bioctr Oulu, Oulu, Finland.
[Jukkola-Vuorinen, Arja] Univ Oulu, Dept Oncol, Oulu, Finland.
[Grip, Mervi] Univ Oulu, Dept Surg, Oulu, Finland.
[Guenel, Pascal; Truong, Therese] INSERM Natl Inst Hlth & Med Res, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Environm Epidemiol Canc, Villejuif, France.
[Guenel, Pascal; Truong, Therese] Univ Paris Sud, UMRS 1018, Villejuif, France.
[Sanchez, Marie] Ctr Ressources Biol EPIGENETEC, Paris, France.
[Sanchez, Marie] INSERM Natl Inst Hlth & Med Res, U775, Paris, France.
[Mulot, Claire; Brenner, Hermann] German Canc Consortium DKTK, Heidelberg, Germany.
[Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany.
[Hooning, Maartje J.; Hollestelle, Antoinette; Jager, Agnes; Seynaeve, Caroline] Erasmus Univ, Med Ctr, Dept Med Oncol, Family Canc Clin, Rotterdam, Netherlands.
[Collee, J. Margriet] Erasmus Univ, Med Ctr, Dept Clin Genet, Family Canc Clin, Rotterdam, Netherlands.
[Cox, Angela; Brock, Ian W.; Reed, Malcolm W. R.] Univ Sheffield, CRUK YCR Sheffield Canc Res Ctr, Dept Oncol, Sheffield, S Yorkshire, England.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
[Tollenaar, Robert A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, Leiden, Netherlands.
[Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Simard, Jacques; Dumont, Martine; Soucy, Penny] Ctr Hosp Univ, Quebec Res Ctr, Canc Genom Lab, Quebec City, PQ, Canada.
[Simard, Jacques; Dumont, Martine; Soucy, Penny] Univ Laval, Quebec City, PQ, Canada.
[Doerk, Thilo; Bogdanova, Natalia V.] Hannover Med Sch, Dept Obstet & Gynaecol, Hannover, Germany.
[Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany.
[Hamann, Ute] Deutsch Krebsforschungszentrum DKFZ, Mol Genet Breast Canc, Heidelberg, Germany.
[Foersti, Asia] Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden.
[Ruediger, Thomas] Stadt Klinikum Karlsruhe, Inst Pathol, Karlsruhe, Germany.
[Ulmer, Hans-Ulrich] Frauenklin Stadtklin Baden Baden, Baden Baden, Germany.
[Fasching, Peter A.; Haeberle, Lothar; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Univ Breast Ctr Franconia, Comprehens Canc Ctr Erlangen EMN, Dept Gynecol & Obstet,Univ Hosp Erlangen, Erlangen, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, D-91054 Erlangen, Germany.
[Silva, Isabel dos Santos; Peto, Julian] London Sch Hyg & Trop Med, London WC1, England.
[Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predict Med, Milan, Italy.
[Peterlongo, Paolo; Mariani, Paolo] IFOM, Fdn Ist FlRC Oncol Mol, Milan, Italy.
[Mariani, Paolo] Cogentech Canc Genet Test Lab, Milan, Italy.
[Sawyer, Elinor] Guys & St Thomas NHS Fdn Trust Partnership Kings, Div Canc Studies, NIHR Comprehens Biomed Res Ctr, London, England.
[Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England.
[Kerin, Michael; Miller, Nicola] Natl Univ Ireland, Sch Med, Inst Clin Sci, Galway, Ireland.
[Marme, Federik; Burwinkei, Barbara] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany.
[Marme, Federik] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Dept Clin Pathol, SF-70210 Kuopio, Finland.
[Kataja, Vesa] Kuopio Univ Hosp, Ctr Canc, SF-70210 Kuopio, Finland.
[Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Sch Med, Inst Clin Med Pathol & Forens Med, Kuopio, Finland.
[Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Bioctr Kuopio, Kuopio, Finland.
[Lambrechts, Diether; Yesilyurt, Betul T.] Univ Hosp Gasthuisberg, Vesalius Res Ctr VRC, VIB, B-3000 Louvain, Belgium.
[Floris, Giuseppe; Leunen, Karin] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium.
[Alnaes, Grethe Grenaker; Kristensen, Vessela; Borresen-Dale, Anne-Lise] Oslo Univ Hosp, Radiumhosp, Dept Genet, Inst Canc Res, Oslo, Norway.
[Kristensen, Vessela; Borresen-Dale, Anne-Lise] UiO, Fac Med, Fac Div Ahus, Oslo, Norway.
[Garcia-Closas, Montserrat; Chanock, Stephen J.; Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Schmidt, Marjanka K.; Broeks, Annegien; Verhoef, Senno; Rutgers, Emiel J.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
[Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
[Bruening, Thomas] Inst Ruhr Univ Bochum IPA, Inst Prevent & Occupat Med German Social Accident, Bochum, Germany.
[Ko, Yon-Dschun] Johanniter Krankenhaus, Dept Internal Med, Evangel Klin Bonn GmbH, Bonn, Germany.
Univ Med Ctr Hamburg Eppendorf, Inst Occupat Med & Maritime Med, Hamburg, Germany.
[Genica Network] Univ Bonn, Inst Pathol, Fac Med, Bonn, Germany.
[Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, INRASTES, Mol Diagnost Lab, Athens, Greece.
[Benitez, Javier] Biomed Network Rare Dis CIBERER, Madrid, Spain.
RP Milne, RL (reprint author), Canc Epidemiol Ctr, Canc Council Victoria, 100 Drummond St, Carlton, Vic 3053, Australia.
EM roger.milne@cancervic.org.au
RI Bruning, Thomas/G-8120-2015; Brenner, Hermann/B-4627-2017; Peissel,
Bernard/E-8187-2017; Knight, Julia/A-6843-2012; Jakubowska,
Anna/O-8050-2014; Li, Jingmei/I-2904-2012; Gonzalez-Neira,
Anna/C-5791-2015; Hartikainen, Jaana/E-6256-2015; Garcia-Closas,
Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015;
Szeszenia-Dabrowska, Neonila/F-7190-2010; Dork, Thilo/J-8620-2012;
Bowtell, David/H-1007-2016; Herranz Valera, Jesus/M-8657-2014;
OI Bruning, Thomas/0000-0001-9560-5464; Brenner,
Hermann/0000-0002-6129-1572; Peissel, Bernard/0000-0001-9233-3571; Li,
Jingmei/0000-0001-8587-7511; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Bowtell,
David/0000-0001-9089-7525; Arndt, Volker/0000-0001-9320-8684;
Schoemaker, Minouk/0000-0001-8403-2234; Nevanlinna,
Heli/0000-0002-0916-2976; Czene, Kamila/0000-0002-3233-5695; Arias
Perez, Jose Ignacio/0000-0003-4500-397X; Herranz Valera,
Jesus/0000-0002-7385-1311; Dunning, Alison Margaret/0000-0001-6651-7166;
Muranen, Taru/0000-0002-5895-1808; dos Santos Silva,
Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099;
Yannoukakos, Drakoulis/0000-0001-7509-3510; Malats,
Nuria/0000-0003-2538-3784
FU European Community [223175, HEALTH-F2-2009-223175]; Cancer Research UK
[C1287/A10118, C1287/A 10710, C122 92/A11174, C1281/A12014, C5047/A8384,
C5047/A15007, C5047/A10692]; National Institutes of Health [CA128978];
Post-cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19
CA148112]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes
of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast
Cancer; Komen Foundation for the Cure; Breast Cancer Research
Foundation; Ovarian Cancer Research Fund; ABCFS; OFBCR; National Cancer
Institute (USA) [UM1 CA 164920]; National Health and Medical Research
Council of Australia; New South Wales Cancer Council; Victorian Health
Promotion Foundation (Australia); Victorian Breast Cancer Research
Consortium; National Health and Medical Research Council (NHMRC);
Canadian Institutes of Health Research 'CIHR Team in Familial Risks of
Breast Cancer' program; Dutch Cancer Society [NK12007-3839,
NKI2009-4363]; ELAN-Programme of the University Hospital of Erlangen;
Cancer Research UK; Breakthrough Breast Cancer; NHS; CR-UK
[C1287/A10118, C1287/A12014]; European Union COST programme [BM0606];
NIHR Comprehensive Biomedical Research Centre; Guy's & St. Thomas' NHS
Foundation; King's College London, UK; Oxford Biomedical Research
Centre; Dietmar-Hopp Foundation; Helmholtz Society; German Cancer
Research Center (DKFZ); Fondation de France; French National Institute
of Cancer (INCa); National League against Cancer; National Agency for
Environmental and Occupational Health and Food Safety (ANSES); National
Agency for Research (ANR); Association for Research against Cancer
(ARC); Chief Physician Johan Bosenip and Lise Bosenip Fund; Danish
Medical Research Council; Herlev Hospital; Genome Spain Foundation; Red
Tematica de Investigacion Cooperativa en Cancer; Asociacion Espanola
Contra el Cancer; Fond de Investigacion Sanitario [PI11/00923,
PI081120]; Institut de Salud Carlos III; California Breast Cancer Act;
California Breast Cancer Research Fund [97-10500]; Lon V. Smith
Foundation [LVS39420]; Baden Wiirttemberg Ministry of Science, Research
and Arts; German Cancer Aid (Deutsche Krebshilfe); Federal Ministry of
Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/ 8,
01KW9977/0, 01KW0114]; Robert Bosch Foundation; Stuttgart; Deutsches
Krebsforschungszentnu-n (DKFZ); Heidelberg; Institute for Prevention and
Occupational Medicine of the German Social Accident Insurance; Institute
of the Ruhr University Bochum (IPA); Department of Internal Medicine,
Evangelische Kliniken Bonn gGmbH; Johanniter Krankenhaus; Associazione
Italiana per la Ricerca sul Cancro
FX Funding for the iCOGS infrastructure came from the European Community's
Seventh Framework Programme under grant agreement number 223175
(HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118,
C1287/A 10710, C122 92/A11174, C1281/Al2014, C5047/A8384, C5047/A15007,
C5047/A10692), the National Institutes of Health (CA128978) and
Post-cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19
CA148112-the GAME-ON initiative), the Department of Defence
(W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR)
for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation
for the Cure, the Breast Cancer Research Foundation and the Ovarian
Cancer Research Fund, The ABCFS and OFBCR work was supported by grant
UM1 CA 164920 from the National Cancer Institute (USA). The content of
this manuscript does not necessarily reflect the views or policies of
the National Cancer Institute or any of the collaborating centers in the
Breast Cancer Family Registry (BUR), nor does mention of trade names,
commercial products or organizations imply endorsement by the U, 5,
Governmentor the BCFR. The ABCFR was also supported by the National
Health and Medical Research Council of Australia, the New South Wales
Cancer Council, the Victorian Health Promotion Foundation (Australia)
and the Victorian Breast Cancer Research Consortium. J.L.H. is a
National Health and Medical Research Council (NHMRC) Senior Principal
Research Fellow and M.C.S. is a NHMRC Senior Research Fellow, The OFBCR
work was also supported by the Canadian Institutes of Health Research
'CIHR Team in Familial Risks of Breast Cancer' program. The ABCS was
funded by Dutch Cancer Society Grant no.NK12007-3839; M.K.S. was funded
by Dutch Cancer Society Grant no. NKI2009-4363. The work of the BBCC was
partly funded by ELAN-Programme of the University Hospital of Erlangen.
The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer
and acknowledges NHS funding to the NIHR Biomedical Research Centre, and
the National Cancer Research Network (NCRN). The BCAC is funded by CR-UK
(C1287/A10118 and C1287/A12014). Meetings of the BCAC have been funded
by the European Union COST programme (BM0606). D.F.E. is a Principal
Research Fellow of CR-UK. E.S. is supported by NIHR Comprehensive
Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in
partnership with King's College London, UK. IT, is supported by the
Oxford Biomedical Research Centre, The BSUCH study was supported by the
Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer
Research Center (DKFZ), The CECILE study was funded by the Fondation de
France, the French National Institute of Cancer (INCa), the National
League against Cancer, the National Agency for Environmental and
Occupational Health and Food Safety (ANSES), the National Agency for
Research (ANR) and the Association for Research against Cancer (ARC).
The CGPS was supported by the Chief Physician Johan Bosenip and Lise
Bosenip Fund, the Danish Medical Research Council and Herlev Hospital.
The CNIOBCS was supported by the Genome Spain Foundation, the Red
Tematica de Investigacion Cooperativa en Cancer and grants from the
Asociacion Espanola Contra el Cancer and the Fond de Investigacion
Sanitario (PI11/00923 and PI081120).; The Human Genotyping-CEGEN Unit,
CNIO is supported by the Institut de Salud Carlos III, The CTS was
initially supported by the California Breast Cancer Act of 1993 and the
California Breast Cancer Research Fund (contract 97-10500) and is
currently funded through the National Institutes of Health (R01
CA77398). Collection of cancer incidence data was supported by the
California Department of Public Health as part of the statewide cancer
reporting program mandated by California Health and Safety Code Section
103885. H.A.C. receives support from the Lon V. Smith Foundation
(LVS39420). The ESTHER study was supported by a grant from the Baden
Wiirttemberg Ministry of Science, Research and Arts. Additional cases
were recruited in the context of the VERDI study, which was supported by
a grant from the German Cancer Aid (Deutsche Krebshilfe). The GENICA was
funded by the Federal Ministry of Education and Research (BMBF) Germany
(grants 01KW9975/5, 01KW9976/ 8, 01KW9977/0 and 01KW0114), the Robert
Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentnu-n (DKFZ),
Heidelberg, the Institute for Prevention and Occupational Medicine of
the German Social Accident Insurance, the Institute of the Ruhr
University Bochum (IPA) and the Department of Internal Medicine,
Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany.
The HEBCS was supported by the Helsinki University Central Hospital
Research Fund, Academy of Finland (132473), the Finnish Cancer Society,
The Nordic Cancer Union and the Sigrid Juselius Foundation, The HMBCS
was supported by short-term fellowships from the German Academic
Exchange Program [to NB], and the Friends of Hannover Medical School [to
N.B.]. Financial support for KARBAC was provided through the regional
agreement on medical training and clinical research (ALF) between
Stockholm County Council and Karolinska lnstitutet, the Swedish Cancer
Society, The Gustav V Jubilee foundatin and Bert on Kantzows foundation,
The KBCP was financially supported by the special Government Funding
(EVO) of Kuopio University Hospital grants, Cancer Fund ofNorth Savo,
the Finnish Cancer Organizations, the Academy of Finland and by the
strategic funding of the University of Eastern Finland, kConFab is
supported by grants from the National Breast Cancer Foundation, the
NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South
Wales, Victoria, Tasmania and South Australia and the Cancer Foundation
of Western Australia. The kConFab Clinical Follow Up Study was funded by
the NHMRC [145684, 288704, 454508]. Financial support for the AOCS was
provided by the United States Army Medical Research and Materiel Command
[DAMD17-01-1-0729], the Cancer Council of Tasmania and Cancer Foundation
of Western Australia and the NHMRC [199600]. G.C.T. and P.W. are
supported by the NHMRC. LMBC is supported by the Stichting tegcn Kanker'
(232-2008 and 196-2010). The MARIE study was supported by the Deutsche
Krebshilfe e.V. [70-2892-BR I], the Hamburg Cancer Society, the German
Cancer Research Center and the genotype work in part by the Federal
Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is
supported by grants from the Italian Association for Cancer Research
(AIRC) and by funds from the Italian citizens who allocated a 5/1000
share of their tax payment in support of the Fondazione IRCCS Istituto
Nazi (male Tumori, according to Italian laws (INT-Institutional
strategic projects '5 x 1000').; The MCBCS was supported by the NIH
grants [CA 122340, CAl28978] and a Specialized Program of Research
Excellence (SPORE) in Breast Cancer [CA116201], the Breast Cancer
Research Foundation and a generous gift from the David F. and Margaret
T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao
Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer
Council Victoria. The MCCS was further supported by Australian NHMRC
grants 209057, 251553 and 504711 and by infrastructure provided by
Cancer Council Victoria. The MEC was supported by NIH grants CA63464,
CA54281, CA098758 and CA132839, The work of MTLGEBCS was supported by
the Quebec Breast Cancer Foundation and the Ministry of Economic
Development, Innovation and Export Trade (grant PSR-SIIRI-701), The NBCS
was supported by grants from the Norwegian Research Council (155218/V40,
175240/S10 to A.L.B.D., FUGE-NFR 181600/V11 to V.N.K. and a Swizz Bridge
Award to A.L.B.D.). The OBCS was supported by research grants from the
Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Academy
of Finland, the University of Oulu and the Oulu University Hospital. The
ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505)
and the Biobanking and Biomolecular Resources Research Infrastructure
(BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the
National Cancer Institute, Department of Health and Human Services, USA,
pKARMA is a combination of the KARMA and LIBRO-1 studies, KARMA was
supported by Marit and Hans Rausings Initiative Against Breast Cancer.
KARMA and LIBRO-1 were supported the Cancer Risk Prediction Center
(CRisP; www.crispcenter.org), a Linnaeus Centre (Contract ID 70867902)
financed by the Swedish Research Council. The RBCS was funded by the
Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SASBAC was
supported by funding from the Agency for Science, Technology and
Research of Singapore (A*STAR), the US National Institute of Health
(NIH) and the Susan G. Komen Breast Cancer Foundation. K.C. was financed
by the Swedish Cancer Society (5128-B07-01PAF). The SBCS was supported
by Yorkshire Cancer Research S305PA. SEARCH is funded by a programme
grant from Cancer Research UK [C490/A10124] and supported by the UK
National Institute for Health Research Biomedical Research Centre at the
University of Cambridge. SKKDKFZS is supported by the DKFZ. Katarzyna
Jaworska is a fellow of International PhD program, Postgraduate School
of Molecular Medicine, Warsaw Medical University, supported by the
Polish Foundation of Science. The TNBCC was supported by the NIH grant
CAl28978, the Breast Cancer Research Foundation, Komen Foundation for
the Cure, the Ohio State University Comprehensive Cancer Center, the
Stefanie Spielman fund for Breast Cancer Research and a generous gift
from the David F. and Margaret T. Grohne Family Foundation and the Ting
Tsung and Wei Fong Chao Foundation. Part of the TNBCC (DEMOKRITOS) has
been co-financed by the European Union (European Social Fund-ESF) and
Greek national funds through the Operational Program 'Education and
Lifelong Learning' of the National Strategic Reference Framework
(NSRF)-Research Funding Program of the General Secretariat for Research
& Technology: ARISTEIA, The UKBGS is funded by Breakthrough Breast
Cancer and the Institute of Cancer Research (ICR). ICR acknowledges NHS
funding to the NIHR Biomedical Research Centre.
NR 44
TC 12
Z9 12
U1 1
U2 23
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD APR 1
PY 2014
VL 23
IS 7
BP 1934
EP 1946
DI 10.1093/hmg/ddt581
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AD5CA
UT WOS:000333267900022
PM 24242184
ER
PT J
AU Yao, C
Joehanes, R
Johnson, AD
Huan, TX
Esko, T
Ying, SX
Freedman, JE
Murabito, J
Lunetta, KL
Metspalu, A
Munson, PJ
Levy, D
AF Yao, Chen
Joehanes, Roby
Johnson, Andrew D.
Huan, Tianxiao
Esko, Tonu
Ying, Saixia
Freedman, Jane E.
Murabito, Joanne
Lunetta, Kathryn L.
Metspalu, Andres
Munson, Peter J.
Levy, Daniel
TI Sex- and age-interacting eQTLs in human complex diseases
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; TISSUE-SPECIFIC EXPRESSION; GLOBAL
GENE-EXPRESSION; MACULAR DEGENERATION; MULTIPLE-SCLEROSIS;
BLOOD-PRESSURE; X-CHROMOSOME; TRAITS; HEART; LOCI
AB Many complex human diseases exhibit sex or age differences in gene expression. However, the presence and the extent of genotype-specific variations in gene regulation are largely unknown. Here, we report results of a comprehensive analysis of expression regulation of genetic variation related to 11 672 complex disease-associated SNPs as a function of sex and age in whole-blood-derived RNA from 5254 individuals. At false discovery rate <0.05, we identified 14 sex- and 10 age-interacting expression quantitative trait loci (eQTLs). We show that these eQTLs are also associated with many sex- or age-associated traits. These findings provide important context regarding the regulation of phenotypes by genotype-environment interaction.
C1 [Yao, Chen; Joehanes, Roby; Johnson, Andrew D.; Huan, Tianxiao; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Yao, Chen; Joehanes, Roby; Johnson, Andrew D.; Huan, Tianxiao; Levy, Daniel] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Yao, Chen; Joehanes, Roby; Huan, Tianxiao; Levy, Daniel] NHLBI, Populat Res Branch, NIH, Bethesda, MD 20892 USA.
[Ying, Saixia; Munson, Peter J.] NIH, Math & Stat Comp Lab, Bethesda, MD 20892 USA.
[Freedman, Jane E.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[Murabito, Joanne] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Lunetta, Kathryn L.] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Esko, Tonu; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Esko, Tonu] Childrens Hosp Boston, Div Endocrinol, Boston, MA USA.
[Esko, Tonu] Broad Inst, Cambridge, MA USA.
[Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
RP Levy, D (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
EM levyd@nih.gov
RI Johnson, Andrew/G-6520-2013
FU National Institutes of Health (NIH) [N01-HC-25195]; FP7 grants [201 413,
245 536]; Estonian Government [SF0180142s08]; Ministries of Research and
Science and Social Affairs; University of Tartu in the framework of the
Center of Translational Genomics; European Union through the European
Regional Development Fund, in the framework of the Centre of Excellence
in Genomics
FX This work was supported by National Institutes of Health (NIH) contract
N01-HC-25195. EGCUT received financing by FP7 grants (201 413, 245 536),
also received targeted financing from the Estonian Government
(SF0180142s08) and direct funding from the Ministries of Research and
Science and Social Affairs, EGCUT studies are funded by the University
of Tartu in the framework of the Center of Translational Genomics and by
the European Union through the European Regional Development Fund, in
the framework of the Centre of Excellence in Genomics.
NR 62
TC 12
Z9 12
U1 0
U2 13
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD APR 1
PY 2014
VL 23
IS 7
BP 1947
EP 1956
DI 10.1093/hmg/ddt582
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AD5CA
UT WOS:000333267900023
PM 24242183
ER
PT J
AU Davidson, B
Abeler, VM
Forsund, M
Holth, A
Yang, YQ
Kobayashi, Y
Chen, L
Kristensen, GB
Shih, LM
Wang, TL
AF Davidson, Ben
Abeler, Vera Maria
Forsund, Mette
Holth, Arild
Yang, Yanqin
Kobayashi, Yusuke
Chen, Lily
Kristensen, Gunnar B.
Shih, Ie-Ming
Wang, Tian-Li
TI Gene expression signatures of primary and metastatic uterine
leiomyosarcoma
SO HUMAN PATHOLOGY
LA English
DT Article; Proceedings Paper
CT 104th Annual Meeting of the American-Association-for-Cancer-Research
(AACR)
CY APR 06-10, 2013
CL Washington, DC
SP Amer Assoc Canc Res
DE Gene expression array; Uterine leiomyosarcoma; Metastasis
ID COMPARATIVE GENOMIC HYBRIDIZATION; SOFT-TISSUE SARCOMAS;
IMMUNOHISTOCHEMISTRY; PROTEINS; TARGETS; TUMOR
AB Leiomyosarcoma (LMS) is the most common uterine sarcoma. Although the disease is relatively rare, it is responsible for considerable mortality due to frequent metastasis and chemoresistance. The molecular events related to LMS metastasis are unknown to date. The present study compared the global gene expression patterns of primary uterine LMSs and LMS metastases. Gene expression profiles of 13 primary and 15 metastatic uterine LMSs were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. To identify differently expressed genes between primary and metastatic tumors, we performed one-way analysis of variance with Benjamini-Hochberg correction. This led to identification of 203 unique probes that were significantly differentially expressed in the 2 tumor groups by greater than 1.58-fold with P < .01, of which 94 and 109 were overexpressed in primary and metastatic LMSs, respectively. Genes overexpressed in primary uterine LMSs included OSTN, NLGN4X, NLGN1, SLITRK4, MASP1, XRN2, ASS1, RORB, HRASLS, and TSPAN7. Genes overexpressed in LMS metastases included TNNT1, FOLR3, TDO2, CRYM, GJA1, TSPAN10, THBS1, SGK1, SHMT1, EGR2, and AGT. Quantitative real-time PCR confirmed significant anatomical site-related differences in FOLR3, OSTN, and NLGN4X levels; and immunohistochemistry showed significant differences in TDO2 expression. Gene expression profiling differentiates primary uterine LMSs from LMS metastases. The molecular signatures unique to primary and metastatic LMSs may aid in understanding tumor progression in this cancer and in providing a molecular basis for prognostic studies and therapeutic target discovery. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Davidson, Ben; Abeler, Vera Maria; Forsund, Mette; Holth, Arild] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Pathol, N-0424 Oslo, Norway.
[Davidson, Ben] Univ Oslo, Fac Med, N-0316 Oslo, Norway.
[Yang, Yanqin] NHLBI, Genom Core Facil, NIH, Bethesda, MD 20892 USA.
[Kobayashi, Yusuke; Chen, Lily; Shih, Ie-Ming; Wang, Tian-Li] Johns Hopkins Med Inst, Dept Gynecol, Baltimore, MD 21231 USA.
[Kobayashi, Yusuke; Chen, Lily; Shih, Ie-Ming; Wang, Tian-Li] Johns Hopkins Med Inst, Dept Obstet, Baltimore, MD 21231 USA.
[Kobayashi, Yusuke; Chen, Lily; Wang, Tian-Li] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21231 USA.
[Kristensen, Gunnar B.] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Gynecol Oncol, N-0424 Oslo, Norway.
[Kristensen, Gunnar B.] Oslo Univ Hosp, Norwegian Radium Hosp, Inst Med Informat, N-0424 Oslo, Norway.
[Shih, Ie-Ming] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21231 USA.
RP Davidson, B (reprint author), Norwegian Radium Hosp, Dept Pathol, N-0310 Oslo, Norway.
EM bend@medisin.uio.no; tlw@welch.jhu.edu
RI Chen, Li/P-5945-2014
FU NCI NIH HHS [R01 CA148826, R01CA148826]
NR 37
TC 16
Z9 16
U1 0
U2 9
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0046-8177
EI 1532-8392
J9 HUM PATHOL
JI Hum. Pathol.
PD APR
PY 2014
VL 45
IS 4
BP 691
EP 700
DI 10.1016/j.humpath.2013.11.003
PG 10
WC Pathology
SC Pathology
GA AE0MG
UT WOS:000333659800004
PM 24485798
ER
PT J
AU Vanderbeck, S
Bockhorst, J
Komorowski, R
Kleiner, DE
Gawrieh, S
AF Vanderbeck, Scott
Bockhorst, Joseph
Komorowski, Richard
Kleiner, David E.
Gawrieh, Samer
TI Automatic classification of white regions in liver biopsies by
supervised machine Learning
SO HUMAN PATHOLOGY
LA English
DT Article
DE NAFLD; Steatosis; Variability; Sensitivity and specificity; Digital
image analysis
ID FATTY LIVER; NONALCOHOLIC STEATOHEPATITIS; HEPATIC STEATOSIS; SAMPLING
VARIABILITY; SCORING SYSTEM; DISEASE; PREVALENCE; CIRRHOSIS; OUTCOMES
AB Automated assessment of histological features of non-alcoholic fatty liver disease (NAFLD) may reduce human variability and provide continuous rather than semiquantitative measurement of these features. As part of a larger effort, we perform automatic classification of steatosis, the cardinal feature of NAFLD, and other regions that manifest as white in images of hematoxylin and eosin stained liver biopsy sections. These regions include macrosteatosis, central veins, portal veins, portal arteries, sinusoids and bile ducts. Digital images of hematoxylin and eosin stained slides of 47 liver biopsies from patients with normal liver histology (n = 20) and NAFLD (n = 27) were obtained at 20x magnification. The images were analyzed using supervised machine learning classifiers created from annotations provided by two expert pathologists. The classification algorithm performs with 89% overall accuracy. It identified macrosteatosis, bile ducts, portal veins and sinusoids with high precision and recall (>= 82%). Identification of central veins and portal arteries was less robust but still good. The accuracy of the classifier in identifying macrosteatosis is the best reported. The accurate automated identification of macrosteatosis achieved with this algorithm has useful clinical and research-related applications. The accurate detection of liver microscopic anatomical landmarks may facilitate important subsequent tasks, such as localization of other histological lesions according to liver microscopic anatomy. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Vanderbeck, Scott; Bockhorst, Joseph] Univ Wisconsin, Dept Elect Engn & Comp Sci, Milwaukee, WI 53211 USA.
[Komorowski, Richard] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA.
[Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Gawrieh, Samer] Med Coll Wisconsin, Div Gastroenterol & Hepatol, Milwaukee, WI 53226 USA.
RP Gawrieh, S (reprint author), Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA.
EM sgawrieh@iu.edu
OI Kleiner, David/0000-0003-3442-4453
FU University of Wisconsin-Milwaukee Research Foundation [PRJ-39IB];
Intramural Research Program of the NIH, National Cancer Institute
FX This research was supported by the University of Wisconsin-Milwaukee
Research Foundation (J.B. and S.G.) grant number PRJ-39IB and in part by
the Intramural Research Program of the NIH, National Cancer Institute
(D.E.K.).
NR 27
TC 4
Z9 4
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0046-8177
EI 1532-8392
J9 HUM PATHOL
JI Hum. Pathol.
PD APR
PY 2014
VL 45
IS 4
BP 785
EP 792
DI 10.1016/j.humpath.2013.11.011
PG 8
WC Pathology
SC Pathology
GA AE0MG
UT WOS:000333659800014
PM 24565203
ER
PT J
AU Shearer, WT
Fleisher, TA
Buckley, RH
Ballas, Z
Ballow, M
Blaese, RM
Bonilla, FA
Conley, ME
Cunningham-Rundles, C
Filipovich, AH
Fuleihan, R
Gelfand, EW
Hernandez-Trujillo, V
Holland, SM
Hong, R
Lederman, HM
Malech, HL
Miles, S
Notarangelo, LD
Ochs, HD
Orange, JS
Puck, JM
Routes, JM
Stiehm, ER
Sullivan, K
Torgerson, T
Winkelstein, J
AF Shearer, William T.
Fleisher, Thomas A.
Buckley, Rebecca H.
Ballas, Zuhair
Ballow, Mark
Blaese, R. Michael
Bonilla, Francisco A.
Conley, Mary Ellen
Cunningham-Rundles, Charlotte
Filipovich, Alexandra H.
Fuleihan, Ramsay
Gelfand, Erwin W.
Hernandez-Trujillo, Vivian
Holland, Steven M.
Hong, Richard
Lederman, Howard M.
Malech, Harry L.
Miles, Stephen
Notarangelo, Luigi D.
Ochs, Hans D.
Orange, Jordan S.
Puck, Jennifer M.
Routes, John M.
Stiehm, E. Richard
Sullivan, Kathleen
Torgerson, Troy
Winkelstein, Jerry
CA Med Advisory Comm Immune Deficienc
TI Recommendations for live viral and bacterial vaccines in immunodeficient
patients and their close contacts
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Live viral and bacterial vaccines; primary immunodeficiency disease;
severe combined immunodeficiency disease; cellular immune reconstitution
ID STEM-CELL TRANSPLANTATION; POLIOVIRUS; VACCINATION; PERSISTENT; CHILDREN
AB The present uncertainty of which live viral or bacterial vaccines can be given to immunodeficient patients and the growing neglect of societal adherence to routine immunizations has prompted the Medical Advisory Committee of the Immune Deficiency Foundation to issue recommendations based on published literature and the collective experience of the committee members. These recommendations address the concern for immunodeficient patients acquiring infections from healthy subjects who have not been immunized or who are shedding live vaccine-derived viral or bacterial organisms. Such transmission of infectious agents can occur within the hospital, clinic, or home or at any public gathering. Collectively, we define this type of transmission as close-contact spread of infectious disease that is particularly relevant in patients with impaired immunity who might have an infection when exposed to subjects carrying vaccine-preventable infectious diseases or who have recently received a live vaccine. Immunodeficient patients who have received therapeutic hematopoietic stem transplantation are also at risk during the time when immune reconstitution is incomplete or while they are receiving immunosuppressive agents to prevent or treat graft-versus-host disease. This review recommends the general education of what is known about vaccine-preventable or vaccine-derived diseases being spread to immunodeficient patients at risk for close-contact spread of infection and describes the relative risks for a child with severe immunodeficiency. The review also recommends a balance between the need to protect vulnerable subjects and their social needs to integrate into society, attend school, and benefit from peer education.
C1 [Shearer, William T.; Orange, Jordan S.] Baylor Coll Med, Houston, TX 77030 USA.
[Shearer, William T.; Orange, Jordan S.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Fleisher, Thomas A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Buckley, Rebecca H.] Duke Univ, Sch Med, Durham, NC 27706 USA.
[Ballas, Zuhair] Univ Iowa, Iowa City, IA USA.
[Ballas, Zuhair] Iowa City Vet Affairs Med Ctr, Iowa City, IA USA.
[Ballow, Mark] SUNY Buffalo, Childrens Hosp Buffalo, Buffalo, NY USA.
[Blaese, R. Michael] Immune Deficiency Fdn, Columbia, SC USA.
[Bonilla, Francisco A.; Notarangelo, Luigi D.] Boston Childrens Hosp, Boston, MA USA.
[Conley, Mary Ellen] Univ Tennessee, Hlth Sci Ctr, Memphis, TN 38163 USA.
[Conley, Mary Ellen] St Jude Childrens Res Ctr, Memphis, TN USA.
[Cunningham-Rundles, Charlotte] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Filipovich, Alexandra H.] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Fuleihan, Ramsay] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA.
[Gelfand, Erwin W.] Natl Jewish Hlth, Denver, CO USA.
[Hernandez-Trujillo, Vivian] Miami Childrens Hosp, Miami, FL USA.
[Holland, Steven M.; Malech, Harry L.] Natl Inst Allergy & Infect Dis, Bethesda, MD USA.
[Lederman, Howard M.; Winkelstein, Jerry] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Ochs, Hans D.; Torgerson, Troy] Seattle Childrens Hosp, Seattle, WA USA.
[Puck, Jennifer M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Routes, John M.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA.
[Stiehm, E. Richard] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
[Sullivan, Kathleen] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
RP Shearer, WT (reprint author), Texas Childrens Hosp, Baylor Coll Med, Dept Pediat & Immunol, Allergy & Immunol Serv, 1102 Bates St,Suite 330, Houston, TX 77030 USA.
EM wtsheare@TexasChildrensHospital.org
RI Notarangelo, Luigi/F-9718-2016;
OI Notarangelo, Luigi/0000-0002-8335-0262; Malech,
Harry/0000-0001-5874-5775; orange, jordan/0000-0001-7117-7725
FU Intramural Research Program of the National Institutes of Health
Clinical Center; National Institute of Allergy and Infectious Diseases;
National Institutes of Health; Department of Health and Human Services;
NIH [USID Net NIH U24 P0027559, PIDTC NIH U54 A1082973]; Immune
Deficiency; Baxter; CSL Behring; Avant; Grifols; Immune Deficiency
Foundation; Pediatric Update; Biotest Pharmaceutical Corporation;
Sanofi; Merck; March of Dimes; Octapharma; Atlantic Research; BPL;
UpToDate; Baxter Biosciences; BD Bioscience
FX Supported by the Intramural Research Program of the National Institutes
of Health Clinical Center (T. A. F.) and the National Institute of
Allergy and Infectious Diseases (S. M. H. and H. L. M.). No official
endorsement of support by the National Institutes of Health or the
Department of Health and Human Services is intended or should be
inferred.; T. A. Fleisher is employed by the National Institutes of
Health (NIH) and has received royalties as the coeditor of a clinical
immunology textbook. R. H. Buckley is employed by the Duke University
Medical Center and has stock/stock options in various entities. Z.
Ballas has received research support from the NIH, has received
consultancy fees from Immune Deficiency, and receives royalties from
UpToDate. M. Ballow has received consultancy fees from Baxter and CSL
Behring; is employed by USF Health and Windom Allergy; has received
research support from CSL Behring; has received lecture fees from Avant,
Grifols, and CSL Behring; and has received payment for manuscript
preparation from Elsevier and UpToDate. R. M. Blaese has received
consultancy fees from the Immune Deficiency Foundation (Consulting
Medical Director and MAC member). F. A. Bonilla has received consultancy
fees from CSL Behring, has received lecture fees from Pediatric Update,
has received royalties from UpToDate, has received travel fees from the
Immune Deficiency Foundation, and is a member of the Blood Product
Advisory Committee (US Food and Drug Administration). E. W. Gelfand has
received consultancy fees from Biotest Pharmaceutical Corporation and
CSL Behring, has received research support from the NIH, and is employed
by National Jewish Health. V. Hernandez-Trujillo has received
consultancy fees from Sanofi and Baxter; has received lecture fees from
Merck, Sanofi, Baxter, and CSL; has received travel fees from Baxter; is
a spokesperson for Sanofi; and is a spokesperson and member of the
Claritin Council for Merck. S. Miles is a voluntary board member for a
medical advisory committee. L. D. Notarangelo is a board member for
Meyer Pediatric University Hospital in Florence, Italy, and for a
program in Molecular and Cellular Medicine; is employed by Boston
Children's Hospital; has received research support from the NIH and
March of Dimes; and receives royalties from UpToDate. H. D. Ochs is a
board member for DSMC and Sigma Tau and has received travel fees from
CSL Behring. J. S. Orange has received consultancy fees from Baxter, CSL
Behring, Octapharma, Atlantic Research, Grifols, and BPL; has provided
expert testimony for the State of Arizona; has received research support
from CSL Behring; has received lecture fees from Baxter; and has
received royalties from UpToDate. J. M. Puck has received research
support from the NIH and has received travel fees from the NIH (USID Net
NIH U24 P0027559 and PIDTC NIH U54 A1082973). E. R. Stiehm has received
consultancy fees from UpToDate, is employed by the UCLA Medical Center,
has received lecture fees and payment for manuscript preparation, and
has stock/stock options not related to this work. K. Sullivan has
received consultancy fees from the Immune Deficiency Foundation and
receives royalties from UpToDate. T. Torgerson has received consultancy
fees from Baxter Biosciences and BD Bioscience, has received research
support from Baxter Biosciences and CSL Behring, has received lecture
fees from Baxter Biosciences, and has received lecture fees from Baxter
Biosciences. The rest of the authors declare that they have no relevant
conflicts of interest.
NR 21
TC 27
Z9 27
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD APR
PY 2014
VL 133
IS 4
BP 961
EP 966
DI 10.1016/j.jaci.2013.11.043
PG 6
WC Allergy; Immunology
SC Allergy; Immunology
GA AD8QW
UT WOS:000333531700003
ER
PT J
AU Shearer, WT
Dunn, E
Notarangelo, LD
Dvorak, CC
Puck, JM
Logan, BR
Griffith, LM
Kohn, DB
O'Reilly, RJ
Fleisher, TA
Pai, SY
Martinez, CA
Buckley, RH
Cowan, MJ
AF Shearer, William T.
Dunn, Elizabeth
Notarangelo, Luigi D.
Dvorak, Christopher C.
Puck, Jennifer M.
Logan, Brent R.
Griffith, Linda M.
Kohn, Donald B.
O'Reilly, Richard J.
Fleisher, Thomas A.
Pai, Sung-Yun
Martinez, Caridad A.
Buckley, Rebecca H.
Cowan, Morton J.
TI Establishing diagnostic criteria for severe combined immunodeficiency
disease (SCID), leaky SCID, and Omenn syndrome: The Primary Immune
Deficiency Treatment Consortium experience
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Allogeneic hematopoietic cell transplantation; gene therapy; primary
immunodeficiency; clinical trial
ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; GENE-THERAPY;
LIGASE-IV; MUTATIONS; RECONSTITUTION; OUTCOMES; COMPLEX; ANTIGEN; HUMANS
AB Background: The approach to the diagnosis of severe combined immunodeficiency disease (SCID) and related disorders varies among institutions and countries.
Objectives: The Primary Immune Deficiency Treatment Consortium attempted to develop a uniform set of criteria for diagnosing SCID and related disorders and has evaluated the results as part of a retrospective study of SCID in North America.
Methods: Clinical records from 2000 through 2009 at 27 centers in North America were collected on 332 children treated with hematopoietic stem cell transplantation (HCT), enzyme replacement therapy, or gene therapy for SCID and related disorders. Eligibility for inclusion in the study and classification into disease groups were established by using set criteria and applied by an expert review group.
Results: Two hundred eighty-five (86%) of the patients were determined to be eligible, and 47 (14%) were not eligible. Of the 285 eligible patients, 84% were classified as having typical SCID; 13% were classified as having leaky SCID, Omenn syndrome, or reticular dysgenesis; and 3% had a history of enzyme replacement or gene therapy. Detection of a genotype predicting an SCID phenotype was accepted for eligibility. Reasons for noneligibility were failure to demonstrate either impaired lymphocyte proliferation or maternal T-cell engraftment. Overall (n = 332) rates of testing were as follows: proliferation to PHA, 77%; maternal engraftment, 35%; and genotype, 79% (mutation identified in 62%).
Conclusion: Lack of complete laboratory evaluation of patients before HCT presents a significant barrier to definitive diagnosis of SCID and related disorders and prevented inclusion of subjects in our observational HCT study. This lesson is critical for patient care, as well as the design of future prospective treatment studies for such children because a well-defined and consistent study population is important for precision in outcomes analysis.
C1 [Shearer, William T.] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Sect Immunol Allergy & Rheumatol, Houston, TX 77030 USA.
[Dunn, Elizabeth; Dvorak, Christopher C.; Puck, Jennifer M.; Cowan, Morton J.] Univ Calif San Francisco, Div Pediat Allergy Immunol & Blood & Marrow Trans, Benioff Childrens Hosp, San Francisco, CA 94143 USA.
[Notarangelo, Luigi D.] Med Coll Wisconsin, Div Biostat, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Logan, Brent R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Immunol, Boston, MA USA.
[Logan, Brent R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA USA.
[Logan, Brent R.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA USA.
[Griffith, Linda M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA.
[Kohn, Donald B.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA.
[Kohn, Donald B.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA USA.
[O'Reilly, Richard J.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA.
[Fleisher, Thomas A.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA.
[Pai, Sung-Yun] Dana Farber Canc Inst, Div Hematol & Oncol, Boston Childrens Hosp, Boston, MA 02115 USA.
[Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Martinez, Caridad A.] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Ctr Canc, Houston, TX 77030 USA.
[Buckley, Rebecca H.] Duke Univ, Med Ctr, Dept Pediat & Immunol, Durham, NC 27706 USA.
RP Shearer, WT (reprint author), Texas Childrens Hosp, Baylor Coll Med, Immunol Allergy & Rheumatol Serv, 1102 Bates St,Suite FC330, Houston, TX 77030 USA.
EM wtshearer@texaschildrens.org
RI Notarangelo, Luigi/F-9718-2016; Kohn, Donald/N-5085-2016
OI Notarangelo, Luigi/0000-0002-8335-0262; Kohn, Donald/0000-0003-1840-6087
FU Division of Allergy, Immunology and Transplantation, National Institute
of Allergy and Infectious Diseases (DAIT-NIAID); Intramural Research
Programs of the National Human Genome Research Institute (NHGRI);
National Institute of Allergy and Infectious Diseases; Office of Rare
Diseases Research, National Center for Advancing Translational Sciences,
National Institutes of Health (ORDR-NACTS-NIH), Bethesda, Maryland
[U54-AI082973, U54-NS064808, R13-AI094943]; Immune Deficiency
Foundation, Towson, Md; Jeffrey Modell Foundation, New York, NY; Robert
A. Good Immunology Society, St Petersburg, Fla; John P. McGovern
Foundation, Houston, Tex; David Center, Texas Children's Hospital,
Baylor College of Medicine, Houston, Tex; Baxter International,
Deerfield, Ill; CSL Behring, King of Prussia, Pa; Sigma-Tau
Pharmaceuticals, Gaithersburg, Md; DAIT-NIAID; NHGRI NIAID;
ORDR-NCATS-NIH; National Institutes of Health (NIH); NIH; March of
Dimes; Jeffrey Modell Foundation; NIAID; NIH-Gene Therapy Resource
Program; [NCI23766]
FX The Primary Immune Deficiency Treatment Consortium (PIDTC) is supported
by the Division of Allergy, Immunology and Transplantation, National
Institute of Allergy and Infectious Diseases (DAIT-NIAID); the
Intramural Research Programs of the National Human Genome Research
Institute (NHGRI) and the National Institute of Allergy and Infectious
Diseases; and the Office of Rare Diseases Research, National Center for
Advancing Translational Sciences, National Institutes of Health
(ORDR-NACTS-NIH), Bethesda, Maryland: U54-AI082973 (PI: M. J. Cowan),
U54-NS064808 (PI: J. P. Krischer), and R13-AI094943 (PIs: M. J. Cowan
and L. D. Notarangelo). This manuscript was presented at the PIDTC Third
Annual Scientific Workshop, Houston, Tex, May 2-4, 2013, supported in
part by the Immune Deficiency Foundation, Towson, Md; the Jeffrey Modell
Foundation, New York, NY; the Robert A. Good Immunology Society, St
Petersburg, Fla; the John P. McGovern Foundation, Houston, Tex; the
David Center, Texas Children's Hospital, Baylor College of Medicine,
Houston, Tex; Baxter International, Deerfield, Ill; CSL Behring, King of
Prussia, Pa; and Sigma-Tau Pharmaceuticals, Gaithersburg, Md. The
opinions expressed are those of the authors and do not represent the
position of the National Institute of Allergy and Infectious Diseases,
the National Human Genome Research Institute, the Office of Rare
Diseases Research, the National Center for Advancing Translational
Sciences, the National Institutes of Health, or the US Government.; W.
T. Shearer has received research support from DAIT-NIAID, NHGRI NIAID,
and ORDR-NCATS-NIH; has received travel support from the PIDTC Workshop;
is employed by Baylor College of Medicine; and has grants/grants pending
with the National Institutes of Health (NIH). E. Dunn has received
research support from DAIT-NIAID, NHGRI NIAID, and ORDR-NCATS-NIH; has
received travel support from the PIDTC Scientific Workshop; is employed
by the University of California-San Francisco (UCSF); and has
grants/grants pending from the NIH. L. D. Notarangelo has received
research support from the NIH, March of Dimes, and the Jeffrey Modell
Foundation; is a board member on the Immune Disease Institute, the Meyer
Pediatric Hospital, DMC, Watermark and DMC, NovImmune, Board of
Scientific Counselors for the NIAID and NIH, is an Associate Editor for
the Journal of Allergy and Clinical Immunology, is an Associate Editor
for Clinical Immunology; is employed by Children's Hospital Boston; and
receives royalties from UpToDate. C. C. Dvorak has received research
support from DAIT-NIAID, NHGRI NIAID, and ORDR-NCATS-NIH and has
received travel support from DAIT-NIAID, NHGR NIAID, and ORDR-NCATS-NIH.
J. M. Puck has received research support from DAIT-NIAID, NHGRI NIAID,
and ORDR-NCATS-NIH; has received travel support from the PIDTC Workshop;
is employed by UCSF; has grants/grants pending from the NIH; and
receives royalties from a published textbook. B. R. Logan has received
research support from the NIAID. L. M. Griffith is a medical officer for
the NIAID and is employed by the NIH. D. B. Kohn has received travel
support from the PIDTC. R. J. O'Reilly has received research support
from the NIAID for the PIDTC and NCI23766, is employed by MSKCC, has
provided expert testimony for Miltenyi Biotech, and has patents pending
for WT1 peptides. S.-Y. Pai has received grants from DAIT-NIAID, has
received support for travel to meetings for study or other purposes from
the PIDTC Workshop, is employed by the Boston Children's Hospital, and
has grants/grants pending from NIH-Gene Therapy Resource Program. R. H.
Buckley has received grants from the NIAID, has received support for
travel to meetings from the PIDTC, is employed by the Duke University
Medical Center, receives royalties from UpToDate, has stock/stock option
in TIAA/CREF, and receives travel expenses from the Foundation for
Primary immunodeficiency disease. M. J. Cowan has received research
support from DAIT-NIAID, NHGRI NIAID, ORDR-NCATS-NIH, and the NIH; has
received travel support to PIDTC workshops; and is employed by the
University of California. These authors declare that they have no
relevant conflicts of interest.
NR 44
TC 48
Z9 48
U1 3
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD APR
PY 2014
VL 133
IS 4
BP 1092
EP 1098
DI 10.1016/j.jaci.2013.09.044
PG 7
WC Allergy; Immunology
SC Allergy; Immunology
GA AD8QW
UT WOS:000333531700020
PM 24290292
ER
PT J
AU Yu, XM
Almeida, JR
Darko, S
van der Burg, M
DeRavin, SS
Malech, H
Gennery, A
Chinn, I
Markert, ML
Douek, DC
Milner, JD
AF Yu, Xiaomin
Almeida, Jorge R.
Darko, Sam
van der Burg, Mirjam
DeRavin, Suk See
Malech, Harry
Gennery, Andrew
Chinn, Ivan
Markert, Mary Louise
Douek, Daniel C.
Milner, Joshua D.
TI Human syndromes of immunodeficiency and dysregulation are characterized
by distinct defects in T-cell receptor repertoire development
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE T-cell receptor; recombination activating gene; Omenn syndrome; T-cell
receptor sequencing
ID OMENN-SYNDROME; V(D)J RECOMBINATION; THYMUS TRANSPLANTATION;
DIGEORGE-SYNDROME; IMMUNE FUNCTION; RAG MUTATIONS; DIVERSITY;
LYMPHOCYTES
AB Background: Human immunodeficiencies characterized by hypomorphic mutations in critical developmental and signaling pathway genes allow for the dissection of the role of these genes in the development of the T-cell receptor (TCR) repertoire and the correlation of alterations of the TCR repertoire with diverse clinical phenotypes.
Objective: The presence of T cells in patients with Omenn syndrome (OS) and patients with atypical presentations of severe combined immunodeficiency gene mutations presents an opportunity to study the effects of the causal genes on TCR repertoires and provides a window into the clinical heterogeneity observed.
Methods: We performed deep sequencing of TCR beta complementarity-determining region 3 (CDR3) regions in subjects with a series of immune dysregulatory conditions caused by mutations in recombination activating gene 1/2 (RAG 1/2), IL-2 receptor gamma (IL2RG), and zeta chain-associated protein kinase 70 (ZAP70); a patient with atypical DiGeorge syndrome; and healthy control subjects.
Results: We found that patients with OS had marked reductions in TCRb diversity compared with control subjects, as expected. Patients with atypical presentations of RAG or IL2RG mutations associated with autoimmunity and granulomatous disease did not have altered overall diversity but instead had skewed V-J pairing and skewed CDR3 amino acid use. Although germline TCRs were more abundant and clonally expanded in patients with OS, nongermline sequences were expanded as well. TCRb from patients with RAG mutations had less junctional diversity and smaller CDR3s than patients with OS caused by other gene mutations and healthy control subjects but relatively similar CDR3 amino acid use.
Conclusions: High-throughput TCR sequencing of rare immune disorders has demonstrated that quantitative TCR diversity can appear normal despite qualitative changes in repertoire and strongly suggests that in human subjects RAG enzymatic function might be necessary for normal CDR3 junctional diversity.
C1 [Yu, Xiaomin; Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Almeida, Jorge R.; Darko, Sam; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[DeRavin, Suk See; Malech, Harry] NIAID, Lab Host Defenses, NIH, Bethesda, MD 20892 USA.
[van der Burg, Mirjam] Univ Med Ctr Rotterdam, Dept Immunol, Erasmus MC, Rotterdam, Netherlands.
[Gennery, Andrew] Newcastle Univ, Dept Pediat, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Gennery, Andrew] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Chinn, Ivan; Markert, Mary Louise] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA.
[Markert, Mary Louise] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA.
RP Douek, DC (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Rm 3504,40 Convent Dr, Bethesda, MD 20892 USA.
EM ddouek@mail.nih.gov; jdmilner@niaid.nih.gov
OI Malech, Harry/0000-0001-5874-5775
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; ZonMW; National
Institutes of Health
FX Supported by the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health.; M. van
der Burg has received research support from ZonMW. I. Chinn has received
research support from the National Institutes of Health. The rest of the
authors declare that they have no relevant conflicts of interest.
NR 24
TC 12
Z9 12
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD APR
PY 2014
VL 133
IS 4
BP 1109
EP +
DI 10.1016/j.jaci.2013.11.018
PG 21
WC Allergy; Immunology
SC Allergy; Immunology
GA AD8QW
UT WOS:000333531700022
PM 24406074
ER
PT J
AU Marciano, BE
Huang, CY
Joshi, G
Rezaei, N
Carvalho, BC
Allwood, Z
Ikinciogullari, A
Reda, SM
Gennery, A
Thon, V
Espinosa-Rosales, F
Al-Herz, W
Porras, O
Shcherbina, A
Szaflarska, A
Kilic, S
Franco, JL
Raccio, ACG
Roxo, P
Esteves, I
Galal, N
Grumach, AS
Al-Tamemi, S
Yildiran, A
Orellana, JC
Yamada, M
Morio, T
Liberatore, D
Ohtsuka, Y
Lau, YL
Nishikomori, R
Torres-Lozano, C
Mazzucchelli, JTL
Vilela, MMS
Tavares, FS
Cunha, L
Pinto, JA
Espinosa-Padilla, SE
Hernandez-Nieto, L
Elfeky, RA
Ariga, T
Toshio, H
Dogu, F
Cipe, F
Formankova, R
Nunez-Nunez, ME
Bezrodnik, L
Marques, JG
Pereira, MI
Listello, V
Slatter, MA
Nademi, Z
Kowalczyk, D
Fleisher, TA
Davies, G
Neven, B
Rosenzweig, SD
AF Marciano, Beatriz E.
Huang, Chiung-Yu
Joshi, Gyan
Rezaei, Nima
Carvalho, Beatriz Costa
Allwood, Zoe
Ikinciogullari, Aydan
Reda, Shereen M.
Gennery, Andrew
Thon, Vojtech
Espinosa-Rosales, Francisco
Al-Herz, Waleed
Porras, Oscar
Shcherbina, Anna
Szaflarska, Anna
Kilic, Sebnem
Franco, Jose L.
Gomez Raccio, Andrea C.
Roxo, Persio, Jr.
Esteves, Isabel
Galal, Nermeen
Grumach, Anete Sevciovic
Al-Tamemi, Salem
Yildiran, Alisan
Orellana, Julio C.
Yamada, Masafumi
Morio, Tomohiro
Liberatore, Diana
Ohtsuka, Yoshitoshi
Lau, Yu-Lung
Nishikomori, Ryuta
Torres-Lozano, Carlos
Mazzucchelli, Juliana T. L.
Vilela, Maria M. S.
Tavares, Fabiola S.
Cunha, Luciana
Pinto, Jorge A.
Espinosa-Padilla, Sara E.
Hernandez-Nieto, Leticia
Elfeky, Reem A.
Ariga, Tadashi
Toshio, Heike
Dogu, Figen
Cipe, Funda
Formankova, Renata
Enriqueta Nunez-Nunez, M.
Bezrodnik, Liliana
Marques, Jose Goncalo
Pereira, Maria I.
Listello, Viviana
Slatter, Mary A.
Nademi, Zohreh
Kowalczyk, Danuta
Fleisher, Thomas A.
Davies, Graham
Neven, Benedicte
Rosenzweig, Sergio D.
TI BCG vaccination in patients with severe combined immunodeficiency:
Complications, risks, and vaccination policies
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Primary immunodeficiency; severe combined immunodeficiency; vaccine;
BCG; mycobacteria; newborn screening; hematopoietic stem cell
transplant; immune reconstitution syndrome
ID BACILLUS-CALMETTE-GUERIN; CENTRAL-NERVOUS-SYSTEM; IMMUNOCOMPROMISED
CHILDREN; TUBERCULOUS MENINGITIS; VACCINES; INFANTS
AB Background: Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected.
Objectives: We sought to describe the complications and risks associated with BCG vaccination in patients with SCID.
Methods: An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed.
Results: Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (<= 3 1 month) showed an increased prevalence of complications (P = 5.006) and death caused by BCG-associated complications (P < .0001). The odds of experiencing complications among patients with T-cell numbers of 250/mu L or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than among those with T-cell numbers of greater than 250/mL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P < .0001).
Conclusions: BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.
C1 [Marciano, Beatriz E.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Huang, Chiung-Yu; Joshi, Gyan] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Rezaei, Nima] Univ Tehran Med Sci, Pediat Ctr Excellence, Childrens Med Ctr Hosp, Tehran, Iran.
[Carvalho, Beatriz Costa; Mazzucchelli, Juliana T. L.; Vilela, Maria M. S.; Tavares, Fabiola S.] Univ Fed Sao Paulo, Dept Pediat, Sao Paulo, Brazil.
[Allwood, Zoe; Davies, Graham] Great Ormond St Hosp Sick Children, Dept Immunol, London, England.
[Ikinciogullari, Aydan; Dogu, Figen; Cipe, Funda] Ankara Univ, Sch Med, Dept Pediat Immunol & Allergy, TR-06100 Ankara, Turkey.
[Reda, Shereen M.; Elfeky, Reem A.] Ain Shams Univ, Dept Pediat Allergy & Immunol, Childrens Hosp, Cairo, Egypt.
[Gennery, Andrew; Slatter, Mary A.; Nademi, Zohreh] Great North Childrens Hosp, Paediat Immunol Dept, Newcastle Upon Tyne, Tyne & Wear, England.
[Thon, Vojtech] Masaryk Univ, Dept Clin Immunol & Allergy, Fac Med, St Annes Univ Hosp, Brno, Czech Republic.
[Espinosa-Rosales, Francisco; Espinosa-Padilla, Sara E.; Hernandez-Nieto, Leticia] Natl Inst Pediat, Mexico City, DF, Mexico.
[Al-Herz, Waleed] Kuwait Univ, Fac Med, Dept Pediat, Al Sabah Hosp, Kuwait, Kuwait.
[Porras, Oscar] Natl Childrens Hosp Dr Carlos Saenz Herrera, Dept Immunol & Rheumatol, San Jose, Costa Rica.
[Shcherbina, Anna] Ctr Pediat Hematol Oncol & Immunol, Dept Clin Immunol, Moscow, Russia.
[Szaflarska, Anna; Kowalczyk, Danuta] Childrens Univ Hosp, Dept Clin Immunol & Transplantol, Krakow, Poland.
[Kilic, Sebnem] Uludag Univ, Fac Med, Pediat Immunol Div, Bursa, Turkey.
[Franco, Jose L.] Univ Antioquia, Primary Immunodeficiency Grp, Medellin, Colombia.
[Gomez Raccio, Andrea C.; Bezrodnik, Liliana] Childrens Hosp Ricardo Gutierrez, Immunol Unit, Buenos Aires, DF, Argentina.
[Roxo, Persio, Jr.] Univ Sao Paulo, Fac Med Ribeirao Preto, BR-05508 Sao Paulo, Brazil.
[Esteves, Isabel; Marques, Jose Goncalo] Hosp Santa Maria, Primary Immunodeficiency Ctr, Lisbon Acad Ctr, Lisbon, Portugal.
[Galal, Nermeen] Cairo Univ, Santo Andre, SP, Brazil.
[Grumach, Anete Sevciovic] ABC, Fac Med, Sao Paulo, Brazil.
[Al-Tamemi, Salem] Sultan Qaboos Univ Hosp, Dept Child Hlth, Muscat, Oman.
[Yildiran, Alisan] Ondokuz Mayis Univ, Dept Pediat Immunol, Atakum, Samsun, Turkey.
[Orellana, Julio C.; Pereira, Maria I.; Listello, Viviana] Santisima Trinidad Childrens Hosp, Div Allergy & Clin Immunol, Cordoba, Argentina.
[Yamada, Masafumi; Ariga, Tadashi] Hokkaido Univ, Dept Pediat, Grad Sch Med, Sapporo, Hokkaido, Japan.
[Morio, Tomohiro] Tokyo Med & Dent Univ, Tokyo, Japan.
[Liberatore, Diana] Italian Hosp, Buenos Aires, DF, Argentina.
[Ohtsuka, Yoshitoshi] Hyogo Coll Med, Nishinomiya, Hyogo, Japan.
[Lau, Yu-Lung] Univ Hong Kong, Dept Pediat & Adolescent Med, LKS Fac Med, Hong Kong, Hong Kong, Peoples R China.
[Nishikomori, Ryuta; Toshio, Heike] Kyoto Univ Hosp, Dept Pediat, Kyoto, Japan.
[Torres-Lozano, Carlos; Enriqueta Nunez-Nunez, M.] Western Natl Med Ctr, Dept Clin Immunol & Allergol, Guadalajara, Jalisco, Mexico.
[Cunha, Luciana; Pinto, Jorge A.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil.
[Formankova, Renata] Charles Univ Prague, Prague, Czech Republic.
[Formankova, Renata] Univ Hosp Motol, Prague, Czech Republic.
[Fleisher, Thomas A.] NIH, Serv Immunol, DLM CC, Bethesda, MD 20892 USA.
[Neven, Benedicte] Hop Necker Enfants Malad, Immunol Hematol & Rheumatol Serv, Paris, France.
[Rosenzweig, Sergio D.] NIAID, Primary Immunodeficiency Clin, LHD, NIH, Bethesda, MD 20892 USA.
[Rosenzweig, Sergio D.] NIAID, Infect Dis Susceptibil Unit, NIH, Bethesda, MD 20892 USA.
RP Rosenzweig, SD (reprint author), NIH, Serv Immunol, DLM CC, 10 Ctr Dr,Bldg 10,2C410F, Bethesda, MD 20892 USA.
EM srosenzweig@cc.nih.gov
RI Rezaei, Nima/B-4245-2008; Vilela, Maria Marluce /G-3916-2013;
OI Rezaei, Nima/0000-0002-3836-1827; Grumach, Anete/0000-0002-9803-0309
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Disease; European Community
[201549 (EURO-PADnet HEALTH-F2-2008-201549)]; Tehran University Med Sci;
American Academy of Allergy, Asthma & Immunology (AAAAI) Young
Investigator Award; EURO-PADnet HEALTH [F2-2008-201549]; Baxter;
Kedrion; Grifols; SHIRE; CSL; Japan Science and Technology Agency;
Ministry of Education, Culture, and Sport; Ministry of Health, Labour,
and Welfare in Japan; Abbvie; CSL Behring; Chugai Pharmaceutical; Meiji
Pharmaceuticals; Teijin Pharma; Toray Medical; InPractice; UpToDate
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Institute of Allergy and Infectious Disease. V. T.
was supported by the European Community's Seventh Framework Program
FP7/2007-2013 under grant agreement no. 201549 (EURO-PADnet
HEALTH-F2-2008-201549).; N. Rezaei is employed by and has received
research support from Tehran University Med Sci, has received royalties
from Springer, and has been supported by an American Academy of Allergy,
Asthma & Immunology (AAAAI) Young Investigator Award. B. Costa Carvalho
has received payment for development of educational presentations from
the Federal University of Sao Paulo (FAPESP) and has received travel
support from Octapharma. V. Thon has received research support from
EURO-PADnet HEALTH (F2-2008-201549). J. L. Franco has received
consultancy fees from Baxter and Kedrion and has received lecture fees
from Grifols. A. Sevciovic Grumach is a board member for Latin American
Society for Immunodeficiencies and has received consultancy fees and
lecture fees from SHIRE and CSL. T. Morio has received grant-in-aids for
scientific research from the Japan Science and Technology Agency; the
Ministry of Education, Culture, and Sport; and the Ministry of Health,
Labour, and Welfare in Japan and has received lecture fees from Abbvie,
CSL Behring, Chugai Pharmaceutical, Meiji Pharmaceuticals, Teijin
Pharma, and Toray Medical. S. D. Rosenzweig has received consultancy
fees from InPractice and UpToDate. The rest of the authors declare that
they have no relevant conflicts of interest.
NR 29
TC 32
Z9 39
U1 0
U2 15
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD APR
PY 2014
VL 133
IS 4
BP 1134
EP 1141
DI 10.1016/j.jaci.2014.02.028
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA AD8QW
UT WOS:000333531700025
PM 24679470
ER
PT J
AU Menard, L
Cantaert, T
Chamberlain, N
Tangye, SG
Riminton, S
Church, JA
Klion, A
Cunningham-Rundles, C
Nichols, KE
Meffre, E
AF Menard, Laurence
Cantaert, Tineke
Chamberlain, Nicolas
Tangye, Stuart G.
Riminton, Sean
Church, Joseph A.
Klion, Amy
Cunningham-Rundles, Charlotte
Nichols, Kim E.
Meffre, Eric
TI Signaling lymphocytic activation molecule (SLAM)/SLAM-associated protein
pathway regulates human B-cell tolerance
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE SLAM-associated protein; signaling lymphocytic activation molecule;
B-cell tolerance; regulatory T cells
ID LINKED LYMPHOPROLIFERATIVE-DISEASE; INVARIANT NKT CELLS; T-CELLS;
HUMORAL IMMUNITY; ENCODING GENE; SAP; SLAM; ASSOCIATION; DEFICIENCY;
MICE
AB Background: Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) can mediate the function of SLAM molecules, which have been proposed to be involved in the development of autoimmunity in mice.
Objective: We sought to determine whether the SLAM/SAP pathway regulates the establishment of human B-cell tolerance and what mechanisms of B-cell tolerance could be affected by SAP deficiency.
Methods: We tested the reactivity of antibodies isolated from single B cells from SAP-deficient patients with X-linked lymphoproliferative disease (XLP). The expressions of SAP and SLAM family members were assessed in human bone marrow-developing B cells. We also analyzed regulatory T (Treg) cell function in patients with XLP and healthy control subjects.
Results: We found that new emigrant/transitional B cells from patients with XLP were enriched in autoreactive clones, revealing a defective central B-cell tolerance checkpoint in the absence of functional SAP. In agreement with a B cell-intrinsic regulation of central tolerance, we identified SAP expression in a discrete subset of bone marrow immature B cells. SAP colocalized with SLAMF6 only in association with clustered B-cell receptors likely recognizing self-antigens, suggesting that SLAM/SAP regulate B-cell receptor-mediated central tolerance. In addition, patients with XLP displayed defective peripheral B-cell tolerance, which is normally controlled by Treg cells. Treg cells in patients with XLP seem functional, but SAP-deficient T cells were resistant to Treg cell-mediated suppression. Indeed, SAP-deficient T cells were hyperresponsive to T-cell receptor stimulation, which resulted in increased secretion of IL-2, IFN-gamma, and TNF-alpha.
Conclusions: SAP expression is required for the counterselection of developing autoreactive B cells and prevents their T cell-dependent accumulation in the periphery.
C1 [Menard, Laurence; Cantaert, Tineke; Chamberlain, Nicolas; Meffre, Eric] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06511 USA.
[Tangye, Stuart G.] Univ New S Wales, Garvan Inst Med Res, Program Immunol, Darlinghurst, NSW, Australia.
[Tangye, Stuart G.] Univ New S Wales, St Vincents Clin Sch, Darlinghurst, NSW, Australia.
[Riminton, Sean] Concord Hosp, Dept Immunol, Sydney, NSW, Australia.
[Church, Joseph A.] Univ So Calif, Childrens Hosp Los Angeles, Div Clin Immunol & Allergy, Los Angeles, CA USA.
[Church, Joseph A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Klion, Amy] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Cunningham-Rundles, Charlotte] Mt Sinai Sch Med, Inst Immunol, Dept Med, New York, NY USA.
[Nichols, Kim E.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
RP Meffre, E (reprint author), Yale Univ, Sch Med, 300 George St, New Haven, CT 06511 USA.
EM eric.meffre@yale.edu
RI Tangye, Stuart/H-4023-2014;
OI Klion, Amy/0000-0002-4986-5326
FU National Institutes of Health (NIH)/National Institute of Allergy and
Infectious Diseases (NAID) [AI061093, AI071087, AI082713, AI095848, T32
AI089704]; Division of Intramural Research, NIH/NIAID; Rubicon grant
from The Netherlands Organization for Scientific Research
FX Supported by National Institutes of Health (NIH)/National Institute of
Allergy and Infectious Diseases (NAID) grants AI061093, AI071087,
AI082713, AI095848 (to E. M.), and T32 AI089704 (to L. M.); the Division
of Intramural Research, NIH/NIAID (to A. K.); and a Rubicon grant from
The Netherlands Organization for Scientific Research (to T.C.).
NR 49
TC 15
Z9 15
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD APR
PY 2014
VL 133
IS 4
BP 1149
EP 1161
DI 10.1016/j.jaci.2013.10.051
PG 13
WC Allergy; Immunology
SC Allergy; Immunology
GA AD8QW
UT WOS:000333531700027
PM 24373350
ER
PT J
AU Chen, YYK
Khoury, P
Ware, JM
Holland-Thomas, NC
Stoddard, JL
Gurprasad, S
Waldner, AJ
Klion, AD
AF Chen, Yun-Yun K.
Khoury, Paneez
Ware, JeanAnne M.
Holland-Thomas, Nicole C.
Stoddard, Jennifer L.
Gurprasad, Shakuntala
Waldner, Amy J.
Klion, Amy D.
TI Marked and persistent eosinophilia in the absence of clinical
manifestations
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Eosinophil; hypereosinophilic syndrome; cytokine; pathogenesis
ID HYPEREOSINOPHILIC SYNDROME; CLASSIFICATION; VARIANT
AB Background: Although most patients with hypereosinophilic syndromes (HES) present with clinical signs and symptoms attributable to eosinophilic tissue infiltration, some untreated patients remain asymptomatic or have signs and symptoms, such as allergic rhinitis, for which the relationship to peripheral eosinophilia is unclear (hypereosinophilia of unknown significance [HEUS]).
Objective: To identify and characterize subjects with HEUS of 5 years duration or more as compared to untreated patients with symptomatic HES and healthy normal volunteers.
Methods: All subjects with eosinophilia underwent yearly evaluation, including a standardized clinical evaluation, whole blood flow cytometry to assess lymphocyte subsets and eosinophil activation, and serum collection. Peripheral blood mononuclear cells were cultured overnight with and without phorbol 12-myristate 13-acetate/ionomycin. Cytokines and chemokines were measured in serum and cell supernatants, and mRNA expression was assessed by using quantitative real-time PCR.
Results: Eight of the 210 subjects referred for the evaluation of eosinophilia (absolute eosinophil count [AEC] > 1500/mu L) met the criteria for HEUS of 5 years duration or more (range, 7-29 years). Peak eosinophil count and surface expression of eosinophil activation markers were similar in subjects with HEUS and in untreated subjects with platelet-derived growth factor alpha-negative HES (n 5 28). Aberrant or clonal T-cell populations were identified in 50% of the subjects with HEUS as compared to 29% of the subjects with HES (P = .12). Increased levels of IL-5, GM-CSF, IL-9, and IL-17A were also comparable in subjects with HEUS and HES. Serum levels of IgE and IL-13 were significantly increased only in subjects with HES.
Conclusions: A small number of patients with persistent peripheral eosinophilia (AEC > 1500/mu L) appear to have clinically benign disease.
C1 [Chen, Yun-Yun K.; Khoury, Paneez; Ware, JeanAnne M.; Waldner, Amy J.; Klion, Amy D.] NIAID, Eosinophil Pathol Unit, Parasit Dis Lab, Frederick, MD USA.
[Holland-Thomas, Nicole C.] SAIC Frederick Inc, Natl Lab Canc Res, Parasit Dis Lab, Clin Res Directorate CMRP, Frederick, MD USA.
[Stoddard, Jennifer L.; Gurprasad, Shakuntala] NIH, Dept Lab Med, Warren Magnusson Clin Ctr, Bethesda, MD 20892 USA.
RP Klion, AD (reprint author), NIH, Parasit Dis Lab, Bldg 4,Rm B1-28,4 Mem Dr, Bethesda, MD 20892 USA.
EM aklion@nih.gov
OI Klion, Amy/0000-0002-4986-5326
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH)
[NCT00001406, NCT00090662]; National Cancer Institute, NIH
[HHSN2610080001E]; NIAID
FX This research was supported by the Division of Intramural Research of
the National Institute of Allergy and Infectious Diseases (NIAID),
National Institutes of Health (NIH; Clinical Trials NCT00001406 and
NCT00090662). This project has been funded in whole or in part with
federal funds from the National Cancer Institute, NIH, under contract
no. HHSN2610080001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US government. This
research was supported in part by the NIAID.
NR 15
TC 14
Z9 14
U1 1
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD APR
PY 2014
VL 133
IS 4
BP 1195
EP +
DI 10.1016/j.jaci.2013.06.037
PG 10
WC Allergy; Immunology
SC Allergy; Immunology
GA AD8QW
UT WOS:000333531700031
PM 23987798
ER
PT J
AU Sabry, A
Hauk, PJ
Jing, H
Su, HC
Stence, NV
Mirsky, DM
Nagel, MA
Abbott, JK
Dragone, LL
Armstrong-Wells, J
Curtis, DJ
Cohrs, R
Schmid, DS
Gilden, D
Gelfand, EW
AF Sabry, Angela
Hauk, Pia J.
Jing, Huie
Su, Helen C.
Stence, Nicholas V.
Mirsky, David M.
Nagel, Maria A.
Abbott, Jordan K.
Dragone, Leonard L.
Armstrong-Wells, Jennifer
Curtis, Donna J.
Cohrs, Randall
Schmid, D. Scott
Gilden, Don
Gelfand, Erwin W.
TI Vaccine strain varicella- zoster virus- induced central nervous system
vasculopathy as the presenting feature of DOCK8 deficiency
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID CLINICAL-MANIFESTATIONS
C1 [Sabry, Angela; Hauk, Pia J.; Abbott, Jordan K.; Dragone, Leonard L.; Gelfand, Erwin W.] Natl Jewish Hlth, Dept Pediat, Div Allergy Immunol, Denver, CO 80206 USA.
[Sabry, Angela; Hauk, Pia J.; Abbott, Jordan K.; Dragone, Leonard L.; Gelfand, Erwin W.] Natl Jewish Hlth, Div Cell Biol, Denver, CO USA.
[Jing, Huie; Su, Helen C.] NIAID, NIH, Bethesda, MD 20892 USA.
[Stence, Nicholas V.; Mirsky, David M.; Armstrong-Wells, Jennifer; Curtis, Donna J.; Cohrs, Randall; Gilden, Don] Univ Colorado, Sch Med, Aurora, CO USA.
[Stence, Nicholas V.; Mirsky, David M.; Nagel, Maria A.; Armstrong-Wells, Jennifer; Curtis, Donna J.] Childrens Hosp Colorado, Aurora, CO USA.
[Schmid, D. Scott] Ctr Dis Control & Prevent, Div Viral Dis, Herpesvirus Team, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
RP Sabry, A (reprint author), Natl Jewish Hlth, Dept Pediat, Div Allergy Immunol, Denver, CO 80206 USA.
EM gelfande@njhealth.org
RI Su, Helen/H-9541-2015; Abbott, Jordan/P-2509-2016
OI Su, Helen/0000-0002-5582-9110; Abbott, Jordan/0000-0001-6334-5266
FU NIAID NIH HHS [R01 AI077609]
NR 12
TC 13
Z9 14
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD APR
PY 2014
VL 133
IS 4
BP 1225
EP 1227
DI 10.1016/j.jaci.2013.11.031
PG 14
WC Allergy; Immunology
SC Allergy; Immunology
GA AD8QW
UT WOS:000333531700040
PM 24418481
ER
PT J
AU Kenworthy, L
Anthony, LG
Naiman, DQ
Cannon, L
Wills, MC
Caroline, LT
Werner, MA
Alexander, KC
Strang, J
Bal, E
Sokoloff, JL
Wallace, GL
AF Kenworthy, Lauren
Anthony, Laura Gutermuth
Naiman, Daniel Q.
Cannon, Lynn
Wills, Meagan C.
Caroline Luong-Tran
Werner, Monica Adler
Alexander, Katie C.
Strang, John
Bal, Elgiz
Sokoloff, Jennifer L.
Wallace, Gregory L.
TI Randomized controlled effectiveness trial of executive function
intervention for children on the autism spectrum
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Autism; executive function; RRBI; intervention; CBT
ID YOUNG-CHILDREN; BEHAVIORAL SUPPORTS; SOCIAL-INTERACTION;
ASPERGERS-SYNDROME; BRAIN-INJURY; REAL-WORLD; DISORDERS; ADOLESCENTS;
ADULTS; MIND
AB BackgroundUnstuck and On Target (UOT) is an executive function (EF) intervention for children with autism spectrum disorders (ASD) targeting insistence on sameness, flexibility, goal-setting, and planning through a cognitive-behavioral program of self-regulatory scripts, guided/faded practice, and visual/verbal cueing. UOT is contextually-based because it is implemented in school and at home, the contexts in which a child uses EF skills.
MethodsTo evaluate the effectiveness of UOT compared with a social skills intervention (SS), 3rd-5th graders with ASD (mean IQ=108; UOT n=47; SS n=20) received interventions delivered by school staff in small group sessions. Students were matched for gender, age, race, IQ, ASD symptomotolgy, medication status, and parents' education. Interventions were matched for dose' of intervention and training. Measures of pre-post change included classroom observations, parent/teacher report, and direct child measures of problem-solving, EF, and social skills. Schools were randomized and evaluators, but not parents or teachers, were blinded to intervention type.
ResultsInterventions were administered with high fidelity. Children in both groups improved with intervention, but mean change scores from pre- to postintervention indicated significantly greater improvements for UOT than SS groups in: problem-solving, flexibility, and planning/organizing. Also, classroom observations revealed that participants in UOT made greater improvements than SS participants in their ability to follow rules, make transitions, and be flexible. Children in both groups made equivalent improvements in social skills.
ConclusionsThese data support the effectiveness of the first contextually-based EF intervention for children with ASD. UOT improved classroom behavior, flexibility, and problem-solving in children with ASD. Individuals with variable background/training in ASD successfully implemented UOT in mainstream educational settings.
C1 [Kenworthy, Lauren; Anthony, Laura Gutermuth; Wills, Meagan C.; Caroline Luong-Tran; Strang, John; Bal, Elgiz; Sokoloff, Jennifer L.] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Rockville, MD USA.
[Kenworthy, Lauren; Anthony, Laura Gutermuth; Strang, John] George Washington Univ, Sch Med, Washington, DC USA.
[Naiman, Daniel Q.] Johns Hopkins Univ, Dept Appl Math & Stat, Baltimore, MD USA.
[Cannon, Lynn; Werner, Monica Adler; Alexander, Katie C.] Ivymount Sch, Rockville, MD USA.
[Wallace, Gregory L.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Anthony, LG (reprint author), 15245 Shady Grove Rd,Suite 350, Rockville, MD 20850 USA.
EM lkenwort@cnmc.org; lanthony@cnmc.org
RI Strang, John/H-5460-2011;
OI Strang, John/0000-0002-5413-2725; Wallace, Gregory/0000-0003-0329-5054
FU National Institute of Mental Health (NIMH) [R34MH083053]; Organization
for Autism Research; Isadore and Bertha Gudelsky Family Foundation; NIH,
NIMH
FX This project was supported by Grant Number R34MH083053 from the National
Institute of Mental Health (NIMH), the Organization for Autism Research,
and the Isadore and Bertha Gudelsky Family Foundation. G. L. W. was
supported by the Intramural Research Program of the NIH, NIMH. L. K.
receives financial compensation for use of the BRIEF. L. C., L. K., K.
A., M. A. W. and L. G. A. receive financial compensation for the use of
Unstuck and On Target manuals. The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the NIMH, the NIH or the other funders. The authors thank the children,
families, and schools who participated (Archdiocese of Washington and
Fairfax County). The authors also thank their many advisors, especially
Connie Kasari, UCLA. The study's statistical expert is Daniel Naiman.
NR 54
TC 22
Z9 23
U1 6
U2 58
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9630
EI 1469-7610
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD APR
PY 2014
VL 55
IS 4
BP 374
EP 383
DI 10.1111/jcpp.12161
PG 10
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA AD4JU
UT WOS:000333218100010
PM 24256459
ER
PT J
AU Kehrl, JH
Wakefield, LM
Roberts, AB
Jakowlew, S
Alvarez-Mon, M
Derynck, R
Sporn, MB
Fauci, AS
AF Kehrl, John H.
Wakefield, Lalage M.
Roberts, Anita B.
Jakowlew, Sonia
Alvarez-Mon, Melchor
Derynck, Rik
Sporn, Michael B.
Fauci, Anthony S.
TI PRODUCTION OF TRANSFORMING GROWTH FACTOR beta BY HUMAN T LYMPHOCYTES AND
ITS POTENTIAL ROLE IN THE REGULATION OF T CELL GROWTH (Reprinted from
The Journal of Experimental Medicine, vol 163, pg 1037-1050, 1986)
SO JOURNAL OF IMMUNOLOGY
LA English
DT Reprint
ID HUMAN-PLATELETS; RECEPTOR GENE; BSC-1 CELLS; EXPRESSION; ANTIGEN;
PROLIFERATION; PURIFICATION; TRANSFERRIN; INVITRO; FIBROBLASTS
C1 [Kehrl, John H.; Fauci, Anthony S.] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
[Wakefield, Lalage M.; Roberts, Anita B.; Jakowlew, Sonia; Sporn, Michael B.] NCI, Lab Chemoprevent, NIH, Bethesda, MD 20892 USA.
[Alvarez-Mon, Melchor] Clin Puerta de Hierro, Serv Internal Med 1, Madrid, Spain.
[Derynck, Rik] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
RP Kehrl, JH (reprint author), NIH, Bldg 10,Room 11B-13, Bethesda, MD 20892 USA.
OI Kehrl, John/0000-0002-6526-159X
NR 40
TC 4
Z9 4
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR 1
PY 2014
VL 192
IS 7
BP 2939
EP 2952
PG 14
WC Immunology
SC Immunology
GA AD6CY
UT WOS:000333342800002
PM 24659787
ER
PT J
AU Sakai, S
Kauffman, KD
Schenkel, JM
McBerry, CC
Mayer-Barber, KD
Masopust, D
Barber, DL
AF Sakai, Shunsuke
Kauffman, Keith D.
Schenkel, Jason M.
McBerry, Cortez C.
Mayer-Barber, Katrin D.
Masopust, David
Barber, Daniel L.
TI Cutting Edge: Control of Mycobacterium tuberculosis Infection by a
Subset of Lung Parenchyma-Homing CD4 T Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MEDIATED IMMUNITY; IN-VIVO; GAMMA; MEMORY; EFFECTOR
AB Th1 cells are critical for containment of Mycobacterium tuberculosis infection, but little else is known about the properties of protective CD4 T cell responses. In this study, we show that the pulmonary Th1 response against M. tuberculosis is composed of two populations that are either CXCR3(hi) and localize to lung parenchyma or are CX3CR1(hi)KLRG1(hi) and are retained within lung blood vasculature. M. tuberculosis-specific parenchymal CD4 T cells migrate rapidly back into the lung parenchyma upon adoptive transfer, whereas the intravascular effectors produce the highest levels of IFN-gamma in vivo. Importantly, parenchymal T cells displayed greater control of infection compared with the intravascular counterparts upon transfer into susceptible T cell-deficient hosts. Thus, we identified a subset of naturally generated M. tuberculosis-specific CD4 T cells with enhanced protective capacity and showed that control of M. tuberculosis correlates with the ability of CD4 T cells to efficiently enter the lung parenchyma rather than produce high levels of IFN-gamma.
C1 [Sakai, Shunsuke; Kauffman, Keith D.; McBerry, Cortez C.; Barber, Daniel L.] NIAID, Lymphocyte Biol Unit T, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Schenkel, Jason M.; Masopust, David] Univ Minnesota, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA.
[Mayer-Barber, Katrin D.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Barber, DL (reprint author), NIAID, Parasit Dis Lab, 33 North Dr,Room 1W20B-7, Bethesda, MD 20892 USA.
EM barberd@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 20
TC 47
Z9 47
U1 1
U2 9
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR 1
PY 2014
VL 192
IS 7
BP 2965
EP 2969
DI 10.4049/jimmunol.1400019
PG 5
WC Immunology
SC Immunology
GA AD6CY
UT WOS:000333342800005
PM 24591367
ER
PT J
AU Giesecke, C
Frolich, D
Reiter, K
Mei, HE
Wirries, I
Kuhly, R
Killig, M
Glatzer, T
Stolzel, K
Perka, C
Lipsky, PE
Dorner, T
AF Giesecke, Claudia
Froelich, Daniela
Reiter, Karin
Mei, Henrik E.
Wirries, Ina
Kuhly, Rainer
Killig, Monica
Glatzer, Timor
Stoelzel, Katharina
Perka, Carsten
Lipsky, Peter E.
Doerner, Thomas
TI Tissue Distribution and Dependence of Responsiveness of Human
Antigen-Specific Memory B Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; VARIABLE REGION GENES; HYPER-IGM SYNDROME;
LIVED PLASMA-CELL; V-H GENES; BONE-MARROW; PERIPHERAL-BLOOD;
IMMUNE-RESPONSE; LYMPHOCYTE MIGRATION; DEPLETION THERAPY
AB Memory B cells (mBCs) are a key to immunologic memory, yet their distribution within lymphoid organs and the individual role of these for mBC functionality remain largely unknown. This study characterized the distribution and phenotype of human (Ag-specific) mBCs in peripheral blood (PB), spleen, tonsil, and bone marrow. We found that the spleen harbors most mBCs, followed by tonsils, BM, and PB, and we detected no major differences in expression of markers associated with higher maturity. Testing the distribution of tetanus toxoid-specific (TT+) mBCs revealed their presence in PB during steady state, yet absolute numbers suggested their largest reservoir in the spleen, followed by tonsils. To explore the role of both tissues in the maintenance of reactive B cell memory, we revaccinated controls and splenectomized and tonsillectomized individuals with TT. All donor groups exhibited comparable emergence of anti-TT IgG, TT+ plasma cells, and TT+ mBCs in the PB, together with similar molecular characteristics of TT+ plasma cells. In summary, human mBCs recirculate through PB and reside in different lymphoid organs that do not reflect different mBC maturity stages. The spleen and tonsil, although harboring the largest number of overall and TT+ mBCs, appear to be dispensable to preserve adequate responsiveness to secondary antigenic challenge.
C1 [Giesecke, Claudia; Froelich, Daniela; Reiter, Karin; Mei, Henrik E.; Wirries, Ina; Doerner, Thomas] Charite, Med Klin Schwerpunkt Rheumatol & Klin Immunol, D-10117 Berlin, Germany.
[Giesecke, Claudia; Froelich, Daniela; Mei, Henrik E.; Wirries, Ina; Killig, Monica; Glatzer, Timor; Doerner, Thomas] Deutsch Rheumaforschungszentrum Berlin, D-10117 Berlin, Germany.
[Kuhly, Rainer] Charite, Klin Anasthesol Urn Operat Intens Med, D-10117 Berlin, Germany.
[Stoelzel, Katharina] Charite, Klin Hals, D-10117 Berlin, Germany.
[Perka, Carsten] Charite, Klin Unfallchirurg & Orthopadie, D-10117 Berlin, Germany.
[Lipsky, Peter E.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Dorner, T (reprint author), Charite, Charite Pl 1, D-10117 Berlin, Germany.
EM thomas.doerner@charite.de
FU Deutsche Forschungsgemeinschaft [Do491/7-2,3, Do 491/5-4]; Deutsche
Forschungsgemeinschaft, Schwerpunkt-programm Immunobone [Do491/8-1,2]
FX This work was supported by Deutsche Forschungsgemeinschaft single
projects Do491/7-2,3, Do 491/5-4, and Deutsche Forschungsgemeinschaft,
Schwerpunkt-programm Immunobone Do491/8-1,2.
NR 63
TC 11
Z9 11
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR 1
PY 2014
VL 192
IS 7
BP 3091
EP 3100
DI 10.4049/jimmunol.1302783
PG 10
WC Immunology
SC Immunology
GA AD6CY
UT WOS:000333342800018
PM 24567530
ER
PT J
AU Levi, YF
Vedin, I
Cederholm, T
Basun, H
Irving, GF
Eriksdotter, M
Hjorth, E
Schultzberg, M
Vessby, B
Wahlund, LO
Salem, N
Palmblad, J
AF Levi, Y. Freund
Vedin, I.
Cederholm, T.
Basun, H.
Irving, G. Faxen
Eriksdotter, M.
Hjorth, E.
Schultzberg, M.
Vessby, B.
Wahlund, L. -O.
Salem, N., Jr.
Palmblad, J.
TI Transfer of omega-3 fatty acids across the blood-brain barrier after
dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty
acid preparation in patients with Alzheimer's disease: the OmegAD study
SO JOURNAL OF INTERNAL MEDICINE
LA English
DT Article
DE omega-3 fatty acids; eicosapentaenoic acid; docosahexaenoic acid;
cerebrospinal fluid; Alzheimer's disease
ID POLYUNSATURATED FATTY-ACID; BETA-INFUSED RATS; COGNITIVE DECLINE;
CEREBROSPINAL-FLUID; AMYLOID-BETA; TRANSGENIC MICE; MOUSE MODEL;
PATHOLOGY; PLASMA; CHOLESTEROL
AB Objective
Little is known about the transfer of essential fatty acids (FAs) across the human blood-brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with omega-3 (n-3) FAs would change the FA profile of the cerebrospinal fluid (CSF).
Methods
A total of 33 patients (18 receiving the n-3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double-blind, placebo-controlled randomized OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3g n-3 FA [high in docosahexaenoic acid (DHA)] or placebo daily for 6months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation.
Results
At 6months, the n-3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n-3 FA levels (P<0.01), whereas no changes were observed in the placebo group. Changes in CSF and plasma levels of EPA and n-3 docosapentaenoic acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin-1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers.
Conclusions
Oral supplementation with n-3 FAs conferred changes in the n-3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults.
C1 [Levi, Y. Freund; Irving, G. Faxen; Eriksdotter, M.; Hjorth, E.; Schultzberg, M.; Wahlund, L. -O.] Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Neurobiol Caring Sci & Soc, SE-14186 Stockholm, Sweden.
[Vedin, I.; Palmblad, J.] Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Med, SE-14186 Stockholm, Sweden.
[Cederholm, T.; Basun, H.; Vessby, B.] Univ Uppsala Hosp, Dept Publ Hlth & Caring Sci, Uppsala, Sweden.
[Cederholm, T.] Univ Uppsala Hosp, Div Clin Nutr & Metab, Uppsala, Sweden.
[Basun, H.; Vessby, B.] Univ Uppsala Hosp, Div Geriatr, Uppsala, Sweden.
[Salem, N., Jr.] NIAAA, NIH, Rockville, MD 20852 USA.
RP Palmblad, J (reprint author), Karolinska Univ Hosp Huddinge, Dept Med M54, SE-14186 Stockholm, Sweden.
EM jan.palmblad@ki.se
RI Eriksdotter, Maria/I-5427-2015; Schultzberg, Marianne/E-7076-2014;
OI Eriksdotter, Maria/0000-0003-2498-4000; Schultzberg,
Marianne/0000-0002-8314-0927; Freund-Levi, Yvonne/0000-0001-6863-6679;
wahlund, lars-olof/0000-0002-9905-8426; Faxen Irving,
Gerd/0000-0002-5866-469X
FU Stockholm County Council; Karolinska Institutet [20110263, 20110604];
Capio; Demensforbundet; Gamla Tjanarinnor; Swedish Alzheimer Foundation;
Odd Fellow Sweden; Swedish Nutrition Foundation; Gun och Bertil Stohnes
Foundation; Swedish Society of Physicians; Lion's Sweden; Pronova
Biocare A/S, Lysaker, Norway
FX Financial support was provided through The Regional Agreement on Medical
Training and Clinical Research (ALF) between Stockholm County Council
and the Karolinska Institutet (20110263, 20110604), and by Funds of
Capio, Demensforbundet, Gamla Tjanarinnor, Swedish Alzheimer Foundation,
Odd Fellow Sweden, Swedish Nutrition Foundation, Gun och Bertil Stohnes
Foundation, Swedish Society of Physicians and Lion's Sweden. The OmegAD
study was initially partly funded by Pronova Biocare A/S, Lysaker,
Norway; the company was represented in the trial steering committee with
regard to study design and provided the EPAX1050TG and placebo
preparations, but was not involved in the data and patient collection
and analyses or interpretation of scientific data.
NR 39
TC 15
Z9 16
U1 6
U2 30
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0954-6820
EI 1365-2796
J9 J INTERN MED
JI J. Intern. Med.
PD APR
PY 2014
VL 275
IS 4
BP 428
EP 436
DI 10.1111/joim.12166
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD5RL
UT WOS:000333310700009
ER
PT J
AU Hofmeyr, F
Groenewald, CA
Nel, DG
Myers, MM
Fifer, WP
Signore, C
Hankins, GDV
Odendaal, HJ
AF Hofmeyr, F.
Groenewald, C. A.
Nel, D. G.
Myers, M. M.
Fifer, W. P.
Signore, C.
Hankins, G. D. V.
Odendaal, H. J.
CA PASS Network
TI Fetal heart rate patterns at 20 to 24 weeks gestation as recorded by
fetal electrocardiography
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Monica AN24; non-invasive FHR monitoring; transabdominal FECG
ID NUMERICAL-ANALYSIS; BEHAVIORAL STATES; MOVEMENTS; TERM; ACCELERATIONS;
PREGNANCY; SYSTEM
AB Introduction: With advancing technology it has become possible to accurately record and assess fetal heart rate (FHR) patterns from gestations as early as 20 weeks. The aim of our study was to describe early patterns of FHR, as recorded by transabdominal fetal electrocardiogram according to the Dawes-Redman criteria. Accordingly, short-term variability, basal heart rate, accelerations and decelerations were quantified at 20-24 weeks gestation among women with uncomplicated pregnancies.
Methods: This study was conducted in a subset of participants enrolled in a large prospective pregnancy cohort study. Our final data set consisted of 281 recordings of women with good perinatal outcomes who had undergone fetal electrocardiographic assessment as part of the Safe Passage Study.
Results: The success rate of the recordings was 95.4%. The mean frequency of small and large accelerations was 0.5 and 0.1 per 10 min, respectively and that of small and large decelerations 0.3 and 0.008 per 10 min, respectively. The mean and basal heart rates were both equal to 148.0 bpm at a median gestation of 161 days. The mean short term variation was 6.2 (SD 1.4) ms and mean minute range 35.1 (SD 7.1) ms.
Conclusion: The 20-24-week fetus demonstrates FHR patterns with more accelerations and decelerations, as well as higher baseline variability than was anticipated. Information from this study provides an important foundation for further, more detailed, studies of early FHR patterns.
C1 [Hofmeyr, F.; Groenewald, C. A.; Odendaal, H. J.] Univ Stellenbosch, Dept Obstet & Gynaecol, ZA-7505 Cape Town, South Africa.
[Nel, D. G.] Univ Stellenbosch, Dept Stat & Actuarial Sci, ZA-7505 Cape Town, South Africa.
[Myers, M. M.; Fifer, W. P.] Columbia Univ, Dept Psychiat, New York, NY USA.
[Myers, M. M.; Fifer, W. P.] Columbia Univ, Dept Pediat, New York, NY 10027 USA.
[Signore, C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Washington, DC USA.
[Hankins, G. D. V.] Univ Texas Med Branch, Dept Obstet & Gynaecol, Galveston, TX 77555 USA.
RP Odendaal, HJ (reprint author), Univ Stellenbosch, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, POB 19063, ZA-7505 Cape Town, South Africa.
EM hjo@sun.ac.za
FU National Institute on Alcohol Abuse and Alcoholism; Eunice Kennedy
Shriver National Institute of Child Health and Human Development;
National Institute on Deafness and other Communication Disorders [U01
HD055154, U01 HD045935, U01 HD055155, U01 HD045991, U01 AA016501]
FX The Safe Passage Study was funded by the following grants from the
National Institute on Alcohol Abuse and Alcoholism, the Eunice Kennedy
Shriver National Institute of Child Health and Human Development and the
National Institute on Deafness and other Communication Disorders: U01
HD055154, U01 HD045935, U01 HD055155, U01 HD045991 and U01 AA016501.
NR 21
TC 6
Z9 9
U1 1
U2 16
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD APR
PY 2014
VL 27
IS 7
BP 714
EP 718
DI 10.3109/14767058.2013.836485
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AD9KE
UT WOS:000333583100012
PM 23991757
ER
PT J
AU Davis, CD
Bailey, RL
Dwyer, JT
Coates, PM
AF Davis, Cindy D.
Bailey, Regan L.
Dwyer, Johanna T.
Coates, Paul M.
TI John Austin Milner, PhD (1947-2013)
SO JOURNAL OF NUTRITION
LA English
DT Biographical-Item
C1 [Davis, Cindy D.; Bailey, Regan L.; Dwyer, Johanna T.; Coates, Paul M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Dwyer, Johanna T.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Dwyer, Johanna T.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Dwyer, Johanna T.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
RP Davis, CD (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA.
EM davisci@mail.nih.gov
OI Dwyer, Johanna/0000-0002-0783-1769
NR 1
TC 1
Z9 1
U1 0
U2 4
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD APR
PY 2014
VL 144
IS 4
BP 411
EP 413
DI 10.3945/jn.114.191064
PG 3
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AE0MU
UT WOS:000333661200001
PM 24500932
ER
PT J
AU Garcia-Cazarin, ML
Wambogo, EA
Regan, KS
Davis, CD
AF Garcia-Cazarin, Mary L.
Wambogo, Edwina A.
Regan, Karen S.
Davis, Cindy D.
TI Dietary Supplement Research Portfolio at the NIH, 2009-2011
SO JOURNAL OF NUTRITION
LA English
DT Article
ID US ADULTS
AB The U.S. dietary supplement market increased by 7.5% in 2012 compared with 2011, reaching $32.5 billion in sales. Therefore, federally supported research on dietary supplements is important to determine their health effects, safety, and efficacy. A portfolio analysis was performed across the NIH and the Office of Dietary Supplements (ODS) for fiscal years (FYs) 2009-2011 by using the databases Human Nutrition Research Information Management (HNRIM) and Computer Access to Research on Dietary Supplements (CARDS). The results indicated that total NIH dietary supplement related funding for FYs 2009-2011 was $855 million ($295 million in 2009, $311 million in 2010, and $249 million in 20:11). The institutes and centers with the highest investment in dietary supplement research were as follows: the National Heart, Lung, and Blood Institute ($135 million); the National Cancer Institute 3188 million); the National Center for Complementary and Alternative Medicine ($99 million); the National Institute of Diabetes and Digestive and Kidney Diseases ($68 million); the National Institute of Environmental Health Sciences ($58 million); and the ODS ($32 million). The dietary supplement ingredients receiving the most funding were botanicals (22%), vitamins (20%), lipids (14%), and minerals and trace elements (10%). The top 3 outcome research areas were cancer (61% of total dietary supplement investment), cardiovascular disease (47%), and women's reproductive health (38%). In FYs 2009, 2010, and 2011, the ODS provided 3.5%, 3.6%, and 4.1%, respectively, of the NIH investment in dietary supplement research. ODS funding focused on cellular, enzymatic, or molecular mechanisms (64% of total ODS funding). This portfolio analysis demonstrates that the NIH has committed substantial funding to dietary supplement research man effort to expand l the scientific knowledge base on the efficacy and safety of dietary supplements.
C1 [Garcia-Cazarin, Mary L.; Wambogo, Edwina A.; Regan, Karen S.; Davis, Cindy D.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Regan, Karen S.] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA.
RP Garcia-Cazarin, ML (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA.
EM mary.garcia-cazarin@nih.gov
NR 9
TC 12
Z9 12
U1 1
U2 15
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD APR
PY 2014
VL 144
IS 4
BP 414
EP 418
DI 10.3945/jn.113.189803
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AE0MU
UT WOS:000333661200002
PM 24523489
ER
PT J
AU Lahat, A
Lamm, C
Chronis-Tuscano, A
Pine, DS
Henderson, HA
Fox, NA
AF Lahat, Ayelet
Lamm, Connie
Chronis-Tuscano, Andrea
Pine, Daniel S.
Henderson, Heather A.
Fox, Nathan A.
TI Early Behavioral Inhibition and Increased Error Monitoring Predict Later
Social Phobia Symptoms in Childhood
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE behavioral inhibition; error monitoring; error-related negativity (ERN);
anxiety; longitudinal
ID OBSESSIVE-COMPULSIVE DISORDER; GENERALIZED ANXIETY DISORDER; BRAIN
ACTIVITY; FUNCTIONAL-SIGNIFICANCE; REVISED VERSION; NEGATIVITY ERN;
SCARED-R; CHILDREN; TEMPERAMENT; ADOLESCENTS
AB Objective: Behavioral inhibition (BI) is an early childhood temperament characterized by fearful responses to novelty and avoidance of social interactions. During adolescence, a subset of children with stable childhood BI develop social anxiety disorder and concurrently exhibit increased error monitoring. The current study examines whether increased error monitoring in 7-year-old, behaviorally inhibited children prospectively predicts risk for symptoms of social phobia at age 9 years. Method: A total of 291 children were characterized on BI at 24 and 36 months of age. Children were seen again at 7 years of age, when they performed a Flanker task, and event-related potential (ER]?) indices of response monitoring were generated. At age 9, self- and maternal-report of social phobia symptoms were obtained. Results: Children high in BI, compared to those low in BI, displayed increased error monitoring at age 7, as indexed by larger (i.e., more negative) error-related negativity (ERN) amplitudes. In addition, early BI was related to later childhood social phobia symptoms at age 9 among children with a large difference in amplitude between ERN and correct-response negativity (CRN) at age 7. Conclusions: Heightened error monitoring predicts risk for later social phobia symptoms in children with high BI. Research assessing response monitoring in children with BI may refine our understanding of the mechanisms underlying risk for later anxiety disorders and inform prevention efforts.
C1 [Lahat, Ayelet] McMaster Univ, Hamilton, ON L8S 4K1, Canada.
[Lamm, Connie] Univ New Orleans, New Orleans, LA 70148 USA.
[Chronis-Tuscano, Andrea; Fox, Nathan A.] Univ Maryland, College Pk, MD 20742 USA.
[Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA.
[Henderson, Heather A.] Univ Miami, Coral Gables, FL 33124 USA.
RP Lahat, A (reprint author), McMaster Univ, Dept Psychol Neurosci & Behav, 1280 Main St W, Hamilton, ON L8S 4K1, Canada.
EM lahata@mcmaster.ca
FU NIMH [U01MH093349]; NIMH Intramural Research Program
FX This project was supported by a grant from NIMH (U01MH093349; NAP.), by
the NIMH Intramural Research Program, and by a Lawson Poundotion
Post-Doctoral Fellowship (A.L).
NR 54
TC 22
Z9 23
U1 5
U2 26
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD APR
PY 2014
VL 53
IS 4
BP 447
EP 455
DI 10.1016/j.jaac.2013.12.019
PG 9
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA AE1YK
UT WOS:000333770200010
PM 24655654
ER
PT J
AU Wallace, GL
White, SF
Robustelli, B
Sinclair, S
Hwang, S
Martin, A
Blair, RJR
AF Wallace, Gregory L.
White, Stuart F.
Robustelli, Briana
Sinclair, Stephen
Hwang, Soo
Martin, Alex
Blair, R. James R.
TI Cortical and Subcortical Abnormalities in Youths With Conduct Disorder
and Elevated Callous-Unemotional Traits
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE conduct disorder; antisocial; amygdala; striatum; cortical thickness
ID DISRUPTIVE BEHAVIOR DISORDERS; VENTROMEDIAL PREFRONTAL CORTEX;
ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; BRAIN STRUCTURE ABNORMALITIES;
HUMAN CEREBRAL-CORTEX; SURFACE-AREA; PSYCHOPATHIC TRAITS; EARLY-ONSET;
AMYGDALA; THICKNESS
AB Objective: Although there is growing evidence of brain abnormalities among individuals with conduct disorder (CD), the structural neuroimaging literature is mixed and frequently aggregates cortical volume rather than differentiating cortical thickness from surface area. The current study assesses CD-related differences in cortical thickness, surface area, and gyrification as well as volume differences in subcortical structures critical to neurodevelopmental models of CD (amygdala; striatum) in a carefully characterized sample. We also examined whether group structural differences were related to severity of callous-unemotional (CU) traits in the CD sample. Method: Participants were 49 community adolescents aged 10 to 18 years, 22 with CD and 27 healthy comparison youth. Structural MRI was collected and the Free Surfer image analysis suite was used to provide measures of cortical thickness, surface area, and local gyrification as well as subcortical (amygdala and striatum) volumes. Results: Youths with CD showed reduced cortical thickness in the superior temporal cortex. There were also indications of reduced gyrification in the ventromedial frontal cortex, particularly for youths with CD without comorbid attention-deficit/hyperactivity disorder. There were no group differences in cortical surface area. However, youths with CD also showed reduced amygdala and striatum (putamen and pallidum) volumes. Right temporal cortical thickness was significantly inversely related to severity of CU traits. Conclusions: Youths with CD show reduced cortical thickness within superior temporal regions, some indication of reduced gyrification within ventromedial frontal cortex and reduced amygdala and striatum (putamen and pallidum) volumes. These results are discussed with reference to neurobiological models of CD.
C1 [Wallace, Gregory L.; White, Stuart F.; Robustelli, Briana; Sinclair, Stephen; Hwang, Soo; Martin, Alex; Blair, R. James R.] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Wallace, GL (reprint author), NIMH, NIH, 10 Ctr Dr,Room 4C104, Bethesda, MD 20892 USA.
OI Wallace, Gregory/0000-0003-0329-5054
FU NIMH [1-ZIA-MH002860-08]; NIH Combined Neuroscience Institutional Review
Board [05-M-0105]
FX This work was supported by the Intramural Research Program at NIMH, NIH
under grant number 1-ZIA-MH002860-08. Ethics approval for this study was
granted by the NIH Combined Neuroscience Institutional Review Board
under protocol number 05-M-0105.
NR 58
TC 26
Z9 28
U1 3
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD APR
PY 2014
VL 53
IS 4
BP 456
EP 465
DI 10.1016/j.jaac.2013.12.008
PG 10
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA AE1YK
UT WOS:000333770200011
PM 24655655
ER
PT J
AU Nikolaitchik, OA
Hu, WS
AF Nikolaitchik, Olga A.
Hu, Wei-Shau
TI Deciphering the Role of the Gag-Pol Ribosomal Frameshift Signal in HIV-1
RNA Genome Packaging
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; CIS-ELEMENTS;
ENCAPSIDATION; DIMERIZATION; REPLICATION; PROTEIN; CELLS; GENE;
IDENTIFICATION
AB A key step of retroviral replication is packaging of the viral RNA genome during virus assembly. Specific packaging is mediated by interactions between the viral protein Gag and elements in the viral RNA genome. In HIV-1, similar to most retroviruses, the packaging signal is located within the 5' untranslated region and extends into the gag-coding region. A recent study reported that a region including the Gag-Pol ribosomal frameshift signal plays an important role in HIV-1 RNA packaging; deletions or mutations that affect the RNA structure of this signal lead to drastic decreases (10- to 50-fold) in viral RNA packaging and virus titer. We examined here the role of the ribosomal frameshift signal in HIV-1 RNA packaging by studying the RNA packaging and virus titer in the context of proviruses. Three mutants with altered ribosomal frameshift signal, either through direct deletion of the signal, mutation of the 6U slippery sequence, or alterations of the secondary structure were examined. We found that RNAs from all three mutants were packaged efficiently, and they generate titers similar to that of a virus containing the wild-type ribosomal frameshift signal. We conclude that although the ribosomal frameshift signal plays an important role in regulating the replication cycle, this RNA element is not directly involved in regulating RNA encapsidation.
IMPORTANCE
To generate infectious viruses, HIV-1 must package viral RNA genome during virus assembly. The specific HIV-1 genome packaging is mediated by interactions between the structural protein Gag and elements near the 5' end of the viral RNA known as packaging signal. In this study, we examined whether the Gag-Pol ribosomal frameshift signal is important for HIV-1 RNA packaging as recently reported. Our results demonstrated that when Gag/Gag-Pol is supplied in trans, none of the tested ribosomal frameshift signal mutants has defects in RNA packaging or virus titer. These studies provide important information on how HIV-1 regulates its genome packaging and generate infectious viruses necessary for transmission to new hosts.
C1 [Nikolaitchik, Olga A.; Hu, Wei-Shau] NCI, Viral Recombinat Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21701 USA.
RP Hu, WS (reprint author), NCI, Viral Recombinat Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21701 USA.
EM Wei-Shau.Hu@nih.gov
FU Intramural AIDS Targeted Antiviral Program, National Institutes of
Health; Intramural Research Program of the Center for Cancer Research,
Nation Cancer Institute
FX This study was funded in part by the Intramural AIDS Targeted Antiviral
Program, National Institutes of Health, and the Intramural Research
Program of the Center for Cancer Research, Nation Cancer Institute.
NR 51
TC 5
Z9 5
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2014
VL 88
IS 8
BP 4040
EP 4046
DI 10.1128/JVI.03745-13
PG 7
WC Virology
SC Virology
GA AE0SL
UT WOS:000333676400011
PM 24453371
ER
PT J
AU Whittle, JRR
Wheatley, AK
Wu, L
Lingwood, D
Kanekiyo, M
Ma, SS
Narpala, SR
Yassine, HM
Frank, GM
Yewdell, JW
Ledgerwood, JE
Wei, CJ
McDermott, AB
Graham, BS
Koup, RA
Nabel, GJ
AF Whittle, James R. R.
Wheatley, Adam K.
Wu, Lan
Lingwood, Daniel
Kanekiyo, Masaru
Ma, Steven S.
Narpala, Sandeep R.
Yassine, Hadi M.
Frank, Gregory M.
Yewdell, Jonathan W.
Ledgerwood, Julie E.
Wei, Chih-Jen
McDermott, Adrian B.
Graham, Barney S.
Koup, Richard A.
Nabel, Gary J.
TI Flow Cytometry Reveals that H5N1 Vaccination Elicits Cross-Reactive
Stem-Directed Antibodies from Multiple Ig Heavy-Chain Lineages
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID INFLUENZA-A VIRUSES; HEMAGGLUTININ STALK ANTIBODIES; MEMORY B-CELLS;
RECEPTOR-BINDING; MONOCLONAL-ANTIBODIES; NEUTRALIZATION; MUTANTS;
RECOGNITION; EPITOPE; HUMANS
AB An understanding of the antigen-specific B-cell response to the influenza virus hemagglutinin (HA) is critical to the development of universal influenza vaccines, but it has not been possible to examine these cells directly because HA binds to sialic acid (SA) on most cell types. Here, we use structure-based modification of HA to isolate HA-specific B cells by flow cytometry and characterize the features of HA stem antibodies (Abs) required for their development. Incorporation of a previously described mutation (Y98F) to the receptor binding site (RBS) causes HA to bind only those B cells that express HA-specific Abs, but it does not bind nonspecifically to B cells, and this mutation has no effect on the binding of broadly neutralizing Abs to the RBS. To test the specificity of the Y98F mutation, we first demonstrated that previously described HA nanoparticles mediate hemagglutination and then determined that the Y98F mutation eliminates this activity. Cloning of immunoglobulin genes from HA-specific B cells isolated from a single human subject demonstrates that vaccination with H5N1 influenza virus can elicit B cells expressing stem monoclonal Abs (MAbs). Although these MAbs originated mostly from the IGHV1-69 germ line, a reasonable proportion derived from other genes. Analysis of stem Abs provides insight into the maturation pathways of IGVH1-69-derived stem Abs. Furthermore, this analysis shows that multiple non-IGHV1-69 stem Abs with a similar neutralizing breadth develop after vaccination in humans, suggesting that the HA stem response can be elicited in individuals with non-stem-reactive IGHV1-69 alleles.
IMPORTANCE
Universal influenza vaccines would improve immune protection against infection and facilitate vaccine manufacturing and distribution. Flu vaccines stimulate B cells in the blood to produce antibodies that neutralize the virus. These antibodies target a protein on the surface of the virus called HA. Flu vaccines must be reformulated annually, because these antibodies are mostly specific to the viral strains used in the vaccine. But humans can produce broadly neutralizing antibodies. We sought to isolate B cells whose genes encode influenza virus antibodies from a patient vaccinated for avian influenza. To do so, we modified HA so it would bind only the desired cells. Sequencing the antibody genes of cells marked by this probe proved that the patient produced broadly neutralizing antibodies in response to the vaccine. Many sequences obtained had not been observed before. There are more ways to generate broadly neutralizing antibodies for influenza virus than previously thought.
C1 [Whittle, James R. R.; Wheatley, Adam K.; Wu, Lan; Lingwood, Daniel; Kanekiyo, Masaru; Ma, Steven S.; Narpala, Sandeep R.; Yassine, Hadi M.; Frank, Gregory M.; Yewdell, Jonathan W.; Ledgerwood, Julie E.; Wei, Chih-Jen; McDermott, Adrian B.; Graham, Barney S.; Koup, Richard A.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Gary.Nabel@sanofi.com
OI Wheatley, Adam/0000-0002-5593-9387
FU Intramural Research Program of the Vaccine Research Center, NIAID,
National Institutes of Health
FX This research was supported by the Intramural Research Program of the
Vaccine Research Center, NIAID, National Institutes of Health.
NR 36
TC 34
Z9 34
U1 1
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2014
VL 88
IS 8
BP 4047
EP 4057
DI 10.1128/JVI.03422-13
PG 11
WC Virology
SC Virology
GA AE0SL
UT WOS:000333676400012
PM 24501410
ER
PT J
AU Liang, B
Munir, S
Amaro-Carambot, E
Surman, S
Mackow, N
Yang, LJ
Buchholz, UJ
Collins, PL
Schaap-Nutt, A
AF Liang, Bo
Munir, Shirin
Amaro-Carambot, Emerito
Surman, Sonja
Mackow, Natalie
Yang, Lijuan
Buchholz, Ursula J.
Collins, Peter L.
Schaap-Nutt, Anne
TI Chimeric Bovine/Human Parainfluenza Virus Type 3 Expressing Respiratory
Syncytial Virus (RSV) F Glycoprotein: Effect of Insert Position on
Expression, Replication, Immunogenicity, Stability, and Protection
against RSV Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ENHANCED PULMONARY PATHOLOGY; LIVE-ATTENUATED VACCINE;
HEMAGGLUTININ-NEURAMINIDASE; HUMAN METAPNEUMOVIRUS; YOUNG-CHILDREN;
COTTON RATS; INACTIVATED VIRUS; ANTIGEN INSERTION; GENE-EXPRESSION;
RHESUS-MONKEYS
AB A recombinant chimeric bovine/human parainfluenza type 3 virus (rB/HPIV3) vector expressing the respiratory syncytial virus (RSV) fusion F glycoprotein previously exhibited disappointing levels of RSV F immunogenicity and genetic stability in children (D. Bernstein et al., Pediatr. Infect. Dis. J. 31: 109-114, 2012; C.-F. Yang et al., Vaccine 31: 2822-2827, 2013). To investigate parameters that might affect vaccine performance and stability, we constructed and characterized rB/HPIV3 viruses expressing RSV F from the first (pre-N), second (N-P), third (P-M), and sixth (HN-L) genome positions. There was a 30- to 69-fold gradient in RSV F expression from the first to the sixth position. The inserts moderately attenuated vector replication in vitro and in the upper and lower respiratory tracts of hamsters: this was not influenced by the level of RSV F expression and syncytium formation. Surprisingly, inserts in the second, third, and sixth positions conferred increased temperature sensitivity: this was greatest for the third position and was the most attenuating in vivo. Each rB/HPIV3 vector induced a high titer of neutralizing antibodies in hamsters against RSV and HPIV3. Protection against RSV challenge was greater for position 2 than for position 6. Evaluation of insert stability suggested that RSV F is under selective pressure to be silenced during vector replication in vivo, but this was not exacerbated by a high level of RSV F expression and generally involved a small percentage of recovered vector. Vector passaged in vitro accumulated mutations in the HN open reading frame, causing a dramatic increase in plaque size that may have implications for vaccine production and immunogenicity.
C1 [Liang, Bo; Munir, Shirin; Amaro-Carambot, Emerito; Surman, Sonja; Mackow, Natalie; Yang, Lijuan; Buchholz, Ursula J.; Collins, Peter L.; Schaap-Nutt, Anne] NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Liang, B (reprint author), NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM liangb@niaid.nih.gov
FU NIAID, NIH
FX This study was supported by the Intramural Research Program of the
NIAID, NIH.
NR 51
TC 8
Z9 9
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2014
VL 88
IS 8
BP 4237
EP 4250
DI 10.1128/JVI.03481-13
PG 14
WC Virology
SC Virology
GA AE0SL
UT WOS:000333676400028
PM 24478424
ER
PT J
AU Monne, I
Fusaro, A
Nelson, MI
Bonfanti, L
Mulatti, P
Hughes, J
Murcia, PR
Schivo, A
Valastro, V
Moreno, A
Holmes, EC
Cattolia, G
AF Monne, Isabella
Fusaro, Alice
Nelson, Martha I.
Bonfanti, Lebana
Mulatti, Paolo
Hughes, Joseph
Murcia, Pablo R.
Schivo, Alessia
Valastro, Viviana
Moreno, Ana
Holmes, Edward C.
Cattolia, Giovanni
TI Emergence of a Highly Pathogenic Avian Influenza Virus from a
Low-Pathogenic Progenitor
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID A VIRUSES; EVOLUTIONARY DYNAMICS; PHYLOGENETIC ANALYSIS; H7N1 EPIDEMIC;
NONSTRUCTURAL GENES; MOLECULAR-CHANGES; CLEAVAGE SITE; NS1 PROTEIN; JULY
2012; HEMAGGLUTININ
AB Avian influenza (AI) viruses of the H7 subtype have the potential to evolve into highly pathogenic (HP) viruses that represent a major economic problem for the poultry industry and a threat to global health. However, the emergence of HPAI viruses from low-pathogenic (LPAI) progenitor viruses currently is poorly understood. To investigate the origin and evolution of one of the most important avian influenza epidemics described in Europe, we investigated the evolutionary and spatial dynamics of the entire genome of 109 H7N1 (46 LPAI and 63 HPAI) viruses collected during Italian H7N1 outbreaks between March 1999 and February 2001. Phylogenetic analysis revealed that the LPAI and HPAI epidemics shared a single ancestor, that the HPAI strains evolved from the LPAI viruses in the absence of reassortment, and that there was a parallel emergence of mutations among HPAI and later LPAI lineages. Notably, an ultradeep-sequencing analysis demonstrated that some of the amino acid changes characterizing the HPAI virus cluster were already present with low frequency within several individual viral populations from the beginning of the LPAI H7N1 epidemic. A Bayesian phylogeographic analysis revealed stronger spatial structure during the LPAI outbreak, reflecting the more rapid spread of the virus following the emergence of HPAI. The data generated in this study provide the most complete evolutionary and phylogeographic analysis of epidemiologically intertwined high- and low-pathogenicity viruses undertaken to date and highlight the importance of implementing prompt eradication measures against LPAI to prevent the appearance of viruses with fitness advantages and unpredictable pathogenic properties.
C1 [Monne, Isabella; Fusaro, Alice; Bonfanti, Lebana; Mulatti, Paolo; Schivo, Alessia; Valastro, Viviana; Cattolia, Giovanni] Ist Zooprofilatt Sperimentale Venezie, Padua, Italy.
[Nelson, Martha I.; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Hughes, Joseph; Murcia, Pablo R.] MRC Univ Glasgow, Ctr Virus Res, Glasgow, Lanark, Scotland.
[Moreno, Ana] Ist Zooprofilatt Sperimentale Lombardia & Emilia, Brescia, Italy.
[Holmes, Edward C.] Univ Sydney, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW 2006, Australia.
RP Monne, I (reprint author), Ist Zooprofilatt Sperimentale Venezie, Padua, Italy.
EM imonne@izsvenezie.it
RI Hughes, Joseph/B-7711-2009;
OI Hughes, Joseph/0000-0003-2556-2563; Mulatti, Paolo/0000-0001-8188-997X;
Fusaro, Alice/0000-0002-8213-5472; Holmes, Edward/0000-0001-9596-3552
FU European project PREDEMICS [278433]; European project Epi-SEQ; EMIDA
ERA-NET [219235]; NHMRC Australia Fellowship; OECD Cooperative Research
Programme: Biological Resource Management for Sustainable Agricultural
Systems
FX This work was financially supported by the European projects PREDEMICS
(grant agreement no. 278433) and Epi-SEQ (research project supported
under the 2nd Joint Call for Transnational Research Projects by EMIDA
ERA-NET [FP7 project no. 219235]). E. C. H. is supported by an NHMRC
Australia Fellowship. A. F. acknowledges the receipt of a fellowship
from the OECD Cooperative Research Programme: Biological Resource
Management for Sustainable Agricultural Systems in 2013.
NR 77
TC 25
Z9 25
U1 4
U2 18
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2014
VL 88
IS 8
BP 4375
EP 4388
DI 10.1128/JVI.03181-13
PG 14
WC Virology
SC Virology
GA AE0SL
UT WOS:000333676400039
PM 24501401
ER
PT J
AU De Ravin, SS
Su, L
Theobald, N
Choi, U
Macpherson, JL
Poidinger, M
Symonds, G
Pond, SM
Ferris, AL
Hughes, SH
Malech, HL
Wu, XL
AF De Ravin, Suk See
Su, Ling
Theobald, Narda
Choi, Uimook
Macpherson, Janet L.
Poidinger, Michael
Symonds, Geoff
Pond, Susan M.
Ferris, Andrea L.
Hughes, Stephen H.
Malech, Harry L.
Wu, Xiaolin
TI Enhancers Are Major Targets for Murine Leukemia Virus Vector Integration
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CHRONIC GRANULOMATOUS-DISEASE; TRANSCRIPTION START SITES; SCID-X1
GENE-THERAPY; HUMAN GENOME; LENTIVIRAL VECTOR; STRUCTURAL BASIS; CELLS;
RECOGNITION; BROMODOMAIN; REGULATORS
AB Retroviral vectors have been used in successful gene therapies. However, in some patients, insertional mutagenesis led to leukemia or myelodysplasia. Both the strong promoter/enhancer elements in the long terminal repeats (LTRs) of murine leukemia virus (MLV)-based vectors and the vector-specific integration site preferences played an important role in these adverse clinical events. MLV integration is known to prefer regions in or near transcription start sites (TSS). Recently, BET family proteins were shown to be the major cellular proteins responsible for targeting MLV integration. Although MLV integration sites are significantly enriched at TSS, only a small fraction of the MLV integration sites (<15%) occur in this region. To resolve this apparent discrepancy, we created a high-resolution genome-wide integration map of more than one million integration sites from CD34(+) hematopoietic stem cells transduced with a clinically relevant MLV-based vector. The integration sites form similar to 60,000 tight clusters. These clusters comprise similar to 1.9% of the genome. The vast majority (87%) of the integration sites are located within histone H3K4me1 islands, a hallmark of enhancers. The majority of these clusters also have H3K27ac histone modifications, which mark active enhancers. The enhancers of some oncogenes, including LMO2, are highly preferred targets for integration without in vivo selection.
C1 [De Ravin, Suk See; Theobald, Narda; Choi, Uimook; Malech, Harry L.] NIAID, Lab Host Defenses, NIH, Bethesda, MD 20892 USA.
[Su, Ling; Wu, Xiaolin] Frederick Natl Lab Canc Res, Lab Mol Technol, Frederick, MD 21702 USA.
[Macpherson, Janet L.; Poidinger, Michael; Symonds, Geoff; Pond, Susan M.] Johnson & Johnson Res Pty Ltd, Sydney, NSW, Australia.
[Ferris, Andrea L.; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
RP Wu, XL (reprint author), Frederick Natl Lab Canc Res, Lab Mol Technol, Frederick, MD 21702 USA.
EM hmalech@nih.gov; forestwu@mail.nih.gov
RI Macpherson, Janet/D-8702-2012;
OI Macpherson, Janet/0000-0003-0702-9546; Poidinger,
Michael/0000-0002-1047-2277
FU National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH) [Z01-AI-000644]; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]; National Cancer
Institute; Johnson & Johnson Research Pty. Limited [CRADAAI-0167]; NIAID
FX This work has been supported in part by the Intramural Program of the
National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH), under project Z01-AI-000644. This work was
also funded in part with federal funds from the National Cancer
Institute, National Institutes of Health, under contract no.
HHSN261200800001E, and by funding from the Intramural Program of the
National Cancer Institute. This work was supported in part by funding
from Johnson & Johnson Research Pty. Limited (a subsidiary of the
Johnson & Johnson group of companies) in the context of a Cooperative
Research and Development Agreement (CRADAAI-0167) with NIAID.
NR 35
TC 31
Z9 31
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2014
VL 88
IS 8
BP 4504
EP 4513
DI 10.1128/JVI.00011-14
PG 10
WC Virology
SC Virology
GA AE0SL
UT WOS:000333676400049
PM 24501411
ER
PT J
AU McGary, CS
Cervasi, B
Chahroudi, A
Micci, L
Taaffe, J
Meeker, T
Silvestri, G
Davenport, MP
Paiardini, M
AF McGary, Colleen S.
Cervasi, Barbara
Chahroudi, Ann
Micci, Luca
Taaffe, Jessica
Meeker, Tracy
Silvestri, Guido
Davenport, Miles P.
Paiardini, Mirko
TI Increased Stability and Limited Proliferation of CD4(+) Central Memory T
Cells Differentiate Nonprogressive Simian Immunodeficiency Virus (SIV)
Infection of Sooty Mangabeys from Progressive SIV Infection of Rhesus
Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LENTIVIRAL INFECTIONS; IMMUNE ACTIVATION; IN-VIVO; AIDS PATHOGENESIS;
ANALYSIS REVEALS; HIV-1 INFECTION; HOST RESPONSES; NATURAL HOSTS;
DEPLETION; MONKEYS
AB Depletion of CD4(+) central memory T (TCM) cells dictates the tempo of progression to AIDS in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) both in the natural history of infection and in the context of vaccination. CD4(+) TCM cells of sooty mangabeys (SMs), a natural host for SIV in which infection is nonpathogenic, are less susceptible to SIV infection than CD4(+) TCM cells of RMs. Whether this relative protection from infection translates into increased stability of CD4(+) TCM cells in natural versus nonnatural hosts has not yet been determined. Here we compared, both cross-sectionally and longitudinally, the levels of CD4(+) TCM cells in a large cohort of SMs and RMs and the association between CD4(+) TCM levels and the main virologic and immunologic markers of disease progression. Consistent with their lower susceptibility to infection, CD4(+) TCM cells of SIV-infected SMs are lost with kinetics 20 times slower than those of SIV-infected RMs. Remarkably, the estimated length of time of SIV infection needed for CD4(+) TCM cells to fall to half of their initial levels is <16 months for RMs but >17 years for SMs. Furthermore, the fraction of proliferating CD4(+) TCM cells is significantly lower in SIV-infected SMs than in SIV-infected RMs, and the extent of CD4(+) TCM cell proliferation is associated positively with CD4(+) T cell levels in SIV-infected SMs but negatively with CD4(+) T cell levels in SIV-infected RMs. Collectively, these findings identify increased stability and maintenance of the prohomeostatic role of CD4(+) TCM cells as features distinguishing nonprogressive from progressive SIV infections and support the hypothesis of a direct mechanistic link between the loss of CD4(+) TCM cells and disease progression.
C1 [McGary, Colleen S.; Cervasi, Barbara; Chahroudi, Ann; Micci, Luca; Meeker, Tracy; Silvestri, Guido; Paiardini, Mirko] Emory Univ, Sch Med, Yerkes Natl Primate Res Ctr, Div Microbiol & Immunol, Atlanta, GA 30322 USA.
[Silvestri, Guido; Paiardini, Mirko] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA USA.
[Silvestri, Guido; Paiardini, Mirko] Emory Univ, Sch Med, Lab Med, Atlanta, GA USA.
[Taaffe, Jessica] NIAID, Lab Malaria Immunol & Vaccinol, Bethesda, MD 20892 USA.
[Davenport, Miles P.] Univ New S Wales, Ctr Vasc Res, Kensington, NSW 2033, Australia.
RP Paiardini, M (reprint author), Emory Univ, Sch Med, Yerkes Natl Primate Res Ctr, Div Microbiol & Immunol, Atlanta, GA 30322 USA.
EM mirko.paiardini@emory.edu
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health [R01AI084836, R56AI087186, R37 AI066998, OD011132,
P30AI50409]; National Health and Medical Research Council (Australia)
FX Research reported in this publication was supported by the National
Institute of Allergy and Infectious Diseases of the National Institutes
of Health under award numbers R01AI084836 and R56AI087186 to M. P. and
R37 AI066998 to G. S. as well as by grants OD011132 (to the Yerkes
National Primate Research Center) and P30AI50409 (to the Emory Center
for AIDS Research). M. P. D. is supported by the National Health and
Medical Research Council (Australia).
NR 49
TC 10
Z9 10
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2014
VL 88
IS 8
BP 4533
EP 4542
DI 10.1128/JVI.03515-13
PG 10
WC Virology
SC Virology
GA AE0SL
UT WOS:000333676400052
PM 24501416
ER
PT J
AU Zumla, AI
Schito, M
Maeurer, M
AF Zumla, Alimuddin I.
Schito, Marco
Maeurer, Markus
TI Advancing the portfolio of tuberculosis diagnostics, drugs, biomarkers,
and vaccines
SO LANCET INFECTIOUS DISEASES
LA English
DT Editorial Material
ID RESISTANT TUBERCULOSIS; SANATORIA; ASSAY
C1 [Zumla, Alimuddin I.] UCL, Div Infect & Immun, London, England.
[Zumla, Alimuddin I.] Univ Coll London Hosp NHS Trust, Dept Med Microbiol, London, England.
[Schito, Marco] NIAID, Henry M Jackson Fdn, Div AIDS, TB Clin Res Branch,NIH, Bethesda, MD 20892 USA.
[Maeurer, Markus] Karolinska Inst, Therapeut Immunol Div, Dept Lab Med, Stockholm, Sweden.
[Maeurer, Markus] Karolinska Univ Hosp, CAST, SE-14186 Stockholm, Sweden.
RP Zumla, AI (reprint author), UCL, Div Infect & Immun, Mortimer St, London, England.
EM markus.maeurer@ki.se
OI Zumla, Alimuddin/0000-0002-5111-5735
NR 18
TC 12
Z9 12
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD APR
PY 2014
VL 14
IS 4
BP 267
EP 269
DI 10.1016/S1473-3099(14)70028-3
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA AD8FJ
UT WOS:000333501600008
PM 24670623
ER
PT J
AU Xing, WJ
Liao, QH
Viboud, C
Zhang, J
Sun, JL
Wu, JT
Chang, ZR
Liu, FF
Fang, VJ
Zheng, YD
Cowling, BJ
Varma, JK
Farrar, JJ
Leung, GM
Yu, HJ
AF Xing, Weijia
Liao, Qiaohong
Viboud, Cecile
Zhang, Jing
Sun, Junling
Wu, Joseph T.
Chang, Zhaorui
Liu, Fengfeng
Fang, Vicky J.
Zheng, Yingdong
Cowling, Benjamin J.
Varma, Jay K.
Farrar, Jeremy J.
Leung, Gabriel M.
Yu, Hongjie
TI Hand, foot, and mouth disease in China, 2008-12: an epidemiological
study
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID ENTEROVIRUS 71 INFECTION; COXSACKIEVIRUS A16; CHILDREN; OUTBREAK;
TAIWAN; SEROEPIDEMIOLOGY; TEMPERATURE; EMERGENCE; SINGAPORE; SHANGHAI
AB Background Hand, foot, and mouth disease is a common childhood illness caused by enteroviruses. Increasingly, the disease has a substantial burden throughout east and southeast Asia. To better inform vaccine and other interventions, we characterised the epidemiology of hand, foot, and mouth disease in China on the basis of enhanced surveillance.
Methods We extracted epidemiological, clinical, and laboratory data from cases of hand, foot, and mouth disease reported to the Chinese Center for Disease Control and Prevention between Jan 1, 2008, and Dec 31, 2012. We then compiled climatic, geographical, and demographic information. All analyses were stratified by age, disease severity, laboratory confirmation status, and enterovirus serotype.
Findings The surveillance registry included 7 200 092 probable cases of hand, foot, and mouth disease (annual incidence, 1.2 per 1000 person-years from 2010-12), of which 267 942 (3.7%) were laboratory confirmed and 2457 (0.03%) were fatal. Incidence and mortality were highest in children aged 12-23 months (38.2 cases per 1000 person-years and 1.5 deaths per 100 000 person-years in 2012). Median duration from onset to diagnosis was 1.5 days (IQR 0.5-2.5) and median duration from onset to death was 3.5 days (2.5-4.5). The absolute number of patients with cardiopulmonary or neurological complications was 82 486 (case-severity rate 1.1%), and 2457 of 82486 patients with severe disease died (fatality rate 3.0%); 1617 of 1737 laboratory confirmed deaths (93%) were associated with enterovirus 71. Every year in June, hand, foot, and mouth disease peaked in north China, whereas southern China had semiannual outbreaks in May and September October. Geographical differences in seasonal patterns were weakly associated with climate and demographic factors (variance explained 8-23% and 3-19%, respectively).
Interpretation This is the largest population-based study up to now of the epidemiology of hand, foot, and mouth disease. Future mitigation policies should take into account the heterogeneities of disease burden identified. Additional epidemiological and serological studies are warranted to elucidate the dynamics and immunity patterns of local hand, foot, and mouth disease and to optimise interventions.
C1 [Xing, Weijia; Liao, Qiaohong; Zhang, Jing; Sun, Junling; Chang, Zhaorui; Liu, Fengfeng; Yu, Hongjie] Chinese Ctr Dis Control & Prevent, Key Lab Surveillance & Early Warning Infect Dis, Div Infect Dis, Beijing, Peoples R China.
[Viboud, Cecile] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Wu, Joseph T.; Fang, Vicky J.; Cowling, Benjamin J.; Leung, Gabriel M.] Univ Hong Kong, Sch Publ Hlth, Div Epidemiol & Biostatist, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China.
[Zheng, Yingdong] Peking Univ, Sch Publ Hlth, Hlth Sci Ctr, Beijing 100871, Peoples R China.
[Varma, Jay K.] New York City Dept Hlth & Mental Hyg, New York, NY USA.
[Farrar, Jeremy J.] Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Programmes, Ho Chi Minh City, Vietnam.
[Farrar, Jeremy J.] Univ Oxford, Churchill Hosp, Int Severe Acute Resp & Emerging Infect Consortiu, Ctr Trop Med, Oxford, England.
[Farrar, Jeremy J.] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore.
[Farrar, Jeremy J.] Li Ka Shing Oxford Global Hlth Programme & Wellco, Oxford, England.
RP Leung, GM (reprint author), Univ Hong Kong, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China.
EM gmleung@hku.hk
OI Farrar, Jeremy/0000-0002-2700-623X
FU China-US Collaborative Program on Emerging and Re-emerging Infectious
Diseases; Li Ka Shing Oxford Global Health Programme; Welkome Trust,
Harvard Center for Communicable Disease Dynamics, and Health and Medical
Research Fund, Government of Hong Kong Special Administrative Region;
WHO
FX Funding China-US Collaborative Program on Emerging and Re-emerging
Infectious Diseases, WHO, The Li Ka Shing Oxford Global Health Programme
and Wellcome Trust, Harvard Center for Communicable Disease Dynamics,
and Health and Medical Research Fund, Government of Hong Kong Special
Administrative Region.
NR 43
TC 143
Z9 182
U1 15
U2 54
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD APR
PY 2014
VL 14
IS 4
BP 308
EP 318
DI 10.1016/S1473-3099(13)70342-6
PG 11
WC Infectious Diseases
SC Infectious Diseases
GA AD8FJ
UT WOS:000333501600020
PM 24485991
ER
PT J
AU Zumla, AI
Gillespie, SH
Hoelscher, M
Philips, PPJ
Cole, ST
Abubakar, I
McHugh, TD
Schito, M
Maeurer, M
Nunn, AJ
AF Zumla, Alimuddin I.
Gillespie, Stephen H.
Hoelscher, Michael
Philips, Patrick P. J.
Cole, Stewart T.
Abubakar, Ibrahim
McHugh, Timothy D.
Schito, Marco
Maeurer, Markus
Nunn, Andrew J.
TI New antituberculosis drugs, regimens, and adjunct therapies: needs,
advances, and future prospects
SO LANCET INFECTIOUS DISEASES
LA English
DT Review
ID MULTIDRUG-RESISTANT TUBERCULOSIS; EARLY BACTERICIDAL ACTIVITY; 2 8-MONTH
REGIMENS; MYCOBACTERIUM-TUBERCULOSIS; ANTIRETROVIRAL THERAPY; PULMONARY
TUBERCULOSIS; IN-VITRO; LATENT TUBERCULOSIS; RANDOMIZED-TRIAL;
TUBERCLE-BACILLI
AB About 1.3 million people died of tuberculosis in 2012, despite availability of effective drug treatment. Barriers to improvements in outcomes include long treatment duration (resulting in poor patient adherence and loss of patients to follow-up), complex regimens that involve expensive and toxic drugs, toxic effects when given with antiretroviral therapy, and multidrug resistance. After 50 years of no antituberculosis drug development, a promising pipeline is emerging through the repurposing of old drugs, re-engineering of existing antibacterial compounds, and discovery of new compounds. A range of novel antituberculosis drugs are in preclinical development, several phase 2 and 3 trials are underway, and use of adjunct therapies is being explored for drug-sensitive and drug-resistant tuberculosis. Historical advances include approval of two new drugs, delamanid and bedaquiline. Combinations of new and existing drugs are being assessed to shorten the duration of therapy and to treat multidrug-resistant tuberculosis. There has also been progress in development of new antituberculosis drugs that are active against dormant or persister populations of Mycobacterium tuberculosis. In this Review, we discuss recent advances in antituberculosis drug discovery and development, clinical trial designs, laboratory methods, and adjunct host-directed therapies, and we provide an update of phase 3 trials of various fluoroquinolones (RIFAQUIN, NIRT, OFLOTUB, and REMoxTB). We also emphasise the need to engage the community in design, implementation, and uptake of research, to increase international cooperation between drug developers and health-care providers adopting new regimens.
C1 [Zumla, Alimuddin I.; McHugh, Timothy D.] UCL, Div Infect & Immun, Ctr Clin Microbiol, London W1T 4JF, England.
[Zumla, Alimuddin I.] UCL, Hosp NHS Fdn Trust, London W1T 4JF, England.
[Gillespie, Stephen H.] Univ St Andrews, Sch Med, St Andrews KY16 9AJ, Fife, Scotland.
[Hoelscher, Michael] Univ Munich, Dept Trop Med & Infect Dis, Munich, Germany.
[Hoelscher, Michael] German Ctr Infect Res, Munich, Germany.
[Philips, Patrick P. J.; Abubakar, Ibrahim; Nunn, Andrew J.] UCL, MRC, Clin Trials Unit, London W1T 4JF, England.
[Cole, Stewart T.] Ecole Polytech Fed Lausanne, Global Hlth Inst, EPFLSV GHI UPCOL, Lausanne, Switzerland.
[Schito, Marco] NIAID, Henry M Jackson Fdn, Div Aids, TB Clin Res Branch,NIH, Bethesda, MD 20892 USA.
[Maeurer, Markus] Karolinska Inst, Ctr Allogene Stem Cell Transplantat, Therapeut Immunol Div, Dept Lab Med, Stockholm, Sweden.
RP Zumla, AI (reprint author), UCL, Div Infect & Immun, Ctr Clin Microbiol, Royal Free Campus, London W1T 4JF, England.
EM a.zumla@ucl.ac.uk
RI Hoelscher, Michael/D-3436-2012;
OI McHugh, Timothy D/0000-0003-4658-8594; Abubakar,
Ibrahim/0000-0002-0370-1430; Zumla, Alimuddin/0000-0002-5111-5735;
Phillips, Patrick/0000-0002-6336-7024
FU UK European Union FP7Rid-RTI programme grant; European Developing
Countries Clinical Trials Partnership TB NEAT; PanACEA; REMox grants;
UBS Optimus Foundation, Switzerland; National Institute for Health
Research Biomedical Research Centre, University College London
Hospitals, London, UK; European Community's Seventh Framework Programme
[FP7/2007-13, 260872]; BmBF grants; European Developing Countries
Clinical Trials Partnership PanACEA [2007.32011.013]; Global Alliance
for Tuberculosis Drug Development; European and Developing Country
Clinical Trials Partnership [IP.200732011.011, IP.200732011.012,
IP.2007.32011.013]; European Developing Countries Clinical Trials
Partnership; TB NEAT; HLF (Heart and Lung foundation) Sweden;
Vetenskapsradet; VINNOVA; National Institute of Allergies and Infectious
Diseases, National Institutes of Health, Department of Health and Human
Services [HHSN272200800014C]
FX For development of table 1, we thank Michael J Vjecha, from the
Institute for Clinical Research, Washington, DC, USA, and Executive
Coordinator for US Centers for Disease Control and Prevention
Tuberculosis Trials Consortium. We thank Adam Zumla (UCL School of
Pharmact University College London, London, UK) for technical and
administrative assistance. AIZ is supported by UK European Union
FP7Rid-RTI programme grant; European Developing Countries Clinical
Trials Partnership TB NEAT, PanACEA, and REMox grants; and grants from
UBS Optimus Foundation, Switzerland, and National Institute for Health
Research Biomedical Research Centre, University College London
Hospitals, London, UK. STC is supported by European Community's Seventh
Framework Programme (FP7/2007-13) under grant agreement number 260872.
MH is supported by BmBF grants, European Developing Countries Clinical
Trials Partnership PanACEA 2007.32011.013, TB NEAT, PanACEA, and REMox
grants. SHG and TDMH are supported by Global Alliance for Tuberculosis
Drug Development; and European and Developing Country Clinical Trials
Partnership (grants IP.200732011.011, IP.200732011.012, and
IP.2007.32011.013), including TB NEAT, PanACEA, and REMox grants; and
Innovative Medicines Initiative Joint Undertaking grant 115337 MM is
supported by the European Developing Countries Clinical Trials
Partnership, TB NEAT, Vetenskapsradet, VINNOVA, and HLF (Heart and Lung
foundation) Sweden. MS is supported by National Institute of Allergies
and Infectious Diseases, National Institutes of Health, Department of
Health and Human Services under contract number HHSN272200800014C.
NR 116
TC 122
Z9 124
U1 8
U2 78
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD APR
PY 2014
VL 14
IS 4
BP 327
EP 340
DI 10.1016/S1473-3099(13)70328-1
PG 14
WC Infectious Diseases
SC Infectious Diseases
GA AD8FJ
UT WOS:000333501600022
PM 24670627
ER
PT J
AU Kumar, D
Raj, KK
Malhotra, SV
Rawat, DS
AF Kumar, Deepak
Raj, K. Kranthi
Malhotra, Sanjay V.
Rawat, Diwan S.
TI Synthesis and anticancer activity evaluation of resveratrol-chalcone
conjugates
SO MEDCHEMCOMM
LA English
DT Article
ID CHEMOPREVENTIVE AGENT RESVERATROL; APOPTOSIS-INDUCING AGENTS;
PYLORI-IN-VITRO; ANTIMALARIAL ACTIVITY; ANTIBACTERIAL ACTIVITY;
BIOLOGICAL EVALUATION; HELICOBACTER-PYLORI; RED WINE; NATURAL-PRODUCTS;
CELL-GROWTH
AB A series of novel resveratrol-chalcone conjugates have been synthesized. Four compounds were evaluated for their anticancer activity against 60 human cancer cell lines. Among all the derivatives, compound 70 was found to be the most active and showed high selectivity towards certain ovarian cancer, non-small cell lung cancer and breast cancer cell lines with GI(50) values in the range of 1.28-34.1 mu M. Docking studies were performed to determine the probable binding mode of these compounds in the colchicine-tubulin binding site. A strong H-bonding interaction (1.852 angstrom) was observed with Cys-241 amino acid present in the binding pocket. Thus we believe that compound 70 may possibly be used as a lead for the development of new anticancer agents.
C1 [Kumar, Deepak; Raj, K. Kranthi; Rawat, Diwan S.] Univ Delhi, Dept Chem, Delhi 110007, India.
[Malhotra, Sanjay V.] SAIC Frederick Inc, NCI, Lab Synthet Chem, Frederick, MD 21702 USA.
RP Rawat, DS (reprint author), Univ Delhi, Dept Chem, Delhi 110007, India.
EM dsrawat@chemistry.du.ac.in
OI Rawat, Diwan/0000-0002-5473-7476
FU Council of Scientific and Industrial Research (CSIR) New Delhi, India
[02(0049)/12/EMR-II]; DU-PURSE grant; CSIR; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]
FX D.S.R. thanks the Council of Scientific and Industrial Research (CSIR)
[no. 02(0049)/12/EMR-II] New Delhi, India and DU-PURSE grant for
financial support. D.K. and K.K.R. are thankful to CSIR for the award of
senior research fellowship and research associate fellowship. S.V.M.
would like to acknowledge the support from the National Cancer
Institute, National Institutes of Health, under contract no.
HHSN261200800001E. The authors are also thankful to CIF-USIC, the
University of Delhi, Delhi for NMR spectral data and RSIC, CDRI, Lucknow
for mass data.
NR 70
TC 8
Z9 8
U1 1
U2 18
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2040-2503
EI 2040-2511
J9 MEDCHEMCOMM
JI MedChemComm
PD APR
PY 2014
VL 5
IS 4
BP 528
EP 535
DI 10.1039/c3md00329a
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA AD9JA
UT WOS:000333580000017
ER
PT J
AU An, P
Miljkovic, I
Thyagarajan, B
Kraja, AT
Daw, EW
Pankow, JS
Selvin, E
Kao, WHL
Maruthur, NM
Nalls, MA
Liu, YM
Harris, TB
Lee, JH
Borecki, IB
Christensen, K
Eckfeldt, JH
Mayeux, R
Perls, TT
Newman, AB
Province, MA
AF An, Ping
Miljkovic, Iva
Thyagarajan, Bharat
Kraja, Aldi T.
Daw, E. Warwick
Pankow, James S.
Selvin, Elizabeth
Kao, W. H. Linda
Maruthur, Nisa M.
Nalls, Micahel A.
Liu, Yongmei
Harris, Tamara B.
Lee, Joseph H.
Borecki, Ingrid B.
Christensen, Kaare
Eckfeldt, John H.
Mayeux, Richard
Perls, Thomas T.
Newman, Anne B.
Province, Michael A.
TI Genome-wide association study identifies common loci influencing
circulating glycated hemoglobin (HbA(1c)) levels in non-diabetic
subjects: The Long Life Family Study (LLFS)
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
DE Genome-wide association study; Non-enzymatic glycation; Glucose; Insulin
resistance and diabetes; Premature aging processes
ID GLYCEMIC CONTROL; GLUCOSE; A1C; MORTALITY; COMMUNITY; VARIANTS; HEALTH;
RISK
AB Objective. Glycated hemoglobin (HbA(1c)) is a stable index of chronic glycemic status and hyperglycemia associated with progressive development of insulin resistance and frank diabetes. It is also associated with premature aging and increased mortality. To uncover novel loci for HbA(1c) that are associated with healthy aging, we conducted a genome-wide association study (GWAS) using non-diabetic participants in the Long Life Family Study (LLFS), a study with familial clustering of exceptional longevity in the US and Denmark.
Methods. A total of 4088 non-diabetic subjects from the LLFS were used for GWAS discoveries, and a total of 8231 non-diabetic subjects from the Atherosclerosis Risk in Communities Study (ARIC, in the MAGIC Consortium) and the Health, Aging, and Body Composition Study (HABC) were used for GWAS replications. HbA(1c) was adjusted for age, sex, centers, 20 principal components, without and with BMI. A linear mixed effects model was used for association testing.
Results. Two known loci at GCK rs730497 (or rs2908282) and HK1 rs17476364 were confirmed (p < 5e-8). Of 25 suggestive (5e-8 < p < 1e-5) loci, one known (G6PC2 rs560887, replication p = 5e-5) and one novel (OR10R3P/SPTA1 - rs12041363, replication p = 1e-17) loci were replicated (p <0.0019). Similar findings resulted when HbA(1c) was further adjusted for BMI. Further validations are crucial for the remaining suggestive loci including the emerged variant near OR10R3P/SPTA1.
Conclusions. The analysis reconfirmed two known GWAS loci (GCK, HK1) and identified 25 suggestive loci including one reconfirmed variant in G6PC2 and one replicated variant near OR10R3P/SPTA1. Future focused survey of sequence elements containing mainly functional and regulatory variants may yield additional findings. (C) 2014 Elsevier Inc. All rights reserved.
C1 [An, Ping; Kraja, Aldi T.; Daw, E. Warwick; Borecki, Ingrid B.; Province, Michael A.] Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63108 USA.
[Miljkovic, Iva; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA USA.
[Thyagarajan, Bharat; Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Selvin, Elizabeth; Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Maruthur, Nisa M.] Johns Hopkins Univ, Div Gen Internal Med, Baltimore, MD USA.
[Nalls, Micahel A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Liu, Yongmei] Wake Forest Univ, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Lee, Joseph H.; Mayeux, Richard] Columbia Univ, Gertrude H Sergieusky Ctr, New York, NY USA.
[Lee, Joseph H.; Mayeux, Richard] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA.
[Christensen, Kaare] Univ Southern Denmark, Danish Aging Res Ctr, Odense, Denmark.
[Christensen, Kaare] Odense Univ Hosp, Dept Clin Biochem & Pharmacol, DK-5000 Odense, Denmark.
[Christensen, Kaare] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark.
[Perls, Thomas T.] Boston Univ, Med Ctr, Dept Med, Div Geriatr, Boston, MA USA.
RP An, P (reprint author), Washington Univ, Sch Med, Div Stat Genom, Dept Genet, Campus Box 8056,4444 Forest Pk Blvd, St Louis, MO 63108 USA.
EM anping@wustl.edu
RI Newman, Anne B./C-6408-2013;
OI Newman, Anne B./0000-0002-0106-1150; Miljkovic, Iva/0000-0002-3155-9777;
Lee, Joseph H/0000-0002-2000-4821
FU National Institute on Aging (NIA) [U01AG023712, U01AG023744,
U01AG023746, U01AG023749, U01AG023755, U19AG023122, K24AG025727,
R01AG032319, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1];
Glenn Medical Research Foundation; National Heart Lung Blood Institute
(NHLBI) [R21HL114237, HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; National Human
Genome Research Institute [U01HG004402]; NIH [HHSN268200625226C,
HHSN268200782096C, UL1RR025005]; NIH/NIDDK [R21DK080294, K01DK076595,
K01067207]; NIH, NIA; [R01HL087641]; [R01HL59367]; [R01HL086694]
FX The Long Life Family Study (LLFS): The Long Life Family Study was
supported by the National Institute on Aging (NIA) grants U01AG023712,
U01AG023744, U01AG023746, U01AG023749, U01AG023755, U19AG023122,
K24AG025727, R01AG032319, the Glenn Medical Research Foundation, and the
National Heart Lung Blood Institute (NHLBI, R21HL114237). The content is
solely the responsibility of the authors, and does not necessarily
represent the official views of the NIA or the National Institutes of
Health (NIH). The Atherosclerosis Risk in Communities (ARIC) Study: The
Atherosclerosis Risk in Communities Study was carried out as a
collaborative study supported by the NHLBI contracts (HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and
HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; the
National Human Genome Research Institute contract U01HG004402; and the
NIH contract HHSN268200625226C. The authors thank the staff and
participants of the ARIC Study for their important contributions.
Infrastructure was partly supported by Grant Number UL1RR025005, a
component of the NIH and NIH Roadmap for Medical Research. This research
was supported in part by NIH/NIDDK grants R21DK080294 and K01DK076595
(E.S.) and K01067207 (W.H.L.K.). The Health, Aging, and Body Composition
(Health ABC) Study: The Health, Aging, and Body Composition Study was
supported by the NIA contracts N01AG62101, N01AG62103, and N01AG62106,
and in part by the Intramural Research Program of the NIH, NIA. The
genome-wide association study was funded by the NIA grant
1R01AG032098-01A1 to Wake Forest University Health Sciences and
genotyping services were provided by the Center for Inherited Disease
Research (CIDR). CIDR is fully funded through a federal contract from
the NIH to the Johns Hopkins University, contract number
HHSN268200782096C.
NR 30
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U1 1
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
EI 1532-8600
J9 METABOLISM
JI Metab.-Clin. Exp.
PD APR
PY 2014
VL 63
IS 4
BP 461
EP 468
DI 10.1016/j.metabol.2013.11.018
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AE0MB
UT WOS:000333659300004
PM 24405752
ER
PT J
AU Jimenez-Morales, S
Jimenez-Ruiz, JL
Del Rio-Navarro, BE
Navarro-Olivos, E
Escamilla-Guerrero, G
Savan, R
Dean, M
Orozco, L
AF Jimenez-Morales, Silvia
Luis Jimenez-Ruiz, Juan
Estela Del Rio-Navarro, Blanca
Navarro-Olivos, Efrain
Escamilla-Guerrero, Guillermo
Savan, Ram
Dean, Michael
Orozco, Lorena
TI CHRM2 but not CHRM1 or CHRM3 polymorphisms are associated with asthma
susceptibility in Mexican patients
SO MOLECULAR BIOLOGY REPORTS
LA English
DT Article
DE Asthma; Cholinergic muscarinic genes; Association study; Susceptibility
genes; Mexican patients
ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; JUVENILE RHEUMATOID-ARTHRITIS;
SYSTEMIC-LUPUS-ERYTHEMATOSUS; G-PROTEIN ACTIVATION; ALCOHOL DEPENDENCE;
GENE; M-2; M2; AIRWAYS; HYPERRESPONSIVENESS
AB Asthma is a complex disease for which genetic predisposition has been widely documented. Considerable evidence supports the hypothesis that polymorphisms in the muscarinic-cholinergic (CHRM) genes could be involved in asthma pathogenesis, bronchial hyperresponsiveness, and mucus secretion. To determine whether single nucleotide polymorphisms (SNPs) or haplotypes in CHRM1, CHRM2, or CHRM3 are associated with asthma in Mexican pediatric population. We performed a case-control study including 398 pediatric cases with asthma and 450 healthy controls. We analyzed 19 SNPs distributed among these three genes. Two of the seven SNPs located in CHRM2, the 3' untranslated region rs8191992 and rs6962027, differed significantly in allele frequencies between patients with asthma and healthy controls [odds ratio (OR) 1.42, 95 % confidence interval (95 % CI) 1.14-1.77, P = 0.001, and OR 1.50, 95 % CI 1.21-1.87, P = 0.0002, respectively]. Statistical significance remained after multiple comparison corrections (P = 0.003 and P = 0.005, respectively). The haplotypes AA and TT, containing both major and minor alleles from rs8191992 and rs6962027, also differed between cases and controls. The haplotype AA occurred at a lower frequency in cases (OR 0.67, 95 % CI 0.53-0.85, P = 0.001) whereas the haplotype TT was overrepresented in cases compared to controls (28 vs 21 %, respectively; OR 1.46, 95 % CI 1.15-1.85, P = 0.002). No association was observed between CHRM1 or CHRM3 SNPs or haplotypes and asthma. CHRM2 polymorphisms are implicated in the genetic etiology of asthma.
C1 [Jimenez-Morales, Silvia; Luis Jimenez-Ruiz, Juan; Orozco, Lorena] Inst Nacl Med Genom, Lab Immunogen & Metab Dis, SS, Mexico City 014610, DF, Mexico.
[Estela Del Rio-Navarro, Blanca] Hosp Infantil Mexico Dr Federico Gomez, Dept Allergy, Mexico City, DF, Mexico.
[Navarro-Olivos, Efrain] Secretaria Salud Estado Guanajuato, Div Res, Guanajuato, Mexico.
[Escamilla-Guerrero, Guillermo] Inst Nacl Pediat, Blood Bank, Mexico City, DF, Mexico.
[Savan, Ram] NCI, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD 21702 USA.
[Dean, Michael] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Orozco, L (reprint author), Inst Nacl Med Genom, Lab Immunogen & Metab Dis, SS, Perifer Sur 4809, Mexico City 014610, DF, Mexico.
EM lorozco@inmegen.gob.mx
RI Dean, Michael/G-8172-2012
OI Dean, Michael/0000-0003-2234-0631
FU Consejo Nacional de Ciencia y Tecnologia, Mexico (CONACyT)
[SALUD-008-2011-C01-161936]
FX This study was supported by a grant from Consejo Nacional de Ciencia y
Tecnologia, Mexico (CONACyT): SALUD-008-2011-C01-161936. Authors would
like to thanks all patients and families for their participation.
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PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0301-4851
EI 1573-4978
J9 MOL BIOL REP
JI Mol. Biol. Rep.
PD APR
PY 2014
VL 41
IS 4
BP 2109
EP 2117
DI 10.1007/s11033-014-3060-6
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AE1DN
UT WOS:000333707100025
PM 24430298
ER
PT J
AU Li, M
Luo, XJ
Rietschel, M
Lewis, CM
Mattheisen, M
Muller-Myhsok, B
Jamain, S
Leboyer, M
Landen, M
Thompson, PM
Cichon, S
Nothen, MM
Schulze, TG
Sullivan, PF
Bergen, SE
Donohoe, G
Morris, DW
Hargreaves, A
Gill, M
Corvin, A
Hultman, C
Toga, AW
Shi, L
Lin, Q
Shi, H
Gan, L
Meyer-Lindenberg, A
Czamara, D
Henry, C
Etain, B
Bis, JC
Ikram, MA
Fornage, M
Debette, S
Launer, LJ
Seshadri, S
Erk, S
Walter, H
Heinz, A
Bellivier, F
Stein, JL
Medland, SE
Vasquez, AA
Hibar, DP
Franke, B
Martin, NG
Wright, MJ
Su, B
AF Li, M.
Luo, X-j
Rietschel, M.
Lewis, C. M.
Mattheisen, M.
Mueller-Myhsok, B.
Jamain, S.
Leboyer, M.
Landen, M.
Thompson, P. M.
Cichon, S.
Noethen, M. M.
Schulze, T. G.
Sullivan, P. F.
Bergen, S. E.
Donohoe, G.
Morris, D. W.
Hargreaves, A.
Gill, M.
Corvin, A.
Hultman, C.
Toga, A. W.
Shi, L.
Lin, Q.
Shi, H.
Gan, L.
Meyer-Lindenberg, A.
Czamara, D.
Henry, C.
Etain, B.
Bis, J. C.
Ikram, M. A.
Fornage, M.
Debette, S.
Launer, L. J.
Seshadri, S.
Erk, S.
Walter, H.
Heinz, A.
Bellivier, F.
Stein, J. L.
Medland, S. E.
Vasquez, A. Arias
Hibar, D. P.
Franke, B.
Martin, N. G.
Wright, M. J.
Su, B.
CA MooDS Bipolar Consortium
Swedish Bipolar Study Group
Alzheimer's Dis Neuroimaging
ENIGMA Consortium
CHARGE Consortium
TI Allelic differences between Europeans and Chinese for CREB1 SNPs and
their implications in gene expression regulation, hippocampal structure
and function, and bipolar disorder susceptibility
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE association; bipolar disorder; CREB1; gene expression; intermediate
phenotype; natural selection
ID GENOME-WIDE ASSOCIATION; MAJOR DEPRESSIVE DISORDER; HUMAN PREFRONTAL
CORTEX; COMMON VARIANTS; STATISTICAL TESTS; SPATIAL LOCATION;
SCHIZOPHRENIA; POPULATION; TRANSCRIPTION; LANDSCAPE
AB Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64 888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P = 6.32 x 10(-5), odds ratio (OR) = 1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P < 0.005) and the prefrontal cortex (P < 1.0 x 10(-6)). Remarkably, population genetic analysis indicated that CREB1 displayed striking differences in allele frequencies between continental populations, and the risk alleles were completely absent in East Asian populations. We demonstrated that the regional prevalence of the CREB1 risk alleles in Europeans is likely caused by genetic hitchhiking due to natural selection acting on a nearby gene. Our results suggest that differential population histories due to natural selection on regional populations may lead to genetic heterogeneity of susceptibility to complex diseases, such as BD, and explain inconsistencies in detecting the genetic markers of these diseases among different ethnic populations.
C1 [Li, M.; Shi, L.; Lin, Q.; Shi, H.; Su, B.] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China.
[Li, M.; Gan, L.] Univ Chinese Acad Sci, Beijing, Peoples R China.
[Luo, X-j] Univ Rochester, Flaum Eye Inst, Rochester, NY USA.
[Rietschel, M.; Schulze, T. G.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.
[Rietschel, M.; Walter, H.] Univ Bonn, Dept Psychiat, Bonn, Germany.
[Lewis, C. M.] Kings Coll London, Inst Psychiat, MRC SGDP Ctr, London WC2R 2LS, England.
[Mattheisen, M.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Mattheisen, M.] Harvard Univ, Sch Med, Boston, MA USA.
[Mueller-Myhsok, B.; Czamara, D.] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Jamain, S.; Leboyer, M.; Henry, C.; Etain, B.; Bellivier, F.] Hop Henri Mondor, INSERM, U955, IMRB, F-94010 Creteil, France.
[Jamain, S.; Leboyer, M.; Henry, C.; Etain, B.; Bellivier, F.] Fdn Fondamental, Creteil, France.
[Leboyer, M.; Henry, C.; Etain, B.] Hop H Mondor A Chenevier, AP HP, Creteil, France.
[Leboyer, M.; Henry, C.] Univ Paris Est, Fac Med, Creteil, France.
[Landen, M.] Gothenburg Univ, Sahlgrenska Acad, Sect Psychiat & Neurochem, Gothenburg, Sweden.
[Landen, M.; Hultman, C.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Thompson, P. M.; Toga, A. W.; Stein, J. L.; Hibar, D. P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Imaging Genet Ctr,Lab Neuro Imaging, Los Angeles, CA 90095 USA.
[Cichon, S.] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany.
[Cichon, S.; Noethen, M. M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany.
[Cichon, S.; Noethen, M. M.] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Noethen, M. M.] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany.
[Schulze, T. G.] Univ Gottingen, Sect Psychiat Genet, Dept Psychiat & Psychotherapy, Univ Med Ctr, D-37073 Gottingen, Germany.
[Sullivan, P. F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Sullivan, P. F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Sullivan, P. F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Bergen, S. E.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Bergen, S. E.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Donohoe, G.; Morris, D. W.; Hargreaves, A.; Gill, M.; Corvin, A.] Univ Dublin Trinity Coll, St James Hosp, Neuropsychiat Genet Grp, Dublin 2, Ireland.
[Donohoe, G.; Morris, D. W.; Hargreaves, A.; Gill, M.; Corvin, A.] Univ Dublin Trinity Coll, St James Hosp, Dept Psychiat, Inst Mol Med, Dublin 2, Ireland.
[Donohoe, G.; Morris, D. W.; Hargreaves, A.; Gill, M.; Corvin, A.] Univ Dublin Trinity Coll, St James Hosp, Inst Neurosci, Dublin 2, Ireland.
[Meyer-Lindenberg, A.] Heidelberg Univ, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, Mannheim, Germany.
[Bis, J. C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Ikram, M. A.] Erasmus MC Univ Med Ctr, Dept Radiol & Epidemiol, Rotterdam, Netherlands.
[Ikram, M. A.] Netherlands Consortium Hlth Aging, Leiden, Netherlands.
[Fornage, M.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Brown Fdn Inst Mol Med, Houston, TX 77030 USA.
[Fornage, M.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
[Debette, S.; Seshadri, S.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Debette, S.] INSERM, U708, Paris, France.
[Debette, S.] Univ Versailles St Quentin En Yvelines, Dept Epidemiol, Paris, France.
[Launer, L. J.] NIA, Neurogenet Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Seshadri, S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Erk, S.; Walter, H.; Heinz, A.] Charite, Dept Psychiat, D-13353 Berlin, Germany.
[Erk, S.; Walter, H.] Charite, Div Mind & Brain Res, D-13353 Berlin, Germany.
[Bellivier, F.] Hop St Louis Lariboisiere F Widal, AP HP, Serv Univ Psychiat, Paris, France.
[Bellivier, F.] Univ Paris 07, Fac Med, Paris, France.
[Stein, J. L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Neurogenet Program, Los Angeles, CA 90095 USA.
[Medland, S. E.; Martin, N. G.; Wright, M. J.] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4006, Australia.
[Medland, S. E.] Queensland Inst Med Res, Quantitat Genet Lab, Brisbane, Qld 4006, Australia.
[Medland, S. E.] Broad Inst Harvard & MIT, Boston, MA USA.
[Vasquez, A. Arias; Franke, B.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Vasquez, A. Arias; Franke, B.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands.
RP Su, B (reprint author), Chinese Acad Sci, Kunming Inst Zool, 32 East Jiao Chang Rd, Kunming 650223, Peoples R China.
EM sub@mail.kiz.ac.cn
RI Lewis, Cathryn/A-5225-2010; Franke, Barbara/D-4836-2009; Medland,
Sarah/C-7630-2013; Walter, Henrik/O-2612-2013; Li, Ming/K-7455-2013;
Mattheisen, Manuel/B-4949-2012; Wright, Margaret/A-4560-2016; Arias
Vasquez, Alejandro/E-4762-2012; BELLIVIER, FRANK/H-5197-2012;
OI Corvin, Aiden/0000-0001-6717-4089; Morris, Derek/0000-0002-3413-570X;
Landen, Mikael/0000-0002-4496-6451; Gill, Michael/0000-0003-0206-5337;
Ikram, Mohammad Arfan/0000-0003-0372-8585; Stein,
Jason/0000-0003-4829-0513; Nothen, Markus/0000-0002-8770-2464; Donohoe,
Gary/0000-0003-3037-7426; Meyer-Lindenberg, Andreas/0000-0001-5619-1123;
Jamain, Stephane/0000-0002-4321-4100; Lewis,
Cathryn/0000-0002-8249-8476; Seshadri, Sudha/0000-0001-6135-2622;
Franke, Barbara/0000-0003-4375-6572; Medland, Sarah/0000-0003-1382-380X;
Li, Ming/0000-0002-8197-6552; Mattheisen, Manuel/0000-0002-8442-493X;
Wright, Margaret/0000-0001-7133-4970; Arias Vasquez,
Alejandro/0000-0002-4786-0169; Bergen, Sarah/0000-0002-5888-0034; Etain,
Bruno/0000-0002-5377-1488; Martin, Nicholas/0000-0003-4069-8020
FU National 973 project of China [2011CBA00401]; National Natural Science
Foundation of China [U1202225, 31130051, 31071101]; German Federal
Ministry of Education and Research (BMBF); National Genome Research
Network (NGFN); Integrated Genome Research Network (IG) MooDS
[01GS08144]; MMR [01GS08147]; TGS
FX We acknowledge the Bipolar Disorder Working Group of Psychiatric GWAS
Consortium for their efforts. We are deeply grateful for Stacy
Steinberg, Hreinn Stefansson, Kari Stefansson (deCODE genetics,
Reykjavik, Iceland) and Engilbert Sigurdsson (Landspitali University
Hospital, Reykjavi ' k, Iceland) for their results in the Icelandic
samples, Angelika Erhardt (Max Planck Institute of Psychiatry,
Kraepelinstr, Munich, Germany) for her assistance in this study, Andrew
Willden (Kunming Institute of Zoology, China) for the language editing
of the manuscript. We wish to thank Xiaosen Guo, Shanshan Dong and Jun
Wang (Shenzhen Key Laboratory of Transomics Biotechnologies,
BGI-Shenzhen, China) for providing sequence data of CREB1 from the
1000-Human-Genome project. We would like to thank Daniel R. Weinberger
(Lieber Institute for Brain Development, Johns Hopkins University
Medical Campus, Baltimore, USA) for his very helpful review of the
manuscript. This work was supported by grants from the National 973
project of China (2011CBA00401), the National Natural Science Foundation
of China (U1202225, 31130051 and 31071101), the German Federal Ministry
of Education and Research (BMBF), the National Genome Research Network
(NGFN), and the Integrated Genome Research Network (IG) MooDS (grant
01GS08144 to SC and MMR, grant 01GS08147 to MR and TGS).
NR 75
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U1 8
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD APR
PY 2014
VL 19
IS 4
BP 452
EP 461
DI 10.1038/mp.2013.37
PG 10
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA AD6ZB
UT WOS:000333409100011
PM 23568192
ER
PT J
AU Guillozet-Bongaarts, AL
Hyde, TM
Dalley, RA
Hawrylycz, MJ
Henry, A
Hof, PR
Hohmann, J
Jones, AR
Kuan, CL
Royall, J
Shen, E
Swanson, B
Zeng, H
Kleinman, JE
AF Guillozet-Bongaarts, A. L.
Hyde, T. M.
Dalley, R. A.
Hawrylycz, M. J.
Henry, A.
Hof, P. R.
Hohmann, J.
Jones, A. R.
Kuan, C. L.
Royall, J.
Shen, E.
Swanson, B.
Zeng, H.
Kleinman, J. E.
TI Altered gene expression in the dorsolateral prefrontal cortex of
individuals with schizophrenia
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE gene expression; in situ hybridization; prefrontal cortex; schizophrenia
ID CALCIUM-BINDING PROTEINS; WORKING-MEMORY IMPAIRMENTS; NURR1-NULL
HETEROZYGOUS MICE; MESSENGER-RNA EXPRESSION; RECEPTOR SUBUNIT GENE;
GABAERGIC NEURONS; BIPOLAR DISORDER; IMMUNOREACTIVE NEURONS;
MORPHOMETRIC ANALYSIS; CHROMOSOME 15Q13-14
AB The underlying pathology of schizophrenia (SZ) is likely as heterogeneous as its symptomatology. A variety of cortical and subcortical regions, including the prefrontal cortex, have been implicated in its pathology, and a number of genes have been identified as risk factors for disease development. We used in situ hybridization (ISH) to examine the expression of 58 genes in the dorsolateral prefrontal cortex (DLPFC, comprised of Brodmann areas 9 and 46) from 19 individuals with a premorbid diagnosis of SZ and 33 control individuals. Genes were selected based on: (1) previous identification as risk factors for SZ; (2) cell type markers or (3) laminar markers. Cell density and staining intensity were compared in the DLPFC, as well as separately in Brodmann areas 9 and 46. The expression patterns of a variety of genes, many of which are associated with the GABAergic system, were altered in SZ when compared with controls. Additional genes, including C8orf79 and NR4A2, showed alterations in cell density or staining intensity between the groups, highlighting the need for additional studies. Alterations were, with only a few exceptions, limited to Brodmann area 9, suggesting regional specificity of pathology in the DLPFC. Our results agree with previous studies on the GABAergic involvement in SZ, and suggest that areas 9 and 46 may be differentially affected in the disease. This study also highlights additional genes that may be altered in SZ, and indicates that these potentially interesting genes can be identified by ISH and high-throughput image analysis techniques.
C1 [Guillozet-Bongaarts, A. L.; Dalley, R. A.; Hawrylycz, M. J.; Henry, A.; Hohmann, J.; Jones, A. R.; Kuan, C. L.; Royall, J.; Shen, E.; Swanson, B.; Zeng, H.] Allen Inst Brain Sci, Seattle, WA 98103 USA.
[Hyde, T. M.; Kleinman, J. E.] Johns Hopkins Med Campus, Lieber Inst Brain Dev, Baltimore, MD USA.
[Hyde, T. M.; Kleinman, J. E.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Hyde, T. M.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Hyde, T. M.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Hof, P. R.] Icahn Sch Med, Fishberg Dept Neurosci & Friedman Brain Inst, New York, NY USA.
RP Guillozet-Bongaarts, AL (reprint author), Allen Inst Brain Sci, 551North 34th St, Seattle, WA 98103 USA.
EM angieb@alleninstitute.org
FU Allen Institute founders
FX We would like to thank the families of the deceased for the donations of
brain tissue, and their time and effort devoted to the consent process
and interviews, and the staff of the Offices of the Chief Medical
Examiner of District of Columbia and Northern Virginia for their
assistance. We would also like to thank the Allen Institute founders, PG
Allen and J Allen, for their vision, encouragement and support.
NR 83
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U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD APR
PY 2014
VL 19
IS 4
BP 478
EP 485
DI 10.1038/mp.2013.30
PG 8
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA AD6ZB
UT WOS:000333409100014
PM 23528911
ER
PT J
AU Roukos, V
Misteli, T
AF Roukos, Vassilis
Misteli, Tom
TI The biogenesis of chromosome translocations
SO NATURE CELL BIOLOGY
LA English
DT Review
ID DOUBLE-STRAND BREAKS; END-JOINING PATHWAY; CLASS SWITCH RECOMBINATION;
DNA-DAMAGE RESPONSE; MAMMALIAN-CELLS; HOMOLOGOUS RECOMBINATION;
SACCHAROMYCES-CEREVISIAE; NUCLEAR ARCHITECTURE; CHROMATIN MOVEMENT;
SPATIAL-ORGANIZATION
AB Chromosome translocations are catastrophic genomic events and often play key roles in tumorigenesis. Yet the biogenesis of chromosome translocations is remarkably poorly understood. Recent work has delineated several distinct mechanistic steps in the formation of translocations, and it has become apparent that non-random spatial genome organization, DNA repair pathways and chromatin features, including histone marks and the dynamic motion of broken chromatin, are critical for determining translocation frequency and partner selection.
C1 [Roukos, Vassilis; Misteli, Tom] NCI, Bethesda, MD 20892 USA.
RP Roukos, V (reprint author), NCI, Bethesda, MD 20892 USA.
EM roukosv@mail.nih.gov; mistelit@mail.nih.gov
RI Roukos, Vassilis/K-6248-2012
FU Intramural Research Program of the National Institutes of Health (NIH),
NCI, Center for Cancer Research
FX The Misteli laboratory is supported by the Intramural Research Program
of the National Institutes of Health (NIH), NCI, Center for Cancer
Research. We dedicate this Review to the memory of Janet Rowley, who
boldly founded and thoughtfully guided the field of chromosome
translocation biology.
NR 124
TC 31
Z9 32
U1 1
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
EI 1476-4679
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD APR
PY 2014
VL 16
IS 4
BP 293
EP 300
DI 10.1038/ncb2941
PG 8
WC Cell Biology
SC Cell Biology
GA AD9AM
UT WOS:000333556900001
PM 24691255
ER
PT J
AU Atwood, BK
Kupferschmidt, DA
Lovinger, DM
AF Atwood, Brady K.
Kupferschmidt, David A.
Lovinger, David M.
TI Opioids induce dissociable forms of long-term depression of excitatory
inputs to the dorsal striatum
SO NATURE NEUROSCIENCE
LA English
DT Article
ID RECEPTOR MESSENGER-RNA; IN-SITU HYBRIDIZATION; RAT-BRAIN;
SYNAPTIC-TRANSMISSION; NUCLEUS-ACCUMBENS; UNITED-STATES; DELTA;
LOCALIZATION; NEURONS; MU
AB As prescription opioid analgesic abuse rates rise, so does the need to understand the long-term effects of opioid exposure on brain function. The dorsal striatum is an important site for drug-induced neuronal plasticity. We found that exogenously applied and endogenously released opioids induced long-term depression (OP-LTD) of excitatory inputs to the dorsal striatum in mice and rats. Mu and delta OP-LTD, although both being presynaptically expressed, were dissociable in that they summated, differentially occluded endocannabinoid-LTD and inhibited different striatal inputs. Kappa OP-LTD showed a unique subregional expression in striatum. A single in vivo exposure to the opioid analgesic oxycodone disrupted mu OP-LTD and endocannabinoid-LTD, but not delta or kappa OP-LTD. These data reveal previously unknown opioid-mediated forms of long-term striatal plasticity that are differentially affected by opioid analgesic exposure and are likely important mediators of striatum-dependent learning and behavior.
C1 [Atwood, Brady K.; Kupferschmidt, David A.; Lovinger, David M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Lovinger, DM (reprint author), NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM lovindav@mail.nih.gov
FU Division of Intramural Clinical and Biological Research of the National
Institute on Alcohol Abuse and Alcoholism, US National Institutes of
Health
FX We extend special thanks to W. Xiong for his efforts in performing
preliminary experiments for this study. This research was supported by
the Division of Intramural Clinical and Biological Research of the
National Institute on Alcohol Abuse and Alcoholism, US National
Institutes of Health.
NR 48
TC 20
Z9 20
U1 2
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD APR
PY 2014
VL 17
IS 4
BP 540
EP U91
DI 10.1038/nn.3652
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA AD6XR
UT WOS:000333405300014
PM 24561996
ER
PT J
AU Awasaki, T
Kao, CF
Lee, YJ
Yang, CP
Huang, YL
Pfeiffer, BD
Luan, HJ
Jing, XT
Huang, YF
He, YS
Schroeder, MD
Kuzin, A
Brody, T
Zugates, CT
Odenwald, WF
Lee, T
AF Awasaki, Takeshi
Kao, Chih-Fei
Lee, Ying-Jou
Yang, Ching-Po
Huang, Yaling
Pfeiffer, Barret D.
Luan, Haojiang
Jing, Xiaotang
Huang, Yu-Fen
He, Yisheng
Schroeder, Mark David
Kuzin, Alexander
Brody, Thomas
Zugates, Christopher T.
Odenwald, Ward F.
Lee, Tzumin
TI Making Drosophila lineage-restricted drivers via patterned recombination
in neuroblasts
SO NATURE NEUROSCIENCE
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; SITE-SPECIFIC RECOMBINATION; TARGETED
GENE-EXPRESSION; EARLY BRAIN-DEVELOPMENT; TRANSGENE EXPRESSION;
DEVELOPMENTAL ORIGIN; MOSAIC ANALYSIS; CELL LINEAGE; MELANOGASTER;
NEURONS
AB The Drosophila cerebrum originates from about 100 neuroblasts per hemisphere, with each neuroblast producing a characteristic set of neurons. Neurons from a neuroblast are often so diverse that many neuron types remain unexplored. We developed new genetic tools that target neuroblasts and their diverse descendants, increasing our ability to study fly brain structure and development. Common enhancer-based drivers label neurons on the basis of terminal identities rather than origins, which provides limited labeling in the heterogeneous neuronal lineages. We successfully converted conventional drivers that are temporarily expressed in neuroblasts, into drivers expressed in all subsequent neuroblast progeny. One technique involves immortalizing GAL4 expression in neuroblasts and their descendants. Another depends on loss of the GAL4 repressor, GAL80, from neuroblasts during early neurogenesis. Furthermore, we expanded the diversity of MARCM-based reagents and established another site-specific mitotic recombination system. Our transgenic tools can be combined to map individual neurons in specific lineages of various genotypes.
C1 [Awasaki, Takeshi; Lee, Ying-Jou; Huang, Yaling; Pfeiffer, Barret D.; Luan, Haojiang; Jing, Xiaotang; Huang, Yu-Fen; He, Yisheng; Schroeder, Mark David; Zugates, Christopher T.; Lee, Tzumin] Howard Hughes Med Inst, Ashburn, VA USA.
[Awasaki, Takeshi] Kyorin Univ, Sch Med, Mitaka, Tokyo 181, Japan.
[Kao, Chih-Fei; Yang, Ching-Po; Lee, Tzumin] Univ Massachusetts, Dept Neurobiol, Worcester, MA 01605 USA.
[Kuzin, Alexander; Brody, Thomas; Odenwald, Ward F.] NINDS, Neural Cell Fate Determinants Sect, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Lee, T (reprint author), Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA USA.
EM leet@janelia.hhmi.org
FU Howard Hughes Medical Institute; US National Institutes of Health
FX We thank Janelia Farm fly core, especially M. Mercer, and Janelia Farm
Fly Light, including R. Johnston, E. Willis, S. Tae and R. Vorimo, for
their essential technical support. We thank S. Murphy, T. Safford, K.
Rokicki, E. Trautman, Y. Yu and the rest of the team that developed the
Janelia Farm fly brain workstation for streamlining our confocal image
analysis. We thank J. Truman and G. Rubin for helpful discussions and
sharing imagery of GR GAL4 lines before publication, and C. Sullivan for
administrative support. This work was supported by Howard Hughes Medical
Institute and the US National Institutes of Health.
NR 45
TC 11
Z9 11
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD APR
PY 2014
VL 17
IS 4
BP 631
EP U203
DI 10.1038/nn.3654
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA AD6XR
UT WOS:000333405300025
PM 24561995
ER
PT J
AU Maurice, DH
Ke, HM
Ahmad, F
Wang, YS
Chung, J
Manganiello, VC
AF Maurice, Donald H.
Ke, Hengming
Ahmad, Faiyaz
Wang, Yousheng
Chung, Jay
Manganiello, Vincent C.
TI Advances in targeting cyclic nucleotide phosphodiesterases
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Review
ID CAMP-SPECIFIC PHOSPHODIESTERASE; OBSTRUCTIVE PULMONARY-DISEASE;
DEPENDENT PROTEIN-KINASE; RANDOMIZED CONTROLLED-TRIALS; CHRONIC
LYMPHOCYTIC-LEUKEMIA; TYPE-2 DIABETES-MELLITUS; AFFINITY
BINDING-PROTEIN; MULTIPLE MOLECULAR-FORMS; PDE10A INHIBITORS; ERECTILE
DYSFUNCTION
AB Cyclic nucleotide phosphodiesterases (PDEs) catalyse the hydrolysis of cyclic AMP and cyclic GMP, thereby regulating the intracellular concentrations of these cyclic nucleotides, their signalling pathways and, consequently, myriad biological responses in health and disease. Currently, a small number of PDE inhibitors are used clinically for treating the pathophysiological dysregulation of cyclic nucleotide signalling in several disorders, including erectile dysfunction, pulmonary hypertension, acute refractory cardiac failure, intermittent claudication and chronic obstructive pulmonary disease. However, pharmaceutical interest in PDEs has been reignited by the increasing understanding of the roles of individual PDEs in regulating the subcellular compartmentalization of specific cyclic nucleotide signalling pathways, by the structure-based design of novel specific inhibitors and by the development of more sophisticated strategies to target individual PDE variants.
C1 [Maurice, Donald H.] Queens Univ, Kingston, ON K7L 3N6, Canada.
[Ke, Hengming] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Ahmad, Faiyaz; Manganiello, Vincent C.] NHLBI, Cardiovasc & Pulm Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Wang, Yousheng] Beijing Technol & Business Univ, Beijing 100048, Peoples R China.
[Chung, Jay] NHLBI, Genet & Dev Biol Ctr, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Manganiello, VC (reprint author), NHLBI, Cardiovasc & Pulm Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM manganiv@nhlbi.nih.gov
FU National Heart, Lung and Blood Institute (NHLBI) Intramural research
Program at the US National Institutes of Health (NIH) in Bethesda,
Maryland, USA; Canadian Institutes of Health Research (CIHR)
FX V.M., J.C. and F.A. were supported by the National Heart, Lung and Blood
Institute (NHLBI) Intramural research Program at the US National
Institutes of Health (NIH) in Bethesda, Maryland, USA. Research funding
for D. H. M. is from the Canadian Institutes of Health Research (CIHR).
NR 272
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U1 7
U2 73
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 APR
PY 2014
VL 13
IS 4
BP 290
EP 314
DI 10.1038/nrd4228
PG 25
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA AE3VJ
UT WOS:000333906200024
PM 24687066
ER
PT J
AU Wang, J
Pang, T
Hafko, R
Benicky, J
Sanchez-Lemus, E
Saavedra, JM
AF Wang, Juan
Pang, Tao
Hafko, Roman
Benicky, Julius
Sanchez-Lemus, Enrique
Saavedra, Juan M.
TI Telmisartan ameliorates glutamate-induced neurotoxicity: Roles of AT(1)
receptor blockade and PPAR gamma activation
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Angiotensin II AT(1) Receptor Blockers; Telmisartan; PPAR gamma;
Neuroprotection; Glutamate neurotoxicity; Apoptosis
ID TRAUMATIC BRAIN-INJURY; SPONTANEOUSLY HYPERTENSIVE-RATS; II TYPE-1
RECEPTOR; INNATE IMMUNE-RESPONSE; FACTOR-KAPPA-B; ANGIOTENSIN-II;
DOWN-REGULATION; VASCULAR INFLAMMATION; HUMAN MONOCYTES; BLOOD-PRESSURE
AB Sartans (Angiotensin II AT(1) Receptor Blockers, ARBs) are powerful neuroprotective agents in vivo and protect against IL-1 beta neurotoxicity in vitro. The purpose of this research was to determine the extent of sartan neuroprotection against glutamate excitotoxicity, a common cause of neuronal injury and apoptosis. The results show that sartans are neuroprotective, significantly reducing glutamate-induced neuronal injury and apoptosis in cultured rat primary cerebellar granule cells (CGCs). Telmisartan was the most potent sartan studied, with an order of potency telmisartan > candesartan > losartan > valsartan. Mechanisms involved reduction of pro-apoptotic caspase-3 activation, protection of the survival PI3K/Akt/GSK-3 beta pathway and prevention of glutamate-induced ERK1/2 activation. NMDA receptor stimulation was essential for glutamate-induced cell injury and apoptosis. Participation of AT(1A) receptor was supported by glutamate-induced upregulation of AT(1A) gene expression and AT(1) receptor binding. Conversely, AT(1B) or AT(2) receptors played no role. Glutamate-induced neuronal injury and the neuroprotective effect of telmisartan were decreased, but not abolished, in CGCs obtained from AT(1A), knock-out mice. This indicates that although AT(1) receptors are necessary for glutamate to exert its full neurotoxic potential, part of the neuroprotective effect of telmisartan is independent of AT(1) receptor blockade. PPAR gamma activation was also involved in the neuroprotective effects of telmisartan, as telmisartan enhanced PPAR gamma nuclear translocation and the PPAR gamma antagonist GW9662 partially reversed the neuroprotective effects of telmisartan. The present results substantiate the therapeutic use of sartans, in particular telmisartan, in neurodegenerative diseases and traumatic brain disorders where glutamate neurotoxicity plays a significant role. Published by Elsevier Ltd.
C1 [Wang, Juan; Pang, Tao; Hafko, Roman; Benicky, Julius; Sanchez-Lemus, Enrique; Saavedra, Juan M.] NIMH, Sect Pharmacol, Div Intramural Res Programs, NIH,US Dept HHS, Bethesda, MD 20892 USA.
[Pang, Tao] China Pharmaceut Univ, New Drug Screening Ctr, Nanjing 210009, Jiangsu, Peoples R China.
[Saavedra, Juan M.] Georgetown Univ, Dept Physiol & Pharmacol, Med Ctr, Washington, DC 20057 USA.
RP Saavedra, JM (reprint author), Georgetown Univ, Dept Physiol & Pharmacol, Med Ctr, Bldg D,Room 287,3970 Reservoir Rd NW, Washington, DC 20057 USA.
EM jw543@georgetown.edu; jb2304@georgetown.edu;
scientificsupport@mesoscale.com; jms522@georgetown.edu
FU Division of Intramural Research Programs, National Institute of Mental
Health, National Institutes of Health, Department Of Health and Human
Services, USA [MH 002762-16]; Natural Science Foundation of Jiangsu
Province, P.R.China [BK 20130653]; Fundamental Research Funds for the
Central Universities, P.R.China [JKZD 2013006]; China Pharmaceutical
University
FX This study was supported by the Division of Intramural Research
Programs, National Institute of Mental Health, National Institutes of
Health, Department Of Health and Human Services, USA (MH 002762-16), the
Natural Science Foundation of Jiangsu Province, P.R.China (BK 20130653),
the Fundamental Research Funds for the Central Universities, P.R.China
(JKZD 2013006), and the Initial Fund of China Pharmaceutical University.
NR 83
TC 24
Z9 26
U1 1
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD APR
PY 2014
VL 79
BP 249
EP 261
DI 10.1016/j.neuropharm.2013.11.022
PG 13
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA AE1ZX
UT WOS:000333774200026
PM 24316465
ER
PT J
AU Wang, XX
Wang, CM
Wang, JM
Zhao, SQ
Zhang, K
Wang, JM
Zhang, W
Wu, CF
Yang, JY
AF Wang, Xiaoxiao
Wang, Chunming
Wang, Jiming
Zhao, Siqi
Zhang, Kuo
Wang, Jingmin
Zhang, Wei
Wu, Chunfu
Yang, Jingyu
TI Pseudoginsenoside-F11 (PF11) exerts anti-neuroinflammatory effects on
LPS-activated microglial cells by inhibiting TLR4-mediated
TAK1/IKK/NF-kappa B, MAPKs and Akt signaling pathways
SO NEUROPHARMACOLOGY
LA English
DT Article
DE PF11; Microglia; TLR4; NF-kappa B; MAPKs; Akt
ID NF-KAPPA-B; OXIDE SYNTHASE GENE; TOLL-LIKE RECEPTORS; NITRIC-OXIDE;
ALZHEIMERS-DISEASE; INFLAMMATORY RESPONSES; OXIDATIVE STRESS;
PROTEIN-KINASES; NADPH OXIDASE; NEURODEGENERATIVE DISEASES
AB Pseudoginsenoside-F11 (PF11), an ocotillol-type ginsenoside, has been shown to possess significant neuroprotective activity. Since microglia-mediated inflammation is critical for induction of neurodegeneration, this study was designed to investigate the effect of PF11 on activated microglia. PF11 significantly suppressed the release of ROS and proinflammatory mediators induced by LPS in a microglial cell line N9 including NO, PGE(2), IL-1 beta, IL-6 and TNF-alpha. Moreover, PF11 inhibited interaction and expression of TLR4 and MyD88 in LPS-activated N9 cells, resulting in an inhibition of the TAK1/IKK/NF-kappa B signaling pathway. PF11 also inhibited the phosphorylation of Akt and MAPKs induced by LPS in N9 cells. Importantly, PF11 significantly alleviated the death of SH-SY5Y neuroblastoma cells and primary cortical neurons induced by the conditioned-medium from activated microglia. At last, the effect of PF11 on neuroinflammation was confirmed in vivo: PF11 mitigated the microglial activation and proinflammatory factors expression obviously in both cortex and hippocampus in mice injected intrahippocampally with LPS. These findings indicate that PF11 exerts anti-neuroinflammatory effects on LPS-activated microglial cells by inhibiting TLR4-mediated TAK1/IKK/NF-kappa B, MAPKs and Akt signaling pathways, suggesting its therapeutic implication for neurodegenerative disease associated with neuroinflammation. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Wang, Xiaoxiao; Wang, Chunming; Zhao, Siqi; Zhang, Kuo; Wang, Jingmin; Zhang, Wei; Wu, Chunfu; Yang, Jingyu] Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China.
[Wang, Jiming] NCI, Lab Mol Immunoregulat, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA.
RP Yang, JY (reprint author), Shenyang Pharmaceut Univ, Dept Pharmacol, Box 31,103 Wenhua Rd, Shenyang 110016, Peoples R China.
EM xiaoxiao86517@163.com; wcm123_80@yahoo.com.cn; wangji@mail.ncifcrf.gov;
zhaosiqi2010@gmail.com; zhangkuosyphu@163.com; 290686748@qq.com;
798891145@qq.com; wucf@syphu.edu.cn; yangjingyu2006@gmail.com
FU National Science Foundation of China [30973890]; National Key Scientific
Project for New Drug Discovery and Development, P.R. China
[2010ZX09401-304]
FX This work was supported by grants from National Science Foundation of
China (30973890), and by the National Key Scientific Project for New
Drug Discovery and Development, P.R. China (2010ZX09401-304).
NR 92
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U1 3
U2 30
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD APR
PY 2014
VL 79
BP 642
EP 656
DI 10.1016/j.neuropharm.2014.01.022
PG 15
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA AE1ZX
UT WOS:000333774200068
PM 24467851
ER
PT J
AU Schank, JR
King, CE
Sun, H
Cheng, KJ
Rice, KC
Heilig, M
Weinshenker, D
Schroeder, JP
AF Schank, Jesse R.
King, Courtney E.
Sun, Hui
Cheng, Kejun
Rice, Kenner C.
Heilig, Markus
Weinshenker, David
Schroeder, Jason P.
TI The Role of the Neurokinin-I Receptor in Stress-Induced Reinstatement of
Alcohol and Cocaine Seeking
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE substance P; self-administration; stress; ethanol; yohimbine; relapse
ID CORTICOTROPIN-RELEASING-FACTOR; ANXIOGENIC DRUG YOHIMBINE; SUBSTANCE-P;
INDUCED RELAPSE; MICE LACKING; RATS; ANTAGONISM; BEHAVIOR; DEPENDENCE;
BRAIN
AB Neurokinin-I receptors (NKIRs) have been shown to mediate alcohol and opiate, but not cocaine reward in rodents. We recently reported that NKIR antagonism also blocks stress-induced reinstatement of alcohol seeking in rats, but it is presently unknown whether these antirelapse properties extend to other drug classes. Although some work has suggested that intracranial substance P (SP) infusion reinstates cocaine seeking following extinction, no studies have indicated a direct role for the NKIR in reinstatement of cocaine seeking. Here, we explored the effect of the NKIR antagonist L822429 on yohimbine-induced reinstatement of alcohol or cocaine seeking in Long Evans rats. Consistent with our previous findings with footshock-induced reinstatement of alcohol seeking in Wistar rats, we found that L822429 attenuates yohimbine-induced reinstatement of alcohol seeking, but does not affect baseline alcohol self-administration. We observed a similar suppression of yohimbine-induced reinstatement of cocaine seeking by L822429, and found that Long Evans rats exhibit greater sensitivity to NKIR antagonism than Wistar rats. Accordingly, Long-Evans rats exhibit differences in the expression of NKIRs in some subcortical brain regions. Combined, our findings suggest that while NKIR antagonism differentially influences alcohol and cocaine-related behavior, this receptor mediates stress-induced seeking of both drugs.
C1 [Schank, Jesse R.; King, Courtney E.; Sun, Hui; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Cheng, Kejun; Rice, Kenner C.] NIAAA, Chem Biol Branch, Bethesda, MD 20892 USA.
[Cheng, Kejun; Rice, Kenner C.] NIDA, NIH, Bethesda, MD 20892 USA.
[Weinshenker, David; Schroeder, Jason P.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA.
RP Schank, JR (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,Bldg 10 CRC,Room 1-5330, Bethesda, MD 20892 USA.
EM Jesse.Schank@nih.gov
FU National Institute on Alcohol Abuse and Alcoholism Intramural Research
Program; National Institute on Drug Abuse Intramural Research Program;
National Institute of Drug Abuse [RO1DA027535, K99AA021805]
FX This work was funded by the National Institute on Alcohol Abuse and
Alcoholism Intramural Research Program, the National Institute on Drug
Abuse Intramural Research Program, and the National Institute of Drug
Abuse (RO1DA027535 to DW), and Grant K99AA021805 (JRS). The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
NR 49
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U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD APR
PY 2014
VL 39
IS 5
BP 1093
EP 1101
DI 10.1038/npp.2013.309
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AD0IQ
UT WOS:000332918100006
PM 24173499
ER
PT J
AU Ni, CP
Hua, Y
Shao, P
Wallen, GR
Xu, SS
Li, L
AF Ni, Chunping
Hua, Yan
Shao, Pei
Wallen, Gwenyth R.
Xu, Shasha
Li, Lu
TI Continuing education among Chinese nurses: A general hospital-based
study
SO NURSE EDUCATION TODAY
LA English
DT Article
DE Continuing education; Nurses; Participation; Perception; Expectation;
Motivation for CE; Barriers to CE
ID PROFESSIONAL-EDUCATION; NURSING-EDUCATION; EXPERIENCES
AB Background: Continuing education (CE) is increasingly critical for nurses to keep abreast of rapid changes in patient care due to advancements in knowledge and technology.
Objective: The objective of this study was to explore Chinese nurses' perceptions on continuing education, how best CE practices meet their learning needs, and the motivation and barriers nurses face in completing CE.
Methods: A cross-sectional study of 2727 hospital-employed Chinese nurses from ten general hospitals was conducted from September to October 2010. Nurses' perceptions on CE, as well as motivational and preventive factors in CE were assessed.
Results: The majority of nurses (973%) attended CE activities in the last twelve months. More than 922% of the nurses were familiar with the value of CE. Nurses expected CE activities to take place within a five-day period and to consist of 2 h per activity. The major factors that motivate nurses to participate in CE are the desire to gain and update their knowledge of the newest nursing development and procedures, to improve their practical skills and comprehensive qualities, to maintain professional status and to receive an academic degree. Factors that hindered nurses' participation in CE included time constraints, work commitments, a lack of opportunity, cost of the courses and previous negative experiences with CE programs.
Conclusion: Chinese nurses considered CE an extremely important measure to further develop their professional competency. Nurses' actual expectations for CE and the motivation and barriers for participation in CE from nurses' individual, family and hospital perspective must be taken into the account in order to make CE programs more effective. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Ni, Chunping; Hua, Yan; Shao, Pei; Xu, Shasha] Fourth Mil Med Univ, Sch Nursing, Xian 710032, Shaanxi Provinc, Peoples R China.
[Wallen, Gwenyth R.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Li, Lu] Fourth Mil Med Univ, Dept Polit Theories Teaching Res, Xian 710032, Shaanxi Provinc, Peoples R China.
RP Xu, SS (reprint author), 169West Changle Rd, Xian 710032, Shaanxi Provinc, Peoples R China.
EM shali50084@163.com; jhfmmu@163.com
RI haron, suhaila/E-9360-2017
FU Department of General Logistics China [10MA030]
FX Funding for this study was provided by the Department of General
Logistics China (10MA030). The Department of General Logistics had no
further role in study design; in the collection, analysis and
interpretation of data; in the writing of the manuscript; and in the
decision to submit the paper for publication.
NR 42
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U1 1
U2 14
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0260-6917
EI 1532-2793
J9 NURS EDUC TODAY
JI Nurse Educ. Today
PD APR
PY 2014
VL 34
IS 4
BP 592
EP 597
DI 10.1016/j.nedt.2013.07.013
PG 6
WC Education, Scientific Disciplines; Nursing
SC Education & Educational Research; Nursing
GA AE2CT
UT WOS:000333781600019
PM 23931929
ER
PT J
AU Huang, K
Nair, AK
Muller, YL
Piaggi, P
Bian, L
del Rosario, M
Knowler, WC
Kobes, S
Hanson, RL
Bogardus, C
Baier, LJ
AF Huang, Ke
Nair, Anup K.
Muller, Yunhua Li
Piaggi, Paolo
Bian, Li
del Rosario, Melissa
Knowler, William C.
Kobes, Sayuko
Hanson, Robert L.
Bogardus, Clifton
Baier, Leslie J.
TI Whole Exome Sequencing Identifies Variation in CYB5A and RNF10
Associated with Adiposity and Type 2 Diabetes
SO OBESITY
LA English
DT Article
ID PIMA-INDIANS; INSULIN-RESISTANCE; INDIVIDUALS; MELLITUS; OBESITY; RISK
AB Objective: Few coding variants in genes associated with type 2 diabetes (T2D) have been identified, and the underlying physiologic mechanisms whereby susceptibility genes influence T2D risk are often unknown. The objective of this study was to identify coding variation that increases risk for T2D via an effect on a pre-diabetic trait.
Methods: Whole exome sequencing was done in 177 Pima Indians. Selected variants (N = 345) were genotyped in 555 subjects characterized for body fatness, glucose disposal rates during a clamp, acute insulin response to glucose, and 2-h plasma glucose concentrations during an OGTT, and were also genotyped in up to 5,880 subjects with longitudinal measures of BMI. Variants associated with quantitative traits were assessed for association with T2D in 7,667 subjects.
Results: rs7238987 in CYB5A associated with body fatness (P = 7.0 x 10(-6)). This SNP and a novel SNP in RNF10 also associated with maximum recorded BMI (P = 6.2 x 10(-7) and P = 7.2 x 10(-4)) and maximum childhood BMI z-score (P = 5.9 x 10(-4) and P = 8.5 x 10 27). The BMI increasing alleles increased the risk for T2D (P = 0.01; OR = 1.13 [1.03-1.24] and 9.5 x 10(-3); OR = 1.49 [1.10-2.02]).
Conclusions: CYB5A, which has a role in stearyl-CoA-desaturase activity, and RNF10, with an unknown role in weight regulating pathways, associated with adiposity and nominally increased the risk for T2D in American Indians.
C1 [Huang, Ke; Nair, Anup K.; Muller, Yunhua Li; Piaggi, Paolo; Bian, Li; del Rosario, Melissa; Knowler, William C.; Kobes, Sayuko; Hanson, Robert L.; Bogardus, Clifton; Baier, Leslie J.] Natl Inst Diabet & Digest & Kidney Dis, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA.
RP Baier, LJ (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA.
EM lbaier@phx.niddk.nih.gov
RI Hanson, Robert/O-3238-2015;
OI Hanson, Robert/0000-0002-4252-7068; Piaggi, Paolo/0000-0003-2774-9161
FU Intramural Program of NIDDK, NIH
FX This work was funded by the Intramural Program of NIDDK, NIH.
NR 16
TC 6
Z9 6
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD APR
PY 2014
VL 22
IS 4
BP 984
EP 988
DI 10.1002/oby.20647
PG 5
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA AE0OY
UT WOS:000333666800004
PM 24151200
ER
PT J
AU Tsai, AG
Fabricatore, AN
Wadden, TA
Higginbotham, AJ
Anderson, A
Foreyt, J
Hill, JO
Jeffery, RW
Gluck, ME
Lipkin, EW
Reeves, RS
Van Dorsten, B
AF Tsai, Adam G.
Fabricatore, Anthony N.
Wadden, Thomas A.
Higginbotham, Allison J.
Anderson, Andrea
Foreyt, John
Hill, James O.
Jeffery, Robert W.
Gluck, Marci E.
Lipkin, Edward W.
Reeves, Rebecca S.
Van Dorsten, Brent
CA Look AHEAD Res Grp
TI Readiness Redefined: A Behavioral Task During Screening Predicted 1-Year
Weight Loss in the Look AHEAD Study
SO OBESITY
LA English
DT Article
ID DIABETES-PREVENTION-PROGRAM; LIFE-STYLE INTERVENTION; DISEASE
RISK-FACTORS; CARDIOVASCULAR-DISEASE; PRETREATMENT PREDICTORS;
RANDOMIZED-TRIAL; OBESITY; INDIVIDUALS; ADULTS; SIBUTRAMINE
AB Objective: Predicting outcome in weight loss trials from baseline characteristics has proved difficult. Readiness to change is typically measured by self-report.
Methods: Performance of a behavioral task, completion of food records, from the screening period in the Look AHEAD study (n = 549 at four clinical centers) was assessed. Completeness of records was measured by the number of words and Arabic numerals (numbers) recorded per day, the number of eating episodes per day, and days per week where physical activity was noted. The primary outcome was weight loss at one year.
Results: In univariable analysis, both the number of words recorded and the number of numbers recorded were associated with greater weight loss. In multivariable analysis, individuals who recorded 20-26, 27-33, and >= 34 words per day lost 9.12%, 11.40%, and 12.08% of initial weight, compared to 8.98% for individuals who recorded less than 20 words per day (P values of 0.87, 0.008, and < 0.001, respectively, compared to <20 words per day).
Conclusions: Participants who kept more detailed food records at screening lost more weight after 1 year than individuals who kept sparser records. The use of objective behavioral screening tools may improve the assessment of weight loss readiness.
C1 [Tsai, Adam G.; Hill, James O.] Univ Colorado, Sch Med, Aurora, CO 80045 USA.
[Fabricatore, Anthony N.] Nutrisystem Inc, Ft Washington, MD USA.
[Wadden, Thomas A.; Higginbotham, Allison J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Anderson, Andrea] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Foreyt, John; Reeves, Rebecca S.] Baylor Coll Med, Houston, TX 77030 USA.
[Jeffery, Robert W.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Gluck, Marci E.] Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ USA.
[Lipkin, Edward W.] Univ Washington, Div Endocrinol, Seattle, WA 98195 USA.
[Van Dorsten, Brent] Colorado Ctr Behav Med, Denver, CO USA.
RP Tsai, AG (reprint author), Univ Colorado, Sch Med, Aurora, CO 80045 USA.
EM adam.tsai@ucdenver.edu
FU National Institutes of Health [DK57136, DK57149, DK56990, DK57177,
DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178,
DK57219, DK57008, DK57135, DK56992]; National Institute of Diabetes and
Digestive and Kidney Diseases; National Heart, Lung, and Blood
Institute; National Institute of Nursing Research; National Center on
Minority Health and Health Disparities; NIH Office of Research on
Women's Health; Centers for Disease Control and Prevention; Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases; University of Colorado Health Sciences Center General
Clinical Research Center [M01RR00051]; Clinical Nutrition Research Unit
[P30 DK48520]; VA Puget Sound Health Care System Medical Research
Service, Department of Veterans Affairs
FX This study is supported by the Department of Health and Human Services
through the following cooperative agreements from the National
Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171,
DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219,
DK57008, DK57135, and DK56992. The following federal agencies have
contributed support: National Institute of Diabetes and Digestive and
Kidney Diseases; National Heart, Lung, and Blood Institute; National
Institute of Nursing Research; National Center on Minority Health and
Health Disparities; NIH Office of Research on Women's Health; and the
Centers for Disease Control and Prevention. This research was supported
in part by the Intramural Research Program of the National Institute of
Diabetes and Digestive and Kidney Diseases. The Indian Health Service
(I.H.S.) provided personnel, medical oversight, and use of facilities.
The opinions expressed in this paper are those of the authors and do not
necessarily reflect the views of the I. H. S. or other funding sources.
Additional support was received from the University of Colorado Health
Sciences Center General Clinical Research Center (M01RR00051) and
Clinical Nutrition Research Unit (P30 DK48520); and the VA Puget Sound
Health Care System Medical Research Service, Department of Veterans
Affairs.
NR 38
TC 3
Z9 3
U1 2
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD APR
PY 2014
VL 22
IS 4
BP 1016
EP 1023
DI 10.1002/oby.20648
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA AE0OY
UT WOS:000333666800009
PM 24151217
ER
PT J
AU Espeland, MA
Lewis, CE
Bahnson, J
Knowler, WC
Regensteiner, JG
Gaussoin, SA
Beavers, D
Johnson, KC
AF Espeland, Mark A.
Lewis, Cora E.
Bahnson, Judy
Knowler, William C.
Regensteiner, Judith G.
Gaussoin, Sarah A.
Beavers, Daniel
Johnson, Karen C.
CA Look AHEAD Res Grp
TI Impact of Weight Loss on Ankle-Brachial Index and Interartery Blood
Pressures
SO OBESITY
LA English
DT Article
ID PERIPHERAL ARTERIAL-DISEASE; LIFE-STYLE INTERVENTION; CARDIOVASCULAR
RISK-FACTORS; INTER-ARM DIFFERENCES; GENERAL-POPULATION;
VASCULAR-DISEASE; DIFFERENCE; ADULTS; ASSOCIATION; PREVALENCE
AB Objective: To assess whether weight loss improves markers of peripheral artery disease and vascular stenosis. Methods: The Action for Health in Diabetes randomized clinical trial compared intensive lifestyle intervention (ILI) for weight loss to a control condition of diabetes support and education (DSE) in overweight or obese adults with type 2 diabetes. Annual ankle and brachial blood pressures over four years were used to compute ankle-brachial indices (ABIs) and to assess interartery blood pressure differences in 5018 participants. Results: ILI, compared to DSE, produced 7.8% (Year 1) to 3.6% (Year 4) greater weight losses. These did not affect prevalence of low (<0.90) ABI (3.60% in DSE versus 3.14% in ILI; P =0.20) or elevated (>1.40) ABI (7.52% in DSE versus 7.59% in ILI: P =0.90), but produced smaller mean (SE) maximum interartery systolic blood pressure differences among ankle sites [ 19.7 (0.2) mmHg for ILI versus 20.6 (0.2) mmHg for DSE (P < 0.001)] and between arms [ 5.8 (0.1) mmHg for ILI versus 6.1 (0.1) mmHg for DSE (P =0.01)]. Conclusions: Four years of intensive behavioral weight loss intervention did not significantly alter prevalence of abnormal ABI, however, it did reduce differences in systolic blood pressures among arterial sites.
C1 [Espeland, Mark A.; Bahnson, Judy; Gaussoin, Sarah A.; Beavers, Daniel; Look AHEAD Res Grp] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA.
[Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA.
[Regensteiner, Judith G.] Univ Colorado, Sch Med, Div Cardiol, Denver, CO USA.
[Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
RP Espeland, MA (reprint author), Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.
EM mespelan@wakehealth.edu
RI Beavers, Daniel/G-5338-2016
FU Department of Health and Human Services; National Institutes of Health
[DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131,
DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992];
National Institute of Diabetes and Digestive and Kidney Diseases;
National Heart, Lung, and Blood Institute; National Institute of Nursing
Research; National Center on Minority Health and Health Disparities; NIH
Office of Research on Women's Health; Centers for Disease Control and
Prevention; Intramural Research Program of the National Institute of
Diabetes and Digestive and Kidney Diseases; Johns Hopkins Medical
Institutions Bayview General Clinical Research Center [M01RR02719];
Massachusetts General Hospital Mallinckrodt General Clinical Research
Center; Massachusetts Institute of Technology General Clinical Research
Center [M01RR01066]; University of Colorado Health Sciences Center
General Clinical Research Center [M01RR00051]; Clinical Nutrition
Research Unit [P30 DK48520]; University of Tennessee at Memphis General
Clinical Research Center [M01RR0021140]; University of Pittsburgh
General Clinical Research Center (GCRC) [M01RR000056]; Clinical
Translational Research Center (CTRC); Clinical & Translational Science
Award [UL1 RR 024153]; NIH grant [DK 046204]; VA Puget Sound Health Care
System Medical Research Service, Department of Veterans Affairs;
Frederic C. Bartter General Clinical Research Center [M01RR01346]
FX This study is supported by the Department of Health and Human Services
through the following cooperative agreements from the National
Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171,
DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219,
DK57008, DK57135, and DK56992. The following federal agencies have
contributed support: National Institute of Diabetes and Digestive and
Kidney Diseases; National Heart, Lung, and Blood Institute; National
Institute of Nursing Research; National Center on Minority Health and
Health Disparities; NIH Office of Research on Women's Health; and the
Centers for Disease Control and Prevention. This research was supported
in part by the Intramural Research Program of the National Institute of
Diabetes and Digestive and Kidney Diseases. The Indian Health Service
(I. H. S.) provided personnel, medical oversight, and use of facilities.
The opinions expressed in this paper are those of the authors and do not
necessarily reflect the views of the I. H. S. or other funding sources.
Additional support was received from The Johns Hopkins Medical
Institutions Bayview General Clinical Research Center (M01RR02719); the
Massachusetts General Hospital Mallinckrodt General Clinical Research
Center and the Massachusetts Institute of Technology General Clinical
Research Center (M01RR01066); the University of Colorado Health Sciences
Center General Clinical Research Center (M01RR00051) and Clinical
Nutrition Research Unit (P30 DK48520); the University of Tennessee at
Memphis General Clinical Research Center (M01RR0021140); the University
of Pittsburgh General Clinical Research Center (GCRC) (M01RR000056), the
Clinical Translational Research Center (CTRC) funded by the Clinical &
Translational Science Award (UL1 RR 024153) and NIH grant (DK 046204);
the VA Puget Sound Health Care System Medical Research Service,
Department of Veterans Affairs; and the Frederic C. Bartter General
Clinical Research Center (M01RR01346).
NR 40
TC 3
Z9 3
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD APR
PY 2014
VL 22
IS 4
BP 1032
EP 1041
DI 10.1002/oby.20658
PG 10
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA AE0OY
UT WOS:000333666800011
PM 24174392
ER
PT J
AU Persky, S
de Heer, HD
McBride, CM
Reid, RJ
AF Persky, Susan
de Heer, Hendrik D.
McBride, Colleen M.
Reid, Robert J.
TI The Role of Weight, Race, and Health Care Experiences in Care Use Among
Young Men and Women
SO OBESITY
LA English
DT Article
ID PATIENT SATISFACTION; MEDICAL-CARE; BODY-WEIGHT; OBESITY; GENDER;
SERVICES; DISCRIMINATION; PERCEPTIONS; ASSOCIATION; DISPARITIES
AB Objective: Increases in overweight and obesity (O/O)-related morbidities and health care costs raise questions about how weight influences patients' health care use and care experiences. Past research has been inconsistent; however, prior study designs and samples have limited exploration of how this association might be influenced by gender, race, and the joint impact of these factors.
Methods: This analysis of 1,036 young, relatively healthy, ethnically diverse, insured adults assessed the influence of O/O, gender, and race on, and the role of health care experiences in primary and preventive care use over a 12-month period.
Results: The association of weight status with care use differed by gender. O/O men used more primary care visits; O/O women used fewer preventive care visits than their healthy weight counterparts. O/O men had poorer health care experiences than healthy weight men. African-American women reported poorer experiences, but those who were O/O reported greater trust in their provider. Care experience ratings did not explain the associations between BMI and care use.
Conclusions: Gender, race, and visit type together provide a context for O/O patient's care that may not be explained by care experiences. This context must be considered in efforts to encourage appropriate use of services.
C1 [Persky, Susan; McBride, Colleen M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[de Heer, Hendrik D.] No Arizona Univ, Dept Phys Therapy & Athlet Training, Flagstaff, AZ 86011 USA.
[Reid, Robert J.] Grp Hlth Res Inst, Seattle, WA USA.
RP Persky, S (reprint author), NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
EM perskys@mail.nih.gov
FU Cancer Research Network [U19 CA 079689]; Intramural Research Program of
the National Human Genome Research Institute (NHGRI); Group Health
Research Institute and Henry Ford Hospital; National Cancer Institute
FX This research was supported by the grant (U19 CA 079689) from the Cancer
Research Network funded by the National Cancer Institute, by the
Intramural Research Program of the National Human Genome Research
Institute (NHGRI), and by the Group Health Research Institute and Henry
Ford Hospital
NR 37
TC 1
Z9 1
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD APR
PY 2014
VL 22
IS 4
BP 1194
EP 1200
DI 10.1002/oby.20677
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA AE0OY
UT WOS:000333666800032
PM 24318861
ER
PT J
AU Furuya, T
Sa, JM
Chitnis, CE
Wellems, TE
Stedman, TT
AF Furuya, Tetsuya
Sa, Juliana M.
Chitnis, Chetan E.
Wellems, Thomas E.
Stedman, Timothy T.
TI Reticuliocytes from cryopreserved erythroblasts support Plasmodium vivax
infection in vitro
SO PARASITOLOGY INTERNATIONAL
LA English
DT Article
DE Plasmodium vivax; Culture system; Hematopoietic stem cells
ID RED-BLOOD-CELLS; CORD BLOOD; INVASION; RETICULOCYTES; CULTURE; AOTUS
AB Plasmodium vivax is the most widely distributed human malaria parasite. Despite its importance, both clinical research and basic research have been hampered by lack of a convenient in vitro culture system, in part due to the parasite's infection preference of reticulocytes rather than mature erythrocytes. The use of reticulocyte-producing hematopoietic stem cell culture has been proposed for the maintenance of the parasite, but good numbers of reticulocytes and P. vivax parasites sufficient for practical use in research have been difficult to produce from this system. Here, we report an improved method of hematopoietic stem cell culture for P. vivax infection, which requires less time and produces higher or equivalent percentage of reticulocytes than previously reported systems. Reticulocytes were cultured from cryopreserved erythroblasts that were frozen after 8 day-cultivation of purified CD34 + cells from human umbilical cord blood. This method of production allowed the recovery of reticulocytes in a shorter time than with continuous stem cell culture. We obtained a relatively high percentage of peak reticulocyte production by using co-cultivation with a mouse stromal cell line. Using P. vivax mature stage parasites obtained from infected Aotus monkeys, we observed substantial numbers (up to 0.8% of the total number of the cells) of newly invaded reticulocytes 24 h after initial cultivation. The addition of fresh reticulocytes after 48 h culture, however, did not result in significant increase of second cycle reticulocyte invasion. Assays of invasion inhibition with specific antibodies were successful with this system, demonstrating potential for study of biological processes as well as the conditions necessary for long-term maintenance of P. vivax in vitro. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Furuya, Tetsuya; Stedman, Timothy T.] ATCC, BioServ, Malaria Res & Reference Reagent Resource Ctr MR4, Manassas, VA 20110 USA.
[Sa, Juliana M.; Wellems, Thomas E.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20852 USA.
[Chitnis, Chetan E.] ICGEB, Malaria Grp, New Delhi, India.
RP Furuya, T (reprint author), Tokyo Univ Agr & Technol, Fac Agr, Dept Vet Med, Fuchu, Tokyo 1838509, Japan.
EM furuyat@cc.tuat.ac.jp
RI Furuya, Tetsuya/J-5916-2013
FU National Institutes of Health grant [1R03AI079475-01]; Intramural
Research Program of the NIH, NIAID
FX This study was partly supported by the National Institutes of Health
grant (1R03AI079475-01) and also partly by the Intramural Research
Program of the NIH, NIAID. We thank Dr. Yves Colin Aronovicz for
providing anti-FY6 monoclonal antibody and Dr. Louis H. Miller for
critical advice on the study. We also thank Sarah Kaslow, Theresa
Aguirre, Faith Sentz, and Ahlin Bruce for support on Aotus research.
NR 14
TC 4
Z9 4
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1383-5769
J9 PARASITOL INT
JI Parasitol. Int.
PD APR
PY 2014
VL 63
IS 2
BP 278
EP 284
DI 10.1016/j.parint.2013.11.011
PG 7
WC Parasitology
SC Parasitology
GA AD8XS
UT WOS:000333549600003
PM 24291603
ER
PT J
AU Harris-Love, MO
Shrader, JA
Davenport, TE
Joe, G
Rakocevic, G
McElroy, B
Dalakas, M
AF Harris-Love, Michael O.
Shrader, Joseph A.
Davenport, Todd E.
Joe, Galen
Rakocevic, Goran
McElroy, Beverly
Dalakas, Marinos
TI Are Repeated Single-Limb Heel Raises and Manual Muscle Testing
Associated With Peak Plantar-Flexor Force in People With Inclusion Body
Myositis?
SO PHYSICAL THERAPY
LA English
DT Article
ID KNEE EXTENSION STRENGTH; RISE TEST; ANKLE; RELIABILITY; PERFORMANCE;
ENDURANCE; DISEASE; OLDER; WORK; AGE
AB Background. Repeated heel raises have been proposed as a method of ankle plantar-flexor strength testing that circumvents the limitations of manual muscle testing (MMT).
Objective. The study objective was to examine the relationships among ankle plantar-flexion isometric maximum voluntary contraction (MVC), repeated single-limb heel raises (SLHRs), and MMT in people with myositis.
Design. This was a cross-sectional study with a between-group design. The ability to complete 1 SLHR determined group assignment (SLHR group, n=24; no-SLHR group, n=19).
Methods. Forty-three participants with myositis (13 women; median age=64.9 years) participated. Outcome measures included MVC, predicted MVC, Kendall MMT, and Daniels-Worthingham MMT.
Results. The Kendall MMT was unable to detect significant ankle plantar-flexor weakness established by quantitative methods and was unable to discriminate between participants who could and those who could not perform the SLHR task. Ankle plantar-flexion MVC was not associated with the number of heel-raise repetitions in the SLHR group (pseudo R-2=.13). No significant relationship was observed between MVC values and MMT grades in the SLHR and no-SLHR groups. However, a moderate relationship between MVC values and MMT grades was evident in a combined-group analysis (rho=.50-.67).
Limitations. The lower half of both MMT grading scales was not represented in the study despite the profound weakness of the participants.
Conclusions. Both Kendall MMT and Daniels-Worthingham MMT had limited utility in the assessment of ankle plantar-flexor strength. Repeated SLHRs should not be used as a proxy measure of ankle plantar-flexion MVC in people with myositis.
C1 [Harris-Love, Michael O.] Washington DC Vet Affairs Med Ctr, Dept Vet Affairs, Res Serv, Geriatr & Extended Care Serv, Washington, DC 20422 USA.
[Harris-Love, Michael O.] George Washington Univ, Dept Exercise Sci, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
[Harris-Love, Michael O.; Shrader, Joseph A.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
[Davenport, Todd E.] Univ Pacific, Dept Phys Therapy, Thomas J Long Sch Pharm & Hlth Sci, Stockton, CA USA.
[Joe, Galen] NIH, Dept Rehabil Med, Rehabil Med Consult Serv, Bethesda, MD 20892 USA.
[Rakocevic, Goran] Thomas Jefferson Univ, Neuromuscular Lab, Philadelphia, PA 19107 USA.
[McElroy, Beverly] NINDS, Parkinson Dis Program, Bethesda, MD 20892 USA.
[Dalakas, Marinos] Thomas Jefferson Univ, Neuromuscular Div, Philadelphia, PA 19107 USA.
[Dalakas, Marinos] Natl Tech Univ Athens, Sch Med, Dept Pathophysiol, Athens, Greece.
RP Harris-Love, MO (reprint author), Washington DC Vet Affairs Med Ctr, Dept Vet Affairs, Res Serv, Geriatr & Extended Care Serv, 50 Irving St NW,Room 11G, Washington, DC 20422 USA.
EM michael.harris-love@va.gov
RI Harris-Love, Michael/J-1359-2014
OI Harris-Love, Michael/0000-0002-1842-3269
FU National Institute of Neurological Disorders and Stroke Intramural
Research Program [02-N-0121]; Rehabilitation Medicine Department,
National Institutes of Health
FX This study was funded by the National Institute of Neurological
Disorders and Stroke (protocol 02-N-0121) Intramural Research Program
and was supported by the Rehabilitation Medicine Department, National
Institutes of Health.
NR 32
TC 2
Z9 2
U1 0
U2 3
PU AMER PHYSICAL THERAPY ASSOC
PI ALEXANDRIA
PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA
SN 0031-9023
EI 1538-6724
J9 PHYS THER
JI Phys. Ther.
PD APR
PY 2014
VL 94
IS 4
BP 543
EP 552
DI 10.2522/ptj.20130100
PG 10
WC Orthopedics; Rehabilitation
SC Orthopedics; Rehabilitation
GA AE3LB
UT WOS:000333876900010
PM 24309617
ER
PT J
AU Vecchiarelli, AG
Neuman, KC
Mizuuchi, K
AF Vecchiarelli, Anthony G.
Neuman, Keir C.
Mizuuchi, Kiyoshi
TI A propagating ATPase gradient drives transport of surface-confined
cellular cargo
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE bacterial chromosome segregation; ParA ATPase; spatial organization;
protein gradients
ID BACTERIAL CHROMOSOME SEGREGATION; PLASMID PARTITION; F-PLASMID; DNA
SEGREGATION; MECHANISM; DYNAMICS; SOPA; PARB; PROTEINS; TRACKING
AB The faithful segregation of duplicated genetic material into daughter cells is critical to all organisms. In many bacteria, the segregation of chromosomes involves transport of "centromere-like" loci over the main body of the chromosome, the nucleoid, mediated by a two-protein partition system: a nonspecific DNA-binding ATPase, ParA, and an ATPase stimulator, ParB, which binds to the centromere-like loci. These systems have previously been proposed to function through a filament-based mechanism, analogous to actin-or microtubule-based movement. Here, we reconstituted the F-plasmid partition system using a DNA-carpeted flow cell as an artificial nucleoid surface and magnetic beads coated with plasmid partition complexes as surface-confined cargo. This minimal system recapitulated directed cargo motion driven by a surface ATPase gradient that propagated with the cargo. The dynamics are consistent with a diffusion-ratchet model, whereby the cargo dynamically establishes, and interacts with, a concentration gradient of the ATPase. A chemophoresis force ensues as the cargo perpetually chases the ATPase gradient, allowing the cargo to essentially "surf" the nucleoid on a continuously traveling wave of the ATPase. Demonstration of this non-filament-based motility mechanism in a biological context establishes a distinct class of motor system used for the transport and positioning of large cellular cargo.
C1 [Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi] NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
[Neuman, Keir C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Mizuuchi, K (reprint author), NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
EM kiyoshimi@helix.nih.gov
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Heart, Lung, and Blood Institute; National Institutes of Health
US Department of Health and Human Services; Nancy Nossal Fellowship
FX We are particularly thankful to Ethan Tyler for model animation and
graphics, Hemai Parthasarathy for editorial assistance, and John Silver
and Yeonee Seol for comments. This work was supported by the intramural
research fund for National Institute of Diabetes and Digestive and
Kidney Diseases (to K.M.) and National Heart, Lung, and Blood Institute
(to K.C.N.), National Institutes of Health US Department of Health and
Human Services, and the Nancy Nossal Fellowship (to A.G.V.).
NR 27
TC 29
Z9 29
U1 1
U2 24
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 1
PY 2014
VL 111
IS 13
BP 4880
EP 4885
DI 10.1073/pnas.1401025111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9IX
UT WOS:000333579700052
PM 24567408
ER
PT J
AU Mistry, PK
Liu, J
Sun, L
Chuang, WL
Yuen, T
Yang, RH
Lu, P
Zhang, KT
Li, JH
Keutzer, J
Stachnik, A
Mennone, A
Boyer, JL
Jain, D
Brady, RO
New, MI
Zaidi, M
AF Mistry, Pramod K.
Liu, Jun
Sun, Li
Chuang, Wei-Lien
Yuen, Tony
Yang, Ruhua
Lu, Ping
Zhang, Kate
Li, Jianhua
Keutzer, Joan
Stachnik, Agnes
Mennone, Albert
Boyer, James L.
Jain, Dhanpat
Brady, Roscoe O.
New, Maria I.
Zaidi, Mone
TI Glucocerebrosidase 2 gene deletion rescues type 1 Gaucher disease
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE macrophage; knockout mice; S1P
ID ACID BETA-GLUCOSIDASE; CONGENITAL ADRENAL-HYPERPLASIA; NONLYSOSOMAL
GLUCOSYLCERAMIDASE; CULTURED FIBROBLASTS; DEFICIENT MICE; BONE-DISEASE;
PHENOTYPE; STORAGE; GLUCOSYLSPHINGOSINE; BETA-GLUCOSIDASE-2
AB The inherited deficiency of the lysosomal glucocerebrosidase (GBA) due to mutations in the GBA gene results in Gaucher disease (GD). A vast majority of patients present with nonneuronopathic, type 1 GD (GD1). GBA deficiency causes the accumulation of two key sphingolipids, glucosylceramide (GL-1) and glucosylsphingosine (LysoGL-1), classically noted within the lysosomes of mononuclear phagocytes. How metabolites of GL-1 or LysoGL-1 produced by extralysosomal glucocerebrosidase GBA2 contribute to the GD1 pathophysiology is not known. We recently recapitulated hepatosplenomegaly, cytopenia, hypercytokinemia, and the bone-formation defect of human GD1 through conditional deletion of Gba in Mx1-Cre(+):GD1 mice. Here we show that the deletion of Gba2 significantly rescues the GD1 clinical phenotype, despite enhanced elevations in GL-1 and LysoGL-1. Most notably, the reduced bone volume and bone formation rate are normalized. These results suggest that metabolism of GL-1 or LysoGL-1 into downstream bioactive lipids is a major contributor to the bone-formation defect. Direct testing revealed a strong inhibition of osteoblast viability by nanomolar concentrations of sphingosine, but not of ceramide. These findings are consistent with toxicity of high circulating sphingosine levels in GD1 patients, which decline upon enzyme-replacement therapy; serum ceramide levels remain unchanged. Together, complementary results from mice and humans affected with GD1 not only pinpoint sphingosine as being an osteoblast toxin, but also set forth Gba2 as a viable therapeutic target for the development of inhibitors to ameliorate certain disabling consequences of GD1.
C1 [Mistry, Pramod K.; Liu, Jun; Yang, Ruhua; Mennone, Albert; Boyer, James L.; Jain, Dhanpat] Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA.
[Sun, Li; Yuen, Tony; Lu, Ping; Li, Jianhua; Stachnik, Agnes; New, Maria I.; Zaidi, Mone] Mt Sinai Sch Med, Mt Sinai Bone Program, New York, NY 10029 USA.
[Sun, Li; Yuen, Tony; Lu, Ping; Li, Jianhua; Stachnik, Agnes; Zaidi, Mone] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA.
[Chuang, Wei-Lien; Zhang, Kate; Keutzer, Joan] Genzyme Sanofi, Framingham, MA 01701 USA.
[Brady, Roscoe O.] NINDS, NIH, Bethesda, MD 20824 USA.
RP Mistry, PK (reprint author), Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA.
EM pramod.mistry@yale.edu; maria.new@mssm.edu; mone.zaidi@mountsinai.org
FU National Institutes of Arthritis, Musculoskeletal and Skin Diseases [AR
65932]; National Institutes of Health [AG23176, DK80490, AG40132,
DK66306]; Silvio O. Conte Digestive Diseases Research Core Center
[DK34989]; Children's Hormone Foundation; Genzyme; Sanofi Company;
Center of Excellence Grant in Clinical Translational Research
FX We thank David W. Russell (University of Texas Southwestern Medical
Center) for providing Gba2-/- mice. This study was supported
in large part by National Institutes of Arthritis, Musculoskeletal and
Skin Diseases Grant AR 65932 (to M.Z. and P.K.M.). This work was also
supported by National Institutes of Health Grants AG23176, DK80490, and
AG40132 (to M.Z. and L.S.); National Institutes of Health Grant DK66306
(to P.K.M.); Silvio O. Conte Digestive Diseases Research Core Center
Grant DK34989 (to J.L.B. and A.M.); and the Children's Hormone
Foundation (M.I.N.). P.K.M. is also supported by a Genzyme, a Sanofi
Company, Center of Excellence Grant in Clinical Translational Research.
NR 33
TC 25
Z9 26
U1 0
U2 11
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 1
PY 2014
VL 111
IS 13
BP 4934
EP 4939
DI 10.1073/pnas.1400768111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9IX
UT WOS:000333579700061
PM 24639522
ER
PT J
AU Koganti, S
Hui-Yuen, J
McAllister, S
Gardner, B
Grasser, F
Palendira, U
Tangye, SG
Freeman, AF
Bhaduri-McIntosh, S
AF Koganti, Siva
Hui-Yuen, Joyce
McAllister, Shane
Gardner, Benjamin
Grasser, Friedrich
Palendira, Umaimainthan
Tangye, Stuart G.
Freeman, Alexandra F.
Bhaduri-McIntosh, Sumita
TI STAT3 interrupts ATR-Chk1 signaling to allow oncovirus-mediated cell
proliferation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE autosomal dominant hyper-IgE syndrome; infectious mononucleosis; latent
membrane protein 1; Epstein-Barr nuclear antigen
ID EPSTEIN-BARR-VIRUS; DNA-DAMAGE RESPONSE; HYPER-IGE SYNDROME;
ONCOGENE-INDUCED SENESCENCE; HUMAN B-CELLS; THERAPEUTIC INTERVENTION;
MOLECULAR TARGETS; CANCER; REPLICATION; PATHWAY
AB DNA damage response (DDR) is a signaling network that senses DNA damage and activates response pathways to coordinate cell-cycle progression and DNA repair. Thus, DDR is critical for maintenance of genome stability, and presents a powerful defense against tumorigenesis. Therefore, to drive cell-proliferation and transformation, viral and cellular oncogenes need to circumvent DDR-induced cell-cycle checkpoints. Unlike in hereditary cancers, mechanisms that attenuate DDR and disrupt cell-cycle checkpoints in sporadic cancers are not well understood. Using Epstein-Barr virus (EBV) as a source of oncogenes, we have previously shown that EBV-driven cell proliferation requires the cellular transcription factor STAT3. EBV infection is rapidly followed by activation and increased expression of STAT3, which mediates relaxation of the intra-S phase cell-cycle checkpoint; this facilitates viral oncogene-driven cell proliferation. We now show that replication stress-associated DNA damage, which results from EBV infection, is detected by DDR. However, signaling downstream of ATR is impaired by STAT3, leading to relaxation of the intra-S phase checkpoint. We find that STAT3 interrupts ATR-to-Chk1 signaling by promoting loss of Claspin, a protein that assists ATR to phosphorylate Chk1. This loss of Claspin which ultimately facilitates cell proliferation is mediated by caspase 7, a protein that typically promotes cell death. Our findings demonstrate how STAT3, which is constitutively active in many human cancers, suppresses DDR, fundamental to tumorigenesis. This newly recognized role for STAT3 in attenuation of DDR, discovered in the context of EBV infection, is of broad interest as the biology of cell proliferation is central to both health and disease.
C1 [Koganti, Siva; Bhaduri-McIntosh, Sumita] SUNY Stony Brook, Sch Med, Dept Pediat, Stony Brook, NY 11794 USA.
[Koganti, Siva; Bhaduri-McIntosh, Sumita] SUNY Stony Brook, Sch Med, Stony Brook Childrens Hosp, Stony Brook, NY 11794 USA.
[Hui-Yuen, Joyce] Columbia Univ, Morgan Stanley Childrens Hosp, New York, NY 10032 USA.
[McAllister, Shane] Univ Minnesota, Minneapolis, MN 55455 USA.
[Gardner, Benjamin] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA.
[Grasser, Friedrich] Univ Klinkum Saarlandes, Inst Virol, D-66421 Homburg, Germany.
[Palendira, Umaimainthan; Tangye, Stuart G.] Garvan Inst Med Res, Immunol Program, Darlinghurst, NSW 2010, Australia.
[Palendira, Umaimainthan; Tangye, Stuart G.] Univ New S Wales, St Vincents Clin Sch, Sydney, NSW 2010, Australia.
[Freeman, Alexandra F.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Bhaduri-McIntosh, Sumita] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA.
RP Bhaduri-McIntosh, S (reprint author), SUNY Stony Brook, Sch Med, Dept Pediat, Stony Brook, NY 11794 USA.
EM sumita.bhaduri-mcintosh@stonybrook.edu
RI Tangye, Stuart/H-4023-2014
FU Research Foundation for the State University of New York; Resident
Research Grant from the American Academy of Pediatrics; National Health
and Medical Research Council of Australia; New South Wales Cancer
Council
FX We are grateful to Dr. Patrick Hearing for his valuable comments. We
thank Dr. Steven Holland at the National Institute for Allergy and
Infectious Diseases for providing access to AD-HIES patient samples, and
AD-HIES patients as well as healthy blood donors at the National
Institutes of Health Primary Immune Deficiency Clinic for their
participation. This study was supported by funds from the Research
Foundation for the State University of New York (to S.B.-M.), by a
Resident Research Grant from the American Academy of Pediatrics (to
J.H.-Y.), and from the National Health and Medical Research Council of
Australia and New South Wales Cancer Council (to S.G.T.).
NR 44
TC 19
Z9 20
U1 2
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 1
PY 2014
VL 111
IS 13
BP 4946
EP 4951
DI 10.1073/pnas.1400683111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9IX
UT WOS:000333579700063
PM 24639502
ER
PT J
AU Deleo, FR
Chen, L
Porcella, SF
Martens, CA
Kobayashi, SD
Porter, AR
Chavda, KD
Jacobs, MR
Mathema, B
Olsen, RJ
Bonomo, RA
Musser, JM
Kreiswirth, BN
AF DeLeo, Frank R.
Chen, Liang
Porcella, Stephen F.
Martens, Craig A.
Kobayashi, Scott D.
Porter, Adeline R.
Chavda, Kalyan D.
Jacobs, Michael R.
Mathema, Barun
Olsen, Randall J.
Bonomo, Robert A.
Musser, James M.
Kreiswirth, Barry N.
TI Molecular dissection of the evolution of carbapenem-resistant multilocus
sequence type 258 Klebsiella pneumoniae
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE antibiotic resistance; carbapenemase; Enterobacteriaceae; plasmid
ID CLONAL EXPANSION; BLA(KPC) GENE; LIVER-ABSCESS; EPIDEMIOLOGY;
INFECTIONS; EMERGENCE; ORIGIN
AB Infections caused by drug-resistant bacteria are a major problem worldwide. Carbapenem-resistant Klebsiella pneumoniae, most notably isolates classified as multilocus sequence type (ST) 258, have emerged as an important cause of hospital deaths. ST258 isolates are predominantly multidrug resistant, and therefore infections caused by them are difficult to treat. It is not known why the ST258 lineage is the most prevalent cause of multidrug-resistant K. pneumoniae infections in the United States and other countries. Here we tested the hypothesis that carbapenem-resistant ST258 K. pneumoniae is a single genetic clone that has disseminated worldwide. We sequenced to closure the genomes of two ST258 clinical isolates and used these genomes as references for comparative genome sequencing of 83 additional clinical isolates recovered from patients at diverse geographic locations worldwide. Phylogenetic analysis of the SNPs in the core genome of these isolates revealed that ST258 K. pneumoniae organisms are two distinct genetic clades. This unexpected finding disproves the single-clone hypothesis. Notably, genetic differentiation between the two clades results from an similar to 215-kb region of divergence that includes genes involved in capsule polysaccharide biosynthesis. The region of divergence appears to be a hotspot for DNA recombination events, and we suggest that this region has contributed to the success of ST258 K. pneumoniae. Our findings will accelerate research on novel diagnostic, therapeutic, and vaccine strategies designed to prevent and/or treat infections caused by multidrug resistant K. pneumoniae.
C1 [DeLeo, Frank R.; Kobayashi, Scott D.; Porter, Adeline R.] NIAID, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA.
[Porcella, Stephen F.; Martens, Craig A.] NIAID, Res Technol Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Chen, Liang; Chavda, Kalyan D.; Mathema, Barun; Kreiswirth, Barry N.] Rutgers State Univ, New Jersey Med Sch, Publ Hlth Res Inst, TB Ctr, Newark, NJ 07103 USA.
[Jacobs, Michael R.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.
[Bonomo, Robert A.] Case Western Reserve Univ, Dept Pharmacol Mol Biol & Microbiol, Cleveland, OH 44106 USA.
[Olsen, Randall J.; Musser, James M.] Houston Methodist Hosp Syst, Dept Pathol & Genom Med, Houston, TX 77204 USA.
[Olsen, Randall J.; Musser, James M.] Houston Methodist Hosp Syst, Houston Methodist Res Inst, Ctr Human Mol & Translat Infect Dis, Houston, TX 77204 USA.
[Bonomo, Robert A.] Louis Stokes Cleveland Vet Affairs Med Ctr, Res Serv, Cleveland, OH 44106 USA.
RP Kreiswirth, BN (reprint author), Rutgers State Univ, New Jersey Med Sch, Publ Hlth Res Inst, TB Ctr, Newark, NJ 07103 USA.
EM kreiswba@njms.rutgers.edu
RI Chavda, Kalyan/L-4311-2014;
OI DeLeo, Frank/0000-0003-3150-2516
FU National Institutes of Health (NIH) [1R01AI090155]; Intramural Research
Program of the NIAID, NIH
FX We thank Dan Bruno, Stacy Ricklefs, Jennifer Hashimoto, and Kent Barbian
of the National Institute of Allergy and Infectious Diseases (NIAID) for
technical assistance with genome sequencing and Anita Mora (NIAID) and
Heather Murphy (NIAID) for assistance with graphic illustration. This
work was supported in part by National Institutes of Health (NIH) Grant
1R01AI090155 (to B.N.K.), and by the Intramural Research Program of the
NIAID, NIH.
NR 24
TC 76
Z9 78
U1 2
U2 19
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 1
PY 2014
VL 111
IS 13
BP 4988
EP 4993
DI 10.1073/pnas.1321364111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9IX
UT WOS:000333579700070
PM 24639510
ER
PT J
AU Azrin, ST
AF Azrin, Susan T.
TI High-Impact Mental Health-Primary Care Research for Patients With
Multiple Comorbidities
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID DEPRESSION
AB Patients with multiple psychiatric and medical comorbidities are common in primary care practices (PCPs), and recent health care reforms will likely lead to an increase in their numbers. PCPs need flexible, integrated mental health primary care interventions that are applicable to these complex patients and compatible with the PCP setting. Generating practice-ready solutions for rapid uptake in typical PCPs requires a new direction for mental health primary care research. This column describes an approach that embraces both real-world relevance and methodological rigor to stimulate such research. The approach emphasizes generating knowledge that decision makers need, using practice-based evidence and efficient methods, and planning for sustainability and broad uptake from the outset.
C1 NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
RP Azrin, ST (reprint author), NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
EM azrinst@mail.nih.gov
NR 14
TC 1
Z9 1
U1 0
U2 0
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
EI 1557-9700
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD APR
PY 2014
VL 65
IS 4
BP 406
EP 409
DI 10.1176/appi.ps.201300537
PG 4
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA AD8WE
UT WOS:000333545600002
PM 24534819
ER
PT J
AU Counotte, DS
Schiefer, C
Shaham, Y
O'Donnell, P
AF Counotte, Danielle S.
Schiefer, Christopher
Shaham, Yavin
O'Donnell, Patricio
TI Time-dependent decreases in nucleus accumbens AMPA/NMDA ratio and
incubation of sucrose craving in adolescent and adult rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE AMPA/NMDA ratio; Extinction; Incubation of reward craving; Nucleus
accumbens; Relapse; Sucrose; Synaptic plasticity
ID CUE-INDUCED REINSTATEMENT; VENTRAL TEGMENTAL AREA; MESOLIMBIC DOPAMINE
SYSTEM; SILENT SYNAPSES; COCAINE-SEEKING; SYNAPTIC PLASTICITY;
DRUG-SEEKING; EXTINCTION BEHAVIOR; NEUROTROPHIC FACTOR; PROTEIN
EXPRESSION
AB There is evidence that cue-induced sucrose seeking progressively increases after cessation of oral sucrose self-administration (incubation of sucrose craving) in both adolescent and adult rats. The synaptic plasticity changes associated with this incubation at different age groups are unknown. We assessed whether incubation of sucrose craving in rats trained to self-administer sucrose as young adolescents, adolescents, or adults is associated with changes in 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA)/N-methyl-d-aspartate (NMDA) ratio (a measure of postsynaptic changes in synaptic strength) in nucleus accumbens.
Three age groups initiated oral sucrose self-administration training (10 days) on postnatal day (P) 35 (young adolescents), P42 (adolescents), or P70 (adults). They were then tested for cue-induced sucrose seeking (assessed in an extinction test) on abstinence days 1 and 21. Separate groups of rats were trained to self-administer sucrose or water (a control condition), and assessed for AMPA/NMDA ratio in nucleus accumbens on abstinence days 1-3 and 21.
Adult rats earned more sucrose rewards, but sucrose intake per body weight was higher in young adolescent rats. Time-dependent increases in cue-induced sucrose seeking (incubation of sucrose craving) were more pronounced in adult rats, less pronounced in adolescents, and not detected in young adolescents. On abstinence day 21, but not days 1-3, AMPA/NMDA ratio in nucleus accumbens were decreased in rats that self-administered sucrose as adults and adolescents, but not young adolescents.
Our data demonstrate age-dependent changes in magnitude of incubation of sucrose craving and nucleus accumbens synaptic plasticity after cessation of sucrose self-administration.
C1 [Counotte, Danielle S.; Schiefer, Christopher; O'Donnell, Patricio] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
[Shaham, Yavin] IRP NIDA, Behav Neurosci Branch, Baltimore, MD USA.
RP Counotte, DS (reprint author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, 20 Penn St,Rm S-251, Baltimore, MD 21201 USA.
EM d.s.counotte@gmail.com
RI shaham, yavin/G-1306-2014;
OI O'Donnell, Patricio/0000-0001-7788-624X
FU NIDA, NIH [R01 DA014020]
FX The research and writing of this paper was supported by extramural (R01
DA014020, PO'D) and intramural (YS) funds from NIDA, NIH.
NR 58
TC 12
Z9 12
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD APR
PY 2014
VL 231
IS 8
BP 1675
EP 1684
DI 10.1007/s00213-013-3294-3
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AD8MX
UT WOS:000333521400019
PM 24114427
ER
PT J
AU Lauer, MS
Bonds, D
AF Lauer, Michael S.
Bonds, Denise
TI Eliminating the "expensive" adjective for clinical trials
SO AMERICAN HEART JOURNAL
LA English
DT Editorial Material
ID ELEVATION MYOCARDIAL-INFARCTION; THROMBUS ASPIRATION; REGISTRY TRIAL
C1 [Lauer, Michael S.; Bonds, Denise] NHLBI, Div Cardiovasc Sci DCVS, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), 6701 Rockledge Dr Room 8128, Bethesda, MD 20892 USA.
EM lauerm@nhlbi.nih.gov
NR 11
TC 1
Z9 1
U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD APR
PY 2014
VL 167
IS 4
BP 419
EP 420
DI 10.1016/j.ahj.2013.12.003
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AD3UE
UT WOS:000333170900001
PM 24655687
ER
PT J
AU Starling, AP
Engel, SM
Richardson, DB
Baird, DD
Haug, LS
Stuebe, AM
Klungsoyr, K
Harmon, Q
Becher, G
Thomsen, C
Sabaredzovic, A
Eggesbo, M
Hoppin, JA
Travlos, GS
Wilson, RE
Trogstad, LI
Magnus, P
Longnecker, MP
AF Starling, Anne P.
Engel, Stephanie M.
Richardson, David B.
Baird, Donna D.
Haug, Line S.
Stuebe, Alison M.
Klungsoyr, Kari
Harmon, Quaker
Becher, Georg
Thomsen, Cathrine
Sabaredzovic, Azemira
Eggesbo, Merete
Hoppin, Jane A.
Travlos, Gregory S.
Wilson, Ralph E.
Trogstad, Lill I.
Magnus, Per
Longnecker, Matthew P.
TI Perfluoroalkyl Substances During Pregnancy and Validated Preeclampsia
Among Nulliparous Women in the Norwegian Mother and Child Cohort Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Norwegian Mother and Child Cohort Study; perfluoroalkyl substances;
perfluorooctanoic acid; perfluorooctane sulfonate; perfluoroundecanoic
acid; preeclampsia
ID PERFLUORINATED COMPOUNDS; PERFLUOROOCTANE SULFONATE; HYPERTENSIVE
DISORDERS; SERUM CONCENTRATIONS; LIPID CONCENTRATIONS; SECULAR TRENDS;
RISK; EXPOSURE; PLASMA; BLOOD
AB Perfluoroalkyl substances (PFAS) are persistent and ubiquitous environmental contaminants, and human exposure to these substances may be related to preeclampsia, a common pregnancy complication. Previous studies have found serum concentrations of PFAS to be positively associated with pregnancy-induced hypertension and preeclampsia in a population with high levels of exposure to perfluorooctanoate. Whether this association exists among pregnant women with background levels of PFAS exposure is unknown. Using data from the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health, we carried out a study of nulliparous pregnant women enrolled in 20032007 (466 cases, 510 noncases) to estimate associations between PFAS concentrations and an independently validated diagnosis of preeclampsia. We measured levels of 9 PFAS in maternal plasma extracted midpregnancy; statistical analyses were restricted to 7 PFAS that were quantifiable in more than 50 of samples. In proportional hazards models adjusted for maternal age, prepregnancy body mass index (weight (kg)/height (m)(2)), educational level, and smoking status, we observed no strongly positive associations between PFAS levels and preeclampsia. We found an inverse association between preeclampsia and the highest quartile of perfluoroundecanoic acid concentration relative to the lowest quartile (hazard ratio 0.55, 95 confidence interval: 0.38, 0.81). Overall, our findings do not support an increased risk of preeclampsia among nulliparous Norwegian women with background levels of PFAS exposure.
C1 [Starling, Anne P.; Baird, Donna D.; Harmon, Quaker; Hoppin, Jane A.; Longnecker, Matthew P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Starling, Anne P.; Engel, Stephanie M.; Richardson, David B.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Haug, Line S.; Becher, Georg; Thomsen, Cathrine; Sabaredzovic, Azemira] Norwegian Inst Publ Hlth, Dept Exposure & Risk Assessment, Div Environm Med, Oslo, Norway.
[Stuebe, Alison M.] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA.
[Stuebe, Alison M.] Univ N Carolina, Dept Maternal & Child Hlth, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Klungsoyr, Kari] Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway.
[Klungsoyr, Kari] Univ Bergen, Dept Global Publ Hlth & Primary Hlth Care, Bergen, Norway.
[Becher, Georg] Univ Oslo, Dept Chem, Oslo, Norway.
[Eggesbo, Merete] Norwegian Inst Publ Hlth, Dept Genes & Environm, Div Epidemiol, Oslo, Norway.
[Travlos, Gregory S.; Wilson, Ralph E.] NIEHS, Cellular & Mol Pathol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Trogstad, Lill I.; Magnus, Per] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway.
RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, Mail Drop A3-05,POB 12233, Res Triangle Pk, NC 27709 USA.
EM longnec1@niehs.nih.gov
RI Baird, Donna/D-5214-2017;
OI Baird, Donna/0000-0002-5544-2653; Harmon, Quaker/0000-0002-5866-848X;
Longnecker, Matthew/0000-0001-6073-5322; Eggesbo,
Merete/0000-0002-0006-5336
FU National Institutes of Health (NIH), National Institute of Environmental
Health Sciences (NIEHS); National Institute of Environmental Health
Sciences [1-F30-ES022 126-01]; National Institute of Child Health and
Human Development [R01HD058008]; Norwegian Ministry of Health; Ministry
of Education and Research, NIH/NIEHS [N01-ES-75558]; NIH/National
Institute of Neurological Disorders and Stroke [UO1 NS 047537-01, UO1 NS
047537-06A1]; Norwegian Research Council/FUGE [151918/S10]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (NIH), National Institute of
Environmental Health Sciences (NIEHS). A. P. S. was supported by an
extramural award (1-F30-ES022 126-01) from the National Institute of
Environmental Health Sciences. The validation of preeclampsia diagnosis
was funded by the National Institute of Child Health and Human
Development (R01HD058008; principal investigator, S. M. E.). The
Norwegian Mother and Child Cohort Study is supported by the Norwegian
Ministry of Health and the Ministry of Education and Research, NIH/NIEHS
(contract N01-ES-75558), NIH/National Institute of Neurological
Disorders and Stroke (grants UO1 NS 047537-01 and UO1 NS 047537-06A1),
and the Norwegian Research Council/FUGE (grant 151918/S10).
NR 51
TC 4
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U1 0
U2 16
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD APR 1
PY 2014
VL 179
IS 7
BP 824
EP 833
DI 10.1093/aje/kwt432
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AD4US
UT WOS:000333247200004
PM 24557813
ER
PT J
AU Engel, SM
Joubert, BR
Wu, MC
Olshan, AF
Haberg, SE
Ueland, PM
Nystad, W
Nilsen, RM
Vollset, SE
Peddada, SD
London, SJ
AF Engel, Stephanie M.
Joubert, Bonnie R.
Wu, Michael C.
Olshan, Andrew F.
Haberg, Siri E.
Ueland, Per Magne
Nystad, Wenche
Nilsen, Roy M.
Vollset, Stein Emil
Peddada, Shyamal D.
London, Stephanie J.
TI Neonatal Genome-Wide Methylation Patterns in Relation to Birth Weight in
the Norwegian Mother and Child Cohort
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE birth weight; cord blood; epigenetics; methylation; MoBa; Norwegian
Mother and Child Cohort Study
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; FOR-GESTATIONAL-AGE; DNA METHYLATION;
JAPANESE POPULATION; MATERNAL SMOKING; MAMMALIAN-CELLS; PREGNANT-WOMEN;
ASSOCIATION; IGF2; GENE
AB Although epigenetic regulation plays a critical role in embryonic development, few studies have examined the relationship of epigenome-wide methylation with fetal growth. Using the Infinium HumanMethylation450 BeadChip (Illumina, Inc., San Diego, California) in a substudy of 1,046 infants from the Norwegian Mother and Child Cohort Study (MoBa) enrolled between 1999 and 2008, we examined epigenome-wide cord blood DNA methylation in relation to birth weight. In multivariable-adjusted robust linear regression models, we identified differential methylation at 19 cytosine-guanine dinucleotides (CpGs) associated with either decreased (AT-rich interactive domain 5B (MRF1-like) (ARID5B), 2 CpGs) or increased (x-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3), 4 CpGs) birth weight. ARID5B knockout mice have less adipose tissue and significantly lower weight in the postnatal period. XRCC3 plays a key role in the maintenance of chromosome stability and the repair of DNA damage. Although there are fewer data on the other implicated genes, many of these genes have been shown to have roles in developmental processes. This constitutes the largest and most robust study of birth weight using an epigenome-wide methylation platform and offers potential insights into epigenetic mechanisms of fetal growth.
C1 [Engel, Stephanie M.; Olshan, Andrew F.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Joubert, Bonnie R.; London, Stephanie J.] NIEHS, Epidemiol Branch, Div Intramural Res, Res Triangle Pk, NC 27709 USA.
[Wu, Michael C.] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Haberg, Siri E.] Norwegian Inst Publ Hlth, Inst Management & Staff, Oslo, Norway.
[Ueland, Per Magne] Univ Bergen, Dept Clin Sci, Bergen, Norway.
[Ueland, Per Magne] Haukeland Hosp, Lab Clin Biochem, N-5021 Bergen, Norway.
[Nystad, Wenche; Vollset, Stein Emil] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway.
[Nilsen, Roy M.; Vollset, Stein Emil] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
[Peddada, Shyamal D.] NIEHS, Biostat Branch, Div Intramural Res, Res Triangle Pk, NC 27709 USA.
RP Engel, SM (reprint author), Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Campus Box 7435, Chapel Hill, NC 27599 USA.
EM stephanie.engel@unc.edu; london2@niehs.nih.gov
RI Ueland, Per/C-7340-2013;
OI London, Stephanie/0000-0003-4911-5290; Wu, Michael
C./0000-0002-3357-6570
FU National Institute of Environmental Health Sciences [Z01-ES-49019,
P30ES0 10126, NO-ES-75558]; Norwegian Ministry of Health; Ministry of
Education and Research; National Institute of Neurological Disorders and
Stroke [1 UO1 NS 047537-01]; Norwegian Research Council/Functional
Genomics [151918/S10]; Eunice Kennedy Shriver National Institute of
Child Health and Human Development [R01HD058008]
FX This research was supported in part by the intramural research program
of the National Institute of Environmental Health Sciences (grant
Z01-ES-49019) and the National Institute of Environmental Health
Sciences (grant P30ES0 10126). The Norwegian Mother and Child Cohort
Study is supported by the Norwegian Ministry of Health and the Ministry
of Education and Research and the National Institute of Environmental
Health Sciences (contract NO-ES-75558), the National Institute of
Neurological Disorders and Stroke (grant 1 UO1 NS 047537-01), and the
Norwegian Research Council/Functional Genomics (grant 151918/S10).
Support for Drs. Engel and Wu was provided by the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (grant
R01HD058008).
NR 54
TC 29
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U1 0
U2 18
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD APR 1
PY 2014
VL 179
IS 7
BP 834
EP 842
DI 10.1093/aje/kwt433
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AD4US
UT WOS:000333247200005
PM 24561991
ER
PT J
AU Mondul, AM
Giovannucci, E
Platz, EA
AF Mondul, Alison M.
Giovannucci, Edward
Platz, Elizabeth A.
TI Re: "A Prospective Study of Statin Drug Use and Lower Urinary Tract
Symptoms in Older Men" REPLY
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Letter
C1 [Mondul, Alison M.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA.
[Giovannucci, Edward] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Platz, Elizabeth A.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
[Platz, Elizabeth A.] Johns Hopkins Univ, Sch Med, Brady Urol Res Inst, Baltimore, MD USA.
RP Mondul, AM (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
EM mondulam@mail.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD APR 1
PY 2014
VL 179
IS 7
BP 928
EP 928
DI 10.1093/aje/kwu044
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AD4US
UT WOS:000333247200015
PM 24651168
ER
PT J
AU Klein, WMP
Ferrer, RA
Graff, KA
Kaufman, AR
Han, PKJ
AF Klein, William M. P.
Ferrer, Rebecca A.
Graff, Kaitlin A.
Kaufman, Annette R.
Han, Paul K. J.
TI Perceived Ambiguity, Fatalism, and Believing Cancer Is More Prevalent
Than Heart Disease
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID PREVENTION; RISK
C1 [Klein, William M. P.; Ferrer, Rebecca A.; Graff, Kaitlin A.; Kaufman, Annette R.] NCI, NIH, Bethesda, MD 20892 USA.
[Han, Paul K. J.] Maine Med Ctr, Portland, ME 04102 USA.
RP Klein, WMP (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM kleinwm@mail.nih.gov
OI Han, Paul/0000-0003-0165-1940
FU Intramural NIH HHS [Z99 CA999999]
NR 10
TC 2
Z9 2
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD APR
PY 2014
VL 46
IS 4
BP E45
EP E47
DI 10.1016/j.amepre.2014.01.003
PG 3
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA AD4YM
UT WOS:000333257900001
PM 24650848
ER
PT J
AU Insel, TR
AF Insel, Thomas R.
TI The NIMH Research Domain Criteria (RDoC) Project: Precision Medicine for
Psychiatry
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Editorial Material
ID DISORDERS
C1 NIMH, Bethesda, MD 20892 USA.
RP Insel, TR (reprint author), NIMH, Bethesda, MD 20892 USA.
EM tinsel@mail.nih.gov
NR 12
TC 210
Z9 212
U1 9
U2 49
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD APR
PY 2014
VL 171
IS 4
BP 395
EP 397
DI 10.1176/appi.ajp.2014.14020138
PG 3
WC Psychiatry
SC Psychiatry
GA AD8FD
UT WOS:000333501000005
PM 24687194
ER
PT J
AU Driver, DI
Anvari, AA
Peroutka, CM
Kataria, R
Overman, J
Lang, D
Tietcheu, M
Parker, R
Baptiste, K
Rapoport, JL
Gogtay, N
AF Driver, David I.
Anvari, Afsoon A.
Peroutka, Christina M.
Kataria, Rachna
Overman, Jerry
Lang, David
Tietcheu, Maria
Parker, Reggie
Baptiste, Keith
Rapoport, Judith L.
Gogtay, Nitin
TI Management of Clozapine-Induced Fever in a Child
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Editorial Material
ID NEUROLEPTIC MALIGNANT SYNDROME; EARLY-ONSET SCHIZOPHRENIA; DOUBLE-BLIND;
INDUCED AGRANULOCYTOSIS; SERUM-LEVELS; CYTOKINE; OLANZAPINE; ALPHA
C1 [Driver, David I.; Anvari, Afsoon A.; Peroutka, Christina M.; Kataria, Rachna; Overman, Jerry; Lang, David; Tietcheu, Maria; Parker, Reggie; Baptiste, Keith; Rapoport, Judith L.; Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Driver, DI (reprint author), NIMH, Child Psychiat Branch, Bldg 10, Bethesda, MD 20892 USA.
EM davididriver@gmail.com
RI Gogtay, Nitin/A-3035-2008
NR 37
TC 3
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U1 2
U2 3
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD APR
PY 2014
VL 171
IS 4
BP 398
EP 402
DI 10.1176/appi.ajp.2013.13070866
PG 5
WC Psychiatry
SC Psychiatry
GA AD8FD
UT WOS:000333501000006
PM 24687195
ER
PT J
AU Romero, R
Miranda, J
Chaiworapongsa, T
Chaemsaithong, P
Gotsch, F
Dong, Z
Ahmed, AI
Yoon, BH
Hassan, SS
Kim, CJ
Korzeniewski, SJ
Yeo, L
AF Romero, Roberto
Miranda, Jezid
Chaiworapongsa, Tinnakorn
Chaemsaithong, Piya
Gotsch, Francesca
Dong, Zhong
Ahmed, Ahmed I.
Yoon, Bo Hyun
Hassan, Sonia S.
Kim, Chong Jai
Korzeniewski, Steven J.
Yeo, Lami
TI A Novel Molecular Microbiologic Technique for the Rapid Diagnosis of
Microbial Invasion of the Amniotic Cavity and Intra- Amniotic Infection
in Preterm Labor with Intact Membranes
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Article
DE Broad-range real-time polymerase chain reaction; electrospray ionization
mass spectrometry; inflammation; preterm delivery; time-of-flight
ID POLYMERASE-CHAIN-REACTION; IONIZATION MASS-SPECTROMETRY; BLOOD-CELL
COUNT; PLACEBO-CONTROLLED TRIAL; REAL-TIME-PCR;
HUMAN-IMMUNODEFICIENCY-VIRUS; FLUID GLUCOSE-CONCENTRATION; SUBCLINICAL
INTRAAMNIOTIC INFECTION; ASYMPTOMATIC BACTERIAL VAGINOSIS; INTRAUTERINE
VIRAL-INFECTION
AB ProblemThe diagnosis of microbial invasion of the amniotic cavity (MIAC) has been traditionally performed using traditional cultivation techniques, which require growth of microorganisms in the laboratory. Shortcomings of culture methods include the time required (days) for identification of microorganisms, and that many microbes involved in the genesis of human diseases are difficult to culture. A novel technique combines broad-range real-time polymerase chain reaction with electrospray ionization time-of-flight mass spectrometry (PCR/ESI-MS) to identify and quantify genomic material from bacteria and viruses.
Method of studyAF samples obtained by transabdominal amniocentesis from 142 women with preterm labor and intact membranes (PTL) were analyzed using cultivation techniques (aerobic, anaerobic, and genital mycoplasmas) as well as PCR/ESI-MS. The prevalence and relative magnitude of intra-amniotic inflammation [AF interleukin 6 (IL-6) concentration 2.6ng/mL], acute histologic chorioamnionitis, spontaneous preterm delivery, and perinatal mortality were examined.
Results(i) The prevalence of MIAC in patients with PTL was 7% using standard cultivation techniques and 12% using PCR/ESI-MS; (ii) seven of ten patients with positive AF culture also had positive PCR/ESI-MS [17 genome equivalents per PCR reaction well (GE/well)]; (iii) patients with positive PCR/ESI-MS (17 GE/well) and negative AF cultures had significantly higher rates of intra-amniotic inflammation and acute histologic chorioamnionitis, a shorter interval to delivery [median (interquartile range-IQR)], and offspring at higher risk of perinatal mortality, than women with both tests negative [90% (9/10) versus 32% (39/122) OR: 5.6; 95% CI: 1.4-22; (P<0.001); 70% (7/10) versus 35% (39/112); (P=0.04); 1 (IQR: <1-2)days versus 25 (IQR: 5-51)days; (P=0.002), respectively]; (iv) there were no significant differences in these outcomes between patients with positive PCR/ESI-MS (17 GE/well) who had negative AF cultures and those with positive AF cultures; and (v) PCR/ESI-MS detected genomic material from viruses in two patients (1.4%).
Conclusion(i) Rapid diagnosis of intra-amniotic infection is possible using PCR/ESI-MS; (ii) the combined use of biomarkers of inflammation and PCR/ESI-MS allows for the identification of specific bacteria and viruses in women with preterm labor and intra-amniotic infection; and (iii) this approach may allow for administration of timely and specific interventions to reduce morbidity attributed to infection-induced preterm birth.
C1 [Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I.; Hassan, Sonia S.; Kim, Chong Jai; Korzeniewski, Steven J.; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA.
[Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I.; Hassan, Sonia S.; Kim, Chong Jai; Korzeniewski, Steven J.; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Miranda, Jezid; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Dong, Zhong; Ahmed, Ahmed I.; Hassan, Sonia S.; Korzeniewski, Steven J.; Yeo, Lami] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Gotsch, Francesca] Azienda Osped Univ, Integrata Verona, Verona, Italy.
[Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Kim, Chong Jai] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea.
RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services (NICHD/NIH); NICHD, NIH [HHSN275201300006C]
FX The authors acknowledge the contributions of Jack Sobel, MD, Chief of
Infectious Diseases at Wayne State University, Ronald Lamont, BSc, MB,
ChB, MD, FRCOG, Jacques Ravel, PhD, David Relman, MD, and Sharon Hillier
PhD, who have worked in collaboration with the Perinatology Research
Branch in previous projects related to microbial invasion of the
amniotic cavity and the vaginal microbiome. This research was supported,
in part, by the Perinatology Research Branch, Division of Intramural
Research, Eunice Kennedy Shriver National Institute of Child Health and
Human Development, National Institutes of Health, Department of Health
and Human Services (NICHD/NIH), and, in part, with Federal funds from
NICHD, NIH under Contract No. HHSN275201300006C.
NR 377
TC 41
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U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1046-7408
EI 1600-0897
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD APR
PY 2014
VL 71
IS 4
BP 330
EP 358
DI 10.1111/aji.12189
PG 29
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA AC4CK
UT WOS:000332468000006
PM 24417618
ER
PT J
AU Strebel, K
AF Strebel, Klaus
TI HIV-1 Vpu - an ion channel in search of a job
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Review
DE HIV-1; Vpu; BST-2; Tetherin; Ion channel; CD4
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHIMERIC ENVELOPE GLYCOPROTEINS;
CLATHRIN-MEDIATED ENDOCYTOSIS; ANTI-TETHERIN ACTIVITIES; B TRANSCRIPTION
FACTORS; VIRAL PARTICLE RELEASE; KAPPA-B; ENDOPLASMIC-RETICULUM;
TRANSMEMBRANE DOMAIN; CELL-SURFACE
AB Vpu is a small membrane protein encoded by HIV-1 and some SIV isolates. The protein is best known for its ability to degrade CD4 and to enhance the release of progeny virions from infected cells. However, Vpu also promotes host-cell apoptosis by deregulating the NF kappa B signaling pathway and it assembles into cation-conducting membrane pores. This review summarizes our current understanding of these various functions of Vpu with particular emphasis on recent progress in the Vpu field. This article is part of a Special Issue entitled: Viral Membrane Proteins Channels for Cellular Networking. Published by Elsevier B.V.
C1 NIAID, Viral Biochem Sect, Mol Microbiol Lab, 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 Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX K. Strebel is supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 115
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U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
EI 0006-3002
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD APR
PY 2014
VL 1838
IS 4
SI SI
BP 1074
EP 1081
DI 10.1016/j.bbamem.2013.06.029
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AD8HS
UT WOS:000333507700004
PM 23831603
ER
PT J
AU Luttge, BG
Panchal, P
Puri, V
Checkley, MA
Freed, EO
AF Luttge, Benjamin G.
Panchal, Prashant
Puri, Vinita
Checkley, Mary Ann
Freed, Eric O.
TI Mutations in the feline immunodeficiency virus envelope glycoprotein
confer resistance to a dominant-negative fragment of Tsg101 by enhancing
infectivity and cell-to-cell virus transmission
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Article
DE FIV; HIV-1; AIDS; ESCRT; Tsg101; Cell-to-cell virus transmission; Late
domain; TSG-5' resistance
ID PROTEIN-SORTING PATHWAY; LATE-BUDDING DOMAINS; ESCRT MACHINERY;
STRUCTURAL-CHARACTERIZATION; REVERSE-TRANSCRIPTASE; SURFACE
GLYCOPROTEIN; RESTRICTION FACTORS; HELICAL DOMAIN; FIV INFECTION; TYPE-1
GP41
AB The Pro-Set-Ala-Pro (PSAP) motif in the p2 domain of feline immunodeficiency virus (FIV) Gag is required for efficient virus release, virus replication, and Gag binding to the ubiquitin-E2-variant (UEV) domain of Tsg101. As a result of this direct interaction, expression of an N-terminal fragment of Tsg101 containing the UEV domain (referred to as TSG-5') inhibits FIV release. In these respects, the FIV p2(Gag) PSAP motif is analogous to the PTAP motif of HIV-1 p6(Gag). To evaluate the feasibility of a late domain-targeted inhibition of virus replication, we created an enriched Crandell-Rees feline kidney (CRFK) cell line (T5'(hi)) that stably expresses high levels of TSG-5'. Here we show that mutations in either the V3 loop or the second heptad repeat (HR2) domain of the FIV envelope glycoprotein (Env) rescue FIV replication in T5'(hi) cells without increasing FIV release efficiency. TSG-5'-resistance mutations in Env enhance virion infectivity and the cell-cell spread of FIV when diffusion is limited using a semisolid growth medium. These findings show that mutations in functional domains of Env confer TSG-5'-resistance, which we propose enhances specific infectivity and the cell-cell transmission of virus to counteract inefficient virus release. This article is part of a Special Issue entitled: Viral Membrane Proteins Channels for Cellular Networking. Published by Elsevier B.V.
C1 [Luttge, Benjamin G.; Panchal, Prashant; Puri, Vinita; Checkley, Mary Ann; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Bg 535,Room 110,1050 Boyles St, Frederick, MD 21702 USA.
EM efreed@nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, NIH; Intramural AIDS Targeted Antiviral Program
FX We thank members of the Freed laboratory for the helpful discussion, and
John Elder and Eric Poeschla for providing the valuable reagents. This
research was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, NIH, and by the
Intramural AIDS Targeted Antiviral Program.
NR 94
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
EI 0006-3002
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD APR
PY 2014
VL 1838
IS 4
SI SI
BP 1143
EP 1152
DI 10.1016/j.bbamem.2013.08.020
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AD8HS
UT WOS:000333507700012
PM 24036228
ER
PT J
AU Li, XX
Brazauskas, R
Wang, ZW
Al-Seraihy, A
Baker, KS
Cahn, JY
Frangoul, HA
Gajewski, JL
Hale, GA
Hsu, JW
Kamble, RT
Lazarus, HM
Marks, DI
Maziarz, RT
Savani, BN
Shah, AJ
Shah, N
Sorror, ML
Wood, WA
Majhail, NS
AF Li, Xiaxin
Brazauskas, Ruta
Wang, Zhiwei
Al-Seraihy, Arnal
Baker, K. Scott
Cahn, Jean-Yves
Frangoul, Haydar A.
Gajewski, James L.
Hale, Gregory A.
Hsu, Jack W.
Kamble, Rammurti T.
Lazarus, Hillard M.
Marks, David I.
Maziarz, Richard T.
Savani, Bipin N.
Shah, Ami J.
Shah, Nirali
Sorror, Mohamed L.
Wood, William A.
Majhail, Navneet S.
TI Avascular Necrosis of Bone after Allogeneic Hematopoietic Cell
Transplantation in Children and Adolescents
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Avascular necrosis; Late complications; Hematopoietic cell;
transplantation
ID LONG-TERM SURVIVORS; MARROW-TRANSPLANTATION; RISK-FACTORS; PREVENTIVE
PRACTICES; CONSENSUS CONFERENCE; MINERAL DENSITY; OSTEONECROSIS;
CHILDHOOD
AB We conducted a nested case-control study within a cohort of 6244 patients to assess risk factors for avascular necrosis (AVN) of bone in children and adolescents after allogeneic transplantation. Eligible patients were <= 21 years of age, received their first allogeneic transplant between 1990 and 2008 in the United States, and had survived >= 6 months from transplantation. Overall, 160 patients with AVN and 478 control subjects matched by year of transplant, length of follow-up and transplant center were identified. Patients and control subjects were confirmed via central review of radiology, pathology, and/or surgical procedure reports. Median time from transplant to diagnosis of AVN was 14 months. On conditional logistic regression, increasing age at transplant (>= 5 years), female gender, and chronic graft-versus-host disease (GVHD) were significantly associated with increased risks of AVN. Compared with patients receiving myeloablative regimens for malignant diseases, lower risks of AVN were seen in patients with nonmalignant diseases and those who had received reduced-intensity conditioning regimens for malignant diseases. Children at high risk for AVN include those within the age group where rapid bone growth occurs as well as those who experience exposure to myeloablative conditioning regimens and immunosuppression after hematopoietic cell transplantation for the treatment of GVHD. More research is needed to determine whether screening strategies specifically for patients at high risk for developing AVN with early interventions may mitigate the morbidity associated with this complication. (c) 2014 American Society for Blood and Marrow Transplantation.
C1 [Li, Xiaxin] Banner Hlth, Banner Childrens Specialists Pediat Hematol Oncol, Mesa, AZ USA.
[Brazauskas, Ruta] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Div Biostat, Milwaukee, WI 53226 USA.
[Wang, Zhiwei] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Al-Seraihy, Arnal] King Faisal Specialist Hosp & Res Ctr, Hematopoiet Stem Cell Transplantat Program, Riyadh 11211, Saudi Arabia.
[Baker, K. Scott; Sorror, Mohamed L.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Cahn, Jean-Yves] Univ Hosp, Clin Univ Hematol, Grenoble, France.
[Frangoul, Haydar A.; Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Pediat Blood & Marrow Transplant Program, Nashville, TN USA.
[Gajewski, James L.; Maziarz, Richard T.] Oregon Hlth & Sci Univ, Bone Marrow & Stem Cell Transplant Program, Portland, OR 97201 USA.
[Hale, Gregory A.] Univ S Florida, All Childrens Hosp, Div Hematol & Oncol, St Petersburg, FL 33701 USA.
[Hsu, Jack W.] Shands HealthCare, Div Hematol & Oncol, Gainesville, FL USA.
[Hsu, Jack W.] Univ Florida, Gainesville, FL USA.
[Kamble, Rammurti T.] Baylor Coll Med, Ctr Cell & Gene Therapy, Sect Hematol Oncol, Houston, TX 77030 USA.
[Lazarus, Hillard M.] Univ Hosp Cleveland, Case Med Ctr, Seidman Canc Ctr, Cleveland, OH 44106 USA.
[Marks, David I.] Bristol Childrens Hosp, BMT Unit, Bristol, Avon, England.
[Shah, Ami J.] Univ Calif Los Angeles, Mattel Childrens Hosp, Dept Pediat, Div Hematol Oncol, Los Angeles, CA USA.
[Shah, Nirali] NCI, NIH, Bethesda, MD 20892 USA.
[Sorror, Mohamed L.] Univ Washington, Sch Med, Dept Med, Div Med Oncol, Seattle, WA 98195 USA.
[Wood, William A.] Univ North Carolina Hosp, Div Hematol & Oncol, Chapel Hill, NC USA.
[Majhail, Navneet S.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[Majhail, Navneet S.] Cleveland Clin, Blood & Marrow Transplant Program, Cleveland, OH 44195 USA.
RP Majhail, NS (reprint author), Cleveland Clin, Blood & Marrow Transplant Program, 9500 Euclid Ave,R35, Cleveland, OH 44195 USA.
EM ksandhya@stanford.edu
RI Cahn, Jean-Yves/M-6493-2014;
OI Wood, William/0000-0001-7439-2543
FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and
Blood Institute (NHLBI); National Institute of Allergy and Infectious
Diseases [5U01HL069294]; NHLBI and NCI [HHSH234200637015]; Health
Resources and Services Administration [NO0014-06-1-0704,
N00014-08-1-0058]
FX Financial disclosure: The CIBMTR is supported by Public Health Service
Grant/Cooperative Agreement U24-CA76518 from the National Cancer
Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI),
and the National Institute of Allergy and Infectious Diseases;
Grant/Cooperative Agreement 5U01HL069294 from the NHLBI and NCI;
contract HHSH234200637015 C from the Health Resources and Services
Administration; 2 grants (NO0014-06-1-0704 and N00014-08-1-0058) from
the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.;
Angioblast; Anonymous donation to the Medical College of Wisconsin;
Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association;
Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix,
GmbH; Children's Leukemia Research Association; Fresenius-Biotech North
America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;
Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis
Pharma; The Leukemia & Lymphoma Society; The Medical College of
Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.;
Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor
Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.;
Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics;
Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord
Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan
Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS,
Inc.; and Wellpoint, Inc. The views expressed in this article do not
reflect the official policy or position of the National Institutes of
Health, the Department of the Navy, the Department of Defense, or any
other agency of the U.S. Government.
NR 24
TC 3
Z9 3
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD APR
PY 2014
VL 20
IS 4
BP 587
EP 592
DI 10.1016/j.bbmt.2013.12.567
PG 6
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA AD5VX
UT WOS:000333322400023
PM 24388803
ER
PT J
AU Brinton, LA
Figueroa, JD
Awuah, B
Yarney, J
Wiafe, S
Wood, SN
Ansong, D
Nyarko, K
Wiafe-Addai, B
Clegg-Lamptey, JN
AF Brinton, Louise A.
Figueroa, Jonine D.
Awuah, Baffour
Yarney, Joel
Wiafe, Seth
Wood, Shannon N.
Ansong, Daniel
Nyarko, Kofi
Wiafe-Addai, Beatrice
Clegg-Lamptey, Joe Nat
TI Breast cancer in Sub-Saharan Africa: opportunities for prevention
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Review
DE Breast cancer; Sub-Saharan Africa; Incidence; Mortality; Etiology;
Prevention
ID GENOME-WIDE ASSOCIATION; NIGERIAN WOMEN; RISK-FACTORS; HORMONE-RECEPTOR;
INDIGENOUS AFRICANS; AMERICAN WOMEN; HAIR RELAXERS; SOUTH-AFRICA;
TRENDS; RADIOTHERAPY
AB Although breast cancer is a growing health problem in sub-Saharan Africa, reasons for its increased occurrence remain unclear. We reviewed the published literature to determine the magnitude of the increase in breast cancer, associated risk factors (including for breast cancer subtypes), and ways to reduce incidence and mortality. Some of the increased breast cancer occurrence likely reflects that women are living longer and adopting lifestyles that favor higher incidence rates. However, a greater proportion of breast cancers occur among premenopausal women as compared to elsewhere, which may reflect unique risk factors. Breast cancers diagnosed among African women reportedly include a disproportionate number of poor prognosis tumors, including hormone receptor negative, triple negative, and core basal phenotype tumors. However, it is unclear how lack of standardized methods for tissue collection, fixation, and classification contribute to these rates. Given appropriate classifications, it will be of interest to compare rates with other populations and to identify risk factors that relate to specific tumor subtypes. This includes not only risk factors that have been recognized in other populations but also some that may play unique roles among African women, such as genetic factors, microbiomata, xenoestrogens, hair relaxers, and skin lighteners. With limited opportunities for effective treatment, a focus is needed on identifying etiologic factors that may be amenable to intervention. It will also be essential to understand reasons why women delay seeking care after the onset of symptoms and for there to be educational campaigns about the importance of early detection.
C1 [Brinton, Louise A.; Figueroa, Jonine D.; Wood, Shannon N.] NCI, NIH, Bethesda, MD 20892 USA.
[Awuah, Baffour; Ansong, Daniel] Komfo Anoyke Teaching Hosp, Kumasi, Ghana.
[Yarney, Joel; Nyarko, Kofi; Clegg-Lamptey, Joe Nat] Korle Bu Teaching Hosp, Accra, Ghana.
[Wiafe, Seth] Loma Linda Univ, Loma Linda, CA 92350 USA.
[Wiafe-Addai, Beatrice] Peace & Love Hosp, Kumasi, Ghana.
RP Brinton, LA (reprint author), NCI, NIH, 9609 Med Ctr Dr,Rm 7E-102,MSC 9774, Bethesda, MD 20892 USA.
EM brintonl@mail.nih.gov
RI Brinton, Louise/G-7486-2015;
OI Brinton, Louise/0000-0003-3853-8562; ANSONG, Daniel/0000-0003-1328-9117
FU National Cancer Institute, National Institutes of Health
FX This research was supported in part by funds from the intramural
research program of the National Cancer Institute, National Institutes
of Health. None of the authors has a financial relationship with the
organization that sponsored the research.
NR 84
TC 13
Z9 13
U1 2
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD APR
PY 2014
VL 144
IS 3
BP 467
EP 478
DI 10.1007/s10549-014-2868-z
PG 12
WC Oncology
SC Oncology
GA AD6IF
UT WOS:000333360700003
PM 24604092
ER
PT J
AU Banegas, MP
Tao, L
Altekruse, S
Anderson, WF
John, EM
Clarke, CA
Gomez, SL
AF Banegas, Matthew P.
Tao, Li
Altekruse, Sean
Anderson, William F.
John, Esther M.
Clarke, Christina A.
Gomez, Scarlett L.
TI Heterogeneity of breast cancer subtypes and survival among Hispanic
women with invasive breast cancer in California
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Hispanic; Latina; Socioeconomic status; Triple negative
ID ESTROGEN-RECEPTOR; DEATH CERTIFICATES; UNITED-STATES; WHITE WOMEN; RISK;
DISPARITIES; POPULATION; REGISTRY; BIRTHPLACE; ETHNICITY
AB There are limited data regarding breast cancer subtypes among Hispanic women. The current study assessed the distribution and prognosis of molecular subtypes defined by joint expression of the hormone receptors (HR; estrogen and progesterone) and human epidermal growth factor receptor 2 (HER2). Using California Cancer Registry data, we identified Hispanic women diagnosed with invasive breast cancer from 2005 to 2010. Breast cancer subtypes were defined as HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2- (triple negative). We estimated breast cancer subtype frequencies and used polytomous logistic regression, Kaplan-Meier survival plots and Cox regression to examine differences in relation to demographic and clinical characteristics. Among 16,380 Hispanic women with breast cancer, HR+/HER- subtype was the most common (63 %), followed by triple negative (16 %), HR+/HER2+ (14 %), and HR-/HER2+ (8 %). Women in lower SES neighborhoods had greater risk of triple negative and HR-/HER2+ subtypes relative to HR+/HER2- (p < 0.05). Hispanic women with triple negative and HR-/HER2+ tumors experienced poorer survival than those with HR+/HER- tumors. Breast cancer-specific mortality increased with decreasing SES, relative to the highest SES quintile, from HR = 1.38 for quintile 4 to HR = 1.76 for quintile 1 (lowest SES level). Our findings indicate that Hispanic women residing in low SES neighborhoods had significantly increased risk of developing and dying from HR- than HR+ breast cancers. Similar patterns of subtype frequency and prognosis among California Hispanic women and studies of other racial/ethnic groups underscore the need to better understand the impact of SES on risk factor exposures that increase the risk of breast cancer subtypes with poor prognosis.
C1 [Banegas, Matthew P.; Anderson, William F.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Tao, Li; John, Esther M.; Clarke, Christina A.; Gomez, Scarlett L.] Canc Prevent Inst Calif, Fremont, CA USA.
[Altekruse, Sean] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[John, Esther M.; Clarke, Christina A.; Gomez, Scarlett L.] Stanford Univ, Dept Hlth Res & Policy, Div Epidemiol, Sch Med, Stanford, CA 94305 USA.
RP Banegas, MP (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,MSC 9762, Bethesda, MD 20892 USA.
EM banegasmp@mail.nih.gov
FU California Department of Health Services as part of the statewide cancer
reporting program [103885]; National Cancer Institute's Surveillance,
Epidemiology, and End Results Program [HHSN261201000140C]; Centers for
Disease Control and Prevention's National Program of Cancer Registries
[1U58 DP000807-01]; [HHSN261201000035C]; [HHSN261201000034C]
FX MPB, SA, and WFA are employees of the National Cancer Institute at the
National Institutes of Health and no additional funding was provided
specifically for this work. The collection of cancer incidence data used
in this study was supported by the California Department of Health
Services as part of the statewide cancer reporting program mandated by
California Health and Safety Code Section 103885; the National Cancer
Institute's Surveillance, Epidemiology, and End Results Program under
contract HHSN261201000140C awarded to the Cancer Prevention Institute of
California, contract HHSN261201000035C awarded to the University of
Southern California, and contract HHSN261201000034C awarded to the
Public Health Institute; and the Centers for Disease Control and
Prevention's National Program of Cancer Registries, under agreement
#1U58 DP000807-01 awarded to the Public Health Institute. The ideas and
opinions expressed herein are those of the authors, and endorsement by
the State of California, the California Department of Health Services,
the National Cancer Institute, or the Centers for Disease Control and
Prevention or their contractors and subcontractors is not intended nor
should be inferred.
NR 42
TC 10
Z9 10
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD APR
PY 2014
VL 144
IS 3
BP 625
EP 634
DI 10.1007/s10549-014-2882-1
PG 10
WC Oncology
SC Oncology
GA AD6IF
UT WOS:000333360700018
PM 24658879
ER
PT J
AU Lash, TL
Thwin, SS
Yood, MU
Geiger, AM
Bosco, J
Quinn, VP
Field, TS
Pawloski, PA
Silliman, RA
AF Lash, Timothy L.
Thwin, Soe Soe
Yood, Marianne Ulcickas
Geiger, Ann M.
Bosco, Jaclyn
Quinn, Virginia P.
Field, Terry S.
Pawloski, Pamala A.
Silliman, Rebecca A.
TI Comprehensive evaluation of the incidence of late effects in 5-year
survivors of breast cancer
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast neoplasms, complications; Breast neoplasms, quality of life;
Breast neoplasms, late effects; Breast neoplasms, survivorship
ID OF-THE-LITERATURE; UNITED-STATES; OLDER WOMEN; RISK; RADIOTHERAPY;
THERAPY; HEALTH; SAFETY
AB Late effects of breast cancer affect the quality of survivorship. Using administrative data, we compared the occurrence of almost all ICD9 codes among older breast cancer survivors to that among a matched comparison cohort to generate new hypotheses. Breast cancer patients 65 years or older diagnosed 1990-1994 in 6 integrated care settings and who survived at least 5 years were matched with a cohort of women without a history of breast cancer on care setting, age, and calendar time. We collected data on the occurrence of incident ICD9 codes beginning 6 years after the breast cancer diagnosis date and continuing to year 15, and comparable data for the matched woman. We calculated hazard ratios (HRs) and 95 % confidence intervals associating breast cancer survivorship with incidence of each ICD9 code. We used semi-Bayes methods to address multiple comparisons. Older breast cancer survivors had about the same occurrence of diseases and conditions 6-15 years after breast cancer diagnosis as comparable women. The median of 564 adjusted HRs equaled 1.06, with interquartile range 0.92-1.3. The distribution of HRs pertaining to cancer-related ICD codes was shifted toward positive associations, and the distribution pertaining to cardiovascular-related ICD codes was shifted toward negative associations. In this hypothesis-scanning study, we observed little difference in the occurrence of non-breast cancer-related diseases and conditions among older, long-term breast cancer survivors, and comparable women without a history of breast cancer.
C1 [Lash, Timothy L.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Thwin, Soe Soe] VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA.
[Yood, Marianne Ulcickas] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Geiger, Ann M.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD USA.
[Bosco, Jaclyn] Real World & Late Phase Res Div Quintiles Inc, Cambridge, MA USA.
[Quinn, Virginia P.] Kaiser Permanente So Calif, Dept Res Evaluat, Pasadena, CA 91101 USA.
[Field, Terry S.] Meyers Primary Care Inst, Worcester, MA USA.
[Pawloski, Pamala A.] HealthPartners Inst Educ & Res, Minneapolis, MN USA.
[Silliman, Rebecca A.] Boston Univ, Sch Med, Boston Med Ctr, Sect Geriatr, Boston, MA 02118 USA.
RP Lash, TL (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, 1518 Clifton Rd, Atlanta, GA 30322 USA.
EM tlash@emory.edu
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services [R01CA093772-05A2]
FX Supported by Public Health Service grant R01CA093772-05A2 (Silliman, PI)
from the National Cancer Institute, National Institutes of Health,
Department of Health and Human Services. The authors wish to thank Dr.
Marianne Prout for her assistance with categorizing individual ICD9
codes into disease groups. This manuscript was prepared while Dr. Geiger
was employed at Wake Forest School of Medicine. The opinions expressed
in this article are the author's own and do not reflect the view of the
National Institutes of Health, the Department of Health and Human
Services, or the United States government.
NR 30
TC 1
Z9 1
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD APR
PY 2014
VL 144
IS 3
BP 643
EP 663
DI 10.1007/s10549-014-2885-y
PG 21
WC Oncology
SC Oncology
GA AD6IF
UT WOS:000333360700020
PM 24584822
ER
PT J
AU Flegel, WA
Natanson, C
Klein, HG
AF Flegel, Willy A.
Natanson, Charles
Klein, Harvey G.
TI Does prolonged storage of red blood cells cause harm?
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Review
DE red blood cells; storage; red cell units; therapy; adverse effects
ID PULMONARY ARTERIAL-HYPERTENSION; CRITICALLY-ILL PATIENTS; IN-HOSPITAL
MORTALITY; ACUTE LUNG INJURY; PILOT FEASIBILITY TRIAL; OLDER
STORED-BLOOD; TRANSFUSED BLOOD; ERYTHROCYTE STORAGE; FREE HEMOGLOBIN;
FRESH BLOOD
AB Red blood cells (RBCs) degrade progressively during the weeks of refrigerated storage. No universally accepted definition of 'fresh' or 'old' RBCs exists. While practices vary from country to country, preservative solutions permitting shelf life as long as 7weeks have been licenced. Transfusion of stored RBCs, particularly those at the end of the approved shelf life, has been implicated in adverse clinical outcomes. The results of observational analyses, animal models and studies in volunteers have proved provocative, controversial and contradictory. A recently completed randomized controlled trial (RCT) in premature infants exemplifies the difficulties with moderately sized clinical studies. Several other RCTs are in progress. The effect of RBC storage may well vary according to the clinical setting. Resolution of the importance of the storage lesion may require large pragmatic clinical trials. In the meantime, institutions involved in blood collection and transfusion should explore strategies that assure blood availability, while limiting the use of the oldest RBCs currently approved by regulation.
C1 [Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Flegel, WA (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C711 MSC 1184,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bill.flegel@nih.gov
FU NIH Clinical Center
FX We thank Arturo Pereira for sharing graphic data files used in Fig 1;
Stephen Thomas, Pieter van der Meer, Dirk de Korte, Thomas Schulzki,
Yoshihiko Tani, Qing Chen, Noorah Salman Almarry, Judith Chapman, Joan
Vidal Cid, Gregory A Denomme, Beat Frey, Catherine Hyland, Sanmukh
Joshi, Wolfgang R Mayr, Kenneth E Nollet, France Noizat-Pirenne, Mouna
Ouchari, Pairaya Rujirojindakul, Addisalem Taye-Makuria, Claudio Velati,
Christof Weinstock, and Silvano Wendel for communicating RBC shelf life
data. All authors performed literature research and designed the review
format; WAF analysed literature and data; WAF wrote and CN and HGK
edited the manuscript. This work was supported by the Intramural
Research Program of the NIH Clinical Center.
NR 129
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U1 3
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD APR
PY 2014
VL 165
IS 1
BP 3
EP 16
DI 10.1111/bjh.12747
PG 14
WC Hematology
SC Hematology
GA AC8BH
UT WOS:000332757500003
PM 24460532
ER
PT J
AU Khalil, MO
Morton, LM
Devesa, SS
Check, DP
Curtis, RE
Weisenburger, DD
Dores, GM
AF Khalil, Mohammad O.
Morton, Lindsay M.
Devesa, Susan S.
Check, David P.
Curtis, Rochelle E.
Weisenburger, Dennis D.
Dores, Graca M.
TI Incidence of marginal zone lymphoma in the United States, 2001-2009 with
a focus on primary anatomic site
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE anatomic site; marginal zone lymphoma; population-based study;
incidence; joinpoint analysis
ID NON-HODGKIN-LYMPHOMA; B-CELL LYMPHOMAS; HELICOBACTER-PYLORI INFECTION;
PRIMARY GASTRIC LYMPHOMA; MALT LYMPHOMAS; VARIABLE FREQUENCIES;
SJOGRENS-SYNDROME; CANCER INCIDENCE; TISSUE LYMPHOMA; RISK-FACTOR
AB The aetiology of marginal zone lymphoma (MZL) is purported to differ by anatomic site. While this is supported by clinical series of single MZL sites, no population-based study has comprehensively assessed incidence patterns across sites. To gain insight into disease aetiology, we assessed MZL incidence by site using data from 18 U.S. Surveillance, Epidemiology and End Results (SEER) Program population-based registries. We calculated age-adjusted incidence rates (IRs) by sex, race, and calendar year. During 2001-2009, 4,081 (IR=5 center dot 7/1,000,000 person-years) and 8,821 (IR=12 center dot 3) individuals were diagnosed with nodal MZL and extranodal MZL, respectively. The most common extranodal sites were stomach (IR=3 center dot 8), spleen (IR=1 center dot 6), eye/adnexa (IR=1 center dot 4), and lung, skin, and salivary glands (IRs=0 center dot 9-1 center dot 0). We observed distinct age-specific patterns by MZL site, with IRs increasing steeply at younger ages and less prominently after mid-life at several sites, except skin. Gender and racial/ethnic disparities were also apparent across sites. Between 2001-2005 and 2006-2009, MZL IRs decreased significantly for gastric (-15%) and soft tissue (-28%) sites, whereas IRs increased significantly for lung (18%), skin (43%), and kidney/renal pelvis (116%). In combination, our findings support the contention that MZL is characterized by aetiological heterogeneity across sites and susceptibility is probably influenced by intrinsic characteristics and environmental exposures.
C1 [Khalil, Mohammad O.; Dores, Graca M.] Dept Vet Affairs Med Ctr, Oklahoma City, OK 73104 USA.
[Khalil, Mohammad O.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Morton, Lindsay M.; Devesa, Susan S.; Check, David P.; Curtis, Rochelle E.; Dores, Graca M.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Weisenburger, Dennis D.] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
RP Khalil, MO (reprint author), Dept Vet Affairs Med Ctr, 921 NE 13th St, Oklahoma City, OK 73104 USA.
EM mohammad-khalil@ouhsc.edu
RI Morton, Lindsay/B-5234-2015; Check, David/J-7184-2015
OI Morton, Lindsay/0000-0001-9767-2310; Check, David/0000-0003-3887-0493
FU Department of Veterans Affairs Medical Center, Oklahoma City, OK;
National Cancer Institute, National Institutes of Health, Department of
Health and Human Services, Bethesda, MD
FX This work was supported by the Department of Veterans Affairs Medical
Center, Oklahoma City, OK and the Intramural Research Program of the
National Cancer Institute, National Institutes of Health, Department of
Health and Human Services, Bethesda, MD. The authors thank Martha S.
Linet, M.D., M.P.H. for important contributions to the design of this
research.
NR 55
TC 12
Z9 13
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD APR
PY 2014
VL 165
IS 1
BP 67
EP 77
DI 10.1111/bjh.12730
PG 11
WC Hematology
SC Hematology
GA AC8BH
UT WOS:000332757500008
PM 24417667
ER
PT J
AU Engelhardt, M
Wasch, R
Landgren, O
Kleber, M
AF Engelhardt, Monika
Waesch, Ralph
Landgren, Ola
Kleber, Martina
TI Multiple Myeloma and Second Malignancies
SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
LA English
DT Editorial Material
ID STEM-CELL TRANSPLANTATION; MYELODYSPLASTIC SYNDROME; ACUTE-LEUKEMIA;
LENALIDOMIDE; NEOPLASMS; CHEMOTHERAPY; MAINTENANCE; MELPHALAN; PATTERNS;
THERAPY
C1 [Engelhardt, Monika; Waesch, Ralph; Kleber, Martina] Univ Freiburg, Med Ctr, Dept Hematol & Oncol, Freiburg, Germany.
[Landgren, Ola] NCI, Multiple Myeloma Sect, Metab Branch, Bethesda, MD 20892 USA.
RP Engelhardt, M (reprint author), Univ Freiburg, Med Ctr, Dept Hematol & Oncol, Freiburg, Germany.
NR 21
TC 2
Z9 2
U1 0
U2 2
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 2152-2650
EI 2152-2669
J9 CL LYMPH MYELOM LEUK
JI Clin. Lymphoma Myeloma Leuk.
PD APR
PY 2014
VL 14
IS 2
BP 98
EP 101
DI 10.1016/j.dml.2013.11.008
PG 4
WC Oncology; Hematology
SC Oncology; Hematology
GA AD8IQ
UT WOS:000333510100002
PM 24445186
ER
PT J
AU Goey, AKL
Beijnen, JH
Schellens, JHM
AF Goey, A. K. L.
Beijnen, J. H.
Schellens, J. H. M.
TI Herb-Drug Interactions in Oncology
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Editorial Material
ID CANCER
C1 [Goey, A. K. L.] NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
[Beijnen, J. H.; Schellens, J. H. M.] Univ Utrecht, Dept Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
[Beijnen, J. H.] Netherlands Canc Inst, Slotervaart Hosp, Dept Pharm & Pharmacol, Amsterdam, Netherlands.
[Schellens, J. H. M.] Netherlands Canc Inst, Dept Clin Pharmacol, Amsterdam, Netherlands.
RP Schellens, JHM (reprint author), Univ Utrecht, Dept Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
EM j.schellens@nki.nl
NR 4
TC 8
Z9 8
U1 3
U2 19
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD APR
PY 2014
VL 95
IS 4
BP 354
EP 355
DI 10.1038/clpt.2014.18
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AD4ZP
UT WOS:000333261200002
PM 24646483
ER
PT J
AU Dotson, WD
Douglas, MP
Kolor, K
Stewart, AC
Bowen, MS
Gwinn, M
Wulf, A
Anders, HM
Chang, CQ
Clyne, M
Lam, TK
Schully, SD
Marrone, M
Feero, WG
Khoury, MJ
AF Dotson, W. D.
Douglas, M. P.
Kolor, K.
Stewart, A. C.
Bowen, M. S.
Gwinn, M.
Wulf, A.
Anders, H. M.
Chang, C. Q.
Clyne, M.
Lam, T. K.
Schully, S. D.
Marrone, M.
Feero, W. G.
Khoury, M. J.
TI Prioritizing Genomic Applications for Action by Level of Evidence: A
Horizon-Scanning Method
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
ID PHARMACOGENETICS IMPLEMENTATION CONSORTIUM; EGAPP-WORKING-GROUP;
THIOPURINE METHYLTRANSFERASE GENOTYPE; SEROTONIN REUPTAKE INHIBITORS;
IMPROVE HEALTH OUTCOMES; HLA-B GENOTYPE; CLINICAL PHARMACOGENETICS;
NONPSYCHOTIC DEPRESSION; CLOPIDOGREL THERAPY; INCIDENTAL FINDINGS
AB As evidence accumulates on the use of genomic tests and other health-related applications of genomic technologies, decision makers may increasingly seek support in identifying which applications have sufficiently robust evidence to suggest they might be considered for action. As an interim working process to provide such support, we developed a horizon-scanning method that assigns genomic applications to tiers defined by availability of synthesized evidence. We illustrate an application of the method to pharmacogenomics tests.
C1 [Dotson, W. D.; Douglas, M. P.; Kolor, K.; Stewart, A. C.; Bowen, M. S.; Gwinn, M.; Wulf, A.; Anders, H. M.; Khoury, M. J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA.
[Douglas, M. P.; Stewart, A. C.; Gwinn, M.; Anders, H. M.] McKing Consulting Corp, Atlanta, GA USA.
[Wulf, A.] Cadence Grp, Atlanta, GA USA.
[Chang, C. Q.; Clyne, M.; Lam, T. K.; Schully, S. D.; Khoury, M. J.] NCI, Epidemiol & Genom Res Program, Bethesda, MD 20892 USA.
[Clyne, M.] Kelly Serv, Troy, MI USA.
[Marrone, M.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Feero, W. G.] Maine Dartmouth Family Med Residency Program, Augusta, ME USA.
RP Dotson, WD (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA.
EM wdotson@cdc.gov
OI Dotson, William David/0000-0002-9606-6594
FU Intramural CDC HHS [CC999999]
NR 70
TC 8
Z9 8
U1 4
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD APR
PY 2014
VL 95
IS 4
BP 394
EP 402
DI 10.1038/clpt.2013.226
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AD4ZP
UT WOS:000333261200013
PM 24398597
ER
PT J
AU Haass-Koffler, CL
Leggio, L
Kenna, GA
AF Haass-Koffler, Carolina L.
Leggio, Lorenzo
Kenna, George A.
TI Pharmacological Approaches to Reducing Craving in Patients with Alcohol
Use Disorders
SO CNS DRUGS
LA English
DT Review
ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; COMPULSIVE
DRINKING SCALE; GAMMA-HYDROXYBUTYRIC ACID;
POSTTRAUMATIC-STRESS-DISORDER; POSITRON-EMISSION-TOMOGRAPHY;
COGNITIVE-BEHAVIORAL THERAPY; ELABORATED INTRUSION THEORY; CUE-INDUCED
ACTIVATION; OPIOID RECEPTOR GENE
AB Research on the concept of craving may lead to better understanding of the biobehavioural circuitries that contribute to the complexity of alcohol use disorders (AUDs). The experiences described as craving or desire to drink are often associated with physical responses such as increased salivation and heart rate, and alteration of stress hormones, as well as psychological responses such as anxiety and depression. Greater craving has been associated with an increased probability of alcohol relapse. Reversal of craving, which is understood as a symptom of protracted abstinence, offers the possibility of preventing relapses and treating alcoholism. Various medications have been studied to establish whether they are able to reduce craving; however, the results obtained from clinical studies have been inconsistent. Here, we review the interdisciplinary models developed to evaluate craving, then the different approaches used to assess and measure craving and, finally, the medications utilized and tested to lessen craving in patients suffering from AUDs.
C1 [Haass-Koffler, Carolina L.; Leggio, Lorenzo; Kenna, George A.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02812 USA.
[Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, LCTS, NIH, Bethesda, MD USA.
[Leggio, Lorenzo] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Kenna, George A.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA.
RP Kenna, GA (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Box G-S121-5, Providence, RI 02812 USA.
EM george_kenna@brown.edu
RI Leggio, Lorenzo/M-2972-2016
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA)
[5T32AA007459-28]; Division of Intramural Clinical and Biological
Research of the National Institute on Alcohol Abuse and Alcoholism
(NIAAA); Intramural Research Program of the National Institute on Drug
Abuse (NIDA); National Institute on Alcohol Abuse and Alcoholism
[R01-AA016079, R03AA020169, R21AA019709, R01 AA015753, R21AA019994,
R21AA021128]; CT San Remo [GET73]
FX Drs Haass-Koffler, Leggio and Kenna have no conflicts of interest that
are directly relevant to the content of this review. The authors would
like to express their thanks for the 5T32AA007459-28 training grant from
the National Institute on Alcohol Abuse and Alcoholism (NIAAA), which
supports the work of Dr Haass-Koffler. Dr Leggio's current work is
supported by the Division of Intramural Clinical and Biological Research
of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and
the Intramural Research Program of the National Institute on Drug Abuse
(NIDA). Dr Kenna has received funding from the National Institute on
Alcohol Abuse and Alcoholism for the following drugs: R01-AA016079
(ondansetron and sertraline), R03AA020169 (baclofen), R21AA019709
(ghrelin), R01 AA015753 (aripiprazole and topiramate), R21AA019994
(doxazosin) and R21AA021128 (metadoxine); and has received a consultancy
fee from CT San Remo (GET73).
NR 250
TC 7
Z9 8
U1 10
U2 18
PU ADIS INT LTD
PI AUCKLAND
PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW
ZEALAND
SN 1172-7047
EI 1179-1934
J9 CNS DRUGS
JI CNS Drugs
PD APR
PY 2014
VL 28
IS 4
BP 343
EP 360
DI 10.1007/s40263-014-0149-3
PG 18
WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AD6ES
UT WOS:000333348700006
PM 24573997
ER
PT J
AU Kimmel, AR
Sztalryd, C
AF Kimmel, Alan R.
Sztalryd, Carole
TI Perilipin 5, a lipid droplet protein adapted to mitochondrial energy
utilization
SO CURRENT OPINION IN LIPIDOLOGY
LA English
DT Review
DE lipolysis; fatty acid toxicity; beta-oxidation; steatosis; ATGL
ID ADIPOSE TRIGLYCERIDE LIPASE; ACTIVATED-RECEPTOR-ALPHA; DIET-INDUCED
OBESITY; SKELETAL-MUSCLE; FATTY-ACID; INSULIN SENSITIVITY; PPAR-ALPHA;
LIPOLYSIS; METABOLISM; MICE
AB Purpose of review
We summarize recent mechanistic and physiological studies related to the role of perilipin 5 (Plin5) in regulating lipid droplet accumulation and protection to fatty acids in tissues with high lipid oxidative metabolism.
Recent findings
Plin5 is a lipid droplet targeting protein that promotes association of lipid droplets with mitochondria and is most highly expressed in oxidative tissues, including cardiac and skeletal muscle. Recent in-vivo and in-vitro data indicate an important role for Plin5 in the regulation of cardiac lipid storage and function. Targeted overexpression of Plin5 in heart causes steatosis, mild mitochondria dysfunction, and hypertrophy in cardiac tissue, but without affecting cardiac function. In contrast, whole body ablation of Plin5 (Plin5 (-/-) mice) reduces cardiac lipid droplet formation, increases cardiac fatty acid oxidation, and promotes cardiac dysfunction; cardiac defects can be prevented with antioxidative therapy. These data suggest a cytoprotective role for Plin5 to promote lipid storage but to limit fatty acid toxicity, parameters critical for tissues with high lipid oxidative metabolism.
In-vivo and in-vitro data suggest that Plin5 is part of a cell-adaptive response to high lipid oxidative metabolism to protect lipid droplet storage against neutral lipases and, so, limit fatty acid accumulation. Although the specific mechanisms that underlie Plin5 lipid droplet storage protection in oxidative tissues remain to be fully elucidated, Plin5 provides a basis for the novel cytoprotective nature of lipid droplets.
C1 [Kimmel, Alan R.] NIDDK, Lab Cellular & Dev Biol 50 3351, NIH, Bethesda, MD 20892 USA.
[Sztalryd, Carole] Univ Maryland, Sch Med, Dept Med,Geriatr Res Educ & Clin Ctr, Baltimore Vet Affairs Healthcare Ctr,Div Endocrin, Baltimore, MD 21201 USA.
RP Sztalryd, C (reprint author), Univ Maryland, Sch Med, Dept Med,Geriatr Res Educ & Clin Ctr, Baltimore Vet Affairs Healthcare Ctr,Div Endocrin, Baltimore, MD 21201 USA.
EM ark1@helix.nih.gov; csztalry@grecc.umaryland.edu
FU National Institutes of Health, the National Institute of Diabetes and
Digestive and Kidney Diseases; NIH [1RO1 DK 075017]; American Heart
Association [11GRNT7600027]; Geriatric Research, Education and Clinical
Center, Baltimore Veterans Affairs Healthcare Center, the Clinical
Nutrition Research Unit of Maryland [DK072488]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, the National Institute of Diabetes and
Digestive and Kidney Diseases (A. R. K.), a grant from NIH 1RO1 DK
075017 (to C. S.), grant in aid 11GRNT7600027 from the American Heart
Association (to C. S.), and the Geriatric Research, Education and
Clinical Center, Baltimore Veterans Affairs Healthcare Center, the
Clinical Nutrition Research Unit of Maryland (DK072488).
NR 74
TC 18
Z9 18
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0957-9672
EI 1473-6535
J9 CURR OPIN LIPIDOL
JI Curr. Opin. Lipidology
PD APR
PY 2014
VL 25
IS 2
BP 110
EP 117
DI 10.1097/MOL.0000000000000057
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral
Vascular Disease
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Cardiovascular System & Cardiology
GA AD5AS
UT WOS:000333264300004
PM 24535284
ER
PT J
AU Resnik, DB
AF Resnik, David B.
TI ETHICAL ISSUES IN FIELD TRIALS OF GENETICALLY MODIFIED DISEASE-RESISTANT
MOSQUITOES
SO DEVELOPING WORLD BIOETHICS
LA English
DT Article
ID CLUSTER-RANDOMIZED-TRIALS; CLINICAL-RESEARCH; HEALTH
C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES102646-04]
NR 37
TC 6
Z9 6
U1 5
U2 34
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1471-8731
EI 1471-8847
J9 DEV WORLD BIOETH
JI Dev. World Bioeth.
PD APR
PY 2014
VL 14
IS 1
BP 37
EP 46
PG 10
WC Ethics; Medical Ethics
SC Social Sciences - Other Topics; Medical Ethics
GA AC7KJ
UT WOS:000332706900005
PM 23279283
ER
PT J
AU Morita, J
Nakamura, M
Kobayashi, Y
Deng, CX
Funato, N
Moriyama, K
AF Morita, Jumpei
Nakamura, Masataka
Kobayashi, Yukiho
Deng, Chu-Xia
Funato, Noriko
Moriyama, Keiji
TI Soluble Form of FGFR2 With S252W Partially Prevents Craniosynostosis of
the Apert Mouse Model
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE craniofacial; Apert syndrome; osteogenesis; pharmacodynamics
ID FACTOR RECEPTOR-2 FGFR2; GROWTH-FACTOR RECEPTORS; ACTIVATION; SKULL;
CHONDROGENESIS; ABNORMALITIES; MUTATIONS; BIOLOGY; LIGAND
AB Background: Apert syndrome (AS) is characterized by craniosynostosis, midfacial hypoplasia, and bony syndactyly. It is an autosomal dominantly inherited disease caused by point mutations (S252W or P253R) in fibroblast growth factor receptor (FGFR) 2. These mutations cause activation of FGFR2 depending on ligand binding. Recently, an AS mouse model, Fgfr2(+/S252W), showed phenotypes similar to those of AS patients. We previously reported that the soluble form of FGFR2(S252W) (sFGFR2IIIc(S252W)) efficiently inhibits enhanced osteoblastic differentiation caused by FGFR2 activation in AS in vitro, presumably because FGFs binding to FGFRs is interrupted. In this study, we developed Fgfr2(+/S252W) (Ap) mice expressing the sFGFR2IIIc(S252W) protein, and we investigated the effects of sFGFR2IIIc(S252W) on AS-like phenotypes. Results: In Ap mice, the coronal suture (CS) was fused prematurely at P1. In addition, the mice exhibited a widened interfrontal suture (IFS) with ectopic bone and thickened cartilage formation. In Fgfr2(+/S252W) sFGFR2IIIc(S252W) (Ap/Sol) mice, the CS was similar to that of wild-type mice. Ap/Sol mice did not show any ectopic bone or cartilage formation in the IFS, but showed a wider IFS than that of the wild-type mice. Conclusions: sFGFR2IIIc(S252W) may partially prevent craniosynostosis in the Apert mouse model by affecting the CS and IFS in vivo. Developmental Dynamics 243:560-567, 2014. (c) 2013 The Authors Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.
C1 [Morita, Jumpei; Kobayashi, Yukiho; Moriyama, Keiji] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Maxillofacial Reconstruct & Funct, Tokyo 1138549, Japan.
[Morita, Jumpei; Nakamura, Masataka; Funato, Noriko] Tokyo Med & Dent Univ, Human Gene Sci Ctr, Tokyo 1138549, Japan.
[Kobayashi, Yukiho; Moriyama, Keiji] Tokyo Med & Dent Univ, Hard Tissue Genome Res Ctr, Tokyo 1138549, Japan.
[Deng, Chu-Xia] Natl Inst Diabet Digest & Kidney Dis, Genet Dev & Dis Branch, US Natl Inst Hlth, Bethesda, MD USA.
RP Moriyama, K (reprint author), Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Maxillofacial Reconstruct & Funct, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138549, Japan.
EM k-moriyama.mort@tmd.ac.jp
RI deng, chuxia/N-6713-2016;
OI FUNATO, NORIKO/0000-0002-1320-3304
FU Japanese Society for the Promotion of Science [18209060, 23390471]
FX Grant sponsor: Grants-in-Aid for Scientific Research from the Japanese
Society for the Promotion of Science; Grant numbers: 18209060, 23390471.
NR 27
TC 6
Z9 7
U1 4
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1058-8388
EI 1097-0177
J9 DEV DYNAM
JI Dev. Dyn.
PD APR
PY 2014
VL 243
IS 4
BP 560
EP 567
DI 10.1002/dvdy.24099
PG 8
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA AD5ZW
UT WOS:000333333300005
PM 24259495
ER
PT J
AU Layfield, LJ
Ehya, H
Filie, AC
Hruban, RH
Jhala, N
Joseph, L
Vielh, P
Pitman, MB
AF Layfield, Lester J.
Ehya, Hormoz
Filie, Armando C.
Hruban, Ralph H.
Jhala, Nirag
Joseph, Loren
Vielh, Philippe
Pitman, Martha B.
TI Utilization of ancillary studies in the cytologic diagnosis of biliary
and pancreatic lesions: The papanicolaou society of cytopathology
guidelines for pancreatobiliary cytology
SO DIAGNOSTIC CYTOPATHOLOGY
LA English
DT Article
DE pancreas; biliary tract; molecular diagnosis; EUS; ancillary studies;
fine-needle aspiration
ID FINE-NEEDLE-ASPIRATION; IN-SITU HYBRIDIZATION; CYST FLUID ANALYSIS;
ACINAR CELL-CARCINOMA; TUMOR-SUPPRESSOR GENE; K-RAS MUTATIONS; PAPILLARY
MUCINOUS NEOPLASMS; ENDOBILIARY BRUSH CYTOLOGY; DIGITAL IMAGE-ANALYSIS;
BILE-DUCT STRICTURES
AB The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound-guided fine-needle aspiration, terminology and nomenclature of pancreatobiliary disease, ancillary testing, and post-biopsy management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings, and synthesis of selected online comments of the draft document. This document presents the results of these discussions regarding the use of ancillary testing in the cytologic diagnosis of biliary and pancreatic lesions. Currently, fluorescence in situ hybridization (FISH) appears to be the most clinically relevant ancillary technique for cytology of bile duct strictures. The addition of FISH analysis to routine cytologic evaluation appears to yield the highest sensitivity without loss in specificity. Loss of immunohistochemical staining for the protein product of the SMAD4 gene and positive staining for mesothelin support a diagnosis of ductal adenocarcinoma. Immunohistochemical markers for endocrine and exocrine differentiation are sufficient for a diagnosis of endocrine and acinar tumors. Nuclear staining for beta-catenin supports a diagnosis of solid-pseudopapilary neoplasm. Cyst fluid analysis for amylase and carcinoembryonic antigen aids in the preoperative classification of pancreatic cysts. Many gene mutations (KRAS, GNAS, VHL, RNF43, and CTNNB1) may be of aid in the diagnosis of cystic neoplasms. Other ancillary techniques do not appear to improve diagnostic sensitivity sufficiently to justify their increased costs. Diagn. Cytopathol. 2014;42:351-362. (c) 2014 Wiley Periodicals, Inc.
C1 [Layfield, Lester J.] Univ Missouri, Dept Pathol & Anatom Sci, Columbia, MO USA.
[Ehya, Hormoz] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA.
[Filie, Armando C.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Hruban, Ralph H.] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD USA.
[Jhala, Nirag] Hosp Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Joseph, Loren] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
[Vielh, Philippe] Inst Gustave Roussy, Villejuif, France.
[Pitman, Martha B.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA.
RP Layfield, LJ (reprint author), Dept Pathol & Anatom Sci, M263 Med Sci Bldg,One Hosp Dr, Columbia, MO 65212 USA.
EM layfieldl@health.missouri.edu
FU NCI NIH HHS [P30 CA006973]
NR 117
TC 26
Z9 26
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 8755-1039
EI 1097-0339
J9 DIAGN CYTOPATHOL
JI Diagn. Cytopathol.
PD APR
PY 2014
VL 42
IS 4
BP 351
EP 362
DI 10.1002/dc.23093
PG 12
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA AC8OI
UT WOS:000332792600012
PM 24639398
ER
PT J
AU Zuber, S
Wesley, R
Prodanov, T
Eisenhofer, G
Pacak, K
Kantorovich, V
AF Zuber, Samuel
Wesley, Robert
Prodanov, Tamara
Eisenhofer, Graeme
Pacak, Karel
Kantorovich, Vitaly
TI Clinical utility of chromogranin A in SDHx-related paragangliomas
SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
DE Chromogranin A; metanephrines; metastatic SDHB; paraganglioma;
pheochromocytoma; SDHD
ID PLASMA METHOXYTYRAMINE; NEUROENDOCRINE TUMORS; BIOCHEMICAL-DIAGNOSIS;
SERUM CREATININE; PHEOCHROMOCYTOMA; METANEPHRINES; SUBUNIT; MUTATIONS;
PREDICTION; PHENOTYPES
AB BackgroundMeasurement of plasma/urinary catecholamine metabolites - especially normetanephrine (NMN) - represents a gold standard in biochemical detection of succinate dehydrogenase subunit B (SDHB) and D (SDHD)-related pheochromocytomas (PHEO) and paragangliomas (PGL). This study was designed to assess diagnostic utility of chromogranin A (CgA) alone or in combination with NMN in patients with PHEO/PGL related to mutations in SDHB and SDHD.
Materials and methodsA retrospective study of SDHB and SDHD NIH patients' cohort, which included 41 patients with SDHB mutation-related PHEO/sPGL and 18 patients with either SDHD or SDHB mutation-related head and neck PGL (HNPGL) with both CgA and NMN measured at the time of diagnosis at NIH.
ResultsIn the SDHB group, CgA showed sensitivity of 73.2% and specificity of 95.9%, while for NMN they were 70.7% and 98.6%, respectively. Elevations in CgA and NMN were complementary in 92.7% of patients with proven tumors. Both tests performed well on receiver operating characteristic curve analysis. CgA levels were elevated in 76.9% of SDHB patients and in 80% of patients with metastatic disease and normal NMN levels. CgA values in patients with HNPGL were significantly lower than in patients with PHEO/sPGL.
ConclusionCgA is a valuable complementary biomarker in work-up of SDHB-related PHEO/sPGL. In combination with plasma NMN, CgA further enhances tumor detection by 22.0% with minimal loss in specificity. Although non-specific for PHEO/PGL, CgA may well supplement plasma NMN to facilitate diagnostic evaluation of SDHB-related PHEO/sPGL, especially where the measurement of plasma metanephrines could otherwise be delayed by decreased availability or cost restriction.
C1 [Zuber, Samuel; Prodanov, Tamara; Pacak, Karel] NIH, Program Reprod & Adult Endocrinol, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Wesley, Robert] NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Eisenhofer, Graeme] Univ Dresden, Inst Clin Chem & Lab Med, Dept Med 3, Dresden, Germany.
[Kantorovich, Vitaly] Univ Connecticut, Ctr Hlth, Div Endocrinol & Metab, Farmington, CT USA.
RP Kantorovich, V (reprint author), Univ CT Hlth Ctr, Div Endocrinol & Metab, Dept Med, 263 Farmington Ave,MC 1850, Farmington, CT 06030 USA.
EM kantorovich@uchc.edu
NR 34
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2972
EI 1365-2362
J9 EUR J CLIN INVEST
JI Eur. J. Clin. Invest.
PD APR
PY 2014
VL 44
IS 4
BP 365
EP 371
DI 10.1111/eci.12245
PG 7
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA AC5UK
UT WOS:000332586300004
PM 24467715
ER
PT J
AU Gonzalez, FJ
Moschetta, A
AF Gonzalez, Frank J.
Moschetta, Antonio
TI Potential Role of the Vitamin D Receptor in Control of Cholesterol
Levels
SO GASTROENTEROLOGY
LA English
DT Editorial Material
ID BILE-ACID SYNTHESIS; FARNESOID-X-RECEPTOR; NUCLEAR RECEPTOR;
1,25-DIHYDROXYVITAMIN D-3; LXR-ALPHA; MICE; 7-ALPHA-HYDROXYLASE;
HOMEOSTASIS; INTESTINE; IDENTIFICATION
C1 [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Moschetta, Antonio] Natl Res Canc Ctr, IRCCS Ist Oncol Giovanni Paolo 2, Bari, Italy.
RP Moschetta, A (reprint author), Natl Res Canc Ctr, IRCCS Ist Oncol Giovanni Paolo 2, Bari, Italy.
EM gonzalef@mail.nih.gov; moschetta@negrisud.it
OI Moschetta, Antonio/0000-0003-2123-6074
NR 31
TC 1
Z9 1
U1 1
U2 11
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD APR
PY 2014
VL 146
IS 4
BP 899
EP 902
DI 10.1053/j.gastro.2014.02.022
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AD4XH
UT WOS:000333254500013
PM 24566107
ER
PT J
AU Kazgan, N
Metukuri, MR
Purushotham, A
Lu, J
Rao, A
Lee, S
Pratt-Hyatt, M
Lickteig, A
Csanaky, IL
Zhao, YM
Dawson, PA
Li, XL
AF Kazgan, Nevzat
Metukuri, Mallikarjuna R.
Purushotham, Aparna
Lu, Jing
Rao, Anuradha
Lee, Sangkyu
Pratt-Hyatt, Matthew
Lickteig, Andrew
Csanaky, Ivan L.
Zhao, Yingming
Dawson, Paul A.
Li, Xiaoling
TI Intestine-Specific Deletion of SIRT1 in Mice Impairs DCoH2-HNF-1
alpha-FXR Signaling and Alters Systemic Bile Acid Homeostasis
SO GASTROENTEROLOGY
LA English
DT Article
DE Ileal Bile Acid Absorption; Bile Acid Synthesis; Liver Damage;
Cholestasis
ID FARNESOID-X-RECEPTOR; NUCLEAR RECEPTOR; PROTEIN DEACETYLASES; MAMMALIAN
SIRTUINS; METABOLIC SYNDROME; ENERGY-METABOLISM; FXR; CHOLESTEROL;
ACETYLATION; EXPRESSION
AB BACKGROUND & AIMS: Sirtuin 1 (SIRT1), the most conserved mammalian oxidized nicotinamide adenine dinucleotide-dependent protein deacetylase, is an important metabolic sensor in many tissues. However, little is known about its role in the small intestine, which absorbs and senses nutrients. We investigated the functions of intestinal SIRT1 in systemic bile acid and cholesterol metabolism in mice. METHODS: SIRT1 was specifically deleted from the intestines of mice using the flox-Villin-Cre system (SIRT1 iKO mice). Intestinal and hepatic tissues were collected, and bile acid absorption was analyzed using the everted gut sac experiment. Systemic bile acid metabolism was studied in SIRT1 iKO and flox control mice placed on standard diets, diets containing 0.5% cholic acid or 1.25% cholesterol, or lithogenic diets. RESULTS: SIRT1 iKO mice had reduced intestinal farnesoid X receptor (FXR) signaling via hepatocyte nuclear factor 1 alpha (HNF-1 alpha) compared with controls, which reduced expression of the bile acid transporter genes Asbt and Mcf2l (encodes Ost) and absorption of ileal bile acids. SIRT1 regulated HNF-1 alpha/FXR signaling partially through dimerization cofactor of HNF-1 alpha (Dcoh2) Dcoh2, which increases dimerization of HNF-1 alpha. SIRT1 was found to deacetylate Dcoh2, promoting its interaction with HNF-1 alpha and inducing DNA binding by HNF-1 alpha. Intestine-specific deletion of SIRT1 increased hepatic bile acid biosynthesis, reduced hepatic accumulation of bile acids, and protected animals from liver damage from a diet high in levels of bile acids. CONCLUSIONS: Intestinal SIRT1, a key nutrient sensor, is required for ileal bile acid absorption and systemic bile acid homeostasis in mice. We delineated the mechanism of metabolic regulation of HNF-1 alpha/FXR signaling. Reagents designed to inhibit intestinal SIRT1 might be developed to treat bile acid-related diseases such as cholestasis.
C1 [Kazgan, Nevzat; Metukuri, Mallikarjuna R.; Purushotham, Aparna; Lu, Jing; Li, Xiaoling] Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
[Rao, Anuradha; Dawson, Paul A.] Wake Forest Sch Med, Dept Internal Med, Gastroenterol Sect, Winston Salem, NC USA.
[Lee, Sangkyu; Zhao, Yingming] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA.
[Pratt-Hyatt, Matthew; Lickteig, Andrew; Csanaky, Ivan L.] Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66103 USA.
RP Li, XL (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
EM lix3@niehs.nih.gov
RI Csanaky, Ivan/N-5312-2015;
OI Csanaky, Ivan/0000-0001-7870-4129; Pratt-Hyatt,
Matthew/0000-0001-5532-9725
FU National Institute of Environmental Health Sciences, National Institutes
of Health (NIH) [Z01 ES102205]; National Institute of Diabetes and
Digestive and Kidney Diseases, NIH [DK047987]; National Cancer
Institute, NIH [CA126832]; NIH grant [R01ES009649]
FX Supported by grants from the Intramural Research Program of the National
Institute of Environmental Health Sciences, National Institutes of
Health (NIH) (Z01 ES102205 to X. L.); the National Institute of Diabetes
and Digestive and Kidney Diseases, NIH (DK047987 to P. A. D.); and the
National Cancer Institute, NIH (CA126832 to Y.Z.) and a NIH grant
(R01ES009649) to Curtis Klaassen, University of Kansas.
NR 37
TC 12
Z9 12
U1 0
U2 13
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD APR
PY 2014
VL 146
IS 4
BP 1006
EP 1016
DI 10.1053/j.gastro.2013.12.029
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AD4XH
UT WOS:000333254500030
PM 24389307
ER
PT J
AU Hovick, SR
Wilkinson, AV
Ashida, S
de Heer, HD
Koehly, LM
AF Hovick, Shelly R.
Wilkinson, Anna V.
Ashida, Sato
de Heer, Hendrik D.
Koehly, Laura M.
TI The impact of personalized risk feedback on Mexican Americans' perceived
risk for heart disease and diabetes
SO HEALTH EDUCATION RESEARCH
LA English
DT Article
ID FAMILY-HISTORY; HEALTH COMMUNICATION; BEHAVIORAL-THEORY; CANCER-RISK;
INFORMATION-SEEKING; PREVENTIVE MEDICINE; BREAST-CANCER; PERCEPTIONS;
BELIEFS; CONTEXT
AB Little is known about the effect of personalized risk information on risk perceptions over time, particularly among ethnically diverse subpopulations. The present study examines Mexican American's (MAs) risk perceptions for heart disease and diabetes at baseline and following receipt of risk feedback based on family health history. Participants comprising 162 households received a pedigree or personalized risk feedback, with or without behavioral risk reduction recommendations. Multiple logistic regression analyses were used to assess lifetime perceived risk (LPR) at baseline, 3 months and 10 months following the receipt of risk feedback. Having an elevated familial risk of heart disease or diabetes increased the odds of an elevated LPR for both diseases at baseline. At 3 months, compared with receipt of a pedigree only, MAs receiving elevated risk feedback for both diseases were more likely to have an elevated LPR for both diseases. At 10 months, participants receiving weak risk feedback for both diseases indicated an adjustment to a lower LPR for heart disease only. Results suggest that communicating risk for multiple diseases may be more effective than a single disease, with responses to increased risk feedback more immediate than to weak risk feedback.
C1 [Hovick, Shelly R.] Ohio State Univ, Sch Commun, Columbus, OH 43210 USA.
[Wilkinson, Anna V.] Univ Texas Austin, Sch Publ Hlth, Austin, TX 78712 USA.
[Ashida, Sato] Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA.
[de Heer, Hendrik D.] No Arizona Univ, Dept Phys Therapy & Athlet Training, Flagstaff, AZ 86011 USA.
[Koehly, Laura M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
RP Hovick, SR (reprint author), Ohio State Univ, Sch Commun, Columbus, OH 43210 USA.
EM hovick.1@osu.edu
RI Hovick, Shelly/J-6965-2013
FU NCI NIH HHS [CA126988]; NHGRI NIH HHS [Z01HG200335]; PHS HHS
[R25TCA57730]
NR 67
TC 5
Z9 5
U1 2
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1153
EI 1465-3648
J9 HEALTH EDUC RES
JI Health Educ. Res.
PD APR
PY 2014
VL 29
IS 2
BP 222
EP 234
DI 10.1093/her/cyt151
PG 13
WC Education & Educational Research; Public, Environmental & Occupational
Health
SC Education & Educational Research; Public, Environmental & Occupational
Health
GA AD5BK
UT WOS:000333266100004
PM 24463396
ER
PT J
AU Newman, JE
Garces, A
Mazariegos, M
Hambidge, KM
Manasyan, A
Tshefu, A
Lokangaka, A
Sami, N
Carlo, WA
Bose, CL
Pasha, O
Goco, N
Chomba, E
Goldenberg, RL
Wright, LL
Koso-Thomas, M
Krebs, NF
AF Newman, Jamie E.
Garces, Ana
Mazariegos, Manolo
Hambidge, K. Michael
Manasyan, Albert
Tshefu, Antoinette
Lokangaka, Adrien
Sami, Neelofar
Carlo, Waldemar A.
Bose, Carl L.
Pasha, Omrana
Goco, Norman
Chomba, Elwyn
Goldenberg, Robert L.
Wright, Linda L.
Koso-Thomas, Marion
Krebs, Nancy F.
TI Theory-driven process evaluation of a complementary feeding trial in
four countries
SO HEALTH EDUCATION RESEARCH
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; EDUCATIONAL INTERVENTION; CHILD
UNDERNUTRITION; HEALTH; IMPLEMENTATION; NUTRITION; TRUJILLO; INFANTS;
GROWTH; PERU
AB We conducted a theory-driven process evaluation of a cluster randomized controlled trial comparing two types of complementary feeding (meat versus fortified cereal) on infant growth in Guatemala, Pakistan, Zambia and the Democratic Republic of Congo. We examined process evaluation indicators for the entire study cohort (N = 1236) using chi-square tests to examine differences between treatment groups. We administered exit interviews to 219 caregivers and 45 intervention staff to explore why caregivers may or may not have performed suggested infant feeding behaviors. Multivariate regression analysis was used to determine the relationship between caregiver scores and infant linear growth velocity. As message recall increased, irrespective of treatment group, linear growth velocity increased when controlling for other factors (P < 0.05), emphasizing the importance of study messages. Our detailed process evaluation revealed few differences between treatment groups, giving us confidence that the main trial's lack of effect to reverse the progression of stunting cannot be explained by differences between groups or inconsistencies in protocol implementation. These findings add to an emerging body of literature suggesting limited impact on stunting of interventions initiated during the period of complementary feeding in impoverished environments. The early onset and steady progression support the provision of earlier and comprehensive interventions.
C1 [Newman, Jamie E.; Goco, Norman] RTI Int, Stat & Epidemiol, Res Triangle Pk, NC 27709 USA.
[Garces, Ana] Francisco Marroquin Univ, Multidisciplinary Hlth Inst, Guatemala City 01011, Guatemala.
[Mazariegos, Manolo] Inst Nutr Cent Amer & Panama, Guatemala City 01011, Guatemala.
[Hambidge, K. Michael; Krebs, Nancy F.] Univ Colorado Denver, Sect Nutr, Dept Pediat, Aurora, CO 80045 USA.
[Manasyan, Albert] Ctr Infect Dis Res Zambia, Lusaka 34681, Zambia.
[Tshefu, Antoinette; Lokangaka, Adrien] Kinshasa Sch Publ Hlth, Kinshasa, Congo.
[Sami, Neelofar] Aga Khan Univ, Coll Med, Dept Community Hlth Sci & Family Med, Karachi 74800, Pakistan.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Div Neonatol, Birmingham, AL 35233 USA.
[Bose, Carl L.] Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA.
[Chomba, Elwyn] Univ Teaching Hosp, Lusaka 34681, Zambia.
[Goldenberg, Robert L.] Columbia Univ, New York, NY 10027 USA.
[Wright, Linda L.; Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD 20852 USA.
RP Newman, JE (reprint author), RTI Int, Stat & Epidemiol, Res Triangle Pk, NC 27709 USA.
EM newman@rti.org
FU NICHD NIH HHS [U01 HD040657, HD040607, HD040657, HD043464, HD043475, U01
HD040607, U10 HD076465, U10 HD076474, U10 HD078437, U10 HD078438]; NIDDK
NIH HHS [9K24 DK083772]
NR 20
TC 2
Z9 2
U1 1
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1153
EI 1465-3648
J9 HEALTH EDUC RES
JI Health Educ. Res.
PD APR
PY 2014
VL 29
IS 2
BP 297
EP 305
DI 10.1093/her/cyt115
PG 9
WC Education & Educational Research; Public, Environmental & Occupational
Health
SC Education & Educational Research; Public, Environmental & Occupational
Health
GA AD5BK
UT WOS:000333266100010
PM 24399265
ER
PT J
AU McManus, DD
Lin, HH
Tanriverdi, K
Quercio, M
Yin, XY
Larson, MG
Elinor, PT
Levy, D
Freedman, JE
Benjamin, EJ
AF McManus, David D.
Lin, Honghuang
Tanriverdi, Kahraman
Quercio, Michael
Yin, Xiaoyan
Larson, Martin G.
Elinor, Patrick T.
Levy, Daniel
Freedman, Jane E.
Benjamin, Emelia J.
TI Relations between circulating microRNAs and atrial fibrillation: Data
from the Framingham Offspring Study
SO HEART RHYTHM
LA English
DT Article
DE Atrial fibrillation; Epidemiology; Circulation; microRNA; Risk factors
ID HEART-FAILURE; CARDIAC-HYPERTROPHY; RISK-FACTORS; FIBROSIS; CONTRIBUTES;
PREVALENCE; EXPRESSION; PREVENTION; PROTECTS; STROKE
AB BACKGROUND MicroRNA (miRNA) expression in atrial tissue has been implicated in pathologic susceptibility to atrial fibrillation (AF). Nevertheless, data on how circulating levels relate to AF are limited.
OBJECTIVE The purpose of this study was to test the hypothesis that circulating miRNAs are associated with AF.
METHODS Among 2445 Framingham Heart Study Offspring participants, we measured the expression of 385 circulating whole blood miRNAs by high-throughput quantitative reverse transcriptase polymerase chain reaction. We related miRNA Levels with prevalent and new-onset AF.
RESULTS Mean age of the cohort was 66.3 +/- 8.9 years, and 56% were women; 153 participants had clinically apparent AF at baseline, and 107 developed AF during median follow-up of 5.4 years. miRNA-328 (miR-328) expression was lower among participants with prevalent AF (8.76 cycle threshold) compared to individuals with no AF (7.75 cycle threshold, P < .001). The association between miR-328 and prevalent AF persisted after adjustment for age, sex, and technical covariates (odds ratio 1.21, P = 1.8 x 10(-4)) but was attenuated in analyses adjusting for clinical AF risk factors (odds ratio 1.14, P = .017). In contrast to the associations between miR-328 and prevalent AF, none of the circulating miRNAs were associated with incident AF.
CONCLUSION Circulating levels of miR-328, a miRNA known to promote atrial electrical remodeling by reducing L-type Ca2+ channel density, were associated with prevalent AF. Adjustment for risk factors that promote atrial remodeling, including hypertension, attenuated the association between miR-328 and AF, potentially implicating miR-328 as a potential mediator of atrial remodeling and AF vulnerability.
C1 [McManus, David D.; Lin, Honghuang; Tanriverdi, Kahraman; Yin, Xiaoyan; Larson, Martin G.; Levy, Daniel; Freedman, Jane E.] NHLBI, Framingham, MA USA.
[McManus, David D.; Lin, Honghuang; Tanriverdi, Kahraman; Yin, Xiaoyan; Larson, Martin G.; Levy, Daniel; Freedman, Jane E.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[McManus, David D.; Tanriverdi, Kahraman; Quercio, Michael; Freedman, Jane E.] Univ Massachusetts, Dept Med, Sch Med, Div Cardiol, Worcester, MA USA.
[McManus, David D.] Univ Massachusetts, Med Sch Worcester, Dept Quantitat Hlth Sci, Epidemiol Div, Worcester, MA 01605 USA.
[Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Computat Biomed Sect, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Elinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Elinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Levy, Daniel] NHLBI, Populat Res Branch, NIH, Bethesda, MD 20892 USA.
[Levy, Daniel] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Benjamin, Emelia J.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02215 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP McManus, DD (reprint author), Univ Massachusetts, Sch Med, Div Cardiol, 55 Lake Ave North, Worcester, MA 01655 USA.
EM mcmanusd@ummhc.org
OI Lin, Honghuang/0000-0003-3043-3942; Benjamin, Emelia/0000-0003-4076-2336
FU National Heart, Lung, and Blood Institute of the National Institutes of
Health [N01-HC 25195, 6R01-NS 17950, RFA-HL-12-008, R01 HL087201A, 1R01
HL64753, R01 HL076784, 1R01 AG028321]; Division of Intramural Research,
National Heart, Lung, and Blood Institute of the National Institutes of
Health, Bethesda, MD; National Institute of Health [1U01HL105268-01,
KL2RR031981]
FX This work was supported by N01-HC 25195, 6R01-NS 17950; RFA-HL-12-008 to
Dr. Freedman; R01 HL087201A to Drs. Freedman and Taariverdi;
RFA-HL-12-008 to Dr. Freedman; and 1R01 HL64753; R01 HL076784; 1R01
AG028321 to Dr. Benjamin from the National Heart, Lung, and Blood
Institute of the National Institutes of Health, and the Division of
Intramural Research, National Heart, Lung, and Blood Institute of the
National Institutes of Health, Bethesda, MD. Partial salary support is
additionally provided by National Institute of Health Grants
1U01HL105268-01 and KL2RR031981 to Dr. McManus.
NR 26
TC 21
Z9 24
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
EI 1556-3871
J9 HEART RHYTHM
JI Heart Rhythm
PD APR
PY 2014
VL 11
IS 4
BP 663
EP 669
DI 10.1016/j.hrthm.2014.01.018
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AD6WL
UT WOS:000333401800023
PM 24444445
ER
PT J
AU Walline, CC
Deffit, SN
Wang, N
Guindon, LM
Crotzer, VL
Liu, JY
Hollister, K
Eisenlohr, LC
Brutkiewicz, RR
Kaplan, MH
Blum, JS
AF Walline, Crystal C.
Deffit, Sarah N.
Wang, Nan
Guindon, Lynette M.
Crotzer, Victoria L.
Liu, Jianyun
Hollister, Kristin
Eisenlohr, Laurence C.
Brutkiewicz, Randy R.
Kaplan, Mark H.
Blum, Janice S.
TI Virus-encoded ectopic CD74 enhances poxvirus vaccine efficacy
SO IMMUNOLOGY
LA English
DT Article
DE CD74; class II; invariant chain; MHC; virus
ID MHC CLASS-II; CD1D1-MEDIATED ANTIGEN PRESENTATION; INVARIANT CHAIN
EXPRESSION; IMMUNE EVASION; HLA-DM; EPITOPE SELECTION; DENDRITIC CELLS;
MICE LACKING; HUMAN CD1D; T-CELLS
AB Vaccinia virus (VV) has been used globally as a vaccine to eradicate smallpox. Widespread use of this viral vaccine has been tempered in recent years because of its immuno-evasive properties, with restrictions prohibiting VV inoculation of individuals with immune deficiencies or atopic skin diseases. VV infection is known to perturb several pathways for immune recognition including MHC class II (MHCII) and CD1d-restricted antigen presentation. MHCII and CD1d molecules associate with a conserved intracellular chaperone, CD74, also known as invariant chain. Upon VV infection, cellular CD74 levels are significantly reduced in antigen-presenting cells, consistent with the observed destabilization of MHCII molecules. In the current study, the ability of sustained CD74 expression to overcome VV-induced suppression of antigen presentation was investigated. Viral inhibition of MHCII antigen presentation could be partially ameliorated by ectopic expression of CD74 or by infection of cells with a recombinant VV encoding murine CD74 (mCD74-VV). In contrast, virus-induced disruptions in CD1d-mediated antigen presentation persisted even with sustained CD74 expression. Mice immunized with the recombinant mCD74-VV displayed greater protection during VV challenge and more robust anti-VV antibody responses. Together, these observations suggest that recombinant VV vaccines encoding CD74 may be useful tools to improve CD4(+) T-cell responses to viral and tumour antigens.
C1 [Walline, Crystal C.; Deffit, Sarah N.; Wang, Nan; Guindon, Lynette M.; Crotzer, Victoria L.; Liu, Jianyun; Hollister, Kristin; Brutkiewicz, Randy R.; Kaplan, Mark H.; Blum, Janice S.] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA.
[Eisenlohr, Laurence C.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
[Kaplan, Mark H.] Herman B Wells Ctr Pediat Res, Dept Pediat, Indianapolis, IN USA.
RP Blum, JS (reprint author), Indiana Univ Sch Med, Dept Microbiol & Immunol, 635 Barnhill Dr, Indianapolis, IN 46202 USA.
EM jblum@iupui.edu
FU NIAID Center of the National Institutes of Health [T32DK007519,
T32HL007910, T32AI106519, PO1AI084853, R01AI46455, RO1AI079065];
Department of Defense [MRMC7065003]
FX Research reported in this publication was supported by the NIAID Center
of the National Institutes of Health under award numbers T32DK007519,
T32HL007910, T32AI106519, PO1AI084853, R01AI46455 and RO1AI079065, and
the Department of Defense under award number MRMC7065003.
NR 52
TC 2
Z9 5
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
EI 1365-2567
J9 IMMUNOLOGY
JI Immunology
PD APR
PY 2014
VL 141
IS 4
BP 531
EP 539
DI 10.1111/imm.12210
PG 9
WC Immunology
SC Immunology
GA AC4EQ
UT WOS:000332474100006
PM 24205828
ER
PT J
AU Melillo, AA
Foreman, O
Bosio, CM
Elkins, KL
AF Melillo, Amanda A.
Foreman, Oded
Bosio, Catharine M.
Elkins, Karen L.
TI T-bet Regulates Immunity to Francisella tularensis Live Vaccine Strain
Infection, Particularly in Lungs
SO INFECTION AND IMMUNITY
LA English
DT Article
ID IFN-GAMMA PRODUCTION; INTRACELLULAR GROWTH; TRANSCRIPTION FACTOR;
PULMONARY INFECTION; LINEAGE COMMITMENT; DISTINCT ROLES; CELL FUNCTION;
CUTTING EDGE; MICE; LVS
AB Upregulation of the transcription factor T-bet is correlated with the strength of protection against secondary challenge with the live vaccine strain (LVS) of Francisella tularensis. Thus, to determine if this mediator had direct consequences in immunity to LVS, we examined its role in infection. Despite substantial in vivo gamma interferon (IFN-gamma) levels, T-bet-knockout (KO) mice infected intradermally (i.d.) or intranasally (i.n.) with LVS succumbed to infection with doses 2 log units less than those required for their wild-type (WT) counterparts, and exhibited significantly increased bacterial burdens in the lung and spleen. Lungs of LVS-infected T-bet-KO mice contained fewer lymphocytes and more neutrophils and interleukin-17 than WT mice. LVS-vaccinated T-bet-KO mice survived lethal LVS intraperitoneal secondary challenge but not high doses of LVS i.n. challenge, independently of the route of vaccination. Immune T lymphocytes from the spleens of i.d. LVS-vaccinated WT or KO mice controlled intracellular bacterial replication in an in vitro coculture system, but cultures with T-bet-KO splenocyte supernatants contained less IFN-gamma and increased amounts of tumor necrosis factor alpha. In contrast, immune T-bet-KO lung lymphocytes were greatly impaired in controlling intramacrophage growth of LVS; this functional defect is the likely mechanism underpinning the lack of respiratory protection. Taken together, T-bet is important in host resistance to primary LVS infection and i.n. secondary challenge. Thus, T-bet represents a true, useful correlate for immunity to LVS.
C1 [Melillo, Amanda A.; Elkins, Karen L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Foreman, Oded] Genentech Inc, San Francisco, CA 94080 USA.
[Bosio, Catharine M.] NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT USA.
RP Elkins, KL (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
EM karen.elkins@fda.hhs.gov
RI Bosio, Catharine/D-7456-2015
FU National Institute of Allergy and Infectious Diseases
[Y1-AI-6153-01/224-06-1322]; Research Participation Program; Oak Ridge
Institute for Science and Education through an interagency agreement
between the U.S. Department of Energy and the U.S. Food and Drug
Administration
FX This work was supported in part by an interagency agreement with the
National Institute of Allergy and Infectious Diseases
(Y1-AI-6153-01/224-06-1322). This project was supported in part by an
appointment to the Research Participation Program at the Center for
Biologics Evaluation and Research administered by the Oak Ridge
Institute for Science and Education through an interagency agreement
between the U.S. Department of Energy and the U.S. Food and Drug
Administration.
NR 41
TC 6
Z9 6
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD APR
PY 2014
VL 82
IS 4
BP 1477
EP 1490
DI 10.1128/IAI.01545-13
PG 14
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AD4BX
UT WOS:000333192300015
PM 24421047
ER
PT J
AU Luckenbaugh, DA
Niciu, MJ
Ionescu, DF
Nolan, NM
Richards, EM
Brutsche, NE
Guevara, S
Zarate, CA
AF Luckenbaugh, David A.
Niciu, Mark J.
Ionescu, Dawn F.
Nolan, Neal M.
Richards, Erica M.
Brutsche, Nancy E.
Guevara, Sara
Zarate, Carlos A.
TI Do the dissociative side effects of ketamine mediate its antidepressant
effects?
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Blood pressure; Psychotomimetic; Predictors; Major depressive disorder;
Bipolar depression; Ketamine
ID STRIATAL DOPAMINE RELEASE; D-ASPARTATE ANTAGONIST;
POSITRON-EMISSION-TOMOGRAPHY; RESISTANT MAJOR DEPRESSION; ADD-ON TRIAL;
NMDA ANTAGONIST; RATING-SCALE; BIPOLAR DEPRESSION; RANDOMIZED-TRIAL;
SYMPTOMS
AB Background: The N-methyl-D-aspartate receptor antagonist ketamine has rapid antidepressant effects in major depression. Psychotomimetic symptoms, dissociation and hemodynamic changes are known side effects of ketamine, but it is unclear if these side effects relate to its antidepressant efficacy.
Methods: Data from 108 treatment-resistant inpatients meeting criteria for major depressive disorder and bipolar disorder who received a single subanesthetic ketamine infusion were analyzed. Pearson correlations were performed to examine potential associations between rapid changes in dissociation and psychotomimesis with the Clinician-Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale (BPRS), respectively, manic symptoms with Young Mania Rating Scale (YMRS), and vital sign changes, with percent change in the 17-item Hamilton Depression Rating scale (HDRS) at 40 and 230 min and Days 1 and 7.
Results: Pearson correlations showed significant association between increased CADSS score at 40 min and percent improvement with ketamine in HDRS at 230 min (r=-0.35, p=0.007) and Day 7 (r=-0.41, p=0.01). Changes in YMRS or BPRS Positive Symptom score at 40 min were not significantly correlated with percent HDRS improvement at any time point with ketamine. Changes in systolic blood pressure, diastolic blood pressure, and pulse were also not significantly related to HDRS change.
Limitations: Secondary data analysis, combined diagnostic groups, potential unblinding.
Conclusions: Among the examined mediators of ketaminers antidepressant response, only dissociative side effects predicted a more robust and sustained antidepressant. Prospective, mechanistic investigations are critically needed to understand why intra-infusion dissociation correlates with a more robust antidepressant efficacy of ketamine. Published by Elsevier B.V.
C1 [Luckenbaugh, David A.; Niciu, Mark J.; Ionescu, Dawn F.; Nolan, Neal M.; Richards, Erica M.; Brutsche, Nancy E.; Guevara, Sara; Zarate, Carlos A.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Zarate, CA (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bldg 10,CRC Room 7-534210 Ctr Dr, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
RI Niciu, Mark/J-1766-2014; Ionescu, Dawn/K-5675-2015
OI Niciu, Mark/0000-0002-5612-3021;
FU Intramural Research Program at the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH); NARSAD Independent
Investigator Award; Brain & Behavior Mood Disorders Research Award
FX Funding for this work was supported by the Intramural Research Program
at the National Institute of Mental Health, National Institutes of
Health (IRP-NIMH-NIH), by a NARSAD Independent Investigator Award to
CAZ, and by the Brain & Behavior Mood Disorders Research Award to CAZ.
NR 35
TC 42
Z9 42
U1 2
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
EI 1573-2517
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD APR
PY 2014
VL 159
BP 56
EP 61
DI 10.1016/j.jad.2014.02.017
PG 6
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AD6VD
UT WOS:000333398400009
PM 24679390
ER
PT J
AU Revell, AD
Wang, DC
Wood, R
Morrow, C
Tempelman, H
Hamers, R
Alvarez-Uria, G
Streinu-Cercel, A
Ene, L
Wensing, A
Reiss, P
van Sighem, AI
Nelson, M
Emery, S
Montaner, JSG
Lane, HC
Larder, BA
AF Revell, Andrew D.
Wang, Dechao
Wood, Robin
Morrow, Carl
Tempelman, Hugo
Hamers, Raph
Alvarez-Uria, Gerardo
Streinu-Cercel, Adrian
Ene, Luminita
Wensing, Annemarie
Reiss, Peter
van Sighem, Ard I.
Nelson, Mark
Emery, Sean
Montaner, Julio S. G.
Lane, H. Clifford
Larder, Brendan A.
CA RDI Study Grp
TI An update to the HIV-TRePS system: the development of new computational
models that do not require a genotype to predict HIV treatment outcomes
SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
LA English
DT Article
DE antiretroviral therapy; resource-limited settings; genotyping
ID RESOURCE-LIMITED SETTINGS; ANTIRETROVIRAL THERAPY
AB The optimal individualized selection of antiretroviral drugs in resource-limited settings is challenging because of the limited availability of drugs and genotyping. Here we describe the development of the latest computational models to predict the response to combination antiretroviral therapy without a genotype, for potential use in such settings.
Random forest models were trained to predict the probability of a virological response to therapy (50 copies HIV RNA/mL) following virological failure using the following data from 22567 treatment-change episodes including 1090 from southern Africa: baseline viral load and CD4 cell count, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. The models were assessed during cross-validation and with an independent global test set of 1000 cases including 100 from southern Africa. The models accuracy [area under the receiver-operating characteristic curve (AUC)] was evaluated and compared with genotyping using rules-based interpretation systems for those cases with genotypes available.
The models achieved AUCs of 0.790.84 (mean 0.82) during cross-validation, 0.80 with the global test set and 0.78 with the southern African subset. The AUCs were significantly lower (0.560.57) for genotyping.
The models predicted virological response to HIV therapy without a genotype as accurately as previous models that included a genotype. They were accurate for cases from southern Africa and significantly more accurate than genotyping. These models will be accessible via the online treatment support tool HIV-TRePS and have the potential to help optimize antiretroviral therapy in resource-limited settings where genotyping is not generally available.
C1 [Revell, Andrew D.; Wang, Dechao; Larder, Brendan A.] HIV Resistance Response Database Initiat RDI, London, England.
[Wood, Robin; Morrow, Carl] Univ Cape Town, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa.
[Tempelman, Hugo] Ndlovu Care Grp, Elandsdoorn, South Africa.
[Hamers, Raph; Reiss, Peter] Univ Amsterdam, Acad Med Ctr, Amsterdam Inst Global Hlth & Dev, Dept Global Hlth, NL-1105 AZ Amsterdam, Netherlands.
[Alvarez-Uria, Gerardo] Rural Dev Trust RDT Hosp, Bathalapalli, AP, India.
[Streinu-Cercel, Adrian] Natl Inst Infect Dis Prof Dr Matei Bals, Bucharest, Romania.
[Ene, Luminita] Dr Victor Babes Hosp Infect & Trop Dis, Bucharest, Romania.
[Wensing, Annemarie] Univ Med Ctr, Dept Virol, Utrecht, Netherlands.
[Reiss, Peter; van Sighem, Ard I.] Stichting HIV Monitoring, Amsterdam, Netherlands.
[Nelson, Mark] Chelsea & Westminster Hosp, London, England.
[Emery, Sean] Univ New S Wales, Kirby Inst, Sydney, NSW, Australia.
[Montaner, Julio S. G.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
[Lane, H. Clifford] NIAID, Bethesda, MD 20892 USA.
RP Revell, AD (reprint author), HIV Resistance Response Database Initiat RDI, London, England.
EM andrewrevell@hivrdi.org
RI Marconi, Vincent/N-3210-2014; Emery, Sean/H-4920-2013;
OI Marconi, Vincent/0000-0001-8409-4689; Emery, Sean/0000-0001-6072-8309;
Zazzi, Maurizio/0000-0002-0344-6281; Streinu-Cercel,
Adrian/0000-0001-6382-5067; Agan, Brian/0000-0002-5114-1669
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Diseases
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. This research was supported by the
National Institute of Allergy and Infectious Diseases.
NR 13
TC 6
Z9 6
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-7453
EI 1460-2091
J9 J ANTIMICROB CHEMOTH
JI J. Antimicrob. Chemother.
PD APR
PY 2014
VL 69
IS 4
BP 1104
EP 1110
DI 10.1093/jac/dkt447
PG 7
WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
GA AD5EQ
UT WOS:000333275000035
PM 24275116
ER
PT J
AU Schafer, AL
Mumm, S
El-Sayed, I
McAlister, WH
Horvai, AE
Tom, AM
Hsiao, EC
Schaefer, FV
Collins, MT
Anderson, MS
Whyte, MP
Shoback, DM
AF Schafer, Anne L.
Mumm, Steven
El-Sayed, Ivan
McAlister, William H.
Horvai, Andrew E.
Tom, Andrea M.
Hsiao, Edward C.
Schaefer, Frederick V.
Collins, Michael T.
Anderson, Mark S.
Whyte, Michael P.
Shoback, Dolores M.
TI Panostotic Expansile Bone Disease With Massive Jaw Tumor Formation and a
Novel Mutation in the Signal Peptide of RANK
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
ID JUVENILE PAGETS-DISEASE; NF-KAPPA-B; RECEPTOR ACTIVATOR; TNFRSF11A GENE;
OSTEOLYSIS; OSTEOCLAST; HYPERPHOSPHATASIA; DUPLICATION; RANK/RANKL;
MYELOMA
C1 [Schafer, Anne L.; Hsiao, Edward C.; Anderson, Mark S.; Shoback, Dolores M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Schafer, Anne L.; Shoback, Dolores M.] Dept Vet Affairs Med Ctr, Endocrine Res Unit, San Francisco, CA USA.
[Mumm, Steven; Whyte, Michael P.] Shriners Hosp Children, Ctr Metab Bone Dis & Mol Res, St Louis, MO USA.
[Mumm, Steven; Whyte, Michael P.] Washington Univ, Sch Med, Barnes Jewish Hosp, Div Bone & Mineral Dis, St Louis, MO USA.
[El-Sayed, Ivan] Univ Calif San Francisco, Dept Otolaryngol, San Francisco, CA 94143 USA.
[McAlister, William H.] Washington Univ, Sch Med, St Louis Childrens Hosp, Mallinckrodt Inst Radiol, St Louis, MO USA.
[Horvai, Andrew E.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA.
[Tom, Andrea M.] Santa Clara Valley Med Ctr, Dept Med, San Jose, CA 95128 USA.
[Schaefer, Frederick V.] Ctr Genet Testing St Francis, Tulsa, OK USA.
[Collins, Michael T.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Schafer, AL (reprint author), 4150 Clement St,111N, San Francisco, CA 94121 USA.
EM anne.schafer@ucsf.edu
FU Department of Veterans Affairs [5 IK2 CX000549-03]; Shriners Hospitals
for Children; National Institutes of Health [DK067145, K08 AR056299-02,
R01 AR055588]; National Institute of Dental and Craniofacial Research
FX Support was provided by the Department of Veterans Affairs under grant 5
IK2 CX000549-03 (to ALS), by Shriners Hospitals for Children, and by the
National Institutes of Health under grants DK067145 (to SM and MPW), K08
AR056299-02 (to ECH), R01 AR055588 (to DMS), and the Division of
Intramural Research funding from the National Institute of Dental and
Craniofacial Research (to MTC).
NR 28
TC 3
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD APR
PY 2014
VL 29
IS 4
BP 911
EP 921
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AD1PE
UT WOS:000333005100014
PM 24014458
ER
PT J
AU Matter, MS
Decaens, T
Andersen, JB
Thorgeirsson, SS
AF Matter, Matthias S.
Decaens, Thomas
Andersen, Jesper B.
Thorgeirsson, Snorri S.
TI Targeting the mTOR pathway in hepatocellular carcinoma: Current state
and future trends
SO JOURNAL OF HEPATOLOGY
LA English
DT Review
DE mTOR; HCC; Rapamycin; Rapalogs; Second generation mTOR inhibitors
ID ADVANCED SOLID TUMORS; CELL-CYCLE ARREST; PHASE-I TRIAL; MAMMALIAN
TARGET; LIVER-CANCER; THERAPEUTIC TARGETS; GENE-EXPRESSION; DEPENDENT
MANNER; ORTHOTOPIC MODEL; CLINICAL-TRIAL
AB Mechanistic target of rapamycin (mTOR) regulates cell growth, metabolism and aging in response to nutrients, cellular energy stage and growth factors. mTOR is frequently up-regulated in cancer including hepatocellular carcinoma (HCC) and is associated with bad prognosis, poorly differentiated tumors, and earlier recurrence. Blocking mTOR with rapamycin and first generation mTOR inhibitors, called rapalogs, has shown promising reduction of HCC tumor growth in preclinical models. Currently, rapamycin/rapalogs are used in several clinical trials for the treatment of advanced HCC, and as adjuvant therapy in HCC patients after liver transplantation and TACE. A second generation of mTOR pathway inhibitors has been developed recently and is being tested in various clinical trials of solid cancers, and has been used in preclinical HCC models. The results of series of clinical trials using mTOR inhibitors in HCC treatment will emerge in the near future. Published by Elsevier B. V. on behalf of the European Association for the Study of the Liver.
C1 [Matter, Matthias S.; Decaens, Thomas; Andersen, Jesper B.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA.
RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 4146A, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
OI Andersen , Jesper B/0000-0003-1760-5244
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research; "Schweizerische Stifung fur Medizinisch-
Biologische Stipendien" [PASMP-3_140071]; "Fondation Monahan"; "Prix
Amgen pour la Recherche et l'Innovation en oncologie digestive"
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. M. S. M. is
supported by "Schweizerische Stifung fur Medizinisch- Biologische
Stipendien" (PASMP-3_140071). T. D. is supported by the "Fondation
Monahan" and "Prix Amgen pour la Recherche et l'Innovation en oncologie
digestive 2011".
NR 102
TC 43
Z9 48
U1 0
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 4
BP 855
EP 865
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AD2ZR
UT WOS:000333106600024
PM 24308993
ER
PT J
AU Rosati, SF
Parkhurst, MR
Hong, Y
Zheng, ZL
Feldman, SA
Rao, M
Abate-Daga, D
Beard, RE
Xu, H
Black, MA
Robbins, PF
Schrump, DA
Rosenberg, SA
Morgan, RA
AF Rosati, Shannon F.
Parkhurst, Maria R.
Hong, Young
Zheng, Zhili
Feldman, Steven A.
Rao, Mahadev
Abate-Daga, Daniel
Beard, Rachel E.
Xu, Hui
Black, Mary A.
Robbins, Paul F.
Schrump, David A.
Rosenberg, Steven A.
Morgan, Richard A.
TI A Novel Murine T-Cell Receptor Targeting NY-ESO-1
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE TCR; synovial cell sarcoma; epigenetics; cancer testis antigens;
immunotherapy; NY-ESO-1
ID TCR GENE-THERAPY; CANCER-CELLS; ANTIGEN-EXPRESSION; IMMUNOTHERAPY;
LYMPHOCYTES; NEUROBLASTOMA; REGRESSION; CARCINOMA; PEPTIDE; MARKER
AB Cancer testis antigens, such as NY-ESO-1, are expressed in a variety of prevalent tumors and represent potential targets for T-cell receptor (TCR) gene therapy. DNA encoding a murine anti-NY-ESO-1 TCR gene (mTCR) was isolated from immunized HLA-A*0201 transgenic mice and inserted into a gamma-retroviral vector. Two mTCR vectors were produced and used to transduce human PBL. Transduced cells were cocultured with tumor target cell lines and T2 cells pulsed with the NY-ESO-1 peptide, and assayed for cytokine release and cell lysis activity. The most active TCR construct was selected for production of a master cell bank for clinical use. mTCR-transduced PBL maintained TCR expression in short-term and long-term culture, ranging from 50% to 90% efficiency 7-11 days after stimulation and 46%-82% 10-20 days after restimulation. High levels of interferon-gamma secretion were observed (1000-12000 pg/mL), in tumor coculture assays and recognition of peptide-pulsed cells was observed at 0.1 ng/mL, suggesting that the new mTCR had high avidity for antigen recognition. mTCR-transduced T cells also specifically lysed human tumor targets. In all assays, the mTCR was equivalent or better than the comparable human TCR. As the functional activity of TCR-transduced cells may be affected by the formation of mixed dimers, mTCRs, which are less likely to form mixed dimers with endogenous hTCRs, may be more effective in vivo. This new mTCR targeted to NY-ESO-1 represents a novel potential therapeutic option for adoptive cell-transfer therapy for a variety of malignancies.
C1 [Rosati, Shannon F.; Parkhurst, Maria R.; Hong, Young; Zheng, Zhili; Feldman, Steven A.; Rao, Mahadev; Abate-Daga, Daniel; Beard, Rachel E.; Xu, Hui; Black, Mary A.; Robbins, Paul F.; Schrump, David A.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Morgan, RA (reprint author), Bluebird Bio, 150 Second St, Cambridge, MA 02141 USA.
EM rmorgan@bluebirdbio.com
FU intramural program of the Center for Cancer Research, National Cancer
Institute, National Institutes of Health, Bethesda, MD
FX This work was supported by the intramural program of the Center for
Cancer Research, National Cancer Institute, National Institutes of
Health, Bethesda, MD.
NR 33
TC 6
Z9 6
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
EI 1537-4513
J9 J IMMUNOTHER
JI J. Immunother.
PD APR
PY 2014
VL 37
IS 3
BP 135
EP 146
DI 10.1097/CJI.0000000000000019
PG 12
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA AD3PN
UT WOS:000333158300001
PM 24598449
ER
PT J
AU Lucotte, B
Balaban, RS
AF Lucotte, B.
Balaban, R. S.
TI Motion compensation for in vivo subcellular optical microscopy
SO JOURNAL OF MICROSCOPY
LA English
DT Review
DE cell biology; real time image processing; active tissue tracking; rigid
body motion; physiological gating; deformation
ID RESOLUTION; EXCITATION; MUSCLE
AB Lay Description
High resolution optical microscopy of cellular events, in vivo is rapidly becoming an important tool in the evaluation of cellular function both in health and disease. The realization that the in vivo environment is critical for interpreting the true function and interactions of cells in the body has driven this interest as well as the development of methodologies to overcome the barriers to high resolution imaging in this dynamic environment. In this brief review we focus on tissue motion as one of the major challenges in high resolution imaging, in vivo. Biological tissues are normally highly dynamic due to blood flow, respiration and physiological functions. This normal tissue motion impacts spatial resolution, signal to noise and importantly the ability to follow sub-cellular events over time. Recent improvements in image acquisition speed is a major advantage to either freeze the motion by sampling faster than the motion can occur or used to actively track the motion in the tissue. We are quickly reaching the point where it is the amount of signal we can get from a sub-cellular volume that is limiting the speed of acquisition rather than the actual speed of the microscope scan rate. In addition to the speed of the tissue motion, the overall displacement can occur over millimeters requiring the active imaging field to move with the tissue to keep a region of interest within the field of view. "Active tracking" requires rapid imaging to follow the motion as well as real time computational capabilities to calculate the displacement and finally a precision stage to move the preparation appropriately. These numerous approaches to compensating tissue motion in high resolution imaging are expanding the field of intra-vital microscopy to explore the biology of the cell in a living body rather than a petri dish.
Summary
In this review, we focus on the impact of tissue motion on attempting to conduct subcellular resolution optical microscopy, in vivo. Our position is that tissue motion is one of the major barriers in conducting these studies along with light induced damage, optical probe loading as well as absorbing and scattering effects on the excitation point spread function and collection of emitted light. Recent developments in the speed of image acquisition have reached the limit, in most cases, where the signal from a subcellular voxel limits the speed and not the scanning rate of the microscope. Different schemes for compensating for tissue displacements due to rigid body and deformation are presented from tissue restriction, gating, adaptive gating and active tissue tracking. We argue that methods that minimally impact the natural physiological motion of the tissue are desirable because the major reason to perform in vivo studies is to evaluate normal physiological functions. Towards this goal, active tracking using the optical imaging data itself to monitor tissue displacement and either prospectively or retrospectively correct for the motion without affecting physiological processes is desirable. Critical for this development was the implementation of near real time image processing in conjunction with the control of the microscope imaging parameters.
Clearly, the continuing development of methods of motion compensation as well as significant technological solutions to the other barriers to tissue subcellular optical imaging in vivo, including optical aberrations and overall signal-to-noise ratio, will make major contributions to the understanding of cell biology within the body.
C1 [Lucotte, B.; Balaban, R. S.] NHLBI, Cardiac Energet Lab, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
EM rsb@nih.gov
FU Intramural NIH HHS [ZIA HL004610-07]
NR 23
TC 2
Z9 2
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-2720
EI 1365-2818
J9 J MICROSC-OXFORD
JI J. Microsc..
PD APR
PY 2014
VL 254
IS 1
BP 9
EP 12
DI 10.1111/jmi.12116
PG 4
WC Microscopy
SC Microscopy
GA AC6CI
UT WOS:000332608200002
PM 24673143
ER
PT J
AU Lodish, MB
Gourgari, E
Sinaii, N
Hill, S
Libuit, L
Mastroyannis, S
Keil, M
Batista, DL
Stratakis, CA
AF Lodish, Maya B.
Gourgari, Evgenia
Sinaii, Ninet
Hill, Suvimol
Libuit, Laura
Mastroyannis, Spyridon
Keil, Margaret
Batista, Dalia L.
Stratakis, Constantine A.
TI Skeletal Maturation in Children with Cushing Syndrome Is Not
Consistently Delayed: The Role of Corticotropin, Obesity, and Steroid
Hormones, and the Effect of Surgical Cure
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID LINEAR GROWTH; FINAL HEIGHT; DISEASE; DIAGNOSIS; THERAPY; AGE;
ADOLESCENTS; SUPPRESSION; CHILDHOOD; PUBERTY
AB Objective To assess skeletal maturity by measuring bone age (BA) in children with Cushing syndrome (CS) before and 1-year after transsphenoidal surgery or adrenalectomy, and to correlate BA with hormone levels and other measurements.
Study design This case series conducted at the National Institutes of Health Clinical Center included 93 children with Cushing disease (CD) (43 females; mean age, 12.3 +/- 2.9 years) and 31 children with adrenocorticotropic hormone-independent CS (AICS) (22 females, mean age 10.3 +/- 4.5 years). BA was obtained before surgery and at follow-up. Outcome measures were comparison of BA in CD vs AICS and analysis of the effects of hypercortisolism, insulin excess, body mass index, and androgen excess on BA.
Results Twenty-six of the 124 children (21.0%) had advanced BA, compared with the expected general population prevalence of 2.5% (P < .0001). Only 4 of 124 (3.2%) had delayed BA. The majority of children (76%) had normal BA. The average BA z-score was similar in the children with CD and those with AICS (0.6 +/- 1.4 vs 0.5 +/- 1.8; P = .8865). Body mass index SDS and normalized values of dehydroepiandrosterone, dehydroepiandrosterone sulfate, androsteonedione, estradiol, and testosterone were all significantly higher in the children with advanced BA vs those with normal or delayed BA. Fifty-nine children who remained in remission from CD had follow-up BA 1.2 +/- 0.3 years after transsphenoidal surgery, demonstrating decreased BA z-score (1.0 +/- 1.6 vs 0.3 +/- 1.4; P < .0001).
Conclusion Contrary to common belief, endogenous CS in children appears to be associated with normal or even advanced skeletal maturation. When present, BA advancement in CS is related to obesity, insulin resistance, and elevated adrenal androgen levels and aromatization. This finding may have significant implications for treatment decisions and final height predictions in these children.
C1 [Lodish, Maya B.; Gourgari, Evgenia; Libuit, Laura; Mastroyannis, Spyridon; Keil, Margaret; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
[Sinaii, Ninet] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA.
[Hill, Suvimol] NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Batista, Dalia L.] Brown Univ, Dept Pediat, Warren Alpert Med Sch, Providence, RI 02912 USA.
RP Lodish, MB (reprint author), NICHD, NIH, Bldg 10 CRC,Rm 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA.
EM lodishma@mail.nih.gov
FU Intramural program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development
FX Supported by the Intramural program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development. The authors
declare no conflicts of interest.
NR 28
TC 8
Z9 8
U1 1
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD APR
PY 2014
VL 164
IS 4
BP 801
EP 806
DI 10.1016/j.jpeds.2013.11.065
PG 6
WC Pediatrics
SC Pediatrics
GA AD4YV
UT WOS:000333258900029
PM 24412141
ER
PT J
AU Opdahl, A
Venkatesh, BA
Fernandes, VRS
Wu, CO
Nasir, K
Choi, EY
Almeida, ALC
Rosen, B
Carvalho, B
Edvardsen, T
Bluemke, DA
Lima, JAC
AF Opdahl, Anders
Venkatesh, Bharath Ambale
Fernandes, Veronica R. S.
Wu, Colin O.
Nasir, Khurram
Choi, Eui-Young
Almeida, Andre L. C.
Rosen, Boaz
Carvalho, Benilton
Edvardsen, Thor
Bluemke, David A.
Lima, Joao A. C.
TI Resting Heart Rate as Predictor for Left Ventricular Dysfunction and
Heart Failure MESA (Multi-Ethnic Study of Atherosclerosis)
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE cardiac MRI; coronary heart disease; heart failure; left ventricular
dysfunction; myocardial strain; resting heart rate
ID CORONARY-ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; RISK-FACTOR; BAROREFLEX
SENSITIVITY; RATE-VARIABILITY; CONTROLLED-TRIAL; MORTALITY; OUTCOMES;
MASS; HYPERTENSION
AB Objectives The objective of this study was to investigate the relationship between baseline resting heart rate and incidence of heart failure (HF) and global and regional left ventricular (LV) dysfunction. Background The association of resting heart rate to HF and LV function has not been well described in an asymptomatic multiethnic population. Methods Resting heart rate was measured in participants in the MESA (Multi-Ethnic Study of Atherosclerosis) trial at inclusion. Incident HF was registered (n = 176) during follow-up (median 7 years) in those who underwent cardiac magnetic resonance imaging (n = 5,000). Changes in ejection fraction (Delta EF) and peak circumferential strain (D epsilon cc) were measured as markers of developing global and regional LV dysfunction in 1,056 participants imaged at baseline and 5 years later. Time to HF (Cox model) and Decc and DEF (multiple linear regression models) were adjusted for demographics, traditional cardiovascular risk factors, calcium score, LV end-diastolic volume, and mass in addition to resting heart rate. Results Cox analysis demonstrated that for 1 beat/min increase in resting heart rate, there was a 4% greater adjusted relative risk for incident HF (hazard ratio: 1.04; 95% CI: 1.02 to 1.06; p < 0.001). Adjusted multiple regression models demonstrated that resting heart rate was positively associated with deteriorating epsilon cc and decrease in EF, even when all coronary heart disease events were excluded from the model. Conclusions Elevated resting heart rate was associated with increased risk for incident HF in asymptomatic participants in the MESA trial. Higher heart rate was related to development of regional and global LV dysfunction independent of subclinical atherosclerosis and coronary heart disease. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487) (C) 2014 by the American College of Cardiology Foundation
C1 [Opdahl, Anders; Nasir, Khurram; Choi, Eui-Young; Almeida, Andre L. C.; Rosen, Boaz; Lima, Joao A. C.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD 21287 USA.
[Opdahl, Anders; Edvardsen, Thor] Oslo Univ Hosp, Dept Cardiol, Rikshosp, Oslo, Norway.
[Opdahl, Anders; Edvardsen, Thor] Univ Oslo, Oslo, Norway.
[Venkatesh, Bharath Ambale; Fernandes, Veronica R. S.] Mt Sinai Sch Med, Dept Radiol, New York, NY USA.
[Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Carvalho, Benilton] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD 21287 USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Bluemke, David A.; Lima, Joao A. C.] Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD USA.
RP Lima, JAC (reprint author), Johns Hopkins Univ, Div Cardiol, 600 North Wolfe St,Blalock 524D1, Baltimore, MD 21287 USA.
EM jlima@jhmi.edu
RI Edvardsen, Thor/F-4079-2012; Carvalho, Benilton/G-1868-2012; Opdahl,
Anders/I-7580-2015; Ambale Venkatesh, Bharath/F-4941-2016;
OI Edvardsen, Thor/0000-0002-3800-765X; Carvalho,
Benilton/0000-0001-5122-5646; Opdahl, Anders/0000-0002-0599-592X; Ambale
Venkatesh, Bharath/0000-0002-2330-2373; Bluemke,
David/0000-0002-8323-8086
FU Raagholt Foundation; Norwegian Society of Cardiology; Caroline Musaeus
Aarsvold's; Norwegian Medical Association; Unger Vetlesen Trust;
Fulbright Foundation
FX Dr. Opdahl received partial grant support from the Raagholt Foundation,
the Norwegian Society of Cardiology, the Caroline Musaeus Aarsvold's
grant from the Norwegian Medical Association, the Unger Vetlesen Trust,
and the Fulbright Foundation. All other authors have reported that they
have no relationships relevant to the contents of this paper to
disclose. Jeffrey S. Borer, MD, served as Guest Editor for this paper.
NR 35
TC 23
Z9 24
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
BP 1182
EP 1189
DI 10.1016/j.jacc.2013.11.027
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AD4XW
UT WOS:000333256100011
PM 24412444
ER
PT J
AU Lubitz, SA
Lunetta, KL
Lin, HH
Arking, DE
Trompet, S
Li, G
Krijthe, BP
Chasman, DI
Barnard, J
Kleber, ME
Dorr, M
Ozaki, K
Smith, AV
Muller-Nurasyid, M
Walter, S
Agarwal, SK
Bis, JC
Brody, JA
Chen, LY
Everett, BM
Ford, I
Franco, OH
Harris, TB
Hofman, A
Kaab, S
Mahida, S
Kathiresan, S
Kubo, M
Launer, LJ
Macfarlane, PW
Magnani, JW
McKnight, B
McManus, DD
Peters, A
Psaty, BM
Rose, LM
Rotter, JI
Silbernagel, G
Smith, JD
Sotoodehnia, N
Stott, DJ
Taylor, KD
Tomaschitz, A
Tsunoda, T
Uitterlinden, AG
Van Wagoner, DR
Volker, U
Volzke, H
Murabito, JM
Sinner, MF
Gudnason, V
Felix, SB
Marz, W
Chung, M
Albert, CM
Stricker, BH
Tanaka, T
Heckbert, SR
Jukema, JW
Alonso, A
Benjamin, EJ
Ellinor, PT
AF Lubitz, Steven A.
Lunetta, Kathryn L.
Lin, Honghuang
Arking, Dan E.
Trompet, Stella
Li, Guo
Krijthe, Bouwe P.
Chasman, Daniel I.
Barnard, John
Kleber, Marcus E.
Doerr, Marcus
Ozaki, Kouichi
Smith, Albert V.
Mueller-Nurasyid, Martina
Walter, Stefan
Agarwal, Sunil K.
Bis, Joshua C.
Brody, Jennifer A.
Chen, Lin Y.
Everett, Brendan M.
Ford, Ian
Franco, Oscar H.
Harris, Tamara B.
Hofman, Albert
Kaab, Stefan
Mahida, Saagar
Kathiresan, Sekar
Kubo, Michiaki
Launer, Lenore J.
Macfarlane, Peter W.
Magnani, Jared W.
McKnight, Barbara
McManus, David D.
Peters, Annette
Psaty, Bruce M.
Rose, Lynda M.
Rotter, Jerome I.
Silbernagel, Guenther
Smith, Jonathan D.
Sotoodehnia, Nona
Stott, David J.
Taylor, Kent D.
Tomaschitz, Andreas
Tsunoda, Tatsuhiko
Uitterlinden, Andre G.
Van Wagoner, David R.
Voelker, Uwe
Voelzke, Henry
Murabito, Joanne M.
Sinner, Moritz F.
Gudnason, Vilmundur
Felix, Stephan B.
Maerz, Winfried
Chung, Mina
Albert, Christine M.
Stricker, Bruno H.
Tanaka, Toshihiro
Heckbert, Susan R.
Jukema, J. Wouter
Alonso, Alvaro
Benjamin, Emelia J.
Ellinor, Patrick T.
TI Novel Genetic Markers Associate With Atrial Fibrillation Risk in
Europeans and Japanese
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE atrial fibrillation; atrial flutter; genetic; prognosis; risk
ID FAMILIAL AGGREGATION; CHROMOSOME 4Q25; VARIANTS; SUSCEPTIBILITY;
POPULATION; METAANALYSIS; PREVALENCE; IDENTITY; ZFHX3; OLDER
AB Objectives This study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk.
Background AF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored.
Methods We performed association testing conditioned on the most significant, independently associated genetic markers at 9 established AF loci using 2 complementary techniques in 64,683 individuals of European ancestry (3,869 incident and 3,302 prevalent AF cases). Genetic risk scores were created and tested for association with AF in Europeans and an independent sample of 11,309 individuals of Japanese ancestry (7,916 prevalent AF cases).
Results We observed at least 4 distinct AF susceptibility signals on chromosome 4q25 upstream of PITX2, but not at the remaining 8 AF loci. A multilocus score comprised 12 genetic markers demonstrated an estimated 5-fold gradient in AF risk. We observed a similar spectrum of risk associated with these markers in Japanese. Regions containing AF signals on chromosome 4q25 displayed a greater degree of evolutionary conservation than the remainder of the locus, suggesting that they may tag regulatory elements.
Conclusions The chromosome 4q25 AF locus is architecturally complex and harbors at least 4 AF susceptibility signals in individuals of European ancestry. Similar polygenic AF susceptibility exists between Europeans and Japanese. Future work is necessary to identify causal variants, determine mechanisms by which associated loci predispose to AF, and explore whether AF susceptibility signals classify individuals at risk for AF and related morbidity. (C) 2014 by the American College of Cardiology Foundation
C1 [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Lunetta, Kathryn L.; Lin, Honghuang; Magnani, Jared W.; Murabito, Joanne M.; Benjamin, Emelia J.] Boston Univ, Boston, MA USA.
[Lunetta, Kathryn L.; Lin, Honghuang; Magnani, Jared W.; Murabito, Joanne M.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA.
[Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Trompet, Stella] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.
[Trompet, Stella] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands.
[Li, Guo; Bis, Joshua C.; Brody, Jennifer A.; Psaty, Bruce M.; Sotoodehnia, Nona; Heckbert, Susan R.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H.] NCHA, Leiden, Netherlands.
[Chasman, Daniel I.; Everett, Brendan M.; Albert, Christine M.] Harvard Univ, Sch Med, Boston, MA USA.
[Chasman, Daniel I.; Albert, Christine M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Barnard, John] Cleveland Clin, Lerner Res Inst, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA.
[Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Mannheim Med Fac, Inst Publ Hlth Social & Prevent Med, Mannheim, Germany.
[Doerr, Marcus; Felix, Stephan B.] Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.
[Doerr, Marcus; Voelker, Uwe; Voelzke, Henry; Felix, Stephan B.] DZHK German Ctr Cardiovasc Res, Greifswald, Germany.
[Ozaki, Kouichi; Tanaka, Toshihiro] RIKEN Ctr Integrat Med Sci, Lab Cardiovasc Dis, Yokohama, Kanagawa, Japan.
[Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Mueller-Nurasyid, Martina; Kaab, Stefan; Sinner, Moritz F.] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.
[Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Walter, Stefan] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Agarwal, Sunil K.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Chen, Lin Y.] Univ Minnesota, Sch Med, Dept Med, Div Cardiovasc, Minneapolis, MN 55455 USA.
[Everett, Brendan M.; Albert, Christine M.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA.
[Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Kaab, Stefan; Peters, Annette] Partner Munich Heart Alliance, DZHK, Munich, Germany.
[Mahida, Saagar] Leeds Gen Infirm, Leeds, W Yorkshire, England.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kubo, Michiaki] RIKEN Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa, Japan.
[Macfarlane, Peter W.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA.
[Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA.
[Rose, Lynda M.] Brigham & Womens Hosp, Div Prevent Med, Div Cardiovasc, Boston, MA 02115 USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
[Silbernagel, Guenther] Univ Hosp Bern, Swiss Cardiovasc Ctr, Dept Angiol, CH-3010 Bern, Switzerland.
[Smith, Jonathan D.] Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.
[Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA.
[Stott, David J.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Taylor, Kent D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Tomaschitz, Andreas] Med Univ Graz, Dept Cardiol, Graz, Austria.
[Tsunoda, Tatsuhiko] RIKEN Ctr Integrat Med Sci, Lab Med Sci Math, Yokohama, Kanagawa, Japan.
[Uitterlinden, Andre G.; Stricker, Bruno H.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Van Wagoner, David R.; Chung, Mina] Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44106 USA.
[Voelker, Uwe] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
[Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02118 USA.
[Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
[Maerz, Winfried] Synlab Serv GmbH, Synlab Acad, Mannheim, Germany.
[Chung, Mina] Cleveland Clin, Inst Heart & Vasc, Dept Cardiovasc Med, Cleveland, OH 44106 USA.
[Stricker, Bruno H.] Inspectorate Hlth Care, The Hague, Netherlands.
[Tanaka, Toshihiro] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Div, Tokyo, Japan.
[Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.
[Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands.
[Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA.
RP Lubitz, SA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 55 Fruit St,GRB 109, Boston, MA 02114 USA.
EM slubitz@partners.org
RI Tsunoda, Tatsuhiko/K-2061-2014; Gudnason, Vilmundur/K-6885-2015; Alonso,
Alvaro/A-4917-2010; Tanaka, Toshihiro/J-9310-2014; Peters,
Annette/A-6117-2011; Smith, Albert/K-5150-2015; Kubo,
Michiaki/N-7947-2015;
OI Kleber, Marcus/0000-0003-0663-7275; Gudnason,
Vilmundur/0000-0001-5696-0084; Alonso, Alvaro/0000-0002-2225-8323;
Tanaka, Toshihiro/0000-0001-6201-9784; Smith,
Albert/0000-0003-1942-5845; Lin, Honghuang/0000-0003-3043-3942;
Benjamin, Emelia/0000-0003-4076-2336
FU AstraZeneca and Amgen; Roche Diagnostics
FX Dr. Chasman has received research grant suppport from AstraZeneca and
Amgen. Dr. Everett has received an investigator-initiated research grant
from Roche Diagnostics. Dr. Kathiresan has received research grant
support from Celera totaling more than $10,000; and serves on scientific
advisory boards for American Genomics and Catabasis. Dr. McManus has
received grants from Biotronic, Philips Healthcare, and Otsuka
Pharmaceuticals. All other authors have reported that they have no
relationships relevant to the contents of this paper to disclose. Drs.
Lubitz, Lunetta, Lin, Arking, Trompet, Li, Krijthe, Chasman, Barnard,
Kleber, Dorr, Ozaki, Smith, Muller-Nurasyid, and Walter are joint first
authors. Drs. Murabito, Sinner, Gudnason, Felix, Marz, Chung, Albert,
Stricker, Tanaka, Heckbert, Jukema, Alonso, Benjamin, and Ellinor are
joint senior authors.
NR 38
TC 43
Z9 44
U1 0
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
BP 1200
EP 1210
DI 10.1016/j.jacc.2013.12.015
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AD4XW
UT WOS:000333256100014
PM 24486271
ER
PT J
AU Sinha, P
Deutsch, N
Ratnayaka, K
Lederman, R
He, DC
Nuszkowski, M
Montague, E
Mikesell, G
Ishibashi, N
Zurakowski, D
Jonas, R
AF Sinha, Pranava
Deutsch, Nina
Ratnayaka, Kanishka
Lederman, Robert
He, Dingchao
Nuszkowski, Mark
Montague, Erin
Mikesell, Gerald
Ishibashi, Nobuyuki
Zurakowski, David
Jonas, Richard
TI Effect of mechanical assistance of the systemic ventricle in single
ventricle circulation with cavopulmonary connection
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID FAILING FONTAN CIRCULATION; BERLIN HEART; DESTINATION THERAPY; SUPPORT;
DEVICE; FLOW; MULTICENTER; PREDICTORS; MORTALITY; OUTCOMES
AB Background: Previous attempts to support single ventricle circulation mechanically have suggested that a custom- built assist device is needed to push, rather than pull, through the pulmonary circulation. We hypothesized that using a conventional ventricular assist device, with or without conversion of a total cavopulmonary connection to a bidirectional Glenn cavopulmonary connection, would allow assistance by pulling blood through the circuit and improve the cardiac index (CI).
Methods: Cavopulmonary connections were established in each of 5 Yorkshire pigs (25 kg) using ePTFE conduits in a Y configuration with appropriate clamping of the limbs of the Y to achieve a total cavopulmonary Fontan connection (TCPC), superior vena cava cavopulmonary connection (SVC Glenn), and inferior vena cava cavopulmonary connection (IVC Glenn). A common atrium had been established previously by balloon septostomy. Mechanical circulatory assistance of the single systemic ventricle was achieved using a centrifugal pump with common atrial inflow and proximal ascending aortic outflow. The CI was calculated using an ultrasonic flow meter placed on the distal ascending aorta and compared between the assisted and nonassisted circulation for 3 conditions: TCPC, SVC Glenn, and IVC Glenn. The mean pulmonary artery pressure, common atrial pressure, arterial oxygen saturation, partial pressure of arterial oxygen, and oxygen delivery were calculated.
Results: The unassisted SVC Glenn CI tended to be greater than the TCPC or IVC Glenn CI. Significant augmentation of total CI was achieved with mechanical assistance for SVC Glenn (109% +/- 24%, P = .04) and TCPC (130% +/- 109%, P = .01). The assisted CI achieved at least a mean baseline biventricular CI for all 3 support modes. Oxygen delivery was greatest for assisted SVC Glenn (1786 +/- 1307 mL/L/min) and lowest for TCPC (1146 +/- 386 mL/L/min), with a trend toward lower common atrial and pulmonary artery pressures for SVC Glenn.
Conclusions: SVC bidirectional Glenn circulation might allow optimal augmentation of the CI and oxygen delivery in a failing single ventricle using a conventional pediatric ventricular assist device. The results from our model also suggest that the Fontan circulation itself can be supported with systemic ventricular assistance of the single ventricle.
C1 [Sinha, Pranava; He, Dingchao; Nuszkowski, Mark; Montague, Erin; Mikesell, Gerald; Ishibashi, Nobuyuki; Jonas, Richard] Childrens Natl Med Ctr, Dept Cardiovasc Surg, Washington, DC 20010 USA.
[Deutsch, Nina] Childrens Natl Med Ctr, Dept Anesthesiol, Washington, DC 20010 USA.
[Ratnayaka, Kanishka] Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA.
[Ratnayaka, Kanishka; Lederman, Robert] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Zurakowski, David] Boston Childrens Hosp, Dept Gen Surg & Anesthesia, Boston, MA USA.
RP Jonas, R (reprint author), Childrens Natl Med Ctr, Dept Cardiovasc Surg, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM rjonas@childrensnational.org
OI lederman, robert/0000-0003-1202-6673
FU Intramural NIH HHS [ZIA HL005062-12]; NHLBI NIH HHS [R01 HL104173]
NR 25
TC 7
Z9 7
U1 0
U2 7
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
EI 1097-685X
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD APR
PY 2014
VL 147
IS 4
BP 1271
EP 1275
DI 10.1016/j.jtcvs.2013.12.018
PG 5
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA AC8GT
UT WOS:000332772200040
PM 24530198
ER
PT J
AU Harden, B
Tian, X
Giese, R
Nakhleh, N
Kureshi, S
Francis, R
Hanumanthaiah, S
Li, Y
Swisher, M
Kuehl, K
Sami, I
Olivier, K
Jonas, R
Lo, CW
Leatherbury, L
AF Harden, Brandon
Tian, Xin
Giese, Rachel
Nakhleh, Nader
Kureshi, Safina
Francis, Richard
Hanumanthaiah, Sridhar
Li, You
Swisher, Matthew
Kuehl, Karen
Sami, Iman
Olivier, Kenneth
Jonas, Richard
Lo, Cecilia W.
Leatherbury, Linda
TI Increased postoperative respiratory complications in heterotaxy
congenital heart disease patients with respiratory ciliary dysfunction
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID PEDIATRIC CARDIAC-SURGERY; BEAT FREQUENCY; PREVALENCE; DYSKINESIA;
DEFECTS; MANAGEMENT; ISOMERISM
AB Objective(s): Congenital heart disease (CHD) and heterotaxy patients have increased postoperative and respiratory complications. We recently showed CHD-heterotaxy patients can have respiratory ciliary dysfunction (CD) similar to that associated with primary ciliary dyskinesia, including low nasal nitric oxide and abnormal ciliary motion. In this study, we investigated whether CHD-heterotaxy patients with CD may have worse postsurgical outcomes.
Methods: We examined postsurgical outcome in 13 heterotaxy-CHD patients with CD (25 surgeries), compared with 14 heterotaxy-CHD patients without CD (27 surgeries). Outcome data were collected for each surgery, including respiratory complications, tracheostomy, use of inhaled beta-agonists or nitric oxide, length of hospital stay, days on ventilator, and death.
Results: The CD versus the no-CD CHD cohorts had similar Risk Adjustment in Congenital Heart Surgery-1 risk categories, repair track, age at surgery, and follow-up evaluation times. Respiratory complications (76% vs 37%; P = .006), need for tracheostomy (16% vs 0%; P = .047), and use of inhaled beta-agonists (64% vs 11%; P = .0001) all were increased significantly in heterotaxy-CHD patients with CD. No significant differences were detected in postoperative hospital stay, days on mechanical ventilation, or surgical mortality. A trend toward increased mortality for the CD group beyond the postoperative period was observed (33% vs 0%; P = .055) in patients younger than age 10 years. Conclusions: Our findings showed that heterotaxy-CHD patients with CD may have increased risks for respiratory deficiencies. Overall, there was a trend toward increased mortality in CD patients with intermediate follow-up evaluation. Because b-agonists are known to increase ciliary beat frequency, presurgical screening for CD and perioperative treatment of CD patients with inhaled beta-agonists may improve postoperative outcomes and survival.
C1 [Harden, Brandon; Hanumanthaiah, Sridhar; Kuehl, Karen; Jonas, Richard; Leatherbury, Linda] Childrens Natl Med Ctr, Childrens Natl Heart Inst, Washington, DC 20010 USA.
[Nakhleh, Nader; Kureshi, Safina; Sami, Iman] Childrens Natl Med Ctr, Dept Pediat Pulmonol, Washington, DC 20010 USA.
[Tian, Xin] NIH, Off Biostat Res, Bethesda, MD 20892 USA.
[Giese, Rachel; Swisher, Matthew] NIH, Howard Hughes Med Inst, Bethesda, MD 20892 USA.
[Olivier, Kenneth] NIAID, NIH, Bethesda, MD 20892 USA.
[Francis, Richard; Li, You; Lo, Cecilia W.] Univ Pittsburgh, Sch Med, Dept Dev Biol, Pittsburgh, PA USA.
RP Harden, B (reprint author), Childrens Healthcare Atlanta, Sibley Heart Ctr, 2835 Brandywine Rd,Suite 300, Atlanta, GA 30341 USA.
EM hardenb@kidsheart.com
RI Francis, Richard/P-2524-2015
FU National Institutes of Health [ZO1-HL005701]; Children's National
Medical Center intramural (RAC); Howard Hughes Medical Institute
FX Supported by a National Institutes of Health grant (ZO1-HL005701 to
C.W.L.), Children's National Medical Center intramural funding (RAC)
2010-2011; and Matthew Swisher and Rachel Giese were generously
supported by a fellowship from Howard Hughes Medical Institute.
NR 19
TC 14
Z9 14
U1 1
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
EI 1097-685X
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD APR
PY 2014
VL 147
IS 4
BP 1291
EP U287
DI 10.1016/j.jtcvs.2013.06.018
PG 10
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA AC8GT
UT WOS:000332772200044
PM 23886032
ER
PT J
AU Kovalchik, SA
Pfeiffer, RM
AF Kovalchik, Stephanie A.
Pfeiffer, Ruth M.
TI Population-based absolute risk estimation with survey data
SO LIFETIME DATA ANALYSIS
LA English
DT Article
DE Absolute risk; Censored data; Crude risk; Cumulative incidence; NHANES;
Survey cohort
ID PROPORTIONAL HAZARDS MODELS; SAMPLE SURVEY DATA; INFERENCE; COHORT;
PARAMETERS; VARIANCE; DESIGNS
AB Absolute risk is the probability that a cause-specific event occurs in a given time interval in the presence of competing events. We present methods to estimate population-based absolute risk from a complex survey cohort that can accommodate multiple exposure-specific competing risks. The hazard function for each event type consists of an individualized relative risk multiplied by a baseline hazard function, which is modeled nonparametrically or parametrically with a piecewise exponential model. An influence method is used to derive a Taylor-linearized variance estimate for the absolute risk estimates. We introduce novel measures of the cause-specific influences that can guide modeling choices for the competing event components of the model. To illustrate our methodology, we build and validate cause-specific absolute risk models for cardiovascular and cancer deaths using data from the National Health and Nutrition Examination Survey. Our applications demonstrate the usefulness of survey-based risk prediction models for predicting health outcomes and quantifying the potential impact of disease prevention programs at the population level.
C1 [Kovalchik, Stephanie A.; Pfeiffer, Ruth M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Kovalchik, SA (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM kovalchiksa@mail.nih.gov; pfeiffer@mail.nih.gov
FU Intramural NIH HHS [Z01 CP010188-03]
NR 36
TC 2
Z9 2
U1 2
U2 10
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1380-7870
EI 1572-9249
J9 LIFETIME DATA ANAL
JI Lifetime Data Anal.
PD APR
PY 2014
VL 20
IS 2
SI SI
BP 252
EP 275
DI 10.1007/s10985-013-9258-4
PG 24
WC Mathematics, Interdisciplinary Applications; Statistics & Probability
SC Mathematics
GA AD6IZ
UT WOS:000333363400006
PM 23686614
ER
PT J
AU Staib, F
Krupp, M
Maass, T
Itzel, T
Weinmann, A
Lee, JS
Schmidt, B
Muller, M
Thorgeirsson, SS
Galle, PR
Teufel, A
AF Staib, Frank
Krupp, Markus
Maass, Thorsten
Itzel, Timo
Weinmann, Arndt
Lee, Ju-Seog
Schmidt, Bertil
Mueller, Martina
Thorgeirsson, Snorri S.
Galle, Peter R.
Teufel, Andreas
TI CellMinerHCC: a microarray-based expression database for hepatocellular
carcinoma cell lines
SO LIVER INTERNATIONAL
LA English
DT Article
DE oncogenomics; bioinformatics; liver cancer; systems biology; HCC
ID CANCER STEM-CELLS; LARGE GENE LISTS; RESOURCES; PREDICTION; PROFILES;
ONTOLOGY; HCC; P53
AB Background & Aims
Therapeutic options for hepatocellular carcinoma (HCC) still remain limited. Development of gene targeted therapies is a promising option. A better understanding of the underlying molecular biology is gained in in vitro experiments. However, even with targeted manipulation of gene expression varying treatment responses were observed in diverse HCC cell lines. Therefore, information on gene expression profiles of various HCC cell lines may be crucial to experimental designs. To generate a publicly available database containing microarray expression profiles of diverse HCC cell lines.
Methods
Microarray data were analyzed using an individually scripted R program package. Data were stored in a PostgreSQL database with a PHP written web interface. Evaluation and comparison of individual cell line expression profiles are supported via public web interface.
Results
This database allows evaluation of gene expression profiles of 18 HCC cell lines and comparison of differential gene expression between multiple cell lines. Analysis of commonly regulated genes for signaling pathway enrichment and interactions demonstrates a liver tumor phenotype with enrichment of major cancer related KEGG signatures like 'cancer' and 'inflammatory response'. Further molecular associations of strong scientific interest, e.g. 'lipid metabolism', were also identified.
Conclusions
We have generated CellMinerHCC (), a publicly available database containing gene expression data of 18 HCC cell lines. This database will aid in the design of in vitro experiments in HCC research, because the genetic specificities of various HCC cell lines will be considered.
C1 [Staib, Frank; Weinmann, Arndt; Galle, Peter R.] Johannes Gutenberg Univ Mainz, Dept Med 1, Mainz, Germany.
[Krupp, Markus; Schmidt, Bertil] Johannes Gutenberg Univ Mainz, Inst Comp Sci, D-55122 Mainz, Germany.
[Maass, Thorsten; Itzel, Timo; Mueller, Martina; Teufel, Andreas] Univ Regensburg, Dept Med 1, D-93053 Regensburg, Germany.
[Lee, Ju-Seog] Univ Texas Houston, MD Anderson Canc Ctr, Dept Syst Biol, Kleberg Ctr Mol Markers, Houston, TX 77030 USA.
[Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Teufel, A (reprint author), Univ Regensburg, Dept Med 1, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany.
EM andreas.teufel@ukr.de
NR 36
TC 3
Z9 4
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1478-3223
EI 1478-3231
J9 LIVER INT
JI Liver Int.
PD APR
PY 2014
VL 34
IS 4
BP 621
EP 631
DI 10.1111/liv.12292
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AC3FQ
UT WOS:000332401300018
PM 24016071
ER
PT J
AU Park, SK
Xiao, HJ
Lei, M
AF Park, Sang-Kyu
Xiao, Haijie
Lei, Ming
TI Nuclear FKBPs, Fpr3 and Fpr4 affect genome-wide genes transcription
SO MOLECULAR GENETICS AND GENOMICS
LA English
DT Article
DE FKBP; Histone chaperone; Genome; Transcriptional profiling;
Transcriptional repression
ID SACCHAROMYCES-CEREVISIAE; HISTONE CHAPERONE; FK506-BINDING PROTEIN;
RIBOSOMAL DNA; YEAST; RAPAMYCIN; EXPRESSION; NUCLEOLUS; TARGET; TOR2
AB Fpr3 and Fpr4 of Saccharomyces cerevisiae are nuclear FK506-binding proteins each containing an extended acidic domain in addition to the conserved FK506-binding/peptidylprolyl isomerase (PPIase) domain. Previous studies have shown that the PPIase domain regulates histone H3 methylation, while the acidic domain facilitates histone deposition and may regulate rDNA silencing. To gain insight into the role of FKBPs in maintaining chromatin structure, we examined the transcriptional profiles of fpr3 (-) and fpr4 (-) cells. Our results show that both proteins modulate the expression of a large number of genes randomly distributed throughout the genome, a pattern resembling those observed with yeast cells lacking other histone chaperones such as CAF1 and Asf1. Significant overlaps are found between nuclear FKBPs-modulated and the Asf1/CAF1-modulated genes. Thus, nuclear FKBPs appear to impact chromatin structure like other histone chaperones. Our analyses show that depleting Fpr4 causes no detectable chromatin structural change at the rDNA locus nor de-repression of transcription silencing at the locus, in contrast to a previous report. Furthermore, we demonstrate PPIase domain of the proteins represses transcription when tethered to the promoter of a reporter gene, suggesting that the PPIase domains can act on non-histone chromatin components, when brought to close proximity. The results thus provide a further demonstration for the elusive role of Fpr3 and Fpr4 in histone chaperones.
C1 [Park, Sang-Kyu] Med Coll Wisconsin, Dept Pediat, Childrens Res Inst, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA.
[Xiao, Haijie] Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA.
[Lei, Ming] Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Park, SK (reprint author), Med Coll Wisconsin, Dept Pediat, Childrens Res Inst, Human & Mol Genet Ctr, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM skpark@mcw.edu
FU National Institutes of Health [GM6264901]
FX This work was supported in part by National Institutes of Health Grant
(GM6264901). We thank Dr. Vaughn Jackson for reading the manuscript, Dr.
Craig Struble for statistical analysis, Mary Goetsch and Megan Morrell
for technical assistance.
NR 35
TC 1
Z9 1
U1 0
U2 6
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1617-4615
EI 1617-4623
J9 MOL GENET GENOMICS
JI Mol. Genet. Genomics
PD APR
PY 2014
VL 289
IS 2
BP 125
EP 136
DI 10.1007/s00438-013-0794-0
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AD7UL
UT WOS:000333472300001
PM 24297734
ER
PT J
AU Liang, Q
Dexheimer, TS
Zhang, P
Rosenthal, AS
Villamil, MA
You, CJ
Zhang, QT
Chen, JJ
Ott, CA
Sun, HM
Luci, DK
Yuan, BF
Simeonov, A
Jadhav, A
Xiao, H
Wang, YS
Maloney, DJ
Zhuang, ZH
AF Liang, Qin
Dexheimer, Thomas S.
Zhang, Ping
Rosenthal, Andrew S.
Villamil, Mark A.
You, Changjun
Zhang, Qiuting
Chen, Junjun
Ott, Christine A.
Sun, Hongmao
Luci, Diane K.
Yuan, Bifeng
Simeonov, Anton
Jadhav, Ajit
Xiao, Hui
Wang, Yinsheng
Maloney, David J.
Zhuang, Zhihao
TI A selective USP1-UAF1 inhibitor links deubiquitination to DNA damage
responses
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID NUCLEAR ANTIGEN PCNA; FANCONI-ANEMIA; HOMOLOGOUS RECOMBINATION;
UBIQUITIN CONJUGATION; TRANSLESION SYNTHESIS; CISPLATIN RESISTANCE;
MAMMALIAN-CELLS; POL-ETA; REPAIR; CANCER
AB Protein ubiquitination and deubiquitination are central to the control of a large number of cellular pathways and signaling networks in eukaryotes. Although the essential roles of ubiquitination have been established in the eukaryotic DNA damage response, the deubiquitination process remains poorly defined. Chemical probes that perturb the activity of deubiquitinases (DUBs) are needed to characterize the cellular function of deubiquitination. Here we report ML323 (2), a highly potent inhibitor of the USP1-UAF1 deubiquitinase complex with excellent selectivity against human DUBs, deSUMOylase, deneddylase and unrelated proteases. Using ML323, we interrogated deubiquitination in the cellular response to UV-and cisplatin-induced DNA damage and revealed new insights into the requirement of deubiquitination in the DNA translesion synthesis and Fanconi anemia pathways. Moreover, ML323 potentiates cisplatin cytotoxicity in non-small cell lung cancer and osteosarcoma cells. Our findings point to USP1-UAF1 as a key regulator of the DNA damage response and a target for overcoming resistance to the platinum-based anticancer drugs.
C1 [Liang, Qin; Zhang, Ping; Villamil, Mark A.; Chen, Junjun; Ott, Christine A.; Zhuang, Zhihao] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
[Dexheimer, Thomas S.; Rosenthal, Andrew S.; Sun, Hongmao; Luci, Diane K.; Simeonov, Anton; Jadhav, Ajit; Maloney, David J.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[You, Changjun; Yuan, Bifeng; Wang, Yinsheng] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA.
[Zhang, Qiuting] Nanchang Univ, State Key Lab Food Sci & Technol, Nanchang, Jiangxi, Peoples R China.
[Xiao, Hui] Albert Einstein Coll Med, Lab Macromol Anal & Prote, Bronx, NY 10467 USA.
RP Zhuang, ZH (reprint author), Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
EM maloneyd@mail.nih.gov; zzhuang@udel.edu
RI liang, qin/C-8284-2016; Yuan, Bi-Feng/K-5803-2013
OI Yuan, Bi-Feng/0000-0001-5223-4659
FU US National Institutes of Health (NIH) [R03DA030552]; National Center
for Advancing Translational Sciences; NIH [R01GM097468, R01DK082779,
T32GM008550]; Molecular Libraries Initiative of the National Institutes
of Health Roadmap for Medical Research [U54MH084681]
FX We thank M. Cordeiro-Stone (University of North Carolina at Chapel Hill)
for xeroderma pigmentosum variant (XPV) human fibroblasts GM02359-hTERT
(XP115LO) and Pol eta-complemented GM02359-hTERT (XPV + Pol eta) and M.
Jasin ( Memorial Sloan-Kettering Cancer Center) for DR-GFP U2OS cells.
We also thank C. Arrowsmith (University of Toronto and Ontario Cancer
Institute) for the USP21 plasmid; A. Tencer for assistance with protein
purification; S. Michael and R. Jones for automation support; P. Shinn
and D. van Leer for assistance with compound management; and W. Leister,
H. Baker, C. Leclair and E. Fernandez for analytical chemistry and
compound purification support. This work was supported by US National
Institutes of Health (NIH) grant R03DA030552 and in part by NIH grant
R01GM097468 to Z.Z. C.A.O. was supported by NIH training grant
T32GM008550. Work in the laboratory of Y.W. was supported by NIH grant
R01DK082779. T.S.D., A.S.R., D.K.L., A.S., A.J. and D.J.M. were
supported by the intramural research program of the National Center for
Advancing Translational Sciences and the Molecular Libraries Initiative
of the National Institutes of Health Roadmap for Medical Research
(U54MH084681).
NR 59
TC 48
Z9 50
U1 3
U2 51
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
EI 1552-4469
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD APR
PY 2014
VL 10
IS 4
BP 298
EP +
DI 10.1038/NCHEMBIO.1455
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD3UY
UT WOS:000333172900013
PM 24531842
ER
PT J
AU Kaila, VRI
Schotte, F
Cho, HS
Hummer, G
Anfinrud, PA
AF Kaila, Ville R. I.
Schotte, Friedrich
Cho, Hyun Sun
Hummer, Gerhard
Anfinrud, Philip A.
TI Contradictions in X-ray structures of intermediates in the photocycle of
photoactive yellow protein
SO NATURE CHEMISTRY
LA English
DT Letter
ID CRYSTALLOGRAPHY
C1 [Kaila, Ville R. I.; Schotte, Friedrich; Cho, Hyun Sun; Hummer, Gerhard; Anfinrud, Philip A.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Kaila, Ville R. I.] Tech Univ Munich, Dept Chem, D-85748 Garching, Germany.
[Hummer, Gerhard] Max Planck Inst Biophys, Dept Theoret Biophys, D-60438 Frankfurt, Germany.
RP Kaila, VRI (reprint author), NIDDK, Chem Phys Lab, NIH, 5 Mem Dr, Bethesda, MD 20892 USA.
EM anfinrud@nih.gov
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
FU Intramural NIH HHS [ZIA DK029058-07]; NIGMS NIH HHS [R24 GM111072]
NR 8
TC 10
Z9 10
U1 0
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1755-4330
EI 1755-4349
J9 NAT CHEM
JI Nat. Chem.
PD APR
PY 2014
VL 6
IS 4
BP 258
EP 259
DI 10.1038/nchem.1898
PG 2
WC Chemistry, Multidisciplinary
SC Chemistry
GA AD6UH
UT WOS:000333396200002
PM 24651178
ER
PT J
AU Wen, PY
Chang, SM
Lamborn, KR
Kuhn, JG
Norden, AD
Cloughesy, TF
Robins, HI
Lieberman, FS
Gilbert, MR
Mehta, MP
Drappatz, J
Groves, MD
Santagata, S
Ligon, AH
Yung, WKA
Wright, JJ
Dancey, J
Aldape, KD
Prados, MD
Ligon, KL
AF Wen, Patrick Y.
Chang, Susan M.
Lamborn, Kathleen R.
Kuhn, John G.
Norden, Andrew D.
Cloughesy, Timothy F.
Robins, H. Ian
Lieberman, Frank S.
Gilbert, Mark R.
Mehta, Minesh P.
Drappatz, Jan
Groves, Morris D.
Santagata, Sandro
Ligon, Azra H.
Yung, W. K. Alfred
Wright, John J.
Dancey, Janet
Aldape, Kenneth D.
Prados, Michael D.
Ligon, Keith L.
TI Phase I/II study of erlotinib and temsirolimus for patients with
recurrent malignant gliomas: North American Brain Tumor Consortium trial
04-02
SO NEURO-ONCOLOGY
LA English
DT Article
DE anaplastic glioma; clinical trial; epidermal growth factor; erlotinib;
glioblastoma; temsirolimus
ID GROWTH-FACTOR-RECEPTOR; EGFR KINASE INHIBITORS; GLIOBLASTOMA-MULTIFORME;
MAMMALIAN TARGET; II TRIAL; RAPAMYCIN INHIBITION; ANTITUMOR-ACTIVITY;
MTOR INHIBITORS; PLUS SIROLIMUS; PTEN-DEFICIENT
AB Inhibition of epidermal growth factor receptor (EGFR) and the mechanistic target of rapamycin (mTOR) may have synergistic antitumor effects in high-grade glioma patients.
We conducted a phase I/II study of the EGFR inhibitor erlotinib (150 mg/day) and the mTOR inhibitor temsirolimus. Patients initially received temsirolimus 50 mg weekly, and the dose adjusted based on toxicities. In the phase II component, the primary endpoint was 6-month progression-free survival (PFS6) among glioblastoma patients.
Twenty-two patients enrolled in phase I, 47 in phase II. Twelve phase I patients treated at the maximum tolerated dosage were included in the phase II cohort for analysis. The maximum tolerated dosage was 15 mg temsirolimus weekly with erlotinib 150 mg daily. Dose-limiting toxicities were rash and mucositis. Among 42 evaluable glioblastoma patients, 12 (29) achieved stable disease, but there were no responses, and PFS6 was 13. Among 16 anaplastic glioma patients, 1 (6) achieved complete response, 1 (6) partial response, and 2 (12.5) stable disease, with PFS6 of 8. Tumor levels of both drugs were low, and posttreatment tissue in 3 patients showed no reduction in the mTOR target phosphorylated (phospho-)S6(S235/236) but possible compensatory increase in phospho-Akt(S473). Presence of EGFR variant III, phospho-EGFR, and EGFR amplification did not correlate with survival, but patients with elevated phosphoextracellular signal-regulated kinase or reduced phosphatase and tensin homolog protein expression had decreased progression-free survival at 4 months.
Because of increased toxicity, the maximum tolerated dosage of temsirolimus in combination with erlotinib proved lower than expected. Insufficient tumor drug levels and redundant signaling pathways may partly explain the minimal antitumor activity noted.
C1 [Wen, Patrick Y.; Norden, Andrew D.; Drappatz, Jan] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA.
[Chang, Susan M.; Lamborn, Kathleen R.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA.
[Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Cloughesy, Timothy F.] Univ Calif Los Angeles, Dept Neurol, Div Neurooncol, Los Angeles, CA 90024 USA.
[Robins, H. Ian; Mehta, Minesh P.] Univ Wisconsin, Madison, WI USA.
[Lieberman, Frank S.] Univ Pittsburgh, Med Ctr, Neurooncol Program, Div Hematol Oncol, Pittsburgh, PA USA.
[Gilbert, Mark R.; Groves, Morris D.; Yung, W. K. Alfred; Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Div Neurooncol, Houston, TX 77030 USA.
[Santagata, Sandro; Ligon, Azra H.] Dana Farber Brigham & Womens Canc Ctr, Ctr Mol Oncol Pathol, Boston, MA 02215 USA.
[Santagata, Sandro; Ligon, Azra H.; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Wright, John J.; Dancey, Janet] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM pwen@partners.org
RI Gilbert, Mark/J-7494-2016;
OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713
FU Ivy Foundation; Sontag Foundation; [U01 CA137443]; [P01CA095616]
FX This study was funded by U01 CA137443. K. L. L. acknowledges support
from P01CA095616, the Ivy Foundation, and the Sontag Foundation.
NR 49
TC 36
Z9 37
U1 1
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD APR
PY 2014
VL 16
IS 4
BP 567
EP 578
DI 10.1093/neuonc/not247
PG 12
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA AD5IS
UT WOS:000333286400011
PM 24470557
ER
PT J
AU Irrechukwu, ON
Von Thaer, S
Frank, EH
Lin, PC
Reiter, DA
Grodzinsky, AJ
Spencer, RG
AF Irrechukwu, Onyi N.
Von Thaer, Sarah
Frank, Eliot H.
Lin, Ping-Chang
Reiter, David A.
Grodzinsky, Alan J.
Spencer, Richard G.
TI Prediction of cartilage compressive modulus usingmultiexponential
analysis of T2 relaxation data and support vector regression
SO NMR IN BIOMEDICINE
LA English
DT Article
DE biomechanical stiffness; multiexponential T-2 relaxation; cartilage;
water compartments
ID MULTIEXPONENTIAL T-2 RELAXATION; MAGNETIC-RESONANCE MICROSCOPY; BOVINE
ARTICULAR-CARTILAGE; ENGINEERED CARTILAGE; IN-VITRO; BIOMECHANICAL
PROPERTIES; BIOCHEMICAL-PROPERTIES; TRANSVERSE RELAXATION;
MULTIVARIATE-ANALYSIS; MECHANICAL-PROPERTIES
AB Evaluation of mechanical characteristics of cartilage by magnetic resonance imaging would provide a noninvasive measure of tissue quality both for tissue engineering and when monitoring clinical response to therapeutic interventions for cartilage degradation. We use results from multiexponential transverse relaxation analysis to predict equilibrium and dynamic stiffness of control and degraded bovine nasal cartilage, a biochemical model for articular cartilage. Sulfated glycosaminoglycan concentration/wet weight (ww) and equilibrium and dynamic stiffness decreased with degradation from 103.6 +/- 37.0 mu g/mg ww, 1.71 +/- 1.10 MPa and 15.3 +/- 6.7 MPa in controls to 8.25 +/- 2.4 mu g/mg ww, 0.015 +/- 0.006 MPa and 0.89 +/- 0.25MPa, respectively, in severely degraded explants. Magnetic resonance measurements were performed on cartilage explants at 4 degrees C in a 9.4 T wide-bore NMR spectrometer using a Carr-Purcell-Meiboom-Gill sequence. Multiexponential T-2 analysis revealed four water compartments with T-2 values of approximately 0.14, 3, 40 and 150 ms, with corresponding weight fractions of approximately 3, 2, 4 and 91%. Correlations between weight fractions and stiffness based on conventional univariate and multiple linear regressions exhibited a maximum r(2) of 0.65, while those based on support vector regression (SVR) had a maximum r(2) value of 0.90. These results indicate that (i) compartment weight fractions derived from multiexponential analysis reflect cartilage stiffness and (ii) SVR-based multivariate regression exhibits greatly improved accuracy in predicting mechanical properties as compared with conventional regression. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Irrechukwu, Onyi N.; Von Thaer, Sarah; Lin, Ping-Chang; Reiter, David A.; Spencer, Richard G.] NIA, NIH, Baltimore, MD 21224 USA.
[Frank, Eliot H.; Grodzinsky, Alan J.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
RP Spencer, RG (reprint author), NIA, NIH, Baltimore, MD 21224 USA.
EM spencerri@mail.nih.gov
OI Lin, Ping-Chang/0000-0003-0918-4072
FU Intramural Research Program of the NIH, National Institute on Aging
FX This work was supported by the Intramural Research Program of the NIH,
National Institute on Aging.
NR 50
TC 0
Z9 0
U1 3
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
EI 1099-1492
J9 NMR BIOMED
JI NMR Biomed.
PD APR
PY 2014
VL 27
IS 4
BP 468
EP 477
DI 10.1002/nbm.3083
PG 10
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA AD1IU
UT WOS:000332988500013
PM 24519878
ER
PT J
AU Eckelman, WC
Lau, CY
Neumann, RD
AF Eckelman, William C.
Lau, Chuen-Yen
Neumann, Ronald D.
TI Perspective, the one most responsive to change
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Editorial Material
ID PROSTATE-CANCER; TARGET; PRECISION; MEDICINE
C1 [Eckelman, William C.] Mol Tracer LLC, Bethesda, MD 20814 USA.
[Lau, Chuen-Yen] NIAID, Bethesda, MD 20817 USA.
[Neumann, Ronald D.] Warren Grant Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20814 USA.
RP Eckelman, WC (reprint author), Mol Tracer LLC, Bethesda, MD 20814 USA.
EM wceckelman@gmail.com
NR 16
TC 3
Z9 3
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
EI 1872-9614
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD APR
PY 2014
VL 41
IS 4
BP 297
EP 298
DI 10.1016/j.nucmedbio.2013.10.002
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AD7JC
UT WOS:000333439100001
PM 24268902
ER
PT J
AU Lau, CY
Maldarelli, F
Eckelman, WC
Neumann, RD
AF Lau, Chuen-Yen
Maldarelli, Frank
Eckelman, William C.
Neumann, Ronald D.
TI Rational development of radiopharmaceuticals for HIV-1
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE Human Immunodeficiency Virus; Radiopharmaceutical; Infectious disease
imaging
ID POSITRON-EMISSION-TOMOGRAPHY; CENTRAL-NERVOUS-SYSTEM;
INFLAMMATORY-BOWEL-DISEASE; SEVERE HUMAN MALARIA; FDG-PET;
ANTIRETROVIRAL TREATMENT; COMPUTED-TOMOGRAPHY; CEREBROSPINAL-FLUID;
PRIMATE MODEL; CANCER-CELLS
AB The global battle against HIV-1 would benefit from a sensitive and specific radiopharmaceutical to localize HIV-infected cells. Ideally, this probe would be able to identify latently infected host cells containing replication competent HIV sequences. Clinical and research applications would include assessment of reservoirs, informing clinical management by facilitating assessment of burden of infection in different compartments, monitoring disease progression and monitoring response to therapy. A "rational" development approach could facilitate efficient identification of an appropriate targeted radiopharmaceutical. Rational development starts with understanding characteristics of the disease that can be effectively targeted and then engineering radiopharmaceuticals to hone in on an appropriate target, which in the case of HIV-1 (HIV) might be an HIV-specific product on or in the host cell, a differentially expressed gene product, an integrated DNA sequence specific enzymatic activity, part of the inflammatory response, or a combination of these. This is different from the current approach that starts with a radiopharmaceutical for a target associated with a disease, mostly from autopsy studies, without a strong rationale for the potential to impact patient care. At present, no targeted therapies are available for HIV latency, although a number of approaches are under study. Here we discuss requirements for a radiopharmaceutical useful in strategies targeting persistently infected cells. The radiopharmaceutical for HIV should be developed based on HIV biology, studied in an animal model and then in humans, and ultimately used in clinical and research settings. Published by Elsevier Inc.
C1 [Lau, Chuen-Yen; Maldarelli, Frank; Neumann, Ronald D.] NIH, Bethesda, MD 20892 USA.
RP Lau, CY (reprint author), NIAID, Collaborat Clin Res Branch, Div Clin Res, NIH, 6700 B Rockledge Dr,Room 1112, Bethesda, MD 20817 USA.
EM lauc@mail.nih.gov
FU National Institute of Allergy and Infectious Disease of the National
Institutes of Health
FX The National Institute of Allergy and Infectious Disease of the National
Institutes of Health supported this publication. Content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 86
TC 2
Z9 2
U1 2
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
EI 1872-9614
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD APR
PY 2014
VL 41
IS 4
BP 299
EP 308
DI 10.1016/j.nucmedbio.2014.01.005
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AD7JC
UT WOS:000333439100002
PM 24607432
ER
PT J
AU Chien, WWD
Leiding, JW
Hsu, AP
Zalewski, C
King, K
Holland, SM
Brewer, C
AF Chien, Wade Wei-De
Leiding, Jennifer W.
Hsu, Amy P.
Zalewski, Christopher
King, Kelly
Holland, Steven M.
Brewer, Carmen
TI Auditory and Vestibular Phenotypes Associated With GATA3 Mutation
SO OTOLOGY & NEUROTOLOGY
LA English
DT Article
DE Hearing loss; Hypothyroidism, deafness, and renal dysplasia syndrome;
GATA3; Hypoparathyroidism; Sensorineural hearing loss; Renal dysplasia
ID RENAL DYSPLASIA SYNDROME; HDR SYNDROME; SENSORINEURAL DEAFNESS;
HEARING-LOSS; HYPOPARATHYROIDISM; PATIENT; FAMILY; HAPLOINSUFFICIENCY;
DELETION; GENE
AB Objective
To report the auditory and vestibular phenotypes of patients with GATA3 mutation.
Study Design
Case series of 6 patients.
Setting
Tertiary referral center.
Patients
All patients had the classic triad of GATA3 deficiency: hypoparathyroidism, hearing loss, and renal dysplasia.
Patients (29-60 yr old; mean age, 42.5 yr; 3 male and 3 female subjects) were confirmed to have heterozygous mutations involving GATA3 by Sanger sequencing.
Interventions
Behavioral audiometry, distortion product otoacoustic emissions (DPOAEs), and auditory brainstem responses (ABRs) were used to assess hearing. Rotational vestibular testing was used to assess vestibular function.
Results
All patients with GATA3 mutation presented with hearing loss during childhood. The mean 3-frequency (0.5/1/2 kHz) pure tone average was 67 dB HL (range, 50-83 dB HL; SD, 9.3). The average speech discrimination score was 73% (range, 36%-100%; SD, 15.9). DPOAEs were absent in all patients. ABRs were remarkably robust and provided no evidence of retrocochlear dysfunction. Some patients complained of dizziness, but rotary chair testing was normal across participants for whom testing occurred.
Conclusion
Patients with GATA3 mutation present with early-onset sensorineural hearing loss (SNHL). DPOAEs were absent, supporting outer hair cell dysfunction, whereas ABRs were present and robust. Rotational vestibular testing revealed no evidence of abnormal horizontal semicircular canal function.
C1 [Chien, Wade Wei-De; Zalewski, Christopher; King, Kelly; Brewer, Carmen] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA.
[Leiding, Jennifer W.; Hsu, Amy P.; Holland, Steven M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Chien, Wade Wei-De] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA.
RP Chien, WWD (reprint author), Johns Hopkins Sch Med, Dept Otolaryngol, Baltimore, MD 21205 USA.
EM wchien1@jhmi.edu
FU National Institute on Deafness and Other Communication Disorders;
National Institute of Allergy and Infectious Diseases
FX The authors thank the National Institute on Deafness and Other
Communication Disorders and National Institute of Allergy and Infectious
Diseases intramural research funds for their support.
NR 24
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1531-7129
EI 1537-4505
J9 OTOL NEUROTOL
JI Otol. Neurotol.
PD APR
PY 2014
VL 35
IS 4
BP 577
EP 581
DI 10.1097/MAO.0000000000000238
PG 5
WC Clinical Neurology; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA AD6SH
UT WOS:000333390700009
PM 24622013
ER
PT J
AU Colloca, L
AF Colloca, Luana
TI Emotional modulation of placebo analgesia
SO PAIN
LA English
DT Editorial Material
ID PAIN
C1 [Colloca, Luana] NIMH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
[Colloca, Luana] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Colloca, L (reprint author), NIMH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
EM luana.colloca@nih.gov
OI Colloca, Luana/0000-0002-6503-4709
FU Intramural NIH HHS [Z99 AT999999]
NR 8
TC 2
Z9 2
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
EI 1872-6623
J9 PAIN
JI Pain
PD APR
PY 2014
VL 155
IS 4
BP 651
EP 651
DI 10.1016/j.pain.2014.01.009
PG 1
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA AD2YG
UT WOS:000333102400002
PM 24447512
ER
PT J
AU Mitchell, K
Lebovitz, EE
Keller, JM
Mannes, AJ
Nemenov, MI
Iadarola, MJ
AF Mitchell, Kendall
Lebovitz, Evan E.
Keller, Jason M.
Mannes, Andrew J.
Nemenov, Michael I.
Iadarola, Michael J.
TI Nociception and inflammatory hyperalgesia evaluated in rodents using
infrared laser stimulation after Trpv1 gene knockout or resiniferatoxin
lesion
SO PAIN
LA English
DT Article
DE Nociception; Analgesia; Chemoreceptors; Chronic Pain; Capsaicin
ID PRIMARY AFFERENT NEURONS; A-DELTA-FIBER; CAPSAICIN RECEPTOR VR1;
DORSAL-ROOT GANGLION; POSITIVE ALLOSTERIC MODULATION; PRIMARY
SOMATOSENSORY CORTEX; RAT SPINAL-CORD; C-FIBER; BREAKTHROUGH PAIN;
DIRECT PHOSPHORYLATION
AB TRPV1 is expressed in a subpopulation of myelinated A delta and unmyelinated C-fibers. TRPV1(+) fibers are essential for the transmission of nociceptive thermal stimuli and for the establishment and maintenance of inflammatory hyperalgesia. We have previously shown that high-power, short-duration pulses from an infrared diode laser are capable of predominantly activating cutaneous TRPV1(+) A delta-fibers. Here we show that stimulating either subtype of TRPV1(+) fiber in the paw during carrageenan-induced inflammation or following hind-paw incision elicits pronounced hyperalgesic responses, including prolonged paw guarding. The ultrapotent TRPV1 agonist resiniferatoxin (RTX) dose-dependently deactivates TRPV1(+) fibers and blocks thermal nociceptive responses in baseline or inflamed conditions. Injecting sufficient doses of RTX peripherally renders animals unresponsive to laser stimulation even at the point of acute thermal skin damage. In contrast, Trpv1-/- mice, which are generally unresponsive to noxious thermal stimuli at lower power settings, exhibit withdrawal responses and inflammation-induced sensitization using high-power, short duration A delta stimuli. In rats, systemic morphine suppresses paw withdrawal, inflammatory guarding, and hyperalgesia in a dose-dependent fashion using the same A delta stimuli. The qualitative intensity of A delta responses, the leftward shift of the stimulus-response curve, the increased guarding behaviors during carrageenan inflammation or after incision, and the reduction of A delta responses with morphine suggest multiple roles for TRPV1(+) A delta fibers in nociceptive processes and their modulation of pathological pain conditions. (C) 2014 Published by Elsevier B.V. on behalf of International Association for the Study of Pain.
C1 [Lebovitz, Evan E.; Mannes, Andrew J.; Iadarola, Michael J.] NIH, Dept Perioperat Med, Ctr Clin, Bethesda, MD 20892 USA.
[Nemenov, Michael I.] Stanford Univ, Dept Anesthesia, Palo Alto, CA 94304 USA.
[Nemenov, Michael I.] Lasmed LLC, Mountain View, CA USA.
[Mitchell, Kendall; Lebovitz, Evan E.; Keller, Jason M.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA.
RP Iadarola, MJ (reprint author), NIH, Dept Perioperat Med, Ctr Clin, Bldg 10,Room 2C401,10 Ctr Dr,MSC 1510, Bethesda, MD 20892 USA.
EM michael.iadarola@nih.gov
FU Intramural Research Programs of the Clinical Center, National Institutes
of Health; National Institute of Dental and Craniofacial Research,
National Institutes of Health
FX This research was supported by the Intramural Research Programs of the
Clinical Center, National Institutes of Health, and by the National
Institute of Dental and Craniofacial Research, National Institutes of
Health. We thank Brian Bates for his expert technical assistance in
parts of this work.
NR 80
TC 14
Z9 15
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
EI 1872-6623
J9 PAIN
JI Pain
PD APR
PY 2014
VL 155
IS 4
BP 733
EP 745
DI 10.1016/j.pain.2014.01.007
PG 13
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA AD2YG
UT WOS:000333102400013
PM 24434730
ER
PT J
AU McCrindle, BW
Zak, V
Breitbart, RE
Mahony, L
Shrader, P
Lai, WW
Burns, KM
Colan, SD
Williams, RV
Goldberg, D
Hill, KD
Khaikin, S
Atz, AM
AF McCrindle, Brian W.
Zak, Victor
Breitbart, Roger E.
Mahony, Lynn
Shrader, Peter
Lai, Wyman W.
Burns, Kristin M.
Colan, Steven D.
Williams, Richard V.
Goldberg, David
Hill, Kevin D.
Khaikin, Svetlana
Atz, Andrew M.
CA Pediatric Heart Network
TI The Relationship of Patient Medical and Laboratory Characteristics to
Changes in Functional Health Status in Children and Adolescents After
the Fontan Procedure
SO PEDIATRIC CARDIOLOGY
LA English
DT Article
DE Fontan procedure; Heart defects; Congenital; Pediatrics; Functional
health status
ID QUALITY-OF-LIFE; EXERCISE PERFORMANCE; ARTERIAL STIFFNESS;
PEDIATRIC-PATIENTS; FAILING FONTAN; HEART-DISEASE; OPERATION; IMPACT;
TRANSPLANTATION; MULTICENTER
AB Despite hypothesized concerns about deterioration beginning in adolescence, longitudinal data and associated factors regarding standardized assessment of physical functioning are not available for Fontan patients. Parents who participated in the Fontan Cross-Sectional Study completed the Child Health Questionnaire at 2 time points for 245 subjects ages 6-18 years. Associations between change in Physical Functioning Summary Score and baseline patient, medical, and laboratory characteristics (mean age 9.5 +/- A 1.7 years) and follow-up patient and medical characteristics (mean age 16.2 +/- A 1.6 years) were determined by regression analyses. During a mean of 6.7 +/- A 0.4 years, a small (not clinically important) but statistically significant decrease in score from 46.2 +/- A 11.7 to 44.5 +/- A 12.1 (p < 0.03) was noted. Subjects with higher baseline scores had a greater decrease in score (r = -0.48; p < 0.001). A multivariable model of patient and medical characteristics (R (2) = 0.11) showed that a greater decrease in score was significantly associated with interim development of asthma (n = 13; parameter estimate [PE] -6.6; p < 0.05) or other chronic respiratory, lung, or breathing problems (n = 13; PE -12.5; p < 0.001) and the presence of protein-losing enteropathy at any time (n = 12; PE -9.4; p = 0.006). Change in score was not significantly associated with baseline laboratory measures of exercise capacity and ventricular characteristics and function. Therefore, although physical functioning may be stable during adolescence for many Fontan patients, deterioration occurs in some in association with respiratory conditions and protein-losing enteropathy. Further longitudinal study is necessary to better understand the relationship between clinical morbidities and functional health status as these patients transition into adulthood.
C1 [McCrindle, Brian W.; Khaikin, Svetlana] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Zak, Victor; Shrader, Peter] New England Res Inst, Watertown, MA 02172 USA.
[Breitbart, Roger E.; Colan, Steven D.] Boston Childrens Hosp, Boston, MA USA.
[Mahony, Lynn] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Lai, Wyman W.] Columbia Univ, Med Ctr, New York, NY USA.
[Burns, Kristin M.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Williams, Richard V.] Univ Utah, Salt Lake City, UT USA.
[Goldberg, David] Childrens Hosp Philadelphia, Phladelphia, PA USA.
[Hill, Kevin D.] Duke Univ, Med Ctr, Durham, NC USA.
[Atz, Andrew M.] Med Univ S Carolina, Charleston, SC 29425 USA.
RP McCrindle, BW (reprint author), Univ Toronto, Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
EM brian.mccrindle@sickkids.ca
FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279,
HL068281, HL068285, HL068292, HL068290, HL068288]
FX See online data supplement for a complete list of investigators.
Supported by U01 grants from the National Heart, Lung, and Blood
Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292,
HL068290, and HL068288). Its contents are solely the responsibility of
the investigators and do not necessarily represent the official views of
National Heart, Lung and Blood Institute or the National Institutes of
Health.
NR 41
TC 2
Z9 2
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0172-0643
EI 1432-1971
J9 PEDIATR CARDIOL
JI Pediatr. Cardiol.
PD APR
PY 2014
VL 35
IS 4
BP 632
EP 640
DI 10.1007/s00246-013-0831-0
PG 9
WC Cardiac & Cardiovascular Systems; Pediatrics
SC Cardiovascular System & Cardiology; Pediatrics
GA AD3SD
UT WOS:000333165400011
PM 24264999
ER
PT J
AU Tamura, D
DiGiovanna, JJ
Khan, SG
Kraemer, KH
AF Tamura, Deborah
DiGiovanna, John J.
Khan, Sikandar G.
Kraemer, Kenneth H.
TI Living with xeroderma pigmentosum: comprehensive photoprotection for
highly photosensitive patients
SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE
LA English
DT Review
DE DNA repair; genetic disease; skin cancer; sun protection; xeroderma
pigmentosum
ID DNA-REPAIR DEFICIENCY; OCULAR MANIFESTATIONS; NEUROLOGICAL DISEASE;
COCKAYNE-SYNDROME; TRICHOTHIODYSTROPHY; DISORDERS; EUROPE
AB Xeroderma pigmentosum (XP) is a rare autosomal recessive disease of deoxyribonucleic acid (DNA) repair with ultraviolet (UV) radiation sensitivity and a 10000-fold increased risk of skin cancer. Symptoms include: freckle-like pigmentation in sun-exposed skin before age 2 years, severe burns after minimal sun exposure (50% of patients) and damage to exposed surfaces of the eyes with loss of vision and ocular cancer. About 25% of patients develop a progressive neurodegeneration. The combination of an inherited inability to repair UV-induced DNA damage and environmental exposure to UV must occur for cutaneous and ocular symptoms to develop. There is no cure for XP, but many of its manifestations may be reduced or prevented through consistent UV protection; thus XP serves as a model for sun protection of patients with marked photosenstivity. Sun protective clothing including hats, sunglasses and face shields, sun screen lotions and avoidance of environmental sources of UV are cornerstones of prevention of skin and eye damage and cancer. Although XP is a serious disease with the potential for limitation of life expectancy, XP patients can live active lives while at the same time avoiding UV.
C1 [Tamura, Deborah; DiGiovanna, John J.; Khan, Sikandar G.; Kraemer, Kenneth H.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kraemer, KH (reprint author), NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res, Bldg 37 Room 4002,MSC 4258, Bethesda, MD 20892 USA.
EM kraemerk@nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX We would like to thank the XP patients, families and support groups for
their ongoing help and participation in our studies. This research was
supported by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 27
TC 7
Z9 7
U1 1
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0905-4383
EI 1600-0781
J9 PHOTODERMATOL PHOTO
JI Photodermatol. Photoimmunol. Photomed.
PD APR
PY 2014
VL 30
IS 2-3
BP 146
EP 152
DI 10.1111/phpp.12108
PG 7
WC Dermatology
SC Dermatology
GA AB8XO
UT WOS:000332073500011
PM 24417420
ER
PT J
AU Kiyatkin, EA
AF Kiyatkin, Eugene A.
TI Critical role of peripheral sensory systems in mediating the neural
effects of nicotine following its acute and repeated exposure
SO REVIEWS IN THE NEUROSCIENCES
LA English
DT Article
DE learning; metabolic brain activation; neuronal activation; peripheral
action of nicotine; pharmacological or within-drug conditioning; sensory
signal
ID INTRAVENOUS NICOTINE; LOCOMOTOR-ACTIVITY; NERVE-ENDINGS; DRUG-ACTION;
SENSITIZATION; DOPAMINE; BRAIN; RATS; SMOKING; TEMPERATURE
AB It is well established that the reinforcing properties of nicotine (NIC) depend on its action on nicotinic acetylcholine receptors expressed by brain neurons. However, when administered systemically, NIC first phasically activates nicotinic receptors located on the afferents of sensory nerves at the sites of drug administration before reaching the brain and directly interacting with central neurons. While this peripheral action of NIC has been known for years, it is usually neglected in any consideration of the drug's reinforcing properties and experiencedependent changes of its behavioral and physiological effects. The goal of this work was to review our recent behavioral, electrophysiological, and physiological data suggesting the critical importance of peripheral actions of NIC in mediating its neural effects following acute drug exposure and their involvement in alterations of NIC effects consistently occurring following repeated drug exposure. Because NIC, by acting peripherally, produces a rapid sensory signal to the central nervous system that is followed by slower, more prolonged direct drug actions in the brain, these two pharmacological actions interact in the central nervous system during repeated drug use with the development of Pavlovian conditioned association. This within-drug conditioning mechanism could explain the experience-dependent changes in the physiological, behavioral, and human psychoemotional effects of NIC, which, in drug-experienced individuals, always represent a combination of pharmacological and learning variables.
C1 NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA.
RP Kiyatkin, EA (reprint author), NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM ekiyatki@intra.nida.nih.gov
FU Intramural Research Program of NIDA-IRP
FX This study was supported by the Intramural Research Program of NIDA-IRP.
The author greatly appreciates the editorial assistance of Drs. Ken
Wakabayashi and Mary Pfeiffer.
NR 52
TC 0
Z9 0
U1 2
U2 7
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0334-1763
EI 1607-8470
J9 REV NEUROSCIENCE
JI Rev. Neurosci.
PD APR
PY 2014
VL 25
IS 2
BP 207
EP 221
DI 10.1515/revneuro-2013-0067
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA AD3YU
UT WOS:000333183200003
PM 24535300
ER
PT J
AU Vedham, V
Divi, RL
Starks, VL
Verma, M
AF Vedham, Vidya
Divi, Rao L.
Starks, Vaurice L.
Verma, Mukesh
TI Multiple Infections and Cancer: Implications in Epidemiology
SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT
LA English
DT Article
DE Cancer; Co-infection; Biomarkers; Cofactors; AIDS-related malignancies;
Targeted therapy; Vaccines
ID EPSTEIN-BARR-VIRUS; HEPATITIS-C-VIRUS; HELICOBACTER-PYLORI INFECTION;
CHLAMYDIA-TRACHOMATIS INFECTION; HUMAN-PAPILLOMAVIRUS INFECTION;
HUMAN-IMMUNODEFICIENCY-VIRUS; INVASIVE CERVICAL-CANCER; RECOMBINANT
VACCINE GARDASIL(R); ENDEMIC BURKITTS-LYMPHOMA; CHRONIC LIVER-DISEASE
AB Approximately 18% of the global cancer burden has been attributed to infectious agents, with estimates ranging from 7% in developed countries to about 22% in developing countries. Chronic infections caused by the hepatitis B and C viruses, human papilloma viruses (HPV), and Helicobacter pylori (H. pylori) are reported to be responsible for approximately 15% of all human cancers. Interestingly, although many of the infectious agents that have been associated with cancer-such as HPV, Epstein-Barr virus (EBV), and H. pylori-are highly prevalent in the world, most infected individuals do not develop cancer but remain lifelong carriers. Malignancies associated with infectious agents may result from prolonged latency as a result of chronic infections. Pathogenic infections are necessary but are not sufficient for cancer initiation or progression. Cancer initiation may require additional cofactors, including secondary infections. Therefore, in patients with chronic infection with one agent, secondary co-infection with another agent may serve as an important co-factor that may cause cancer initiation and progression. Additionally, opportunistic co-infections could significantly inhibit response to cancer treatment and increase cancer mortality. Co-infections are relatively common in areas with a high prevalence of infectious agents, especially in developing countries. These co-infections can cause an imbalance in the host immune system by affecting persistence of and susceptibility to malignant infections. Several articles have been published that focus on infectious agents and cancer. In this article, we discuss the role of infectious agents in malignancies, highlight the role of multiple/co-infections in cancer etiology, and review implications for cancer epidemiology.
C1 [Vedham, Vidya; Divi, Rao L.; Starks, Vaurice L.; Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA.
RP Verma, M (reprint author), NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, 6130 Execut Blvd,Suite 5100, Bethesda, MD 20892 USA.
EM vermam@mail.nih.gov
NR 256
TC 5
Z9 5
U1 1
U2 27
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1533-0346
EI 1533-0338
J9 TECHNOL CANCER RES T
JI Technol. Cancer Res. Treat.
PD APR
PY 2014
VL 13
IS 2
BP 177
EP 194
DI 10.7785/tcrt.2012.500366
PG 18
WC Oncology
SC Oncology
GA AD4NC
UT WOS:000333226800010
PM 23919392
ER
PT J
AU Rao, DB
Little, PB
Sills, RC
AF Rao, Deepa B.
Little, Peter B.
Sills, Robert C.
TI Subsite Awareness in Neuropathology Evaluation of National Toxicology
Program (NTP) Studies: A Review of Select Neuroanatomical Structures
with Their Functional Significance in Rodents
SO TOXICOLOGIC PATHOLOGY
LA English
DT Review
DE neuropathology; neuroanatomy; NTP; brain; spinal cord; nerve; functional
neuroanatomy
ID CENTRAL-NERVOUS-SYSTEM; DEFICIT HYPERACTIVITY DISORDER; CARBON-DISULFIDE
NEUROTOXICITY; AMYOTROPHIC-LATERAL-SCLEROSIS; WHITE-MATTER
ABNORMALITIES; NASAL DRUG-DELIVERY; RAT-BRAIN; OLFACTORY-BULB; AREA
POSTREMA; SUPERIOR COLLICULUS
AB This review article is designed to serve as an introductory guide in neuroanatomy for toxicologic pathologists evaluating general toxicity studies. The article provides an overview of approximately 50 neuroanatomical subsites and their functional significance across 7 transverse sections of the brain. Also reviewed are 3 sections of the spinal cord, cranial and peripheral nerves (trigeminal and sciatic, respectively), and intestinal autonomic ganglia. The review is limited to the evaluation of hematoxylin and eosin-stained tissue sections, as light microscopic evaluation of these sections is an integral part of the first-tier toxicity screening of environmental chemicals, drugs, and other agents. Prominent neuroanatomical sites associated with major neurological disorders are noted. This guide, when used in conjunction with detailed neuroanatomic atlases, may aid in an understanding of the significance of functional neuroanatomy, thereby improving the characterization of neurotoxicity in general toxicity and safety evaluation studies.
C1 [Rao, Deepa B.] Integrated Lab Syst Inc, Res Triangle Pk, NC USA.
[Little, Peter B.] Expt Pathol Labs Inc, Res Triangle Pk, NC USA.
[Sills, Robert C.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Rao, DB (reprint author), NIEHS, POB 12233,MS B3-06,111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM sills@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
research was supported (in part) by the Intramural Research Program of
the NIH, National Institute of Environmental Health Sciences.
NR 144
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U1 1
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PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD APR
PY 2014
VL 42
IS 3
BP 487
EP 509
DI 10.1177/0192623313501893
PG 23
WC Pathology; Toxicology
SC Pathology; Toxicology
GA AD3ML
UT WOS:000333143100003
PM 24135464
ER
PT J
AU Bhusari, S
Malarkey, DE
Hong, HH
Wang, Y
Masinde, T
Nolan, M
Hooth, MJ
Lea, IA
Vasconcelos, D
Sills, RC
Hoenerhoff, MJ
AF Bhusari, Sachin
Malarkey, David E.
Hong, Hue-Hua
Wang, Yu
Masinde, Tiwanda
Nolan, Michael
Hooth, Michelle J.
Lea, Isabel A.
Vasconcelos, Daphne
Sills, Robert C.
Hoenerhoff, Mark J.
TI Mutation Spectra of Kras and Tp53 in Urethral and Lung Neoplasms in
B6C3F1 Mice Treated with 3,3 ',4,4 '-Tetrachloroazobenzene
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE environmental toxicology; agricultural products; animal models;
carcinogenesis; genotoxins; nongenotoxins; mechanisms of toxicity;
molecular pathology
ID URINARY-BLADDER CANCER; UROPLAKIN GENE-EXPRESSION; P53 GENE; CELL
CARCINOMA; MOUSE; TUMORS; RATS; N-BUTYL-N-(4-HYDROXYBUTYL)NITROSAMINE;
3,4-DICHLOROANILINE; OVEREXPRESSION
AB 3,3,4,4-tetrachloroazobenzene (TCAB) is a contaminant formed during manufacture of various herbicide compounds. A recent National Toxicology Program study showed B6C3F1 mice exposed to TCAB developed a treatment-related increase in lung carcinomas in the high-dose group, and urethral carcinomas, an extremely rare lesion in rodents, in all dose groups. As the potential for environmental exposure to TCAB is widespread, and the mechanisms of urethral carcinogenesis are unknown, TCAB-induced urethral and pulmonary tumors were evaluated for alterations in critical human cancer genes, Kras and Tp53. Uroplakin III, CK20, and CK7 immunohistochemistry was performed to confirm the urothelial origin of urethral tumors. TCAB-induced urethral carcinomas harbored transforming point mutations in K-ras (38%) and Tp53 (63%), and 71% displayed nuclear TP53 expression, consistent with formation of mutant protein. Transition mutations accounted for 88% of Tp53 mutations in urethral carcinomas, suggesting that TCAB or its metabolites target guanine or cytosine bases and that these mutations are involved in urethral carcinogenesis. Pulmonary carcinomas in TCAB-exposed animals harbored similar rates of Tp53 (55%) and Kras (36%) mutations as urethral carcinomas, suggesting that TCAB may induce mutations at multiple sites by a common mechanism. In conclusion, TCAB is carcinogenic at multiple sites in male and female B6C3F1 mice through mechanisms involving Tp53 and Kras mutation.
C1 [Bhusari, Sachin; Malarkey, David E.; Hong, Hue-Hua; Wang, Yu; Masinde, Tiwanda; Sills, Robert C.; Hoenerhoff, Mark J.] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Nolan, Michael] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA.
[Hooth, Michelle J.] NIEHS, Toxicol Branch, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Lea, Isabel A.] Integrated Lab Syst Inc, Res Triangle Pk, NC USA.
[Vasconcelos, Daphne] Toxicol Battelle Columbus, Battelle Mem Inst, Columbus, OH USA.
RP Hoenerhoff, MJ (reprint author), NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, Bldg 101,B350 MSC B3-06,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM hoenerhm@niehs.nih.gov
FU National Institutes of Environmental Health Sciences (NIEHS), National
Institutes of Health (NIH); The Division of the National Toxicology
Program (DNTP)
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This work
was supported by the National Institutes of Environmental Health
Sciences (NIEHS), National Institutes of Health (NIH), and The Division
of the National Toxicology Program (DNTP).
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U1 0
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PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD APR
PY 2014
VL 42
IS 3
BP 555
EP 564
DI 10.1177/0192623313491169
PG 10
WC Pathology; Toxicology
SC Pathology; Toxicology
GA AD3ML
UT WOS:000333143100007
PM 23703846
ER
PT J
AU Dunnick, JK
Brix, A
Sanders, JM
Travlos, GS
AF Dunnick, June K.
Brix, A.
Sanders, J. M.
Travlos, G. S.
TI N,N-Dimethyl-p-toluidine, a Component in Dental Materials, Causes
Hematologic Toxic and Carcinogenic Responses in Rodent Model Systems
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE N,N-dimethyl-p-toluidine; carcinogenic effects; hematologic toxicity
ID ZERO DOSE CONTROL; F344 RATS; MEDICAL DEVICES; BONE CEMENTS;
METHEMOGLOBINEMIA; METABOLITES; ANTIOXIDANTS; DISPOSITION; INGESTION;
MICE
AB Because of the potential for exposure to N,N-dimethyl-p-toluidine (DMPT) in medical devices and the lack of toxicity and carcinogenicity information available in the literature, the National Toxicology Program conducted toxicity and carcinogenicity studies of DMPT in male and female F344/N rats and B6C3F1/N mice. In these studies, a treatment-related macrocytic regenerative anemia characterized by increased levels of methemoglobin and Heinz body formation developed within a few weeks of DMPT exposure in rats and mice. DMPT induced nasal cavity, splenic, and liver toxicity in rats and mice at 3 months and 2 years. DMPT carcinogenic effects were seen in the liver of male and female rats and mice, the nasal cavity of male and female rats, and the lung and forestomach of female mice. In rodents, DMPT is distributed to many of the sites where toxic and carcinogenic effects occurred. DMPT-induced oxidative damage at these target sites may be one mechanism for the treatment-related lesions. Methemoglobinemia, as seen in these DMPT studies, is caused by oxidation of the heme moiety, and this end point served as an early alert for other target organ toxicities and carcinogenic responses that followed with longer term exposure.
C1 [Dunnick, June K.; Brix, A.; Sanders, J. M.; Travlos, G. S.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Dunnick, JK (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM dunnickj@niehs.nih.gov
FU National Institute of Environmental Health Sciences (NIEHS), Research
Triangle Park, NC
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This work
was supported by the intramural program of the National Institute of
Environmental Health Sciences (NIEHS), Research Triangle Park, NC.
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PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD APR
PY 2014
VL 42
IS 3
BP 603
EP 615
DI 10.1177/0192623313489604
PG 13
WC Pathology; Toxicology
SC Pathology; Toxicology
GA AD3ML
UT WOS:000333143100012
PM 23867143
ER
PT J
AU Smith, MJ
Brown, JM
Zamboni, WC
Walker, NJ
AF Smith, Matthew J.
Brown, Jared M.
Zamboni, William C.
Walker, Nigel J.
TI From Immunotoxicity to Nanotherapy: The Effects of Nanomaterials on the
Immune System
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE nanomaterials; immune system; immunotoxicity; mast cells; drug carrier
agents
ID TITANIUM-DIOXIDE NANOPARTICLES; MULTIWALLED CARBON NANOTUBES;
MAST-CELLS; IN-VITRO; INFLAMMATORY RESPONSES; PULMONARY EXPOSURE; TIO2
NANOPARTICLES; DENDRITIC CELLS; IL-33/ST2 AXIS; B6C3F1 MOUSE
AB The potential for human exposure to the diverse and ever-changing world of nanoscale materials has raised concerns about their influence on health and disease. The novel physical and chemical properties of these materials, which are associated with their small size, complicate toxicological evaluations. Further, these properties may make engineered nanomaterials (ENMs) a prime target for interaction with the immune system following uptake by phagocytes. Undesired effects on antigen-presenting cells and other phagocytic cells are of concern due to the high likelihood of ENM uptake by these cells. In addition, ENM interactions with lymphocytes and other cell types can contribute to a varied spectrum of possible effects, including inflammation, hypersensitivity, and immunomodulation. Furthermore, the mast cell (a type of immune cell traditionally associated with allergy) appears to contribute to certain inflammatory and toxic effects associated with some ENMs. Although incidental exposure may be undesirable, nanomedicines engineered for various clinical applications provide opportunities to develop therapies that may or may not intentionally target the immune system. The interaction between ENMs and the immune system and the resulting pharmacokinetic and phenotypic responses are critical factors that dictate the balance between toxicity and clinical efficacy of nanotherapeutics.
C1 [Smith, Matthew J.] ImmunoTox Inc, Richmond, VA 23219 USA.
[Smith, Matthew J.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23284 USA.
[Brown, Jared M.] Univ Colorado, Skaggs Sch Pharm, Dept Pharmaceut Sci, Aurora, CO 80045 USA.
[Zamboni, William C.] Univ N Carolina, UNC Inst Individualized Therapy & Pharmacogen, Carolina Ctr Canc Nanotechnol Excellence, Eshelman Sch Pharm,UNC Lineberger Comprehens Canc, Chapel Hill, NC 27599 USA.
[Walker, Nigel J.] NIEHS, Div Natl Toxicol Program NTP, NIH, Res Triangle Pk, NC 27709 USA.
RP Smith, MJ (reprint author), POB 326, Dinwiddie, VA 23841 USA.
EM drmatthewjsmith@gmail.com
RI Walker, Nigel/D-6583-2012
OI Walker, Nigel/0000-0002-9111-6855
FU National Institute of Environmental Health Sciences [NIEHS-N01-ES-55538,
NIEHS-R01-ES-019311, NIEHS-U19-ES019525]; National Institute of Health
[NIH/NCI 1-U54-CA151652-01, NIH/NCI 2-P30-CA016086]; UNC University
Cancer Research Fund; Lilly Research Awards Program (LRAP)
FX National Institute of Environmental Health Sciences (NIEHS-N01-ES-55538
to M.J.S., NIEHS-R01-ES-019311 and NIEHS-U19-ES019525 to J.M.B.);
National Institute of Health (NIH/NCI 1-U54-CA151652-01, NIH/NCI
2-P30-CA016086, and NIH/NCI 1-U54-CA151652-01 to W.C.Z); UNC University
Cancer Research Fund (W.C.Z.); Lilly Research Awards Program (LRAP) 2013
(W.C.Z.).
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PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD APR
PY 2014
VL 138
IS 2
BP 249
EP 255
DI 10.1093/toxsci/kfu005
PG 7
WC Toxicology
SC Toxicology
GA AD5LE
UT WOS:000333293500001
PM 24431216
ER
PT J
AU Ngalame, NNO
Tokar, EJ
Person, RJ
Xu, YY
Waalkes, MP
AF Ngalame, Ntube N. O.
Tokar, Erik J.
Person, Rachel J.
Xu, Yuanyuan
Waalkes, Michael P.
TI Aberrant microRNA Expression Likely Controls RAS Oncogene Activation
During Malignant Transformation of Human Prostate Epithelial and Stem
Cells by Arsenic
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE arsenic; prostate cells; stem; progenitor cells; microRNA; KRAS; cancer
ID CANCER STEM/PROGENITOR CELLS; DOWN-REGULATION; PTEN; PROGRESSION; MICE;
DIFFERENTIATION; METASTASIS; INITIATION; DELETION; EXPOSURE
AB Inorganic arsenic (iAs), a human carcinogen, potentially targets the prostate. iAs malignantly transforms the RWPE-1 human prostate epithelial line to CAsE-PE cells, and a derivative normal stem cell (SC) line, WPE-stem, to As-Cancer SC (As-CSC) line. MicroRNAs (miRNA) are noncoding but exert negative control on expression by degradation or translational repression of target mRNAs. Aberrant miRNA expression is important in carcinogenesis. A miRNA array of CAsE-PE and As-CSC revealed common altered expression in both for pathways concerning oncogenesis, miRNA biogenesis, cell signaling, proliferation, and tumor metastasis and invasion. The KRAS oncogene is overexpressed in CAsE-PE cells but not by mutation or promoter hypomethylation, and is intensely overexpressed in As-CSC cells. In both transformants, decreased miRNAs targeting KRAS and RAS superfamily members occurred. Reduced miR-134, miR-373, miR-155, miR-138, miR-205, miR-181d, miR-181c, and let-7 in CAsE-PE cells correlated with increased target RAS oncogenes, RAN, RAB27A, RAB22A mRNAs, and KRAS protein. Reduced miR-143, miR-34c-5p, and miR-205 in As-CSC correlated with increased target RAN mRNA, and KRAS, NRAS, and RRAS proteins. The RAS/ERK and PI3K/PTEN/AKT pathways control cell survival, differentiation, and proliferation, and when dysregulated promote a cancer phenotype. iAs transformation increased expression of activated ERK kinase in both transformants and altered components of the PI3K/PTEN/AKT pathway including decreased PTEN and increases in BCL2, BCL-X-L, and VEGF in the absence of AKT activation. Thus, dysregulated miRNA expression may be linked to RAS activation in both transformants.
C1 [Ngalame, Ntube N. O.; Tokar, Erik J.; Person, Rachel J.; Xu, Yuanyuan; Waalkes, Michael P.] NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program Lab, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Waalkes, MP (reprint author), NIEHS, Div Natl Toxicol Program Lab, DNTP, 111 TW Alexander Dr,MD E1-07, Res Triangle Pk, NC 27709 USA.
EM waalkes@niehs.nih.gov
FU National Institute of Environmental Health Sciences of the National
Institutes of Health
FX National Institute of Environmental Health Sciences of the National
Institutes of Health.
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PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD APR
PY 2014
VL 138
IS 2
BP 268
EP 277
DI 10.1093/toxsci/kfu002
PG 10
WC Toxicology
SC Toxicology
GA AD5LE
UT WOS:000333293500003
PM 24431212
ER
PT J
AU Smith, DL
Perkins, TA
Reiner, RC
Barker, CM
Niu, TC
Chaves, LF
Ellis, AM
George, DB
Le Menach, A
Pulliam, JRC
Bisanzio, D
Buckee, C
Chiyaka, C
Cummings, DAT
Garcia, AJ
Gatton, ML
Gething, PW
Hartley, DM
Johnston, G
Klein, EY
Michael, E
Lloyd, AL
Pigott, DM
Reisen, WK
Ruktanonchai, N
Singh, BK
Stoller, J
Tatem, AJ
Kitron, U
Godfray, HCJ
Cohen, JM
Hay, SI
Scott, TW
AF Smith, David L.
Perkins, T. Alex
Reiner, Robert C., Jr.
Barker, Christopher M.
Niu, Tianchan
Chaves, Luis Fernando
Ellis, Alicia M.
George, Dylan B.
Le Menach, Arnaud
Pulliam, Juliet R. C.
Bisanzio, Donal
Buckee, Caroline
Chiyaka, Christinah
Cummings, Derek A. T.
Garcia, Andres J.
Gatton, Michelle L.
Gething, Peter W.
Hartley, David M.
Johnston, Geoffrey
Klein, Eili Y.
Michael, Edwin
Lloyd, Alun L.
Pigott, David M.
Reisen, William K.
Ruktanonchai, Nick
Singh, Brajendra K.
Stoller, Jeremy
Tatem, Andrew J.
Kitron, Uriel
Godfray, H. Charles J.
Cohen, Justin M.
Hay, Simon I.
Scott, Thomas W.
TI Recasting the theory of mosquito-borne pathogen transmission dynamics
and control
SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
DE Dengue; Filariasis; Malaria; Mosquito-borne pathogen transmission;
Vector control; West Nile virus
ID DENGUE VIRUS TRANSMISSION; ENTOMOLOGICAL INOCULATION RATE;
PLASMODIUM-FALCIPARUM MALARIA; MATHEMATICAL-MODELS; HUMAN MOVEMENT;
LYMPHATIC FILARIASIS; POPULATION-DYNAMICS; ANOPHELES-GAMBIAE;
AEDES-AEGYPTI; VECTOR
AB Mosquito-borne diseases pose some of the greatest challenges in public health, especially in tropical and sub-tropical regions of the world. Efforts to control these diseases have been underpinned by a theoretical framework developed for malaria by Ross and Macdonald, including models, metrics for measuring transmission, and theory of control that identifies key vulnerabilities in the transmission cycle. That framework, especially Macdonalds formula for R-0 and its entomological derivative, vectorial capacity, are now used to study dynamics and design interventions for many mosquito-borne diseases. A systematic review of 388 models published between 1970 and 2010 found that the vast majority adopted the RossMacdonald assumption of homogeneous transmission in a well-mixed population. Studies comparing models and data question these assumptions and point to the capacity to model heterogeneous, focal transmission as the most important but relatively unexplored component in current theory. Fine-scale heterogeneity causes transmission dynamics to be nonlinear, and poses problems for modeling, epidemiology and measurement. Novel mathematical approaches show how heterogeneity arises from the biology and the landscape on which the processes of mosquito biting and pathogen transmission unfold. Emerging theory focuses attention on the ecological and social context for mosquito blood feeding, the movement of both hosts and mosquitoes, and the relevant spatial scales for measuring transmission and for modeling dynamics and control.
C1 [Smith, David L.; Cummings, Derek A. T.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA.
[Smith, David L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD USA.
[Smith, David L.; Perkins, T. Alex; Reiner, Robert C., Jr.; Barker, Christopher M.; Niu, Tianchan; Ellis, Alicia M.; George, Dylan B.; Pulliam, Juliet R. C.; Cummings, Derek A. T.; Hartley, David M.; Lloyd, Alun L.; Reisen, William K.; Tatem, Andrew J.; Kitron, Uriel; Hay, Simon I.; Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Smith, David L.; Le Menach, Arnaud; Klein, Eili Y.] Ctr Dis Dynam Econ & Policy, Washington, DC USA.
[Perkins, T. Alex; Reiner, Robert C., Jr.; Scott, Thomas W.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.
[Barker, Christopher M.; Reisen, William K.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA.
[Barker, Christopher M.; Reisen, William K.] Univ Calif Davis, Ctr Vectorborne Dis, Davis, CA 95616 USA.
[Niu, Tianchan] Georgetown Univ, Med Ctr, Div Integrated Biodefense, Washington, DC 20007 USA.
[Chaves, Luis Fernando] Nagasaki Univ, Inst Trop Med NEKKEN, Nagasaki 852, Japan.
[Chaves, Luis Fernando] Univ Nacl, Escuela Med Vet, Programa Invest Enfermedades Trop, Heredia, Costa Rica.
[George, Dylan B.] Dept Def, Ft Detrick, MD USA.
[George, Dylan B.] US Dept HHS, Biomed Adv Res & Dev Author, Washington, DC 20201 USA.
[Le Menach, Arnaud; Cohen, Justin M.] Clinton Hlth Access Initiat, Boston, MA USA.
[Pulliam, Juliet R. C.; Chiyaka, Christinah; Garcia, Andres J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Chiyaka, Christinah] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Pulliam, Juliet R. C.; Ruktanonchai, Nick] Univ Florida, Dept Biol, Gainesville, FL USA.
[Bisanzio, Donal; Kitron, Uriel] Emory Univ, Dept Environm Sci, Atlanta, GA 30322 USA.
[Buckee, Caroline] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.
[Garcia, Andres J.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Gatton, Michelle L.] Queensland Univ Technol, Sch Publ Hlth & Social Work, Brisbane, Qld 4001, Australia.
[Gething, Peter W.; Pigott, David M.; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
[Hartley, David M.] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA.
[Johnston, Geoffrey] Columbia Univ, Sch Int & Publ Affairs, New York, NY USA.
[Johnston, Geoffrey] Columbia Univ Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA.
[Klein, Eili Y.] Johns Hopkins Univ, Dept Emergency Med, Ctr Adv Modeling, Baltimore, MD USA.
[Michael, Edwin; Singh, Brajendra K.] Univ Notre Dame, Dept Biol Sci, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
[Michael, Edwin] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London, England.
[Lloyd, Alun L.] N Carolina State Univ, Grad Program, Dept Math & Biomath, Raleigh, NC 27695 USA.
[Stoller, Jeremy] Stoller Design Associates, Culver City, CA USA.
[Stoller, Jeremy] Calif Sci Ctr, Los Angeles, CA USA.
[Godfray, H. Charles J.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
RP Smith, DL (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA.
EM dlsmith@jhsph.edu
RI Singh, Brajendra/C-3787-2012; Hay, Simon/F-8967-2015; Smith,
David/L-8850-2013;
OI Singh, Brajendra/0000-0001-5847-8750; Bisanzio,
Donal/0000-0002-7832-2291; Hay, Simon/0000-0002-0611-7272; Pigott,
David/0000-0002-6731-4034; Smith, David/0000-0003-4367-3849; Cohen,
Justin/0000-0003-4481-6784; Klein, Eili/0000-0002-1304-5289; Chaves,
Luis Fernando/0000-0002-5301-2764; Gatton, Michelle/0000-0003-1188-609X;
Pulliam, Juliet/0000-0003-3314-8223; , David/0000-0003-2589-2538
FU Research and Policy for Infectious Disease Dynamics (RAPIDD) program of
the Science and Technology Directory, Department of Homeland Security,
and Fogarty International Center, National Institutes of Health; NIH
[R01-AI091980, R01 AI069387-01A1, R01-AI069341, R01-GM08322,
DP1OD003874]; NSF [RTG/DMS -1246991]; NIH/NIAID [U19AI089674]; Bill and
Melinda Gates Foundation [49446, 1032350, OPP1068048, OPP52250]; US
Centers for Disease Control and Prevention [5 U01 EH000418]; Leading
Program in Tropical and Emerging Communicable Diseases of Nagasaki
University; Senior Research Fellowship from the Wellcome Trust [095066];
Innovative Vector Control Consortium; MIDAS [U01GM070708]; National
Science Foundation [0801544]; Foundation for the National Institutes of
Health through the Vector-Based Control of Transmission: Discovery
Research program of the Grand Challenges in Global Health Initiative
FX This work was primarily supported by the Research and Policy for
Infectious Disease Dynamics (RAPIDD) program of the Science and
Technology Directory, Department of Homeland Security, and Fogarty
International Center, National Institutes of Health. DLS acknowledges
funding from the Bloomberg Family Foundation. ALL acknowledges funding
from the NIH [R01-AI091980] and NSF [RTG/DMS -1246991]. DLS and AJT
acknowledge funding from NIH/NIAID [U19AI089674] and the Bill and
Melinda Gates Foundation [49446]. AJT is also supported by a grant from
the Bill and Melinda Gates Foundation [1032350]. CMB acknowledges
additional funding from the US Centers for Disease Control and
Prevention [5 U01 EH000418]. LFC is funded by the Leading Program in
Tropical and Emerging Communicable Diseases of Nagasaki University. EM
and BKS acknowledge funding from the NIH [R01 AI069387-01A1]. SIH is
also funded by a Senior Research Fellowship from the Wellcome Trust
[095066]. PWG is a Medical Research Council Career Development Fellow
[K00669X] and receives support from the Bill and Melinda Gates
Foundation [OPP1068048]. TWS acknowledges funding from the Bill &
Melinda Gates Foundation [OPP52250], the Innovative Vector Control
Consortium, and the NIH [R01-AI069341, R01-AI091980, and R01-GM08322].
EYK acknowledges funding from MIDAS [U01GM070708] and NIH [DP1OD003874].
AJG is partially supported by the National Science Foundation under
Grant No. 0801544 in the Quantitative Spatial Ecology, Evolution and
Environment Program at the University of Florida. HCJG is supported by
the Foundation for the National Institutes of Health through the
Vector-Based Control of Transmission: Discovery Research program of the
Grand Challenges in Global Health Initiative.
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PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0035-9203
EI 1878-3503
J9 T ROY SOC TROP MED H
JI Trans. Roy. Soc. Trop. Med. Hyg.
PD APR
PY 2014
VL 108
IS 4
BP 185
EP 197
DI 10.1093/trstmh/tru026
PG 13
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA AD2TQ
UT WOS:000333088700004
PM 24591453
ER
PT J
AU Harrison, DE
Strong, R
Allison, DB
Ames, BN
Astle, CM
Atamna, H
Fernandez, E
Flurkey, K
Javors, MA
Nadon, NL
Nelson, JF
Pletcher, S
Simpkins, JW
Smith, D
Wilkinson, JE
Miller, RA
AF Harrison, David E.
Strong, Randy
Allison, David B.
Ames, Bruce N.
Astle, Clinton M.
Atamna, Hani
Fernandez, Elizabeth
Flurkey, Kevin
Javors, Martin A.
Nadon, Nancy L.
Nelson, James F.
Pletcher, Scott
Simpkins, James W.
Smith, Daniel
Wilkinson, J. Erby
Miller, Richard A.
TI Acarbose, 17-alpha-estradiol, and nordihydroguaiaretic acid extend mouse
lifespan preferentially in males
SO AGING CELL
LA English
DT Article
DE acarbose; estradiol; heterogeneous mice; lifespan; methylene blue; NDGA
ID GENETICALLY HETEROGENEOUS MICE; N-SH CELLS; POSTPRANDIAL HYPERGLYCEMIA;
ESTROGEN-RECEPTOR; DIABETES-MELLITUS; ALPHA-GLUCOSIDASE; HORMONE-LEVELS;
RAPAMYCIN; 17-BETA-ESTRADIOL; MODULATION
AB Four agents acarbose (ACA), 17--estradiol (EST), nordihydroguaiaretic acid (NDGA), and methylene blue (MB) were evaluated for lifespan effects in genetically heterogeneous mice tested at three sites. Acarbose increased male median lifespan by 22% (P<0.0001), but increased female median lifespan by only 5% (P=0.01). This sexual dimorphism in ACA lifespan effect could not be explained by differences in effects on weight. Maximum lifespan (90th percentile) increased 11% (P<0.001) in males and 9% (P=0.001) in females. EST increased male median lifespan by 12% (P=0.002), but did not lead to a significant effect on maximum lifespan. The benefits of EST were much stronger at one test site than at the other two and were not explained by effects on body weight. EST did not alter female lifespan. NDGA increased male median lifespan by 8-10% at three different doses, with P-values ranging from 0.04 to 0.005. Females did not show a lifespan benefit from NDGA, even at a dose that produced blood levels similar to those in males, which did show a strong lifespan benefit. MB did not alter median lifespan of males or females, but did produce a small, statistically significant (6%, P=0.004) increase in female maximum lifespan. These results provide new pharmacological models for exploring processes that regulate the timing of aging and late-life diseases, and in particular for testing hypotheses about sexual dimorphism in aging and health.
C1 [Harrison, David E.; Astle, Clinton M.; Flurkey, Kevin] Jackson Lab, Bar Harbor, ME 04609 USA.
[Strong, Randy; Fernandez, Elizabeth; Javors, Martin A.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA.
[Strong, Randy; Fernandez, Elizabeth] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA.
[Strong, Randy; Fernandez, Elizabeth] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA.
[Strong, Randy; Fernandez, Elizabeth] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Allison, David B.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
[Ames, Bruce N.; Atamna, Hani] Childrens Hosp Oakland Res Inst, Oakland, CA 94609 USA.
[Javors, Martin A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Nadon, Nancy L.] NIA, Div Aging Biol, Bethesda, MD 20892 USA.
[Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Pletcher, Scott] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Pletcher, Scott; Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA.
[Simpkins, James W.] Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA.
[Smith, Daniel] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Wilkinson, J. Erby] Univ Michigan, Sch Med, Unit Lab Anim Med, Ann Arbor, MI 48109 USA.
[Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
RP Harrison, DE (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
EM david.harrison@jax.org
OI Allison, David/0000-0003-3566-9399
FU NIA [AG022308, AG022303, AG022307]; Department of Veterans Affairs
Office of Research and Development; [CA034196]
FX This work was funded in part by NIA Grants AG022308 (D. E. H.), AG022303
(R. A. M.), and AG022307 (R. S.), with important facilities supported by
CA034196 (TJL). RS is supported by a Senior Research Career Scientist
Award from the Department of Veterans Affairs Office of Research and
Development. We wish to thank P. J. Krason, V. Ingalls, Lisa Burmeister,
Sabrina van Roekel, N. Durgin, and Vivian Diaz for reliable technical
assistance.
NR 36
TC 56
Z9 56
U1 3
U2 22
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD APR
PY 2014
VL 13
IS 2
BP 273
EP 282
DI 10.1111/acel.12170
PG 10
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA AC4VG
UT WOS:000332518600009
PM 24245565
ER
PT J
AU Fok, WC
Bokov, A
Gelfond, J
Yu, Z
Zhang, YQ
Doderer, M
Chen, YD
Javors, M
Wood, WH
Zhang, YQ
Becker, KG
Richardson, A
Perez, VI
AF Fok, Wilson C.
Bokov, Alex
Gelfond, Jonathan
Yu, Zhen
Zhang, Yiqiang
Doderer, Mark
Chen, Yidong
Javors, Martin
Wood, William H., III
Zhang, Yongqing
Becker, Kevin G.
Richardson, Arlan
Perez, Viviana I.
TI Combined treatment of rapamycin and dietary restriction has a larger
effect on the transcriptome and metabolome of liver
SO AGING CELL
LA English
DT Article
DE dietary restriction; metabolome; rapamycin; transcriptome
ID GENETICALLY HETEROGENEOUS MICE; EXTENDS LIFE-SPAN; CALORIE RESTRICTION;
MAMMALIAN PROTEIN; YEAST; LONGEVITY; TOR; MECHANISMS; CELLS;
IDENTIFICATION
AB Rapamycin (Rapa) and dietary restriction (DR) have consistently been shown to increase lifespan. To investigate whether Rapa and DR affect similar pathways in mice, we compared the effects of feeding mice ad libitum (AL), Rapa, DR, or a combination of Rapa and DR (Rapa+DR) on the transcriptome and metabolome of the liver. The principal component analysis shows that Rapa and DR are distinct groups. Over 2500 genes are significantly changed with either Rapa or DR when compared with mice fed AL; more than 80% are unique to DR or Rapa. A similar observation was made when genes were grouped into pathways; two-thirds of the pathways were uniquely changed by DR or Rapa. The metabolome shows an even greater difference between Rapa and DR; no metabolites in Rapa-treated mice were changed significantly from AL mice, whereas 173 metabolites were changed in the DR mice. Interestingly, the number of genes significantly changed by Rapa+DR when compared with AL is twice as large as the number of genes significantly altered by either DR or Rapa alone. In summary, the global effects of DR or Rapa on the liver are quite different and a combination of Rapa and DR results in alterations in a large number of genes and metabolites that are not significantly changed by either manipulation alone, suggesting that a combination of DR and Rapa would be more effective in extending longevity than either treatment alone.
C1 [Fok, Wilson C.; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[Bokov, Alex; Zhang, Yiqiang; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[Bokov, Alex; Gelfond, Jonathan; Chen, Yidong] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Yu, Zhen; Perez, Viviana I.] Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA.
[Zhang, Yiqiang] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Doderer, Mark; Chen, Yidong] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA.
[Chen, Yidong] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA.
[Javors, Martin] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Wood, William H., III; Zhang, Yongqing; Becker, Kevin G.] NIA, Baltimore, MD 21224 USA.
[Richardson, Arlan] Audie Murphy VA Hosp STVHCS, Res Serv, San Antonio, TX 78229 USA.
[Perez, Viviana I.] Oregon State Univ, Dept Biochem & Biophys, Corvallis, OR 97331 USA.
RP Perez, VI (reprint author), Oregon State Univ, Dept Biochem & Biophys, Linus Pauling Inst, 307 Linus Pauling Sci Ctr, Corvallis, OR 97331 USA.
EM viviana.perez@oregonstate.edu
OI Fok, Wilson Chun Yim/0000-0003-3289-2093
FU San Antonio Nathan Shock Aging Center [1p30-AG-13319]; National
Institutes of Health (NIH) RC2 Grand Opportunity grant [AG036613]; NIH
T32 Training Grant [AG021890]; Ellison Medical Foundation; Intramural
Research Program of the NIH, National Institute on Aging
FX Financial support was provided by The San Antonio Nathan Shock Aging
Center (1p30-AG-13319, AR), National Institutes of Health (NIH) RC2
Grand Opportunity grant (AG036613, AR), NIH T32 Training Grant
(AG021890, WF), the Ellison Medical Foundation (VP), and the Intramural
Research Program of the NIH, National Institute on Aging.
NR 44
TC 15
Z9 15
U1 2
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD APR
PY 2014
VL 13
IS 2
BP 311
EP 319
DI 10.1111/acel.12175
PG 9
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA AC4VG
UT WOS:000332518600013
PM 24304444
ER
PT J
AU Belzer, ME
Naar-King, S
Olson, J
Sarr, M
Thornton, S
Kahana, SY
Gaur, AH
Clark, LF
AF Belzer, Marvin E.
Naar-King, Sylvie
Olson, Johanna
Sarr, Moussa
Thornton, Sarah
Kahana, Shoshana Y.
Gaur, Aditya H.
Clark, Leslie F.
CA Adolescent Med Trials Network HIV
TI The Use of Cell Phone Support for Non-adherent HIV-Infected Youth and
Young Adults: An Initial Randomized and Controlled Intervention Trial
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Adherence; Adolescent; HIV; Cell phone; Support
ID ANTIRETROVIRAL THERAPY; MEDICATION ADHERENCE; BEHAVIOR-CHANGE;
PREVENTION; ADOLESCENTS; PREDICTORS; MULTISITE; BARRIERS; HAART
AB This randomized behavioral trial examined whether youth living with HIV (YLH) receiving cell-phone support with study funded phone plans, demonstrated improved adherence and viral control during the 24 week intervention and 24 weeks post-intervention compared to controls. Monday through Friday phone calls confirmed medications were taken, provided problem-solving support, and referred to services to address adherence barriers. Of 37 participants (ages 15-24), 62 % were male and 70 % were African American. Self-reported adherence was significantly higher in the intervention group compared to the control at 24 and 48 weeks for the past month (P = 0.007) and log 10 HIV VL was significantly lower at both 24 weeks (2.82 versus 4.52 P = 0.002) and 48 weeks (3.23 versus 4.23 P = 0.043). Adherence and viral load showed medium to large effect sizes across the 48 week study. This is the first study to demonstrate sustained clinically significant reductions in HIV VL using youth friendly technology.
C1 [Belzer, Marvin E.; Olson, Johanna; Clark, Leslie F.] Childrens Hosp Los Angeles, Dept Pediat, Los Angels, CA 90027 USA.
[Belzer, Marvin E.; Olson, Johanna; Clark, Leslie F.] Univ So Calif, Los Angels, CA 90027 USA.
[Naar-King, Sylvie] Wayne State Univ, Pediat Prevent Ctr, Detroit, MI USA.
[Sarr, Moussa; Thornton, Sarah] WESTAT Corp, Rockville, MD 20850 USA.
[Kahana, Shoshana Y.] NIDA, Bethesda, MD 20892 USA.
[Gaur, Aditya H.] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA.
RP Belzer, ME (reprint author), Childrens Hosp Los Angeles, Dept Pediat, 4650 Sunset Blvd MS 2, Los Angels, CA 90027 USA.
EM mbelzer@chla.usc.edu
RI Emchi, Karma/Q-1952-2016
FU NCRR NIH HHS [M01 RR005096]; NICHD NIH HHS [5 UO1 HD 40474, 5U01-HD
40533, U01 HD040463, U01 HD040470, U01 HD040474, U01 HD040533]
NR 23
TC 21
Z9 21
U1 0
U2 11
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
EI 1573-3254
J9 AIDS BEHAV
JI AIDS Behav.
PD APR
PY 2014
VL 18
IS 4
BP 686
EP 696
DI 10.1007/s10461-013-0661-3
PG 11
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA AD4ED
UT WOS:000333198900009
PM 24271347
ER
PT J
AU Mertins, SD
AF Mertins, Susan D.
TI Cancer stem cells: a systems biology view of their role in prognosis and
therapy
SO ANTI-CANCER DRUGS
LA English
DT Review
DE therapeutics; systems biology; prognosis; plasticity; signal
transduction pathways; cancer stem cells; dynamic modeling
ID TUMOR-INITIATING CELLS; SALINOMYCIN INDUCES APOPTOSIS;
SIGNAL-TRANSDUCTION PATHWAYS; HUMAN PANCREATIC-CANCER; ACUTE
MYELOID-LEUKEMIA; BREAST-CANCER; WNT/BETA-CATENIN; DRUG-RESISTANCE;
SELF-RENEWAL; PROSPECTIVE IDENTIFICATION
AB Evidence has accumulated that characterizes highly tumorigenic cancer cells residing in heterogeneous populations. The accepted term for such a subpopulation is cancer stem cells (CSCs). While many questions still remain about their precise role in the origin, progression, and drug resistance of tumors, it is clear they exist. In this review, a current understanding of the nature of CSC, their potential usefulness in prognosis, and the need to target them will be discussed. In particular, separate studies now suggest that the CSC is plastic in its phenotype, toggling between tumorigenic and nontumorigenic states depending on both intrinsic and extrinsic conditions. Because of this, a static view of gene and protein levels defined by correlations may not be sufficient to either predict disease progression or aid in the discovery and development of drugs to molecular targets leading to cures. Quantitative dynamic modeling, a bottom up systems biology approach whereby signal transduction pathways are described by differential equations, may offer a novel means to overcome the challenges of oncology today. In conclusion, the complexity of CSCs can be captured in mathematical models that may be useful for selecting molecular targets, defining drug action, and predicting sensitivity or resistance pathways for improved patient outcomes.
C1 NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Diag & Treatment, Ft Detrick, MD 21702 USA.
RP Mertins, SD (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Diag & Treatment, POB B,Bldg 315,Room 6, Ft Detrick, MD 21702 USA.
EM smertins@mail.nih.gov
FU Developmental Therapeutics Program, Division of Cancer Diagnosis and
Treatment, National Cancer Institute
FX The views in this paper are those of the author and do not necessarily
reflect the position of the US Government. This work was supported by
the Developmental Therapeutics Program, Division of Cancer Diagnosis and
Treatment, National Cancer Institute.
NR 145
TC 8
Z9 10
U1 0
U2 40
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-4973
EI 1473-5741
J9 ANTI-CANCER DRUG
JI Anti-Cancer Drugs
PD APR
PY 2014
VL 25
IS 4
BP 353
EP 367
DI 10.1097/CAD.0000000000000075
PG 15
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA AC6AM
UT WOS:000332602500001
PM 24418909
ER
PT J
AU Liu, AM
Krausz, KW
Fang, ZZ
Brocker, C
Qu, AJ
Gonzalez, FJ
AF Liu, Aiming
Krausz, Kristopher W.
Fang, Zhong-Ze
Brocker, Chad
Qu, Aijuan
Gonzalez, Frank J.
TI Gemfibrozil disrupts lysophosphatidylcholine and bile acid homeostasis
via PPAR alpha and its relevance to hepatotoxicity
SO ARCHIVES OF TOXICOLOGY
LA English
DT Article
DE Metabolomics; PPAR alpha ; Gemfibrozil; Hepatotoxicity; Bile acid;
Phospholipid
ID ACTIVATED RECEPTOR-ALPHA; METABOLOMICS REVEALS; CHOLESTEROL
7-ALPHA-HYDROXYLASE; MASS-SPECTROMETRY; DOWN-REGULATION; HEPATITIS-B;
LIVER; MOUSE; EXPRESSION; GENE
AB Gemfibrozil, a ligand of peroxisome proliferator-activated receptor alpha (PPAR alpha), is one of the most widely prescribed anti-dyslipidemia fibrate drugs. Among the adverse reactions observed with gemfibrozil are alterations in liver function, cholestatic jaundice, and cholelithiasis. However, the mechanisms underlying these toxicities are poorly understood. In this study, wild-type and Ppara-null mice were dosed with a gemfibrozil-containing diet for 14 days. Ultra-performance chromatography electrospray ionization quadrupole time-of-flight mass spectrometry-based metabolomics and traditional approaches were used to assess the mechanism of gemfibrozil-induced hepatotoxicity. Unsupervised multivariate data analysis revealed four lysophosphatidylcholine components in wild-type mice that varied more dramatically than those in Ppara-null mice. Targeted metabolomics revealed taurocholic acid and tauro-alpha-muricholic acid/tauro-beta-muricholic acid were significantly increased in wild-type mice, but not in Ppara-null mice. In addition to the above perturbations in metabolite homeostasis, phenotypic alterations in the liver were identified. Hepatic genes involved in metabolism and transportation of lysophosphatidylcholine and bile acid compounds were differentially regulated between wild-type and Ppara-null mice, in agreement with the observed downstream metabolic alterations. These data suggest that PPAR alpha mediates gemfibrozil-induced hepatotoxicity in part by disrupting phospholipid and bile acid homeostasis.
C1 [Liu, Aiming] Ningbo Univ, Sch Med, Ningbo 315211, Zhejiang, Peoples R China.
[Liu, Aiming; Krausz, Kristopher W.; Fang, Zhong-Ze; Brocker, Chad; Qu, Aijuan; Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Liu, AM (reprint author), Ningbo Univ, Sch Med, Ningbo 315211, Zhejiang, Peoples R China.
EM liuaiming@nbu.edu.cn
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health; Ningbo Natural Science
Foundation [2011A610059]; Zhejiang Provincial Natural Science Foundation
of China [Y2110016]; Zhejiang Provincial Education Department
[Y201329949]; National Natural Science Foundation of China [81273582,
81302848, 81202586]
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health. It was in part supported by Ningbo Natural Science Foundation
[Grant 2011A610059], Zhejiang Provincial Natural Science Foundation of
China [Grant Y2110016], Zhejiang Provincial Education Department [Grant
Y201329949], and National Natural Science Foundation of China [Grant
81273582, 81302848, and 81202586].
NR 35
TC 16
Z9 19
U1 5
U2 24
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5761
EI 1432-0738
J9 ARCH TOXICOL
JI Arch. Toxicol.
PD APR
PY 2014
VL 88
IS 4
BP 983
EP 996
DI 10.1007/s00204-013-1188-0
PG 14
WC Toxicology
SC Toxicology
GA AD3BZ
UT WOS:000333113600010
PM 24385052
ER
PT J
AU Kitanaka, N
Kitanaka, J
Hall, FS
Uhl, GR
Watabe, K
Kubo, H
Takahashi, H
Tanaka, K
Nishiyama, N
Takemura, M
AF Kitanaka, Nobue
Kitanaka, Junichi
Hall, F. Scott
Uhl, George R.
Watabe, Kaname
Kubo, Hitoshi
Takahashi, Hitoshi
Tanaka, Koh-ichi
Nishiyama, Nobuyoshi
Takemura, Motohiko
TI Agmatine attenuates methamphetamine-induced hyperlocomotion and
stereotyped behavior in mice
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Article
DE methamphetamine; agmatine; hyperlocomotion; agmatinase inhibitor; mouse;
stereotyped behavior
ID CONDITIONED PLACE PREFERENCE; RECEPTOR ANTAGONIST; NMDA RECEPTOR;
SENSITIZATION; MK-801; BRAIN; AMPHETAMINE; NOMIFENSINE; INHIBITOR;
STRIATUM
AB We investigated whether pretreatment with the neurotransmitter/neuromodulator agmatine (decarboxylated l-arginine) affected methamphetamine (METH)-induced hyperlocomotion and stereotypy in male ICR mice. Agmatine pretreatment alone had no effects on locomotion or stereotypy, but it produced a dose-dependent attenuation of locomotion and the total incidence of stereotyped behavior induced by a low dose of METH (5 mg/kg). The stereotypy induced by this dose was predominantly characterized by stereotyped sniffing. By contrast, agmatine did not affect the total incidence of stereotypy induced by a higher dose of METH (10 mg/kg). However, the nature of stereotypy induced by this dose of METH was substantially altered; agmatine pretreatment significantly reduced stereotyped biting but significantly increased stereotyped sniffing and persistent locomotion. Agmatine pretreatment therefore appears to produce a rightward shift in the dose-response curve for METH. Pretreatment of mice with piperazine-1-carboxamidine (a putative agmatinase inhibitor) had no effect on locomotion or stereotypy induced by a low dose of METH, suggesting that endogenous agmatine may not regulate the METH action.
C1 [Kitanaka, Nobue; Kitanaka, Junichi; Takemura, Motohiko] Hyogo Coll Med, Dept Pharmacol, Nishinomiya, Hyogo 6638501, Japan.
[Tanaka, Koh-ichi; Nishiyama, Nobuyoshi] Hyogo Univ Hlth Sci, Dept Pharm, Div Pharmacol, Sch Pharm, Hyogo, Japan.
[Watabe, Kaname; Kubo, Hitoshi; Takahashi, Hitoshi] Muromachi Kikai Co Ltd, Tokyo, Japan.
[Hall, F. Scott; Uhl, George R.] NIDA, Mol Neurobiol Branch, Intramural Res Program, Baltimore, MD USA.
RP Kitanaka, J (reprint author), Hyogo Coll Med, Dept Pharmacol, 1-1 Mukogawa Cho, Nishinomiya, Hyogo 6638501, Japan.
EM kitanaka-hyg@umin.net
RI Hall, Frank/C-3036-2013
OI Hall, Frank/0000-0002-0822-4063
FU Hyogo College of Medicine; National Institute on Drug Abuse, USA
FX This research was supported, in part, by Grants-in-Aid for Researchers,
Hyogo College of Medicine (2013 to N.K.; 2012 to J.K.), and by
intramural funding from the National Institute on Drug Abuse, USA
(G.R.U. and F.S.H.).
NR 37
TC 4
Z9 5
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0955-8810
EI 1473-5849
J9 BEHAV PHARMACOL
JI Behav. Pharmacol.
PD APR
PY 2014
VL 25
IS 2
BP 158
EP 165
DI 10.1097/FBP.0000000000000030
PG 8
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA AC5ZU
UT WOS:000332600400007
PM 24557322
ER
PT J
AU Fang, ZZ
Krausz, KW
Nagaoka, K
Tanaka, N
Gowda, K
Amin, SG
Perdew, GH
Gonzalez, FJ
AF Fang, Zhong-Ze
Krausz, Kristopher W.
Nagaoka, Kenjiro
Tanaka, Naoki
Gowda, Krishne
Amin, Shantu G.
Perdew, Gary H.
Gonzalez, Frank J.
TI In vivo effects of the pure aryl hydrocarbon receptor antagonist GNF-351
after oral administration are limited to the gastrointestinal tract
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE GNF-351; metabolic map; absorption; AHR antagonist
ID ARRIVE GUIDELINES; AH RECEPTOR; MICE
AB Background and Purpose
GNF-351 is a potent aryl hydrocarbon receptor (AHR) antagonist that inhibits dioxin response element-dependent and independent activities. Here, the absorption, metabolism and in vivo AHR antagonist activity of GNF-351 were investigated.
Experimental Approach
LC-MS metabolomics was used to analyse GNF-351 metabolism in vitro and in vivo. Recombinant drug-metabolizing enzymes were employed to determine the enzymes involved in GNF-351 metabolism. Analysis of target AHR genes was performed to investigate the inhibitory effects of GNF-351 towards AHR activation.
Key Results
Several phase I metabolites were generated after GNF-351 was incubated with microsomes from human or mouse liver and intestine, including two oxidized GNF-351 and one tri-demethylated GNF-351. Poor absorption from the intestine resulted in no detectable levels of GNF-351 in mouse serum (0-6 h) and urine (24 h) and almost all GNF-351 was found in the faeces after 24 h. Analysis of faeces further revealed all the in vitro phase I metabolites. Novel metabolites were detected, including one di-oxidized GNF-351, two oxidized and tri-demethylated GNF-351, one dehydrogenated product of oxidized GNF-351, and one sulfation product of di-oxidized GNF-351. Cytochromes P450 were demonstrated to be the major enzymes involved in metabolism of GNF-351. After oral administration to mice, GNF-351 readily inhibited beta-naphthoflavone-induced AHR activation in ileum and colon, but not that in the liver.
Conclusion and Implications
While poor absorption and extensive metabolism after oral administration limited the in vivo effects of the pure AHR antagonist GNF-351 in liver, it could be used to inhibit AHR activation in intestine and colon.
C1 [Fang, Zhong-Ze; Krausz, Kristopher W.; Nagaoka, Kenjiro; Tanaka, Naoki; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Gowda, Krishne; Amin, Shantu G.] Penn State Univ, Coll Med, Dept Pharmacol, Hershey, PA USA.
[Perdew, Gary H.] Penn State Univ, Dept Vet & Biochem Sci, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
OI GOWDA, KRISHNE/0000-0002-6042-0520
FU National Cancer Institute Intramural Research Program; National
Institutes of Health [ES004869, ES019964, CA141029]
FX This study was funded by the National Cancer Institute Intramural
Research Program and grants ES004869, ES019964 and CA141029 from the
National Institutes of Health.
NR 22
TC 14
Z9 14
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
EI 1476-5381
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD APR
PY 2014
VL 171
IS 7
BP 1735
EP 1746
DI 10.1111/bph.12576
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AD0CX
UT WOS:000332903000013
PM 24417285
ER
PT J
AU Jochems, C
Tucker, JA
Tsang, KY
Madan, RA
Dahut, WL
Liewehr, DJ
Steinberg, SM
Gulley, JL
Schlom, J
AF Jochems, Caroline
Tucker, Jo A.
Tsang, Kwong-Yok
Madan, Ravi A.
Dahut, William L.
Liewehr, David J.
Steinberg, Seth M.
Gulley, James L.
Schlom, Jeffrey
TI A combination trial of vaccine plus ipilimumab in metastatic
castration-resistant prostate cancer patients: immune correlates
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE Ipilimumab; Vaccine; PROSTVAC; T cells; NK cells; Immunotherapy
ID TUMOR-INFILTRATING LYMPHOCYTES; DOSE-ESCALATION TRIAL; REGULATORY
T-CELLS; CTLA-4 BLOCKADE; RADICAL PROSTATECTOMY; ANTI-CTLA-4 THERAPY;
ANTITUMOR-ACTIVITY; MELANOMA PATIENTS; SUPPRESSOR-CELLS; SURVIVAL
AB We recently reported the clinical results of a Phase I trial combining ipilimumab with a vaccine containing transgenes for prostate-specific antigen (PSA) and for a triad of costimulatory molecules (PROSTVAC) in patients with metastatic castration-resistant prostate cancer. Thirty patients were treated with escalating ipilimumab and a fixed dose of vaccine. Of 24 chemotherapy-na < ve patients, 58 % had a PSA decline. Combination therapy did not exacerbate the immune-related adverse events associated with ipilimumab. Here, we present updated survival data and an evaluation of 36 immune cell subsets pre- and post-therapy. Peripheral blood mononuclear cells were collected before therapy, at 13 days and at 70 days post-initiation of therapy, and phenotyped by flow cytometry for the subsets of T cells, regulatory T cells, natural killer cells, and myeloid-derived suppressor cells. Associations between overall survival (OS) and immune cell subsets prior to treatment, and the change in a given immune cell subset 70 days post-initiation of therapy, were evaluated. The median OS was 2.63 years (1.77-3.45). There were trends toward associations for longer OS and certain immune cell subsets before immunotherapy: lower PD-1(+)Tim-3(NEG)CD4(EM) (P = 0.005, adjusted P = 0.010), higher PD-1(NEG)Tim-3(+)CD8 (P = 0.002, adjusted P = 0.004), and a higher number of CTLA-4(NEG) Tregs (P = 0.005, adjusted P = 0.010). We also found that an increase in Tim-3(+) natural killer cells post- versus pre-vaccination associated with longer OS (P = 0.0074, adjusted P = 0.015). These results should be considered as hypothesis generating and should be further evaluated in larger immunotherapy trials.
C1 [Jochems, Caroline; Tucker, Jo A.; Tsang, Kwong-Yok; Madan, Ravi A.; Gulley, James L.; Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Madan, Ravi A.; Dahut, William L.; Gulley, James L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Liewehr, David J.; Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA.
EM js141c@nih.gov
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX Grant support was provided by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health. The authors thank Debra Weingarten for her
editorial assistance in the preparation of this manuscript.
NR 51
TC 36
Z9 36
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
EI 1432-0851
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD APR
PY 2014
VL 63
IS 4
BP 407
EP 418
DI 10.1007/s00262-014-1524-0
PG 12
WC Oncology; Immunology
SC Oncology; Immunology
GA AD1WB
UT WOS:000333023300009
PM 24514956
ER
PT J
AU Sarker, MMH
Zhou, MC
Rameshwar, P
Hanover, JA
AF Sarker, Md Mosharrof Hossain
Zhou, Meng Chu
Rameshwar, Pranela
Hanover, John A.
TI Functions and Roles of a Protein-Associated Factor
SO CELL BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Article
DE Associated factor; Signal guide; Stem cells
ID HEDGEHOG SIGNAL-TRANSDUCTION; BEHAVIOR; BRAIN
AB The divergence of protein (Hedgehog) in different organisms remains an unresolved issue to comprehend how the pathway in Hh signaling evolves. Insights into this question can help one identify the key molecules in Hh signaling. This work proposes a protein-associated factor in cells. The development of a non-reductionist theory of cellular functions in medicine is not sufficient. It is necessary to find the parameters with regards to molecules/genes that can elicit functions. This work shows that molecular interactions of gene products can be accomplished by biophysics logic. Defining the protein-associated factors in molecular activities and identifying its roles in molecular transduction are important. A misregulation in molecular switch can account for complex biomolecular consequences. This work shows the potential of the factor on homo-sapiens and unlocks its implications to gene multi-tasking functionality. The associated factor notion should facilitate the medical development in cancer therapeutics.
C1 [Sarker, Md Mosharrof Hossain; Zhou, Meng Chu] New Jersey Inst Technol, Dept Elect & Comp Engn, Newark, NJ 07102 USA.
[Rameshwar, Pranela] New Jersey Inst Technol, Sch Biomed Sci, Dept Med Hematol Oncol, Newark, NJ 07103 USA.
[Hanover, John A.] NIDDK, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Sarker, MMH (reprint author), New Jersey Inst Technol, Dept Elect & Comp Engn, Newark, NJ 07102 USA.
EM mhs43@njit.edu; zhou@njit.edu; rameshwa@njms.rutgers.edu;
jah@helix.nih.gov
NR 21
TC 0
Z9 0
U1 1
U2 9
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1085-9195
EI 1559-0283
J9 CELL BIOCHEM BIOPHYS
JI Cell Biochem. Biophys.
PD APR
PY 2014
VL 68
IS 3
BP 577
EP 582
DI 10.1007/s12013-013-9743-0
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA AD0XQ
UT WOS:000332958100019
PM 24036680
ER
PT J
AU Murray, JD
Anticevic, A
Gancsos, M
Ichinose, M
Corlett, PR
Krystal, JH
Wang, XJ
AF Murray, John D.
Anticevic, Alan
Gancsos, Mark
Ichinose, Megan
Corlett, Philip R.
Krystal, John H.
Wang, Xiao-Jing
TI Linking Microcircuit Dysfunction to Cognitive Impairment: Effects of
Disinhibition Associated with Schizophrenia in a Cortical Working Memory
Model
SO CEREBRAL CORTEX
LA English
DT Article
DE disinhibition; NMDAR hypofunction; prefrontal cortex; schizophrenia;
working memory
ID DORSOLATERAL PREFRONTAL CORTEX; GLUTAMATE-RECEPTOR AGONIST; NETWORK
MODEL; INHIBITORY NEURONS; PREPULSE INHIBITION; NMDA RECEPTORS; NEURAL
SYSTEMS; KETAMINE; INTERNEURONS; DISORDER
AB Excitationinhibition balance (E/I balance) is a fundamental property of cortical microcircuitry. Disruption of E/I balance in prefrontal cortex is hypothesized to underlie cognitive deficits observed in neuropsychiatric illnesses such as schizophrenia. To elucidate the link between these phenomena, we incorporated synaptic disinhibition, via N-methyl-D-aspartate receptor perturbation on interneurons, into a network model of spatial working memory (WM). At the neural level, disinhibition broadens the tuning of WM-related, stimulus-selective persistent activity patterns. The model predicts that this change at the neural level leads to 2 primary behavioral deficits: 1) increased behavioral variability that degrades the precision of stored information and 2) decreased ability to filter out distractors during WM maintenance. We specifically tested the main model prediction, broadened WM representation under disinhibition, using behavioral data from human subjects performing a spatial WM task combined with ketamine infusion, a pharmacological model of schizophrenia hypothesized to induce disinhibition. Ketamine increased errors in a pattern predicted by the model. Finally, as proof-of-principle, we demonstrate that WM deteriorations in the model can be ameliorated by compensations that restore E/I balance. Our findings identify specific ways by which cortical disinhibition affects WM, suggesting new experimental designs for probing the brain mechanisms of WM deficits in schizophrenia.
C1 [Murray, John D.] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
[Murray, John D.; Wang, Xiao-Jing] Yale Univ, Sch Med, Kavli Inst Neurosci, Dept Neurobiol, New Haven, CT 06510 USA.
[Anticevic, Alan; Gancsos, Mark; Ichinose, Megan; Corlett, Philip R.; Krystal, John H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA.
[Anticevic, Alan; Krystal, John H.] Yale Univ, CTNA, NIAAA, New Haven, CT 06519 USA.
[Anticevic, Alan; Corlett, Philip R.; Krystal, John H.] Yale Univ, Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, Dept Psychiat, New Haven, CT 06519 USA.
[Krystal, John H.] Yale New Haven Med Ctr, Dept Psychiat, Psychiat Serv, New Haven, CT 06504 USA.
[Krystal, John H.] VA Connecticut Healthcare Syst, Vet Affairs VA Natl Ctr Post Traumat Stress Disor, Div Clin Neurosci, West Haven, CT 06516 USA.
[Wang, Xiao-Jing] NYU, Ctr Neural Sci, New York, NY 10003 USA.
RP Wang, XJ (reprint author), NYU, Ctr Neural Sci, 4 Washington Pl, New York, NY 10003 USA.
EM xjwang@nyu.edu
RI Wang, Xiao-Jing/D-2722-2009; Murray, John/B-2835-2009
OI Murray, John/0000-0003-4115-8181
FU National Institutes of Health [T15-LM07056, DP5-OD012109-01,
R01-MH062349]; AstraZeneca Pharmaceuticals
FX This work was supported by the National Institutes of Health
(T15-LM07056 to J.D.M., DP5-OD012109-01 to A. A., and R01-MH062349 to
X.-J.W.) AstraZeneca Pharmaceuticals.
NR 87
TC 38
Z9 38
U1 2
U2 16
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD APR
PY 2014
VL 24
IS 4
BP 859
EP 872
DI 10.1093/cercor/bhs370
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA AD2FC
UT WOS:000333048200002
PM 23203979
ER
PT J
AU Tomasi, D
Volkow, ND
AF Tomasi, Dardo
Volkow, Nora D.
TI Functional Connectivity of Substantia Nigra and Ventral Tegmental Area:
Maturation During Adolescence and Effects of ADHD
SO CEREBRAL CORTEX
LA English
DT Article
DE addiction; attention-deficit; hyperactivity disorder; connectivity;
dopamine; maturation
ID DEFAULT MODE NETWORK; DEFICIT/HYPERACTIVITY DISORDER;
INDIVIDUAL-DIFFERENCES; PREFRONTAL CORTEX; DOPAMINE; ATTENTION; FMRI;
ACTIVATION; CHILDREN; METHYLPHENIDATE
AB Dopaminergic (DArgic) pathways play crucial roles in brain function and their disruption is implicated in various neuropsychiatric diseases. Here, we demonstrate in 402 healthy children/adolescents (12 3 years) and 704 healthy young adults (23 5 years) that the functional connectivity of DA pathways matures significantly from childhood to adulthood and is different for healthy children and children with attention-deficit/hyperactivity disorder (ADHD; N 203; 12 3 years). This transition is characterized by age-related increases in the functional connectivity of the ventral tegmental area (VTA) with limbic regions and with the default mode network and by decreases in the connectivity of the substantia nigra (SN) with motor and medial temporal cortices. The changes from a predominant influence of SN in childhood/adolescence to a combined influence of SN and VTA in young adulthood might explain the increased vulnerability to psychiatric disorders, such as ADHD, early in life. We also show that VTA and SN connectivity networks were highly reproducible, which highlights their potential value as biomarkers for evaluating DArgic dysfunction in neuropsychiatric disorders.
C1 [Tomasi, Dardo; Volkow, Nora D.] NIAAA, Bethesda, MD USA.
[Tomasi, Dardo; Volkow, Nora D.] Brookhaven Natl Lab, Lab Neuroimaging LNI NIAAA, Dept Med, Upton, NY 11973 USA.
[Volkow, Nora D.] NIA, Bethesda, MD 20892 USA.
RP Tomasi, D (reprint author), Brookhaven Natl Lab, Lab Neuroimaging LNI NIAAA, Dept Med, Bldg 490,30 Bell Ave, Upton, NY 11973 USA.
EM tomasi@bnl.gov
RI Tomasi, Dardo/J-2127-2015
FU National Institute on Alcohol Abuse and Alcoholism [2RO1AA09481]
FX This work was accomplished with support from the National Institute on
Alcohol Abuse and Alcoholism (2RO1AA09481).
NR 48
TC 23
Z9 23
U1 1
U2 16
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD APR
PY 2014
VL 24
IS 4
BP 935
EP 944
DI 10.1093/cercor/bhs382
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA AD2FC
UT WOS:000333048200008
PM 23242198
ER
PT J
AU Zimerman, M
Heise, KF
Gerloff, C
Cohen, LG
Hummel, FC
AF Zimerman, Maximo
Heise, Kirstin-F.
Gerloff, Christian
Cohen, Leonardo G.
Hummel, Friedhelm C.
TI Disrupting the Ipsilateral Motor Cortex Interferes with Training of a
Complex Motor Task in Older Adults
SO CEREBRAL CORTEX
LA English
DT Article
DE aging; brain stimulation; motor cortex; neuroplasticity; tDCS
ID DIRECT-CURRENT STIMULATION; TRANSCRANIAL MAGNETIC STIMULATION;
NONINVASIVE BRAIN-STIMULATION; AGE-RELATED DIFFERENCES; AGING BRAIN;
CORTICAL STIMULATION; PLASTICITY; PERFORMANCE; MODULATION; STROKE
AB Performance of unimanual movements is associated with bihemispheric activity in the motor cortex in old adults. However, the causal functional role of the ipsilateral MC (iMC) for motor control is still not completely known. Here, the behavioral consequences of interference of the iMC during training of a complex motor skill were tested. Healthy old (5885 years) and young volunteers (2235 years) were tested in a double-blind, cross-over, sham-controlled design. Participants attended 2 different study arms with either cathodal transcranial direct current stimulation (ctDCS) or sham concurrent with training. Motor performance was evaluated before, during, 90 min, and 24 h after training. During training, a reduced slope of performance with ctDCS relative to sham was observed in old compared with young (F 5.8, P 0.02), with a decrease of correctly rehearsed sequences, an effect that was evident even after 2 consecutive retraining periods without intervention. Furthermore, the older the subject, the more prominent was the disruptive effect of ctDCS (R-2 0.50, P 0.01). These data provide direct evidence for a causal functional link between the iMC and motor skill acquisition in old subjects pointing toward the concept that the recruitment of iMC in old is an adaptive process in response to age-related declines in motor functions.
C1 [Zimerman, Maximo; Heise, Kirstin-F.; Gerloff, Christian; Hummel, Friedhelm C.] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Brain Imaging & Neurostimulat BINS Lab, D-20246 Hamburg, Germany.
[Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
RP Hummel, FC (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Brain Imaging & Neurostimulat BINS Lab, D-20246 Hamburg, Germany.
EM f.hummel@uke.uni-hamburg.de
OI Heise, Kirstin-Friederike/0000-0003-3666-8531
FU DAAD (German Academic Exchange Service) [A/07/95990]; Alexander von
Humboldt Foundation (Feodor-Lynen); Forschungsforderungsfonds Medizin of
the University of Hamburg [NWF-04/07, NWF-11/09]; German Research
Foundation [SFB 936]
FX This research was supported by a grant from the DAAD (German Academic
Exchange Service) to M.Z. (A/07/95990), Alexander von Humboldt
Foundation (Feodor-Lynen) to F. C. H., the Forschungsforderungsfonds
Medizin of the University of Hamburg (NWF-04/07 to F. C. H.; NWF-11/09
to M.Z.) and by the SFB 936 Multi-Site Communication in the Brain (C4 to
F. C. H.) of the German Research Foundation.
NR 55
TC 9
Z9 9
U1 0
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD APR
PY 2014
VL 24
IS 4
BP 1030
EP 1036
DI 10.1093/cercor/bhs385
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA AD2FC
UT WOS:000333048200017
PM 23242199
ER
PT J
AU Marques, A
Telford, SR
Turk, SP
Chung, E
Williams, C
Dardick, K
Krause, PJ
Brandeburg, C
Crowder, CD
Carolan, HE
Eshoo, MW
Shaw, PA
Hu, LT
AF Marques, Adriana
Telford, Sam R., III
Turk, Siu-Ping
Chung, Erin
Williams, Carla
Dardick, Kenneth
Krause, Peter J.
Brandeburg, Christina
Crowder, Christopher D.
Carolan, Heather E.
Eshoo, Mark W.
Shaw, Pamela A.
Hu, Linden T.
TI Xenodiagnosis to Detect Borrelia burgdorferi Infection: A First-in-Human
Study
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE xenodiagnosis; Ixodes scapularis; Lyme disease; Borrelia burgdorferi;
human
ID IONIZATION MASS-SPECTROMETRY; POLYMERASE-CHAIN-REACTION; LYME-DISEASE;
ANTIBIOTIC-TREATMENT; ERYTHEMA MIGRANS; MICE; SKIN; IDENTIFICATION;
THERAPY; LESIONS
AB Background. Animal studies suggest that Borrelia burgdorferi, the agent of Lyme disease, may persist after antibiotic therapy and can be detected by various means including xenodiagnosis using the natural tick vector (Ixodes scapularis). No convincing evidence exists for the persistence of viable spirochetes after recommended courses of antibiotic therapy in humans. We determined the safety of using I. scapularis larvae for the xenodiagnosis of B. burgdorferi infection in humans.
Methods. Laboratory-reared larval I. scapularis ticks were placed on 36 subjects and allowed to feed to repletion. Ticks were tested for B. burgdorferi by polymerase chain reaction (PCR), culture, and/or isothermal amplification followed by PCR and electrospray ionization mass spectroscopy. In addition, attempts were made to infect immunodeficient mice by tick bite or inoculation of tick contents. Xenodiagnosis was repeated in 7 individuals.
Results. Xenodiagnosis was well tolerated with no severe adverse events. The most common adverse event was mild itching at the tick attachment site. Xenodiagnosis was negative in 16 patients with posttreatment Lyme disease syndrome (PTLDS) and/or high C6 antibody levels and in 5 patients after completing antibiotic therapy for erythema migrans. Xenodiagnosis was positive for B. burgdorferi DNA in a patient with erythema migrans early during therapy and in a patient with PTLDS. There is insufficient evidence, however, to conclude that viable spirochetes were present in either patient.
Conclusions. Xenodiagnosis using Ixodes scapularis larvae was safe and well tolerated. Further studies are needed to determine the sensitivity of xenodiagnosis in patients with Lyme disease and the significance of a positive result.
C1 [Marques, Adriana; Turk, Siu-Ping] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Telford, Sam R., III] Tufts Univ, Dept Infect Dis & Global Hlth, Cummings Sch Vet Med, Boston, MA 02111 USA.
[Chung, Erin; Brandeburg, Christina; Hu, Linden T.] Tufts Med Ctr, Div Geog Med & Infect Dis, Dept Med, Boston, MA USA.
[Williams, Carla] NCI Frederick, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Dardick, Kenneth] Mansfield Family Practice, Storrs, CT USA.
[Krause, Peter J.] Yale Univ, Sch Med, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA.
[Crowder, Christopher D.; Carolan, Heather E.; Eshoo, Mark W.] Ibis Biosci Inc, Carlsbad, CA USA.
[Shaw, Pamela A.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Hu, LT (reprint author), Tufts Med Ctr, 800 Washington St,Box 41, Boston, MA 02111 USA.
EM lhu@tuftsmedicalcenter.org
RI Hu, Linden/L-6314-2016
OI Hu, Linden/0000-0003-1659-5558
FU NIH, NIAID; NIH Bench; NIAID [R21AI082436]; NIH [2R44AI077156]; Gordon
and Llura Gund Foundation
FX Financial support. This research was supported by the Intramural
Research Program of the NIH, NIAID (A. M., S. P. T., C. W., P. W.), the
NIH Bench to Bedside program (A. M., L. T. H.), and the NIAID (grant
number R21AI082436 to L. T. H.). This work was also partially supported
by the NIH (grant number 2R44AI077156 to M. W. E., C. D. C., H. E. C.)
and the Gordon and Llura Gund Foundation (to P. J. K.).
NR 30
TC 24
Z9 25
U1 0
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD APR 1
PY 2014
VL 58
IS 7
BP 937
EP 945
DI 10.1093/cid/cit939
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AD2HM
UT WOS:000333055400006
PM 24523212
ER
PT J
AU Lee, JK
Chung, HJ
Fischer, L
Fischer, J
Gonzalez, FJ
Jeong, H
AF Lee, Jin Kyung
Chung, Hye Jin
Fischer, Liam
Fischer, James
Gonzalez, Frank J.
Jeong, Hyunyoung
TI Human Placental Lactogen Induces CYP2E1 Expression via PI3-Kinase
Pathway in Female Human Hepatocytes
SO DRUG METABOLISM AND DISPOSITION
LA English
DT Article
ID GROWTH-HORMONE; CYTOCHROME-P450 EXPRESSION; PROLACTIN INCREASES;
GENE-EXPRESSION; PROTEIN-KINASE; IN-VITRO; PREGNANCY; INDUCTION; LIVER;
CELLS
AB The state of pregnancy is known to alter hepatic drug metabolism. Hormones that rise during pregnancy are potentially responsible for the changes. Here we report the effects of prolactin (PRL), placental lactogen (PL), and growth hormone variant (GH-v) on expression of major hepatic cytochromes P450 expression and a potential molecular mechanism underlying CYP2E1 induction by PL. In female human hepatocytes, PRL and GH-v showed either no effect or small and variable effects on mRNA expression of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4, and 3A5. On the other hand, PL increased expression level of CYP2E1 mRNA with corresponding increases in CYP2E1 protein and activity levels. Results from hepatocytes and HepaRG cells indicate that PL does not affect the expression or activity of HNF1 alpha, the known transcriptional activator of basal CYP2E1 expression. Furthermore, transient transfection studies and Western blot results showed that STAT signaling, the previously known mediator of PL actions in certain tissues, does not play a role in CYP2E1 induction by PL. A chemical inhibitor of PI3-kinase signaling significantly repressed the CYP2E1 induction by PL in human hepatocytes, suggesting involvement of PI3-kinase pathway in CYP2E1 regulation by PL. CYP2E1-humanized mice did not exhibit enhanced CYP2E1 expression during pregnancy, potentially because of interspecies differences in PL physiology. Taken together, these results indicate that PL induces CYP2E1 expression via PI3-kinase pathway in human hepatocytes.
C1 [Lee, Jin Kyung; Chung, Hye Jin; Fischer, Liam; Fischer, James; Jeong, Hyunyoung] Univ Illinois, Coll Pharm, Dept Pharm Practice, Chicago, IL 60612 USA.
[Chung, Hye Jin] Gyeongsang Natl Univ, Coll Pharm, Jinju, South Korea.
[Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Jeong, Hyunyoung] Univ Illinois, Coll Pharm, Dept Biopharmaceut Sci, Chicago, IL 60612 USA.
RP Jeong, H (reprint author), Univ Illinois, Coll Pharm, Dept Pharm Practice MC 886, 833 S Wood St, Chicago, IL 60612 USA.
EM yjeong@uic.edu
OI Chung, Hye Jin/0000-0003-2274-6607
FU National Institutes of Health Eunice Kennedy Shriver National Institute
of Child Health and Human Development [HD065532]; Liver Tissue Cell
Distribution System [NIH] [N01-DK-7-0004/HHSN267200700004C]
FX This work was supported by the National Institutes of Health Eunice
Kennedy Shriver National Institute of Child Health and Human Development
[Grant HD065532]. Human hepatocytes were obtained through the Liver
Tissue Cell Distribution System [NIH Contract
#N01-DK-7-0004/HHSN267200700004C].
NR 41
TC 5
Z9 5
U1 0
U2 6
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0090-9556
EI 1521-009X
J9 DRUG METAB DISPOS
JI Drug Metab. Dispos.
PD APR
PY 2014
VL 42
IS 4
BP 492
EP 499
DI 10.1124/dmd.113.055384
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AC9GN
UT WOS:000332842500002
PM 24408518
ER
PT J
AU DeGrazia, D
AF DeGrazia, David
TI On the Moral Status of Infants and the Cognitively Disabled: A Reply to
Jaworska and Tannenbaum
SO ETHICS
LA English
DT Editorial Material
AB Agnieszka Jaworska and Julie Tannenbaum address a central problem confronting efforts to understand moral status: the Problem of Nonparadigm Humans. The authors contend that human infants and cognitively disabled human beings whose capacities are comparable to those of dogs nevertheless have higher moral status. In this discussion, I will first reconstruct the authors'' assumptions and argumentative goals. In the article''s two major sections, I will examine the authors'' reasoning in pursuit of those goals and contend that the chain of argumentation contains several weak links. The discussion will close with brief reflections on how the problem might be addressed.
C1 [DeGrazia, David] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
[DeGrazia, David] George Washington Univ, Washington, DC 20052 USA.
RP DeGrazia, D (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA.
EM ddd@gwu.edu
NR 9
TC 2
Z9 2
U1 0
U2 2
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0014-1704
EI 1539-297X
J9 ETHICS
JI Ethics
PD APR 1
PY 2014
VL 124
IS 3
BP 543
EP 556
DI 10.1086/675077
PG 14
WC Ethics; Philosophy
SC Social Sciences - Other Topics; Philosophy
GA AD2OQ
UT WOS:000333075400004
ER
PT J
AU Christen, WG
Chew, EY
AF Christen, William G.
Chew, Emily Y.
TI Does long-term aspirin use increase the risk of neovascular age-related
macular degeneration?
SO EXPERT OPINION ON DRUG SAFETY
LA English
DT Review
DE age-related macular degeneration; aspirin; observational studies;
randomized trials
ID MASSIVE INTRAOCULAR HEMORRHAGE; BEAVER DAM EYE; CARDIOVASCULAR-DISEASE;
UNITED-STATES; LASER PHOTOCOAGULATION; VISUAL IMPAIRMENT; MACULOPATHY;
OLDER; ANTICOAGULANTS; ADULTS
AB Introduction: Aspirin is used regularly for rheumatoid pain management and cardioprotection. However, aspirin has also been associated with significant adverse events, such as cerebral and gastrointestinal bleeding. Recent findings from several observational epidemiologic studies indicate that regular aspirin use may also be associated with increased risks of some forms of age-related macular degeneration (AMD).
Areas covered: In this report, we review recent findings from observational epidemiologic studies suggesting a possible adverse effect of regular aspirin use in AMD, and in particular, neovascular AMD. These findings are considered in light of the relative strengths and limitations of observational studies and randomized trials.
Expert opinion: While the findings are important and warrant further investigation, the inherent limitations of observational studies, most notably uncontrolled confounding, preclude an interpretation of causality. Alternatively, the most reliable evidence with which to evaluate the effects of regular aspirin use in AMD will derive from well-designed randomized trials of sufficient size and duration. Such information is unlikely to alter current recommendations for persons at high risk of cardiovascular disease, but should help clarify the benefit-to-risk ratio of regular aspirin use in the large majority of individuals at low-to-moderate risk.
C1 [Christen, William G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med,Dept Med, Boston, MA 02115 USA.
[Chew, Emily Y.] NEI, NIH, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
RP Christen, WG (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med,Dept Med, Boston, MA 02115 USA.
EM wchristen@rics.bwh.harvard.edu
NR 44
TC 6
Z9 6
U1 2
U2 16
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1474-0338
EI 1744-764X
J9 EXPERT OPIN DRUG SAF
JI Expert Opin. Drug Saf.
PD APR
PY 2014
VL 13
IS 4
BP 421
EP 429
DI 10.1517/14740338.2014.889680
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AD2ET
UT WOS:000333047200003
PM 24547895
ER
PT J
AU Bauler, LD
Hackstadt, T
AF Bauler, Laura D.
Hackstadt, Ted
TI Expression and Targeting of Secreted Proteins from Chlamydia trachomatis
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID OBLIGATE INTRACELLULAR PATHOGEN; GENOME SEQUENCE; III SECRETION;
DEVELOPMENTAL CYCLE; INCLUSION MEMBRANE; HOST-CELLS; TRANSLOCATED
PROTEIN; GENE-EXPRESSION; IN-VITRO; PNEUMONIAE
AB Chlamydia trachomatis is an obligate intracellular pathogen that replicates in a vacuole termed the inclusion. Many of the interactions of chlamydiae with the host cell are dependent upon bacterial protein synthesis and presumably exposure of these proteins to the cytosol. Because of the dearth of genetic tools for chlamydiae, previous studies examining secreted proteins required the use of heterologous bacterial systems. Recent advances in genetic manipulation of chlamydia now allow for transformation of the bacteria with plasmids. We describe here a shuttle vector system, pBOMB4, that permits expression of recombinant proteins under constitutive or conditional promoter control. We show that the inclusion membrane protein IncD is secreted in a type III-dependent manner from Yersinia pseudotuberculosis and also secreted from C. trachomatis in infected cells where it localizes appropriately to the inclusion membrane. IncD truncated of the first 30 amino acids containing the secretion signal is no longer secreted and is retained by the bacteria. Cytosolic exposure of secreted proteins can be confirmed by using CyaA, GSK, or microinjection assays. A protein predicted to be retained within the bacteria, NrdB is indeed localized to the chlamydia. In addition, we have shown that the chlamydial effector protein, CPAF, which is secreted into the host cell cytosol by a Sec-dependent pathway, also accesses the cytosol when expressed from this system. These assays should prove useful to assess the secretion of other chlamydial proteins that are potentially exposed to the cytosol of the host cell.
C1 [Bauler, Laura D.; Hackstadt, Ted] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
EM ted_hackstadt@nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Disease, National Institutes of Health
FX This study was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Disease, National
Institutes of Health
NR 78
TC 26
Z9 28
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
EI 1098-5530
J9 J BACTERIOL
JI J. Bacteriol.
PD APR
PY 2014
VL 196
IS 7
BP 1325
EP 1334
DI 10.1128/JB.01290-13
PG 10
WC Microbiology
SC Microbiology
GA AC6JW
UT WOS:000332629800004
PM 24443531
ER
PT J
AU Platts-Mills, JA
Liu, J
Gratz, J
Mduma, E
Amour, C
Swai, N
Taniuchi, M
Begum, S
Yori, PP
Tilley, DH
Lee, G
Shen, ZL
Whary, MT
Fox, JG
McGrath, M
Kosek, M
Haque, R
Houpt, ER
AF Platts-Mills, James A.
Liu, Jie
Gratz, Jean
Mduma, Esto
Amour, Caroline
Swai, Ndealilia
Taniuchi, Mami
Begum, Sharmin
Penataro Yori, Pablo
Tilley, Drake H.
Lee, Gwenyth
Shen, Zeli
Whary, Mark T.
Fox, James G.
McGrath, Monica
Kosek, Margaret
Haque, Rashidul
Houpt, Eric R.
TI Detection of Campylobacter in Stool and Determination of Significance by
Culture, Enzyme Immunoassay, and PCR in Developing Countries
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID MULTIPLEX PCR; CHILDREN; ASSAY; INFECTIONS; JEJUNI; POPULATION;
ETIOLOGY; INFANTS; ANTIGEN
AB Campylobacter is a common bacterial enteropathogen that can be detected in stool by culture, enzyme immunoassay (EIA), or PCR. We compared culture for C. jejuni/C. coli, EIA (ProSpecT), and duplex PCR to distinguish Campylobacter jejuni/C. coli and non-jejuni/coli Campylobacter on 432 diarrheal and matched control stool samples from infants in a multisite longitudinal study of enteric infections in Tanzania, Bangladesh, and Peru. The sensitivity and specificity of culture were 8.5% and 97.6%, respectively, compared with the results of EIA and 8.7% and 98.0%, respectively, compared with the results of PCR for C. jejuni/C. coli. Most (71.6%) EIA-positive samples were positive by PCR for C. jejuni/C. coli, but 27.6% were positive for nonjejuni/coli Campylobacter species. Sequencing of 16S rRNA from 53 of these non-jejuni/coli Campylobacter samples showed that it most closely matched the 16S rRNA of C. hyointestinalis subsp. lawsonii (56%), C. troglodytis (33%), C. upsaliensis (7.7%), and C. jejuni/C. coli (2.6%). Campylobacter-negative stool spiked with each of the above-mentioned Campylobacter species revealed reactivity with EIA. PCR detection of Campylobacter species was strongly associated with diarrhea in Peru (odds ratio [OR] = 3.66, P < 0.001) but not in Tanzania (OR = 1.56, P = 0.24) or Bangladesh (OR = 1.13, P = 0.75). According to PCR, Campylobacter jejuni/C. coli infections represented less than half of all infections with Campylobacter species. In sum, in infants in developing country settings, the ProSpecT EIA and PCR for Campylobacter reveal extremely high rates of positivity. We propose the use of PCR because it retains high sensitivity, can ascertain burden, and can distinguish between Campylobacter infections at the species level.
C1 [Platts-Mills, James A.; Liu, Jie; Gratz, Jean; Taniuchi, Mami; Houpt, Eric R.] Univ Virginia, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA.
[Mduma, Esto] Haydom Lutheran Hosp, Haydom, Tanzania.
[Amour, Caroline; Swai, Ndealilia] Kilimanjaro Clin Res Inst, Moshi, Tanzania.
[Begum, Sharmin; Haque, Rashidul] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh.
[Penataro Yori, Pablo; Kosek, Margaret] Asociac Benef PRISMA, Iquitos, Peru.
[Penataro Yori, Pablo; Lee, Gwenyth; Kosek, Margaret] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Tilley, Drake H.] US Naval Med Res Unit 6, Lima, Peru.
[Shen, Zeli; Whary, Mark T.; Fox, James G.] MIT, Cambridge, MA USA.
[McGrath, Monica] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Houpt, ER (reprint author), Univ Virginia, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA.
EM erh6k@virginia.edu
FU Bill & Melinda Gates Foundation [OPP1019093]; Foundation for the NIH;
National Institutes of Health/Fogarty International Center; American
College of Gastroenterology Clinical Research Award
FX This project was undertaken in collaboration with the Etiology, Risk
Factors and Interactions of Enteric Infections and Malnutrition and the
Consequences for Child Health and Development (MAL-ED) network. The
MAL-ED project is carried out as a collaborative project supported by
the Bill & Melinda Gates Foundation, the Foundation for the NIH, and the
National Institutes of Health/Fogarty International Center. This work
was also supported by the Bill & Melinda Gates Foundation (OPP1019093)
and an American College of Gastroenterology Clinical Research Award.
NR 28
TC 18
Z9 18
U1 1
U2 14
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD APR
PY 2014
VL 52
IS 4
BP 1074
EP 1080
DI 10.1128/JCM.02935-13
PG 7
WC Microbiology
SC Microbiology
GA AC9CS
UT WOS:000332832300010
PM 24452175
ER
PT J
AU Compton, SN
Peris, TS
Almirall, D
Birmaher, B
Sherrill, J
Kendall, PC
March, JS
Gosch, EA
Ginsburg, GS
Rynn, MA
Piacentini, JC
McCracken, JT
Keeton, CP
Suveg, CM
Aschenbrand, SG
Sakolsky, D
Iyengar, S
Walkup, JT
Albano, AM
AF Compton, Scott N.
Peris, Tara S.
Almirall, Daniel
Birmaher, Boris
Sherrill, Joel
Kendall, Phillip C.
March, John S.
Gosch, Elizabeth A.
Ginsburg, Golda S.
Rynn, Moira A.
Piacentini, John C.
McCracken, James T.
Keeton, Courtney P.
Suveg, Cynthia M.
Aschenbrand, Sasha G.
Sakolsky, Dara
Iyengar, Satish
Walkup, John T.
Albano, Anne Marie
TI Predictors and Moderators of Treatment Response in Childhood Anxiety
Disorders: Results From the CAMS Trial
SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
LA English
DT Article
DE childhood; adolescent; anxiety disorders; predictors; moderators
ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED
CLINICAL-TRIAL; CAREGIVER STRAIN QUESTIONNAIRE; GLOBAL ASSESSMENT SCALE;
FALSE DISCOVERY RATE; PSYCHOMETRIC PROPERTIES; PSYCHOSOCIAL TREATMENTS;
EMOTIONAL DISORDERS; FAMILY TREATMENT
AB Objective: We sought to examine predictors and moderators of treatment outcomes among 488 youths ages 7-17 years (50% female; 74% <= 12 years) meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000) criteria for diagnoses of separation anxiety disorder, social phobia, or generalized anxiety disorder who were randomly assigned to receive either cognitive behavioral therapy (CBT), sertraline (SRT), their combination (COMB), or medication management with pill placebo (PBO) in the Child/Adolescent Anxiety Multimodal Study (CAMS). Method: Six classes of predictor and moderator variables (22 variables) were identified from the literature and examined using continuous (Pediatric Anxiety Ratings Scale; PARS) and categorical (Clinical Global Impression Scale-Improvement; CGI-I) outcome measures. Results: Three baseline variables predicted better outcomes (independent of treatment condition) on the PARS, including low anxiety severity (as measured by parents and independent evaluators) and caregiver strain. No baseline variables were found to predict Week 12 responder status (CGI-I). Participants' principal diagnosis moderated treatment outcomes but only on the PARS. No baseline variables were found to moderate treatment outcomes on Week 12 responder status (CGI-I). Discussion: Overall, anxious children responded favorably to CAMS treatments. However, having more severe and impairing anxiety, greater caregiver strain, and a principal diagnosis of social phobia were associated with less favorable outcomes. Clinical implications of these findings are discussed.
C1 [Compton, Scott N.; March, John S.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA.
[Peris, Tara S.; Piacentini, John C.; McCracken, James T.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA.
[Almirall, Daniel] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48109 USA.
[Birmaher, Boris; Sakolsky, Dara; Iyengar, Satish] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA.
[Sherrill, Joel] NIMH, Div Serv & Intervent Res, Rockville, MD 20857 USA.
[Kendall, Phillip C.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA.
[Gosch, Elizabeth A.] Philadelphia Coll Osteopath Med, Dept Psychol, Philadelphia, PA USA.
[Ginsburg, Golda S.; Keeton, Courtney P.] Johns Hopkins Univ Hosp, Div Child & Adolescent Psychiat, Baltimore, MD 21287 USA.
[Rynn, Moira A.; Aschenbrand, Sasha G.; Albano, Anne Marie] Columbia Univ, Med Ctr, Dept Child Psychiat, New York, NY 10027 USA.
[Suveg, Cynthia M.] Univ Georgia, Dept Psychol, Athens, GA 30602 USA.
[Walkup, John T.] Weill Cornell Med Coll, Div Child & Adolescent Psychiat, New York, NY USA.
RP Compton, SN (reprint author), Duke Univ, Med Ctr, DUMC Box 3527, Durham, NC 27710 USA.
EM scompton@duke.edu
FU NIDA NIH HHS [P50 DA010075]; NIMH NIH HHS [U01 MH063747, K23 MH075843,
K24 MH096760, L40 MH072315, R03 MH097954, U01 MH064003, U01 MH064088,
U01 MH064089, U01 MH064092, U01 MH064107, U01 MH63747, U01 MH64003, U01
MH64088, U01 MH64092, U01 MH64107]
NR 87
TC 37
Z9 37
U1 7
U2 41
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-006X
EI 1939-2117
J9 J CONSULT CLIN PSYCH
JI J. Consult. Clin. Psychol.
PD APR
PY 2014
VL 82
IS 2
BP 212
EP 224
DI 10.1037/a0035458
PG 13
WC Psychology, Clinical
SC Psychology
GA AD7RR
UT WOS:000333463400004
PM 24417601
ER
PT J
AU Lambert, LC
AF Lambert, Linda C.
TI Pertussis Vaccine Trials in the 1990s
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Bordetella; pertussis; vaccine; whole-cell; acellular; DTwP; DTaP;
efficacy
ID WHOOPING-COUGH; 3-COMPONENT; 2-COMPONENT; EFFICACY; CHILDREN;
IMMUNIZATION; EXPERIENCE; INFANCY; AGE
AB The significant burden of disease due to pertussis, which predominantly affects newborns during their first few months of life, was substantially decreased following the introduction of inactivated whole-bacterial-cell vaccines in the middle of the 20th century. Although these vaccines were effective in reducing the incidence of pertussis in the countries that implemented their widespread use, increasing concerns about pertussis vaccine-associated adverse events led the development of acellular pertussis vaccines containing 1 or more purified Bordetella pertussis proteins. During the 1990s, collaborative international clinical trials were conducted to evaluate the safety, immunogenicity, and/or efficacy of different acellular vaccines.
C1 [Lambert, Linda C.] NIAID, Div Microbiol & Infect Dis, Bethesda, MD 20817 USA.
RP Lambert, LC (reprint author), NIAID, Resp Dis Branch, Div Microbiol & Infect Dis, NIH,DHHS, Rm 3401,6610 Rockledge Dr, Bethesda, MD 20817 USA.
EM LL153P@nih.gov
NR 22
TC 10
Z9 10
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD APR 1
PY 2014
VL 209
SU 1
BP S4
EP S9
DI 10.1093/infdis/jit592
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AD2TN
UT WOS:000333088400002
PM 24626871
ER
PT J
AU Okiyama, N
Furumoto, Y
Villarroel, VA
Linton, JT
Tsai, WL
Gutermuth, J
Ghoreschi, K
Gadina, M
O'Shea, JJ
Katz, SI
AF Okiyama, Naoko
Furumoto, Yasuko
Villarroel, Vadim A.
Linton, Jay T.
Tsai, Wanxia L.
Gutermuth, Jan
Ghoreschi, Kamran
Gadina, Massimo
O'Shea, John J.
Katz, Stephen I.
TI Reversal of CD8 T-Cell-Mediated Mucocutaneous Graft-Versus-Host-Like
Disease by the JAK Inhibitor Tofacitinib
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID JANUS KINASE INHIBITOR; ACTIVE RHEUMATOID-ARTHRITIS; BONE-MARROW
TRANSPLANTATION; SKIN-DISEASE; MURINE MODEL; DOUBLE-BLIND; CP-690550;
PLACEBO; CP-690,550; PSORIASIS
AB The utility of allogeneic hematopoietic stem cell transplantation is limited by graft-versus-host disease (GVHD), a significant cause of morbidity and mortality. Patients with GVHD exhibit cutaneous manifestations with histological features of interface dermatitis followed by scleroderma-like changes. JAK inhibitors represent a class of immunomodulatory drugs that inhibit signaling by multiple cytokines. Herein we report the effects of tofacitinib in a murine model of GVHD. Oral administration of tofacitinib prevented GVHD-like disease manifested by weight loss and mucocutaneous lesions. More importantly, tofacitinib was also effective in reversing established disease. Tofacitinib diminished the expansion and activation of murine CD8 T cells in this model, and had similar effects on IL-2-stimulated human CD8 T cells. Tofacitinib also inhibited the expression of IFN-gamma-inducible chemoattractants by keratinocytes, and IFN-gamma-inducible cell death of keratinocytes. Tofacitinib may be an effective drug for treatment against CD8 T-cell-mediated mucocutaneous diseases in patients with GVHD.
C1 [Okiyama, Naoko; Villarroel, Vadim A.; Linton, Jay T.; Gutermuth, Jan; Katz, Stephen I.] NCI, Dermatol Branch, Bethesda, MD 20892 USA.
[Furumoto, Yasuko; Tsai, Wanxia L.; Gadina, Massimo] NIAMSD, Translat Immunol Sect, NIH, Bethesda, MD 20892 USA.
[Ghoreschi, Kamran; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
RP Katz, SI (reprint author), NIH, Dermatol Branch, Bldg 31,Room 4C32, Bethesda, MD 20892 USA.
EM katzs@od.niams.nih.gov
FU Pfizer
FX YF, KG, MG, and JJO'S receive research funding from Pfizer under a
Collaborative Research Agreement and Development Award. JJO'S receives
royalties from a US Patent related to targeting JAKs.
NR 39
TC 10
Z9 10
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD APR
PY 2014
VL 134
IS 4
BP 992
EP 1000
DI 10.1038/jid.2013.476
PG 9
WC Dermatology
SC Dermatology
GA AD4DQ
UT WOS:000333197500019
PM 24213371
ER
PT J
AU Matsuzawa, T
Kawamura, T
Ogawa, Y
Maeda, K
Nakata, H
Moriishi, K
Koyanagi, Y
Gatanaga, H
Shimada, S
Mitsuya, H
AF Matsuzawa, Takamitsu
Kawamura, Tatsuyoshi
Ogawa, Youichi
Maeda, Kenji
Nakata, Hirotomo
Moriishi, Kohji
Koyanagi, Yoshio
Gatanaga, Hiroyuki
Shimada, Shinji
Mitsuya, Hiroaki
TI EFdA, a Reverse Transcriptase Inhibitor, Potently Blocks HIV-1 Ex Vivo
Infection of Langerhans Cells within Epithelium
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Letter
ID DENDRITIC CELLS; HIGHLY POTENT; 2'-DEOXY-4'-C-ETHYNYL-2-FLUOROADENOSINE;
MICROBICIDES; STRATEGIES; MUCOSA; TYPE-1
C1 [Matsuzawa, Takamitsu; Kawamura, Tatsuyoshi; Ogawa, Youichi; Shimada, Shinji] Univ Yamanashi, Dept Dermatol, Fac Med, Yamanashi, Japan.
[Maeda, Kenji; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Nakata, Hirotomo; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Infect Dis & Hematol, Kumamoto 860, Japan.
[Moriishi, Kohji] Univ Yamanashi, Dept Microbiol, Fac Med, Yamanashi, Japan.
[Koyanagi, Yoshio] Kyoto Univ, Inst Virus Res, Lab Viral Pathogenesis, Kyoto 606, Japan.
[Gatanaga, Hiroyuki] Natl Ctr Global Hlth & Med, AIDS Clin Ctr, Tokyo, Japan.
RP Matsuzawa, T (reprint author), Univ Yamanashi, Dept Dermatol, Fac Med, Yamanashi, Japan.
EM tkawa@yamanashi.ac.jp
FU Intramural NIH HHS
NR 15
TC 2
Z9 2
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD APR
PY 2014
VL 134
IS 4
BP 1158
EP 1161
DI 10.1038/jid.2013.467
PG 4
WC Dermatology
SC Dermatology
GA AD4DQ
UT WOS:000333197500046
PM 24384694
ER
PT J
AU Rid, A
Wendler, D
AF Rid, Annette
Wendler, David
TI Use of a Patient Preference Predictor to Help Make Medical Decisions for
Incapacitated Patients
SO JOURNAL OF MEDICINE AND PHILOSOPHY
LA English
DT Article
DE advance care planning; advance directives; decisional incapacity;
surrogates; treatment decision making
ID LIFE-SUSTAINING TREATMENT; RANDOMIZED CONTROLLED-TRIAL; HEALTH-STATE
EVALUATIONS; SERIOUSLY ILL PATIENTS; QUALITY-OF-LIFE; ADVANCE
DIRECTIVES; CARDIOPULMONARY-RESUSCITATION; SUBSTITUTED JUDGMENTS;
POSTTRAUMATIC STRESS; ADULTS PREFERENCES
AB The standard approach to treatment decision making for incapacitated patients often fails to provide treatment consistent with the patient's preferences and values and places significant stress on surrogate decision makers. These shortcomings provide compelling reason to search for methods to improve current practice. Shared decision making between surrogates and clinicians has important advantages, but it does not provide a way to determine patients' treatment preferences. Hence, shared decision making leaves families with the stressful challenge of identifying the patient's preferred treatment option. To address this concern, the present paper proposes to incorporate the use of a "Patient Preference Predictor" (PPP) into the shared decision-making process between surrogates and clinicians. A PPP would predict which treatment option a given incapacitated patient would most likely prefer, based on the individual's characteristics and information on what treatment preferences are correlated with these characteristics. Use of a PPP is likely to increase the chances that incapacitated patients are treated consistent with their preferences and values and might reduce the stress and burden on their surrogates. Including a PPP in the shared decision-making process therefore has the potential to realize important ethical goals for making treatment decisions for incapacitated patients. The present paper justifies this approach on conceptual and normative grounds.
C1 [Rid, Annette] Kings Coll London, Dept Social Sci Hlth & Med, London WC2R 2LS, England.
[Rid, Annette] Univ Zurich, Inst Biomed Eth, Zurich, Switzerland.
[Wendler, David] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Rid, A (reprint author), Kings Coll London, Dept Social Sci Hlth & Med, London WC2R 2LS, England.
EM annette.rid@kcl.ac.uk
NR 62
TC 16
Z9 16
U1 2
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0360-5310
EI 1744-5019
J9 J MED PHILOS
JI J. Med. Philos.
PD APR
PY 2014
VL 39
IS 2
BP 104
EP 129
DI 10.1093/jmp/jhu001
PG 26
WC Ethics; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Biomedical Social Sciences
GA AD2TT
UT WOS:000333089000002
PM 24526785
ER
PT J
AU Rid, A
Wendler, D
AF Rid, Annette
Wendler, David
TI Treatment Decision Making for Incapacitated Patients: Is Development and
Use of a Patient Preference Predictor Feasible?
SO JOURNAL OF MEDICINE AND PHILOSOPHY
LA English
DT Article
DE advance care planning; advance directives; decisional incapacity;
surrogates; treatment decision making
ID LIFE-SUSTAINING TREATMENT; SERIOUSLY ILL PATIENTS; OF-LIFE; ADVANCE
DIRECTIVES; CARDIOPULMONARY-RESUSCITATION; ADULTS PREFERENCES; TREATMENT
CHOICES; CARE PREFERENCES; CANCER-PATIENTS; VALUES HISTORY
AB It has recently been proposed to incorporate the use of a Patient Preference Predictor (PPP) into the process of making treatment decisions for incapacitated patients. A PPP would predict which treatment option a given incapacitated patient would most likely prefer, based on the individuals characteristics and information on what treatment preferences are correlated with these characteristics. Including a PPP in the shared decision-making process between clinicians and surrogates has the potential to better realize important ethical goals for making treatment decisions for incapacitated patients. However, developing and implementing a PPP poses significant practical challenges. The present paper discusses these practical challenges and considers ways to address them.
C1 [Rid, Annette] Kings Coll London, Dept Social Sci Hlth & Med, London WC2R 2LS, England.
[Rid, Annette] Univ Zurich, Inst Biomed Eth, Zurich, Switzerland.
[Wendler, David] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
RP Rid, A (reprint author), Kings Coll London, Dept Social Sci Hlth & Med, London WC2R 2LS, England.
EM annette.rid@kcl.ac.uk
NR 44
TC 12
Z9 13
U1 2
U2 11
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0360-5310
EI 1744-5019
J9 J MED PHILOS
JI J. Med. Philos.
PD APR
PY 2014
VL 39
IS 2
BP 130
EP 152
DI 10.1093/jmp/jhu006
PG 23
WC Ethics; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Biomedical Social Sciences
GA AD2TT
UT WOS:000333089000003
PM 24556152
ER
PT J
AU Dennis, AF
McDonald, SM
Payne, DC
Mijatovic-Rustempasic, S
Esona, MD
Edwards, KM
Chappell, JD
Patton, JT
AF Dennis, Allison F.
McDonald, Sarah M.
Payne, Daniel C.
Mijatovic-Rustempasic, Slavica
Esona, Mathew D.
Edwards, Kathryn M.
Chappell, James D.
Patton, John T.
TI Molecular Epidemiology of Contemporary G2P[4] Human Rotaviruses
Cocirculating in a Single US Community: Footprints of a Globally
Transitioning Genotype
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID GROUP-A ROTAVIRUS; IMMUNIZATION PRACTICES ACIP;
LINKED-IMMUNOSORBENT-ASSAY; PHYLOGENETIC ANALYSIS; ADVISORY-COMMITTEE;
UNITED-STATES; STRAINS; GASTROENTERITIS; CHILDREN; VACCINATION
AB Group A rotaviruses (RVs) remain a leading cause of childhood gastroenteritis worldwide. Although the G/P types of locally circulating RVs can vary from year to year and differ depending upon geographical location, those with G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], and G12P[8] specificities typically dominate. Little is known about the evolution and diversity of G2P[4] RVs and the possible role that widespread vaccine use has had on their increased frequency of detection. To address these issues, we analyzed the 12 G2P[4] RV isolates associated with a rise in RV gastroenteritis cases at Vanderbilt University Medical Center (VUMC) during the 2010-2011 winter season. Full-genome sequencing revealed that the isolates had genotype 2 constellations typical of DS-1-like viruses (G2P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2). Phylogenetic analyses showed that the genome segments of the isolates were comprised of two or three different subgenotype alleles; this enabled recognition of three distinct clades of G2P[4] viruses that caused disease at VUMC in the 2010-2011 season. Although the three clades cocirculated in the same community, there was no evidence of interclade reassortment. Bayesian analysis of 328 VP7 genes of G2 viruses isolated in the last 39 years indicate that existing G2 VP7 gene lineages continue to evolve and that novel lineages, as represented by the VUMC isolates, are constantly being formed. Moreover, G2 lineages are characteristically shaped by lineage turnover events that introduce new globally dominant strains every 7 years, on average. The ongoing evolution of G2 VP7 lineages may give rise to antigenic changes that undermine vaccine effectiveness in the long term.
C1 [Dennis, Allison F.; McDonald, Sarah M.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Payne, Daniel C.; Mijatovic-Rustempasic, Slavica; Esona, Mathew D.] Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
[Edwards, Kathryn M.; Chappell, James D.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA.
[Chappell, James D.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA.
RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM jpatton@niaid.nih.gov
RI Patton, John/P-1390-2014
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID) of the National Institutes of Health (NIH)
FX A.F.D., S.M.M., and J.T.P. were supported by the Intramural Research
Program of the National Institute of Allergy and Infectious Diseases
(NIAID) of the National Institutes of Health (NIH).
NR 68
TC 25
Z9 25
U1 1
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2014
VL 88
IS 7
BP 3789
EP 3801
DI 10.1128/JVI.03516-13
PG 13
WC Virology
SC Virology
GA AC6IH
UT WOS:000332624700015
PM 24429371
ER
PT J
AU Nair, S
Sanchez-Martinez, S
Ji, XH
Rein, A
AF Nair, Smita
Sanchez-Martinez, Silvia
Ji, Xinhua
Rein, Alan
TI Biochemical and Biological Studies of Mouse APOBEC3
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MURINE LEUKEMIA-VIRUS; REVERSE TRANSCRIPTION; CYTIDINE DEAMINATION;
TYPE-1 INFECTION; HIV-1 VIRIONS; 7SL RNA; PROTEIN; VIF; DNA; REPLICATION
AB Many murine leukemia viruses (MLVs) are partially resistant to restriction by mouse APOBEC3 (mA3) and essentially fully resistant to induction of G-to-A mutations by mA3. In contrast, Vif-deficient HIV-1 (Delta Vif HIV-1) is profoundly restricted by mA3, and the restriction includes high levels of G-to-A mutation. Human APOBEC3G (hA3G), unlike mA3, is fully active against MLVs. We produced a glutathione S-transferase-mA3 fusion protein in insect cells and demonstrated that it possesses cytidine deaminase activity, as expected. This activity is localized within the N-terminal domain of this 2-domain protein; the C-terminal domain is enzymatically inactive but required for mA3 encapsidation into retrovirus particles. We found that a specific arginine residue and several aromatic residues, as well as the zinc-coordinating cysteines in the C-terminal domain, are necessary for mA3 packaging; a structural model of this domain suggests that these residues line a potential nucleic acid-binding interface. Mutation of a few potential phosphorylation sites in mA3 drastically reduces its antiviral activity by impairing either deaminase activity or its encapsidation. mA3 deaminates short single-stranded DNA oligonucleotides preferentially toward their 3 ' ends, whereas hA3G exhibits the opposite polarity. However, when packaged into infectious Delta VifHIV-1 virions, both mA3 and hA3G preferentially induce deaminations toward the 5 ' end of minus-strand viral DNA, presumably because of the sequence of events during reverse transcription in vivo. Despite the fact that mA3 in MLV particles does not induce detectable deaminations upon infection, its deaminase activity is easily detected in virus lysates. We still do not understand how MLV resists mA3-induced G-to-A mutation.
C1 [Nair, Smita; Sanchez-Martinez, Silvia; Rein, Alan] NIH, Ctr Canc Res, HIV Drug Resistance Program, Frederick, MD USA.
[Ji, Xinhua] NIH, Ctr Canc Res, Macromol Crystallog Lab, Frederick, MD USA.
RP Rein, A (reprint author), NIH, Ctr Canc Res, HIV Drug Resistance Program, Frederick, MD USA.
EM reina@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 53
TC 8
Z9 8
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2014
VL 88
IS 7
BP 3850
EP 3860
DI 10.1128/JVI.03456-13
PG 11
WC Virology
SC Virology
GA AC6IH
UT WOS:000332624700020
PM 24453360
ER
PT J
AU Mach, J
Huizer-Pajkos, A
Cogger, VC
McKenzie, C
Le Couteur, DG
Jones, BE
de Cabo, R
Hilmer, SN
AF Mach, John
Huizer-Pajkos, Aniko
Cogger, Victoria C.
McKenzie, Catriona
Le Couteur, David G.
Jones, Brett E.
de Cabo, Rafael
Hilmer, Sarah N.
TI The Effect of Aging on Acetaminophen Pharmacokinetics, Toxicity and Nrf2
in Fischer 344 Rats
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Acetaminophen; Toxicity; Aging; Pharmacokinetics
ID OXIDATIVE STRESS; INDUCED HEPATOTOXICITY; WISTAR RATS; DIETARY
RESTRICTION; SPRAGUE-DAWLEY; LIVER-INJURY; AGE; PARACETAMOL; MICE;
NEPHROTOXICITY
AB We investigated the effect of aging on hepatic pharmacokinetics and the degree of hepatotoxicity following a toxic dose of acetaminophen. Young and old male Fischer 344 rats were treated with 800 mg/kg acetaminophen (young n = 8, old n = 5) or saline (young n = 9, old n = 9). Serum measurements showed old rats treated with acetaminophen had significantly lower serum alanine aminotransferase and higher acetaminophen and acetaminophen glucuronide levels and creatinine, compared with acetaminophen treated young rats (p < .05). Immunoblotting and activity assays showed old saline-treated rats had twofold lower cytochrome P450 2E1 activity and threefold higher NAD(P)H quinone oxireductase 1 protein expression and activity than young saline-treated rats (p < .05), although Nrf2, glutathione cysteine ligase-modulatory subunit, glutathione cysteine ligase-catalytic subunit, and cytochrome P450 2E1 protein expressions were unchanged. Primary hepatocytes isolated from young rats treated with 10 mM acetaminophen had lower survival than those from old rats (52.4% +/- 5.8%, young; 83.6% +/- 1.7%, old, p < .05). The pharmacokinetic changes described may decrease susceptibility to acetaminophen-induced hepatotoxicity but may increase risk of nephrotoxicity in old age.
C1 [Mach, John; Huizer-Pajkos, Aniko; Hilmer, Sarah N.] Kolling Inst Med Res, Lab Ageing & Pharmacol, Sydney, NSW, Australia.
[Mach, John; Huizer-Pajkos, Aniko; Hilmer, Sarah N.] Royal N Shore Hosp, Dept Clin Pharmacol, Sydney, NSW, Australia.
[Mach, John; Huizer-Pajkos, Aniko; Hilmer, Sarah N.] Royal N Shore Hosp, Dept Aged Care, Sydney, NSW, Australia.
[Mach, John; Cogger, Victoria C.; Le Couteur, David G.; Jones, Brett E.; Hilmer, Sarah N.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Cogger, Victoria C.; Le Couteur, David G.] Concord Hosp, Ctr Educ & Res Aging, Concord, NSW, Australia.
[Cogger, Victoria C.; Le Couteur, David G.] Concord Hosp, Anzac Res Inst, Concord, NSW, Australia.
[Cogger, Victoria C.; Le Couteur, David G.] Univ Sydney, Sydney, NSW 2006, Australia.
[McKenzie, Catriona] Royal Prince Alfred Hosp, Dept Pathol, Sydney, NSW, Australia.
[Jones, Brett E.] Royal N Shore Hosp, Kolling Inst Med Res, Dept Gastroenterol, Sydney, NSW, Australia.
[de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
RP Hilmer, SN (reprint author), Royal N Shore Hosp, Dept Clin Pharmacol, Level 1,Acute Serv Bldg, St Leonards, NSW 2065, Australia.
EM sarah.hilmer@sydney.edu.au
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; Hilmer, Sarah/0000-0002-5970-1501;
, rafael/0000-0003-2830-5693
FU National Health and Medical Research Council [570968, 570937]; Geoff and
Elaine Penney Ageing Research Unit, Royal North Shore Hospital
FX The work was supported by the National Health and Medical Research
Council (# 570968, # 570937) and the Geoff and Elaine Penney Ageing
Research Unit, Royal North Shore Hospital.
NR 52
TC 6
Z9 6
U1 1
U2 6
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 APR
PY 2014
VL 69
IS 4
BP 387
EP 397
DI 10.1093/gerona/glt095
PG 11
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AD6QI
UT WOS:000333385500003
PM 23863315
ER
PT J
AU Volpato, S
Bianchi, L
Cherubini, A
Landi, F
Maggio, M
Savino, E
Bandinelli, S
Ceda, GP
Guralnik, JM
Zuliani, G
Ferrucci, L
AF Volpato, Stefano
Bianchi, Lara
Cherubini, Antonio
Landi, Francesco
Maggio, Marcello
Savino, Elisabetta
Bandinelli, Stefania
Ceda, Gian Paolo
Guralnik, Jack M.
Zuliani, Giovanni
Ferrucci, Luigi
TI Prevalence and Clinical Correlates of Sarcopenia in Community-Dwelling
Older People: Application of the EWGSOP Definition and Diagnostic
Algorithm
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Sarcopenia; Community-dwelling older people; Frail elderly
ID BIOELECTRICAL-IMPEDANCE ANALYSIS; SKELETAL-MUSCLE; IGF-I; INCHIANTI;
MEN; TESTOSTERONE; WOMEN; RISK; ASSOCIATION; MOBILITY
AB Background. Muscle impairment is a common condition in older people and a powerful risk factor for disability and mortality. The aim of this study was to apply the European Working Group on Sarcopenia in Older People criteria to estimate the prevalence and investigate the clinical correlates of sarcopenia, in a sample of Italian community-dwelling older people.
Methods. Cross-sectional analysis of 730 participants (74% aged 65 years and older) enrolled in the InCHIANTI study. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People criteria using bioimpedance analysis for muscle mass assessment. Logistic regression analysis was used to identify the factors independently associated with sarcopenia.
Results. Sarcopenia defined by the European Working Group on Sarcopenia in Older People criteria increased steeply with age (p < .001), with 31.6% of women and 17.4% of men aged 80 years or older being affected by this condition. Higher education (odds ratio: 0.85; 95% CI: 0.74-0.98), lower insulin-like growth factor I (lowest vs highest tertile, odds ratio: 3.89; 95% CI: 1.03-14.1), and low bioavailable testosterone (odds ratio: 2.67; 95% CI: 1.31-5.44) were independently associated with the likelihood of being sarcopenic. Nutritional intake, physical activity, and level of comorbidity were not associated with sarcopenia.
Conclusions. Sarcopenia identified by the European Working Group on Sarcopenia in Older People criteria is a relatively common condition in Italian octogenarians, and its prevalence increases with aging. Correlates of sarcopenia identified in this study might suggest new approaches for prevention and treatment of sarcopenia.
C1 [Volpato, Stefano; Bianchi, Lara; Savino, Elisabetta; Zuliani, Giovanni] Univ Ferrara, Dept Med Sci, I-44100 Ferrara, Italy.
[Cherubini, Antonio] IRCCS INRCA, Dept Geriatr, Ancona, Italy.
[Cherubini, Antonio] Univ Perugia, Inst Gerontol & Geriatr, I-06100 Perugia, Italy.
[Landi, Francesco] Univ Cattolica Sacro Cuore, Dept Gerontol & Geriatr Sci, Rome, Italy.
[Maggio, Marcello; Ceda, Gian Paolo] Univ Parma, Dept Clin & Expt Med, Sect Geriatr, I-43100 Parma, Italy.
[Maggio, Marcello; Ceda, Gian Paolo] Univ Hosp Parma, Geriatr Clin Unit, Parma, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
RP Volpato, S (reprint author), Univ Ferrara, Dept Med Sci, Via Savonarola 9, I-44100 Ferrara, Italy.
EM vlt@unife.it
RI VOLPATO, STEFANO/H-2977-2014;
OI VOLPATO, STEFANO/0000-0003-4335-6034; Ceda, Gian
Paolo/0000-0002-9648-8295; Cherubini, Antonio/0000-0003-0261-9897
FU U.S. National Institute on Aging [N01-AG-5-0002]; Intramural research
program of the National Institute on Aging, National Institutes of
Health, Baltimore, Maryland
FX The InCHIANTI Follow-up 2 study (2004-2006) was financed by the U.S.
National Institute on Aging (Contract: N01-AG-5-0002); supported in part
by the Intramural research program of the National Institute on Aging,
National Institutes of Health, Baltimore, Maryland.
NR 33
TC 53
Z9 56
U1 1
U2 12
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 APR
PY 2014
VL 69
IS 4
BP 438
EP 446
DI 10.1093/gerona/glt149
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AD6QI
UT WOS:000333385500008
PM 24085400
ER
PT J
AU Wendell, CR
Gunstad, J
Waldstein, SR
Wright, JG
Ferrucci, L
Zonderman, AB
AF Wendell, Carrington R.
Gunstad, John
Waldstein, Shari R.
Wright, Jeanette G.
Ferrucci, Luigi
Zonderman, Alan B.
TI Cardiorespiratory Fitness and Accelerated Cognitive Decline With Aging
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Cardiorespiratory fitness; Aerobic fitness; Maximal oxygen consumption;
Cognitive function; Neuropsychology
ID RANDOMIZED CONTROLLED-TRIAL; TIME PHYSICAL-ACTIVITY; AEROBIC FITNESS;
OLDER-ADULTS; ALZHEIMERS-DISEASE; EXERCISE; BRAIN; DEMENTIA; GENOTYPE;
HEALTH
AB Background. Growing evidence suggests that self-reported physical activity accounts for variability in cognitive function among older adults, and aerobic intervention may improve cognitive function in this population. However, much less is known about the longitudinal association between direct measures of cardiorespiratory fitness and cognitive function across the life span. The present study examined the prospective association between symptom-limited maximal oxygen consumption (VO(2)max) and longitudinal performance on a comprehensive neuropsychological battery.
Methods. Up to 1,400 participants aged 19-94 years underwent initial VO(2)max assessment and completed subsequent tests of memory, attention, perceptuomotor speed, language, and executive function, in addition to cognitive screening measures, on up to six occasions (mean, M = 2; standard deviation, SD = 1) for up to 18 years (M = 7, SD = 3). Mixed-effects regression models were adjusted for demographic, biomedical, and behavioral confounders.
Results. Analyses revealed significant longitudinal associations between baseline VO(2)max and trajectory of performance on multiple measures of verbal and visual memory, as well as on a cognitive screening test (all ps < .05). Individuals with lower VO(2)max demonstrated accelerated trajectories of cognitive decline over time.
Conclusions. Baseline cardiorespiratory fitness is related to longitudinal neuropsychological performance, and memory appears to be a particularly vulnerable domain. Evidence that aerobic fitness is associated with accelerated cognitive decline emphasizes the possible importance of behavioral interventions to optimize cognitive aging over time.
C1 [Wendell, Carrington R.; Wright, Jeanette G.; Ferrucci, Luigi; Zonderman, Alan B.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Wendell, Carrington R.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA.
[Gunstad, John] Kent State Univ, Dept Psychol, Kent, OH USA.
[Waldstein, Shari R.] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA.
[Waldstein, Shari R.] Univ Maryland, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Baltimore, MD 21201 USA.
[Waldstein, Shari R.] Baltimore Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA.
RP Wendell, CR (reprint author), NIA, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM rice3@umbc.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health [Z01-AG000195]
FX This research was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health
(Z01-AG000195).
NR 41
TC 18
Z9 18
U1 5
U2 24
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 APR
PY 2014
VL 69
IS 4
BP 455
EP 462
DI 10.1093/gerona/glt144
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AD6QI
UT WOS:000333385500010
PM 24192540
ER
PT J
AU Patel, MR
Taylor, RJ
Hackman, TG
Germanwala, AV
Sasaki-Adams, D
Ewend, MG
Zanation, AM
AF Patel, Mihir R.
Taylor, Robert J.
Hackman, Trevor G.
Germanwala, Anand V.
Sasaki-Adams, Deanna
Ewend, Matthew G.
Zanation, Adam M.
TI Beyond the nasoseptal flap: Outcomes and pearls with secondary flaps in
endoscopic endonasal skull base reconstruction
SO LARYNGOSCOPE
LA English
DT Article
DE skull base surgery; vascularized tissue reconstruction; Flaps
ID TRANSPTERYGOID TRANSPOSITION; PERICRANIAL FLAP; TURBINATE FLAP; DEFECTS;
SURGERY; REPAIR; OPTIONS
AB Objectives/Hypothesis
Endoscopic endonasal skull base surgery defects require effective reconstruction. Although the nasoseptal flap (NSF) has become our institution's workhorse for large skull base defects with cerebrospinal fluid (CSF) leaks, situations where it is unavailable require secondary flaps. Clinical outcomes, pearls and pitfalls, and an algorithm will be presented for these secondary flaps.
Study Design
Clinical case series.
Methods
Medical records of all endoscopic endonasal skull base surgeries at a tertiary care academic medical center were reviewed for skull base defect type, reconstruction method, CSF leak rate, and flap necrosis rate.
Results
Of 330 flaps for reconstructing endoscopic endonasal skull base defects, secondary flaps were used in 34 cases (10%). These included 16 endoscopic-assisted pericranial flaps, seven tunneled temporoparietal fascia flaps, three inferior turbinate flaps, two middle turbinate flaps, two anterior lateral nasal wall flaps, two palatal flaps, one occipital flap, and one facial artery buccinator flap. There were 19 anterior cranial fossa defects, 10 clival defects, three sellar defects, and one frontal and one lateral orbit/middle fossa defect. Twenty-five of the 34 cases (73.5%) had either prior or postoperative radiation therapy. The most common pathology was sinonasal cancer, with 16 cases (47.1%). The postoperative CSF leak rate was 3.6% due to one middle turbinate flap necrosis.
Conclusions
Secondary flaps for skull base reconstruction can be harvested with minimally invasive techniques and demonstrate excellent success rates (97%) that are comparable to that of the NSF (>95%). Multiple flaps for complex skull base defects should be in the armamentarium of comprehensive skull base surgery centers.
Level of Evidence
4. Laryngoscope, 124:846-852, 2014
C1 [Patel, Mihir R.; Taylor, Robert J.; Hackman, Trevor G.; Zanation, Adam M.] Univ N Carolina, Dept Otolaryngol Head & Neck Surg, Chapel Hill, NC 27599 USA.
[Germanwala, Anand V.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Sasaki-Adams, Deanna; Ewend, Matthew G.] Univ N Carolina, Dept Neurosurg, Chapel Hill, NC 27599 USA.
RP Zanation, AM (reprint author), Univ N Carolina, Dept Otolaryngol Head & Neck Surg, 170 Manning Dr,Phys Off Bldg,Ground Floor,CB 7070, Chapel Hill, NC 27599 USA.
EM adam_zanation@med.unc.edu
OI Patel, Mihir/0000-0001-6477-9728
FU Doris Duke Charitable Foundation
FX This work was supported by a grant from the Doris Duke Charitable
Foundation to the University of North Carolina at Chapel Hill to fund
Clinical Research Fellow R.J.T.
NR 29
TC 29
Z9 29
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0023-852X
EI 1531-4995
J9 LARYNGOSCOPE
JI Laryngoscope
PD APR
PY 2014
VL 124
IS 4
BP 846
EP 852
DI 10.1002/lary.24319
PG 7
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA AD1AB
UT WOS:000332965100017
PM 23877996
ER
PT J
AU Ramakrishnan, SK
Taylor, M
Qu, AJ
Ahn, SH
Suresh, MV
Raghavendran, K
Gonzalez, FJ
Shah, YM
AF Ramakrishnan, Sadeesh K.
Taylor, Matthew
Qu, Aijuan
Ahn, Sung-Hoon
Suresh, Madathilparambil V.
Raghavendran, Krishnan
Gonzalez, Frank J.
Shah, Yatrik M.
TI Loss of von Hippel-Lindau Protein (VHL) Increases Systemic Cholesterol
Levels through Targeting Hypoxia-Inducible Factor 2 alpha and Regulation
of Bile Acid Homeostasis
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID OBSTRUCTIVE SLEEP-APNEA; FARNESOID-X-RECEPTOR; DENSITY-LIPOPROTEIN
RECEPTOR; 7-ALPHA-HYDROXYLASE GENE; INTERMITTENT HYPOXIA; TRANSCRIPTION
FACTOR; LUNG CONTUSION; MESSENGER-RNA; LDL RECEPTOR; RISK-FACTORS
AB Cholesterol synthesis is a highly oxygen-dependent process. Paradoxically, hypoxia is correlated with an increase in cellular and systemic cholesterol levels and risk of cardiovascular diseases. The mechanism for the increase in cholesterol during hypoxia is unclear. Hypoxia signaling is mediated through hypoxia-inducible factor 1 alpha (HIF-1 alpha) and HIF-2 alpha. The present study demonstrates that activation of HIF signaling in the liver increases hepatic and systemic cholesterol levels due to a decrease in the expression of cholesterol hydroxylase CYP7A1 and other enzymes involved in bile acid synthesis. Specifically, activation of hepatic HIF-2 alpha (but not HIF-1 alpha) led to hypercholesterolemia. HIF-2 alpha repressed the circadian expression of Rev-erb alpha, resulting in increased expression of E4BP4, a negative regulator of Cyp7a1. To understand if HIF-mediated decrease in bile acid synthesis is a physiologically relevant pathway by which hypoxia maintains or increases systemic cholesterol levels, two hypoxic mouse models were assessed, an acute lung injury model and mice exposed to 10% O-2 for 3 weeks. In both models, cholesterol levels increased with a concomitant decrease in expression of genes involved in bile acid synthesis. The present study demonstrates that hypoxic activation of hepatic HIF-2 alpha leads to an adaptive increase in cholesterol levels through inhibition of bile acid synthesis.
C1 [Ramakrishnan, Sadeesh K.; Taylor, Matthew; Shah, Yatrik M.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Shah, Yatrik M.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA.
[Suresh, Madathilparambil V.; Raghavendran, Krishnan] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI USA.
[Qu, Aijuan; Ahn, Sung-Hoon; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Shah, YM (reprint author), Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
EM shahy@umich.edu
FU NIH [CA148828, DK095201, HL-102013]; University of Michigan
Gastrointestinal Peptide Center; National Cancer Institute Intramural
Research Program
FX This work was supported by NIH grants (CA148828 and DK095201 to Y.M.S
and HL-102013 to K.R.), the University of Michigan Gastrointestinal
Peptide Center (Y.M.S.), and the National Cancer Institute Intramural
Research Program (F.J.G).
NR 58
TC 4
Z9 4
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD APR
PY 2014
VL 34
IS 7
BP 1208
EP 1220
DI 10.1128/MCB.01441-13
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AC7GS
UT WOS:000332696800003
PM 24421394
ER
PT J
AU Guo, JX
Lang, LX
Hu, S
Guo, N
Zhu, L
Sun, ZC
Ma, Y
Kiesewetter, DO
Niu, G
Xie, QG
Chen, XY
AF Guo, Jinxia
Lang, Lixin
Hu, Shuo
Guo, Ning
Zhu, Lei
Sun, Zhongchan
Ma, Ying
Kiesewetter, Dale O.
Niu, Gang
Xie, Qingguo
Chen, Xiaoyuan
TI Comparison of Three Dimeric F-18-AlF-NOTA-RGD Tracers
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Article
DE NOTA; Arginine-glycine-aspartic acid (RGD); PET; Integrin
alpha(v)beta(3); Aluminum-fluoride complex
ID INTEGRIN ALPHA(V)BETA(3) EXPRESSION; CYCLIC RGD PEPTIDES; TUMOR
ANGIOGENESIS; CANCER-PATIENTS; PET; MICE; PHARMACOKINETICS;
BIODISTRIBUTION; TRANSCHELATION; F-18-FPPRGD2
AB RGD peptide-based radiotracers are well established as integrin alpha(v)beta(3) imaging probes to evaluate tumor angiogenesis or tissue remodeling after ischemia or infarction. In order to optimize the labeling process and pharmacokinetics of the imaging probes, we synthesized three dimeric RGD peptides with or without PEGylation and performed in vivo screening.
Radiolabeling was achieved through the reaction of F-18 aluminum-fluoride complex with the cyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). Three imaging probes were synthesized as F-18-AlF-NOTA-E[c(RGDfK)](2), F-18-AlF-NOTA-PEG(4)-E[c(RGDfK)](2), and F-18-AlF-NOTA-E[PEG(4)-c(RGDfk)](2). The receptor binding affinity was determined by competitive cell binding assay, and the stability was evaluated by mouse serum incubation. Tumor uptake and whole body distribution of the three tracers were compared through direct tissue sampling and PET quantification of U87MG tumor-bearing mice.
All three compounds remained intact after 120 min incubation with mouse serum. They all had a rapid and relatively high tracer uptake in U87MG tumors with good target-to-background ratios. Compared with the other two tracers, F-18-AlF-NOTA-E[PEG(4)-c(RGDfk)](2) had the highest tumor uptake and the lowest accumulation in the liver. The integrin receptor specificity was confirmed by co-injection of unlabeled dimeric RGD peptide.
The rapid one-step radiolabeling strategy by the complexation of F-18-aluminum fluoride with NOTA-peptide conjugates was successfully applied to synthesize three dimeric RGD peptides. Among the three probes developed, F-18-AlF-NOTA-E[PEG(4)-c(RGDfk)](2) with relatively low liver uptake and high tumor accumulation appears to be a promising candidate for further translational research.
C1 [Guo, Jinxia; Xie, Qingguo] Huazhong Univ Sci & Technol, Dept Biomed Engn, Wuhan 430074, Peoples R China.
[Guo, Jinxia; Xie, Qingguo] Huazhong Univ Sci & Technol, Wuhan Natl Lab Optoelect, Wuhan 430074, Peoples R China.
[Guo, Jinxia; Lang, Lixin; Guo, Ning; Zhu, Lei; Sun, Zhongchan; Ma, Ying; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Hu, Shuo] Cent S Univ, Dept Nucl Med, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China.
[Zhu, Lei] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China.
RP Xie, QG (reprint author), Huazhong Univ Sci & Technol, Dept Biomed Engn, Wuhan 430074, Peoples R China.
EM qgxie@mail.hust.edu.cn; shawn.chen@nih.gov
RI Zhu, Lei/P-9786-2016
OI Zhu, Lei/0000-0002-1820-4795
FU National Basic Research Program of China (973 Program) [2013CB733800,
2013CB733802, 2014CB744503]; National Science Foundation of China (NSFC)
[81201129, 81371596, 51373144, 81101068]; Intramural Research Program of
the National Institute of Biomedical Imaging and Bioengineering (NIBIB),
National Institutes of Health (NIH)
FX This work was supported in part by the National Basic Research Program
of China (973 Program) (No. 2013CB733800, 2013CB733802, 2014CB744503),
the National Science Foundation of China (NSFC) (81201129, 81371596,
51373144 and 81101068), and the Intramural Research Program of the
National Institute of Biomedical Imaging and Bioengineering (NIBIB),
National Institutes of Health (NIH).
NR 39
TC 13
Z9 13
U1 3
U2 29
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
EI 1860-2002
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD APR
PY 2014
VL 16
IS 2
BP 274
EP 283
DI 10.1007/s11307-013-0668-1
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AC9BE
UT WOS:000332828200015
PM 23982795
ER
PT J
AU Brunoni, AR
Machado-Vieira, R
Zarate, CA
Valiengo, L
Vieira, EL
Bensenor, IM
Lotufo, PA
Gattaz, WF
Teixeira, AL
AF Brunoni, Andre R.
Machado-Vieira, Rodrigo
Zarate, Carlos A.
Valiengo, Leandro
Vieira, Erica L. M.
Bensenor, Isabela M.
Lotufo, Paulo A.
Gattaz, Wagner F.
Teixeira, Antonio L.
TI Cytokines plasma levels during antidepressant treatment with sertraline
and transcranial direct current stimulation (tDCS): results from a
factorial, randomized, controlled trial
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Major depressive disorder; Transcranial direct current stimulation;
Sertraline; Cytokines; Interleukins; Randomized; Controlled trial;
Placebo response; Placebo effect
ID MAJOR DEPRESSIVE DISORDER; ELECTRICAL-CURRENT THERAPY;
HEART-RATE-VARIABILITY; NECROSIS-FACTOR-ALPHA; MAGNETIC STIMULATION;
TREATMENT RESPONSE; BRAIN-STIMULATION; NERVOUS-SYSTEM; INTERLEUKIN-6;
METAANALYSIS
AB The inflammatory hypothesis of depression states that increased levels of pro-inflammatory cytokines triggered by external and internal stressors are correlated to the acute depressive state. This hypothesis also suggests that pharmacotherapy partly acts in depression through anti-inflammatory effects. Transcranial direct current stimulation (tDCS) is a novel, promising, non-invasive somatic treatment for depression, although its antidepressant mechanisms are only partly understood.
We explored the effects of tDCS and sertraline over the immune system during an antidepressant treatment trial.
In a 6-week, double-blind, placebo-controlled trial, 73 antidepressant-free patients with unipolar depression were randomized to active/sham tDCS and sertraline/placebo (2 x 2 design). Plasma levels of several cytokines (IL-2, IL-4, IL-6, IL-10, IL-17a, IFN-gamma, and TNF-alpha) were determined to investigate the effects of the interventions and of clinical response on them.
All cytokines, except TNF-alpha, decreased over time, these effects being similar across the different intervention-groups and in responders vs. non-responders.
tDCS and sertraline (separately and combined) acute antidepressant effects might not specifically involve normalization of the immune system. In addition, being one of the first placebo-controlled trials measuring cytokines over an antidepressant treatment course, our study showed that the decrease in cytokine levels during the acute depressive episode could involve a placebo effect, highlighting the need of further placebo-controlled trials and observational studies examining cytokine changes during depression treatment and also after remission of the acute depressive episode.
C1 [Brunoni, Andre R.; Valiengo, Leandro; Bensenor, Isabela M.; Lotufo, Paulo A.] Univ Sao Paulo, Univ Hosp, Ctr Clin & Epidemiol Res, BR-05508000 Sao Paulo, Brazil.
[Brunoni, Andre R.; Valiengo, Leandro; Bensenor, Isabela M.; Lotufo, Paulo A.] Univ Sao Paulo, Univ Hosp, Interdisciplinary Ctr Appl Neuromodulat CINA, BR-05508000 Sao Paulo, Brazil.
[Machado-Vieira, Rodrigo; Valiengo, Leandro; Gattaz, Wagner F.] Univ Sao Paulo, Lab Neurosci LIM27, Dept & Inst Psychiat, BR-05508000 Sao Paulo, Brazil.
[Machado-Vieira, Rodrigo; Zarate, Carlos A.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Vieira, Erica L. M.; Teixeira, Antonio L.] Fac Med Minas Gerais, Interdisciplinary Lab Med Invest, Belo Horizonte, MG, Brazil.
[Brunoni, Andre R.; Valiengo, Leandro] Univ Sao Paulo, Serv Interdisciplinary Neuromodulat SIN, Dept & Inst Psychiat, BR-05508000 Sao Paulo, Brazil.
RP Brunoni, AR (reprint author), Univ Sao Paulo, Univ Hosp, Ctr Clin & Epidemiol Res, Av Prof Lineu Prestes 2565,3o andar, BR-05508000 Sao Paulo, Brazil.
EM brunoni@usp.br
RI Vieira, Erica/A-1976-2013; Gattaz, Wagner/C-4456-2012; Brunoni,
Andre/H-8394-2012; MACHADO-VIEIRA, RODRIGO/D-8293-2012; Lotufo,
Paulo/A-9843-2008
OI Vieira, Erica/0000-0002-4147-5614; Brunoni, Andre/0000-0002-6310-3571;
MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Lotufo,
Paulo/0000-0002-4856-8450
FU FAPESP (Sao Paulo Research Foundation) [2009/05728-7]; FAPEMIG; CNPq;
FAPESP [2012/20911-5]; NARSAD
FX This study was partially funded by FAPESP (Sao Paulo Research
Foundation, Grant number: 2009/05728-7), FAPEMIG and CNPq. ARB receives
a research grant from FAPESP (2012/20911-5) and is recipient of a 2013
NARSAD Young Investigator Award. The sponsors played no role in the
design and conduct of the study, collection, management, analysis and
interpretation of the data, and preparation, review or approval of the
manuscript.
NR 53
TC 10
Z9 10
U1 1
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD APR
PY 2014
VL 231
IS 7
BP 1315
EP 1323
DI 10.1007/s00213-013-3322-3
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AD0WI
UT WOS:000332954600005
PM 24150249
ER
PT J
AU Sukhtankar, DD
Lee, H
Rice, KC
Ko, MC
AF Sukhtankar, Devki D.
Lee, Heeseung
Rice, Kenner C.
Ko, Mei-Chuan
TI Differential effects of opioid-related ligands and NSAIDs in nonhuman
primate models of acute and inflammatory pain
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Opioids; Opioid receptors; NSAIDs; Monkey pain model; Carrageenan;
Nociceptin/orphanin FQ; NOP receptors; Hyperalgesia
ID CARRAGEENAN-INDUCED INFLAMMATION; DORSAL-ROOT GANGLIA; RHESUS-MONKEYS;
DOUBLE-BLIND; RECEPTOR AGONIST; NEUROPATHIC PAIN; THERMAL HYPERALGESIA;
INDUCED ITCH; DELTA; RAT
AB Carrageenan-induced hyperalgesia is a widely used pain model in rodents. However, characteristics of carrageenan-induced hyperalgesia and effects of analgesic drugs under these conditions are unknown in nonhuman primates.
The aims of this study were to develop carrageenan-induced hyperalgesia in rhesus monkeys and determine the efficacy and potency of agonists selective for the four opioid receptor subtypes in this model versus acute pain, as compared to non-steroidal anti-inflammatory drugs (NSAIDs).
Tail injection of carrageenan produced long-lasting thermal hyperalgesia in monkeys. Systemically administered agonists selective for opioid receptor subtypes, i.e., fentanyl (mu/MOP), U-50488H (kappa/KOP), SNC80 (delta/DOP) and Ro 64-6198 (nociceptin/orphanin FQ/NOP) dose-dependently attenuated carrageenan-induced thermal hyperalgesia with different potencies. In absence of carrageenan, these agonists, except SNC80, blocked acute thermal nociception. Opioid-related ligands, especially Ro 64-6198, were much more potent for their antihyperalgesic than antinociceptive effects. Both effects were mediated by the corresponding receptor mechanisms. Only fentanyl produced scratching at antihyperalgesic and antinociceptive doses consistent with its pruritic effects in humans, illustrating a translational profile of MOP agonists in nonhuman primates. Similar to SNC80, systemically administered NSAIDs ketorolac and naproxen dose-dependently attenuated carrageenan-induced hyperalgesia but not acute nociception.
Using two different pain modalities in nonhuman primates, effectiveness of clinically available analgesics like fentanyl, ketorolac and naproxen was distinguished and their efficacies and potencies were compared with the selective KOP, DOP, and NOP agonists. The opioid-related ligands displayed differential pharmacological properties in regulating hyperalgesia and acute nociception in the same subjects. Such preclinical primate models can be used to investigate novel analgesic agents.
C1 [Sukhtankar, Devki D.; Ko, Mei-Chuan] Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA.
[Lee, Heeseung] Ewha Womans Univ, Sch Med, Dept Anesthesiol & Pain Med, Seoul 158710, South Korea.
[Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Ko, Mei-Chuan] Wake Forest Univ, Bowman Gray Sch Med, Ctr Comparat Med Res, Winston Salem, NC 27157 USA.
RP Sukhtankar, DD (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
EM dsukhtan@wakehealth.edu; leehee@ewha.ac.kr
RI Ko, Mei-Chuan/C-9468-2009
OI Ko, Mei-Chuan/0000-0003-2436-4506
FU National Institutes of Health, the National Institute of Arthritis and
Musculoskeletal and Skin Diseases [R01-AR-059193]; National Institute on
Drug Abuse [R01-DA-032568]
FX We thank Tristan Edwards and John Busenbark for technical assistance of
data collection. Research reported in this publication was supported by
the National Institutes of Health, the National Institute of Arthritis
and Musculoskeletal and Skin Diseases under Award number R01-AR-059193,
and the National Institute on Drug Abuse under Award number
R01-DA-032568. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the National
Institutes of Health.
NR 57
TC 10
Z9 10
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD APR
PY 2014
VL 231
IS 7
BP 1377
EP 1387
DI 10.1007/s00213-013-3341-0
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AD0WI
UT WOS:000332954600010
PM 24217900
ER
PT J
AU Hiramoto, JS
Katz, R
Ix, JH
Wassel, C
Rodondi, N
Windham, BG
Harris, T
Koster, A
Satterfield, S
Newman, A
Shlipak, MG
AF Hiramoto, Jade S.
Katz, Ronit
Ix, Joachim H.
Wassel, Christina
Rodondi, Nicolas
Windham, B. Gwen
Harris, Tamara
Koster, Annemarie
Satterfield, Suzanne
Newman, Anne
Shlipak, Michael G.
CA Hlth ABC Study
TI Sex differences in the prevalence and clinical outcomes of subclinical
peripheral artery disease in the Health, Aging, and Body Composition
(Health ABC) study
SO VASCULAR
LA English
DT Article
DE women; peripheral artery disease; epidemiology; sex-specific
ID ANKLE-BRACHIAL INDEX; CRITICAL LIMB ISCHEMIA; PREDICT CARDIOVASCULAR
EVENTS; NUTRITION EXAMINATION SURVEY; AMERICAN-HEART-ASSOCIATION;
MIDDLE-AGED POPULATION; BLOOD-PRESSURE INDEX; LOWER-EXTREMITY; ARM
INDEX; NATIONAL-HEALTH
AB The objective of the study was to determine if there are sex-based differences in the prevalence and clinical outcomes of subclinical peripheral artery disease (PAD). We evaluated the sex-specific associations of ankle-brachial index (ABI) with clinical cardiovascular disease outcomes in 2797 participants without prevalent clinical PAD and with a baseline ABI measurement in the Health, Aging, and Body Composition study. The mean age was 74 years, 40% were black, and 52% were women. Median follow-up was 9.37 years. Women had a similar prevalence of ABI < 0.9 (12% women versus 11% men; P = 0.44), but a higher prevalence of ABI 0.9-1.0 (15% versus 10%, respectively; P < 0.001). In a fully adjusted model, ABI < 0.9 was significantly associated with higher coronary heart disease (CHD) mortality, incident clinical PAD and incident myocardial infarction in both women and men. ABI < 0.9 was significantly associated with incident stroke only in women. ABI 0.9-1.0 was significantly associated with CHD death in both women (hazard ratio 4.84, 1.53-15.31) and men (3.49, 1.39-8.72). However, ABI 0.9-1.0 was significantly associated with incident clinical PAD (3.33, 1.44-7.70) and incident stroke (2.45, 1.38-4.35) only in women. Subclinical PAD was strongly associated with adverse CV events in both women and men, but women had a higher prevalence of subclinical PAD.
C1 [Hiramoto, Jade S.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA.
[Katz, Ronit] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA.
[Wassel, Christina] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, La Jolla, CA 92093 USA.
[Rodondi, Nicolas] Univ Bern, Inselspital, Dept Gen Internal Med, CH-3012 Bern, Switzerland.
[Windham, B. Gwen] Univ Mississippi, Med Ctr, Dept Internal Med, Jackson, MS 39216 USA.
[Harris, Tamara] NIA, Intramural Res Program, Bethesda, MD 20892 USA.
[Koster, Annemarie] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Koster, Annemarie] Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Social Med, Maastricht, Netherlands.
[Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
[Newman, Anne] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Newman, Anne] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Hiramoto, JS (reprint author), UCSF Vasc Surg, 400 Parnassus Ave,A-581,Box 0222, San Francisco, CA 94143 USA.
EM jade.hiramoto@ucsfmedctr.org
RI Koster, Annemarie/E-7438-2010; Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU NIH/NCRR/OD UCSF-CTSI [KL2 RR024130, IH R01DK087961-01A1,
R01AG027002-05A1, R01AG034853]; National Institute on Aging (NIA)
[N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050]; NINR
[R01-NR012459]; Intramural Research Program of the NIH, National
Institute on Aging
FX This publication was supported by NIH/NCRR/OD UCSF-CTSI grant Number KL2
RR024130 (Dr Hiramoto), NIH R01DK087961-01A1, R01AG027002-05A1 and
R01AG034853 (Dr Shlipak). Its contents are the responsibility of the
authors and do not necessarily represent the official views of the NIH.
This research was also supported by National Institute on Aging (NIA)
Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant
R01-AG028050 and NINR grant R01-NR012459, and in part by the Intramural
Research Program of the NIH, National Institute on Aging.
NR 36
TC 9
Z9 10
U1 0
U2 6
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1708-5381
EI 1708-539X
J9 VASCULAR
JI Vascular
PD APR
PY 2014
VL 22
IS 2
BP 142
EP 148
DI 10.1177/1708538113476023
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AC9HY
UT WOS:000332846400011
PM 23512905
ER
PT J
AU Wang, YF
Zhang, W
He, KF
Liu, B
Zhang, L
Zhang, WF
Kulkarni, AB
Zhao, YF
Sun, ZJ
AF Wang, Yu-Fan
Zhang, Wei
He, Ke-Fei
Liu, Bing
Zhang, Lu
Zhang, Wen-Feng
Kulkarni, Ashok B.
Zhao, Yi-Fang
Sun, Zhi-Jun
TI Induction of autophagy-dependent cell death by the survivin suppressant
YM155 in salivary adenoid cystic carcinoma
SO APOPTOSIS
LA English
DT Article
DE Survivin; Adenoid cystic carcinoma; YM155; Apoptosis; Autophagy
ID ADVANCED SOLID TUMORS; MAMMALIAN TARGET; CANCER DEVELOPMENT; TREATMENT
RESPONSE; PHASE-I; APOPTOSIS; TFEB; MTORC1; RAPAMYCIN; ISOLIQUIRITIGENIN
AB Adenoid cystic carcinoma (ACC) is one of the most common malignancies of the major and minor salivary glands. However, the molecular mechanism underlying the aggressive growth of human salivary ACC remains unclear. In the present study, we showed that survivin, which belongs to the family of inhibitors of apoptosis, is closely related to the high expression of CDK4 and cyclin D1 in human ACC specimens. By employing the small-molecule drug YM155, we found that the inhibition of survivin in ACC cells caused significant cell death and induced autophagy. Chloroquine, an autophagy inhibitor, prevented cell death induced by YM155, suggesting YM155-induced autophagy contributed to the cell death effects in ACC cells. More importantly, evidence obtained from a xenograft model using ACC-2 cells proved the occurrence of YM155-induced autophagy and cell death in vivo was correlated with the suppression of Erk1/2 and S6 activation as well as increased TFEB nuclear translocation. Taken together, our results indicate YM155 is a novel inducer of autophagy-dependent cell death and possesses therapeutic potential in ACC.
C1 [Wang, Yu-Fan; Zhang, Wei; He, Ke-Fei; Liu, Bing; Zhang, Lu; Zhang, Wen-Feng; Zhao, Yi-Fang; Sun, Zhi-Jun] Wuhan Univ, Sch & Hosp Stomatol, Dept Oral & Maxillofacial Head & Neck Oncol, State Key Lab Breeding Base Basic Sci Stomatol, Wuhan 430079, Peoples R China.
[Wang, Yu-Fan; Zhang, Wei; He, Ke-Fei; Liu, Bing; Zhang, Lu; Zhang, Wen-Feng; Zhao, Yi-Fang; Sun, Zhi-Jun] Wuhan Univ, Sch & Hosp Stomatol, Dept Oral & Maxillofacial Head & Neck Oncol, Key Lab Oral Biomed,Minist Educ, Wuhan 430079, Peoples R China.
[Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Zhao, YF (reprint author), Wuhan Univ, Sch & Hosp Stomatol, Dept Oral & Maxillofacial Head & Neck Oncol, State Key Lab Breeding Base Basic Sci Stomatol, Wuhan 430079, Peoples R China.
EM yifang@whu.edu.cn; zhijundejia@163.com
FU National Natural Science Foundation of China [81072203, 81272963,
81371106, 81272946, 81170977]; Fundamental Research Funds for the
Central Universities of China [2012304020203]
FX This work was supported by grants from National Natural Science
Foundation of China (81072203, 81272963) to Z.-J. Sun (81371106) to L.
Zhang (81272946) to W.-F. Zhang and (81170977) to Y.-F. Zhao.
Fundamental Research Funds for the Central Universities of China
(2012304020203) to W. Zhang.
NR 39
TC 15
Z9 18
U1 0
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1360-8185
EI 1573-675X
J9 APOPTOSIS
JI Apoptosis
PD APR
PY 2014
VL 19
IS 4
BP 748
EP 758
DI 10.1007/s10495-013-0960-1
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AC4IX
UT WOS:000332485700016
PM 24370995
ER
PT J
AU Mooreville, M
Shomaker, LB
Reina, SA
Hannallah, LM
Cohen, LA
Courville, AB
Kozlosky, M
Brady, SM
Condarco, T
Yanovski, SZ
Tanofsky-Kraff, M
Yanovski, JA
AF Mooreville, Mira
Shomaker, Lauren B.
Reina, Samantha A.
Hannallah, Louise M.
Cohen, L. Adelyn
Courville, Amber B.
Kozlosky, Merel
Brady, Sheila M.
Condarco, Tania
Yanovski, Susan Z.
Tanofsky-Kraff, Marian
Yanovski, Jack A.
TI Depressive symptoms and observed eating in youth
SO APPETITE
LA English
DT Article
DE Depression; Obesity; Eating; Child; Adolescent
ID BODY-MASS INDEX; SCALES VALID MEASURES; DIETARY RESTRAINT;
FOOD-CONSUMPTION; ADOLESCENT GIRLS; GENDER-DIFFERENCES;
AFRICAN-AMERICAN; PUBERTAL CHANGES; ENERGY-INTAKE; DATA SUGGEST
AB Depressive symptoms in youth may be a risk factor for obesity, with altered eating behaviors as one possible mechanism. We tested whether depressive symptoms were associated with observed eating patterns expected to promote excessive weight gain in two separate samples. In Study 1, 228 nontreatment-seeking youth, ages 12-17 y (15.3 +/- 1.4 y; 54.7% female), self-reported depressive symptoms using the Beck Depression Inventory. Energy intake was measured as consumption from a 10,934-kcal buffet meal served at 11:00 am after an overnight fast. In Study 2,204 non-treatment-seeking youth, ages 8-17 y (13.0 +/- 2.8 y; 49.5% female), self-reported depressive symptoms using the Children's Depression Inventory. Energy intake was measured as consumption from a 9835-kcal buffet meal served at 2:30 pm after a standard breakfast. In Study 1, controlling for body composition and other relevant covariates, depressive symptoms were positively related to total energy intake in girls and boys. In Study 2, adjusting for the same covariates, depressive symptoms among girls only were positively associated with total energy intake. Youth high in depressive symptoms and dietary restraint consumed the most energy from sweets. In both studies, the effects of depressive symptoms on intake were small. Nevertheless, depressive symptoms were associated with significantly greater consumption of total energy and energy from sweet snack foods, which, over time, could be anticipated to promote excess weight gain. (c) 2014 Elsevier Ltd. All rights reserved.
C1 [Mooreville, Mira; Shomaker, Lauren B.; Reina, Samantha A.; Hannallah, Louise M.; Cohen, L. Adelyn; Brady, Sheila M.; Condarco, Tania; Yanovski, Susan Z.; Tanofsky-Kraff, Marian; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Shomaker, Lauren B.] Colorado State Univ, Dept Human Dev & Family Studies, Ft Collins, CO 80524 USA.
[Cohen, L. Adelyn; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Courville, Amber B.; Kozlosky, Merel] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA.
[Hannallah, Louise M.; Yanovski, Susan Z.] Natl Inst Diabet & Digest & Kidney Dis NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD 20817 USA.
RP Shomaker, LB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM Lauren.Shomaker@ColoState.edu
OI Yanovski, Jack/0000-0001-8542-1637
FU USUHS [R072IC]; NICHD [ZIAHD000641]; NIH; Office of Disease Prevention;
Office of Behavioral and Social Sciences Research; [K99/R00HD069516]
FX Research support: K99/R00HD069516 (to L. Shomaker), USUHS R072IC (to M.
Tanofsky-Kraff), and the intramural research program of NICHD
ZIAHD000641 with supplemental funding from the NIH Bench to Bedside
Program, the Office of Disease Prevention, and the Office of Behavioral
and Social Sciences Research (to J. Yanovski).
NR 80
TC 6
Z9 6
U1 5
U2 23
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0195-6663
EI 1095-8304
J9 APPETITE
JI Appetite
PD APR 1
PY 2014
VL 75
BP 141
EP 149
DI 10.1016/j.appet.2013.12.024
PG 9
WC Behavioral Sciences; Nutrition & Dietetics
SC Behavioral Sciences; Nutrition & Dietetics
GA AC8TU
UT WOS:000332808500019
PM 24424352
ER
PT J
AU Roberts, SA
Gordenin, DA
AF Roberts, Steven A.
Gordenin, Dmitry A.
TI Clustered and genome-wide transient mutagenesis in human cancers:
Hypermutation without permanent mutators or loss of fitness
SO BIOESSAYS
LA English
DT Review
DE APOBEC; DNA damage; DNA repair; hypermutation; kataegis; mutation
cluster
ID INDUCED CYTIDINE DEAMINASE; SINGLE-STRANDED-DNA; ACTIVATION-INDUCED
DEAMINASE; B MESSENGER-RNA; ANTIBODY DIVERSIFICATION ENZYME;
ONCOGENE-INDUCED SENESCENCE; CLASS SWITCH RECOMBINATION; 21 BREAST
CANCERS; SOMATIC HYPERMUTATION; SACCHAROMYCES-CEREVISIAE
AB The gain of a selective advantage in cancer as well as the establishment of complex traits during evolution require multiple genetic alterations, but how these mutations accumulate over time is currently unclear. There is increasing evidence that a mutator phenotype perpetuates the development of many human cancers. While in some cases the increased mutation rate is the result of a genetic disruption of DNA repair and replication or environmental exposures, other evidence suggests that endogenous DNA damage induced by AID/APOBEC cytidine deaminases can result in transient localized hypermutation generating simultaneous, closely spaced (i.e. clustered) multiple mutations. Here, we discuss mechanisms that lead to mutation cluster formation, the biological consequences of their formation in cancer and evidence suggesting that APOBEC mutagenesis can also occur genome-wide. This raises the possibility that dysregulation of these enzymes may enable rapid malignant transformation by increasing mutation rates without the loss of fitness associated with permanent mutators.
C1 [Roberts, Steven A.; Gordenin, Dmitry A.] NIEHS, Chromosome Stabil Grp, Mol Genet Lab, Durham, NC 27709 USA.
RP Roberts, SA (reprint author), NIEHS, Chromosome Stabil Grp, Mol Genet Lab, Durham, NC 27709 USA.
EM robertssa2@niehs.nih.gov
OI Gordenin, Dmitry/0000-0002-8399-1836
FU NIH, National Institute of Environmental Health Sciences [ES065073]; NIH
[K99ES022633-01]
FX The authors thank Drs. Mike Resnick, Kin Chan, and Scott Lujan for
helpful discussion of this manuscript. This research was supported by
the Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences (project ES065073: PI - Mike Resnick).
S.A.R. is supported by NIH Pathway to Independence Award K99ES022633-01.
NR 120
TC 16
Z9 17
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0265-9247
EI 1521-1878
J9 BIOESSAYS
JI Bioessays
PD APR
PY 2014
VL 36
IS 4
BP 382
EP 393
DI 10.1002/bies.201300140
PG 12
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA AC2XE
UT WOS:000332378800008
ER
PT J
AU Felix, AS
Yang, HP
Gierach, GL
Park, Y
Brinton, LA
AF Felix, Ashley S.
Yang, Hannah P.
Gierach, Gretchen L.
Park, Yikyung
Brinton, Louise A.
TI Cigarette smoking and endometrial carcinoma risk: the role of effect
modification and tumor heterogeneity
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Cohort study; Cigarette smoking; Endometrial carcinoma; Effect
modification
ID MENOPAUSAL HORMONE-THERAPY; NIH-AARP DIET; CANCER-RISK; POSTMENOPAUSAL
WOMEN; REPLACEMENT THERAPY; NATIONAL-INSTITUTES; ALCOHOL-CONSUMPTION;
OVARIAN-CANCER; BREAST-CANCER; SEX-HORMONES
AB The inverse relationship between cigarette smoking and endometrial carcinoma risk is well established. We examined effect modification of this relationship and associations with tumor characteristics in the National Institutes of Health-AARP Diet and Health Study.
We examined the association between cigarette smoking and endometrial carcinoma risk among 110,304 women. During 1,029,041 person years of follow-up, we identified 1,476 incident endometrial carcinoma cases. Multivariable Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95 % confidence intervals (CIs) for the association between smoking status, years since smoking cessation, and endometrial carcinoma risk overall and within strata of endometrial carcinoma risk factors. Effect modification was assessed using likelihood ratio test statistics. Smoking associations by histologic subtype/grade and stage at diagnosis were also evaluated.
Reduced endometrial carcinoma risk was evident among former (RR 0.89, 95 % CI 0.80, 1.00) and current (RR 0.65, 95 % CI 0.55, 0.78) smokers compared with never smokers. Smoking cessation 1-4 years prior to baseline was significantly associated with endometrial carcinoma risk (RR 0.65, 95 % CI 0.48, 0.89), while cessation a parts per thousand yen10 years before baseline was not. The association between smoking and endometrial carcinoma risk was not significantly modified by any endometrial carcinoma risk factor, nor did we observe major differences in risk associations by tumor characteristics.
The cigarette smoking-endometrial carcinoma risk relationship was consistent within strata of important endometrial carcinoma risk factors and by clinically relevant tumor characteristics.
C1 [Felix, Ashley S.; Yang, Hannah P.; Gierach, Gretchen L.; Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Felix, Ashley S.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Felix, AS (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM ashley.felix@gmail.com
RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016; Felix,
Ashley/A-3240-2016;
OI Brinton, Louise/0000-0003-3853-8562; Gierach,
Gretchen/0000-0002-0165-5522; Park, Yikyung/0000-0002-6281-489X
FU Intramural Research Program of the NIH, National Cancer Institute
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute. Cancer incidence data from the Atlanta
metropolitan area were collected by the Georgia Center for Cancer
Statistics, Department of Epidemiology, Rollins School of Public Health,
Emory University. Cancer incidence data from California were collected
by the California Department of Health Services, Cancer Surveillance
Section. Cancer incidence data from the Detroit metropolitan area were
collected by the Michigan Cancer Surveillance Program, Community Health
Administration, State of Michigan. The Florida cancer incidence data
used in this report were collected by the Florida Cancer Data System
under contract to the Department of Health. Cancer incidence data from
Louisiana were collected by the Louisiana Tumor Registry, Louisiana
State University Medical Center in New Orleans. Cancer incidence data
from New Jersey were collected by the New Jersey State Cancer Registry,
Cancer Epidemiology Services, New Jersey State Department of Health and
Senior Services. Cancer incidence data from North Carolina were
collected by the North Carolina Central Cancer Registry. Cancer
incidence data from Pennsylvania were supplied by the Division of Health
Statistics and Research, Pennsylvania Department of Health, Harrisburg,
Pennsylvania. Cancer incidence data from Arizona were collected by the
Arizona Cancer Registry, Division of Public Health Services, Arizona
Department of Health Services. Cancer incidence data from Texas were
collected by the Texas Cancer Registry, Cancer Epidemiology and
Surveillance Branch, Texas Department of State Health Services. The
views expressed herein are solely those of the authors and do not
necessarily reflect those of the contractor or the Florida Department of
Health. The Pennsylvania Department of Health specifically disclaims
responsibility for any analyses, interpretations, or conclusions.
NR 62
TC 5
Z9 5
U1 0
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD APR
PY 2014
VL 25
IS 4
BP 479
EP 489
DI 10.1007/s10552-014-0350-1
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA AC6PY
UT WOS:000332647500008
PM 24487725
ER
PT J
AU Seol, HS
Kang, H
Lee, SI
Kim, NE
Kim, TI
Chun, SM
Kim, TW
Yu, CS
Suh, YA
Singh, SR
Chang, S
Jang, SJ
AF Seol, Hyang Sook
Kang, HyoJeong
Lee, Seul-I.
Kim, Na Eun
Kim, Tae Im
Chun, Sung Min
Kim, Tae Won
Yu, Chang Sik
Suh, Young-Ah
Singh, Shree Ram
Chang, Suhwan
Jang, Se Jin
TI Development and characterization of a colon PDX model that reproduces
drug responsiveness and the mutation profiles of its original tumor
SO CANCER LETTERS
LA English
DT Article
DE Patient derived xenograft (PDX); Colon cancer; Oncomap analysis; Primary
culture; Drug sensitivity
ID METASTATIC COLORECTAL-CANCER; CELL LUNG-CANCER; PATIENT-DERIVED
XENOGRAFTS; MOLECULAR-FEATURES; TARGETED THERAPIES; CHEMOTHERAPY; EGFR;
MICE; FLUOROURACIL; OXALIPLATIN
AB Cultures of primary tumors are very useful as a personalized screening system for effective therapeutic options. We here describe an effective method of reproducing human primary colon tumors through primary culture and a mouse xenograft model. A total of 199 primary colon tumor cultures were successfully established under optimized conditions to enrich for tumor cells and to expand it for long-term storage in liquid nitrogen. To examine whether these stored cultures retained original tumor properties, fifty primary cultures were xenografted into NOD-SCID mouse. Histological and tumor marker analysis of four representative tumor xenografts revealed that all of the xenograft retained its primary tumor characteristics. Oncomap analysis further showed no change in the major mutations in the xenografts, confirming that our method faithfully reproduced human colon tumors. A drug sensitivity assay revealed that two of the primary cultures were hypersensitive to oxaliplatin rather than 5-FU, which was used in the patients, suggesting it as an effective therapeutic option. We thus present an effective, reproducible preclinical model for testing various personalized therapeutic options in colon cancer patients. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Seol, Hyang Sook; Lee, Seul-I.; Kim, Na Eun; Kim, Tae Im; Suh, Young-Ah; Chang, Suhwan; Jang, Se Jin] Univ Ulsan, Coll Med, Asan Med Ctr, Asan Inst Life Sci, Seoul, South Korea.
[Kang, HyoJeong; Chun, Sung Min; Jang, Se Jin] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea.
[Kim, Tae Won; Yu, Chang Sik] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiat Oncol, Seoul, South Korea.
[Singh, Shree Ram] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Chang, Suhwan] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Biomed Sci, Seoul, South Korea.
RP Chang, S (reprint author), Univ Ulsan, Dept Pathol, Coll Med, Asan Med Ctr, Seoul, South Korea.
EM singhshr@mail.nih.gov; suhwan.chang@amc.seoul.kr; jangsejin@amc.seoul.kr
RI Singh, Shree Ram/B-7614-2008
OI Singh, Shree Ram/0000-0001-6545-583X
FU Korean Health Technology R&D Project, Ministry of Health & Welfare,
Republic of Korea [A062254]; National Research Foundation of Korea;
Korean Government (Ministry of Education, Science and Technology)
[NRF-355-2010-1-C00071]; Leading Foreign Research Institute Recruitment
Program through the National Research Foundation of Korea (NRF);
Ministry of Education, Science and Technology (MEST) [2011-0030105]
FX This study was supported by a grant of the Korean Health Technology R&D
Project, Ministry of Health & Welfare, Republic of Korea (A062254), the
National Research Foundation of Korea Grant funded by the Korean
Government (Ministry of Education, Science and Technology,
[NRF-355-2010-1-C00071]), and a grant of the Leading Foreign Research
Institute Recruitment Program through the National Research Foundation
of Korea (NRF) funded by the Ministry of Education, Science and
Technology (MEST) (2011-0030105).
NR 38
TC 8
Z9 8
U1 3
U2 18
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
EI 1872-7980
J9 CANCER LETT
JI Cancer Lett.
PD APR 1
PY 2014
VL 345
IS 1
BP 56
EP 64
DI 10.1016/j.canlet.2013.11.010
PG 9
WC Oncology
SC Oncology
GA AB8RE
UT WOS:000332056900007
PM 24333725
ER
PT J
AU Chen, H
Lumley, T
Brody, J
Heard-Costa, NL
Fox, CS
Cupples, LA
Dupuis, J
AF Chen, Han
Lumley, Thomas
Brody, Jennifer
Heard-Costa, Nancy L.
Fox, Caroline S.
Cupples, L. Adrienne
Dupuis, Josee
TI Sequence Kernel Association Test for Survival Traits
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE rare variant analysis; variance component test; likelihood ratio test;
Cox proportional hazard model
ID GENOME-WIDE ASSOCIATION; COMMON DISEASES; RARE VARIANTS
AB Rare variant tests have been of great interest in testing genetic associations with diseases and disease-related quantitative traits in recent years. Among these tests, the sequence kernel association test (SKAT) is an omnibus test for effects of rare genetic variants, in a linear or logistic regression framework. It is often described as a variance component test treating the genotypic effects as random. When the linear kernel is used, its test statistic can be expressed as a weighted sum of single-marker score test statistics. In this paper, we extend the test to survival phenotypes in a Cox regression framework. Because of the anticonservative small-sample performance of the score test in a Cox model, we substitute signed square-root likelihood ratio statistics for the score statistics, and confirm that the small-sample control of type I error is greatly improved. This test can also be applied in meta-analysis. We show in our simulation studies that this test has superior statistical power except in a few specific scenarios, as compared to burden tests in a Cox model. We also present results in an application to time-to-obesity using genotypes from Framingham Heart Study SNP Health Association Resource.
C1 [Chen, Han; Cupples, L. Adrienne; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Chen, Han] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand.
[Brody, Jennifer] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Heard-Costa, Nancy L.; Fox, Caroline S.; Cupples, L. Adrienne; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Heard-Costa, Nancy L.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Dupuis, J (reprint author), 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA.
EM dupuis@bu.edu
OI Chen, Han/0000-0002-9510-4923
FU NIH [R01DK078616, U01 DK85526, K24 DK080140]; National Heart, Lung, and
Blood Institute (NHLBI); Boston University [N01-HC-25195]; Affymetrix,
Inc for genotyping services [N02-HL-6-4278]
FX This research was partially supported by NIH awards R01DK078616, U01
DK85526, and K24 DK080140. A portion of this research was conducted
using the Linux Clusters for Genetic Analysis (LinGA) computing
resources at Boston University Medicine Campus. The Framingham Heart
Study is conducted and supported by the National Heart, Lung, and Blood
Institute (NHLBI) in collaboration with Boston University (Contract No.
N01-HC-25195). This work was partially supported by a contract with
Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278).
NR 18
TC 18
Z9 18
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD APR
PY 2014
VL 38
IS 3
BP 191
EP 197
DI 10.1002/gepi.21791
PG 7
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA AC7IB
UT WOS:000332700300002
PM 24464521
ER
PT J
AU Pan, QX
Hu, T
Malley, JD
Andrew, AS
Karagas, MR
Moore, JH
AF Pan, Qinxin
Hu, Ting
Malley, James D.
Andrew, Angeline S.
Karagas, Margaret R.
Moore, Jason H.
TI A System-Level Pathway-Phenotype Association Analysis Using Synthetic
Feature Random Forest
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE statistical epistasis network (SEN); interactions; synthetic feature
random forest (SF-RF); epistasis; pathway analysis
ID GENOME-WIDE ASSOCIATION; SET ENRICHMENT ANALYSIS; BLADDER-CANCER RISK;
TELOMERASE ACTIVITY; COMPLEX DISEASES; GENE-EXPRESSION; NETWORKS;
SUSCEPTIBILITY; CLASSIFICATION; INFORMATION
AB As the cost of genome-wide genotyping decreases, the number of genome-wide association studies (GWAS) has increased considerably. However, the transition from GWAS findings to the underlying biology of various phenotypes remains challenging. As a result, due to its system-level interpretability, pathway analysis has become a popular tool for gaining insights on the underlying biology from high-throughput genetic association data. In pathway analyses, gene sets representing particular biological processes are tested for significant associations with a given phenotype. Most existing pathway analysis approaches rely on single-marker statistics and assume that pathways are independent of each other. As biological systems are driven by complex biomolecular interactions, embracing the complex relationships between single-nucleotide polymorphisms (SNPs) and pathways needs to be addressed. To incorporate the complexity of gene-gene interactions and pathway-pathway relationships, we propose a system-level pathway analysis approach, synthetic feature random forest (SF-RF), which is designed to detect pathway-phenotype associations without making assumptions about the relationships among SNPs or pathways. In our approach, the genotypes of SNPs in a particular pathway are aggregated into a synthetic feature representing that pathway via Random Forest (RF). Multiple synthetic features are analyzed using RF simultaneously and the significance of a synthetic feature indicates the significance of the corresponding pathway. We further complement SF-RF with pathway-based Statistical Epistasis Network (SEN) analysis that evaluates interactions among pathways. By investigating the pathway SEN, we hope to gain additional insights into the genetic mechanisms contributing to the pathway-phenotype association. We apply SF-RF to a population-based genetic study of bladder cancer and further investigate the mechanisms that help explain the pathway-phenotype associations using SEN. The bladder cancer associated pathways we found are both consistent with existing biological knowledge and reveal novel and plausible hypotheses for future biological validations.
C1 [Pan, Qinxin; Moore, Jason H.] Dartmouth Coll, Geisel Sch Med, Dept Genet, Hanover, NH 03755 USA.
[Hu, Ting; Andrew, Angeline S.; Karagas, Margaret R.; Moore, Jason H.] Dartmouth Coll, Inst Quantitat Biomed Sci, Hanover, NH 03755 USA.
[Malley, James D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Andrew, Angeline S.; Karagas, Margaret R.; Moore, Jason H.] Dartmouth Coll, Geisel Sch Med, Dept Community & Family Med, Hanover, NH 03755 USA.
RP Moore, JH (reprint author), Dartmouth Coll, Inst Quantitat Biomed Sci, Hanover, NH 03755 USA.
EM jason.h.moore@dartmouth.edu
FU National Institutes of Health (NIH) [R01-LM009012, R01-LM010098,
R01-AI59694, P20-GM103534, P42-ES007373, R01-CA5749367]
FX This work was supported by the National Institutes of Health (NIH)
grants R01-LM009012, R01-LM010098, R01-AI59694, and P20-GM103534 to
J.H.M., and P42-ES007373 and R01-CA5749367 to M.R.K.
NR 69
TC 6
Z9 6
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD APR
PY 2014
VL 38
IS 3
BP 209
EP 219
DI 10.1002/gepi.21794
PG 11
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA AC7IB
UT WOS:000332700300004
PM 24535726
ER
PT J
AU Charles, BA
Shriner, D
Rotimi, CN
AF Charles, Bashira A.
Shriner, Daniel
Rotimi, Charles N.
TI Accounting for Linkage Disequilibrium in Association Analysis of Diverse
Populations
SO GENETIC EPIDEMIOLOGY
LA English
DT Review
DE fine-mapping; African ancestry; genome-wide association study
ID GENOME-WIDE ASSOCIATION; SERUM BILIRUBIN LEVELS; MODERN HUMAN ORIGINS;
MACULAR DEGENERATION; AFRICAN-AMERICANS; URIC-ACID; METAANALYSIS;
REPLICATION; DISEASE; VARIANTS
AB The National Human Genome Research Institute's catalog of published genome-wide association studies (GWAS) lists over 10,000 genetic variants collectively associated with over 800 human diseases or traits. Most of these GWAS have been conducted in European-ancestry populations. Findings gleaned from these studies have led to identification of disease-associated loci and biologic pathways involved in disease etiology. In multiple instances, these genomic findings have led to the development of novel medical therapies or evidence for prescribing a given drug as the appropriate treatment for a given individual beyond phenotypic appearances or socially defined constructs of race or ethnicity. Such findings have implications for populations throughout the globe and GWAS are increasingly being conducted in more diverse populations. A major challenge for investigators seeking to follow up genomic findings between diverse populations is discordant patterns of linkage disequilibrium (LD). We provide an overview of common measures of LD and opportunities for their use in novel methods designed to address challenges associated with following up GWAS conducted in European-ancestry populations in African-ancestry populations or, more generally, between populations with discordant LD patterns. We detail the strengths and weaknesses associated with different approaches. We also describe application of these strategies in follow-up studies of populations with concordant LD patterns (replication) or discordant LD patterns (transferability) as well as fine-mapping studies. We review application of these methods to a variety of traits and diseases.
C1 [Charles, Bashira A.; Shriner, Daniel; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
RP Charles, BA (reprint author), NHGRI, Ctr Res Genom & Global Hlth, Bldg 12A,Room 4047,12 South Dr,MSC 5635, Bethesda, MD 20892 USA.
EM rotimic@mail.nih.gov
FU National Human Genome Research Institute (NHGRI); National Institute of
Diabetes and Digestive and Kidney Diseases; Center for Information
Technology; Office of the Director at the National Institutes of Health
[Z01HG200362]; NHGRI Health Disparity Post-doctoral Fellowship
FX Grants and fellowships supporting the writing of the paper: Intramural
Research Program of the Center for Research on Genomics and Global
Health supported by the National Human Genome Research Institute
(NHGRI), the National Institute of Diabetes and Digestive and Kidney
Diseases, the Center for Information Technology, the Office of the
Director at the National Institutes of Health (Z01HG200362) and the
NHGRI Health Disparity Post-doctoral Fellowship.
NR 67
TC 8
Z9 9
U1 2
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD APR
PY 2014
VL 38
IS 3
BP 265
EP 273
DI 10.1002/gepi.21788
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA AC7IB
UT WOS:000332700300009
PM 24464495
ER
PT J
AU Richter, S
Bedard, PL
Chen, EX
Clarke, BA
Tran, B
Hotte, SJ
Stathis, A
Hirte, HW
Razak, ARA
Reedijk, M
Chen, Z
Cohen, B
Zhang, WJ
Wang, L
Ivy, SP
Moore, MJ
Oza, AM
Siu, LL
McWhirter, E
AF Richter, Suzanne
Bedard, Philippe L.
Chen, Eric Xueyu
Clarke, Blaise A.
Tran, Ben
Hotte, Sebastien J.
Stathis, Anastasios
Hirte, Hal W.
Razak, Albiruni R. A.
Reedijk, Michael
Chen, Zhuo
Cohen, Brenda
Zhang, Wen-Jiang
Wang, Lisa
Ivy, S. Percy
Moore, Malcolm J.
Oza, Amit M.
Siu, Lillian L.
McWhirter, Elaine
TI A phase I study of the oral gamma secretase inhibitor R04929097 in
combination with gemcitabine in patients with advanced solid tumors
(PHL-078/CTEP 8575)
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE Phase I; RO4929097; Notch inhibition; Gemcitabine
ID BREAST-CANCER; NOTCH; ANGIOGENESIS; RO4929097; TARGET
AB Purpose To establish the recommended phase II dose of the oral gamma-secretase inhibitor RO4929097 (RO) in combination with gemcitabine; secondary objectives include the evaluation of safety, tolerability, pharmacokinetics, biomarkers of Notch signaling and preliminary anti-tumor activity. Methods Patients with advanced solid tumors were enrolled in cohorts of escalating RO dose levels (DLs). Tested RO DLs were 20 mg, 30 mg, 45 mg and 90 mg. RO was administered orally, once daily on days 1-3, 8-10, 15-17, 22-24. Gemcitabine was administered at 1,000 mg/m(2) on d1, 8, and 15 in 28 d cycles. Dose limiting toxicities (DLTs) were assessed by CTCAE v4. Serial plasma was collected for RO (total and unbound) and gemcitabine pharmacokinetic analysis. Biomarkers of Notch signaling were assessed by immunohistochemistry in archival tissue. Antitumor activity was evaluated (RECIST 1.1). Results A total of 18 patients were enrolled to establish the recommended phase II dose. Of these, 3 patients received 20 mg RO, 7 patients received 30 mg RO, 6 patients received 45 mg RO and 2 patients received 90 mg RO. DLTs were grade 3 transaminitis (30 mg RO), grade 3 transaminitis and maculopapular rash (45 mg RO), and grade 3 transaminitis and failure to receive 75 % of planned RO doses secondary to prolonged neutropenia (90 mg); all were reversible. The maximum tolerated dose was exceeded at 90 mg RO. Pharmacokinetic analysis of both total and free RO confirmed the presence of autoinduction at 45 and 90 mg. Median levels of Notch3 staining were higher in individuals who received fewer than 4 cycles (p = 0.029). Circulating angiogenic factor levels did not correlate with time to progression or a parts per thousand yen grade 3 adverse events. Best response (RECIST 1.1) was partial response (nasopharyngeal cancer) and stable disease > 4 months was observed in 3 patients (pancreas, tracheal, and breast primary cancers). Conclusions RO and gemcitabine can be safely combined. The recommended phase II dose of RO was 30 mg in combination with gemcitabine 1,000 mg/m(2). Although RO exposure was limited by the presence of autoinduction, RO levels achieved exceeded the area under the concentration-time curve for 0-24 h (AUC(0-24)) predicted for efficacy in preclinical models using daily dosing. Evidence of clinical antitumor activity and prolonged stable disease were identified.
C1 [Richter, Suzanne; Bedard, Philippe L.; Chen, Eric Xueyu; Tran, Ben; Stathis, Anastasios; Razak, Albiruni R. A.; Zhang, Wen-Jiang; Moore, Malcolm J.; Oza, Amit M.; Siu, Lillian L.] Princess Margaret Canc Ctr, Drug Dev Program, Toronto, ON M5G 2M9, Canada.
[Clarke, Blaise A.] Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2C4, Canada.
[Hotte, Sebastien J.; Hirte, Hal W.; McWhirter, Elaine] Juravinski Canc Ctr, Hamilton, ON L8V 5C2, Canada.
[Reedijk, Michael] Univ Hlth Network, Dept Surg Oncol, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada.
[Chen, Zhuo] Univ Hlth Network, Appl Mol Profiling Lab, Toronto, ON M5G 2M9, Canada.
[Cohen, Brenda] Univ Hlth Network, Toronto, ON M5G 2C4, Canada.
[Wang, Lisa] Princess Margaret Canc Ctr, Dept Biostat, Toronto, ON M5G 2M9, Canada.
[Ivy, S. Percy] NCI, Canc Evaluat Program, Rockville, MD 20852 USA.
RP McWhirter, E (reprint author), Juravinski Canc Ctr, 699 Concess St, Hamilton, ON L8V 5C2, Canada.
EM elaine.mcwhirter@jcc.hhsc.ca
FU US National Cancer Institute [U01-CA132123]
FX This study (PHL-078/CTEP 8575) is conducted by the Princess Margaret
Hospital Phase I Consortium with support from the US National Cancer
Institute U01 Cooperative Agreement Award (U01-CA132123)
NR 23
TC 22
Z9 23
U1 1
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
EI 1573-0646
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD APR
PY 2014
VL 32
IS 2
BP 243
EP 249
DI 10.1007/s10637-013-9965-4
PG 7
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA AC7NH
UT WOS:000332715900004
PM 23645447
ER
PT J
AU Schelman, WR
Mohammed, TA
Traynor, AM
Kolesar, JM
Marnocha, RM
Eickhoff, J
Keppen, M
Alberti, DB
Wilding, G
Takebe, N
Liu, G
AF Schelman, William R.
Mohammed, Tabraiz A.
Traynor, Anne M.
Kolesar, Jill M.
Marnocha, Rebecca M.
Eickhoff, Jens
Keppen, Michael
Alberti, Dona B.
Wilding, George
Takebe, Naoko
Liu, Glenn
TI A phase I study of AT-101 with cisplatin and etoposide in patients with
advanced solid tumors with an expanded cohort in extensive-stage small
cell lung cancer
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE AT-101; Cisplatin; Etoposide; Phase I; Extensive-stage small cell lung
cancer
ID RESISTANT PROSTATE-CANCER; BCL-2 PROTEIN FAMILY; III TRIAL; MULTICENTER;
DISEASE; COMBINATION; TOPOTECAN; APOPTOSIS; GOSSYPOL; SURVIVAL
AB Background. A phase I, dose-escalation study of AT-101 with cisplatin and etoposide was conducted to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), safety and pharmacokinetics in patients with advanced solid tumors, with an expanded cohort in patients with extensive-stage small cell lung cancer (ES-SCLC) to assess preliminary activity. Methods. In the dose escalation portion, increasing doses of AT-101 were administered orally BID on days 1-3 along with cisplatin on day 1 and etoposide on days 1-3 of a 21 day cycle. At the RP2D, an additional 7 patients with untreated ES-SCLC were enrolled. Results. Twenty patients were enrolled in the dose-escalation cohort, and 7 patients with ES-SCLC were enrolled in the expanded cohort. The MTD/RP2D was established at AT-101 40 mg BID days 1-3 with cisplatin 60 mg/m2 and etoposide 120 mg/m2 on day 1 of a 21 day cycle with pegfilgrastim support. Two DLTs of neutropenic fever were seen at dose level 1. After the addition of pegfilgrastim, no additional DLTs were observed. Grade 3/4 treatment-related toxicities included: diarrhea, increased AST, neutropenia, hypophosphatemia, hyponatremia, myocardial infarction and pulmonary embolism. No apparent PK interactions were observed between the agents. Preliminary activity was observed with PRs in patients with ES-SCLC, high-grade neuroendocrine tumor, esophageal cancer and NSCLC. Conclusions. AT-101 with cisplatin and etoposide is well tolerated with growth factor support. Anti-tumor activity was observed in a variety of cancers including ES-SCLC, supporting further investigation with BH-3 mimetics in combination with standard chemotherapy for ES-SCLC.
C1 [Schelman, William R.; Mohammed, Tabraiz A.; Traynor, Anne M.; Kolesar, Jill M.; Marnocha, Rebecca M.; Eickhoff, Jens; Alberti, Dona B.; Wilding, George; Liu, Glenn] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53792 USA.
[Keppen, Michael] Sanford Canc Ctr, Sioux Falls, SD USA.
[Takebe, Naoko] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Schelman, WR (reprint author), Univ Wisconsin, Carbone Canc Ctr, 600 Highland Ave,K4-530 CSC, Madison, WI 53792 USA.
EM wrs@medicine.wisc.edu
FU NCI; [NCI UO1 CA062491]; [SAIC 25XS097]; [1ULRR025011]
FX This study was supported by NCI and the following grants - NCI UO1
CA062491, SAIC 25XS097, and 1ULRR025011.
NR 33
TC 11
Z9 11
U1 0
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
EI 1573-0646
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD APR
PY 2014
VL 32
IS 2
BP 295
EP 302
DI 10.1007/s10637-013-9999-7
PG 8
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA AC7NH
UT WOS:000332715900010
PM 23860642
ER
PT J
AU Deming, DA
Ninan, J
Bailey, HH
Kolesar, JM
Eickhoff, J
Reid, JM
Ames, MM
McGovern, RM
Alberti, D
Marnocha, R
Espinoza-Delgado, I
Wright, J
Wilding, G
Schelman, WR
AF Deming, Dustin A.
Ninan, Jacob
Bailey, Howard H.
Kolesar, Jill M.
Eickhoff, Jens
Reid, Joel M.
Ames, Matthew M.
McGovern, Renee M.
Alberti, Dona
Marnocha, Rebecca
Espinoza-Delgado, Igor
Wright, John
Wilding, George
Schelman, William R.
TI A Phase I study of intermittently dosed vorinostat in combination with
bortezomib in patients with advanced solid tumors
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE SAHA; Vorinostat; PS-341; Bortezomib; Phase I
ID HISTONE DEACETYLASE INHIBITORS; CANCER; APOPTOSIS; EPIGENETICS
AB Background Accumulating evidence shows evidence of efficacy with the combination of vorinostat and bortezomib in solid tumors. We previously examined a once-daily continuous dosing schedule of vorinostat in combination with bortezomib which was well tolerated in cycles 1 and 2; however, there was concern regarding the tolerability through multiple cycles. This study was conducted to evaluate an intermittent dosing schedule of vorinostat with bortezomib. Methods Vorinostat was initially administered orally twice daily on days 1-14 with bortezomib IV on days 1, 4, 8, and 11 of a 21 day cycle. Two DLTs (elevated ALT and fatigue) were observed at dose level 1, thus the protocol was amended to administer vorinostat intermittently twice daily on days 1-4 and 8-11. Results 29 patients were enrolled; 13 men and 16 women. Common cancer types included sarcoma, pancreatic, colorectal, GIST, and breast. The most common Grade 3-4 toxicities at any dose level included thrombocytopenia, fatigue, increased ALT, elevated INR, and diarrhea. DLTs in the intermittent dosing scheduled included thrombocytopenia and fatigue. The Cmax and AUC for the intermittent dosing regimen were similar to those observed in the daily dosing. In this heavily pretreated population, stable disease was observed in patients with sarcoma, colorectal adenocarcinoma and GIST. Conclusions The MTD was established at vorinostat 300 mg BID on days 1-4 and 8-11 and bortezomib 1.3 mg/m(2) IV on days 1, 4, 8, and 11 of a 21 day cycle. Tolerability was not improved with the intermittent dosing schedule of vorinostat when compared to continuous dosing.
C1 [Deming, Dustin A.; Ninan, Jacob; Bailey, Howard H.; Kolesar, Jill M.; Eickhoff, Jens; Alberti, Dona; Marnocha, Rebecca; Wilding, George; Schelman, William R.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53792 USA.
[Reid, Joel M.; Ames, Matthew M.; McGovern, Renee M.] Mayo Clin, Ctr Comprehens Canc, Rochester, MN USA.
[Espinoza-Delgado, Igor; Wright, John] NCI, Clin Trials Evaluat Program, Bethesda, MD 20892 USA.
RP Schelman, WR (reprint author), Univ Wisconsin, Carbone Canc Ctr, 600 Highland Ave,K4-530 CSC, Madison, WI 53792 USA.
EM wrs@medicine.wisc.edu
FU NCI [UO1]; Merck; [CA062491]; [NCI P30]; [CA014520]; [SAIC 25XS097];
[1ULRR025011]
FX NCI, UO1, CA062491, NCI P30, CA014520, SAIC 25XS097, and 1ULRR025011.
U01 CA69912, Phase I Trials of Anticancer Agents (Mayo Clinic); 23XS026,
CTEP Translational Research Initiative - Support Subcontracts,
Correlative Studies Core Laboratory for SAHA Phase I and Phase II
Clinical Protocols (Mayo Clinic), SAIC-FREDERICK, INC.; funding from
Merck.
NR 15
TC 10
Z9 11
U1 2
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
EI 1573-0646
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD APR
PY 2014
VL 32
IS 2
BP 323
EP 329
DI 10.1007/s10637-013-0035-8
PG 7
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA AC7NH
UT WOS:000332715900013
PM 24114123
ER
PT J
AU Jeong, W
Park, SR
Rapisarda, A
Fer, N
Kinders, RJ
Chen, A
Melillo, G
Turkbey, B
Steinberg, SM
Choyke, P
Doroshow, JH
Kummar, S
AF Jeong, Woondong
Park, Sook Ryun
Rapisarda, Annamaria
Fer, Nicole
Kinders, Robert J.
Chen, Alice
Melillo, Giovanni
Turkbey, Baris
Steinberg, Seth M.
Choyke, Peter
Doroshow, James H.
Kummar, Shivaani
TI Weekly EZN-2208 (PEGylated SN-38) in combination with bevacizumab in
patients with refractory solid tumors
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE Topoisomerase 1 inhibitor; HIF-1 alpha; Irinotecan; Anti-angiogenic
therapy; VEGF
ID INDUCIBLE FACTOR 1-ALPHA; HYPOXIA; CANCER; SN38; IRINOTECAN; CONJUGATE;
FACTOR-1-ALPHA; EXPRESSION; GLYCOL
AB Background Anti-angiogenic therapies such as bevacizumab upregulate hypoxia-inducible factor-1 alpha (HIF-1 alpha), a possible mechanism of drug resistance. Camptothecin analogues, including SN-38, have been shown to reduce the expression and transcriptional activity of HIF-1 alpha in preclinical models. We hypothesized that co-administration of pegylated SN-38 (EZN-2208) may offset the induction of HIF-1 alpha following bevacizumab treatment, resulting in synergistic antitumor effects. Patients and Methods Patients with refractory solid tumors were enrolled. Objectives were to evaluate the modulation of HIF-1 alpha protein and target genes in tumor biopsies following administration of the combination of EZN-2208 administered weekly x 3 (days 1, 8, 15) and bevacizumab administered every 2 weeks, in 28-day cycles, and to establish the safety and tolerability of the combination. Tumor biopsies and dynamic contrast enhanced MRI (DCE-MRI) were obtained following bevacizumab alone (before EZN-2208) and after administration of both study drugs. Results Twelve patients were enrolled; ten were evaluable for response. Prolonged stable disease was observed in 2 patients, one with HCC (16 cycles) and another with desmoplastic round cell tumor (7 cycles). Reduction in HIF-1 alpha protein levels in tumor biopsies compared to baseline was observed in 5 of 7 patients. Quantitative analysis of DCE-MRI from 2 patients revealed changes in K-trans and k(ep). The study closed prematurely as further clinical development of EZN-2208 was suspended by the pharmaceutical sponsor. Conclusion Preliminary proof-of-concept for modulation of HIF-1 alpha protein in tumor biopsies following administration of EZN-2208 was observed. Two of 10 patients had prolonged disease stabilization following treatment with the EZN-2208 and bevacizumab combination.
C1 [Jeong, Woondong; Park, Sook Ryun; Chen, Alice; Doroshow, James H.; Kummar, Shivaani] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Rapisarda, Annamaria; Fer, Nicole; Kinders, Robert J.; Melillo, Giovanni] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Turkbey, Baris; Steinberg, Seth M.; Choyke, Peter; Doroshow, James H.; Kummar, Shivaani] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Kummar, S (reprint author), NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
EM kummars@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX We thank Drs. Yvonne A. Evrard and Yiping Zhang for assistance with
pharmacodynamic analysis in the preparation of this manuscript. This
project has been funded in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 22
TC 10
Z9 12
U1 2
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
EI 1573-0646
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD APR
PY 2014
VL 32
IS 2
BP 340
EP 346
DI 10.1007/s10637-013-0048-3
PG 7
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA AC7NH
UT WOS:000332715900015
PM 24242862
ER
PT J
AU Xu, GF
Jing, J
Bowers, K
Liu, BY
Bao, W
AF Xu, Guifeng
Jing, Jin
Bowers, Katherine
Liu, Buyun
Bao, Wei
TI Maternal Diabetes and the Risk of Autism Spectrum Disorders in the
Offspring: A Systematic Review and Meta-Analysis
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Article
DE Autism spectrum disorders; Diabetes; Pregnancy
ID COMPREHENSIVE METAANALYSIS; AUTOIMMUNE-DISEASES; LIPID-PEROXIDATION;
OXIDATIVE STRESS; NEONATAL FACTORS; PREGNANCY; COMPLICATIONS;
POPULATION; PREVALENCE; MELLITUS
AB We performed a systematic literature search regarding maternal diabetes before and during pregnancy and the risk of autism spectrum disorders (ASD) in the offspring. Of the 178 potentially relevant articles, 12 articles including three cohort studies and nine case-control studies were included in the meta-analysis. Both the meta-analyses of cohort studies and case-control studies showed significant associations. The pooled relative risk and 95 % confidence interval (CI) among cohort studies was 1.48 (1.25-1.75, p < 0.001). For case-control studies, the pooled odds ratio and 95 % CI was 1.72 (1.24-2.41, p = 0.001). No indication of significant heterogeneity across studies or publication bias was observed. In conclusion, maternal diabetes was significantly associated with a greater risk of ASD in the offspring.
C1 [Xu, Guifeng; Jing, Jin; Liu, Buyun] Sun Yat Sen Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, Guangzhou 510080, Guangdong, Peoples R China.
[Bowers, Katherine] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Coll Med, Cincinnati, OH 45229 USA.
[Bao, Wei] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA.
RP Jing, J (reprint author), Sun Yat Sen Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, Guangzhou 510080, Guangdong, Peoples R China.
EM jingjin@mail.sysu.edu.cn; baow2@mail.nih.gov
RI Bowers, Katherine/N-5226-2015;
OI Bao, Wei/0000-0002-7301-5786
FU Intramural NIH HHS
NR 60
TC 22
Z9 22
U1 2
U2 26
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0162-3257
EI 1573-3432
J9 J AUTISM DEV DISORD
JI J. Autism Dev. Disord.
PD APR
PY 2014
VL 44
IS 4
BP 766
EP 775
DI 10.1007/s10803-013-1928-2
PG 10
WC Psychology, Developmental
SC Psychology
GA AC7EB
UT WOS:000332688900004
PM 24057131
ER
PT J
AU de la Haye, K
de Heer, HD
Wilkinson, AV
Koehly, LM
AF de la Haye, Kayla
de Heer, Hendrik Dirk
Wilkinson, Anna V.
Koehly, Laura M.
TI Predictors of parent-child relationships that support physical activity
in Mexican-American families
SO JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Physical activity; Parent; Child; Mexican-American; Support
ID NUTRITION EXAMINATION SURVEY; NATIONAL-HEALTH; UNITED-STATES;
PREVALENCE; ACCULTURATION; BEHAVIORS; ADULTS; AGGREGATION; EXPOSURE;
SMOKING
AB Family-based physical activity (PA) interventions would benefit from research that identifies how to build support for PA among family members. This study examined the extent to which relationships of encouragement to do PA, and co-engagement in PA, exist among Mexican-American parents and children, and sought to identify individual, relational, and household factors associated with these dimensions of support. Participants were 224 Mexican-origin adults, with at least one child aged 5-20 years, participating in a larger study conducted between 2008 and 2010. In baseline surveys, adult participants enumerated the names and attributes of their family and kin; this study focuses on 455 parent-child dyads, nested in 118 households. Parental encouragement of PA in their children was found in about half of dyads, and in 20 % of dyads children encouraged parents. Encouragement relationships were highly reciprocal. Reciprocal parent-child encouragement was also positively associated with co-participation in PA; the latter found in just 17 % of dyads. Results indicated that relational, individual, and socio-cultural attributes were associated with PA support among parents and children, and provide insights into how these relationships might be fostered within Mexican-American families.
C1 [de la Haye, Kayla] RAND Corp, Santa Monica, CA 90407 USA.
[de Heer, Hendrik Dirk] Univ Arizona, Dept Phys Therapy & Athlet Training, Flagstaff, AZ USA.
[Wilkinson, Anna V.] Univ Texas Austin, Sch Publ Hlth, Austin, TX 78712 USA.
[Koehly, Laura M.] NHGRI, Social Network Methods Sect, Social & Behav Res Branch, Bethesda, MD 20892 USA.
RP de la Haye, K (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA.
EM delahaye@rand.org
FU NCI NIH HHS [K07 CA126988]; NHGRI NIH HHS [Z01 HG200335]
NR 41
TC 4
Z9 4
U1 0
U2 10
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0160-7715
EI 1573-3521
J9 J BEHAV MED
JI J. Behav. Med.
PD APR
PY 2014
VL 37
IS 2
BP 234
EP 244
DI 10.1007/s10865-012-9471-8
PG 11
WC Psychology, Clinical
SC Psychology
GA AC7EF
UT WOS:000332689300006
PM 23203139
ER
PT J
AU Chalermchatvichien, P
Jumreornvong, S
Jiraporn, P
Singh, M
AF Chalermchatvichien, Pichaphop
Jumreornvong, Seksak
Jiraporn, Pornsit
Singh, Manohar
TI The Effect of Bank Ownership Concentration on Capital Adequacy,
Liquidity, and Capital Stability
SO JOURNAL OF FINANCIAL SERVICES RESEARCH
LA English
DT Article
DE Basel III; Bank ownership; Capital adequacy; Capital stability;
Financial crisis
ID RISK-TAKING; GREAT-DEPRESSION; GOVERNANCE; CONSEQUENCES; DISTRESS;
CRISIS; FIRM
AB We explore the effects of ownership concentration on the risk-taking behavior of banks. Our analysis focuses on East Asian countries because these nations have successfully implemented the Basel standards and demonstrate a high degree of regulatory convergence. For the period from 2005 to 2009, we analyzed the relation between ownership concentration and capital adequacy (Basel II) and find that an increase in ownership concentration by one standard deviation results in an improvement in capital adequacy by 7.64 %. Although Basel III does not go into effect until 2013, we retroactively apply the standards for capital stability on our sample. We find that ownership concentration would have been a significant determinant of capital stability. While at lower levels of ownership concentration, an increase in concentrated ownership would have reduced capital stability; at higher ownership levels, greater ownership concentration would have increased capital stability. We also find that concentrated ownership improves banks' liquidity. Further, the recent financial crisis does not appear to change the fundamental associations among ownership concentration, capital adequacy, and liquidity.
C1 [Chalermchatvichien, Pichaphop] Bank Thailand, Bangkok, Thailand.
[Jumreornvong, Seksak] Thammasat Univ, Bangkok, Thailand.
[Jiraporn, Pornsit; Singh, Manohar] Penn State Univ Great Valley, Malvern, PA 19355 USA.
[Jiraporn, Pornsit] Mahidol Univ, Thammasat Univ, NIDA, Bangkok 10700, Thailand.
RP Singh, M (reprint author), Penn State Univ Great Valley, 30 E Swedesford Rd, Malvern, PA 19355 USA.
EM m.singh@psu.edu
NR 36
TC 4
Z9 4
U1 0
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0920-8550
EI 1573-0735
J9 J FINANC SERV RES
JI J. Financ. Serv. Res.
PD APR
PY 2014
VL 45
IS 2
BP 219
EP 240
DI 10.1007/s10693-013-0160-8
PG 22
WC Business, Finance
SC Business & Economics
GA AC9AK
UT WOS:000332826000004
ER
PT J
AU Deter, RL
Lee, W
Sangi-Haghpeykar, H
Tarca, AL
Yeo, L
Romero, R
AF Deter, Russell L.
Lee, Wesley
Sangi-Haghpeykar, Haleh
Tarca, Adi L.
Yeo, Lami
Romero, Roberto
TI Individualized fetal growth assessment: critical evaluation of key
concepts in the specification of third trimester size trajectories
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Fetal growth; Rossavik size models; ultrasound
ID MENSTRUAL AGE; CURVE STANDARDS; BIRTH CHARACTERISTICS; ENDOCRINE
REGULATION; ASSESSMENT SCORE; NORMAL FETUSES; CIRCUMFERENCE; WEIGHT;
REEVALUATION; ULTRASOUND
AB Objectives: To characterize second and third trimester fetal growth using Individualized Growth Assessment methods in a larger cohort of fetuses with normal neonatal growth outcomes.
Methods: A prospective longitudinal study of 119 pregnancies was performed from 18 weeks, MA, to delivery. Measurements of several 1D and 3D fetal size parameters were obtained from 3D volume data sets at 3-4 week intervals. Regression analyses were used to determine Start Points (SP) and Rossavik model (P = c {t} (k + st)) coefficients c, k and s for each parameter in each fetus. Second trimester growth velocity reference ranges were determined and size model specification functions re-established, the latter used to generate individual size models. Actual measurements were compared to predicted third trimester size trajectories using Percent Deviations. New age-specific reference ranges for the Percent Deviations of each parameter were defined using 2-level statistical modeling.
Results: Rossavik models fit the data for all parameters very well (R-2: 99%), with SP's and k values similar to those found in much smaller cohorts. The c* values were strongly related to the second trimester slope (R-2: 97%), as was predicted s* to estimated c* (R-2: 54-95%). Rossavik models predicted third trimester growth with systematic errors close to 0%; random errors (95% range) ranged between 5.7 and 10.9% and 20.0 and 24.3% for 1D and 3D parameters, respectively.
Conclusions: IGA procedures for evaluating second and third trimester growth are now established based on a larger cohort (4-6 fold larger). New, more rigorously defined, age-specific standards for the evaluation of third trimester size deviations are now available for nine anatomical parameters and a weight estimation procedure that incorporates a soft tissue parameter (fractional thigh volume). These results provide a means for more reliably assessing fetal growth on an individualized basis, thus minimizing the effect of biological differences in growth.
C1 [Deter, Russell L.; Lee, Wesley; Sangi-Haghpeykar, Haleh] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA.
[Lee, Wesley] Oakland Univ, William Beaumont Sch Med, Dept Obstet & Gynecol, Rochester, MI 48063 USA.
[Lee, Wesley; Tarca, Adi L.; Yeo, Lami; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Lee, Wesley; Tarca, Adi L.; Yeo, Lami] Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA.
RP Deter, RL (reprint author), Baylor Coll Med, Dept Obstet & Gynecol, 1 Baylor Plaza, Houston, TX 77030 USA.
EM russelld@bcm.edu
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported (in part) by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.
NR 39
TC 10
Z9 10
U1 0
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD APR
PY 2014
VL 27
IS 6
BP 543
EP 551
DI 10.3109/14767058.2013.833904
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AC7RH
UT WOS:000332728600002
PM 23962305
ER
PT J
AU Perez, P
Jang, SI
Alevizos, I
AF Perez, P.
Jang, S-I
Alevizos, I.
TI Emerging landscape of non-coding RNAs in oral health and disease
SO ORAL DISEASES
LA English
DT Review
DE non-coding RNAs; long non-coding RNA; short non-coding RNA; oral
diseases
ID NATURAL ANTISENSE TRANSCRIPTS; SMALL INTERFERING RNAS; SMALL NUCLEOLAR
RNAS; ENDOGENOUS SIRNAS; Y RNAS; GENE-EXPRESSION;
SACCHAROMYCES-CEREVISIAE; EPIGENETIC REGULATION; SEQUENCING DATA;
QUALITY-CONTROL
AB The world of non-coding RNAs has only recently started being discovered. For the past 40years, coding genes, mRNA, and proteins have been the center of cellular and molecular biology, and pathologic alterations were attributed to either the aberration of gene sequence or altered promoter activity. It was only after the completion of the human genome sequence that the scientific community started seriously wondering why only a very small portion of the genome corresponded to protein-coding genes. New technologies such as the whole-genome and whole-transcriptome sequencing demonstrated that at least 90% of the genome is actively transcribed. The identification and cataloguing of multiple kinds of non-coding RNA (ncRNA) have exponentially increased, and it is now widely accepted that ncRNAs play major biological roles in cellular physiology, development, metabolism, and are also implicated in a variety of diseases. The aim of this review is to describe the two major classes (long and short forms) of non-coding RNAs and describe their subclasses in terms of function and their relevance and potential in oral diseases.
C1 [Perez, P.; Jang, S-I; Alevizos, I.] Natl Inst Dent & Craniofacial Res, Sjogrens Clin, Bethesda, MD 20892 USA.
RP Alevizos, I (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, NIH, 10 Ctr Dr,1N110, Bethesda, MD 20892 USA.
EM alevizosi@nidcr.nih.gov
FU Intramural NIH HHS [ZIA DE000733-03]
NR 103
TC 3
Z9 4
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1354-523X
EI 1601-0825
J9 ORAL DIS
JI Oral Dis.
PD APR
PY 2014
VL 20
IS 3
BP 226
EP 235
DI 10.1111/odi.12142
PG 10
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA AC8BE
UT WOS:000332757200020
PM 23781896
ER
PT J
AU Sohl, SJ
Weaver, KE
Birdee, G
Kent, EE
Danhauer, SC
Hamilton, AS
AF Sohl, Stephanie J.
Weaver, Kathryn E.
Birdee, Gurjeet
Kent, Erin E.
Danhauer, Suzanne C.
Hamilton, Ann S.
TI Characteristics associated with the use of complementary health
approaches among long-term cancer survivors
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Complementary health approaches; Oncology; Symptoms; Quality of life;
Optimism; Long-term cancer survivors
ID ALTERNATIVE MEDICINE USE; QUALITY-OF-LIFE; BREAST-CANCER; LYMPHOMA
SURVIVORS; THERAPIES; DISTRESS; CARE; POPULATION; PREDICTORS; SYMPTOMS
AB This study aims to identify the prevalence and characteristics of long-term adult cancer survivors who use complementary health approaches (CHA).
Participants completed the Follow-up Care Use Among Survivors (FOCUS) Survey, a cross-sectional investigation of long-term cancer survivors. The use of CHA and reasons for use were assessed. A multivariable logistic regression model was applied to identify if predisposing, enabling, and need characteristics described in the Complementary and Alternative Medicine Healthcare Model were associated with CHA use in the past year.
Long-term cancer survivors in the study (N = 1,666) were predominately female (62 %) and older (mean age = 69.5), with breast, prostate, colorectal, ovarian, and endometrial cancers. Thirty-three percent of survivors used CHA in the past year. Common reasons for CHA use were to relieve stress (28 %), treat or prevent cancer (21 %), relieve cancer-related symptoms (18 %), and deal with another condition (18 %). Predisposing (i.e., higher optimism) and need factors (i.e., experienced cancer-related symptoms, ever had depression/anxiety) were significantly associated with CHA (p-values < .05). Enabling factors (i.e., insurance coverage, financial resources) were not.
Cancer survivors continue to report a high prevalence of recent CHA use more than 5 years after initial diagnosis. Healthcare providers should be aware of increased use of CHA among subgroups of long-term cancer survivors in order to guide safe and optimal use.
C1 [Sohl, Stephanie J.; Birdee, Gurjeet] Vanderbilt Univ, Dept Med, Med Ctr, Nashville, TN 37203 USA.
[Weaver, Kathryn E.; Danhauer, Suzanne C.] Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC 27157 USA.
[Kent, Erin E.] NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, Appl Res Program, Bethesda, MD 20892 USA.
[Hamilton, Ann S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA.
RP Sohl, SJ (reprint author), Vanderbilt Univ, Dept Med, Med Ctr, Sixth Floor,Suite 600,2525 West End Ave, Nashville, TN 37203 USA.
EM Stephanie.Sohl@Vanderbilt.edu
FU National Cancer Institute SEER [N01-PC-35136, N01-PC-35139]; National
Cancer Institute [R25 CA122061]; National Center for Complementary &
Alternative Medicine [K23 AT006965-01A1]
FX Research reported in this publication was supported by the National
Cancer Institute SEER Contract Numbers: N01-PC-35136, N01-PC-35139
(http://cancercontrol.cancer.gov/ocs/focus.html); the National Cancer
Institute grant: R25 CA122061; and the National Center for Complementary
& Alternative Medicine grant: K23 AT006965-01A1. The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Cancer Institute, National Center For
Complementary & Alternative Medicine or the National Institutes of
Health.
NR 45
TC 9
Z9 10
U1 2
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
EI 1433-7339
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD APR
PY 2014
VL 22
IS 4
BP 927
EP 936
DI 10.1007/s00520-013-2040-z
PG 10
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA AC4QM
UT WOS:000332505800011
PM 24263621
ER
PT J
AU Chandrasekar, I
Goeckeler, ZM
Turney, SG
Wang, P
Wysolmerski, RB
Adelstein, RS
Bridgman, PC
AF Chandrasekar, Indra
Goeckeler, Zoe M.
Turney, Stephen G.
Wang, Peter
Wysolmerski, Robert B.
Adelstein, Robert S.
Bridgman, Paul C.
TI Nonmuscle Myosin II Is a Critical Regulator of Clathrin- Mediated
Endocytosis
SO TRAFFIC
LA English
DT Article
DE actin; clathrin; endocytosis; myosin II
ID ACTIN CYTOSKELETON; MEMBRANE TENSION; EPITHELIAL-CELLS; MAMMALIAN-CELLS;
PLASMA-MEMBRANE; COATED PITS; DYNAMIN; FISSION; PROTEINS; DOMAIN
AB Variable requirements for actin during clathrin-mediated endocytosis (CME) may be related to regional or cellular differences in membrane tension. To compensate, local regulation of force generation may be needed to facilitate membrane curving and vesicle budding. Force generation is assumed to occur primarily through actin polymerization. Here we examine the role of myosin II using loss of function experiments. Our results indicate that myosin II acts on cortical actin scaffolds primarily in the plane of the plasma membrane (bottom arrow) to generate changes that are critical for enhancing CME progression.
C1 [Chandrasekar, Indra; Wang, Peter; Bridgman, Paul C.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
[Goeckeler, Zoe M.; Wysolmerski, Robert B.] W Virginia Univ, Sch Med, Mary Babb Randolph Canc Ctr, Dept Neurobiol & Anat, Morgantown, WV 26506 USA.
[Turney, Stephen G.] Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA.
[Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
RP Bridgman, PC (reprint author), Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
EM bridgmap@pcg.wustl.edu
OI Adelstein, Robert/0000-0002-8683-2144
FU NIH [R21 MH081260, R21EB9776, L-090937, P20RR016440]; Bakewell
Neuroimaging Core; Bakewell Family Foundation; National Institutes of
Health Neuroscience Blueprint Interdisciplinary Center Core Grant [P30
(NS057105)]; NHLB (DIR)
FX This work was supported by grants to P. C. B. from NIH (R21 MH081260,
R21EB9776) and in part by the Bakewell Neuroimaging Core, supported by
the Bakewell Family Foundation and the National Institutes of Health
Neuroscience Blueprint Interdisciplinary Center Core Grant P30
(NS057105) to Washington University. Support was also provided by NHLB
(DIR) to R. S. A. and grants to R. B. W.(HL-090937, P20RR016440) from
NIH. We thank Robyn Roth and Dr. John E. Heuser for their help with the
electron microscopy and Marcy Hartstein for the table of contents
graphic. The authors have no conflict of interest to declare.
NR 45
TC 7
Z9 7
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-9219
EI 1600-0854
J9 TRAFFIC
JI Traffic
PD APR
PY 2014
VL 15
IS 4
BP 418
EP 432
DI 10.1111/tra.12152
PG 15
WC Cell Biology
SC Cell Biology
GA AC0LL
UT WOS:000332186000005
PM 24443954
ER
PT J
AU Schulze, TG
Akula, N
Breuer, R
Steele, J
Nalls, MA
Singleton, AB
Degenhardt, FA
Nothen, MM
Cichon, S
Rietschel, M
Mcmahon, FJ
AF Schulze, Thomas G.
Akula, Nirmala
Breuer, Rene
Steele, Jo
Nalls, Michael A.
Singleton, Andrew B.
Degenhardt, Franziska A.
Noethen, Markus M.
Cichon, Sven
Rietschel, Marcella
Mcmahon, Francis J.
CA Bipolar Genome Study
TI Molecular genetic overlap in bipolar disorder, schizophrenia, and major
depressive disorder
SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Genome-wide association; polygenic model; allele burden; psychosis;
prediction
ID GENOME-WIDE ASSOCIATION; PHENOTYPE CHARACTERIZATION; PARKINSONS-DISEASE;
CONTROLLED FAMILY; COMMON DISEASES; DAOA/G30 LOCUS; HUMAN HEIGHT;
PREDICTION; VARIANTS; RISK
AB Objectives. Genome-wide association studies (GWAS) in complex phenotypes, including psychiatric disorders, have yielded many replicated findings, yet individual markers account for only a small fraction of the inherited differences in risk. We tested the performance of polygenic models in discriminating between cases and healthy controls and among cases with distinct psychiatric diagnoses. Methods. GWAS results in bipolar disorder (BD), major depressive disorder (MDD), schizophrenia (SZ), and Parkinson's disease (PD) were used to assign weights to individual alleles, based on odds ratios. These weights were used to calculate allele scores for individual cases and controls in independent samples, summing across many single nucleotide polymorphisms (SNPs). How well allele scores discriminated between cases and controls and between cases with different disorders was tested by logistic regression. Results. Large sets of SNPs were needed to achieve even modest discrimination between cases and controls. The most informative SNPs were overlapping in BD, SZ, and MDD, with correlated effect sizes. Little or no overlap was seen between allele scores for psychiatric disorders and those for PD. Conclusions. BD, SZ, and MDD all share a similar polygenic component, but the polygenic models tested lack discriminative accuracy and are unlikely to be useful for clinical diagnosis.
C1 [Schulze, Thomas G.] Univ Gottingen, Dept Psychiat & Psychotherapy, D-537075 Gottingen, Germany.
[Schulze, Thomas G.; Akula, Nirmala; Steele, Jo; Mcmahon, Francis J.] NIMH, Human Genet Branch, Intramural Res Program, NIH,US Dept HHS, Bethesda, MD 20892 USA.
[Schulze, Thomas G.; Breuer, Rene; Rietschel, Marcella] Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.
[Schulze, Thomas G.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA.
[Nalls, Michael A.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Degenhardt, Franziska A.; Noethen, Markus M.; Cichon, Sven] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Degenhardt, Franziska A.; Noethen, Markus M.; Cichon, Sven] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany.
[Cichon, Sven] Res Ctr Julich, Inst Neurosci & Med INM 1, Struct & Funct Org Brain, Genom Imaging, Julich, Germany.
RP Schulze, TG (reprint author), Univ Gottingen, Sect Psychiat Genet, Dept Psychiat & Psychotherapy, von Siebold Str, D-537075 Gottingen, Germany.
EM thomas.schulze@med.uni-goettingen.de
RI Singleton, Andrew/C-3010-2009; Zhang, Peng/N-2920-2014;
OI Zhang, Peng/0000-0003-1182-1392; McMahon, Francis/0000-0002-9469-305X;
Nothen, Markus/0000-0002-8770-2464
FU National Institute of Mental Health (NIMH), National Institutes of
Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS);
Deutsche Forschungsgemeinschaft (DFG); National German Genome Research
Network (NGFN); NARSAD; Alfried Krupp von Bohlen und Halbach-Stiftung;
Intramural Research Program of the National Institute on Aging, National
Institutes of Health, Department of Health and Human Services [Z01
AG000932-02]
FX The authors are greatly indebted to Naomi Wray for highly inspirational
discussions. Ioline Henter provided outstanding editorial assistance.
Funded by the Intramural Research Program of the National Institute of
Mental Health (NIMH), National Institutes of Health, Department of
Health and Human Services (IRP-NIMH-NIH-DHHS), Deutsche
Forschungsgemeinschaft (DFG), the National German Genome Research
Network (NGFN), NARSAD (Independent/Junior Investigator Awards to
FJM/TGS), and the Alfried Krupp von Bohlen und Halbach-Stiftung.
Genotyping of the GAIN BD, GAIN MDD, and GAIN SZ samples was provided
through the Genetic Association Information Network (GAIN). The datasets
used for the analyses described in this manuscript were obtained from
the database of Genotypes and Phenotypes (dbGaP). Samples and associated
phenotype data were provided by the contributing studies. We thank the
Wellcome Trust Case Control Consortium, The Netherlands Study of
Depression and Anxiety, and the Netherlands Twin Registry for making
data/results available for analysis. The contributions of ABS and MAN
were supported by the Intramural Research Program of the National
Institute on Aging, National Institutes of Health, Department of Health
and Human Services (project Z01 AG000932-02, human subjects protocols
2004-147 and 2003-081).
NR 32
TC 22
Z9 23
U1 2
U2 13
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1562-2975
EI 1814-1412
J9 WORLD J BIOL PSYCHIA
JI World J. Biol. Psychiatry
PD APR
PY 2014
VL 15
IS 3
BP 200
EP 208
DI 10.3109/15622975.2012.662282
PG 9
WC Psychiatry
SC Psychiatry
GA AC8QJ
UT WOS:000332798400004
PM 22404658
ER
PT J
AU Haws, ME
Jaramillo, TC
Espinosa, F
Widman, AJ
Stuber, GD
Sparta, DR
Tye, KM
Russo, SJ
Parada, LF
Stavarache, M
Kaplitt, M
Bonci, A
Powell, CM
AF Haws, Michael E.
Jaramillo, Thomas C.
Espinosa, Felipe
Widman, Allie J.
Stuber, Garret D.
Sparta, Dennis R.
Tye, Kay M.
Russo, Scott J.
Parada, Luis F.
Stavarache, Mihaela
Kaplitt, Michael
Bonci, Antonello
Powell, Craig M.
TI PTEN Knockdown Alters Dendritic Spine/Protrusion Morphology, not Density
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE dendrite; spine; amygdale; dentate gyrus; AKT; mTOR; PTEN
ID AUTISM SPECTRUM DISORDERS; LHERMITTE-DUCLOS-DISEASE; TUMOR-SUPPRESSOR
GENE; BEHAVIORAL-TEST BATTERIES; RILEY-RUVALCABA-SYNDROME; GERMLINE
MUTATIONS; MICROSCOPY IMAGES; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS;
PHOSPHATASE GENE
AB Mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) are implicated in neuropsychiatric disorders including autism. Previous studies report that PTEN knockdown in neurons in vivo leads to increased spine density and synaptic activity. To better characterize synaptic changes in neurons lacking PTEN, we examined the effects of shRNA knockdown of PTEN in basolateral amygdala neurons on synaptic spine density and morphology by using fluorescent dye confocal imaging. Contrary to previous studies in the dentate gyrus, we find that knockdown of PTEN in basolateral amygdala leads to a significant decrease in total spine density in distal dendrites. Curiously, this decreased spine density is associated with increased miniature excitatory postsynaptic current frequency and amplitude, suggesting an increase in number and function of mature spines. These seemingly contradictory findings were reconciled by spine morphology analysis demonstrating increased mushroom spine density and size with correspondingly decreased thin protrusion density at more distal segments. The same analysis of PTEN conditional deletion in the dentate gyrus demonstrated that loss of PTEN does not significantly alter total density of dendritic protrusions in the dentate gyrus, but does decrease thin protrusion density and increases density of more mature mushroom spines. These findings suggest that, contrary to previous reports, PTEN knockdown may not induce de novo spinogenesis, but instead may increase synaptic activity by inducing morphological and functional maturation of spines. Furthermore, behavioral analysis of basolateral amygdala PTEN knockdown suggests that these changes limited only to the basolateral amygdala complex may not be sufficient to induce increased anxiety-related behaviors. J. Comp. Neurol. 522:1171-1190, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Haws, Michael E.; Jaramillo, Thomas C.; Espinosa, Felipe; Widman, Allie J.; Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA.
[Haws, Michael E.; Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Neurosci Grad Program, Dallas, TX 75390 USA.
[Russo, Scott J.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA.
[Parada, Luis F.] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA.
[Stavarache, Mihaela; Kaplitt, Michael] Weill Cornell Med Coll, Dept Neurol Surg, New York, NY 10065 USA.
[Bonci, Antonello] Natl Inst Drug Abuse, Intramural Res Program, Bethesda, MD 21224 USA.
[Stuber, Garret D.; Sparta, Dennis R.; Tye, Kay M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Bonci, Antonello] Johns Hopkins Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21287 USA.
[Bonci, Antonello] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21287 USA.
[Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
RP Powell, CM (reprint author), 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM craig.powell@utsouthwestern.edu
RI Espinosa, Free/H-8963-2015; Stuber, Garret/E-1160-2011;
OI Espinosa, Free/0000-0002-1409-5106; Powell, Craig/0000-0001-5451-2165;
Haws, Michael/0000-0002-5468-6218
FU National Institute of Mental Health, National Institutes of Health
[MH081164]; National Institute of Child Health and Human Development,
National Institutes of Health [HD069560]; Autism Speaks; Lowe
Foundation; Crystal Charity Ball; Hartwell Foundation
FX Grant sponsor: National Institute of Mental Health, National Institutes
of Health; Grant number: MH081164 (to C. M. P.); Grant sponsor: National
Institute of Child Health and Human Development, National Institutes of
Health; Grant number: HD069560 (to C. M. P.); Grant sponsor: Autism
Speaks (to C. M. P.); Grant sponsor: Lowe Foundation (to C. M. P.);
Grant sponsor: Crystal Charity Ball (to C. M. P.); Grant sponsor: The
Hartwell Foundation (to C.M.P.).
NR 74
TC 15
Z9 15
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9967
EI 1096-9861
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD APR 1
PY 2014
VL 522
IS 5
BP 1171
EP 1190
DI 10.1002/cne.23488
PG 20
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA AA3QF
UT WOS:000331006700010
PM 24264880
ER
PT J
AU Yang, Z
Chang, C
Xu, T
Jiang, LL
Handwerker, DA
Castellanos, FX
Milham, MP
Bandettini, PA
Zuo, XN
AF Yang, Zhi
Chang, Catie
Xu, Ting
Jiang, Lili
Handwerker, Daniel A.
Castellanos, F. Xavier
Milham, Michael P.
Bandettini, Peter A.
Zuo, Xi-Nian
TI Connectivity trajectory across lifespan differentiates the precuneus
from the default network
SO NEUROIMAGE
LA English
DT Article
DE Default network; Precuneus; Independent component analysis; Lifespan
trajectory; Functional connectome; gRAICAR
ID POSTERIOR CINGULATE CORTEX; INDEPENDENT COMPONENT ANALYSIS; INTRINSIC
FUNCTIONAL ARCHITECTURE; RESTING-STATE FMRI; BRAIN-FUNCTION; MODE
NETWORK; PARIETAL CORTEX; AGE; ORGANIZATION; DISEASE
AB The default network of the human brain has drawn much attention due to its relevance to various brain disorders, cognition, and behavior. However, its functional components and boundaries have not been precisely defined. There is no consensus as to whether the precuneus, a hub in the functional connectome, acts as part of the default network This discrepancy is more critical for brain development and aging studies: it is not clear whether age has a stronger impact on the default network or precuneus, or both. We used Generalized Ranking and Averaging Independent Component Analysis by Reproducibility (gRAICAR) to investigate the lifespan trajectories of intrinsic functional networks. By estimating individual-specific spatial components and aligning them across subjects, gRAICAR measures the spatial variation of component maps across a population without constraining the same components to appear in every subject In a cross-lifespan fMRI dataset (N = 126, 7-85 years old), we observed stronger age dependence in the spatial pattern of a precuneus-dorsal posterior cingulate cortex network compared to the default network, despite the fact that the two networks exhibit considerable spatial overlap and temporal correlation. These results remained even when analyses were restricted to a subpopulation with very similar head motion across age. Our analyses further showed that the two networks tend to merge with increasing age. Post-hoc analyses of functional connectivity confirmed the distinguishable cross-lifespan trajectories between the two networks. Based on these observations, we proposed a dynamic model of cross-lifespan functional segregation and integration between the two networks, suggesting that the precuneus network may have a different functional role than the default network, which declines with age. These findings have implications for understanding the functional roles of the default network, gaining insight into its dynamics throughout life, and guiding interpretation of alterations in brain disorders. Published by Elsevier Inc.
C1 [Yang, Zhi; Xu, Ting; Jiang, Lili; Zuo, Xi-Nian] Chinese Acad Sci, Inst Psychol, Magnet Resonance Imaging Res Ctr, Lab Funct Connectome & Dev,Key Lab Behav Sci, Beijing 100101, Peoples R China.
[Yang, Zhi; Handwerker, Daniel A.; Bandettini, Peter A.] NIMH, NIH, Lab Brain & Cognit, Sect Funct Imaging Methods, Bethesda, MD 20892 USA.
[Chang, Catie] Natl Inst Neurol Disorders & Stroke, NIH, Lab Funct & Mol Imaging, Adv MRI Sect, Bethesda, MD 20892 USA.
[Castellanos, F. Xavier; Milham, Michael P.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA.
[Castellanos, F. Xavier] NYU, Langone Med Ctr, Ctr Child Study, Ctr Neurodev Disorders, New York, NY 10016 USA.
[Milham, Michael P.] Child Mind Inst, Ctr Developing Brain, New York, NY 10022 USA.
RP Yang, Z (reprint author), Chinese Acad Sci, Inst Psychol, 16 Lincui Rd, Beijing 100101, Peoples R China.
EM yangz@psych.ac.cn; zuoxn@psych.ac.cn
RI Milham, Michael/K-9501-2014;
OI Zuo, Xi-Nian/0000-0001-9110-585X; Yang, Zhi/0000-0002-2222-2312;
Castellanos, Francisco/0000-0001-9192-9437
FU National Key Technologies R&D Program of China [2012BAI36B01]; Natural
Science Foundation of China [81270023, 81171409, 81220108014]; Key
Research Program; Hundred Talents Program of the Chinese Academy of
Sciences [KSZDEW-TZ-002]; Intramural Research Program of the National
Institute of Neurological Disorders and Stroke, National Institutes of
Health; Intramural Research Program of the National Institute of Mental
Health, National Institutes of Health; NIMH BRAINS [R01MH094639-01]
FX The authors would like to thank Dr. Gang Chen for the help in
statistical tests. This work was supported by the National Key
Technologies R&D Program of China (No. 2012BAI36B01) and the Natural
Science Foundation of China (81270023, 81171409, 81220108014). XNZ
acknowledges the support from the Key Research Program and the Hundred
Talents Program of the Chinese Academy of Sciences (KSZDEW-TZ-002). CC
is supported by the Intramural Research Program of the National
Institute of Neurological Disorders and Stroke, National Institutes of
Health. DH and PAB are supported by the Intramural Research Program of
the National Institute of Mental Health, National Institutes of Health.
MPM is supported by NIMH BRAINS R01MH094639-01 and gifts from Joseph P.
Healey and the Stavros Niarchos Foundation to the Child Mind Institute.
NR 73
TC 32
Z9 34
U1 1
U2 16
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD APR 1
PY 2014
VL 89
BP 45
EP 56
DI 10.1016/j.neuroimage.2013.10.039
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AB8RJ
UT WOS:000332057400005
PM 24287438
ER
PT J
AU Ferre, S
Casado, V
Devi, LA
Filizola, M
Jockers, R
Lohse, MJ
Milligan, G
Pin, JP
Guitart, X
AF Ferre, Sergi
Casado, Vicent
Devi, Lakshmi A.
Filizola, Marta
Jockers, Ralf
Lohse, Martin J.
Milligan, Graeme
Pin, Jean-Philippe
Guitart, Xavier
TI G Protein-Coupled Receptor Oligomerization Revisited: Functional and
Pharmacological Perspectives
SO PHARMACOLOGICAL REVIEWS
LA English
DT Review
ID ADENOSINE A(2A) RECEPTORS; HIGHER-ORDER OLIGOMERS; TIME-RESOLVED FRET;
OPIOID RECEPTOR; DOPAMINE-RECEPTOR; CRYSTAL-STRUCTURE; LIGAND-BINDING;
ALLOSTERIC MODULATION; MONOMERIC RHODOPSIN; PHYSIOLOGICAL RELEVANCE
AB Most evidence indicates that, as for family C G protein-coupled receptors (GPCRs), family A GPCRs form homo- and heteromers. Homodimers seem to be a predominant species, with potential dynamic formation of higher-order oligomers, particularly tetramers. Although monomeric GPCRs can activate G proteins, the pentameric structure constituted by one GPCR homodimer and one heterotrimeric G protein may provide a main functional unit, and oligomeric entities can be viewed as multiples of dimers. It still needs to be resolved if GPCR heteromers are preferentially heterodimers or if they are mostly constituted by heteromers of homodimers. Allosteric mechanisms determine a multiplicity of possible unique pharmacological properties of GPCR homomers and heteromers. Some general mechanisms seem to apply, particularly at the level of ligand-binding properties. In the frame of the dimer-cooperativity model, the two-state dimer model provides the most practical method to analyze ligand-GPCR interactions when considering receptor homomers. In addition to ligand-binding properties, unique properties for each GPCR oligomer emerge in relation to different intrinsic efficacy of ligands for different signaling pathways (functional selectivity). This gives a rationale for the use of GPCR oligomers, and particularly heteromers, as novel targets for drug development. Herein, we review the functional and pharmacological properties of GPCR oligomers and provide some guidelines for the application of discrete direct screening and high-throughput screening approaches to the discovery of receptor-heteromer selective compounds.
C1 [Ferre, Sergi; Guitart, Xavier] NIDA, Integrat Neurobiol Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Casado, Vicent] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, Barcelona, Spain.
[Casado, Vicent] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain.
[Devi, Lakshmi A.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, Mt Sinai, NY USA.
[Filizola, Marta] Icahn Sch Med Mt Sinai, Dept Struct & Chem Biol, Mt Sinai, NY USA.
[Jockers, Ralf] INSERM, Inst Cochin, U1016, Paris, France.
[Jockers, Ralf] CNRS, Unite Mixte Rech 8104, Paris, France.
[Jockers, Ralf] Univ Paris 05, Sorbone Paris Cite, Paris, France.
[Lohse, Martin J.] Univ Wurzburg, Inst Pharmacol & Toxicol, D-97070 Wurzburg, Germany.
[Lohse, Martin J.] Univ Wurzburg, Rudolf Virchow Ctr, D-97070 Wurzburg, Germany.
[Milligan, Graeme] Univ Glasgow, Coll Med Vet & Life Sci, Inst Mol Cell & Syst Biol, Mol Pharmacol Grp, Glasgow, Lanark, Scotland.
[Pin, Jean-Philippe] Univ Montpellier, CNRS, Unite Mixte Rech 5203, Inst Genom Fonct, F-34059 Montpellier, France.
[Pin, Jean-Philippe] INSERM, U661, Montpellier, France.
RP Ferre, S (reprint author), NIDA, Integrat Neurobiol Sect, Intramural Res Program, Dept Hlth & Human Serv, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM sferre@intra.nida.nih.gov
RI Lohse, Martin/A-7160-2012; Ferre, Sergi/K-6115-2014; Casado,
Vicent/K-1660-2014;
OI Lohse, Martin/0000-0002-0599-3510; Ferre, Sergi/0000-0002-1747-1779;
Filizola, Marta/0000-0002-4382-8276; Casado, Vicent/0000-0002-1764-3825
FU National Institutes of Health [National Institute on Drug Abuse];
National Institutes of Health National Institute on Drug Abuse
[DA026434, DA034049, DA008863, DA019521]; Ministerio de Ciencia y
Tecnologia [SAF2011-23813]; Centro de Investigacion Biomedica en Red
sobre Enfermedades Neurodegenerativas [PI2011/02-7]; Fondation Jerome
Lejeune [FJL-01/01/2013]; Agence Nationale de la Recherche [ANR RPIB
2012 "MED-HET-REC-2", ANR-11-IDEX-0005-01, ANR-11-LABX-0071,
ANR-12-BSV2-0015, ARN-09-BIOT-018]; Fondation Recherche Medicale [FRM
DEQ20130326503]; Institut National de la Sante et de la Recherche
Medicale; Centre National de la Recherche Scientifique; European
Research Council; Medical Research Council [G0900050]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health [National Institute on Drug Abuse] (to
S.F. and X.G.); the National Institutes of Health National Institute on
Drug Abuse [Grants DA026434 and DA034049 (to M.F.) and Grants DA008863
and DA019521 (to L.A.D.)]; "Ministerio de Ciencia y Tecnologia" [Grant
SAF2011-23813], "Centro de Investigacion Biomedica en Red sobre
Enfermedades Neurodegenerativas" [Grant PI2011/02-7], and "Fondation
Jerome Lejeune" [FJL-01/01/2013] (to V.C.); "Agence Nationale de la
Recherche" [Grants ANR RPIB 2012 "MED-HET-REC-2", ANR-11-IDEX-0005-01,
and ANR-11-LABX-0071 (to R.J.) and ANR-12-BSV2-0015 and ARN-09-BIOT-018
(to J.-P.P.)]; "Fondation Recherche Medicale" [Grant FRM
DEQ20130326503], "Institut National de la Sante et de la Recherche
Medicale," and "Centre National de la Recherche Scientifique" (to R.J.);
European Research Council Advanced Grant "Topas" (to M.J.L.); and
Medical Research Council [Grant G0900050] (to G.M.).
NR 159
TC 118
Z9 120
U1 4
U2 70
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0031-6997
EI 1521-0081
J9 PHARMACOL REV
JI Pharmacol. Rev.
PD APR
PY 2014
VL 66
IS 2
BP 413
EP 434
DI 10.1124/pr.113.008052
PG 22
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AB8JC
UT WOS:000332035200002
PM 24515647
ER
PT J
AU McGrath, M
Seidman, J
Nelson, M
Lang, D
Gratz, J
Knobler, S
Platts-Mills, J
Houpt, E
AF McGrath, M.
Seidman, J.
Nelson, M.
Lang, D.
Gratz, J.
Knobler, S.
Platts-Mills, J.
Houpt, E.
TI The prevalence of norovirus in the MAL-ED cohort
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [McGrath, M.; Seidman, J.; Knobler, S.] Fogarty Int Ctr, Bethesda, MD USA.
[Nelson, M.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Lang, D.] Fdn Natl Inst Hlth, Bethesda, MD USA.
[Gratz, J.; Platts-Mills, J.; Houpt, E.] Div Infect Dis & Int Hlth, Charlottesville, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
EI 1878-3511
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD APR
PY 2014
VL 21
SU 1
MA 41.029
BP 117
EP 117
DI 10.1016/j.ijid.2014.03.669
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA V43TP
UT WOS:000209704000254
ER
PT J
AU Singh, N
Kumar, R
Gautam, S
Singh, OP
Gidwani, K
Rai, M
Sundar, S
Nylen, S
Sacks, D
AF Singh, N.
Kumar, R.
Gautam, S.
Singh, O. P.
Gidwani, K.
Rai, M.
Sundar, S.
Nylen, S.
Sacks, D.
TI Leishmania specific CD4 T cells release IFN-gamma that limits parasite
replication in patients with visceral leishmaniasis
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Singh, N.; Kumar, R.; Gautam, S.; Singh, O. P.; Gidwani, K.; Rai, M.; Sundar, S.] Inst Med Sci, Varanasi, Uttar Pradesh, India.
[Nylen, S.] Karolinska Inst, Stockholm, Sweden.
[Sacks, D.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
EI 1878-3511
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD APR
PY 2014
VL 21
SU 1
MA 45.012
BP 158
EP 158
DI 10.1016/j.ijid.2014.03.752
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA V43TP
UT WOS:000209704000337
ER
PT J
AU Doumbia, S
Kamhawi, S
Keita, S
Anderson, JM
Sissoko, IM
Samake, S
Coulibaly, CA
Teixeira, C
Faye, O
Traore, B
Oliveira, FL
Valenzuela, JC
AF Doumbia, S.
Kamhawi, S.
Keita, S.
Anderson, J. M.
Sissoko, I. M.
Samake, S.
Coulibaly, C. A.
Teixeira, C.
Faye, O.
Traore, B.
Oliveira, F. L.
Valenzuela, J. C.
TI Cutaneous leishmaniasis: the parasite and immune response to sand fly
saliva in endemic areas of Mali
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Doumbia, S.; Keita, S.; Sissoko, I. M.; Samake, S.; Coulibaly, C. A.; Faye, O.; Traore, B.] Univ Bamako, USTTB, Bamako, Mali.
[Kamhawi, S.; Anderson, J. M.; Teixeira, C.; Oliveira, F. L.; Valenzuela, J. C.] NIAID, LMVR, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
EI 1878-3511
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD APR
PY 2014
VL 21
SU 1
MA 45.016
BP 160
EP 160
DI 10.1016/j.ijid.2014.03.756
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA V43TP
UT WOS:000209704000341
ER
PT J
AU Morens, D
AF Morens, D.
TI How the 1917 army measles epidemics changed emerging infectious disease
awareness
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Morens, D.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
EI 1878-3511
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD APR
PY 2014
VL 21
SU 1
MA 51.047
BP 237
EP 237
DI 10.1016/j.ijid.2014.03.915
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA V43TP
UT WOS:000209704000499
ER
PT J
AU Salie, M
van der Merwe, L
Moller, M
Daya, M
van der Spuy, G
van Helden, PD
Martin, MP
Gao, XJ
Warren, RM
Carrington, M
Hoal, EG
AF Salie, M.
van der Merwe, L.
Moller, M.
Daya, M.
van der Spuy, G.
van Helden, P. D.
Martin, M. P.
Gao, X. -J.
Warren, R. M.
Carrington, M.
Hoal, E. G.
TI Associations between human leukocyte antigen class I variants and the
Mycobacterium tuberculosis subtypes causing disease
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Salie, M.; van der Merwe, L.; Moller, M.; Daya, M.; van der Spuy, G.; van Helden, P. D.; Warren, R. M.; Hoal, E. G.] Univ Stellenbosch, ZA-7505 Tygerberg, South Africa.
[Martin, M. P.; Gao, X. -J.; Carrington, M.] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 3
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
EI 1878-3511
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD APR
PY 2014
VL 21
SU 1
MA 56.004
BP 300
EP 300
DI 10.1016/j.ijid.2014.03.1043
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA V43TP
UT WOS:000209704000626
ER
PT J
AU Dhanda, A
Liu, B
Nussenblatt, R
Dick, AD
Lee, RW
Collins, PL
AF Dhanda, A.
Liu, B.
Nussenblatt, R.
Dick, A. D.
Lee, R. W.
Collins, P. L.
TI CD14(++)CD16(-) MONOCYTES FROM PATIENTS WITH SEVERE ALCOHOLIC HEPATITIS
DRIVE MEMORY T CELL PROLIFERATION AND POLARISE THEM TO A STEROID
RESISTANT TH17 PHENOTYPE
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 49th Annual International Liver Congress of the
European-Association-for-the-Study-of-the-Liver
CY APR 09-13, 2014
CL London, ENGLAND
SP European Assoc Study Liver
C1 [Dhanda, A.; Collins, P. L.] Univ Hosp Bristol NHS Fdn Trust, Bristol, Avon, England.
[Dhanda, A.; Dick, A. D.; Lee, R. W.] Univ Bristol, Sch Clin Sci, Bristol, Avon, England.
[Liu, B.; Nussenblatt, R.] NEI, NIH, Bethesda, MD 20892 USA.
EM ashwin.dhanda@bristol.ac.uk
RI Lee, Richard/A-3116-2017
OI Lee, Richard/0000-0002-9480-6843
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 1
SU S
MA P161
BP S119
EP S119
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CS3HB
UT WOS:000361961700322
ER
PT J
AU Gane, EJ
Gordon, S
Kottili, S
Massetto, B
Gaggar, A
Stem, S
Pflanz, S
Ye, Z
Subramanian, M
McHutchison, JG
Lim, YS
Kim, YJ
AF Gane, E. J.
Gordon, S.
Kottili, S.
Massetto, B.
Gaggar, A.
Stem, S.
Pflanz, S.
Ye, Z.
Subramanian, M.
McHutchison, J. G.
Lim, Y. -S.
Kim, Y. J.
TI DETERMINANTS OF VARIABILITY IN ISG15 GENE EXPRESSION IN PATIENTS WITH
CHRONIC HEPATITIS B (CHB) INFECTION DURING TREATMENT WITH ORAL TLR7
AGONIST GS-9620
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 49th Annual International Liver Congress of the
European-Association-for-the-Study-of-the-Liver
CY APR 09-13, 2014
CL London, ENGLAND
SP European Assoc Study Liver
C1 [Gane, E. J.] Auckland Clin Studies, Auckland, New Zealand.
[Gordon, S.] Henry Ford Hlth Syst, Detroit, MI USA.
[Kottili, S.] NIH, DHHS, Bethesda, MD 20892 USA.
[Massetto, B.; Gaggar, A.; Stem, S.; Pflanz, S.; Ye, Z.; Subramanian, M.; McHutchison, J. G.] Gilead Sci Inc, Foster City, CA 94404 USA.
[Lim, Y. -S.] Asan Med Ctr, Seoul, South Korea.
[Kim, Y. J.] Seoul Natl Univ Hosp, Seoul 110744, South Korea.
EM edgane@adhb.govt.nz
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 1
SU S
MA P1052
BP S426
EP S427
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CT5DT
UT WOS:000362828600468
ER
PT J
AU Marquardt, JU
Seo, D
Andersen, JB
Gillen, MC
Kim, MS
Conner, EC
Galle, PR
Factor, VM
Park, YN
Thorgeirsson, SS
AF Marquardt, J. U.
Seo, D.
Andersen, J. B.
Gillen, M. C.
Kim, M. S.
Conner, E. C.
Galle, P. R.
Factor, V. M.
Park, Y. N.
Thorgeirsson, S. S.
TI SEQUENTIAL TRANSCRIPTOME ANALYSIS OF HUMAN HEPATOCARCINOGENESIS BY RNA
SEQUENCING SUPPORTS INTENSIFIED SURVEILLANCE OF EARLY LESIONS TO PREVENT
LATE STAGE ACQUISITION OF MALIGNANT TRAITS
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 49th Annual International Liver Congress of the
European-Association-for-the-Study-of-the-Liver
CY APR 09-13, 2014
CL London, ENGLAND
SP European Assoc Study Liver
C1 [Marquardt, J. U.; Galle, P. R.] Johannes Gutenberg Univ Mainz, Dept Med 1, Mainz, Germany.
[Marquardt, J. U.; Seo, D.; Andersen, J. B.; Gillen, M. C.; Conner, E. C.; Factor, V. M.; Thorgeirsson, S. S.] NCI, Expt Carcinogenesis Lab, CCR, NIH, Bethesda, MD 20892 USA.
[Kim, M. S.; Park, Y. N.] Yonsei Univ, Dept Pathol, Seoul 120749, South Korea.
EM marquarj@uni-mainz.de
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 1
SU S
MA P45
BP S82
EP S82
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CS3HB
UT WOS:000361961700207
ER
PT J
AU Maslak, E
Jasztal, A
Kochan, K
Sitek, B
Zabielski, P
Chabowski, A
Kus, K
Walczak, M
Proniewski, B
Baranska, M
Keefer, L
Chlopicki, S
AF Maslak, E.
Jasztal, A.
Kochan, K.
Sitek, B.
Zabielski, P.
Chabowski, A.
Kus, K.
Walczak, M.
Proniewski, B.
Baranska, M.
Keefer, L.
Chlopicki, S.
TI EFFECTS OF LIVER-SPECIFIC NO-DONOR, V-PYRRO/NO ON LIVER STEATOSIS IN
MICE FED HIGH FAT DIET
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 49th Annual International Liver Congress of the
European-Association-for-the-Study-of-the-Liver
CY APR 09-13, 2014
CL London, ENGLAND
SP European Assoc Study Liver
C1 [Maslak, E.; Jasztal, A.; Kochan, K.; Sitek, B.; Kus, K.; Walczak, M.; Proniewski, B.; Baranska, M.; Chlopicki, S.] Jagiellonian Univ, JCET, Krakow, Poland.
[Kochan, K.; Baranska, M.] Jagiellonian Univ, Fac Chem, Krakow, Poland.
[Zabielski, P.; Chabowski, A.] Med Univ Bialystok, Dept Physiol, Bialystok, Poland.
[Walczak, M.] Jagiellonian Univ, Dept Pharmacokinet & Phys Pharm, Krakow, Poland.
[Keefer, L.] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA.
[Chlopicki, S.] Jagiellonian Univ, Dept Expt Pharmacol, Krakow, Poland.
EM edyta.maslak@jcet.eu
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 1
SU S
MA P286
BP S161
EP S161
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CS3HB
UT WOS:000361961700447
ER
PT J
AU O'Brien, T
Pfeiffer, R
Tang, W
Kuhs, K
Chen, S
Howell, C
Prokunina-Olsson, L
AF O'Brien, T.
Pfeiffer, R.
Tang, W.
Kuhs, K.
Chen, S.
Howell, C.
Prokunina-Olsson, L.
TI COMPARISON OF IFNL4-Delta G AND IFNL3 3 ' UTR rs4803217 GENOTYPES FOR
ASSOCIATION WITH HCV TREATMENT RESPONSE
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 49th Annual International Liver Congress of the
European-Association-for-the-Study-of-the-Liver
CY APR 09-13, 2014
CL London, ENGLAND
SP European Assoc Study Liver
C1 [O'Brien, T.; Pfeiffer, R.; Tang, W.; Kuhs, K.; Prokunina-Olsson, L.] NCI, Div Canc Epidemiol &, Bethesda, MD 20892 USA.
[Chen, S.] Informat Management Serv Inc, Calverton, MD USA.
[Howell, C.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
EM obrient@mail.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 1
SU S
MA P1306
BP S530
EP S530
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CT5DT
UT WOS:000362828600729
ER
PT J
AU Osinusi, A
Marti, M
Townsend, K
Nelson, A
Kohli, A
Silk, R
Pang, P
Symonds, WT
McHutchison, J
Masur, H
Kottilil, S
AF Osinusi, A.
Marti, M.
Townsend, K.
Nelson, A.
Kohli, A.
Silk, R.
Pang, P.
Symonds, W. T.
McHutchison, J.
Masur, H.
Kottilil, S.
CA NIAID Hepatitis C Synergy Team
TI RETREATMENT OF RELAPSERS TO SOFOSBUVIR/RIBAVIRIN WITH
SOFOSBUVIR/LEDIPASVIR: COMPLETE AND RAPID VIROLOGIC SUPPRESSION BY WEEK
4
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 49th Annual International Liver Congress of the
European-Association-for-the-Study-of-the-Liver
CY APR 09-13, 2014
CL London, ENGLAND
SP European Assoc Study Liver
C1 [Osinusi, A.; Marti, M.; Townsend, K.; Nelson, A.; Kottilil, S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Osinusi, A.] Univ Maryland, Dept Infect Dis, Baltimore, MD 21201 USA.
[Kohli, A.; Silk, R.] Leidos Biomed Res Inc, Clin Monitoring Res Program, Clin Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Kohli, A.; Masur, H.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Pang, P.; Symonds, W. T.; McHutchison, J.] Gilead Sci Inc, Foster City, CA 94404 USA.
EM anuoluwapo.osinusi@nih.gov
NR 0
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 1
SU S
MA O11
BP S5
EP S6
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CS3HB
UT WOS:000361961700012
ER
PT J
AU Osinusi, A
Townsend, K
Nelson, A
Kohli, A
Gross, C
Polis, MA
Pang, PS
Symonds, WT
Talwani, R
Sajadi, MM
Hogan, J
Benator, D
Subramanian, M
Mchutchison, J
Masur, H
Kottilil, S
AF Osinusi, A.
Townsend, K.
Nelson, A.
Kohli, A.
Gross, C.
Polis, M. A.
Pang, P. S.
Symonds, W. T.
Talwani, R.
Sajadi, M. M.
Hogan, J.
Benator, D.
Subramanian, M.
Mchutchison, J.
Masur, H.
Kottilil, S.
CA NIAID ERADICATE Study Team
TI USE OF SOFOSBUVIR/LEDIPASVIR FIXED DOSE COMBINATION FOR TREATMENT OF HCV
GENOTYPE-1 IN PATIENTS COINFECTED WITH HIV
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 49th Annual International Liver Congress of the
European-Association-for-the-Study-of-the-Liver
CY APR 09-13, 2014
CL London, ENGLAND
SP European Assoc Study Liver
C1 [Osinusi, A.; Townsend, K.; Nelson, A.; Polis, M. A.; Kottilil, S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Osinusi, A.; Talwani, R.; Sajadi, M. M.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Kohli, A.; Gross, C.] Leidos Biomed Res Inc, Clin Monitoring Res Program, Clin Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Kohli, A.; Masur, H.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Pang, P. S.; Symonds, W. T.; Subramanian, M.; Mchutchison, J.] Gilead Sci Inc, Foster City, CA 94404 USA.
[Hogan, J.] Unity Hlth Care Inc, Washington, DC USA.
[Benator, D.] DC Vet Affairs Med Ctr, Infect Dis Sect, Washington, DC USA.
[Benator, D.] George Washington Univ, Med Ctr, Washington, DC 20037 USA.
EM anuoluwapo.osinusi@nih.gov
NR 0
TC 5
Z9 5
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 1
SU S
MA O14
BP S7
EP S7
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CS3HB
UT WOS:000361961700015
ER
PT J
AU Raggi, C
Factor, VM
Daekwan, S
Gillen, MC
Holczbauer, A
Marquardt, JU
Andersen, JB
Thorgeirsson, SS
AF Raggi, C.
Factor, V. M.
Daekwan, S.
Gillen, M. C.
Holczbauer, A.
Marquardt, J. U.
Andersen, J. B.
Thorgeirsson, S. S.
TI IMPACT OF EPIGENETIC REPROGRAMMING ON HEPATIC TUMORIGENIC PROPERTIES
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 49th Annual International Liver Congress of the
European-Association-for-the-Study-of-the-Liver
CY APR 09-13, 2014
CL London, ENGLAND
SP European Assoc Study Liver
C1 [Raggi, C.; Factor, V. M.; Daekwan, S.; Gillen, M. C.; Holczbauer, A.; Marquardt, J. U.; Andersen, J. B.; Thorgeirsson, S. S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM chiara.raggi@umanitasresearch.it
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 1
SU S
MA P69
BP S89
EP S89
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CS3HB
UT WOS:000361961700231
ER
PT J
AU Rose, R
Sheridan, I
Suchard, MA
Lemey, P
Farci, P
Klenerman, P
Pybus, OG
AF Rose, R.
Sheridan, I.
Suchard, M. A.
Lemey, P.
Farci, P.
Klenerman, P.
Pybus, O. G.
TI HETEROGENEOUS EVOLUTIONARY DYNAMICS OF CHRONIC HEPATITIS-C INFECTION
PREDICT LONG-TERM PERSISTENCE OF VIRUS THROUGH TREATMENT
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 49th Annual International Liver Congress of the
European-Association-for-the-Study-of-the-Liver
CY APR 09-13, 2014
CL London, ENGLAND
SP European Assoc Study Liver
C1 [Rose, R.; Sheridan, I.; Klenerman, P.; Pybus, O. G.] Univ Oxford, Oxford, England.
[Rose, R.; Klenerman, P.; Pybus, O. G.] Oxford Martin Sch Infect Dis Grp, Oxford, England.
[Suchard, M. A.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Lemey, P.] Rega Inst KU Leuven, Leuven, Belgium.
[Farci, P.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 1
SU S
MA P1191
BP S483
EP S483
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CT5DT
UT WOS:000362828600607
ER
PT J
AU Ruhl, CE
Everhart, JE
AF Ruhl, C. E.
Everhart, J. E.
TI EVALUATION OF THE FATTY LIVER INDEX (FLI) IN A MULTIETHNIC UNITED STATES
POPULATION
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 49th Annual International Liver Congress of the
European-Association-for-the-Study-of-the-Liver
CY APR 09-13, 2014
CL London, ENGLAND
SP European Assoc Study Liver
C1 [Ruhl, C. E.] Social & Sci Syst Inc, Silver Spring, MD USA.
[Everhart, J. E.] NIDDK, Bethesda, MD 20892 USA.
EM cruhl@s-3.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 1
SU S
MA P807
BP S339
EP S340
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CT5DT
UT WOS:000362828600224
ER
PT J
AU Solomon, SS
Mehta, SH
Srikrishnan, AK
Kumar, MS
McFall, A
Laeyendecker, O
Iqbal, SH
Solomon, S
Lucas, GM
Quinn, TC
AF Solomon, S. S.
Mehta, S. H.
Srikrishnan, A. K.
Kumar, M. S.
McFall, A.
Laeyendecker, O.
Iqbal, S. H.
Solomon, S.
Lucas, G. M.
Quinn, T. C.
CA NCA Study Grp
TI LIMITED ACCESS TO HCV TESTING AND TREATMENT AMONG INJECTION DRUG USERS
ACROSS INDIA
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 49th Annual International Liver Congress of the
European-Association-for-the-Study-of-the-Liver
CY APR 09-13, 2014
CL London, ENGLAND
SP European Assoc Study Liver
C1 [Solomon, S. S.; Laeyendecker, O.; Lucas, G. M.; Quinn, T. C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Solomon, S. S.; Mehta, S. H.; McFall, A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Srikrishnan, A. K.; Kumar, M. S.; Iqbal, S. H.; Solomon, S.] YR Gaitonde Ctr AIDS Res & Educ, Madras, Tamil Nadu, India.
[Laeyendecker, O.] NIAID, NIH, Bethesda, MD 20892 USA.
EM sss@jhmi.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 1
SU S
MA O34
BP S15
EP S15
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CS3HB
UT WOS:000361961700035
ER
PT J
AU Solomon, SS
Mehta, SH
Srikrishnan, AK
Lucas, GM
McFall, A
Laeyendecker, O
Kumar, MS
Iqbal, SH
Solomon, S
Quinn, TC
AF Solomon, S. S.
Mehta, S. H.
Srikrishnan, A. K.
Lucas, G. M.
McFall, A.
Laeyendecker, O.
Kumar, M. S.
Iqbal, S. H.
Solomon, S.
Quinn, T. C.
CA NCA Study Grp
TI HIGH BURDEN OF HCV AND HCV/HIV COINFECTION AMONG INJECTION DRUG USERS IN
INDIA: NEED FOR INTEGRATION OF HIV AND HCV SERVICES
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 49th Annual International Liver Congress of the
European-Association-for-the-Study-of-the-Liver
CY APR 09-13, 2014
CL London, ENGLAND
SP European Assoc Study Liver
C1 [Solomon, S. S.; Lucas, G. M.; Laeyendecker, O.; Quinn, T. C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Solomon, S. S.; Srikrishnan, A. K.; Kumar, M. S.; Iqbal, S. H.; Solomon, S.] YR Gaitonde Ctr AIDS Res & Educ, Madras, Tamil Nadu, India.
[Mehta, S. H.; McFall, A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Laeyendecker, O.; Quinn, T. C.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 1
SU S
MA P1279
BP S516
EP S516
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CT5DT
UT WOS:000362828600694
ER
PT J
AU Werner, JM
Serti, E
Chepa-Lotrea, X
Ahlenstiel, G
Feld, J
Liang, TJ
Rehermann, B
AF Werner, J. M.
Serti, E.
Chepa-Lotrea, X.
Ahlenstiel, G.
Feld, J.
Liang, T. J.
Rehermann, B.
TI RIBAVIRIN PRETREATMENT IMPROVES THE IFN-gamma RESPONSE OF NATURAL KILLER
CELLS TO IFN-BASED THERAPY OF HEPATITIS C VIRUS INFECTION
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 49th Annual International Liver Congress of the
European-Association-for-the-Study-of-the-Liver
CY APR 09-13, 2014
CL London, ENGLAND
SP European Assoc Study Liver
C1 [Werner, J. M.; Serti, E.; Chepa-Lotrea, X.; Ahlenstiel, G.; Feld, J.; Liang, T. J.; Rehermann, B.] NIDDK, Liver Dis Branch, Bethesda, MD 20892 USA.
EM jens.werner@ukr.de
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2014
VL 60
IS 1
SU S
MA P156
BP S117
EP S117
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CS3HB
UT WOS:000361961700317
ER
PT J
AU AlGhatrif, M
Scuteri, A
Morrell, C
Canepa, M
Strait, J
Tarasov, K
Orru, M
Schlessinger, D
Lakatta, E
AF AlGhatrif, Majd
Scuteri, Angelo
Morrell, Christopher
Canepa, Marco
Strait, James
Tarasov, Kirill
Orru, Marco
Schlessinger, David
Lakatta, Edward
TI GENDER DIFFERENCES IN EARLY MANIFESTATIONS OF ARTERIAL STIFFNESS:
RESULTS FROM THE SARDINIA PROJECT
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 NIA, Baltimore, MD 21224 USA.
Johns Hopkins Sch Med, Baltimore, MD USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1207M-369B
BP A2037
EP A2037
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102795
ER
PT J
AU Awad, KS
Elinoff, J
Danner, RL
AF Awad, Keytam Salem
Elinoff, Jason
Danner, Robert L.
TI BMPR2 SILENCING ACTIVATES ERK1/2-AP1 SIGNALING THROUGH UPSTREAM EFFECTS
OF RAF
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Awad, Keytam Salem; Elinoff, Jason; Danner, Robert L.] NIH, Bethesda, MD 20892 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1188-210
BP A1489
EP A1489
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102247
ER
PT J
AU Beliveau, P
Cheriet, F
Anderson, SA
Taylor, J
Arai, A
Hsu, LY
AF Beliveau, Pascale
Cheriet, Farida
Anderson, Stasia A.
Taylor, Joni
Arai, Andrew
Hsu, Li-Yueh
TI TEXTURE ANALYSIS OF DIFFUSE MYOCARDIAL FIBROSIS FROM LATE GADOLINIUM
ENHANCED MAGNETIC RESONANCE IMAGING IN AGING RATS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 NIH, Bethesda, MD 20892 USA.
Ecole Polytech, Montreal, PQ H3C 3A7, Canada.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1103-58
BP A1045
EP A1045
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101703
ER
PT J
AU Choudhary, C
Malik, R
Choi, A
Weigold, WG
Weissman, G
AF Choudhary, Chitra
Malik, Rahul
Choi, Andrew
Weigold, William Guy
Weissman, Gaby
TI EFFECT OF ADAPTIVE STATISTICAL ITERATIVE RECONSTRUCTION ON CORONARY
ARTERY CALCIUM SCORING
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Medstar Washington Hosp Ctr, Medstar Heart Inst, Div Cardiol, Washington, DC USA.
NHLBI, Adv Cardiovasc Imaging Lab, NIH, Bethesda, MD 20892 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1176-65
BP A1157
EP A1157
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101815
ER
PT J
AU Chuang, ML
Gona, P
Salton, C
O'Donnell, C
Manning, W
AF Chuang, Michael L.
Gona, Philimon
Salton, Carol
O'Donnell, Christopher
Manning, Warren
TI PROLONGED QRS DURATION PREDICTS INCREASED INDEXED LEFT VENTRICULAR
VOLUME AND MASS BY CMR: THE FRAMINGHAM HEART STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 NHLBI, Framingham Heart Study, Framingham, MA USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1103-53
BP A1042
EP A1042
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101700
ER
PT J
AU Elinoff, JM
Doughtery, EJ
Solomon, M
Danner, RL
AF Elinoff, Jason M.
Doughtery, Edward J.
Solomon, Michael
Danner, Robert L.
TI SPIRONOLACTONE SUPRESSES NF-boxed times B AND AP-1 INFLAMMATORY
SIGNALING INDEPENDENT OF THE MINERALOCORTICOID RECEPTOR
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Elinoff, Jason M.; Doughtery, Edward J.; Solomon, Michael; Danner, Robert L.] NIH, Dept Crit Care Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1263-211
BP A1502
EP A1502
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102260
ER
PT J
AU Jellis, CL
Yingchoncharoen, T
Gai, N
Popovic, Z
Flamm, S
Kwon, D
AF Jellis, Christine L.
Yingchoncharoen, Teerapat
Gai, Neville
Popovic, Zoran
Flamm, Scott
Kwon, Deborah
TI ASSESSMENT OF RIGHT VENTRICULAR STRUCTURE AND FUNCTION: NOVEL CMR T1
MAPPING AND STRAIN TECHNIQUES
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA.
NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1211-53
BP A1198
EP A1198
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101856
ER
PT J
AU Naik, HB
Krishnamoorthy, P
Dave, J
Rose, S
Mehta, NN
AF Naik, Haley B.
Krishnamoorthy, Parasuram
Dave, Jenny
Rose, Shawn
Mehta, Nehal N.
TI DIRECTLY MEASURED INFLAMMATION IN PSORIASIS SKIN ASSOCIATES WITH
VASCULAR INFLAMMATION BEYOND TRADITIONAL RISK FACTORS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 NHLBI, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1112-148
BP A1323
EP A1323
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102081
ER
PT J
AU Powell-Wiley, T
Krishnamoorthy, P
Dave, J
Sadek, A
Mehta, N
AF Powell-Wiley, Tiffany
Krishnamoorthy, Parasuram
Dave, Jenny
Sadek, Ahmed
Mehta, Nehal
TI DIRECTLY QUANTIFIED VISCERAL ADIPOSE TISSUE PREDICTS VASCULAR
INFLAMMATION INDEPENDENT OF TRADITIONAL CARDIOVASCULAR RISK FACTORS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 NIH, Bethesda, MD 20892 USA.
Englewood Hosp, Englewood, NJ USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1202M-363C
BP A981
EP A981
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101639
ER
PT J
AU Rose, SM
Krishnamoorthy, P
Dave, J
Naik, H
Playford, M
Mehta, N
AF Rose, Shawn M.
Krishnamoorthy, Parasuram
Dave, Jenny
Naik, Haley
Playford, Martin
Mehta, Nehal
TI CARDIOMETABOLIC RISK FACTORS PREDICT VASCULAR DISEASE BEYOND FRAMINGHAM
RISK SCORE IN PSORIASIS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Rose, Shawn M.; Krishnamoorthy, Parasuram; Dave, Jenny; Naik, Haley; Playford, Martin; Mehta, Nehal] NIH, Bethesda, MD 20892 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1112-157
BP A1332
EP A1332
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102090
ER
PT J
AU Sadek, A
Dave, J
Hasan, J
Krishnamoorthy, P
Rose, S
Naik, H
Weiner, E
Ahlman, MA
Bluemke, DA
Mehta, NN
AF Sadek, Ahmed
Dave, Jenny
Hasan, Josh
Krishnamoorthy, Parasuram
Rose, Shawn
Naik, Haley
Weiner, Elizabeth
Ahlman, Mark A.
Bluemke, David A.
Mehta, Nehal N.
TI VASCULAR INFLAMMATION BY [18F]-FLUORODEOXYGLUCOSE POSITRON EMISSION
TOMOGRAPHY-COMPUTED TOMOGRAPHY IS ASSOCIATED WITH AORTIC WALL PROPERTIES
BY MAGNETIC RESONANCE IMAGING
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Sadek, Ahmed; Dave, Jenny; Hasan, Josh; Krishnamoorthy, Parasuram; Rose, Shawn; Naik, Haley; Weiner, Elizabeth; Ahlman, Mark A.; Bluemke, David A.; Mehta, Nehal N.] NIH, Bethesda, MD 20892 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1101-23
BP A1013
EP A1013
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101671
ER
PT J
AU Stansky, E
Rose, S
Krishnamoorthy, P
Weiner, E
Dave, J
Mehta, NN
AF Stansky, Elena
Rose, Shawn
Krishnamoorthy, Parasuram
Weiner, Elizabeth
Dave, Jenny
Mehta, Nehal N.
TI MONOCYTE SUBSETS PREDICT VASCULAR INFLAMMATION BEYOND TRADITIONAL RISK
FACTORS OF CARDIOVASCULAR DISEASE IN PSORIASIS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 NIH, Bethesda, MD 20892 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1139-74
BP A2076
EP A2076
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102834
ER
PT J
AU Wong, TC
Piehler, K
Kellman, P
Schelbert, E
AF Wong, Timothy C.
Piehler, Kayla
Kellman, Peter
Schelbert, Erik
TI EXTRACELLULAR MATRIX EXPANSION IS MORE STRONGLY ASSOCIATED WITH
CARDIOVASCULAR OUTCOMES THAN LEFT VENTRICULAR MASS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1277M-363B
BP A986
EP A986
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101644
ER
PT J
AU Pilkington, CA
Tjarnlund, A
Bottai, M
Rider, LG
Werth, VP
De Visser, M
Alfredsson, L
Amato, AA
Barohn, RJ
Liang, MH
Singh, JA
Miller, FW
Lundberg, IE
AF Pilkington, Clarissa A.
Tjarnlund, Anna
Bottai, Matteo
Rider, Lisa G.
Werth, Victoria P.
De Visser, Marianne
Alfredsson, Lars
Amato, Anthony A.
Barohn, Richard J.
Liang, Matthew H.
Singh, Jasvinder A.
Miller, Frederick W.
Lundberg, Ingrid E.
TI PROGRESS REPORT ON THE DEVELOPMENT OF NEW CLASSIFICATION CRITERIA FOR
ADULT AND JUVENILE IDIOPATHIC INFLAMMATORY MYOPATHIES
SO RHEUMATOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the British-Society-for-Rheumatology and
British-Health-Professionals-in-Rheumatology
CY APR 29-MAY 01, 2014
CL Liverpool, ENGLAND
SP British Soc Rheumatol, British Hlth Profess Rheumatol
C1 [Pilkington, Clarissa A.] Great Ormond St Hosp Sick Children, Dept Paediat Rheumatol, London WC1N 3JH, England.
[Tjarnlund, Anna] Karolinska Univ Hosp, Dept Rheumatol, Stockholm, Sweden.
[Bottai, Matteo; Alfredsson, Lars] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Rider, Lisa G.; Miller, Frederick W.] NIH, Environm Autoimmun Grp, Bethesda, MD 20892 USA.
[Werth, Victoria P.] Philadelphia VAMC, Dept Dermatol, Philadelphia, PA USA.
[Werth, Victoria P.] Hosp Univ Penn, Philadelphia, PA USA.
[De Visser, Marianne] Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands.
[Amato, Anthony A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA USA.
[Barohn, Richard J.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA.
[Liang, Matthew H.] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA.
[Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Singh, Jasvinder A.] VA Med Ctr, Birmingham, AL USA.
[Lundberg, Ingrid E.] Karolinska Inst, Dept Rheumatol, Stockholm, Sweden.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-0324
EI 1462-0332
J9 RHEUMATOLOGY
JI RHEUMATOLOGY
PD APR
PY 2014
VL 53
SU 1
MA 182
BP 127
EP 128
PG 2
WC Rheumatology
SC Rheumatology
GA CV8EM
UT WOS:000364513000356
ER
PT J
AU McArdle, JJ
Hamagami, F
Bautista, R
Onoye, J
Hishinuma, ES
Prescott, CA
Takeshita, J
Zonderman, AB
Johnson, RC
AF McArdle, John J.
Hamagami, Fumiaki
Bautista, Randy
Onoye, Jane
Hishinuma, Earl S.
Prescott, Carol A.
Takeshita, Junji
Zonderman, Alan B.
Johnson, Ronald C.
TI Multilevel Factor Analyses of Family Data From the Hawai'i Family Study
of Cognition
SO EDUCATIONAL AND PSYCHOLOGICAL MEASUREMENT
LA English
DT Article
DE multilevel modeling; cognition; factor analysis
ID 2 ETHNIC-GROUPS; COVARIANCE STRUCTURE-ANALYSIS; LINEAR STRUCTURAL
RELATIONS; GENERAL INTELLIGENCE; MEASUREMENT INVARIANCE; STRUCTURE
MODELS; INCOMPLETE DATA; AGE-DIFFERENCES; 2-LEVEL DATA; ABILITIES
AB In this study, we reanalyzed the classic Hawai'i Family Study of Cognition (HFSC) data using contemporary multilevel modeling techniques. We used the HFSC baseline data (N = 6,579) and reexamined the factorial structure of 16 cognitive variables using confirmatory (restricted) measurement models in an explicit sequence. These models were initially fitted using multilevel confirmatory factor analysis techniques and the invariant six-factor models with two higher order factors fit fairly well (epsilon(a) < 0.08) to the total, between- and within-family data. More crucially, a model requiring metric factorial invariance proved to be a reasonable fit to the between and within matrices, and allowed the ratio of the between-family variation to total family variation (eta-squared) to be calculated separately for each common factor (eta(2): Gc = .27, Gf = .22, Gm = .15, Gs = .04, Gv = .30, and SP = .16). Higher order factors were fitted using multilevel structural equation modeling techniques and these suggested a reasonable two-factor solution with unequal family impacts. These results suggest that (a) A "G only model" does not fit the data very well, and there are many sources of individual differences in cognitive abilities; (b) the sources of the individual differences in cognition can be measured the same way between and within families; and (c) even after the unique test components are removed, cognitive differences are larger within families than between families. We consider other general multivariate family models, and we raise questions about family influences.
C1 [McArdle, John J.; Bautista, Randy; Prescott, Carol A.] Univ So Calif, Los Angeles, CA 90089 USA.
[Hamagami, Fumiaki; Onoye, Jane; Hishinuma, Earl S.; Takeshita, Junji; Johnson, Ronald C.] Univ Hawaii Manoa, Honolulu, HI 96822 USA.
[Zonderman, Alan B.] NIA, Baltimore, MD 21224 USA.
RP McArdle, JJ (reprint author), Univ So Calif, Dept Psychol, 3620 S McClintock Ave, Los Angeles, CA 90089 USA.
EM jmcardle@usc.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institute on Aging [AG-07137-21]; National Institute on Aging
Intramural Research Program
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
research was supported by the National Institute on Aging (Grant No.
AG-07137-21) and the National Institute on Aging Intramural Research
Program.
NR 96
TC 1
Z9 1
U1 1
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0013-1644
EI 1552-3888
J9 EDUC PSYCHOL MEAS
JI Educ. Psychol. Meas.
PD APR
PY 2014
VL 74
IS 2
BP 292
EP 342
DI 10.1177/0013164413506113
PG 51
WC Psychology, Educational; Mathematics, Interdisciplinary Applications;
Psychology, Mathematical
SC Psychology; Mathematics
GA AB2IK
UT WOS:000331616200007
ER
PT J
AU Haznadar, M
Maruvada, P
Mette, E
Milner, J
Moore, SC
Nicastro, HL
Sampson, JN
Su, LJ
Verma, M
Zanetti, KA
AF Haznadar, Majda
Maruvada, Padma
Mette, Eliza
Milner, John
Moore, Steven C.
Nicastro, Holly L.
Sampson, Joshua N.
Su, L. Joseph
Verma, Mukesh
Zanetti, Krista A.
TI Navigating the road ahead: addressing challenges for use of metabolomics
in epidemiology studies
SO METABOLOMICS
LA English
DT Article
ID CANCER RISK
C1 [Haznadar, Majda] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Maruvada, Padma] Natl Inst Diabet & Digest & Kidney Dis, Div Digest Dis & Nutr, Bethesda, MD 20817 USA.
[Mette, Eliza; Su, L. Joseph; Verma, Mukesh; Zanetti, Krista A.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20892 USA.
[Milner, John] ARS, USDA, Beltsville, MD 20705 USA.
[Moore, Steven C.; Sampson, Joshua N.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
[Nicastro, Holly L.] NCI, Canc Prevent Div, Rockville, MD 20892 USA.
RP Zanetti, KA (reprint author), NCI, Div Canc Control & Populat Sci, Rockville, MD 20892 USA.
EM zanettik@mail.nih.gov
RI Moore, Steven/D-8760-2016
OI Moore, Steven/0000-0002-8169-1661
FU Intramural NIH HHS [Z99 HL999999]
NR 8
TC 3
Z9 3
U1 3
U2 24
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1573-3882
EI 1573-3890
J9 METABOLOMICS
JI Metabolomics
PD APR
PY 2014
VL 10
IS 2
BP 176
EP 178
DI 10.1007/s11306-014-0636-z
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AB7YJ
UT WOS:000332007000001
PM 25914611
ER
PT J
AU Moore, SC
Matthews, CE
Sampson, JN
Stolzenberg-Solomon, RZ
Zheng, W
Cai, QY
Tan, YT
Chow, WH
Ji, BT
Liu, DK
Xiao, Q
Boca, SM
Leitzmann, MF
Yang, G
Xiang, YB
Sinha, R
Shu, XO
Cross, AJ
AF Moore, Steven C.
Matthews, Charles E.
Sampson, Joshua N.
Stolzenberg-Solomon, Rachael Z.
Zheng, Wei
Cai, Qiuyin
Tan, Yu Ting
Chow, Wong-Ho
Ji, Bu-Tian
Liu, Da Ke
Xiao, Qian
Boca, Simina M.
Leitzmann, Michael F.
Yang, Gong
Xiang, Yong Bing
Sinha, Rashmi
Shu, Xiao Ou
Cross, Amanda J.
TI Human metabolic correlates of body mass index
SO METABOLOMICS
LA English
DT Article
DE BMI; Adiposity; Metabolomics; Epidemiology; Obesity
ID CHAIN AMINO-ACIDS; INSULIN-RESISTANCE; CHOLESTEROL ABSORPTION;
PHYSICAL-ACTIVITY; OBESITY; RISK; METAANALYSIS; CANCER; IDENTIFICATION;
HETEROGENEITY
AB A high body mass index (BMI) is a major risk factor for several chronic diseases, but the biology underlying these associations is not well-understood. Dyslipidemia, inflammation, and elevated levels of growth factors and sex steroid hormones explain some of the increased disease risk, but other metabolic factors not yet identified may also play a role. In order to discover novel metabolic biomarkers of BMI, we used non-targeted metabolomics to assay 317 metabolites in blood samples from 947 participants and examined the cross-sectional associations between metabolite levels and BMI. Participants were from three studies in the United States and China. Height, weight, and potential confounders were ascertained by questionnaire (US studies) or direct measurement (Chinese study). Metabolite levels were measured using liquid-phase chromatography and gas chromatography coupled with mass spectrometry. We evaluated study-specific associations using linear regression, adjusted for age, gender, and smoking, and we estimated combined associations using random effects meta-analysis. The meta-analysis revealed 37 metabolites significantly associated with BMI, including 19 lipids, 12 amino acids, and 6 others, at the Bonferroni significance threshold (P < 0.00016). Eighteen of these associations had not been previously reported, including histidine, an amino acid neurotransmitter, and butyrylcarnitine, a lipid marker of whole-body fatty acid oxidation. Heterogeneity by study was minimal (all P (heterogeneity) > 0.05). In total, 110 metabolites were associated with BMI at the P < 0.05 level. These findings establish a baseline for the BMI metabolome, and suggest new targets for researchers attempting to clarify mechanistic links between BMI and disease risk.
C1 [Moore, Steven C.; Matthews, Charles E.; Sampson, Joshua N.; Stolzenberg-Solomon, Rachael Z.; Ji, Bu-Tian; Xiao, Qian; Boca, Simina M.; Sinha, Rashmi; Cross, Amanda J.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20850 USA.
[Zheng, Wei; Cai, Qiuyin; Yang, Gong; Shu, Xiao Ou] Vanderbilt Univ, Sch Med, Inst Med & Publ Hlth,Dept Med,Div Epidemiol, Vanderbilt Epidemiol Ctr,Vanderbilt Ingram Canc C, Nashville, TN 37212 USA.
[Tan, Yu Ting; Liu, Da Ke; Xiang, Yong Bing] Shanghai Canc Inst, Shanghai, Peoples R China.
[Chow, Wong-Ho] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Leitzmann, Michael F.] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, D-93053 Regensburg, Germany.
RP Moore, SC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM moorest@mail.nih.gov
RI matthews, Charles/E-8073-2015; Moore, Steven/D-8760-2016
OI matthews, Charles/0000-0001-8037-3103; Moore, Steven/0000-0002-8169-1661
FU Breast Cancer Research Stamp Fund; National Cancer Institute, National
Institutes of Health, Department of Health and Human Services; Shanghai
Women's Health Study [R37CA70867]; Shanghai Men's Health Study
[R01CA082729]
FX We thank David P. Check of the Division of Cancer Epidemiology and
Genetics of the U. S. National Cancer Institute for preparation of the
figures and Nathan Appel, Dominick Parisi, and Adam Risch of Information
Management Services for programming support. Finally, we thank the
participants for their involvement in our research studies. This work
was supported, in part, by the Breast Cancer Research Stamp Fund,
awarded through competitive peer review and the Intramural Research
Program of the National Cancer Institute, National Institutes of Health,
Department of Health and Human Services. The Shanghai Women's Health
Study was supported primarily by R37CA70867 and the Shanghai Men's
Health Study was supported by R01CA082729.
NR 41
TC 30
Z9 30
U1 3
U2 36
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1573-3882
EI 1573-3890
J9 METABOLOMICS
JI Metabolomics
PD APR
PY 2014
VL 10
IS 2
BP 259
EP 269
DI 10.1007/s11306-013-0574-1
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AB7YJ
UT WOS:000332007000009
PM 25254000
ER
PT J
AU Reiner, DJ
Yu, SJ
Shen, H
He, Y
Bae, E
Wang, Y
AF Reiner, David J.
Yu, Seong-Jin
Shen, Hui
He, Yi
Bae, Eunkyung
Wang, Yun
TI 9-Cis Retinoic Acid Protects Against Methamphetamine-Induced
Neurotoxicity in Nigrostriatal Dopamine Neurons
SO NEUROTOXICITY RESEARCH
LA English
DT Article
DE BMP7; Methamphetamine; Retinoic acid; Nur77; Neurotoxicity; Dopamine
ID BONE MORPHOGENETIC PROTEIN; MESSENGER-RNA EXPRESSION; ISCHEMIC
BRAIN-INJURY; X-RECEPTOR; INDUCED APOPTOSIS; MOUSE-BRAIN;
DOCOSAHEXAENOIC ACID; PARKINSONS-DISEASE; CELLS; MICE
AB Methamphetamine (MA) is a drug of abuse as well as a dopaminergic neurotoxin. 9-Cis retinoic acid (9cRA), a biologically active derivative of vitamin A, has protective effects against damage caused by H2O2 and oxygen-glucose deprivation in vitro as well as infarction and terminal deoxynucleotidyl transferase-mediated dNTP nick-end labeling (TUNEL) labeling in ischemic brain. The purpose of this study was to examine if there was a protective role for 9cRA against MA toxicity in nigrostriatal dopaminergic neurons. Primary dopaminergic neurons, prepared from rat embryonic ventral mesencephalic tissue, were treated with MA. High doses of MA decreased tyrosine hydroxylase (TH) immunoreactivity while increasing TUNEL labeling. These toxicities were significantly reduced by 9cRA. 9cRA also inhibited the export of Nur77 from nucleus to cytosol, a response that activates apoptosis. The interaction of 9cRA and MA in vivo was next examined in adult rats. 9cRA was delivered intracerebroventricularly; MA was given (5 mg/kg, 4x) one day later. Locomotor behavior was measured 2 days after surgery for a period of 48 h. High doses of MA significantly reduced locomotor activity and TH immunoreactivity in striatum. Administration of 9cRA antagonized these changes. Previous studies have shown that 9cRA can induce bone morphogenetic protein-7 (BMP7) expression and that administration of BMP7 attenuates MA toxicity. We demonstrated that MA treatment significantly reduced BMP7 mRNA expression in nigra. Noggin (a BMP antagonist) antagonized 9cRA-induced behavioral recovery and 9cRA-induced normalization of striatal TH levels. Our data suggest that 9cRA has a protective effect against MA-mediated neurodegeneration in dopaminergic neurons via upregulation of BMP.
C1 [Reiner, David J.; Yu, Seong-Jin; Shen, Hui; He, Yi; Bae, Eunkyung; Wang, Yun] NIDA, Neural Protect & Regenerat Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Yu, Seong-Jin; Bae, Eunkyung; Wang, Yun] Natl Hlth Res Inst, Ctr Neuropsychiat Res, Zhunan 35053, Taiwan.
RP Wang, Y (reprint author), Natl Hlth Res Inst, Ctr Neuropsychiat Res, Zhunan 35053, Taiwan.
EM ywang@nhri.org.tw
FU National Health Research Institutes, Taiwan; National Institute on Drug
Abuse, NIH
FX Funding for this study was provided by National Health Research
Institutes, Taiwan and National Institute on Drug Abuse, NIH.
NR 38
TC 2
Z9 3
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1029-8428
EI 1476-3524
J9 NEUROTOX RES
JI Neurotox. Res.
PD APR
PY 2014
VL 25
IS 3
BP 248
EP 261
DI 10.1007/s12640-013-9413-4
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA AB8FK
UT WOS:000332025300002
PM 23884514
ER
PT J
AU Cho, H
Kim, S
Shin, HY
Chung, EJ
Kitano, H
Park, JH
Park, L
Chung, JY
Hewitt, SM
Kim, JH
AF Cho, Hanbyoul
Kim, Sunghoon
Shin, Ha-Yeon
Chung, Eun Joo
Kitano, Haruhisa
Park, Jae Hyon
Park, Lucienne
Chung, Joon-Yong
Hewitt, Stephen M.
Kim, Jae-Hoon
TI Expression of Stress-Induced Phosphoprotein1 (STIP1) is Associated with
Tumor Progression and Poor Prognosis in Epithelial Ovarian Cancer
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID HSP70/HSP90 ORGANIZING PROTEIN; CELL-PROLIFERATION; AUTOANTIBODIES; HOP;
BIOMARKERS; CANDIDATE; INVASION; SERA; LINE
C1 [Cho, Hanbyoul; Shin, Ha-Yeon; Park, Jae Hyon; Park, Lucienne; Kim, Jae-Hoon] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, Seoul 135720, South Korea.
[Cho, Hanbyoul; Kim, Jae-Hoon] Yonsei Univ, Coll Med, Inst Womens Life Med Sci, Seoul 135720, South Korea.
[Kim, Sunghoon] Yonsei Univ, Coll Med, Severance Hosp, Dept Obstet & Gynecol, Seoul 135720, South Korea.
[Chung, Eun Joo] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kitano, Haruhisa; Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Kitano, Haruhisa; Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Appl Mol Pathol Lab, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Kitano, Haruhisa] Shiga Univ Med Sci, Dept Thorac Surg, Otsu, Shiga 52021, Japan.
RP Kim, JH (reprint author), Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, 146-92 Dogok Dong, Seoul 135720, South Korea.
EM jaehoonkim@yuhs.ac
OI Hewitt, Stephen/0000-0001-8283-1788; Chung,
Joon-Yong/0000-0001-5041-5982
FU National Research Foundation of Korea (NRF); Ministry of Education,
Science and Technology [2010-0011153, 2011-0010286, 2011-0007146];
Yonsei University College of Medicine [3-2010-0072, 6-2011-0073,
6-2013-0106]; NIH, National Cancer Institute, and Center for Cancer
Research
FX Grant sponsor: Basic Science Research Program through the National
Research Foundation of Korea (NRF) funded by the Ministry of Education,
Science and Technology; Grant numbers: 2010-0011153, 2011-0010286, and
2011-0007146.; Grant sponsor: Yonsei University College of Medicine for
2010, 2011, and 2013; Grant numbers: 3-2010-0072, 6-2011-0073, and
6-2013-0106.; Grant sponsor: Intramural Research Program of the NIH,
National Cancer Institute, and Center for Cancer Research.
NR 24
TC 3
Z9 3
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1045-2257
EI 1098-2264
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD APR
PY 2014
VL 53
IS 4
BP 277
EP 288
PG 12
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA AA9TO
UT WOS:000331436000002
PM 24488757
ER
PT J
AU McShane, CM
Murray, LJ
Engels, EA
Landgren, O
Anderson, LA
AF McShane, Charlene M.
Murray, Liam J.
Engels, Eric A.
Landgren, Ola
Anderson, Lesley A.
TI Common community-acquired infections and subsequent risk of multiple
myeloma: A population-based study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE multiple myeloma; infections; respiratory tract infections; herpes
zoster
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MONOCLONAL GAMMOPATHY; UNDETERMINED
SIGNIFICANCE; MEDICAL HISTORY; TRANSPLANT RECIPIENTS; HERPES-ZOSTER;
CANCER; DISORDERS; ABNORMALITIES; ONCOGENESIS
AB The role of bacteria and viruses as aetiological agents in the pathogenesis of cancer has been well established for several sites, including a number of haematological malignancies. Less clear is the impact of such exposures on the subsequent development of multiple myeloma (MM). Using the population-based U.S. Surveillance Epidemiology and End Results-Medicare dataset, 15,318 elderly MM and 200,000 controls were identified to investigate the impact of 14 common community-acquired infections and risk of MM. Odds ratios (ORs) and associated 95% confidence intervals (CIs) were adjusted for sex, age and calendar year of selection. The 13-month period prior to diagnosis/selection was excluded. Risk of MM was increased by 5-39% following Medicare claims for eight of the investigated infections. Positive associations were observed for several infections including bronchitis (adjusted OR 1.14, 95% CI 1.09-1.18), sinusitis (OR 1.15, 95% CI 1.10-1.20) pneumonia (OR 1.27, 95% CI 1.21-1.33), herpes zoster (OR 1.39, 95% CI 1.29-1.49) and cystitis (OR 1.09, 95% CI 1.05-1.14). Each of these infections remained significantly elevated following the exclusion of more than 6 years of claims data. Exposure to infectious antigens may therefore play a role in the development of MM. Alternatively, the observed associations may be a manifestation of an underlying immune disturbance present several years prior to MM diagnosis and thereby part of the natural history of disease progression.
What's new? Although bacterial and viral infections have been sporadically associated with an increased risk of developing multiple myeloma (MM), a B cell malignancy mostly found in the elderly, the precise role of infectious pathogens in the aetiology of MM remains unclear. In this large population-based study, the authors confirm that the risk of MM is increased by 5-39% following a range of common community-acquired infections, particularly those of the respiratory tract. For a number of infections, a long time interval between infections and diagnosis of MM was observed, reducing the possibility of undetected MM explaining the associations observed. Thus, exposure to infectious agents may promote the malignant transformation of premalignant B cell abnormalities to MM or may reflect a compromised immune system preceding MM diagnosis.
C1 [McShane, Charlene M.; Murray, Liam J.; Anderson, Lesley A.] Queens Univ Belfast, Ctr Publ Hlth, Canc Epidemiol & Hlth Serv Res Grp, Belfast, Antrim, North Ireland.
[Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Landgren, Ola] NCI, Multiple Myeloma Sect, NIH, Bethesda, MD 20892 USA.
RP Anderson, LA (reprint author), Ctr Publ Hlth, Canc Epidemiol & Hlth Serv Res Grp, Inst Clin Sci Block B,Grosvenor Rd, Belfast BT12 6BJ, Antrim, North Ireland.
EM l.anderson@qub.ac.uk
OI Anderson, Lesley/0000-0002-1000-3649
FU Intramural Research Program of the National Cancer Institute; Department
for Learning and Employment (Northern Ireland)
FX Grant sponsor: Intramural Research Program of the National Cancer
Institute; Grant sponsor: Department for Learning and Employment
(Northern Ireland) (scholarship to C. M. c. S. [Ph.D candidate at
Queen's University Belfast])
NR 44
TC 5
Z9 5
U1 2
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD APR 1
PY 2014
VL 134
IS 7
BP 1734
EP 1740
DI 10.1002/ijc.28479
PG 7
WC Oncology
SC Oncology
GA 287YW
UT WOS:000329579500021
PM 24105662
ER
PT J
AU Philogene, GS
AF Philogene, G. Stephane
TI Foreword
SO EDUCATIONAL GERONTOLOGY
LA English
DT Editorial Material
C1 NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
RP Philogene, GS (reprint author), NIH, Off Behav & Social Sci Res, 31 Ctr Dr,Suite B1C19, Bethesda, MD 20892 USA.
EM philoges@od.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 0360-1277
EI 1521-0472
J9 EDUC GERONTOL
JI Educ. Gerontol.
PD APR 1
PY 2014
VL 40
IS 4
SI SI
BP 241
EP 241
DI 10.1080/03601277.2014.852929
PG 1
WC Education & Educational Research; Gerontology
SC Education & Educational Research; Geriatrics & Gerontology
GA 268SY
UT WOS:000328192000001
ER
PT J
AU Kepka, D
Smith, A
Zeruto, C
Yabroff, KR
AF Kepka, Deanna
Smith, Alexandria
Zeruto, Christopher
Yabroff, K. Robin
TI Is provider type associated with cancer screening and prevention:
advanced practice registered nurses, physician assistants, and
physicians
SO BMC CANCER
LA English
DT Article
ID PRIMARY-CARE; UNITED-STATES; HEALTH; VALIDITY; WOMEN; PRACTITIONERS;
MAMMOGRAPHY; DISPARITIES; SMOKING
AB Background: Physician recommendations for cancer screening and prevention are associated with patient compliance. However, time constraints may limit physicians' ability to provide all recommended preventive services, especially with increasing demand from the Affordable Care Act in the United States. Team-based practice that includes advanced practice registered nurses and physician assistants (APRN/PA) may help meet this demand. This study investigates the relationship between an APRN/PA visit and receipt of guideline-consistent cancer screening and prevention recommendations.
Methods: Data from the 2010 National Health Interview Survey were analyzed with multivariate logistic regression to assess provider type seen and receipt of guideline-consistent cancer screening and prevention recommendations (n = 26,716).
Results: In adjusted analyses, women who saw a primary care physician (PCP) and an APRN/PA or a PCP without an APRN/PA in the past 12 months were more likely to be compliant with cervical and breast cancer screening guidelines than women who did not see a PCP or APRN/PA (all p < 0.0001 for provider type). Women and men who saw a PCP and an APRN/PA or a PCP without an APRN/PA were also more likely to receive guideline consistent colorectal cancer screening and advice to quit smoking and participate in physical activity than women and men who did not see a PCP or APRN/PA (all p < 0.01 for provider type).
Conclusions: Seeing a PCP alone, or in conjunction with an APRN/PA is associated with patient receipt of guideline-consistent cancer prevention and screening recommendations. Integrating APRN/PA into primary care may assist with the delivery of cancer prevention and screening services. More intervention research efforts are needed to explore how APRN/PA will be best able to increase cancer screening, HPV vaccination, and receipt of behavioral counseling, especially during this era of healthcare reform.
C1 [Kepka, Deanna; Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Kepka, Deanna] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA.
[Kepka, Deanna] Huntsman Canc Inst, Salt Lake City, UT USA.
[Smith, Alexandria] Amer Legacy Fdn, Washington, DC USA.
[Zeruto, Christopher] Informat Management Serv Inc, Silver Spring, MD USA.
RP Kepka, D (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM deanna.kepka@hci.utah.edu
OI Yabroff, K. Robin/0000-0003-0644-5572
FU Huntsman Cancer Foundation; University of Utah College of Nursing;
University of Utah Center for Clinical and Translational Science;
National Center for Advancing Translational Sciences of the National
Institutes of Health [1ULTR001067]
FX Dr. Kepka has received some support from the Huntsman Cancer Foundation,
the University of Utah College of Nursing, and the University of Utah
Center for Clinical and Translational Science for this study. Research
reported in this publication was supported by the National Center for
Advancing Translational Sciences of the National Institutes of Health
under Award Number 1ULTR001067. The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the NIH. Alexandria Smith volunteered her time on this study.
Christopher Zeruto is employed by a contractor to the National Cancer
Institute and did not receive specific funding for this work. Dr.
Yabroff is a federal employee with no external source of support for the
work. Dr. Kepka would also like to acknowledge the assistance of Echo
Warner, Research Analyst, and Djin Lai, Graduate Research Assistant, at
the Huntsman Cancer Institute, on the text and revisions of this
manuscript.
NR 36
TC 4
Z9 4
U1 1
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD MAR 31
PY 2014
VL 14
AR 233
DI 10.1186/1471-2407-14-233
PG 9
WC Oncology
SC Oncology
GA AF2LA
UT WOS:000334542400002
PM 24685149
ER
PT J
AU Pantelic, RS
Fu, WY
Schoenenberger, C
Stahlberg, H
AF Pantelic, Radosav S.
Fu, Wangyang
Schoenenberger, Christian
Stahlberg, Henning
TI Rendering graphene supports hydrophilic with non-covalent aromatic
functionalization for transmission electron microscopy
SO APPLIED PHYSICS LETTERS
LA English
DT Article
ID BIOLOGICAL MACROMOLECULES; CRYOELECTRON MICROSCOPY; SPECIMEN
PREPARATION; CARBON NANOTUBES; RESOLUTION; FILMS; OXIDE; CRYOMICROSCOPY;
COMPOSITES; REDUCTION
AB Amorphous carbon films have been routinely used to enhance the preparation of frozen-hydrated samples for transmission electron microscopy (TEM), either in retaining protein concentration, providing mechanical stability or dissipating sample charge. However, strong background signal from the amorphous carbon support obstructs that of the sample, and the insulating properties of thin amorphous carbon films preclude any efficiency in dispersing charge. Graphene addresses the limitations of amorphous carbon. Graphene is a crystalline material with virtually no phase or amplitude contrast and unparalleled, high electrical carrier mobility. However, the hydrophobic properties of graphene have prevented its routine application in Cryo-TEM. This Letter reports a method for rendering graphene TEM supports hydrophilic-a convenient approach maintaining graphene's structural and electrical properties based on non-covalent, aromatic functionalization. (C) 2014 AIP Publishing LLC.
C1 [Pantelic, Radosav S.] NCI, Bethesda, MD 20892 USA.
[Fu, Wangyang; Schoenenberger, Christian] Univ Basel, Dept Phys, CH-4056 Basel, Switzerland.
[Stahlberg, Henning] Univ Basel, Biozentrum, Ctr Cellular Imaging & NanoAnalyt, CH-4058 Basel, Switzerland.
RP Pantelic, RS (reprint author), NCI, 50 South Dr,Bldg 50,Room 4306, Bethesda, MD 20892 USA.
EM pantelic@imbb.forth.gr
RI Stahlberg, Henning/H-1868-2011
OI Stahlberg, Henning/0000-0002-1185-4592
FU National Cancer Institute/National Institutes for Health at the National
Institutes for Health (NIH); NFS Nanoscience and Nanotechnology;
Nano-Tera.ch; Swiss Nanoscience Institute; ESF-Eurographene
FX Dr Radosav Pantelic wishes to thank Dr Sriram Subramaniam (National
Cancer Institute/National Institutes for Health) as sponsor of his
fellowship at the National Institutes for Health (NIH) and access to TEM
resources. Professor Henning Stahlberg appreciates the support of the
Swiss National Science Foundation (NCCR Nano and Structural Biology) and
Swiss Initiative for Systems Biology (SystemsX.ch, RTD CINA). Professor
Christian Schoenenberger and DrWangyang Fu gratefully acknowledge
Funding from NFS Nanoscience and Nanotechnology, Nano-Tera.ch, Swiss
Nanoscience Institute, and ESF-Eurographene.
NR 45
TC 1
Z9 1
U1 5
U2 29
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0003-6951
EI 1077-3118
J9 APPL PHYS LETT
JI Appl. Phys. Lett.
PD MAR 31
PY 2014
VL 104
IS 13
AR 134103
DI 10.1063/1.4870531
PG 5
WC Physics, Applied
SC Physics
GA AF0MK
UT WOS:000334408500079
ER
PT J
AU Lim, J
Ritt, DA
Zhou, M
Morrison, DK
AF Lim, Junghwa
Ritt, Daniel A.
Zhou, Ming
Morrison, Deborah K.
TI The CNK2 Scaffold Interacts with Vilse and Modulates Rac Cycling during
Spine Morphogenesis in Hippocampal Neurons
SO CURRENT BIOLOGY
LA English
DT Article
ID LINKED MENTAL-RETARDATION; NEURITE OUTGROWTH; SYNAPSE FORMATION; RHO
GTPASES; PROTEIN; KINASES; DOMAINS; GROWTH
AB Protein scaffolds play an important role in signal transduction, functioning to facilitate protein interactions and localize key pathway components to specific signaling sites. Connector enhancer of KSR-2 (CNK2) is a neuronally expressed scaffold recently implicated in nonsyndromic, X-linked intellectual disability (NS-XLID) [1-3]. NS-XLID patients have deficits in cognitive function and their neurons often exhibit dendritic spine abnormalities [4], suggesting a role for CNK2 in synaptic signaling and/or spine formation. To gain insight regarding how CNK2 might contribute to these processes, we used mass spectrometry to identify proteins that interact with the endogenous CNK2 scaffold. Here, we report that the major binding partner of CNK2 is Vilse/ARHGAP39 and that CNK2 complexes are enriched for proteins involved in Rac/Cdc42 signaling, including Rac1 itself, alpha-PIX and beta-PIX, GIT1 and GIT2, PAK3 and PAK4, and members of the cytohesin family. Binding between CNK2 and Vilse was found to be constitutive, mediated by the WW domains of Vilse and a proline motif in CNK2. Through mutant analysis, protein depletion and rescue experiments, we identify CNK2 as a spatial modulator of Rac cycling during spine morphogenesis and find that the interaction with Vilse is critical for maintaining RacGDP/GTP levels at a balance required for spine formation.
C1 [Lim, Junghwa; Ritt, Daniel A.; Morrison, Deborah K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
[Zhou, Ming] Leidos Frederick Natl Lab Canc Res, Lab Prote & Analyt Technol, Frederick, MD 21702 USA.
RP Morrison, DK (reprint author), NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
EM morrisod@mail.nih.gov
FU National Cancer Institute
FX We thank Elizabeth Terrell and Suzanne Specht for technical support and
Dr. Stephen Lockett and Alla Brafman at Leidos-FNL for assistance with
FRET imaging and analysis. This project was funded by federal funds from
the National Cancer Institute.
NR 26
TC 6
Z9 7
U1 1
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
EI 1879-0445
J9 CURR BIOL
JI Curr. Biol.
PD MAR 31
PY 2014
VL 24
IS 7
BP 786
EP 792
DI 10.1016/j.cub.2014.02.036
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AE2LA
UT WOS:000333803200028
PM 24656827
ER
PT J
AU Sheng, ZH
AF Sheng, Zu-Hang
TI Mitochondrial trafficking and anchoring in neurons: New insight and
implications
SO JOURNAL OF CELL BIOLOGY
LA English
DT Review
ID AMYOTROPHIC-LATERAL-SCLEROSIS; FAST AXONAL-TRANSPORT; KINESIN
HEAVY-CHAIN; NERVE GROWTH-FACTOR; SYNAPTIC-TRANSMISSION;
NEURODEGENERATIVE DISEASES; SYMPATHETIC NEURONS; HIPPOCAMPAL-NEURONS;
ALZHEIMERS-DISEASE; CORTICAL-NEURONS
AB Mitochondria are essential organelles for neuronal growth, survival, and function. Neurons use specialized mechanisms to drive mitochondria transport and to anchor them in axons and at synapses. Stationary mitochondria buffer intracellular Ca2+ and serve as a local energy source by supplying ATP. The balance between motile and stationary mitochondria responds quickly to changes in axonal and synaptic physiology. Defects in mitochondrial transport are implicated in the pathogenesis of several major neurological disorders. Recent work has provided new insight in the regulation of microtubule-based mitochondrial trafficking and anchoring, and on how mitochondrial motility influences neuron growth, synaptic function, and mitophagy.
C1 NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Sheng, ZH (reprint author), NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
EM shengz@ninds.nih.gov
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke, National Institutes of Health
FX Work of the author's laboratory is supported by the Intramural Research
Program of the National Institute of Neurological Disorders and Stroke,
National Institutes of Health.
NR 122
TC 81
Z9 82
U1 2
U2 25
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD MAR 31
PY 2014
VL 204
IS 7
BP 1087
EP 1098
DI 10.1083/jcb.201312123
PG 12
WC Cell Biology
SC Cell Biology
GA AE3UK
UT WOS:000333903600004
PM 24687278
ER
PT J
AU Hwang, BS
Pennell, ML
AF Hwang, Beom Seuk
Pennell, Michael L.
TI Semiparametric Bayesian joint modeling of a binary and continuous
outcome with applications in toxicological risk assessment
SO STATISTICS IN MEDICINE
LA English
DT Article
DE benchmark dose; developmental toxicology study; kernel stick-breaking
process; nonparametric Bayes
ID LATENT VARIABLE MODELS; NONPARAMETRIC PROBLEMS; DIRICHLET PROCESSES;
CLUSTERED BINARY; MIXTURES
AB Many dose-response studies collect data on correlated outcomes. For example, in developmental toxicity studies, uterine weight and presence of malformed pups are measured on the same dam. Joint modeling can result in more efficient inferences than independent models for each outcome. Most methods for joint modeling assume standard parametric response distributions. However, in toxicity studies, it is possible that response distributions vary in location and shape with dose, which may not be easily captured by standard models. To address this issue, we propose a semiparametric Bayesian joint model for a binary and continuous response. In our model, a kernel stick-breaking process prior is assigned to the distribution of a random effect shared across outcomes, which allows flexible changes in distribution shape with dose shared across outcomes. The model also includes outcome-specific fixed effects to allow different location effects. In simulation studies, we found that the proposed model provides accurate estimates of toxicological risk when the data do not satisfy assumptions of standard parametric models. We apply our method to data from a developmental toxicity study of ethylene glycol diethyl ether. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Hwang, Beom Seuk] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
[Pennell, Michael L.] Ohio State Univ, Div Biostat, Coll Publ Hlth, Columbus, OH 43210 USA.
RP Hwang, BS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
EM beomseuk.hwang@nih.gov
NR 32
TC 1
Z9 1
U1 1
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD MAR 30
PY 2014
VL 33
IS 7
BP 1162
EP 1175
DI 10.1002/sim.6007
PG 14
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA AD1RQ
UT WOS:000333011600006
PM 24123309
ER
PT J
AU Erdemir, HH
Li, ZG
Sacks, DB
AF Erdemir, Huseyin H.
Li, Zhigang
Sacks, David B.
TI IQGAP1 Binds to Estrogen Receptor-alpha and Modulates Its Function
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Cell Signaling; Estrogen; Estrogen Receptor; Nuclear Receptors;
Protein-Protein Interactions; Scaffold Proteins; Transcription; IQGAP1
ID BREAST-CANCER; TRANSCRIPTION FACTOR; CELL MOTILITY; PROTEIN; CALMODULIN;
GROWTH; ACTIVATION; STABILITY; BETA; CA2+/CALMODULIN
AB Background: IQGAP1 is a scaffold protein that modulates diverse signaling pathways. Results: IQGAP1 binds to estrogen receptor- (ER) and ER, and knockdown of IQGAP1 impairs 17-estradiol (E-2)-stimulated transcriptional activation in human breast epithelial cells. Conclusion: IQGAP1 modulates ER function and is required for maximal E-2 function. Significance: IQGAP1 might be a therapeutic target for patients with breast carcinoma.
The estrogen receptor (ER) is a steroid hormone receptor that acts as a transcription factor, modulating genes that regulate a vast range of cellular functions. IQGAP1 interacts with several signaling proteins, cytoskeletal components, and transmembrane receptors, thereby serving as a scaffold to integrate signaling pathways. Both ER and IQGAP1 contribute to breast cancer. In this study, we report that IQGAP1 binds ER and ER. In vitro analysis with pure proteins revealed a direct interaction between IQGAP1 and ER. Investigation with multiple short fragments of each protein showed that ER binds to the IQ domain of IQGAP1, whereas the hinge region of ER is responsible for binding IQGAP1. In addition, IQGAP1 and ER co-immunoprecipitated from cells, and the association was modulated by estradiol. The interaction has functional effects. Knockdown of endogenous IQGAP1 attenuated the ability of estradiol to induce transcription of the estrogen-responsive genes pS2, progesterone receptor, and cyclin D1. These data reveal that IQGAP1 binds to ER and modulates its transcriptional function, suggesting that IQGAP1 might be a target for therapy in patients with breast carcinoma.
C1 [Erdemir, Huseyin H.; Li, Zhigang; Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
RP Sacks, DB (reprint author), NIH, Dept Lab Med, 10 Ctr Dr,10-2C306, Bethesda, MD 20892 USA.
EM david.sacks2@nih.gov
FU National Institutes of Health Intramural Research Program
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program.
NR 48
TC 14
Z9 15
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 28
PY 2014
VL 289
IS 13
BP 9100
EP 9112
DI 10.1074/jbc.M114.553511
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD7UJ
UT WOS:000333472100030
PM 24550401
ER
PT J
AU Donigan, KA
McLenigan, MP
Yang, W
Goodman, MF
Woodgate, R
AF Donigan, Katherine A.
McLenigan, Mary P.
Yang, Wei
Goodman, Myron F.
Woodgate, Roger
TI The Steric Gate of DNA Polymerase iota Regulates Ribonucleotide
Incorporation and Deoxyribonucleotide Fidelity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE DNA-binding Protein; DNA Repair; DNA Synthesis; Enzyme Kinetics;
Mutagenesis; DNA Polymerase Iota; Ribonucleotide Incorporation; Steric
Gate Mutant; Y Family DNA Polymerase
ID INSERTION FIDELITY; ESCHERICHIA-COLI; MISMATCH REPAIR; ACTIVE-SITE;
Y-FAMILY; REPLICATION; BYPASS; BASE; ETA; DISCRIMINATION
AB Background: Accurate bypass of DNA damage by translesion DNA polymerases is critical for cell survival. Results: Wild-type human DNA polymerase incorporates ribonucleotides, and a steric gate mutant increases both ribonucleotide incorporation and deoxyribonucleotide selectivity. Conclusion: A single amino acid residue in DNA polymerase limits incorporation of ribonucleotides into DNA. Significance: DNA polymerase may incorporate ribonucleotides during translesion DNA synthesis.
Accurate DNA synthesis in vivo depends on the ability of DNA polymerases to select dNTPs from a nucleotide pool dominated by NTPs. High fidelity replicative polymerases have evolved to efficiently exclude NTPs while copying long stretches of undamaged DNA. However, to bypass DNA damage, cells utilize specialized low fidelity polymerases to perform translesion DNA synthesis (TLS). Of interest is human DNA polymerase (pol ), which has been implicated in TLS of oxidative and UV-induced lesions. Here, we evaluate the ability of pol to incorporate NTPs during DNA synthesis. pol incorporates and extends NTPs opposite damaged and undamaged template bases in a template-specific manner. The Y39A steric gate pol mutant is considerably more active in the presence of Mn2+ compared with Mg2+ and exhibits a marked increase in NTP incorporation and extension, and surprisingly, it also exhibits increased dNTP base selectivity. Our results indicate that a single residue in pol is able to discriminate between NTPs and dNTPs during DNA synthesis. Because wild-type pol incorporates NTPs in a template-specific manner, certain DNA sequences may be at risk for elevated mutagenesis during pol -dependent TLS. Molecular modeling indicates that the constricted active site of wild-type pol becomes more spacious in the Y39A variant. Therefore, the Y39A substitution not only permits incorporation of ribonucleotides but also causes the enzyme to favor faithful Watson-Crick base pairing over mutagenic configurations.
C1 [Donigan, Katherine A.; McLenigan, Mary P.; Woodgate, Roger] NICHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA.
[Yang, Wei] NICHD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Goodman, Myron F.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.
[Goodman, Myron F.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
RP Woodgate, R (reprint author), NICHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA.
EM woodgate@nih.gov
RI Yang, Wei/D-4926-2011
OI Yang, Wei/0000-0002-3591-2195
FU National Institutes of Health [GM21422, ESO12259]; NICHD, National
Institutes of Health Intramural Research Program
FX This work was supported, in whole or in part, by National Institutes of
Health Grants GM21422 and ESO12259 (to M. F. G.). This work was also
supported by funds from the NICHD, National Institutes of Health
Intramural Research Program (to R. W.) and the NICHD, National
Institutes of Health Intramural Research Program (to W. Y.).
NR 44
TC 11
Z9 11
U1 1
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 28
PY 2014
VL 289
IS 13
BP 9136
EP 9145
DI 10.1074/jbc.M113.545442
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD7UJ
UT WOS:000333472100033
PM 24532793
ER
PT J
AU Schlaff, CD
Krauze, A
Belard, A
O'Connell, JJ
Camphausen, KA
AF Schlaff, Cody D.
Krauze, Andra
Belard, Arnaud
O'Connell, John J.
Camphausen, Kevin A.
TI Bringing the heavy: carbon ion therapy in the radiobiological and
clinical context
SO RADIATION ONCOLOGY
LA English
DT Review
DE Radiotherapy; Radiobiology; Carbon ions; Hypoxia; a/beta ratio; Tumor
microenvironment; Tumor metabolism; Cancer stem cells
ID STEREOTACTIC BODY RADIOTHERAPY; CELL LUNG-CANCER; SOFT-TISSUE SARCOMAS;
PROTON-BEAM THERAPY; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; LOCALIZED
PROSTATE-CANCER; ADENOID CYSTIC CARCINOMA; SKULL BASE CHORDOMA; HUMAN
BRAIN-TUMORS; RADIATION-THERAPY
AB Radiotherapy for the treatment of cancer is undergoing an evolution, shifting to the use of heavier ion species. For a plethora of malignancies, current radiotherapy using photons or protons yields marginal benefits in local control and survival. One hypothesis is that these malignancies have acquired, or are inherently radioresistant to low LET radiation. In the last decade, carbon ion radiotherapy facilities have slowly been constructed in Europe and Asia, demonstrating favorable results for many of the malignancies that do poorly with conventional radiotherapy. However, from a radiobiological perspective, much of how this modality works in overcoming radioresistance, and extending local control and survival are not yet fully understood. In this review, we will explain from a radiobiological perspective how carbon ion radiotherapy can overcome the classical and recently postulated contributors of radioresistance (a/beta ratio, hypoxia, cell proliferation, the tumor microenvironment and metabolism, and cancer stem cells). Furthermore, we will make recommendations on the important factors to consider, such as anatomical location, in the future design and implementation of clinical trials. With the existing data available we believe that the expansion of carbon ion facilities into the United States is warranted.
C1 [Schlaff, Cody D.; Krauze, Andra; Camphausen, Kevin A.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Belard, Arnaud; O'Connell, John J.] Walter Reed Natl Mil Med Ctr, Radiat Oncol Serv, Proton Beam Program, Bethesda, MD 20889 USA.
[Belard, Arnaud; O'Connell, John J.] Walter Reed Natl Mil Med Ctr, John P Murtha Canc Ctr, Bethesda, MD USA.
RP Camphausen, KA (reprint author), NCI, Radiat Oncol Branch, 10 Ctr Dr Magnuson Clin Ctr Room B3B100, Bethesda, MD 20892 USA.
EM camphauk@mail.nih.gov
FU Intramural Research Program of the NIH, NCI
FX We would like to thank BodyParts3D, The Database Center for Life
Science, Japan Copyright c 2010 for the skeletal model and Peppe Cirotti
from the Universidad de Costa Rica for the conversion of the skeletal
model to Blender for its use in Figure 3. This research was supported
[in part] by the Intramural Research Program of the NIH, NCI.
NR 172
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Z9 36
U1 2
U2 20
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-717X
J9 RADIAT ONCOL
JI Radiat. Oncol.
PD MAR 28
PY 2014
VL 9
AR 88
DI 10.1186/1748-717X-9-88
PG 19
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA AG5CO
UT WOS:000335437000001
PM 24679134
ER
PT J
AU Moody, TW
Chan, DC
Mantey, SA
Moreno, P
Jensen, RT
AF Moody, Terry W.
Chan, Daniel C.
Mantey, Samuel A.
Moreno, Paola
Jensen, Robert T.
TI SR48692 inhibits non-small cell lung cancer proliferation in an EGF
receptor-dependent manner
SO LIFE SCIENCES
LA English
DT Article
DE Neurotensin; Epidermal growth factor receptor; Transactivation; Lung
cancer; siRNA
ID GROWTH-FACTOR RECEPTOR; FOCAL ADHESION KINASE; CAUSES TYROSINE
PHOSPHORYLATION; NEUROTENSIN RECEPTOR; PROSTATE-CANCER; DNA-SYNTHESIS;
GEFITINIB; ANTAGONIST; MUTATIONS; PATHWAY
AB Aims: The mechanism by which SR48692 inhibits non-small cell lung cancer (NSCLC) proliferation was investigated.
Main methods: The ability of SR48692 to inhibit the proliferation of NSCLC cell lines NCI-H1299 and A549 was investigated in vitro in the presence or absence of neurotensin (NIS). The ability of NTS to cause epidermal growth factor receptor (EGFR) transactivation was investigated by Western blot using NSCLC cells and various inhibitors. The growth effects and Western blot results were determined in cell lines treated with siRNA for NTSR1.
Key findings: Treatment of A549 or NCI-H1299 cells with siRNA for NTSR1 reduced significantly NTSR1 protein and the ability of SR48692 to inhibit the proliferation of A549 or NCI-H1299 NSCLC cells. Treatment of A549 and NCI-H1299 cells with siRNA for NTSR1 reduced the ability of NTS to cause epidermal growth factor receptor (EGFR) transactivation. SR48692 or gefitinib (EGFR tyrosine kinase inhibitor) inhibited the ability of NTS to cause EGFR and ERK tyrosine phosphorylation. NTS transactivation of the EGFR was inhibited by GM6001 ( matrix metalloprotease inhibitor), Tiron (superoxide scavenger) or U73122 (phospholipase C inhibitor) but not H89 (PKA inhibitor). NTS stimulates whereas SR48692 or gefitinib inhibits the clonal growth of NSCLC cells.
Significance: These results suggest that SR48692 may inhibit NSCLC proliferation in an EGFR-dependent mechanism. Published by Elsevier Inc.
C1 [Moody, Terry W.] NCI, Dept Hlth & Human Serv, Ctr Canc Res, Off Director, Bethesda, MD 20892 USA.
[Chan, Daniel C.] Univ Colorado, Sch Med, Div Med Oncol, Aurora, CO 80045 USA.
[Mantey, Samuel A.; Moreno, Paola; Jensen, Robert T.] NIDDK, Digest Dis Branch, Bethesda, MD 20892 USA.
RP Moody, TW (reprint author), NCI, Off Director, CCR, 9609 Med Ctr Dr,Room 2W-130, Bethesda, MD 20892 USA.
EM moodyt@mail.nih.gov
FU intramural research program of the NIDDK; NCI, of NIH
FX The authors thank Dr. David Wink for helpful discussions. This research
is partially supported by the intramural research program of the NIDDK
and NCI, of NIH.
NR 41
TC 6
Z9 7
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0024-3205
EI 1879-0631
J9 LIFE SCI
JI Life Sci.
PD MAR 28
PY 2014
VL 100
IS 1
BP 25
EP 34
DI 10.1016/j.lfs.2014.01.072
PG 10
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA AE9JH
UT WOS:000334323600004
PM 24496038
ER
PT J
AU Lauer, MS
AF Lauer, Michael S.
TI Personal Reflections on Big Science, Small Science, or the Right Mix
SO CIRCULATION RESEARCH
LA English
DT Article
DE biomedical research; economics; National Heart; Lung; and Blood
Institute
ID INNOVATION
C1 NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA.
EM lauerm@nhlbi.nih.gov
FU NHLBI NIH HHS [R01 HL066004, P50 HL077107, R01 HL072771]
NR 16
TC 4
Z9 4
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD MAR 28
PY 2014
VL 114
IS 7
BP 1080
EP 1082
DI 10.1161/CIRCRESAHA.114.303627
PG 3
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA AE0KY
UT WOS:000333656400005
PM 24677234
ER
PT J
AU Abate-Daga, D
Speiser, DE
Chinnasamy, N
Zheng, ZL
Xu, H
Feldman, SA
Rosenberg, SA
Morgan, RA
AF Abate-Daga, Daniel
Speiser, Daniel E.
Chinnasamy, Nachimuthu
Zheng, Zhili
Xu, Hui
Feldman, Steven A.
Rosenberg, Steven A.
Morgan, Richard A.
TI Development of a T Cell Receptor Targeting an HLA-A*0201 Restricted
Epitope from the Cancer-Testis Antigen SSX2 for Adoptive Immunotherapy
of Cancer
SO PLOS ONE
LA English
DT Article
ID HUMAN SYNOVIAL SARCOMA; TCR GENE-THERAPY; METASTATIC MELANOMA;
MULTIPLE-MYELOMA; PROSTATE-CANCER; ENGINEERED LYMPHOCYTES; CANCER/TESTIS
ANTIGENS; EXPRESSION; REGRESSION; RESPONSES
AB The clinical success of adoptive immunotherapy of cancer relies on the selection of target antigens that are highly expressed in tumor cells but absent in essential normal tissues. A group of genes that encode the cancer/testis or cancer germline antigens have been proposed as ideal targets for immunotherapy due to their high expression in multiple cancer types and their restricted expression in immunoprivileged normal tissues. In the present work we report the isolation and characterization of human T cell receptors (TCRs) with specificity for synovial sarcoma X breakpoint 2 (SSX2), a cancer/testis antigen expressed in melanoma, prostate cancer, lymphoma, multiple myeloma and pancreatic cancer, among other tumors. We isolated seven HLA-A2 restricted T cell receptors from natural T cell clones derived from tumor-infiltrated lymph nodes of two SSX2-seropositive melanoma patients, and selected four TCRs for cloning into retroviral vectors. Peripheral blood lymphocytes (PBL) transduced with three of four SSX2 TCRs showed SSX2(41-49) (KASEKIFYV) peptide specific reactivity, tumor cell recognition and tetramer binding. One of these, TCR-5, exhibited tetramer binding in both CD4 and CD8 cells and was selected for further studies. Antigen-specific and HLA-A*0201-restricted interferon-gamma release, cell lysis and lymphocyte proliferation was observed following culture of TCR engineered human PBL with relevant tumor cell lines. Codon optimization was found to increase TCR-5 expression in transduced T cells, and this construct has been selected for development of clinical grade viral vector producing cells. The tumor-specific pattern of expression of SSX2, along with the potent and selective activity of TCR-5, makes this TCR an attractive candidate for potential TCR gene therapy to treat multiple cancer histologies.
C1 [Abate-Daga, Daniel; Chinnasamy, Nachimuthu; Zheng, Zhili; Xu, Hui; Feldman, Steven A.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Speiser, Daniel E.] Univ Lausanne, Dept Oncol, Ludwig Ctr, Lausanne, Switzerland.
RP Abate-Daga, D (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM daniel.abate-daga@nih.gov
FU Milstein Family Foundation; Intramural Research Program of The Center
for Cancer Research, National Cancer Institute, Bethesda MD
FX This project was supported in part by a contribution from the Milstein
Family Foundation and by the Intramural Research Program of The Center
for Cancer Research, National Cancer Institute, Bethesda MD. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 49
TC 10
Z9 11
U1 1
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 28
PY 2014
VL 9
IS 3
AR e93321
DI 10.1371/journal.pone.0093321
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0TC
UT WOS:000333678100042
PM 24681846
ER
PT J
AU Pollack, AZ
Sjaarda, L
Ahrens, KA
Mumford, SL
Browne, RW
Wactawski-Wende, J
Schisterman, EF
AF Pollack, Anna Z.
Sjaarda, Lindsey
Ahrens, Katherine A.
Mumford, Sunni L.
Browne, Richard W.
Wactawski-Wende, Jean
Schisterman, Enrique F.
TI Association of Cadmium, Lead and Mercury with Paraoxonase 1 Activity in
Women
SO PLOS ONE
LA English
DT Article
ID OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; MENSTRUAL-CYCLE; BLOOD
CADMIUM; EXPOSURE; RISK; ATHEROSCLEROSIS; POLYMORPHISMS; PEROXIDATION;
BIOCYCLE
AB Background: The activity of paraoxonase 1 (PON1), an antioxidant enzyme whose polymorphisms have been associated with cancer risk, may be associated with metals exposure.
Objective: To evaluate PON1 activity in relation to cadmium, lead, and mercury levels in healthy, premenopausal women.
Methods: Women from upstate New York were followed for >= two menstrual cycles. Repeated measures linear mixed models estimated the association between cadmium, lead, and mercury levels (by tertile: T1, T2, T3) and PON1 arylesterase (PON1A) and PON1 paraoxonase (PON1P) activity, separately. Analyses were stratified by PON1 Q192R phenotype and unstratified.
Results: Median blood cadmium, lead, and mercury concentrations were 0.30 mu g/L, 0.87 mu g/dL, and 1.15 mu g/L. In unstratified analyses cadmium and mercury were associated with decreased PON1A activity (T2 vs. T1; not T3 vs. T1) but metals were not associated with PON1P. Phenotypes were distributed between QQ (n = 99), QR (n = 117), and RR (n = 34). Cadmium was associated with decreased PON1A activity for QR and RR phenotypes comparing T2 vs. T1 (-14.4% 95% confidence interval [CI] [-20.1, -8.4] and -27.9% [-39.5, -14.0],). Lead was associated with decreased PON1A (RR phenotype, T3 vs. T1 -18.9% [-32.5, -2.5]; T2 vs. T1 -19.6% [-32.4, -4.4]). Cadmium was associated with lower PON1P comparing T2 vs. T1 for the RR (-34.9% [-51.5, -12.5]) and QR phenotypes (-9.5% [-18.1, 0.0]) but not comparing T3 vs. T1. Cadmium was associated with increases in PON1P levels (QQ phenotype, T3 vs. T1 24.5% [7.0, 44.9]) and mercury was associated with increased PON1A levels (QQ phenotype, T3 vs. T1 6.2% [0.2, 12.6]). Mercury was associated with decreased PON1P (RR phenotype, T2 vs. T1 -22.8 [-37.8, -4.1]).
Conclusion: Blood metals were associated with PON1 activity and these effects varied by phenotype. However, there was not a linear dose-response and these findings await replication.
C1 [Pollack, Anna Z.; Sjaarda, Lindsey; Ahrens, Katherine A.; Mumford, Sunni L.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
[Pollack, Anna Z.] George Mason Univ, Dept Global & Community Hlth, Sch Hlth & Human Serv, Fairfax, VA 22030 USA.
[Browne, Richard W.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14260 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
EM schistee@mail.nih.gov
OI Pollack, Anna/0000-0002-4313-3298; Sjaarda, Lindsey/0000-0003-0539-8110;
Schisterman, Enrique/0000-0003-3757-641X
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health [HHSN275200403394C]; Long-Range Research Initiative grant of the
American Chemistry Council
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health (Contract #
HHSN275200403394C). Anna Z. Pollack was partially supported by the
Long-Range Research Initiative grant of the American Chemistry Council
to Dr. Schisterman, PI, and partially supported by the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, 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 42
TC 3
Z9 3
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 28
PY 2014
VL 9
IS 3
AR e92152
DI 10.1371/journal.pone.0092152
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0TC
UT WOS:000333678100007
PM 24682159
ER
PT J
AU Mortha, A
Chudnovskiy, A
Hashimoto, D
Bogunovic, M
Spencer, SP
Belkaid, Y
Merad, M
AF Mortha, Arthur
Chudnovskiy, Aleksey
Hashimoto, Daigo
Bogunovic, Milena
Spencer, Sean P.
Belkaid, Yasmine
Merad, Miriam
TI Microbiota-Dependent Crosstalk Between Macrophages and ILC3 Promotes
Intestinal Homeostasis
SO SCIENCE
LA English
DT Article
ID COLONY-STIMULATING FACTOR; ROR-GAMMA-T; INFLAMMATORY-BOWEL-DISEASE;
CYTOKINE GM-CSF; DENDRITIC CELLS; STEADY-STATE; COMMENSAL MICROFLORA;
NKP46(+) CELLS; CROHNS-DISEASE; LYMPHOID-CELLS
AB The intestinal microbiota and tissue-resident myeloid cells promote immune responses that maintain intestinal homeostasis in the host. However, the cellular cues that translate microbial signals into intestinal homeostasis remain unclear. Here, we show that deficient granulocyte-macrophage colony-stimulating factor (GM-CSF) production altered mononuclear phagocyte effector functions and led to reduced regulatory T cell (T-reg) numbers and impaired oral tolerance. We observed that ROR gamma t(+) innate lymphoid cells (ILCs) are the primary source of GM-CSF in the gut and that ILC-driven GM-CSF production was dependent on the ability of macrophages to sense microbial signals and produce interleukin-1 beta. Our findings reveal that commensal microbes promote a crosstalk between innate myeloid and lymphoid cells that leads to immune homeostasis in the intestine.
C1 [Mortha, Arthur; Chudnovskiy, Aleksey; Hashimoto, Daigo; Bogunovic, Milena; Merad, Miriam] Dept Oncol Sci, New York, NY 10029 USA.
[Mortha, Arthur; Chudnovskiy, Aleksey; Hashimoto, Daigo; Bogunovic, Milena; Merad, Miriam] Tisch Canc Inst, New York, NY 10029 USA.
[Mortha, Arthur; Chudnovskiy, Aleksey; Hashimoto, Daigo; Bogunovic, Milena; Merad, Miriam] Mt Sinai Sch Med, Inst Immunol, New York, NY 10029 USA.
[Spencer, Sean P.; Belkaid, Yasmine] NIAID, Program Barrier Immun & Repair, Mucosal Immunol Sect, Lab Parasit Dis, Bethesda, MD 20892 USA.
RP Merad, M (reprint author), Dept Oncol Sci, 1470 Madison Ave, New York, NY 10029 USA.
EM miriam.merad@mssm.edu
RI Hashimoto, Daigo/O-1013-2013
OI Hashimoto, Daigo/0000-0001-9489-9704
FU NIH [R01 CA154947A, R01 CA173861, U01 AI095611]; German Research
Foundation (DFG) [MO2380/1-1]; Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases
FX We thank the Merad laboratory for helpful discussions and input. We are
grateful to W.-H. Kwan and W. van der Touw for assistance with the
Treg induction assay. We thank R. Huq and L. O'Rourke at the
Icahn School of Medicine at Mount Sinai Microscopy Shared Resource
Facility for their training, helpful advice, and support with microscopy
imaging. We are grateful to C. Berin and A. Belen Blazquez for support
with the oral tolerance and DTH models. We thank J. Ochando and the Flow
Cytometry facility for technical support and assistance with cell
sorting. The data presented in this paper are tabulated in the main
paper and in the supporting materials. M. M. is funded by NIH grants R01
CA154947A, R01 CA173861, and U01 AI095611. A. M. is funded by the German
Research Foundation (DFG) grant MO2380/1-1. Y.B. was supported by the
Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases.
NR 58
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Z9 183
U1 5
U2 62
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD MAR 28
PY 2014
VL 343
IS 6178
BP 1477
EP +
AR 1249288
DI 10.1126/science.1249288
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD7TZ
UT WOS:000333471000038
PM 24625929
ER
PT J
AU Eun, SH
Shi, Z
Cui, KR
Zhao, KJ
Chen, X
AF Eun, Suk Ho
Shi, Zhen
Cui, Kairong
Zhao, Keji
Chen, Xin
TI A Non-Cell Autonomous Role of E(z) to Prevent Germ Cells from Turning on
a Somatic Cell Marker
SO SCIENCE
LA English
DT Article
ID DROSOPHILA TESTIS; SELF-RENEWAL; DIRECT CONVERSION; GENE-EXPRESSION;
STEM-CELLS; NICHE; LESSONS; POLYCOMB; FATE; LINE
AB In many metazoans, germ cells are separated from somatic lineages early in development and maintain their identity throughout life. Here, we show that a Polycomb group (PcG) component, Enhancer of Zeste [E(z)], a histone transferase that generates trimethylation at lysine 27 of histone H3, maintains germline identity in Drosophila adult testes. We find excessive early-stage somatic gonadal cells in E(z) mutant testes, which originate from both overproliferative cyst stem cells and germ cells turning on an early-stage somatic cell marker. Using complementary lineage-tracing experiments in E(z) mutant testes, a portion of excessive early-stage somatic gonadal cells are found to originate from early-stage germ cells, including germline stem cells. Moreover, knocking down E(z) specifically in somatic cells caused this change, which suggests a non-cell autonomous role of E(z) to antagonize somatic identity in germ cells.
C1 [Eun, Suk Ho; Shi, Zhen; Chen, Xin] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
[Cui, Kairong; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Chen, X (reprint author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
EM xchen32@jhu.edu
FU National Institute of Child Health and Human Development (NIH)
[R00HD055052, R01HD065816]; David and Lucile Packard Foundation; March
of Dimes [05-FY09-88]; Johns Hopkins University; Division of Intramural
Research, NHLBI, NIH
FX We thank C. Choi for technical assistance and D. Drummond-Barbosa, M.
Van Doren, H. Zhao, Y. Yamashita, and the Chen laboratory members for
suggestions. ChIP-Seq libraries were sequenced at National Heart, Lung,
and Blood Institute (NHLBI) Sequencing and Computation Core facility
(NIH); the GEO accession number is GSE53238. Supported by National
Institute of Child Health and Human Development (NIH) grants R00HD055052
and R01HD065816, the David and Lucile Packard Foundation, March of Dimes
#05-FY09-88, Johns Hopkins University start-up (X. C.), and Division of
Intramural Research, NHLBI, NIH (K.Z.).
NR 30
TC 17
Z9 17
U1 0
U2 15
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD MAR 28
PY 2014
VL 343
IS 6178
BP 1513
EP 1516
DI 10.1126/science.1246514
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD7TZ
UT WOS:000333471000048
PM 24675960
ER
PT J
AU Price, S
Shaw, PA
Seitz, A
Joshi, G
Davis, J
Niemela, JE
Perkins, K
Hornung, RL
Folio, L
Rosenberg, PS
Puck, JM
Hsu, AP
Lo, B
Pittaluga, S
Jaffe, ES
Fleisher, TA
Rao, VK
Lenardo, MJ
AF Price, Susan
Shaw, Pamela A.
Seitz, Amy
Joshi, Gyan
Davis, Joie
Niemela, Julie E.
Perkins, Katie
Hornung, Ronald L.
Folio, Les
Rosenberg, Philip S.
Puck, Jennifer M.
Hsu, Amy P.
Lo, Bernice
Pittaluga, Stefania
Jaffe, Elaine S.
Fleisher, Thomas A.
Rao, V. Koneti
Lenardo, Michael J.
TI Natural history of autoimmune lymphoproliferative syndrome associated
with FAS gene mutations
SO BLOOD
LA English
DT Article
ID T-LYMPHOCYTE APOPTOSIS; DEFECTIVE LYMPHOCYTE; DOMINANT INHIBITION;
DISEASE; DEATH; FEATURES; PATIENT; HAPLOINSUFFICIENCY; CYTOPENIAS;
FAMILIES
AB Autoimmune lymphoproliferative syndrome (ALPS) presents in childhood with nonmalignant lymphadenopathy and splenomegaly associated with a characteristic expansion of mature CD4 and CD8 negative or double negative T-cell receptor alpha beta(+) T lymphocytes. Patients often present with chronic multilineage cytopenias due to autoimmune peripheral destruction and/or splenic sequestration of blood cells and have an increased risk of B-cell lymphoma. Deleterious heterozygous mutations in the FAS gene are the most common cause of this condition, which is termed ALPS-FAS. We report the natural history and pathophysiology of 150 ALPS-FAS patients and 63 healthy mutation-positive relatives evaluated in our institution over the last 2 decades. Our principal findings are that FAS mutations have a clinical penetrance of <60%, elevated serum vitamin B-12 is a reliable and accurate biomarker of ALPS-FAS, and the major causes of morbidity and mortality in these patients are the overwhelming postsplenectomy sepsis and development of lymphoma. With longer follow-up, we observed a significantly greater relative risk of lymphoma than previously reported. Avoiding splenectomy while controlling hypersplenism by using corticosteroid-sparing treatments improves the outcome in ALPS-FAS patients.
C1 [Price, Susan; Davis, Joie; Lo, Bernice; Rao, V. Koneti; Lenardo, Michael J.] NIAID, Mol Dev Sect, Immunol Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
[Shaw, Pamela A.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Seitz, Amy; Hsu, Amy P.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Joshi, Gyan] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Biostat Res Branch, Frederick, MD USA.
[Niemela, Julie E.; Fleisher, Thomas A.] NIH, Serv Immunol, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Perkins, Katie; Hornung, Ronald L.] Leidos Biomed Res Inc, Clin Serv Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Folio, Les] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Rosenberg, Philip S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Puck, Jennifer M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
[Puck, Jennifer M.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Rao, VK (reprint author), NIAID, NIH, Bldg 10,Room 12C106,10 Ctr Dr,MSC 1899, Bethesda, MD 20892 USA.
EM koneti@nih.gov
RI Jaffe, Elaine/G-8984-2014;
OI Jaffe, Elaine/0000-0003-4632-0301; Niemela, Julie/0000-0003-4197-3792;
Lo, Bernice/0000-0002-1087-6845
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases; NIH Clinical Center; National Cancer Institute
[HHSN261200800001E.]
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases and the NIH
Clinical Center. This project has been funded in whole or in part with
federal funds from National Cancer Institute grant HHSN261200800001E.
NR 57
TC 47
Z9 50
U1 0
U2 11
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 27
PY 2014
VL 123
IS 13
BP 1989
EP 1999
DI 10.1182/blood-2013-10-535393
PG 11
WC Hematology
SC Hematology
GA AH1AP
UT WOS:000335852200010
PM 24398331
ER
PT J
AU Dandekar, VK
Bauml, MA
Ertel, AW
Dickens, C
Gonzalez, RC
Farzaneh-Far, A
AF Dandekar, Vineet K.
Bauml, Michael A.
Ertel, Andrew W.
Dickens, Carolyn
Gonzalez, Rosalia C.
Farzaneh-Far, Afshin
TI Assessment of global myocardial perfusion reserve using cardiovascular
magnetic resonance of coronary sinus flow at 3 Tesla
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Cardiovascular magnetic resonance; Stress testing; Perfusion;
Regadenoson
ID POSITRON-EMISSION-TOMOGRAPHY; PROGNOSTIC VALUE; ARTERY-DISEASE;
BLOOD-FLOW; NONINVASIVE QUANTIFICATION; NORMAL REGADENOSON;
HEART-DISEASE; ADENOSINE; DYSFUNCTION; DIAGNOSIS
AB Background: Despite increasing clinical use, there is limited data regarding regadenoson in stress perfusion cardiovascular magnetic resonance (CMR). In particular, given its long half-life the optimal stress protocol remains unclear. Although Myocardial Perfusion Reserve (MPR) may provide additive prognostic information, current techniques for its measurement are cumbersome and challenging for routine clinical practice. The aims of this study were: 1) To determine the feasibility of MPR quantification during regadenoson stress CMR by measurement of Coronary Sinus (CS) flow; and 2) to investigate the role of aminophylline reversal during regadenoson stress-CMR.
Methods: 117 consecutive patients with possible myocardial ischemia were prospectively enrolled. Perfusion imaging was performed at 1 minute and 15 minutes after administration of 0.4 mg regadenoson. A subgroup of 41 patients was given aminophylline (100 mg) after stress images were acquired. CS flow was measured using phase-contrast imaging at baseline (pre CS flow), and immediately after the stress (peak CS flow) and rest (post CS flow) perfusion images.
Results: CS flow measurements were obtained in 92% of patients with no adverse events. MPR was significantly underestimated when calculated as peak CS flow/ post CS flow as compared to peak CS flow/ pre CS flow (2.43 +/- 0.20 vs. 3.28 +/- 0.32, p = 0.03). This difference was abolished when aminophylline was administered (3.35 +/- 0.44 vs. 3.30 +/- 0.52, p = 0.95). Impaired MPR (peak CS flow/ pre CS flow < 2) was associated with advanced age, diabetes, current smoking and higher Framingham risk score.
Conclusions: Regadenoson stress CMR with MPR measurement from CS flow can be successfully performed in most patients. This measurement of MPR appears practical to perform in the clinical setting. Residual hyperemia is still present even 15 minutes after regadenoson administration, at the time of resting-perfusion acquisition, and is completely reversed by aminophylline. Our findings suggest routine aminophylline administration may be required when performing stress CMR with regadenoson.
C1 [Dandekar, Vineet K.; Bauml, Michael A.; Dickens, Carolyn; Gonzalez, Rosalia C.; Farzaneh-Far, Afshin] Univ Illinois, Dept Med, Sect Cardiol, Chicago, IL 60612 USA.
[Ertel, Andrew W.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Farzaneh-Far, Afshin] Univ Illinois, Dept Radiol, Chicago, IL 60612 USA.
[Farzaneh-Far, Afshin] Duke Univ, Dept Med, Div Cardiol, Durham, NC USA.
RP Farzaneh-Far, A (reprint author), Univ Illinois, Dept Med, Sect Cardiol, 840 South Wood St,M-C 715,Suite 920 S, Chicago, IL 60612 USA.
EM afshin@uic.edu
NR 29
TC 7
Z9 7
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
EI 1532-429X
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD MAR 27
PY 2014
VL 16
AR 24
DI 10.1186/1532-429X-16-24
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA AF9UM
UT WOS:000335060200001
PM 24674383
ER
PT J
AU Belkaid, Y
Hand, TW
AF Belkaid, Yasmine
Hand, Timothy W.
TI Role of the Microbiota in Immunity and Inflammation
SO CELL
LA English
DT Review
ID SEGMENTED FILAMENTOUS BACTERIA; REGULATORY T-CELLS; INTESTINAL DENDRITIC
CELLS; INNATE LYMPHOID-CELLS; TOLL-LIKE RECEPTORS; CHAIN FATTY-ACIDS;
ACUTE GASTROINTESTINAL INFECTION; ORAL TOLERANCE INDUCTION; GUT
COMMENSAL BACTERIA; LECTIN REGIII-GAMMA
AB The microbiota plays a fundamental role on the induction, training, and function of the host immune system. In return, the immune system has largely evolved as a means to maintain the symbiotic relationship of the host with these highly diverse and evolving microbes. When operating optimally, this immune system-microbiota alliance allows the induction of protective responses to pathogens and the maintenance of regulatory pathways involved in the maintenance of tolerance to innocuous antigens. However, in high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses. This phenomenon is proposed to account for some of the dramatic rise in autoimmune and inflammatory disorders in parts of the world where our symbiotic relationship with the microbiota has been the most affected.
C1 [Belkaid, Yasmine; Hand, Timothy W.] NIAID, Immun Barrier Sites Initiat, NIH, Bethesda, MD 20892 USA.
[Hand, Timothy W.] NIAID, Parasit Dis Lab, Mucosal Immunol Sect, NIH, Bethesda, MD 20892 USA.
RP Belkaid, Y (reprint author), NIAID, Immun Barrier Sites Initiat, NIH, Bethesda, MD 20892 USA.
EM ybelkaid@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health. We would like to thank the members of the Belkaid laboratory for
helpful discussions and, more particularly, John Grainger, Sean Spencer,
and Nicolas Bouladoux for critical reading of the manuscript. We would
like to also apologize to our colleagues for not having cited all papers
relevant to this expanding field because of space constraints.
NR 244
TC 266
Z9 273
U1 52
U2 280
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD MAR 27
PY 2014
VL 157
IS 1
BP 121
EP 141
DI 10.1016/j.cell.2014.03.011
PG 21
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AE4QW
UT WOS:000333968900012
PM 24679531
ER
PT J
AU O'Shea, JJ
Kanno, Y
Chan, AC
AF O'Shea, John J.
Kanno, Yuka
Chan, Andrew C.
TI In Search of Magic Bullets: The Golden Age of Immunotherapeutics
SO CELL
LA English
DT Review
ID B-CELL DEPLETION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; REMITTING
MULTIPLE-SCLEROSIS; MONOCLONAL-ANTIBODY THERAPY; JANUS KINASE INHIBITOR;
TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; INFLAMMATORY DISEASE;
AUTOIMMUNE-DISEASES; TARGETING BTK
AB Once upon a time, immunology was a black box, inflammatory and autoimmune diseases were a mystery, and relatively blunt tools were used to treat these diseases. In the last 40 years, advances in molecular biology, DNA recombination technology, and genome sequencing allowed immunologists to open the box. As the complexity and diversity of the immune response are unveiled, targeted cellular and molecular therapies now offer rational approaches to treat immune-mediated diseases. Here, we discuss how the tried and true bench-to-bedside strategies resulted in some spectacular successes, along with some puzzling failures. Conversely, the advent of targeted therapies in the clinic has led to a wealth of information that changes how we think about the pathogenesis of immune-mediated diseases and how we categorize disease. In turn, these insights can inform next-generation drug discovery and refine targeted therapies for the appropriate patient subsets.
C1 [O'Shea, John J.; Kanno, Yuka] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Chan, Andrew C.] Genentech Inc, San Francisco, CA 94080 USA.
RP O'Shea, JJ (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM osheajo@mail.nih.gov; acc@gene.com
RI Kanno, Yuka/B-5802-2013;
OI Kanno, Yuka/0000-0001-5668-9319
FU Intramural NIH HHS [ZIA AR041106-19]
NR 74
TC 19
Z9 19
U1 2
U2 27
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD MAR 27
PY 2014
VL 157
IS 1
BP 227
EP 240
DI 10.1016/j.cell.2014.03.010
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AE4QW
UT WOS:000333968900019
PM 24679538
ER
PT J
AU Ui, A
Ogiwara, H
Nakajima, S
Kanno, S
Watanabe, R
Harata, M
Okayama, H
Harris, CC
Yokota, J
Yasui, A
Kohno, T
AF Ui, A.
Ogiwara, H.
Nakajima, S.
Kanno, S.
Watanabe, R.
Harata, M.
Okayama, H.
Harris, C. C.
Yokota, J.
Yasui, A.
Kohno, T.
TI Possible involvement of LKB1-AMPK signaling in non-homologous end
joining
SO ONCOGENE
LA English
DT Article
DE LKB1-AMPK signaling; non-homologous end joining; chromatin remodeling;
tumor suppressor gene; genome instability
ID DOUBLE-STRAND BREAKS; ACTIVATED PROTEIN-KINASE; DNA-DAMAGE RESPONSE;
CANCER CELL-LINES; HISTONE ACETYLATION; REPAIR PROTEINS; LKB1; LUNG;
PHOSPHORYLATION; COMPLEX
AB LKB1/STK11 is a tumor suppressor gene responsible for Peutz-Jeghers syndrome, an inherited cancer disorder associated with genome instability. The LKB1 protein functions in the regulation of cell proliferation, polarization and differentiation. Here, we suggest a role of LKB1 in non-homologous end joining (NHEJ), a major DNA double-strand break (DSB) repair pathway. LKB1 localized to DNA ends upon the generation of micro-irradiation and I-SceI endonuclease-induced DSBs. LKB1 inactivation either by RNA interference or by kinase-dead mutation compromised NHEJ-mediated DNA repair by suppressing the accumulation of BRM, a catalytic subunit of the SWI/SNF complex, at DSB sites, which promotes the recruitment of an essential NHEJ factor, KU70. AMPK2, a major substrate of LKB1 and a histone H2B kinase, was recruited to DSBs in an LKB1-dependent manner. AMPK2 depletion and a mutation of H2B that disrupted the AMPK2 phoshorylation site impaired KU70 and BRM recruitment to DSB sites. LKB1 depletion induced the formation of chromosome breaks and radials. These results suggest that LKB1-AMPK signaling controls NHEJ and contributes to genome stability.
C1 [Ui, A.; Ogiwara, H.; Kohno, T.] Natl Canc Ctr, Res Inst, Div Genome Biol, Chuo Ku, Tokyo 1040045, Japan.
[Ui, A.; Kanno, S.; Watanabe, R.; Yasui, A.] Tohoku Univ, Inst Dev Aging & Canc, Div Dynam Proteome, Sendai, Miyagi 980, Japan.
[Nakajima, S.; Yasui, A.] Tohoku Univ, Inst Dev Aging & Canc, Dept Mol Genet, Sendai, Miyagi 980, Japan.
[Harata, M.] Tohoku Univ, Grad Sch Agr Sci, Dept Mol & Cell Biol, Div Life Sci,Lab Mol Biol, Sendai, Miyagi 980, Japan.
[Okayama, H.; Harris, C. C.] NCI, Ctr Canc Res, Human Carcinogenesis Lab, NIH, Bethesda, MD USA.
[Yokota, J.] Natl Canc Ctr, Res Inst, Div Multistage Carcinogenesis, Tokyo 104, Japan.
RP Kohno, T (reprint author), Natl Canc Ctr, Res Inst, Div Genome Biol, Chuo Ku, Tsukiji 5-1-1, Tokyo 1040045, Japan.
EM tkkohno@ncc.go.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan
for Scientific Research on Innovative Areas [22131006, 22131005]; Japan
Society for the Promotion of Science for Young Scientists (B) KAKENHI
[23701110, 24710057]; Government to the National Cancer Center
FX This work was supported by Grants-in-Aid from the Ministry of Education,
Culture, Sports, Science and Technology of Japan for Scientific Research
on Innovative Areas (22131006 to TK and HO; and 22131005 to AY), from
the Japan Society for the Promotion of Science for Young Scientists (B)
KAKENHI (23701110 to HO and 24710057 to AU) and Management Expenses
Grants from the Government to the National Cancer Center. A part of this
work was carried out under the Cooperative Research Project Program of
the Institute of Development, Aging and Cancer, Tohoku University.
NR 38
TC 9
Z9 9
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD MAR 27
PY 2014
VL 33
IS 13
BP 1640
EP 1648
DI 10.1038/onc.2013.125
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AE9QY
UT WOS:000334344700004
PM 23584481
ER
PT J
AU Cook, KL
Soto-Pantoja, DR
Abu-Asab, M
Clarke, PAG
Roberts, DD
Clarke, R
AF Cook, Katherine L.
Soto-Pantoja, David R.
Abu-Asab, Mones
Clarke, Pamela A. G.
Roberts, David D.
Clarke, Robert
TI Mitochondria directly donate their membrane to form autophagosomes
during a novel mechanism of parkin-associated mitophagy
SO CELL AND BIOSCIENCE
LA English
DT Article
DE Breast cancer; Mitochondria; Autophagy; Mitophagy; Parkin; Antiestrogen
resistance; Fulvestrant; Imatinib; Estrogen receptor-a
ID BREAST-CANCER CELLS; ANTIESTROGEN RESISTANCE; RESPONSIVENESS;
BIOGENESIS; APOPTOSIS; VACUOLE
AB Background: Autophagy (macroautophagy), a cellular process of "self-eating", segregates damaged/aged organelles into vesicles, fuses with lysosomes, and enables recycling of the digested materials. The precise origin (s) of the autophagosome membrane is unclear and remains a critical but unanswered question. Endoplasmic reticulum, mitochondria, Golgi complex, and the plasma membrane have been proposed as the source of autophagosomal membranes.
Findings: Using electron microscopy, immunogold labeling techniques, confocal microscopy, and flow cytometry we show that mitochondria can directly donate their membrane material to form autophagosomes. We expand upon earlier studies to show that mitochondria donate their membranes to form autophagosomes during basal and drug-induced autophagy. Moreover, electron microscopy and immunogold labeling studies show the first physical evidence of mitochondria forming continuous structures with LC3-labeled autophagosomes. The mitochondria forming these structures also stain positive for parkin, indicating that these mitochondrial-formed autophagosomes represent a novel mechanism of parkin-associated mitophagy.
Conclusions: With the on-going debate regarding autophagosomal membrane origin, this report demonstrates that mitochondria can donate membrane materials to form autophagosomes. These structures may also represent a novel form of mitophagy where the mitochondria contribute to the formation of autophagosomes. This novel form of parkin-associated mitophagy may be a more efficient bio-energetic process compared with de novo biosynthesis of a new membrane, particularly if the membrane is obtained, at least partly, from the organelle being targeted for later degradation in the mature autolysosome.
C1 [Cook, Katherine L.; Clarke, Pamela A. G.; Clarke, Robert] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20057 USA.
[Cook, Katherine L.; Clarke, Pamela A. G.; Clarke, Robert] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
[Soto-Pantoja, David R.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Abu-Asab, Mones] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Clarke, R (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20057 USA.
EM clarker@georgetown.edu
RI Clarke, Robert/A-6485-2008; Roberts, David/A-9699-2008;
OI Clarke, Robert/0000-0002-9278-0854; Roberts, David/0000-0002-2481-2981;
Cook, Katherine/0000-0001-6241-0214
FU DOD Breast Cancer Research Program Postdoctoral Fellowship [BC112023];
US Department of Health and Human Services [R01-CA131465, U54-CA149147];
Intramural Research Program of the NIH/NCI
FX Katherine Cook is supported by a DOD Breast Cancer Research Program
Postdoctoral Fellowship (BC112023). This research was also supported in
part by awards from the US Department of Health and Human Services
(R01-CA131465 and U54-CA149147) to Robert Clarke and from the Intramural
Research Program of the NIH/NCI to David Roberts.
NR 22
TC 19
Z9 21
U1 1
U2 15
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD MAR 27
PY 2014
VL 4
AR 16
DI 10.1186/2045-3701-4-16
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AF0AR
UT WOS:000334374400001
PM 24669863
ER
PT J
AU Maciag, AE
Holland, RJ
Kim, Y
Kumari, V
Luthers, CE
Sehareen, WS
Biswas, D
Morris, NL
Ji, XH
Anderson, LM
Saavedra, JE
Keefer, LK
AF Maciag, Anna E.
Holland, Ryan J.
Kim, Youseung
Kumari, Vandana
Luthers, Christina E.
Sehareen, Waheed S.
Biswas, Debanjan
Morris, Nicole L.
Ji, Xinhua
Anderson, Lucy M.
Saavedra, Joseph E.
Keefer, Larry K.
TI Nitric Oxide (NO) Releasing Poly ADP-ribose Polymerase 1 (PARP-1)
Inhibitors Targeted to Glutathione S-Transferase P1-Overexpressing
Cancer Cells
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID LUNG-CANCER; JS-K; PROTEASOME INHIBITOR; IN-VITRO; PHASE-I;
ANTINEOPLASTIC ACTIVITY; HISTONE DEACETYLASE; SOLID TUMORS; DNA-DAMAGE;
APOPTOSIS
AB We report the antitumor effects of nitric oxide (NO) releasing derivatives of the PARP-1 inhibitor olaparib (1). Compound 5b was prepared by coupling the carboxyl group of 3b and the free amino group of arylated diazeniumdiolated piperazine 4. Analogue 5a has the same structure except that the F is replaced by H. Compound 13 is the same as 5b except that a Me2N-N(O)=NO- group was added para and ortho to the nitro groups of the dinitrophenyl ring. The resulting prodrugs are activated by glutathione in a reaction accelerated by glutathione S-transferase P1 (GSTP1), an enzyme frequently overexpressed in cancers. This metabolism generates NO plus a PARP-1 inhibitor simultaneously, consuming reducing equivalents, leading to DNA damage concomitant with inhibition of DNA repair, and in the case of 13 inducing cross-linking glutathionylation of proteins. Compounds 5b and 13 reduced the growth rates of A549 human lung adenocarcinoma xenografts with no evidence of systemic toxicity.
C1 [Maciag, Anna E.; Saavedra, Joseph E.] Leidos Biomed Res Inc, Biol Chem Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Holland, Ryan J.; Kim, Youseung; Luthers, Christina E.; Sehareen, Waheed S.; Biswas, Debanjan; Anderson, Lucy M.; Keefer, Larry K.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
[Kumari, Vandana; Ji, Xinhua] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
[Morris, Nicole L.] Leidos Biomed Res Inc, Lab Anim Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Maciag, AE (reprint author), Leidos Biomed Res Inc, Biol Chem Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM maciaga@mail.nih.gov
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU National Cancer Institute, National Institutes of Health
[HHSN26120080001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX We thank Dr. Sergey Tarasov and Marzena A. Dyba of the Biophysics
Resource in the Structural Biophysics Laboratory, NCI-Frederick, for
assistance with the high resolution mass spectrometry studies. This
project has been funded in part with federal funds from the National
Cancer Institute, National Institutes of Health, under Contract
HHSN26120080001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. This research
was supported [in part] by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 27
TC 8
Z9 9
U1 1
U2 16
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD MAR 27
PY 2014
VL 57
IS 6
BP 2292
EP 2302
DI 10.1021/jm401550d
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AD9IK
UT WOS:000333578400009
PM 24521039
ER
PT J
AU Lee, S
Bhattacharya, S
Grissharnmer, R
Tate, C
Vaidehi, N
AF Lee, Sangbae
Bhattacharya, Supriyo
Grissharnmer, Reinhard
Tate, Christopher
Vaidehi, Nagarajan
TI Dynamic Behavior of the Active and Inactive States of the Adenosine
A(2A) Receptor
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; PARTICLE MESH EWALD; O HYDROGEN-BONDS;
CRYSTAL-STRUCTURE; MOLECULAR SIMULATION; TRANSMEMBRANE HELIX;
MEMBRANE-PROTEINS; ASSOCIATION; INTERMEDIATE; SPECIFICITY
AB The adenosine A(2A) receptor (A(2A)R) belongs to the superfamily of membrane proteins called the G-protein-coupled receptors (GPCRs) that form one of the largest superfamilies of drug targets. Deriving thermostable mutants has been one of the strategies used for crystallization of A(2A)R in both the agonist and antagonist bound conformational states. The crystal structures do not reveal differences in the activation mechanism of the mutant receptors compared to the wild type receptor, that have been observed experimentally. These differences stem from the dynamic behavior of the mutant receptors. Furthermore, it is not understood how the mutations confer thermostability. Since these details are difficult to obtain from experiments, we have used atomic level simulations to elucidate the dynamic behavior of the agonist and antagonist bound mutants as well the wild type A(2A)R. We found that significant enthalpic contribution leads to stabilization of both the inactive state (StaR2) and active-like state (GL31) thermostable mutants of A(2A)R. Stabilization resulting from mutations of bulky residues to alanine is due to the formation of interhelical hydrogen bonds and van der Waals packing that improves the transmembrane domain packing. The thermostable mutant GL31 shows less movement of the transmembrane helix TM6 with respect to TM3 than the wild type receptor. While restricted dynamics of GL31 is advantageous in its purification and crystallization, it could also be the reason why these mutants are not efficient in activating the G proteins. We observed that the calculated stress on each residue is higher in the wild type receptor compared to the thermostable mutants, and this stress is required for activation to occur. Thus, reduced dynamic behavior of the thermostable mutants leading to lowered activation of these receptors originates from reduced stress on each residue. Finally, accurate calculation of the change in free energy for single mutations shows good correlation with the change in the measured thermostability. These results provide insights into the effect of mutations that can be incorporated in deriving thermostable mutants for other GPCRs.
C1 [Lee, Sangbae; Bhattacharya, Supriyo; Vaidehi, Nagarajan] Beckman Res Inst City Hope, Div Immunol, Duarte, CA 91010 USA.
[Grissharnmer, Reinhard] Natl Inst Neurol Disorders & Stroke, NIH, Dept Hlth & Human Serv, Membrane Prot Struct Funct Unit, Rockville, MD 20852 USA.
[Tate, Christopher] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
RP Vaidehi, N (reprint author), Beckman Res Inst City Hope, Div Immunol, 1500 E Duarte Rd, Duarte, CA 91010 USA.
EM NVaidehi@coh.org
RI Grisshammer, Reinhard/C-3089-2015;
OI Tate, Christopher/0000-0002-2008-9183
FU Medical Research Council [MRC U105197215]; Intramural Research Program
of the National Institute of Neurological Disorders and Stroke, The
National Institute of Health; [NIH-RO1GM097261]
FX Funding for this work was provided by NIH-RO1GM097261. Chris Tate is
funded by the Medical Research Council (MRC U105197215), and the
research of Reinhard Grisshammer is supported by the Intramural Research
Program of the National Institute of Neurological Disorders and Stroke,
The National Institute of Health. We thank Michiel Niessen for giving
suggestions on the manuscript.
NR 50
TC 10
Z9 10
U1 0
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD MAR 27
PY 2014
VL 118
IS 12
BP 3355
EP 3365
DI 10.1021/jp411618h
PG 11
WC Chemistry, Physical
SC Chemistry
GA AD9IG
UT WOS:000333578000012
PM 24579769
ER
PT J
AU Liu, XD
Chen, X
Zhong, B
Wang, AB
Wang, XH
Chu, FL
Nurieva, RI
Yan, XW
Chen, P
van der Flier, LG
Nakatsukasa, H
Neelapu, SS
Chen, WJ
Clevers, H
Tian, Q
Qi, H
Wei, L
Dong, C
AF Liu, Xindong
Chen, Xin
Zhong, Bo
Wang, Aibo
Wang, Xiaohu
Chu, Fuliang
Nurieva, Roza I.
Yan, Xiaowei
Chen, Ping
van der Flier, Laurens G.
Nakatsukasa, Hiroko
Neelapu, Sattva S.
Chen, Wanjun
Clevers, Hans
Tian, Qiang
Qi, Hai
Wei, Lai
Dong, Chen
TI Transcription factor achaete-scute homologue 2 initiates follicular
T-helper-cell development
SO NATURE
LA English
DT Article
ID GERMINAL CENTER FORMATION; B-CELLS; C-MAF; DIFFERENTIATION; EXPRESSION;
FATE; BCL6; REGULATORS; STAT5; IL-21
AB In immune responses, activated T cells migrate to B-cell follicles and develop into follicular T-helper (T-FH) cells, a recently identified subset of CD4(+) T cells specialized in providing help to B lymphocytes in the induction of germinal centres(1,2). Although Bcl6 has been shown to be essential in T-FH-cell function, it may not regulate the initial migration of T cells(3) or the induction of the T-FH program, as exemplified by C-X-C chemokine receptor type 5 (CXCR5) upregulation(4). Here we show that expression of achaete-scute homologue 2 (Ascl2)-a basic helix-loop-helix (bHLH) transcription factor(5)-is ;selectively upregulated in T-FH cells. Ectopic expression of Ascl2 upregulates CXCR5 but not Bcl6, and downregulates C-C chemokine receptor 7 (CCR7) expression in T cells in vitro, as well as accelerating T-cell migration to the follicles and T-FH-cell development in vivo in mice. Genome-wide analysis indicates that Ascl2 directly regulates T-FH-related genes whereas it inhibits expression of T-helper cell 1 (T(H)1) and T(H)17 signature genes. Acute deletion of Ascl2, as well as blockade of its function with the Id3 protein in CD4(+) T cells, results in impaired T-FH-cell development and germinal centre response. Conversely, mutation of Id3, known to cause antibody-mediated autoimmunity, greatly enhances T-FH-cell generation. Thus, Ascl2 directly initiates T-FH-cell development.
C1 [Liu, Xindong; Chen, Xin; Wang, Aibo; Wang, Xiaohu; Qi, Hai; Dong, Chen] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
[Liu, Xindong; Zhong, Bo; Wang, Aibo; Wang, Xiaohu; Nurieva, Roza I.; Dong, Chen] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77054 USA.
[Chu, Fuliang; Neelapu, Sattva S.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77054 USA.
[Yan, Xiaowei; Tian, Qiang] Inst Syst Biol, Seattle, WA 98103 USA.
[Chen, Ping] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[van der Flier, Laurens G.; Clevers, Hans] Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands.
[van der Flier, Laurens G.; Clevers, Hans] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
[Nakatsukasa, Hiroko; Chen, Wanjun] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
[Wei, Lai] Sun Yat Sen Univ, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China.
RP Dong, C (reprint author), Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
EM xindongliu@hotmail.com; cdonglab@hotmail.com
RI liu, xindong/F-8422-2014; dong, chen /B-3181-2009
OI dong, chen /0000-0002-0084-9130
FU National Institutes of Health (NIH) [AI106654]; NIDCR; NIH Lymphoma
SPORE; MD Anderson Cancer Center; Chinese Ministry of Science and
Technology '973' program [2014CB542501, 2012CB910402]; National Natural
Science Foundation of China [81361120397]
FX We thank J. A. Whitsett and J. P. Bridges at the University of
Cincinnati for their provision of Ascl2 conditional knockout mice, D. Yi
for help with ChIP-seq and microarray analysis, R. Dalla-Favera for
Bcl6-/- mice, H. Hu for histochemistry staining, and the Dong
laboratory members for their help. This work was supported in part by a
grant from the National Institutes of Health (NIH; AI106654 to C. D.),
an intramural research program (NIDCR to W. C. and H.N.), an NIH
Lymphoma SPORE (to X. L.), an Odyssey fellowship from the MD Anderson
Cancer Center (to X. L. and B.Z.), Chinese Ministry of Science and
Technology '973' program grants (2014CB542501 and 2012CB910402), and a
National Natural Science Foundation of China grant (81361120397 to
H.Q.).
NR 30
TC 86
Z9 93
U1 3
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 27
PY 2014
VL 507
IS 7493
BP 513
EP +
DI 10.1038/nature12910
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000044
PM 24463518
ER
PT J
AU Baker, JV
Hullsiek, KH
Singh, A
Wilson, E
Henry, K
Lichtenstein, K
Onen, N
Kojic, E
Patel, P
Brooks, JT
Hodis, HN
Budoff, M
Sereti, I
AF Baker, Jason V.
Hullsiek, Katherine Huppler
Singh, Amrit
Wilson, Eleanor
Henry, Keith
Lichtenstein, Ken
Onen, Nur
Kojic, Erna
Patel, Pragna
Brooks, John T.
Hodis, Howard N.
Budoff, Matt
Sereti, Irini
CA CDC SUN Study Investigators
TI Immunologic predictors of coronary artery calcium progression in a
contemporary HIV cohort
SO AIDS
LA English
DT Article
DE cardiovascular disease; coronary artery calcium; HIV; immune activation;
inflammation; monocyte activation
ID T-CELL-ACTIVATION; CARDIOVASCULAR-DISEASE EVENTS; ACUTE
MYOCARDIAL-INFARCTION; COMPUTED-TOMOGRAPHY; IMMUNE ACTIVATION; INFECTED
WOMEN; RISK-FACTORS; MICROBIAL TRANSLOCATION; ANTIRETROVIRAL DRUGS;
MONOCYTE ACTIVATION
AB Background:Identifying immunologic mechanisms that contribute to premature cardiovascular disease (CVD) among HIV-positive patients will inform prevention strategies.Methods:Coronary artery calcium (CAC) progression was studied in an HIV cohort. Immunophenotypes were measured on baseline cryopreserved peripheral blood mononuclear cells using multicolor flow cytometry. Logistic regression identified predictors of CAC progression after adjusting for traditional and HIV-related risk factors.Results:Baseline characteristics for the analysis cohort (n=436) were median age 42 years, median CD4(+) cell count 481cells/l, and 78% receiving antiretroviral therapy. Higher frequencies of CD16(+) monocytes were associated with greater likelihood of CAC progression, after adjusting for traditional and HIV risk factors [odds ratio per doubling was 1.66 for CD14(+)/CD16(+) (P=0.02), 1.36 for CD14(dim)/CD16(+) (P=0.06), and 1.69 for CD14(var)/CD16(+) (P=0.01)]. Associations for CD16(+) monocytes persisted when restricted to participants with viral suppression. We found no significant associations for CAC progression with other cellular phenotypes, including T-cell activation and senescence markers.Conclusion:Circulating CD16(+) monocytes, potentially reflecting a more pro-atherogenic subpopulation, independently predicted greater CAC progression among HIV-infected persons at low risk for AIDS. In contrast to T-cell abnormalities classically associated with AIDS-related disease progression, these data highlight the potential role of monocyte activation in HIV-related CVD risk.
C1 [Baker, Jason V.; Henry, Keith] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Baker, Jason V.; Henry, Keith] Univ Minnesota, Hennepin Cty Med Ctr, Div Infect Dis, Minneapolis, MN 55415 USA.
[Hullsiek, Katherine Huppler] Univ Minnesota, Div Biostat, Minneapolis, MN USA.
[Singh, Amrit; Wilson, Eleanor; Sereti, Irini] NIAID, NIH, Bethesda, MD 20892 USA.
[Lichtenstein, Ken] Natl Jewish Med & Res Ctr, Denver, CO USA.
[Onen, Nur] Washington Univ, Sch Med, St Louis, MO USA.
[Kojic, Erna] Miriam Hosp, Providence, RI 02906 USA.
[Patel, Pragna; Brooks, John T.] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA.
[Hodis, Howard N.] Univ So Calif, Atherosclerosis Res Unit, Los Angeles, CA USA.
[Budoff, Matt] Harbor UCLA, Los Angeles Biomed Res Inst, Los Angeles, CA USA.
RP Baker, JV (reprint author), 701 Pk Ave MC G5, Minneapolis, MN 55415 USA.
EM baker459@umn.edu
OI Wilson, Eleanor/0000-0002-4855-514X
FU Centers for Disease Control and Prevention [200-2002-00610,
200-2002-00611, 200-2002-00612, 200-2002-00613, 200-2007-23633,
200-2007-23634, 200-2007-23635,, 200-2007-23636]; NIH [1KL2RR033182-01];
NIAID
FX The study received financial support from Centers for Disease Control
and Prevention contract numbers 200-2002-00610, 200-2002-00611,
200-2002-00612, 200-2002-00613, 200-2007-23633, 200-2007-23634,
200-2007-23635, and 200-2007-23636. Additional support was provided by
the NIH 1KL2RR033182-01. The work of E.W., A.S., and I.S. was supported
by the intramural program of NIAID.
NR 52
TC 33
Z9 33
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD MAR 27
PY 2014
VL 28
IS 6
BP 831
EP 840
DI 10.1097/QAD.0000000000000145
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AD5MH
UT WOS:000333296600004
PM 24370480
ER
PT J
AU Solomon, MM
Lama, JR
Glidden, DV
Mulligan, K
McMahan, V
Liu, AY
Guanira, JV
Veloso, VG
Mayer, KH
Chariyalertsak, S
Schechter, M
Bekker, LG
Kallas, EG
Burns, DN
Grant, RM
AF Solomon, Marc M.
Lama, Javier R.
Glidden, David V.
Mulligan, Kathleen
McMahan, Vanessa
Liu, Albert Y.
Vicente Guanira, Juan
Veloso, Valdilea G.
Mayer, Kenneth H.
Chariyalertsak, Suwat
Schechter, Mauro
Bekker, Linda-Gail
Kallas, Esper Georges
Burns, David N.
Grant, Robert M.
CA IPrEx Study Team
TI Changes in renal function associated with oral emtricitabine/tenofovir
disoproxil fumarate use for HIV pre- exposure prophylaxis
SO AIDS
LA English
DT Article
DE chemoprophylaxis; HIV prevention; MSM; pre-exposure prophylaxis; renal;
side effects; tenofovir
ID GLOMERULAR-FILTRATION-RATE; CHRONIC HEPATITIS-B; ANTIRETROVIRAL-NAIVE
PATIENTS; TUBULAR DYSFUNCTION; INFECTED PATIENTS; TENOFOVIR DF;
PREEXPOSURE PROPHYLAXIS; SERUM CREATININE; KIDNEY-DISEASE; THERAPY
AB Objective:Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons.Design and methods:The Iniciativa Profilaxis Pre-Exposicion (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily TDF coformulated with emtricitabine (FTC/TDF) or placebo. Serum creatinine and phosphorus during randomized treatment and after discontinuation were measured, and creatinine clearance (CrCl) was estimated by the Cockcroft-Gault equation. Indicators of proximal renal tubulopathy (fractional excretion of phosphorus and uric acid, urine protein, and glucose) were measured in a substudy.Results:There was a small but statistically significant decrease in CrCl from baseline in the active arm, compared to placebo, which was first observed at week 4 (mean change: -2.4 vs. -1.1ml/min; P=0.02), persisted through the last on-treatment visit (mean change: +0.3 vs. +1.8ml/min; P=0.02), and resolved after stopping pre-exposure prophylaxis (mean change: -0.1 vs. 0.0ml/min; P=0.83). The effect was confirmed when stratifying by drug detection. The effect of FTC/TDF on CrCl did not vary by race, age, or history of hypertension. There was no difference in serum phosphate trends between the treatment arms. In the substudy, two participants receiving placebo had indicators of tubulopathy.Conclusions:In HIV-seronegative MSM, randomization to FTC/TDF was associated with a very mild nonprogressive decrease in CrCl that was reversible and managed with routine serum creatinine monitoring.
C1 [Solomon, Marc M.; McMahan, Vanessa; Grant, Robert M.] Gladstone Inst, San Francisco, CA USA.
[Solomon, Marc M.; Glidden, David V.; Mulligan, Kathleen; Liu, Albert Y.; Grant, Robert M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Liu, Albert Y.] San Francisco Dept Publ Hlth, Bridge HIV, San Francisco, CA USA.
[Vicente Guanira, Juan] Invest Med Salud, Lima, Peru.
[Lama, Javier R.] Asociac Civil Impacta Salud & Educ, Lima, Peru.
[Veloso, Valdilea G.] Fundacao Oswaldo Cruz, Inst Pesquisa Clin Evandro Chagas, Rio De Janeiro, Brazil.
[Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA.
[Chariyalertsak, Suwat] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand.
[Chariyalertsak, Suwat] Chiang Mai Univ, Fac Med, Dept Community Med, Chiang Mai 50000, Thailand.
[Schechter, Mauro] Univ Fed Rio de Janeiro, Hosp Escola Sao Francisco Assis, Projeto Praca Onze, Rio De Janeiro, Brazil.
[Bekker, Linda-Gail] Univ Cape Town, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa.
[Bekker, Linda-Gail] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa.
[Kallas, Esper Georges] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, BR-05403900 Sao Paulo, Brazil.
[Kallas, Esper Georges] Inst Invest Imunol, BR-05403900 Sao Paulo, Brazil.
[Burns, David N.] NIAID, Bethesda, MD 20892 USA.
RP Grant, RM (reprint author), 1650 Owens St, San Francisco, CA 94158 USA.
EM rgrant@gladstone.ucsf.edu
OI Guanira, Juan/0000-0002-2746-3086
FU Gilead; Division of Acquired Immunodeficiency Syndrome (DAIDS), National
Institute of Allergy and Infectious Diseases, National Institutes of
Health [UO1 AI64002]; Bill and Melinda Gates Foundation; DAIDS [RO1
AI062333]; J. David Gladstone Institutes; National Institutes of Health
[UL1 RR024131]
FX Source of funding: K. H. M. and M. S. have received research funding
from Gilead for unrelated research. For the remaining authors none were
declared.; The work was supported by the Division of Acquired
Immunodeficiency Syndrome (DAIDS), National Institute of Allergy and
Infectious Diseases, National Institutes of Health, as a cooperative
agreement (UO1 AI64002, to R. M. G.) and by the Bill and Melinda Gates
Foundation. Study drugs were donated by Gilead Sciences. Support for
some specimen handling came from a grant from DAIDS (RO1 AI062333, to R.
M. G.) and by the J. David Gladstone Institutes. Some infrastructure
support at the University of California at San Francisco was provided by
a grant from the National Institutes of Health (UL1 RR024131).
NR 38
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Z9 42
U1 1
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD MAR 27
PY 2014
VL 28
IS 6
BP 851
EP 859
DI 10.1097/QAD.0000000000000156
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AD5MH
UT WOS:000333296600006
PM 24499951
ER
PT J
AU Robbins, HA
Shiels, MS
Pfeiffer, RM
Engels, EA
AF Robbins, Hilary A.
Shiels, Meredith S.
Pfeiffer, Ruth M.
Engels, Eric A.
TI Epidemiologic contributions to recent cancer trends among HIV- infected
people in the United States
SO AIDS
LA English
DT Article
DE cancer; HIV; AIDS; statistical modeling; trends; United States
ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS;
LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; HODGKIN-LYMPHOMA; ANAL CANCER;
AIDS; RISK; MALIGNANCIES; METAANALYSIS
AB Objective:HIV-infected people have elevated risk for some cancers. Changing incidence of these cancers over time may reflect changes in three factors: HIV population demographic structure (e.g. age distribution), general population (background) cancer rates, and HIV-associated relative risks. We assessed the contributions of these factors to time trends for 10 cancers during 1996-2010.Design:Population-based registry linkage study.Methods:We applied Poisson models to data from the U.S. HIV/AIDS Cancer Match Study to estimate annual percentage changes (APCs) in incidence rates of AIDS-defining cancers [ADCs: Kaposi sarcoma, non-Hodgkin lymphoma (NHL), and cervical cancer] and seven non-AIDS-defining cancers (NADCs). We evaluated HIV-infected cancer trends with and without adjustment for demographics, trends in background rates, and trends in standardized incidence ratios (SIRs, to capture relative risk).Results:Cancer rates among HIV-infected people rose over time for anal (APC 3.8%), liver (8.5%), and prostate (9.8%) cancers, but declined for Kaposi sarcoma (1996-2000: -29.3%; 2000-2010: -7.8%), NHL (1996-2003: -15.7%; 2003-2010: -5.5%), cervical cancer (-11.1%), Hodgkin lymphoma (-4.0%), and lung cancer (-2.8%). Breast and colorectal cancer incidence did not change over time. Based on comparison to adjusted models, changing demographics contributed to trends for Kaposi sarcoma and breast, colorectal, liver, lung, and prostate cancers (all P<0.01). Trends in background rates were notable for liver (APC 5.6%) and lung (-3.2%) cancers. SIRs declined for ADCs, Hodgkin lymphoma (APC -3.2%), and lung cancer (-4.4%).Conclusion:Demographic shifts influenced several cancer trends among HIV-infected individuals. Falling relative risks largely explained ADC declines, while background incidence contributed to some NADC trends.
C1 [Robbins, Hilary A.; Shiels, Meredith S.; Pfeiffer, Ruth M.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Robbins, HA (reprint author), 9609 Med Ctr Dr,6-E228, Bethesda, MD 20892 USA.
EM hilary.robbins@nih.gov
FU SEER Program of the National Cancer Institute, Connecticut
[HHSN261201000024C]; SEER Program of the National Cancer Institute, New
Jersey [HHSN261201000027C, N01-PC-2010-0027]; National Program of Cancer
Registries of the Centers for Disease Control and Prevention, Colorado
[U58 DP000848-04]; National Program of Cancer Registries of the Centers
for Disease Control and Prevention, Georgia [5U58DP003875-01]; National
Program of Cancer Registries of the Centers for Disease Control and
Prevention, Michigan [5U58DP000812-03]; National Program of Cancer
Registries of the Centers for Disease Control and Prevention, New Jersey
[1US58/DP0039311-01]; National Program of Cancer Registries of the
Centers for Disease Control and Prevention, Texas [5U58DP000824-04];
state of New Jersey; National Cancer Institute, National Institutes of
Health
FX The following cancer registries were supported by the SEER Program of
the National Cancer Institute: Connecticut (HHSN261201000024C) and New
Jersey (HHSN261201000027C, N01-PC-2010-0027). The following cancer
registries were supported by the National Program of Cancer Registries
of the Centers for Disease Control and Prevention: Colorado (U58
DP000848-04), Georgia (5U58DP003875-01), Michigan (5U58DP000812-03), New
Jersey (1US58/DP0039311-01), and Texas (5U58DP000824-04). The New Jersey
Cancer Registry was also supported by the state of New Jersey.; This
research was supported, in part, by the Intramural Research Program of
the National Cancer Institute, National Institutes of Health.
NR 32
TC 46
Z9 48
U1 2
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD MAR 27
PY 2014
VL 28
IS 6
BP 881
EP 890
DI 10.1097/QAD.0000000000000163
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AD5MH
UT WOS:000333296600010
PM 24300545
ER
PT J
AU Bang, A
Bellad, R
Gisore, P
Hibberd, P
Patel, A
Goudar, S
Esamai, F
Goco, N
Meleth, S
Derman, RJ
Liechty, EA
McClure, E
Carlo, WA
Wright, LL
AF Bang, Akash
Bellad, Roopa
Gisore, Peter
Hibberd, Patricia
Patel, Archana
Goudar, Shivaprasad
Esamai, Fabian
Goco, Norman
Meleth, Sreelatha
Derman, Richard J.
Liechty, Edward A.
McClure, Elizabeth
Carlo, Waldemar A.
Wright, Linda L.
TI Implementation and evaluation of the Helping Babies Breathe curriculum
in three resource limited settings: does Helping Babies Breathe save
lives? A study protocol
SO BMC PREGNANCY AND CHILDBIRTH
LA English
DT Article
DE Neonatal mortality; Perinatal mortality; Asphyxia; Stillbirth; Helping
Babies Breathe; Resuscitation; Bag and mask ventilation; >= 1500 grams
ID NEONATAL RESUSCITATION; PERINATAL-MORTALITY; DEVELOPING-COUNTRY
AB Background: Neonatal deaths account for over 40% of all under-5 year deaths; their reduction is increasingly critical for achieving Millennium Development Goal 4. An estimated 3 million newborns die annually during their first month of life; half of these deaths occur during delivery or within 24 hours. Every year, 6 million babies require help to breathe immediately after birth. Resuscitation training to help babies breathe and prevent/manage birth asphyxia is not routine in low-middle income facility settings. Helping Babies Breathe (HBB), a simulation-training program for babies wherever they are born, was developed for use in low-middle income countries. We evaluated whether HBB training of facility birth attendants reduces perinatal mortality in the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Global Network research sites.
Methods/design: We hypothesize that a two-year prospective pre-post study to evaluate the impact of a facility-based training package, including HBB and essential newborn care, will reduce all perinatal mortality (fresh stillbirth or neonatal death prior to 7 days) among the Global Network's Maternal Neonatal Health Registry births >= 1500 grams in the study clusters served by the facilities. We will also evaluate the effectiveness of the HBB training program changing on facility-based perinatal mortality and resuscitation practices. Seventy-one health facilities serving 52 geographically-defined study clusters in Belgaum and Nagpur, India, and Eldoret, Kenya, and 30,000 women will be included. Primary outcome data will be collected by staff not involved in the HBB intervention. Additional data on resuscitations, resuscitation debriefings, death audits, quality monitoring and improvement will be collected. HBB training will include training of MTs, facility level birth attendants, and quality monitoring and improvement activities.
Discussion: Our study will evaluate the effect of a HBB/ENC training and quality monitoring and improvement package on perinatal mortality using a large multicenter design and approach in 71 resource-limited health facilities, leveraging an existing birth registry to provide neonatal outcomes through day 7. The study will provide the evidence base, lessons learned, and best practices that will be essential to guiding future policy and investment in neonatal resuscitation.
C1 [Bang, Akash] Mahatma Gandhi Inst Med Sci, Sevagram, India.
[Bellad, Roopa; Goudar, Shivaprasad] KLEs Jawaharlal Nehru Med Coll, Belgaum, India.
[Gisore, Peter; Esamai, Fabian] Moi Univ, Eldoret, Kenya.
[Hibberd, Patricia] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Goco, Norman; Meleth, Sreelatha; McClure, Elizabeth] RTI Int, Durham, NC USA.
[Derman, Richard J.] Christiana Care, Newark, DE USA.
[Liechty, Edward A.] Indiana Univ, Indianapolis, IN 46204 USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Bang, A (reprint author), Mahatma Gandhi Inst Med Sci, Sevagram, India.
EM drakashbang@gmail.com
OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053
FU Laerdal Foundation; Norad; NICHD [U01 HD040636, U01 HD058322, U01
HD042372, U01 HD058326]
FX We thank the Scientific Advisory Board members, Alan H Jobe, MD, PhD;
William J Keenan, MD and Petter Andreas Steen, MD for their oversight
and guidance. This study was funded with grants from the Laerdal
Foundation, Norad, and the NICHD (grant numbers U01 HD040636; U01
HD058322; U01 HD042372; U01 HD058326).
NR 18
TC 18
Z9 18
U1 2
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2393
J9 BMC PREGNANCY CHILDB
JI BMC Pregnancy Childbirth
PD MAR 26
PY 2014
VL 14
AR 116
DI 10.1186/1471-2393-14-116
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AF8CK
UT WOS:000334942700001
PM 24670013
ER
PT J
AU Moutsopoulos, NM
Konkel, J
Sarmadi, M
Eskan, MA
Wild, T
Dutzan, N
Abusleme, L
Zenobia, C
Hosur, KB
Abe, T
Uzel, G
Chen, WJ
Chavakis, T
Holland, SM
Hajishengallis, G
AF Moutsopoulos, Niki M.
Konkel, Joanne
Sarmadi, Mojgan
Eskan, Mehmet A.
Wild, Teresa
Dutzan, Nicolas
Abusleme, Loreto
Zenobia, Camille
Hosur, Kavita B.
Abe, Toshiharu
Uzel, Gulbu
Chen, WanJun
Chavakis, Triantafyllos
Holland, Steven M.
Hajishengallis, George
TI Defective Neutrophil Recruitment in Leukocyte Adhesion Deficiency Type I
Disease Causes Local IL-17-Driven Inflammatory Bone Loss
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID PERIODONTAL-DISEASE; TISSUE HOMEOSTASIS; T-CELLS; LFA-1; MIGRATION;
HEALTH; MAC-1; VLA-4; IL-17; MANIFESTATIONS
AB Leukocyte adhesion deficiency type I (LAD-I), a disease syndrome associated with frequent microbial infections, is caused by mutations on the CD18 subunit of beta(2) integrins. LAD-I is invariably associated with severe periodontal bone loss, which historically has been attributed to the lack of neutrophil surveillance of the periodontal infection. We provide an alternative mechanism by showing that the cytokine interleukin-17 (IL-17) plays a major role in the oral pathology of LAD-I. Defective neutrophil recruitment in LAD-I patients or in LFA-1 (CD11a/CD18)-deficient mice-which exhibit the LAD-I periodontal phenotype-was associated with excessive production of predominantly T cell-derived IL-17 in the periodontal tissue, although innate lymphoid cells also contributed to pathological IL-17 elevation in the LFA-1-deficient mice. Local treatment with antibodies to IL-17 or IL-23 in LFA-1-deficient mice not only blocked inflammatory periodontal bone loss but also caused a reduction in the total bacterial burden, suggesting that the IL-17-driven pathogenesis of LAD-I periodontitis leads to dysbiosis. Therefore, our findings support an IL-17-targeted therapy for periodontitis in LAD-I patients.
C1 [Moutsopoulos, Niki M.; Sarmadi, Mojgan; Wild, Teresa; Dutzan, Nicolas; Abusleme, Loreto] Natl Inst Dent & Craniofacial Res, Oral Immun & Infect Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Konkel, Joanne; Chen, WanJun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Eskan, Mehmet A.] Univ Louisville, Sch Dent, Oral Hlth & System Dis Res Grp, Louisville, KY 40202 USA.
[Zenobia, Camille; Hosur, Kavita B.; Abe, Toshiharu; Hajishengallis, George] Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA.
[Uzel, Gulbu; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Chavakis, Triantafyllos] Tech Univ Dresden, Dept Med, Dept Clin Pathobiochem, D-01307 Dresden, Germany.
[Chavakis, Triantafyllos] Tech Univ Dresden, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany.
RP Moutsopoulos, NM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Immun & Infect Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
EM nmoutsop@mail.nih.gov; geoh@upenn.edu
FU NIH, National Institute of Dental and Craniofacial Research (NIDCR);
Deutsche Forschungsgemeinschaft [CH279/5-1]; European Research Council;
U.S. Public Health Service from the NIH/NIDCR [DE015254, DE017138,
DE021685]; NIH, National Institute of Allergy and Infectious Diseases
FX Funding: Supported in part by the Intramural Research Program of the
NIH, National Institute of Dental and Craniofacial Research (NIDCR) and
National Institute of Allergy and Infectious Diseases, the Deutsche
Forschungsgemeinschaft (CH279/5-1), and the European Research Council
(to T. C.), and U.S. Public Health Service grants DE015254, DE017138,
and DE021685 from the NIH/NIDCR (to G.H.).
NR 54
TC 16
Z9 18
U1 2
U2 12
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 26
PY 2014
VL 6
IS 229
AR 229ra40
DI 10.1126/scitranslmed.3007696
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AE3UR
UT WOS:000333904300003
PM 24670684
ER
PT J
AU Boye, SE
Huang, WC
Roman, AJ
Sumaroka, A
Boye, SL
Ryals, RC
Olivares, MB
Ruan, Q
Tucker, BA
Stone, EM
Swaroop, A
Cideciyan, AV
Hauswirth, WW
Jacobson, SG
AF Boye, Shannon E.
Huang, Wei-Chieh
Roman, Alejandro J.
Sumaroka, Alexander
Boye, Sanford L.
Ryals, Renee C.
Olivares, Melani B.
Ruan, Qing
Tucker, Budd A.
Stone, Edwin M.
Swaroop, Anand
Cideciyan, Artur V.
Hauswirth, William W.
Jacobson, Samuel G.
TI Natural History of Cone Disease in the Murine Model of Leber Congenital
Amaurosis Due to CEP290 Mutation: Determining the Timing and Expectation
of Therapy
SO PLOS ONE
LA English
DT Article
ID ADENOASSOCIATED VIRAL VECTORS; HUMAN GENE-THERAPY; CAUSES RETINAL
DEGENERATION; RHODOPSIN KINASE PROMOTER; LENTIVIRAL VECTOR; MOUSE MODEL;
SUBRETINAL INJECTION; STARGARDT DISEASE; MAMMALIAN RETINA; RPE65
MUTATIONS
AB Background: Mutations in the CEP290 (cilia-centrosomal protein 290 kDa) gene in Leber congenital amaurosis (LCA) cause early onset visual loss but retained cone photoreceptors in the fovea, which is the potential therapeutic target. A cone-only mouse model carrying a Cep290 gene mutation, rd16;Nrl(-/-), was engineered to mimic the human disease. In the current study, we determined the natural history of retinal structure and function in this murine model to permit design of preclinical proof-of-concept studies and allow progress to be made toward human therapy. Analyses of retinal structure and visual function in CEP290-LCA patients were also performed for comparison with the results in the model.
Methods: Rd16;Nrl(-/-) mice were studied in the first 90 days of life with optical coherence tomography (OCT), electroretinography (ERG), retinal histopathology and immunocytochemistry. Structure and function data from a cohort of patients with CEP290-LCA (n = 15; ages 7-48) were compared with those of the model.
Results: CEP290-LCA patients retain a central island of photoreceptors with normal thickness at the fovea (despite severe visual loss); the extent of this island declined slowly with age. The rd16; Nrl(-/-) model also showed a relatively slow photoreceptor layer decline in thickness with similar to 80% remaining at 3 months. The number of pseudorosettes also became reduced. By comparison to single mutant Nrl(-/-) mice, UV- and M-cone ERGs of rd16; Nrl(-/-) were at least 1 log unit reduced at 1 month of age and declined further over the 3 months of monitoring. Expression of GNAT2 and S-opsin also decreased with age.
Conclusions: The natural history of early loss of photoreceptor function with retained cone cell nuclei is common to both CEP290-LCA patients and the rd16; Nrl(-/-) murine model. Pre-clinical proof-of-concept studies for uniocular therapies would seem most appropriate to begin with intervention at P35-40 and re-study after one month by assaying interocular difference in the UV-cone ERG.
C1 [Boye, Shannon E.; Boye, Sanford L.; Ryals, Renee C.; Ruan, Qing; Hauswirth, William W.] Univ Florida, Coll Med, Dept Ophthalmol, Gainesville, FL 32610 USA.
[Huang, Wei-Chieh; Roman, Alejandro J.; Sumaroka, Alexander; Olivares, Melani B.; Cideciyan, Artur V.; Jacobson, Samuel G.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Tucker, Budd A.; Stone, Edwin M.] Univ Iowa, Carver Coll Med, Stephen A Wynn Inst Vis Res, Iowa City, IA USA.
[Stone, Edwin M.] Univ Iowa, Howard Hughes Med Inst, Carver Coll Med, Iowa City, IA 52242 USA.
[Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
RP Boye, SE (reprint author), Univ Florida, Coll Med, Dept Ophthalmol, Gainesville, FL 32610 USA.
EM shaire@ufl.edu; jacobsos@mail.med.upenn.edu
OI Swaroop, Anand/0000-0002-1975-1141; Tucker, Budd/0000-0003-2178-1742
FU Grousbeck Foundation; NEI intramural research program; Foundation
Fighting Blindness; Macula Vision Research Foundation; Hope for Vision
FX This study was supported by grants from the Grousbeck Foundation, The
Foundation Fighting Blindness, Macula Vision Research Foundation, Hope
for Vision, and the NEI intramural research program. AVC is a RPB
(Research to Prevent Blindness) Senior Scientific Investigator. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 68
TC 5
Z9 5
U1 2
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 26
PY 2014
VL 9
IS 3
AR e92928
DI 10.1371/journal.pone.0092928
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SR
UT WOS:000333677000093
PM 24671090
ER
PT J
AU Dulebohn, DP
Hayes, BM
Rosa, PA
AF Dulebohn, Daniel P.
Hayes, Beth M.
Rosa, Patricia A.
TI Global Repression of Host-Associated Genes of the Lyme Disease
Spirochete through Post-Transcriptional Modulation of the Alternative
Sigma Factor RpoS
SO PLOS ONE
LA English
DT Article
ID OUTER-SURFACE PROTEIN; BORRELIA-BURGDORFERI OSPC; ESCHERICHIA-COLI;
STRESS-RESPONSE; REGULATORY PATHWAY; MAMMALIAN HOST; IMMUNE EVASION;
MESSENGER-RNA; FACTOR RSSB; LIFE-CYCLE
AB Borrelia burgdorferi, the agent of Lyme disease, is a vector-borne pathogen that transits between Ixodes ticks and vertebrate hosts. During the natural infectious cycle, spirochetes must globally adjust their transcriptome to survive in these dissimilar environments. One way B. burgdorferi accomplishes this is through the use of alternative sigma factors to direct transcription of specific genes. RpoS, one of only three sigma factors in B. burgdorferi, controls expression of genes required during tick-transmission and infection of the mammalian host. How spirochetes switch between different sigma factors during the infectious cycle has remained elusive. Here we establish a role for a novel protein, BBD18, in the regulation of the virulence-associated sigma factor RpoS. Constitutive expression of BBD18 repressed transcription of RpoS-dependent genes to levels equivalent to those observed in an rpoS mutant. Consistent with the global loss of RpoS-dependent transcripts, we were unable to detect RpoS protein. However, constitutive expression of BBD18 did not diminish the amount of rpoS transcript, indicating post-transcriptional regulation of RpoS by BBD18. Interestingly, BBD18-mediated repression of RpoS is independent of both the rpoS promoter and the 5' untranslated region, suggesting a mechanism of protein destabilization rather than translational control. We propose that BBD18 is a novel regulator of RpoS and its activity likely represents a first step in the transition from an RpoS-ON to an RpoS-OFF state, when spirochetes transition from the host to the tick vector.
C1 [Dulebohn, Daniel P.; Hayes, Beth M.; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, Div Intramural Res,NIH, Hamilton, MT USA.
RP Dulebohn, DP (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, Div Intramural Res,NIH, Hamilton, MT USA.
EM dulebohnd@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH),
National Institute of Allergy and Infectious Diseases (NIAID)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Institute of Allergy and
Infectious Diseases (NIAID). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 104
TC 10
Z9 10
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 26
PY 2014
VL 9
IS 3
AR e93141
DI 10.1371/journal.pone.0093141
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SR
UT WOS:000333677000118
PM 24671196
ER
PT J
AU Nettiksimmons, J
Simonsick, EM
Harris, T
Satterfield, S
Rosano, C
Yaffe, K
AF Nettiksimmons, Jasmine
Simonsick, Eleanor M.
Harris, Tamara
Satterfield, Suzanne
Rosano, Caterina
Yaffe, Kristine
CA Hlth ABC Study
TI The Associations between Serum Brain-Derived Neurotrophic Factor,
Potential Confounders, and Cognitive Decline: A Longitudinal Study
SO PLOS ONE
LA English
DT Article
ID BDNF MESSENGER-RNA; ALZHEIMERS-DISEASE; CARDIORESPIRATORY FITNESS;
DECREASED-LEVELS; BLOOD-BRAIN; IMPAIRMENT; DEPRESSION; SURVIVAL;
NEURONS; MEN
AB Brain-derived neurotrophic factor (BDNF) plays a role in the maintenance and function of neurons. Although persons with Alzheimer's disease have lower cortical levels of BDNF, evidence regarding the association between circulating BDNF and cognitive function is conflicting. We sought to determine the correlates of BDNF level and whether BDNF level was prospectively associated with cognitive decline in healthy older adults. We measured serum BDNF near baseline in 912 individuals. Cognitive status was assessed repeatedly with the modified Mini-Mental Status Examination and the Digit Symbol Substitution test over the next 10 years. We evaluated the association between BDNF and cognitive decline with longitudinal models. We also assessed the association between BDNF level and demographics, comorbidities and health behaviors. We found an association between serum BDNF and several characteristics that are also associated with dementia (race and depression), suggesting that future studies should control for these potential confounders. We did not find evidence of a longitudinal association between serum BDNF and subsequent cognitive test trajectories in older adults, although we did identify a potential trend toward a cross-sectional association. Our results suggest that serum BDNF may have limited utility as a biomarker of prospective cognitive decline.
C1 [Nettiksimmons, Jasmine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Harris, Tamara] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Rosano, Caterina] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
RP Nettiksimmons, J (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
EM Jasmine.nettiksimmons@ucsf.edu
OI Rosano, Caterina/0000-0002-0909-1506; Rosano,
Caterina/0000-0002-4271-6010
FU NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; NINR
[R01-NR012459]; Intramural Research Program of the NIH, National
Institute of Aging; American Health Assistance Foundation [A201-0029];
National Institute of Aging [K24AG031155]
FX This research was supported by the following: NIA contract numbers:
N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant numbers:
R01-AG028050, NINR grant R01-NR012459. This research was supported in
part by the Intramural Research Program of the NIH, National Institute
of Aging and by a grant from the American Health Assistance Foundation,
grant number A201-0029. Dr. Yaffe is supported in part by a National
Institute of Aging Grant (K24AG031155). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 35
TC 16
Z9 17
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 26
PY 2014
VL 9
IS 3
AR e91339
DI 10.1371/journal.pone.0091339
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SR
UT WOS:000333677000018
PM 24670553
ER
PT J
AU Varma, S
Pommier, Y
Sunshine, M
Weinstein, JN
Reinhold, WC
AF Varma, Sudhir
Pommier, Yves
Sunshine, Margot
Weinstein, John N.
Reinhold, William C.
TI High Resolution Copy Number Variation Data in the NCI-60 Cancer Cell
Lines from Whole Genome Microarrays Accessible through CellMiner
SO PLOS ONE
LA English
DT Article
ID HUMAN BREAST-TUMORS; DRUG-SENSITIVITY; MULTIDRUG-RESISTANCE; EXPRESSION
PROFILES; GENE-EXPRESSION; MESSENGER-RNA; ARRAY-CGH; PANEL;
MALIGNANCIES; PHARMACOLOGY
AB Array-based comparative genomic hybridization (aCGH) is a powerful technique for detecting gene copy number variation. It is generally considered to be robust and convenient since it measures DNA rather than RNA. In the current study, we combine copy number estimates from four different platforms Agilent 44 K, NimbleGen 385 K, Affymetrix 500 K and Illumina Human1Mv1_C) to compute a reliable, high-resolution, easy to understand output for the measure of copy number changes in the 60 cancer cells of the NCI-DTP (the NCI-60). We then relate the results to gene expression. We explain how to access that database using our CellMiner web-tool and provide an example of the ease of comparison with transcript expression, whole exome sequencing, rnicroRNA expression and response to 20,000 drugs and other chemical compounds. We then demonstrate how the data can be analyzed integratively with transcript expression data for the whole genome (26,065 genes). Comparison of copy number and expression levels shows an overall medium high correlation (median r=0.247), with significantly higher correlations (median r=0.408) for the known tumor suppressor genes. That observation is consistent with the hypothesis that gene loss IS an important mechanism for tumor suppressor inactivation. An integrated analysis of concurrent DNA copy number and gene expression change is presented. Limiting attention to focal DNA gains or losses we identify and reveal novel candidate tumor suppressors With matching alterations in transcript level.
C1 [Varma, Sudhir; Pommier, Yves; Sunshine, Margot; Reinhold, William C.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Varma, Sudhir] HiThru Analyt Inc, Laurel, MD USA.
[Sunshine, Margot] Syst Res & Applicat Corp, Fairfax, VA USA.
[Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat, Houston, TX 77030 USA.
[Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Computat Biol, Houston, TX 77030 USA.
[Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM pommier@nih.gov; wcr@mail.nih.gov
RI Varma, Sudhir/N-8763-2014
OI Varma, Sudhir/0000-0002-4096-4782
FU Center for Cancer Research, Intramural Program of the National Cancer
Institute
FX This work was supported by the Center for Cancer Research, Intramural
Program of the National Cancer Institute. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 42
TC 10
Z9 10
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 26
PY 2014
VL 9
IS 3
AR e92047
DI 10.1371/journal.pone.0092047
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SR
UT WOS:000333677000031
PM 24670534
ER
PT J
AU Sengupta, P
van Engelenburg, SB
Lippincott-Schwartz, J
AF Sengupta, Prabuddha
van Engelenburg, Schuyler B.
Lippincott-Schwartz, Jennifer
TI Superresolution Imaging of Biological Systems Using Photoactivated
Localization Microscopy
SO CHEMICAL REVIEWS
LA English
DT Review
ID SINGLE-MOLECULE LOCALIZATION; PAIR-CORRELATION-ANALYSIS;
PHOTOCONVERTIBLE FLUORESCENT PROTEIN; STRUCTURED-ILLUMINATION
MICROSCOPY; GENETICALLY EXPRESSED PROBES; HIGH-DENSITY LOCALIZATION;
3-DIMENSIONAL SUPERRESOLUTION; QUANTITATIVE-ANALYSIS;
SPATIAL-ORGANIZATION; RESOLUTION LIMIT
C1 [Sengupta, Prabuddha; van Engelenburg, Schuyler B.; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Lippincott-Schwartz, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM lippincj@mail.nih.gov
OI Sengupta, Prabuddha/0000-0001-7094-6967
FU Intramural NIH HHS [Z99 HD999999, ZIA HD008850-07]
NR 91
TC 30
Z9 32
U1 5
U2 73
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
EI 1520-6890
J9 CHEM REV
JI Chem. Rev.
PD MAR 26
PY 2014
VL 114
IS 6
SI SI
BP 3189
EP 3202
DI 10.1021/cr400614m
PG 14
WC Chemistry, Multidisciplinary
SC Chemistry
GA AD8YQ
UT WOS:000333552000005
PM 24417572
ER
PT J
AU Millum, J
Wendler, D
Emanuel, EJ
AF Millum, Joseph
Wendler, David
Emanuel, Ezekiel J.
TI Declaration of Helsinki and Protection for Vulnerable Research
Participants Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Millum, Joseph; Wendler, David] NIH, Bethesda, MD 20892 USA.
[Emanuel, Ezekiel J.] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA.
RP Emanuel, EJ (reprint author), Univ Penn, 122 Coll Hall, Philadelphia, PA 19104 USA.
EM vp-global@upenn.edu
NR 2
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 26
PY 2014
VL 311
IS 12
BP 1252
EP 1253
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD6CE
UT WOS:000333340500036
PM 24668114
ER
PT J
AU Tapocik, JD
Barbier, E
Flanigan, M
Solomon, M
Pincus, A
Pilling, A
Sun, H
Schank, JR
King, C
Heilig, M
AF Tapocik, Jenica D.
Barbier, Estelle
Flanigan, Meghan
Solomon, Matthew
Pincus, Alexandra
Pilling, Andrew
Sun, Hui
Schank, Jesse R.
King, Courtney
Heilig, Markus
TI microRNA-206 in Rat Medial Prefrontal Cortex Regulates BDNF Expression
and Alcohol Drinking
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE addiction; alcohol dependence; BDNF; medial prefrontal cortex; microRNA;
self-administration
ID LONG-TERM POTENTIATION; NEUROTROPHIC FACTOR; UP-REGULATION;
ETHANOL-CONSUMPTION; ADULT HIPPOCAMPUS; NUCLEUS-ACCUMBENS; COCAINE
SEEKING; GENE-EXPRESSION; DENTATE GYRUS; IN-VIVO
AB Escalation of voluntary alcohol consumption is a hallmark of alcoholism, but its neural substrates remain unknown. In rats, escalation occurs following prolonged exposure to cycles of alcohol intoxication, and is associated with persistent, wide-ranging changes in gene expression within the medial prefrontal cortex (mPFC). Here, we examined whether induction of microRNA (miR) 206 in mPFC contributes to escalated alcohol consumption. Following up on a microarray screen, quantitative real-time reverse transcription PCR (qPCR) confirmed that a history of dependence results in persistent (> 3weeks) up-regulation of miR-206 expression in the mPFC, but not in the ventral tegmental area, amygdala, or nucleus accumbens. Viral-mediated overexpression of miR-206 in the mPFC of nondependent rats reproduced the escalation of alcohol self-administration seen following a history of dependence and significantly inhibited BDNF expression. Bioinformatic analysis identified three conserved target sites for miR-206 in the 3 ' -UTR of the rat BDNF transcript. Accordingly, BDNF was downregulated in post-dependent rats on microarray analysis, and this was confirmed by qPCR. In vitro, BDNF expression was repressed by miR-206 but not miR-9 in a 3 ' -UTR reporter assay, confirming BDNF as a functional target of miR-206. Mutation analysis showed that repression was dependent on the presence of all three miR-206 target sites in the BDNF 3 ' -UTR. Inhibition of miR-206 expression in differentiated rat cortical primary neurons significantly increased secreted levels of BDNF. In conclusion, recruitment of miR-206 in the mPFC contributes to escalated alcohol consumption following a history of dependence, with BDNF as a possible mediator of its action.
C1 [Tapocik, Jenica D.; Barbier, Estelle; Flanigan, Meghan; Solomon, Matthew; Pincus, Alexandra; Pilling, Andrew; Sun, Hui; Schank, Jesse R.; King, Courtney; Heilig, Markus] NIAAA, LCTS, NIH, Bethesda, MD 20892 USA.
RP Tapocik, JD (reprint author), NIAAA, LCTS, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM tapocikjd@mail.nih.gov
OI Flanigan, Meghan/0000-0002-3185-7459
NR 45
TC 37
Z9 42
U1 0
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 26
PY 2014
VL 34
IS 13
BP 4581
EP 4588
DI 10.1523/JNEUROSCI.0445-14.2014
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA AE0RP
UT WOS:000333674200014
PM 24672003
ER
PT J
AU Fukushima, M
Saunders, RC
Leopold, DA
Mishkin, M
Averbeck, BB
AF Fukushima, Makoto
Saunders, Richard C.
Leopold, David A.
Mishkin, Mortimer
Averbeck, Bruno B.
TI Differential Coding of Conspecific Vocalizations in the Ventral Auditory
Cortical Stream
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE auditory cortex; ECoG; evoked potential; LFP; monkey; multielectrode
ID HUMAN BRAIN ACTIVITY; PREFRONTAL CORTEX; FACIAL EXPRESSIONS; MACAQUE
MONKEY; MACACA-MULATTA; RHESUS-MONKEYS; NATURAL IMAGES; VISUAL-CORTEX;
HUMAN SPEECH; REPRESENTATION
AB The mammalian auditory cortex integrates spectral and temporal acoustic features to support the perception of complex sounds, including conspecific vocalizations. Here we investigate coding of vocal stimuli in different subfields in macaque auditory cortex. We simultaneously measured auditory evoked potentials over a large swath of primary and higher order auditory cortex along the supratemporal plane in three animals chronically using high-density microelectrocorticographic arrays. To evaluate the capacity of neural activity to discriminate individual stimuli in these high-dimensional datasets, we applied a regularized multivariate classifier to evoked potentials to conspecific vocalizations. We found a gradual decrease in the level of overall classification performance along the caudal to rostral axis. Furthermore, the performance in the caudal sectors was similar across individual stimuli, whereas the performance in the rostral sectors significantly differed for different stimuli. Moreover, the information about vocalizations in the caudal sectors was similar to the information about synthetic stimuli that contained only the spectral or temporal features of the original vocalizations. In the rostral sectors, however, the classification for vocalizations was significantly better than that for the synthetic stimuli, suggesting that conjoined spectral and temporal features were necessary to explain differential coding of vocalizations in the rostral areas. We also found that this coding in the rostral sector was carried primarily in the theta frequency band of the response. These findings illustrate a progression in neural coding of conspecific vocalizations along the ventral auditory pathway.
C1 [Fukushima, Makoto; Saunders, Richard C.; Leopold, David A.; Mishkin, Mortimer; Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Fukushima, M (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,49 Convent Dr, Bethesda, MD 20892 USA.
EM makoto_fukushima@me.com
OI Fukushima, Makoto/0000-0002-8809-7892; Leopold,
David/0000-0002-1345-6360
FU Intramural Research Program of the National Institute of Mental Health;
National Institutes of Health; Department of Health and Human Services
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health, and
Department of Health and Human Services. We thank K. King for audiologic
evaluation of the monkeys' peripheral hearing, and M. Mullarkey, R.
Reoli, and D. Rickrode for technical assistance. This study utilized the
high-performance computational capabilities of the Helix Systems
(http://helix.nih.gov) and the Biowulf Linux cluster
(http://biowulf.nih.gov) at the National Institutes of Health, Bethesda,
MD.
NR 54
TC 15
Z9 15
U1 0
U2 11
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 26
PY 2014
VL 34
IS 13
BP 4665
EP 4676
DI 10.1523/JNEUROSCI.3969-13.2014
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA AE0RP
UT WOS:000333674200023
PM 24672012
ER
PT J
AU Boucetta, S
Cisse, Y
Mainville, L
Morales, M
Jones, BE
AF Boucetta, Soufiane
Cisse, Youssouf
Mainville, Lynda
Morales, Marisela
Jones, Barbara E.
TI Discharge Profiles across the Sleep-Waking Cycle of Identified
Cholinergic, GABAergic, and Glutamatergic Neurons in the
Pontomesencephalic Tegmentum of the Rat
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE EEG; EMG; paradoxical sleep; REM sleep; slow-wave sleep
ID PONTINE RETICULAR-FORMATION; BASAL FOREBRAIN NEURONS; FREELY MOVING
CATS; C-FOS EXPRESSION; REM-SLEEP; PARADOXICAL SLEEP; CELL AREA;
PEDUNCULOPONTINE NUCLEUS; MESOPONTINE TEGMENTUM; PROJECTING NEURONS
AB Distributed within the laterodorsal tegmental and pedunculopontine tegmental nuclei (LDT and PPT), cholinergic neurons in the pontomesencephalic tegmentum have long been thought to play a critical role in stimulating cortical activation during waking (W) and paradoxical sleep (PS, also called REM sleep), yet also in promoting PS with muscle atonia. However, the discharge profile and thus precise roles of the cholinergic neurons have remained uncertain because they lie intermingled with GABAergic and glutamatergic neurons, which might also assume these roles. By applying juxtacellular recording and labeling in naturally sleeping-waking, head-fixed rats, we investigated the discharge profiles of histochemically identified cholinergic, GABAergic, and glutamatergic neurons in the LDT, SubLDT, and adjoining medial part of the PPT (MPPT) in relation to sleep-wake states, cortical activity, and muscle tone. We found that all cholinergic neurons were maximally active duringWand PS in positive correlation with fast (gamma) cortical activity, as "W/PS-max active neurons." Like cholinergic neurons, many GABAergic and glutamatergic neurons were also "W/PS-max active." Other GABAergic and glutamatergic neurons were "PS-max active," being minimally active duringWand maximally active during PS in negative correlation with muscle tone. Conversely, some glutamatergic neurons were "W-max active," being maximally active duringWand minimally active during PS in positive correlation with muscle tone. Through different discharge profiles, the cholinergic, GABAergic, and glutamatergic neurons of the LDT, SubLDT, andMPPTthus appear to play distinct roles in promotingWand PS with cortical activation, PS with muscle atonia, orWwith muscle tone.
C1 [Boucetta, Soufiane; Cisse, Youssouf; Mainville, Lynda; Jones, Barbara E.] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada.
[Morales, Marisela] NIDA, Neuronal Networks Sect, NIH, Baltimore, MD 21224 USA.
RP Jones, BE (reprint author), McGill Univ, Montreal Neurol Inst, 3801 Univ St, Montreal, PQ H3A 2B4, Canada.
EM barbara.jones@mcgill.ca
RI Jones, Barbara/A-8033-2017
FU Canadian Institutes of Health Research Grant [CIHR MOP-13458]; National
Institutes of Health Grant [NIH R01 MH-60119-01A]; Intramural Research
Program of the National Institute on Drug Abuse
FX This work was supported by the Canadian Institutes of Health Research
Grant CIHR MOP-13458 to B.E.J., the National Institutes of Health Grant
NIH R01 MH-60119-01A to B.E.J., and the Intramural Research Program of
the National Institute on Drug Abuse to M.M. We thank Oum Kaltoum
Hassani (Montreal) for assistance with electrophysiological recordings
and advice and Liu Bing (Baltimore) for assistance with histochemical
processing.
NR 68
TC 47
Z9 47
U1 1
U2 9
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 26
PY 2014
VL 34
IS 13
BP 4708
EP 4727
DI 10.1523/JNEUROSCI.2617-13.2014
PG 20
WC Neurosciences
SC Neurosciences & Neurology
GA AE0RP
UT WOS:000333674200027
PM 24672016
ER
PT J
AU Zhu, R
Lu, XP
Pradhan, M
Armstrong, SP
Storchan, GB
Chow, CC
Simons, SS
AF Zhu, Rong
Lu, Xinping
Pradhan, Madhumita
Armstrong, Stephen P.
Storchan, Geoffrey B.
Chow, Carson C.
Simons, S. Stoney, Jr.
TI A Kinase-Independent Activity of Cdk9 Modulates Glucocorticoid
Receptor-Mediated Gene Induction
SO BIOCHEMISTRY
LA English
DT Article
ID RNA-POLYMERASE-II; SERINE 81 PHOSPHORYLATION; ELONGATION-FACTOR ELL;
DOSE-RESPONSE CURVES; P-TEFB KINASE; TRANSCRIPTION ELONGATION; IN-VIVO;
CHROMATIN ACCESSIBILITY; PRODUCTIVE ELONGATION; MYB GENE
AB A gene induction competition assay has recently uncovered new inhibitory activities of two transcriptional cofactors, NELF-A and NELF-B, in glucocorticoid-regulated transactivation. NELF-A and -B are also components of the NELF complex, which participates in RNA polymerase II pausing shortly after the initiation of gene transcription. We therefore asked if cofactors (Cdk9 and ELL) best known to affect paused polymerase could reverse the effects of NELF-A and -B. Unexpectedly, Cdk9 and ELL augmented, rather than prevented, the effects of NELF-A and -B. Furthermore, Cdk9 actions are not blocked either by Ckd9 inhibitors (DRB or flavopiridol) or by two Cdk9 mutants defective in kinase activity. The mode and site of action of NELF-A and -B mutants with an altered NELF domain are similarly affected by wild-type and kinase-dead Cdk9. We conclude that Cdk9 is a new modulator of GR action, that Ckd9 and ELL have novel activities in GR-regulated gene expression, that NELF-A and -B can act separately from the NELF complex, and that Cdk9 possesses activities that are independent of Cdk9 kinase activity. Finally, the competition assay has succeeded in ordering the site of action of several cofactors of GR transactivation. Extension of this methodology should be helpful in determining the site and mode of action of numerous additional cofactors and in reducing unwanted side effects.
C1 [Zhu, Rong; Lu, Xinping; Pradhan, Madhumita; Armstrong, Stephen P.; Storchan, Geoffrey B.; Simons, S. Stoney, Jr.] NIDDK, Steroid Hormones Sect, Lab Endocrinol & Receptor Biol, Bethesda, MD 20892 USA.
[Chow, Carson C.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Simons, SS (reprint author), NIDDK, LERB, NIH, Bldg 10,Room 8N-307B, Bethesda, MD 20892 USA.
EM stoneys@helix.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.
NR 59
TC 6
Z9 6
U1 1
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 25
PY 2014
VL 53
IS 11
BP 1753
EP 1767
DI 10.1021/bi5000178
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD8TR
UT WOS:000333539100005
PM 24559102
ER
PT J
AU Oertell, K
Chamberlain, BT
Wu, Y
Ferri, E
Kashemirov, BA
Beard, WA
Wilson, SH
McKenna, CE
Goodman, MF
AF Oertell, Keriann
Chamberlain, Brian T.
Wu, Yue
Ferri, Elena
Kashemirov, Boris A.
Beard, William A.
Wilson, Samuel H.
McKenna, Charles E.
Goodman, Myron F.
TI Transition State in DNA Polymerase beta Catalysis: Rate-Limiting
Chemistry Altered by Base-Pair Configuration
SO BIOCHEMISTRY
LA English
DT Article
ID NUCLEAR-MAGNETIC-RESONANCE; REPLICATION FIDELITY; CRYSTAL-STRUCTURES;
TERNARY COMPLEX; MECHANISM; CANCER; ALPHA; NMR; 5'-TRIPHOSPHATES;
THERMODYNAMICS
AB Kinetics studies of dNTP analogues having pyrophosphate-mimicking beta,gamma-pCXYp leaving groups with variable X and Y substitution reveal striking differences in the chemical transition-state energy for DNA polymerase beta that depend on all aspects of base7pairing configurations, including whether the incoming dNTP is a purine or pyrimidine and if base-pairings are right (T.A and G.C) or wrong (T.G and G.T). Bronsted plots of the catalytic rate constant (log(k(pol))) versus pK(a4) for the leaving group exhibit linear free energy relationships (LFERs)with negative slopes ranging from 0.6 to 2.0, consistent with chemical rate-determining transition-states in which the active-site adjusts to charge-stabilization demand during chemistry depending on base-pair configuration. The Bronsted slopes as well as the intercepts differ dramatically and provide the first direct evidence that dNTP base recognition by the enzyme-primer-template complex triggers a conformational change in the catalytic region of the active-site that significantly modifies the rate-determining chemical step.
C1 [Oertell, Keriann; Goodman, Myron F.] Univ So Calif, Dept Biol Sci, Dana & David Dornsife Coll Letters Arts & Sci, Los Angeles, CA 90089 USA.
[Chamberlain, Brian T.; Wu, Yue; Ferri, Elena; Kashemirov, Boris A.; McKenna, Charles E.; Goodman, Myron F.] Univ So Calif, Dept Chem, Dana & David Dornsife Coll Letters Arts & Sci, Los Angeles, CA 90089 USA.
[Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP McKenna, CE (reprint author), Univ So Calif, Dept Chem, Dana & David Dornsife Coll Letters Arts & Sci, Univ Pk Campus, Los Angeles, CA 90089 USA.
EM mckenna@usc.edu; mgoodman@usc.edu
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences; National Institutes of Health
[1U19CA105010, 1U19CA177547]; [Z01-ES050158]; [Z01-ES050159]
FX This research was supported by research project nos. Z01-ES050158 and
Z01-ES050159 to S.H.W. by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences and was in
association with National Institutes of Health grant nos. 1U19CA105010
and 1U19CA177547.
NR 49
TC 10
Z9 10
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 25
PY 2014
VL 53
IS 11
BP 1842
EP 1848
DI 10.1021/bi500101z
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD8TR
UT WOS:000333539100013
PM 24580380
ER
PT J
AU McKenzie, AT
Pomerantsev, AP
Sastalla, I
Martens, C
Ricklefs, SM
Virtaneva, K
Anzick, S
Porcella, SF
Leppla, SH
AF McKenzie, Andrew T.
Pomerantsev, Andrei P.
Sastalla, Inka
Martens, Craig
Ricklefs, Stacy M.
Virtaneva, Kimmo
Anzick, Sarah
Porcella, Stephen F.
Leppla, Stephen H.
TI Transcriptome analysis identifies Bacillus anthracis genes that respond
to CO2 through an AtxA-dependent mechanism
SO BMC GENOMICS
LA English
DT Article
DE Bacillus anthracis; pXO1; Illumina; RNA sequencing; AtxA; Toxin
production; Small RNA; Gene-environment interaction
ID PROTECTIVE ANTIGEN GENE; VIRULENCE FACTOR; TOXIN GENES; GENOME SEQUENCE;
EXPRESSION; CEREUS; RNA; PROMOTERS; REGULATOR; GROWTH
AB Background: Upon infection of a mammalian host, Bacillus anthracis responds to host cues, and particularly to elevated temperature (37 degrees C) and bicarbonate/CO2 concentrations, with increased expression of virulence factors that include the anthrax toxins and extracellular capsular layer. This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA. To better understand the genetic basis of this response, we utilized a controlled in vitro system and Next Generation sequencing to determine and compare RNA expression profiles of the parental strain and an isogenic AtxA-deficient strain in a 2 x 2 factorial design with growth environments containing or lacking carbon dioxide.
Results: We found 15 pXO1-encoded genes and 3 chromosomal genes that were strongly regulated by the separate or synergistic actions of AtxA and carbon dioxide. The majority of the regulated genes responded to both AtxA and carbon dioxide rather than to just one of these factors. Interestingly, we identified two previously unrecognized small RNAs that are highly expressed under physiological carbon dioxide concentrations in an AtxA-dependent manner. Expression levels of the two small RNAs were found to be higher than that of any other gene differentially expressed in response to these conditions. Secondary structure and small RNA-mRNA binding predictions for the two small RNAs suggest that they may perform important functions in regulating B. anthracis virulence.
Conclusions: A majority of genes on the virulence plasmid pXO1 that are regulated by the presence of either CO2 or AtxA separately are also regulated synergistically in the presence of both. These results also elucidate novel pXO1-encoded small RNAs that are associated with virulence conditions.
C1 [McKenzie, Andrew T.; Pomerantsev, Andrei P.; Sastalla, Inka; Leppla, Stephen H.] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Martens, Craig; Ricklefs, Stacy M.; Virtaneva, Kimmo; Anzick, Sarah; Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs, Hamilton, MT 59840 USA.
[Pomerantsev, Andrei P.] NIH, Bethesda, MD 20892 USA.
RP Pomerantsev, AP (reprint author), NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
EM apomerantsev@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID), Bethesda, MD, USA
FX We thank Kishore Kanakabandi and Matt Hernandez for assistance in qPCR
primer design and members of the Leppla lab for helpful comments and
advice. We thank Zonglin Hu for performing the tiled microarray that
defined the orientations of the sRNAs. This work was supported by the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID), Bethesda, MD, USA.
NR 60
TC 6
Z9 6
U1 2
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD MAR 25
PY 2014
VL 15
AR 229
DI 10.1186/1471-2164-15-229
PG 14
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AD8RI
UT WOS:000333532900001
PM 24661624
ER
PT J
AU Bhattacharyya, N
Hu, X
Chen, CZ
Griner, LAM
Zheng, W
Inglese, J
Austin, CP
Marugan, JJ
Southall, N
Neumann, S
Northup, JK
Ferrer, M
Collins, MT
AF Bhattacharyya, Nisan
Hu, Xin
Chen, Catherine Z.
Griner, Lesley A. Mathews
Zheng, Wei
Inglese, James
Austin, Christopher P.
Marugan, Juan J.
Southall, Noel
Neumann, Susanne
Northup, John K.
Ferrer, Marc
Collins, Michael T.
TI A High Throughput Screening Assay System for the Identification of Small
Molecule Inhibitors of gsp
SO PLOS ONE
LA English
DT Article
ID MCCUNE-ALBRIGHT-SYNDROME; STIMULATORY G-PROTEIN; ADENYLYL-CYCLASE;
ALPHA; CELLS; MUTATIONS; LIBRARIES; TUMORS
AB Mis-sense mutations in the alpha-subunit of the G-protein, G(s)alpha, cause fibrous dysplasia of bone/McCune-Albright syndrome. The biochemical outcome of these mutations is constitutively active Gsa and increased levels of cAMP. The aim of this study was to develop an assay system that would allow the identification of small molecule inhibitors specific for the mutant G(s)alpha protein, the so-called gsp oncogene. Commercially available Chinese hamster ovary cells were stably transfected with either wild-type (WT) or mutant G(s)alpha proteins (R201C and R201H). Stable cell lines with equivalent transfected G(s)alpha protein expression that had relatively lower (WT) or higher (R201C and R201H) cAMP levels were generated. These cell lines were used to develop a fluorescence resonance energy transfer (FRET)-based cAMP assay in 1536-well microplate format for high throughput screening of small molecule libraries. A small molecule library of 343,768 compounds was screened to identify modulators of gsp activity. A total of 1,356 compounds with inhibitory activity were initially identified and reconfirmed when tested in concentration dose responses. Six hundred eighty-six molecules were selected for further analysis after removing cytotoxic compounds and those that were active in forskolin-induced WT cells. These molecules were grouped by potency, efficacy, and structural similarities to yield 22 clusters with more than 5 of structurally similar members and 144 singleton molecules. Seven chemotypes of the major clusters were identified for further testing and analyses.
C1 [Bhattacharyya, Nisan; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Hu, Xin; Chen, Catherine Z.; Griner, Lesley A. Mathews; Zheng, Wei; Inglese, James; Austin, Christopher P.; Marugan, Juan J.; Southall, Noel; Ferrer, Marc] NIH, Dept Preclin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Neumann, Susanne] NIDDK, Clin Endocrinol Branch, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
[Northup, John K.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
RP Collins, MT (reprint author), Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
EM mc247k@nih.gov
RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014
OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757
FU Division of Intramural Research, National Institute of Dental Research,
National Center for Advancing Translational Sciences; National Institute
of Diabetes, Digestive and Kidney Diseases; National Institute of
Alcoholism and Alcohol Abuse, National Institutes of Health
FX This study was supported by the Division of Intramural Research,
National Institute of Dental Research, National Center for Advancing
Translational Sciences, National Institute of Diabetes, Digestive and
Kidney Diseases, and National Institute of Alcoholism and Alcohol Abuse,
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 23
TC 4
Z9 4
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 25
PY 2014
VL 9
IS 3
AR e90766
DI 10.1371/journal.pone.0090766
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SD
UT WOS:000333675600003
PM 24667240
ER
PT J
AU Momot, D
Zheng, CY
Yin, HG
Elbekai, RH
Vallant, M
Chiorini, JA
AF Momot, Dariya
Zheng, Changyu
Yin, Hongen
Elbekai, Reem H.
Vallant, Molly
Chiorini, John A.
TI Toxicity and Biodistribution of the Serotype 2 Recombinant
Adeno-Associated Viral Vector, Encoding Aquaporin-1, after Retroductal
Delivery to a Single Mouse Parotid Gland
SO PLOS ONE
LA English
DT Article
ID ADENOVIRAL-MEDIATED TRANSFER; RAT SALIVARY-GLANDS; FLUID SECRETION; CDNA
AB In preparation for testing the safety of using serotype 2 recombinant adeno-associated vector, encoding Aquaporin-1 to treat radiation-induced salivary gland damage in a phase 1 clinical trial, we conducted a 13 week GLP biodistribution and toxicology study using Balb/c mice. To best assess the safety of rAAV2hAQP1 as well as resemble clinical delivery, vector (10(6), 10(9), 10(10), or 4.4x10(10) vector particles/gland) or saline was delivered to the right parotid gland of mice via retroductal cannulation. Very mild surgically induced inflammation was caused by this procedure, seen in 3.6% of animals for the right parotid gland, and 5.3% for the left parotid gland. Long term distribution of vector appeared to be localized to the site of cannulation as well as the right and left draining submandibular lymph nodes at levels >50 copies/mu g in some animals. As expected, there was a dose-related increase in neutralizing antibodies produced by day 29. Overall, animals appeared to thrive, with no differences in mean body weight, food or water consumption between groups. There were no significant adverse effects due to treatment noted by clinical chemistry and pathology evaluations. Hematology assessment of serum demonstrated very limited changes to the white blood cell, segmented neutrophils, and hematocrit levels and were concluded to not be vector-associated. Indicators for liver, kidney, cardiac functions and general tissue damage showed no changes due to treatment. All of these indicators suggest the treatment is clinically safe.
C1 [Momot, Dariya; Zheng, Changyu; Yin, Hongen; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Elbekai, Reem H.] BioReliance SAFC, Div Toxicol, Rockville, MD USA.
[Vallant, Molly] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
RP Chiorini, JA (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
EM jchiorini@dir.nidcr.nih.gov
FU NTP/NIEHS (National Toxicology Program, National Institute of
Environmental Health Sciences) [NO1-ES-55536]
FX This study was conducted at BioReliance, supported by NTP/NIEHS
(National Toxicology Program, National Institute of Environmental Health
Sciences) contract NO1-ES-55536. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 11
TC 4
Z9 4
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 25
PY 2014
VL 9
IS 3
AR e92832
DI 10.1371/journal.pone.0092832
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SD
UT WOS:000333675600085
PM 24667436
ER
PT J
AU Smedley, J
Turkbey, B
Bernardo, ML
Del Prete, GQ
Estes, JD
Griffiths, GL
Kobayashi, H
Choyke, PL
Lifson, JD
Keele, BF
AF Smedley, Jeremy
Turkbey, Baris
Bernardo, Marcelino L.
Del Prete, Gregory Q.
Estes, Jacob D.
Griffiths, Gary L.
Kobayashi, Hisataka
Choyke, Peter L.
Lifson, Jeffrey D.
Keele, Brandon F.
TI Tracking the Luminal Exposure and Lymphatic Drainage Pathways of
Intravaginal and Intrarectal Inocula Used in Nonhuman Primate Models of
HIV Transmission
SO PLOS ONE
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; RHESUS MACAQUES; BLUE-DYE; INFECTION;
SIVMAC251; VARIANTS
AB Over 80% of sexual HIV-1 transmissions originate from a single viral variant, but the underlying basis for this transmission bottleneck remains to be elucidated. Nonhuman primate models of mucosal virus transmission allow opportunities to gain insight into the basis of this mucosal bottleneck. We used simulated inocula consisting of either non-infectious vital dye or contrast dye with non-invasive magnetic resonance imaging (MRI) to visualize mucosal exposure and passive lymphatic drainage patterns following vaginal and rectal exposures in Indian origin rhesus macaques. Results revealed a limited overall distance of dye coverage from the anal verge following 1 ml (n = 8) intrarectally administered, which greatly increased with a 3 ml (n = 8) volume. Intravaginal dye exposure using 2 ml revealed complete coverage of the mucosa of the vagina and ectocervix, however dye was not detectable in the endocervix, uterus, fallopian tubes or ovaries in nuliparous sexually mature rhesus macaques (n = 9). In addition, following submucosal and intranodal injections of vital dye or MRI contrast dye in the rectum (n = 9), or distal and proximal vagina (n = 4), the lymphatic drainage pathways were identified as first the internal then common iliac chain followed by para-aortic lymph nodes. Drainage from the distal descending colon (n = 8) was via the para-colonic lymph nodes followed by the inferior mesenteric and para-aortic lymph nodes. Analysis after vaginal challenge with infectious SIVmac239 followed by euthanasia at day 3 revealed a pattern of viral dissemination consistent with the imaging results. These results provide insights into potential patterns of viral dissemination that can help guide efforts to better elucidate the earliest events of virus transmission and potential intervention strategies.
C1 [Smedley, Jeremy] Frederick Natl Lab, Leidos Biomed Res Inc, Lab Anim Sci Program, Frederick, MD USA.
[Turkbey, Baris; Bernardo, Marcelino L.; Kobayashi, Hisataka; Choyke, Peter L.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
[Del Prete, Gregory Q.; Estes, Jacob D.; Lifson, Jeffrey D.; Keele, Brandon F.] Frederick Natl Lab, AIDS & Canc Virus Program, Leidos Biomed Res Inc, Frederick, MD 21702 USA.
[Griffiths, Gary L.] Frederick Natl Lab, Clin Monitoring Res Program, Leidos Biomed Res Inc, Frederick, MD USA.
RP Keele, BF (reprint author), Frederick Natl Lab, AIDS & Canc Virus Program, Leidos Biomed Res Inc, Frederick, MD 21702 USA.
EM keelebf@mail.nih.gov
OI Smedley, Jeremy/0000-0003-3369-4662
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government. The
funder had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 26
TC 8
Z9 8
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 25
PY 2014
VL 9
IS 3
AR e92830
DI 10.1371/journal.pone.0092830
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SD
UT WOS:000333675600084
PM 24667371
ER
PT J
AU Gaspar, AH
Machner, MP
AF Gaspar, Andrew H.
Machner, Matthias P.
TI VipD is a Rab5-activated phospholipase A(1) that protects Legionella
pneumophila from endosomal fusion
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID MYCOBACTERIUM-TUBERCULOSIS; ACTIVATION; PHAGOSOME; EFFECTOR; RAB5;
CHOLESTEROL; BIOGENESIS; PROTEINS; EXOU
AB A crucial step in the elimination of invading microbes by macrophages is phagosomal maturation through heterotypic endosomal fusion. This process is controlled by the guanine nucleotide binding protein Rab5, which assembles protein microdomains that include the tethering protein early endosomal antigen (EEA) 1 and the phosphatidylinositol (PI) 3-kinase hVps34, which generates PI(3) P, a phospholipid required for membrane association of EEA1 and other fusion factors. During infection of macrophages, the pathogen Legionella pneumophila bypasses the microbicidal endosomal compartment by an unknown mechanism. Here, we show that the effector protein VipD from L. pneumophila exhibits phospholipase A(1) activity that is activated only upon binding to endosomal Rab5 or Rab22. Within mammalian cells, VipD localizes to endosomes and catalyzes the removal of PI(3) P from endosomal membranes. EEA1 and other transport and fusion factors are consequently depleted from endosomes, rendering them fusion-incompetent. During host cell infection, VipD reduces exposure of L. pneumophila to the endosomal compartment and protects their surrounding vacuoles from acquiring Rab5. Thus, by catalyzing PI(3) P depletion in a Rab5-dependent manner, VipD alters the protein composition of endosomes thereby blocking fusion with Legionella-containing vacuoles.
C1 [Gaspar, Andrew H.; Machner, Matthias P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Machner, MP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM machnerm@mail.nih.gov
RI Machner, Matthias/G-2758-2015
FU National Institutes of Health
FX We thank all members of the M. P. M. laboratory, and Drs. G. Storz, J.
Donaldson, T. Updegrove, M. Barzik, and J. Bonifacino for critical
reading of the manuscript and insightful discussion. This work was
supported by the Intramural Research Program of the National Institutes
of Health.
NR 23
TC 34
Z9 36
U1 1
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 25
PY 2014
VL 111
IS 12
BP 4560
EP 4565
DI 10.1073/pnas.1316376111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6CK
UT WOS:000333341100054
PM 24616501
ER
PT J
AU Yang, CX
Wang, HY
Qiao, T
Yang, B
Aliaga, L
Qiu, LH
Tan, WJ
Salameh, J
McKenna-Yasek, DM
Smith, T
Peng, LT
Moore, MJ
Brown, RH
Cai, HB
Xu, ZS
AF Yang, Chunxing
Wang, Hongyan
Qiao, Tao
Yang, Bin
Aliaga, Leonardo
Qiu, Linghua
Tan, Weijia
Salameh, Johnny
McKenna-Yasek, Diane M.
Smith, Thomas
Peng, Lingtao
Moore, Melissa J.
Brown, Robert H., Jr.
Cai, Huaibin
Xu, Zuoshang
TI Partial loss of TDP-43 function causes phenotypes of amyotrophic lateral
sclerosis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE FTD; FTLD; neurodegenerative disease; noncell autonomous toxicity; Lou
Gehrig's disease
ID FRONTOTEMPORAL LOBAR DEGENERATION; MOTOR-NEURON DEGENERATION; ALS-LINKED
TDP-43; TRANSGENIC MICE; MESSENGER-RNA; MUTANT TDP-43; TARDBP MUTATIONS;
SKELETAL-MUSCLE; ALPHA-SYNUCLEIN; PRIMARY TARGET
AB Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease that causes motor neuron degeneration, progressive motor dysfunction, paralysis, and death. Although multiple causes have been identified for this disease, >95% of ALS cases show aggregation of transactive response DNA binding protein (TDP-43) accompanied by its nuclear depletion. Therefore, the TDP-43 pathology may be a converging point in the pathogenesis that originates from various initial triggers. The aggregation is thought to result from TDP-43 misfolding, which could generate cellular toxicity. However, the aggregation as well as the nuclear depletion could also lead to a partial loss of TDP-43 function or TDP-43 dysfunction. To investigate the impact of TDP-43 dysfunction, we generated a transgenic mouse model for a partial loss of TDP-43 function using transgenic RNAi. These mice show ubiquitous transgene expression and TDP-43 knockdown in both the periphery and the central nervous system (CNS). Strikingly, these mice develop progressive neurodegeneration prominently in cortical layer V and spinal ventral horn, motor dysfunction, paralysis, and death. Furthermore, examination of splicing patterns of TDP-43 target genes in human ALS revealed changes consistent with TDP-43 dysfunction. These results suggest that the CNS, particularly motor neurons, possess a heightened vulnerability to TDP-43 dysfunction. Additionally, because TDP-43 knockdown predominantly occur in astrocytes in the spinal cord of these mice, our results suggest that TDP-43 dysfunction in astrocytes is an important driver for motor neuron degeneration and clinical phenotypes of ALS.
C1 [Yang, Chunxing; Wang, Hongyan; Qiao, Tao; Yang, Bin; Qiu, Linghua; Tan, Weijia; Peng, Lingtao; Moore, Melissa J.; Xu, Zuoshang] Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01605 USA.
[Salameh, Johnny; McKenna-Yasek, Diane M.; Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA.
[Smith, Thomas] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA.
[Xu, Zuoshang] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01605 USA.
[Peng, Lingtao; Moore, Melissa J.; Xu, Zuoshang] Univ Massachusetts, Sch Med, RNA Therapeut Inst, Worcester, MA 01605 USA.
[Moore, Melissa J.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA.
[Xu, Zuoshang] Univ Massachusetts, Sch Med, Neurosci Program, Worcester, MA 01605 USA.
[Aliaga, Leonardo; Cai, Huaibin] NIA, Transgen Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Xu, ZS (reprint author), Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01605 USA.
EM zuoshang.xu@umassmed.edu
FU National Center for Research Resources [S10RR027897]; National
Institutes of Health/National Institute of Neurological Disorders and
Stroke [R21NS062230, R01NS059708]; ALS Association; ALS Therapeutic
Alliance; Packard Center for ALS Research at Johns Hopkins; National
Institute on Aging/National Institutes of Health Intramural Research
Program [AG000943]
FX We thank Drs. Jemeen Sreedharan and Daryl Bosco for critically reading
the manuscript; Drs. Alonzo Ross and Phillip D. Zamore for sharing
equipment; Dr. Hong Cao for assisting with confocal imaging; the UMass
Transgenic Animal Modeling Core for pronuclear injection; and the
technical support from the Core Electron Microscopy Facility, which
receives support from the National Center for Research Resources
(S10RR027897). This work was supported by National Institutes of
Health/National Institute of Neurological Disorders and Stroke Grants
R21NS062230 and R01NS059708, the ALS Association, ALS Therapeutic
Alliance, and the Packard Center for ALS Research at Johns Hopkins (to
Z.X.); and in part by National Institute on Aging/National Institutes of
Health Intramural Research Program AG000943.
NR 78
TC 35
Z9 35
U1 1
U2 21
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 25
PY 2014
VL 111
IS 12
BP E1121
EP E1129
DI 10.1073/pnas.1322641111
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6CK
UT WOS:000333341100010
PM 24616503
ER
PT J
AU Zhang, XX
Liang, JR
Liu, JL
Zhao, Y
Gao, J
Sun, WJ
Ito, Y
AF Zhang, Xinxin
Liang, Jinru
Liu, Jianli
Zhao, Ye
Gao, Juan
Sun, Wenji
Ito, Yoichiro
TI Quality control and identification of steroid saponins from Dioscorea
zingiberensis C. H. Wright by fingerprint with HPLC-ELSD and
HPLC-ESI-Quadrupole/Time-of-fight tandem mass spectrometry
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Dioscorea zingiberensis C. H. Wright; Fingerprint; Steroid saponins;
HPLC-ELSD; HPLC-ESI-QJTOF
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DIODE-ARRAY DETECTION;
ELECTROSPRAY-IONIZATION; ANTIOXIDANT-ACTIVITY; DIFFERENTIATION;
GLYCOSIDES; EXTRACT; GINSENG; HERBS
AB In this study, a fingerprint of steroid saponins, the major bioactive constituents in the crude extracts from Dioscorea zingiberensis C. H. Wright (DZW), has been established for the first time by combined use of the following two methods: high-performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD) and the simultaneous characterization of the steroid saponins by high-performance liquid chromatography coupled with electrospray ionization-mass spectrometry and quadrupole tandem time-of-fight mass analyzers detection (HPLC-ESI-QJTOF). All HPLC analyses were carried out on a Welchrom C-18 column (250 mm x 4.6 mm I.D., 5 mu m) with a mobile phase composed of water and acetonitrile under gradient elution. There were 68 common characteristic peaks in the fingerprints, in which 12 of them were confirmed by comparing their mass spectra and retention times with those of the reference compounds. In order to identify other unknown peaks, their fragmentation behaviors characteristic of the major groups of steroid saponins from DZW with six types of aglycone skeletons were discussed in detail, and possible MS/MS fragmentation pathways were proposed for aiding the structural identification of these components. According to the summarized fragmentation patterns, these peaks were tentatively assigned by matching their empirical molecular formula with those of the published compounds, or by elucidating their quasi-molecular ions and fragment ions referring to available literature information when the reference standards were unavailable. As a result, 22 new steroid saponins were found in DZW for the first time. In addition, the quantitative analysis of the nine (except for the reference compounds A, B, and C) known peaks was accomplished at the same time which indicated that there was a great variability in the amount of these active compounds in different batches in the crude extracts. This approach could demonstrate that the fingerprint could be considered to be a suitable tool to comprehensively improve the quality control of DZW. The identification and structural elucidation of the peaks in the fingerprint may provide important experimental data for further pharmacological and clinical researches. (C) 2014 Published by Elsevier B.V.
C1 [Zhang, Xinxin; Liang, Jinru; Liu, Jianli; Zhao, Ye; Sun, Wenji] NW Univ Xian, Biomed Key Lab Shaanxi Prov, Xian 710069, Peoples R China.
[Gao, Juan] Shaanxi Jiahe Phytochem Co Ltd, Xian 710069, Peoples R China.
[Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Sun, WJ (reprint author), NW Univ Xian, Biomed Key Lab Shaanxi Prov, 229 Taibai North Rd, Xian 710069, Peoples R China.
EM guoxiaolizhang@163.com; itoy@nhlbi.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 32
TC 15
Z9 16
U1 4
U2 50
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
EI 1873-264X
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD MAR 25
PY 2014
VL 91
BP 46
EP 59
DI 10.1016/j.jpba.2013.11.023
PG 14
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA AC2QJ
UT WOS:000332348700008
PM 24418811
ER
PT J
AU Tedesco, D
Zanasi, R
Wainer, IW
Bertucci, C
AF Tedesco, Daniele
Zanasi, Riccardo
Wainer, Irving W.
Bertucci, Carlo
TI Stereochemical and conformational study on fenoterol by ECD spectroscopy
and TD-DFT calculations
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Fenoterol; Absolute stereochemistry; ECD spectroscopy; TD-DFT
calculations; Conformational analysis
ID DENSITY-FUNCTIONAL THEORY; MOLECULAR-FIELD ANALYSIS; APPROXIMATION;
DERIVATIVES; AGONISTS
AB Fenoterol and its derivatives are selective beta(2)-adrenergic receptor (beta(2)-AR) agonists whose stereoselective biological activities have been extensively investigated in the past decade: a complete stereochemical characterization of fenoterol derivatives is therefore crucial for a better understanding of the effects of stereochemistry on beta(2)-AR binding. In the present project, the relationship between chiroptical properties and absolute stereochemistry of the stereoisomers of fenoterol (1) was investigated by experimental ECD spectroscopy and time-dependent density functional theory (TD-DFT). DFT geometry optimizations were carried out at the RI-97D/TZVP/IEFPCM(MeOH) level and subsequent TD-DFT calculations were performed using the PBEO hybrid functional.
Despite the large pool of equilibrium conformers found for the investigated compounds and the known limitations of the level of theory employed, the computational protocol was able to reproduce the experimental ECD spectra of the stereoisomers of 1. The main contribution to the overall chiroptical properties was found to arise from the absolute configuration of the chiral center in a-position to the resorcinol moiety. Based on this evidence, a thorough conformational analysis was performed on the optimized DFT conformers, which revealed the occurrence of a different equilibrium between conformational patterns for the diastereomers of fenoterol: the (R,R')/(S,S') enantiomeric pair showed a higher population of folded conformations than the (R,S')I(S,R') pair. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Tedesco, Daniele; Bertucci, Carlo] Univ Bologna, Dept Pharm & Biotechnol, I-40126 Bologna, Italy.
[Zanasi, Riccardo] Univ Salerno, Dept Biol & Chem, I-84084 Fisciano, Italy.
[Wainer, Irving W.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Bertucci, C (reprint author), Univ Bologna, Dept Pharm & Biotechnol, Via Belmeloro 6, I-40126 Bologna, Italy.
EM carlo.bertucci@unibo.it
RI Tedesco, Daniele/L-1591-2015;
OI Tedesco, Daniele/0000-0003-2585-7791; Zanasi,
Riccardo/0000-0002-8374-6080
FU Intramural NIH HHS
NR 30
TC 1
Z9 2
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
EI 1873-264X
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD MAR 25
PY 2014
VL 91
BP 92
EP 96
DI 10.1016/j.jpba.2013.12.018
PG 5
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA AC2QJ
UT WOS:000332348700013
PM 24441217
ER
PT J
AU Shi, YB
AF Shi, Yun-Bo
TI The 2013 Ming K Jeang award for excellence in Cell & Bioscience
SO CELL AND BIOSCIENCE
LA English
DT Editorial Material
AB Two research groups led by Yihong Ye of National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, MD, USA and Dr. Lixin Wei of Medical Sciences Research Center, Renji hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China, won the 2013 Ming K Jeang Award for Excellence in Cell & Bioscience.
C1 NIH, Bethesda, MD 20892 USA.
RP Shi, YB (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM shi@helix.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD MAR 24
PY 2014
VL 4
AR 15
DI 10.1186/2045-3701-4-15
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AF0AK
UT WOS:000334373600001
PM 24655893
ER
PT J
AU Song, MJ
San, H
Anderson, SA
Cannon, RO
Orlic, D
AF Song, Minjung
San, Hong
Anderson, Stasia A.
Cannon, Richard O., III
Orlic, Donald
TI Shear stress-induced mechanotransduction protein deregulation and
vasculopathy in a mouse model of progeria
SO STEM CELL RESEARCH & THERAPY
LA English
DT Article
ID MICE LACKING VIMENTIN; NUCLEAR LAMINS; AORTIC-ARCH; BLOOD-FLOW;
APOPTOSIS; CELLS; MUTATIONS; PHENOTYPE
AB Introduction: A mouse model of progeria derived by insertion of the human mutant LMNA gene (mLMNA), producing mutant lamin A, shows loss of smooth muscle cells in the media of the ascending aorta. We hypothesized that high shear stress, in the presence of mutant lamin A, induces this vasculopathy and tried to define the molecular and cellular basis for aortic vasculopathy.
Methods: Ascending and descending aortas from wild type (WT) and mLMNA(+) mice were compared using proteomics, Western blots, PCR and immunostaining. To determine whether high fluidic shear stress, known to occur in the ascending aorta, contributed to the vasculopathy, we exposed descending aortas of mLMNA(+) mice, with no apparent vasculopathy, to 75 dynes/cm(2) shear stress for 30 minutes using a microfluidic system.
Results: When the mice were one year of age, expression of several mechanotransduction proteins in the ascending aorta, including vimentin, decreased in mLMNA(+) mice but no decrease occurred in the descending aorta. High fluidic shear stress produced a significant reduction in vimentin of mLMNA(+) mice but not in similarly treated WT mice.
Conclusions: The occurrence of mutant lamin A and high shear stress correlate with a reduction in the level of mechanotransduction proteins in smooth muscle cells of the media. Reduction of these proteins may contribute over time to development of vasculopathy in the ascending aorta in progeria syndrome.
C1 [Song, Minjung; Anderson, Stasia A.; Cannon, Richard O., III; Orlic, Donald] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[San, Hong] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Orlic, D (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM dorlic@nhlbi.nih.gov
FU NHLBI, National Institutes of Health, Bethesda, MD, USA
FX This study was supported by the intramural research program of the
NHLBI, National Institutes of Health, Bethesda, MD, USA. We thank Angel
Aponte (Proteomics Core Facility, NHLBI, NIH), Christian A. Combs and
Daniela Malide (Light Microscopy Core Facility, NHLBI, NIH), Ricardo
Dreyfuss (Medical Arts Department, NIH) and Kimberly Woodhouse and
Yanqin Yang (Genomics Core, NHLBI, NIH) for help with qRT-PCR and
statistical analysis. We thank Francis S. Collins whose laboratory
provided the LMNA+ mice used in this study and the primer
sequences used for genotyping.
NR 30
TC 3
Z9 3
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1757-6512
J9 STEM CELL RES THER
JI Stem Cell Res. Ther.
PD MAR 24
PY 2014
VL 5
AR 41
DI 10.1186/scrt429
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AF3UF
UT WOS:000334637100001
PM 24661531
ER
PT J
AU Alves, G
Yu, YK
AF Alves, Gelio
Yu, Yi-Kuo
TI Accuracy Evaluation of the Unified P-Value from Combining Correlated
P-Values
SO PLOS ONE
LA English
DT Article
ID WEIGHTED Z-TEST; INDEPENDENT TESTS; PROBABILITIES; COMBINATION;
STATISTICS
AB Meta-analysis methods that combine P-values into a single unified P-value are frequently employed to improve confidence in hypothesis testing. An assumption made by most meta-analysis methods is that the P-values to be combined are independent, which may not always be true. To investigate the accuracy of the unified P-value from combining correlated P-values, we have evaluated a family of statistical methods that combine: independent, weighted independent, correlated, and weighted correlated P-values. Statistical accuracy evaluation by combining simulated correlated P-values showed that correlation among P-values can have a significant effect on the accuracy of the combined P-value obtained. Among the statistical methods evaluated those that weight P-values compute more accurate combined P-values than those that do not. Also, statistical methods that utilize the correlation information have the best performance, producing significantly more accurate combined P-values. In our study we have demonstrated that statistical methods that combine P-values based on the assumption of independence can produce inaccurate P-values when combining correlated P-values, even when the P-values are only weakly correlated. Therefore, to prevent from drawing false conclusions during hypothesis testing, our study advises caution be used when interpreting the P-value obtained from combining P-values of unknown correlation. However, when the correlation information is available, the weighting-capable statistical method, first introduced by Brown and recently modified by Hou, seems to perform the best amongst the methods investigated.
C1 [Alves, Gelio; Yu, Yi-Kuo] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Yu, YK (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM yyu@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Library of Medicine at the
National Institutes of Health/Department of Health and Human Services;
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Library of Medicine at the National Institutes of
Health/Department of Health and Human Services. Funding for Open Access
publication charges for this article was provided by 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 35
TC 6
Z9 6
U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 24
PY 2014
VL 9
IS 3
AR e91225
DI 10.1371/journal.pone.0091225
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD7QO
UT WOS:000333459900016
PM 24663491
ER
PT J
AU Do, AN
Rosenberg, ES
Sullivan, PS
Beer, L
Strine, TW
Schulden, JD
Fagan, JL
Freedman, MS
Skarbinski, J
AF Do, Ann N.
Rosenberg, Eli S.
Sullivan, Patrick S.
Beer, Linda
Strine, Tara W.
Schulden, Jeffrey D.
Fagan, Jennifer L.
Freedman, Mark S.
Skarbinski, Jacek
TI Excess Burden of Depression among HIV-Infected Persons Receiving Medical
Care in the United States: Data from the Medical Monitoring Project and
the Behavioral Risk Factor Surveillance System
SO PLOS ONE
LA English
DT Article
ID PATIENT HEALTH QUESTIONNAIRE; HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE
ANTIRETROVIRAL THERAPY; INJECTION-DRUG USERS; PSYCHIATRIC-DISORDERS;
PUBLIC-HEALTH; POSITIVE PATIENTS; SUBSTANCE-ABUSE; IMMUNE FUNCTION; MOOD
DISORDERS
AB Background: With increased life expectancy for HIV-infected persons, there is concern regarding comorbid depression because of its common occurrence and association with behaviors that may facilitate HIV transmission. Our objectives were to estimate the prevalence of current depression among HIV-infected persons receiving care and assess the burden of major depression, relative to that in the general population.
Methods and Findings: We used data from the Medical Monitoring Project (MMP) and the Behavioral Risk Factors Surveillance System (BRFSS). The eight-item Patient Health Questionnaire was used to identify depression. To assess the burden of major depression among HIV-infected persons receiving care, we compared the prevalence of current major depression between the MMP and BRFSS populations using stratified analyses that simultaneously controlled for gender and, in turn, each of the potentially confounding demographic factors of age, race/ethnicity, education, and income. Each unadjusted comparison was summarized as a prevalence ratio (PR), and each of the adjusted comparisons was summarized as a standardized prevalence ratio (SPR). Among HIV-infected persons receiving care, the prevalence of a current episode of major depression and other depression, respectively, was 12.4% (95% CI: 11.2, 13.7) and 13.2% (95% CI: 12.0%, 14.4%). Overall, the PR comparing the prevalence of current major depression between HIV-infected persons receiving care and the general population was 3.1. When controlling for gender and each of the factors age, race/ethnicity, and education, the SPR (3.3, 3.0, and 2.9, respectively) was similar to the PR. However, when controlling for gender and annual household income, the SPR decreased to 1.5.
Conclusions: Depression remains a common comorbidity among HIV-infected persons. The overall excess burden among HIV-infected persons receiving care is about three-times that among the general population and is associated with differences in annual household income between the two populations. Relevant efforts are needed to reduce this burden.
C1 [Do, Ann N.; Beer, Linda; Fagan, Jennifer L.; Freedman, Mark S.; Skarbinski, Jacek] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA 30333 USA.
[Rosenberg, Eli S.; Sullivan, Patrick S.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Strine, Tara W.] Ctr Dis Control & Prevent, Off Publ Hlth Preparedness & Response, Atlanta, GA USA.
[Schulden, Jeffrey D.] NIDA, Rockville, MD USA.
RP Do, AN (reprint author), Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA 30333 USA.
EM aad9@cdc.gov
FU Centers for Disease Control and Prevention
FX Funding was exclusively provided by the Centers for Disease Control and
Prevention, which conceived the project, developed project-associated
materials including data collection instruments, provided oversight of
implementation, conducted analytic procedures, and developed this
report.
NR 93
TC 21
Z9 21
U1 8
U2 21
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 24
PY 2014
VL 9
IS 3
AR e92842
DI 10.1371/journal.pone.0092842
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD7QO
UT WOS:000333459900124
PM 24663122
ER
PT J
AU Leibovitch, EC
Brunetto, GS
Caruso, B
Fenton, K
Ohayon, J
Reich, DS
Jacobson, S
AF Leibovitch, Emily C.
Brunetto, Giovanna S.
Caruso, Breanna
Fenton, Kaylan
Ohayon, Joan
Reich, Daniel S.
Jacobson, Steven
TI Coinfection of Human Herpesviruses 6A (HHV-6A) and HHV-6B as
Demonstrated by Novel Digital Droplet PCR Assay
SO PLOS ONE
LA English
DT Article
ID MULTIPLE-SCLEROSIS PATIENTS; POLYMERASE-CHAIN-REACTION; BLOOD
MONONUCLEAR-CELLS; CENTRAL-NERVOUS-SYSTEM; REAL-TIME PCR;
PERIPHERAL-BLOOD; HEALTHY-ADULTS; HUMAN-HERPESVIRUS-6 VARIANT; ACTIVE
REPLICATION; DNA
AB The human herpesviruses HHV-6A and HHV-6B have been associated with various neurologic disorders partly due to the detection of elevated viral DNA levels in patients compared to controls. However the reported frequency of these viruses varies widely, likely reflecting differences in PCR methodologies used for detection. Digital droplet PCR (ddPCR) is a third generation PCR technology that enables the absolute quantification of target DNA molecules. Mounting evidence of the biological differences between HHV-6A and HHV-6B has led to their recent reclassification as separate species. As it is now especially relevant to investigate each virus, our objectives were to first design a multiplex HHV-6A and HHV-6B ddPCR assay and then to investigate the incidence of HHV-6A and HHV-6B coinfection in samples from healthy donors and patients with MS, a disease in which HHV-6 is thought to play a role. In our assessment of healthy donors, we observed a heretofore-underappreciated high frequency of coinfection in PBMC and serum, and found that our assay precisely detects both HHV6A and HHV-6B chromosomally integrated virus, which has important implications in clinical settings. Interestingly, upon comparing the saliva from MS patients and healthy donors, we detected a significantly elevated frequency of coinfection in MS saliva; increased detection of HHV-6A in MS patients is consistent with other studies suggesting that this viral species (thought to be more neurotropic than HHV-6B) is more prevalent among MS patients compared to healthy donors. As the biology and disease associations between these two viral species differ, identifying and quantifying both species of HHV-6 may provide clinically relevant information, as well as enhance our understanding of the roles of each in health and disease.
C1 [Leibovitch, Emily C.; Brunetto, Giovanna S.; Caruso, Breanna; Fenton, Kaylan; Ohayon, Joan; Reich, Daniel S.; Jacobson, Steven] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Leibovitch, Emily C.] George Washington Univ, Sch Med & Hlth Sci, Inst Biomed Sci, Washington, DC 20052 USA.
RP Jacobson, S (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM jacobsons@ninds.nih.gov
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU NINDS
FX This work was supported by the intramural research program of NINDS, and
the funders had no role in study design, data collection and analysis,
decision to publish or preparation of the manuscript. The authors thank
Sandy Chiang, John Chuckalovcak and Dr. Bo Song from Bio-Rad
laboratories for technical support. No funding was received from
Bio-Rad.
NR 61
TC 15
Z9 15
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 24
PY 2014
VL 9
IS 3
AR e92328
DI 10.1371/journal.pone.0092328
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD7QO
UT WOS:000333459900051
PM 24663487
ER
PT J
AU Pongsiri, A
Ponlawat, A
Thaisomboonsuk, B
Jarman, RG
Scott, TW
Lambrechts, L
AF Pongsiri, Arissara
Ponlawat, Alongkot
Thaisomboonsuk, Butsaya
Jarman, Richard G.
Scott, Thomas W.
Lambrechts, Louis
TI Differential Susceptibility of Two Field Aedes aegypti Populations to a
Low Infectious Dose of Dengue Virus
SO PLOS ONE
LA English
DT Article
ID FRENCH-POLYNESIA; DISEASE SEVERITY; VIREMIA; THAILAND; TRANSMISSION;
CHILDREN; VILLAGES; STRAINS; BURDEN
AB Background: The infectious dose required to infect mosquito vectors when they take a blood meal from a viremic person is a critical parameter underlying the probability of dengue virus (DENV) transmission. Because experimental vector competence studies typically examine the proportion of mosquitoes that become infected at intermediate or high DENV infectious doses in the blood meal, the minimum blood meal titer required to infect mosquitoes is poorly documented. Understanding the factors influencing the lower infectiousness threshold is epidemiologically significant because it determines the transmission potential of humans with a low DENV viremia, possibly including inapparent infections, and during the onset and resolution of the viremic period of acutely infected individuals.
Methodology/Principal Findings: We compared the susceptibility of two field-derived Aedes aegypti populations from Kamphaeng Phet, Thailand when they were orally exposed to low titers of six DENV-2 isolates derived from the serum of naturally infected humans living in the same region. The infectious dose, time-point post-blood feeding, viral isolate and mosquito population, were significant predictors of the proportion of mosquitoes that became infected. Importantly, the dose-response profile differed significantly between the two Ae. aegypti populations. Although both mosquito populations had a similar 50% oral infectious dose (OID50), the slope of the dose-response was shallower in one population, resulting in a markedly higher susceptibility at low blood meal titers.
Conclusions/Significance: Our results indicate that mosquitoes in nature vary in their infectious dose-response to DENV. Thus, different mosquito populations have a differential ability to acquire DENV infection at low viremia levels. Future studies on human-to-mosquito DENV transmission should not be limited to OID50 values, but rather they should be expanded to account for the shape of the dose-response profile across a range of virus titers.
C1 [Pongsiri, Arissara; Ponlawat, Alongkot] Armed Forces Res Inst Med Sci, Dept Entomol, Bangkok 10400, Thailand.
[Thaisomboonsuk, Butsaya; Jarman, Richard G.] Armed Forces Res Inst Med Sci, Dept Virol, Bangkok 10400, Thailand.
[Scott, Thomas W.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.
[Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Lambrechts, Louis] Inst Pasteur, CNRS, Dept Genomes & Genet, Insect Virus Interact Grp,Unite Rech Associee 301, Paris, France.
RP Lambrechts, L (reprint author), Inst Pasteur, CNRS, Dept Genomes & Genet, Insect Virus Interact Grp,Unite Rech Associee 301, Paris, France.
EM louis.lambrechts@pasteur.fr
RI Lambrechts, Louis/A-2057-2010
OI Lambrechts, Louis/0000-0001-5958-2138
FU United States National Institutes of Health [R01 GM083224]; United
States Military Infectious Diseases Research Program; French Agence
Nationale de la Recherche [ANR-09-RPDOC-007-01]; French Government's
Investissement d'Avenir program, Laboratoire d'Excellence Integrative
Biology of Emerging Infectious Diseases [ANR-10-LABX-62-IBEID]; Research
and Policy for Infectious Disease Dynamics program of the Science and
Technology Directorate, Department of Homeland Security; Fogarty
International Center, United States National Institutes of Health
FX This study was primarily supported by grant R01 GM083224 from the United
States National Institutes of Health and by the United States Military
Infectious Diseases Research Program. L. L. received funding from the
French Agence Nationale de la Recherche (grant ANR-09-RPDOC-007-01) and
from the French Government's Investissement d'Avenir program,
Laboratoire d'Excellence Integrative Biology of Emerging Infectious
Diseases (grant ANR-10-LABX-62-IBEID). T. W. S. received support from
the Research and Policy for Infectious Disease Dynamics program of the
Science and Technology Directorate, Department of Homeland Security, and
Fogarty International Center, United States National Institutes of
Health. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 30
TC 8
Z9 8
U1 0
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 24
PY 2014
VL 9
IS 3
AR e92971
DI 10.1371/journal.pone.0092971
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD7QO
UT WOS:000333459900135
PM 24664142
ER
PT J
AU Rudrabhatla, P
Utreras, E
Jaffe, H
Kulkarni, AB
AF Rudrabhatla, Parvathi
Utreras, Elias
Jaffe, Howard
Kulkarni, Ashok B.
TI Regulation of Sox6 by Cyclin Dependent Kinase 5 in Brain
SO PLOS ONE
LA English
DT Article
ID APOPTOTIC CELL-DEATH; PROTEIN-KINASE; OLIGODENDROCYTE DIFFERENTIATION;
NERVOUS-SYSTEM; CDK5; MOUSE; GENE; EXPRESSION; SURVIVAL; P35
AB Cyclin dependent kinase 5 (Cdk5) is a proline-directed Ser/Thr kinase involved in various biological functions during normal brain development and neurodegeneration. In brain, Cdk5 activity is specific to post-mitotic neurons, due to neuronal specific expression of its activator p35. The biological functions of Cdk5 have been ascribed to its cytoplasmic substrates, however not much is known in nucleus. Here, we show that nuclear transcription factor Sox6 is a direct nuclear target of Cdk5. Sox6 is expressed in Tuj1 positive neurons, suggesting that Sox6 is expressed in differentiating neurons. The expression of Sox6 is high in mitotic nuclei during embryonic day 12 (E12) and gradually decreases during development into adult. On the other hand, Cdk5 expression gradually increases during its development. We show that Sox6 is expressed in mitotic nuclei in embryonic day 12 (E12) and in migrating neurons of E16. Sox6 is phosphorylated in vivo. Sox6 was detected by phospho-Ser/Thr and phospho-Ser/Thr-Pro and MPM-2 (Mitotic protein # 2) antibodies in brain. Furthermore, calf intestinal alkaline phosphatase (CIAP) digestion resulted in faster migration of Sox6 band. The GST-Sox6 was phosphorylated by Cdk5/p35. The mass spectrometry analysis revealed that Sox6 is phosphorylated at T 119 PER motif. We show that Sox6 steady state levels are regulated by Cdk5. Cdk5 knockout mice die in utero and Sox6 protein expression is remarkably high in Cdk52/2 brain, however, there is no change in mRNA expression, suggesting a post-translational regulation of Sox6 by Cdk5. Transfection of primary cortical neurons with WT Cdk5 reduced Sox6 levels, while dominant negative (DN) Cdk5 and p35 increased Sox6 levels. Thus, our results indicate that Cdk5 regulates Sox6 steady state protein level that has an important role in brain development and function.
C1 [Rudrabhatla, Parvathi] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
[Rudrabhatla, Parvathi] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
[Jaffe, Howard] NINDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA.
[Utreras, Elias; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
RP Rudrabhatla, P (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM parvathir@ninds.nih.gov
NR 41
TC 0
Z9 0
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 24
PY 2014
VL 9
IS 3
AR e89310
DI 10.1371/journal.pone.0089310
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD7QO
UT WOS:000333459900003
PM 24662752
ER
PT J
AU Machado-Vieira, R
AF Machado-Vieira, Rodrigo
TI The next generation of clinical studies with antidepressants in bipolar
disorder
SO FRONTIERS IN PSYCHIATRY
LA English
DT Editorial Material
DE bipolar disorder; depression; treatment; antidepressants; biomarkers
C1 [Machado-Vieira, Rodrigo] Univ Sao Paulo, Inst & Dept Psychiat, LIM 27, Sao Paulo, Brazil.
[Machado-Vieira, Rodrigo] NIMH, NIH, Bethesda, MD 20892 USA.
RP Machado-Vieira, R (reprint author), Univ Sao Paulo, Inst & Dept Psychiat, LIM 27, Sao Paulo, Brazil.; Machado-Vieira, R (reprint author), NIMH, NIH, Bethesda, MD 20892 USA.
EM machadovieirar@gmail.com
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190
NR 3
TC 0
Z9 0
U1 0
U2 1
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-0640
J9 FRONT PSYCHIATRY
JI Front. Psychiatry
PD MAR 24
PY 2014
VL 5
AR 27
DI 10.3389/fpsyt.2014.00027
PG 2
WC Psychiatry
SC Psychiatry
GA V46RI
UT WOS:000209900900001
PM 24715878
ER
PT J
AU Psaki, SR
Seidman, JC
Miller, M
Gottlieb, M
Bhutta, ZA
Ahmed, T
Ahmed, AMS
Bessong, P
John, SM
Kang, G
Kosek, M
Lima, A
Shrestha, P
Svensen, E
Checkley, W
AF Psaki, Stephanie R.
Seidman, Jessica C.
Miller, Mark
Gottlieb, Michael
Bhutta, Zulfiqar A.
Ahmed, Tahmeed
Ahmed, A. M. Shamsir
Bessong, Pascal
John, Sushil M.
Kang, Gagandeep
Kosek, Margaret
Lima, Aldo
Shrestha, Prakash
Svensen, Erling
Checkley, William
CA MAL-ED Network Investigators
TI Measuring socioeconomic status in multicountry studies: results from the
eight-country MAL-ED study
SO POPULATION HEALTH METRICS
LA English
DT Article
DE Socioeconomic status; Child growth; Classification; Measurement
ID HEALTH RESEARCH; WEALTH
AB Background: There is no standardized approach to comparing socioeconomic status (SES) across multiple sites in epidemiological studies. This is particularly problematic when cross-country comparisons are of interest. We sought to develop a simple measure of SES that would perform well across diverse, resource-limited settings.
Methods: A cross-sectional study was conducted with 800 children aged 24 to 60 months across eight resource-limited settings. Parents were asked to respond to a household SES questionnaire, and the height of each child was measured. A statistical analysis was done in two phases. First, the best approach for selecting and weighting household assets as a proxy for wealth was identified. We compared four approaches to measuring wealth: maternal education, principal components analysis, Multidimensional Poverty Index, and a novel variable selection approach based on the use of random forests. Second, the selected wealth measure was combined with other relevant variables to form a more complete measure of household SES. We used child height-for-age Z-score (HAZ) as the outcome of interest.
Results: Mean age of study children was 41 months, 52% were boys, and 42% were stunted. Using cross-validation, we found that random forests yielded the lowest prediction error when selecting assets as a measure of household wealth. The final SES index included access to improved water and sanitation, eight selected assets, maternal education, and household income (the WAMI index). A 25% difference in the WAMI index was positively associated with a difference of 0.38 standard deviations in HAZ (95% CI 0.22 to 0.55).
Conclusions: Statistical learning methods such as random forests provide an alternative to principal components analysis in the development of SES scores. Results from this multicountry study demonstrate the validity of a simplified SES index. With further validation, this simplified index may provide a standard approach for SES adjustment across resource-limited settings.
C1 [Psaki, Stephanie R.; Seidman, Jessica C.; Miller, Mark; Checkley, William] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Psaki, Stephanie R.; Seidman, Jessica C.; Kosek, Margaret; Checkley, William] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Program Global Dis Epidemiol & Control, Baltimore, MD USA.
[Gottlieb, Michael] Fdn Natl Inst Hlth, Div Sci, Bethesda, MD USA.
[Bhutta, Zulfiqar A.] Aga Khan Univ, Div Women & Child Hlth, Karachi, Pakistan.
[Ahmed, Tahmeed; Ahmed, A. M. Shamsir] Int Ctr Diarrheal Dis Res, Div Nutr & Food Secur, Matlab, Bangladesh.
[Bessong, Pascal] Univ Venda, HIV AIDS & Global Hlth Res Programme, Thohoyandou, South Africa.
[John, Sushil M.; Kang, Gagandeep] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India.
[Lima, Aldo] Univ Fed Ceara, Clin Res Unit, Fortaleza, Ceara, Brazil.
[Lima, Aldo] Univ Fed Ceara, Inst Biomed, Fortaleza, Ceara, Brazil.
[Shrestha, Prakash] Tribhuvan Univ, Inst Med, Kathmandu, Nepal.
[Svensen, Erling] Univ Bergen, Ctr Int Hlth, Bergen, Norway.
[Svensen, Erling] Haydom Lutheran Hosp, Haydom, Tanzania.
RP Checkley, W (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM wcheckl1@jhmi.edu
OI Bessong, Pascal/0000-0003-0561-272X; Mohan, Venkata
Raghava/0000-0001-5787-7223; Kang, Gagandeep/0000-0002-3656-564X
NR 28
TC 10
Z9 10
U1 1
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1478-7954
J9 POPUL HEALTH METR
JI Popul. Health Metr.
PD MAR 21
PY 2014
VL 12
AR 8
DI 10.1186/1478-7954-12-8
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AH0FF
UT WOS:000335793900001
PM 24656134
ER
PT J
AU Li, KG
Iannotti, RJ
Haynie, DL
Perlus, JG
Simons-Morton, BG
AF Li, Kaigang
Iannotti, Ronald J.
Haynie, Denise L.
Perlus, Jessamyn G.
Simons-Morton, Bruce G.
TI Motivation and planning as mediators of the relation between social
support and physical activity among U. S. adolescents: a nationally
representative study
SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
LA English
DT Article
DE Physical activity; Motivation; Planning; Social support; Adolescents;
SDT
ID INTRINSIC MOTIVATION; BEHAVIOR; EXERCISE; SPORT; PEER; PREDICTORS;
ENGAGEMENT; EDUCATION; FRIENDS; MODELS
AB Background: More than half of U. S. high-school students do not meet the moderate and vigorous physical activity (MVPA) 5 hours per week recommendation. The purpose of this study was to determine how individual dimensions (motivation and planning) mediate the relationship of social context with physical activity by integrating available measures of personal characteristic including internal/external motivations (derived from Self-Determination Theory -SDT]) for MVPA, MVPA planning, peer MVPA, and parental support to better understand adolescent MVPA. Methods: Survey responses of a nationally representative cohort of 11th graders (N = 2439) in the NEXT Generation Health Study were analyzed with structural equation modeling. Results: Adolescent MVPA was directly, significantly associated with MVPA planning (beta = 0.17), peer MVPA (beta = 0.21), and internal motivation (beta = 0.50). Internal motivation was associated with peer MVPA (beta = 0.31), parental support for MVPA (beta = 0.16), and external motivation (beta = 0.40). A significant relation between parental support and external motivation (beta = 0.31) was also found. Conclusions: Adolescents with higher internal motivation and more active friends were more likely to engage in MVPA. The results are consistent with SDT and suggest that planning is an important construct for adolescent MVPA.
C1 [Li, Kaigang; Haynie, Denise L.; Perlus, Jessamyn G.; Simons-Morton, Bruce G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Bethesda, MD 20892 USA.
[Iannotti, Ronald J.] Univ Massachusetts, Boston, MA 02125 USA.
RP Li, KG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, 6100 Execut Blvd, Bethesda, MD 20892 USA.
EM Kaigang.li@nih.gov
OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie,
Denise/0000-0002-8270-6079
FU intramural research program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD)
[HHSN267200800009C]; National Heart, Lung and Blood Institute (NHLBI);
National Institute on Alcohol Abuse and Alcoholism (NIAAA); Maternal and
Child Health Bureau (MCHB) of the Health Resources and Services
Administration (HRSA); National Institute on Drug Abuse (NIDA)
FX This project (contract number HHSN267200800009C) was supported in part
by the intramural research program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD), and
the National Heart, Lung and Blood Institute (NHLBI), the National
Institute on Alcohol Abuse and Alcoholism (NIAAA), and Maternal and
Child Health Bureau (MCHB) of the Health Resources and Services
Administration (HRSA), with supplemental support from the National
Institute on Drug Abuse (NIDA).
NR 49
TC 7
Z9 7
U1 4
U2 25
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5868
J9 INT J BEHAV NUTR PHY
JI Int. J. Behav. Nutr. Phys. Act.
PD MAR 21
PY 2014
VL 11
AR 42
DI 10.1186/1479-5868-11-42
PG 9
WC Nutrition & Dietetics; Physiology
SC Nutrition & Dietetics; Physiology
GA AF4VJ
UT WOS:000334712100001
PM 24656181
ER
PT J
AU Prustel, T
Meier-Schellersheim, M
AF Pruestel, Thorsten
Meier-Schellersheim, Martin
TI The area reactivity model of geminate recombination
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID DIFFUSION-INFLUENCED REACTIONS; BROWNIAN DYNAMICS SIMULATIONS; 3
DIMENSIONS; SPACE
AB We investigate the reversible diffusion-influenced reaction of an isolated pair in the context of the area reactivity model that describes the reversible binding of a single molecule in the presence of a binding site in terms of a generalized version of the Feynman-Kac equation in two dimensions. We compute the corresponding exact Green's function in the Laplace domain for both the initially unbound and bound molecule. We discuss convolution relations that facilitate the calculation of the binding and survival probabilities. Furthermore, we calculate an exact analytical expression for the Green's function in the time domain by inverting the Laplace transform via the Bromwich contour integral and derive expressions for the binding and survival probability in the time domain as well. We numerically confirm the accuracy of the obtained expressions by propagating the generalized Feynman- Kac equation in the time domain. Our results should be useful for comparing the area reactivity model with the contact reactivity model.
C1 [Pruestel, Thorsten; Meier-Schellersheim, Martin] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Prustel, T (reprint author), NIAID, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM prustelt@niaid.nih.gov; mms@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH),
National Institute of Allergy and Infectious Diseases (NIAID)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Institute of Allergy and
Infectious Diseases (NIAID).
NR 31
TC 2
Z9 2
U1 1
U2 7
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0021-9606
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD MAR 21
PY 2014
VL 140
IS 11
AR 114106
DI 10.1063/1.4868554
PG 12
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA AE7HP
UT WOS:000334168400010
PM 24655171
ER
PT J
AU Barnwell, E
Padmaraju, V
Baranello, R
Pacheco-Quinto, J
Crosson, C
Ablonczy, Z
Eckman, E
Eckman, CB
Ramakrishnan, V
Greig, NH
Pappolla, MA
Sambamurti, K
AF Barnwell, Eliza
Padmaraju, Vasudevaraju
Baranello, Robert
Pacheco-Quinto, Javier
Crosson, Craig
Ablonczy, Zsolt
Eckman, Elizabeth
Eckman, Christopher B.
Ramakrishnan, Viswanathan
Greig, Nigel H.
Pappolla, Miguel A.
Sambamurti, Kumar
TI Evidence of a Novel Mechanism for Partial gamma-Secretase Inhibition
Induced Paradoxical Increase in Secreted Amyloid beta Protein
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIN-CONVERTING ENZYME; CARBOXYL-TERMINAL FRAGMENTS; TRANS-GOLGI
NETWORK; ALZHEIMERS-DISEASE; A-BETA; PRECURSOR PROTEIN; CELL-SURFACE;
THERAPEUTIC TARGETS; BACE PROMOTER; APP
AB BACE1 (beta-secretase) and alpha-secretase cleave the Alzheimer's amyloid beta protein (A beta) precursor (APP) to C-terminal fragments of 99 aa (CTF beta) and 83 aa (CTF alpha), respectively, which are further cleaved by gamma-secretase to eventually secrete A beta and A alpha (a.k.a. P3) that terminate predominantly at residues 40 and 42. A number of gamma-secretase inhibitors (GSIs), such as N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT), have been developed with the goal of reducing A beta to treat Alzheimer's disease (AD). Although most studies show that DAPT inhibits A beta in a dose-dependent manner several studies have also detected a biphasic effect with an unexpected increase at low doses of DAPT in cell cultures, animal models and clinical trials. In this article, we confirm the increase in A beta 40 and A beta 42 in SH-SY5Y human neuroblastoma cells treated with low doses of DAPT and identify one of the mechanisms for this paradox. We studied the pathway by first demonstrating that stimulation of A beta, a product of gamma-secretase, was accompanied by a parallel increase of its substrate CTF beta, thereby demonstrating that the inhibitor was not anomalously stimulating enzyme activity at low levels. Secondly, we have demonstrated that inhibition of an A beta degrading activity, endothelin converting enzyme (ECE), yielded more A beta, but Abolished the DAPT-induced stimulation. Finally, we have demonstrated that A alpha, which is generated in the secretory pathway before endocytosis, is not subject to the DAPT-mediated stimulation. We therefore conclude that impairment of gamma-secretase can paradoxically increase A beta by transiently skirting A beta degradation in the endosome. This study adds to the growing body of literature suggesting that preserving gamma-secretase activity, rather than inhibiting it, is important for prevention of neurodegeneration.
C1 [Barnwell, Eliza; Padmaraju, Vasudevaraju; Baranello, Robert; Sambamurti, Kumar] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Pacheco-Quinto, Javier; Eckman, Elizabeth; Eckman, Christopher B.] MidAtlantic Neonatol Associates & Atlant Hlth Sy, Biomed Res Inst New Jersey, Morristown, NJ USA.
[Crosson, Craig; Ablonczy, Zsolt] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
[Ramakrishnan, Viswanathan] Med Univ S Carolina, Dept Biostat, Charleston, SC 29425 USA.
[Greig, Nigel H.] Natl Inst Aging, Intramural Res Program, Translat Gerontol Branch, Drug Design & Dev Sect, Baltimore, MD USA.
[Pappolla, Miguel A.] Univ Texas Med Branch, Dept Neurol, Galveston, TX 77555 USA.
RP Sambamurti, K (reprint author), Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
EM sambak@musc.edu
FU Alzheimer's Association [IIRG 10-173-180]; NIH [AG046200, EY019065,
NS073512]; Research to Prevent Blindness; Intramural NIA
FX Alzheimer's Association IIRG 10-173-180 and NIH AG046200 to KS, EY019065
to ZA, NIH NS073512 to EE, an unrestricted grant of Research to Prevent
Blindness to the Department of Ophthalmology at MUSC and Intramural NIA
to NHG supported this work. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 80
TC 5
Z9 5
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 21
PY 2014
VL 9
IS 3
AR e91531
DI 10.1371/journal.pone.0091531
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6GL
UT WOS:000333355300037
PM 24658363
ER
PT J
AU Contreras-Vallejos, E
Utreras, E
Borquez, DA
Prochazkova, M
Terse, A
Jaffe, H
Toledo, A
Arruti, C
Pant, HC
Kulkarni, AB
Gonzalez-Billault, C
AF Contreras-Vallejos, Erick
Utreras, Elias
Borquez, Daniel A.
Prochazkova, Michaela
Terse, Anita
Jaffe, Howard
Toledo, Andrea
Arruti, Cristina
Pant, Harish C.
Kulkarni, Ashok B.
Gonzalez-Billault, Christian
TI Searching for Novel Cdk5 Substrates in Brain by Comparative
Phosphoproteomics of Wild Type and Cdk5(-/-) Mice
SO PLOS ONE
LA English
DT Article
ID CYCLIN-DEPENDENT KINASE-5; ACTIVATED PROTEIN-KINASE; NEURONAL MIGRATION;
ALZHEIMERS-DISEASE; IN-VIVO; DIFFERENTIATING NEURONS; SYNAPTIC
PLASTICITY; MONOCLONAL-ANTIBODY; PERINATAL DEATH; MARCKS PROTEIN
AB Protein phosphorylation is the most common post-translational modification that regulates several pivotal functions in cells. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase which is mostly active in the nervous system. It regulates several biological processes such as neuronal migration, cytoskeletal dynamics, axonal guidance and synaptic plasticity among others. In search for novel substrates of Cdk5 in the brain we performed quantitative phosphoproteomics analysis, isolating phosphoproteins from whole brain derived from E18.5 Cdk5(+/+) and Cdk5(-/-) embryos, using an Immobilized Metal-Ion Affinity Chromatography (IMAC), which specifically binds to phosphorylated proteins. The isolated phosphoproteins were eluted and isotopically labeled for relative and absolute quantitation (iTRAQ) and mass spectrometry identification. We found 40 proteins that showed decreased phosphorylation at Cdk5(-/-) brains. In addition, out of these 40 hypophosphorylated proteins we characterized two proteins, : MARCKS (Myristoylated Alanine-Rich protein Kinase C substrate) and Grin1 (G protein regulated inducer of neurite outgrowth 1). MARCKS is known to be phosphorylated by Cdk5 in chick neural cells while Grin1 has not been reported to be phosphorylated by Cdk5. When these proteins were overexpressed in N2A neuroblastoma cell line along with p35, serine phosphorylation in their Cdk5 motifs was found to be increased. In contrast, treatments with roscovitine, the Cdk5 inhibitor, resulted in an opposite effect on serine phosphorylation in N2A cells and primary hippocampal neurons transfected with MARCKS. In summary, the results presented here identify Grin 1 as novel Cdk5 substrate and confirm previously identified MARCKS as a a bona fide Cdk5 substrate.
C1 [Contreras-Vallejos, Erick; Utreras, Elias; Borquez, Daniel A.; Gonzalez-Billault, Christian] Univ Chile, Dept Biol, Lab Cellular & Neuronal Dynam, Fac Sci, Santiago, Chile.
[Prochazkova, Michaela; Terse, Anita; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, NIH, Bethesda, MD 20892 USA.
[Jaffe, Howard] NINDS, Prot & Peptide Facil, NIH, Bethesda, MD 20892 USA.
[Toledo, Andrea; Arruti, Cristina] Univ Repub, Fac Ciencias, Dept Biol Celular & Mol, Secci Biol Celular,Lab Cultivo Tejidos, Montevideo, Uruguay.
[Pant, Harish C.] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Sect, NIH, Bethesda, MD 20892 USA.
EM ak40m@nih.gov; chrgonza@uchile.cl
FU Fondecyt [1095089, ACT1114, PAI 79100009, 11110136]; Divisions of
Intramural Research, National Institute of Dental and Craniofacial
Research; National Institute of Neurological Disorders and Stroke,
National Institutes of Health, Bethesda, Maryland, United States of
America; [CONICYT-24120958]; [MECESUP-UCH7013]
FX The work was supported by CONICYT-24120958 and MECESUP-UCH7013 (EC)
Fondecyt 1095089 and ACT1114 (to CG-B), PAI 79100009 and Fondecyt
11110136 (EU), and the Divisions of Intramural Research, National
Institute of Dental and Craniofacial Research (ABK) and the National
Institute of Neurological Disorders and Stroke (HCP), National
Institutes of Health, Bethesda, Maryland, United States of America. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 72
TC 9
Z9 10
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 21
PY 2014
VL 9
IS 3
AR e90363
DI 10.1371/journal.pone.0090363
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6GL
UT WOS:000333355300016
PM 24658276
ER
PT J
AU Montasser, ME
Shimmin, LC
Gu, DF
Chen, J
Gu, C
Kelly, TN
Jaquish, CE
Rice, TK
Rao, DC
Cao, J
Chen, JC
De-Peliu
Whelton, PK
Hamm, LL
He, J
Hixson, JE
AF Montasser, May E.
Shimmin, Lawrence C.
Gu, Dongfeng
Chen, Jing
Gu, Charles
Kelly, Tanika N.
Jaquish, Cashell E.
Rice, Treva K.
Rao, Dabeeru C.
Cao, Jie
Chen, Jichun
De-Peliu
Whelton, Paul K.
Hamm, Lotuce Lee
He, Jiang
Hixson, James E.
TI Variation in Genes that Regulate Blood Pressure Are Associated with
Glomerular Filtration Rate in Chinese
SO PLOS ONE
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; RENIN-ANGIOTENSIN SYSTEM; ALPHA-ADDUCIN GENE;
11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; WHOLE-GENOME ASSOCIATION;
CHANNEL GAMMA-SUBUNIT; BETA(2)-ADRENERGIC RECEPTOR;
ESSENTIAL-HYPERTENSION; LINKAGE ANALYSIS; DIABETIC-NEPHROPATHY
AB Chronic kidney disease (CKD) can be a consequence of diabetes, hypertension, immunologic disorders, and other exposures, as well as genetic factors that are still largely unknown. Glomerular filtration rate (GFR), which is widely used to measure kidney function, has a heritability ranging from 25% to 75%, but only 1.5% of this heritability is explained by genetic loci that have been identified to date. In this study we tested for associations between GFR and 234 SNPs in 26 genes from pathways of blood pressure regulation in 3,025 rural Chinese participants of the "Genetic Epidemiology Network of Salt Sensitivity" (GenSalt) study. We estimated GFR (eGFR) using baseline serum creatinine measurements obtained prior to dietary intervention. We identified significant associations between eGFR and 12 SNPs in 6 genes (ACE, ADD1, AGT, GRK4, HSD11B1, and SCNN1G). The cumulative effect of the protective alleles was an increase in mean eGFR of 4 mL/min per 1.73 m(2), while the cumulative effect of the risk alleles was a decrease in mean eGFR of 3 mL/min per 1.73 m(2). In addition, we identified a significant interaction between SNPs in CYP11B1 and ADRB2. We have identified common variants in genes from pathways that regulate blood pressure and influence kidney function as measured by eGFR, providing new insights into the genetic determinants of kidney function. Complex genetic effects on kidney function likely involve interactions among genes as we observed for CYP11B1 and ADRB2.
C1 [Montasser, May E.; Shimmin, Lawrence C.; Hixson, James E.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA.
[Gu, Dongfeng; Cao, Jie; Chen, Jichun] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100730, Peoples R China.
[Gu, Dongfeng; Cao, Jie; Chen, Jichun] Chinese Acad Med Sci, Fu Wai Hosp, Beijing 100730, Peoples R China.
[Chen, Jing; Hamm, Lotuce Lee] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
[Gu, Charles; Rice, Treva K.; Rao, Dabeeru C.] Washington Univ, Sch Med, St Louis, MO USA.
[Kelly, Tanika N.; Whelton, Paul K.; He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Jaquish, Cashell E.] NHLBI, NIH, Bethesda, MD 20892 USA.
[De-Peliu] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100730, Peoples R China.
RP Montasser, ME (reprint author), Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
EM mmontass@medicine.umaryland.edu
FU National Heart, Lung and Blood Institute, National Institutes of Health,
Bethesda, Maryland [U01HL072507, R01HL087263, R01HL090682]
FX The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is
supported by several grants (U01HL072507, R01HL087263, and R01HL090682)
from the National Heart, Lung and Blood Institute, National Institutes
of Health, Bethesda, Maryland. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 75
TC 5
Z9 5
U1 2
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 21
PY 2014
VL 9
IS 3
AR e92468
DI 10.1371/journal.pone.0092468
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6GL
UT WOS:000333355300086
PM 24658007
ER
PT J
AU Prasad, V
Rho, J
Selvaraj, S
Cheung, M
Vandross, A
Ho, N
AF Prasad, Vinay
Rho, Jason
Selvaraj, Senthil
Cheung, Mike
Vandross, Andrae
Ho, Nancy
TI Can a Resident's Publication Record Predict Fellowship Publications?
SO PLOS ONE
LA English
DT Article
ID MEDICAL-SCHOOL; APPLICANTS; BEHAVIOR; SURGERY
AB Background: Internal medicine fellowship programs have an incentive to select fellows who will ultimately publish. Whether an applicant's publication record predicts long term publishing remains unknown.
Methods: Using records of fellowship bound internal medicine residents, we analyzed whether publications at time of fellowship application predict publications more than 3 years (2 years into fellowship) and up to 7 years after fellowship match. We calculate the sensitivity, specificity, positive and negative predictive values and likelihood ratios for every cutoff number of application publications, and plot a receiver operator characteristic curve of this test.
Results: Of 307 fellowship bound residents, 126 (41%) published at least one article 3 to 7 years after matching, and 181 (59%) of residents do not publish in this time period. The area under the receiver operator characteristic curve is 0.59. No cutoff value for application publications possessed adequate test characteristics.
Conclusion: The number of publications an applicant has at time of fellowship application is a poor predictor of who publishes in the long term. These findings do not validate the practice of using application publications as a tool for selecting fellows.
C1 [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Rho, Jason; Cheung, Mike] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Selvaraj, Senthil] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Vandross, Andrae] Yale Univ, Dept Med, New Haven, CT 06520 USA.
[Ho, Nancy] Univ Maryland, Dept Med, Baltimore, MD 21201 USA.
RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov
NR 12
TC 1
Z9 1
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 21
PY 2014
VL 9
IS 3
AR e90140
DI 10.1371/journal.pone.0090140
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6GL
UT WOS:000333355300011
PM 24658088
ER
PT J
AU Weinstein, JN
Akbani, R
Broom, BM
Wang, WY
Verhaak, RGW
McConkey, D
Lerner, S
Morgan, M
Creighton, CJ
Smith, C
Kwiatkowski, DJ
Cherniack, AD
Kim, J
Pedamallu, CS
Noble, MS
Al-Ahmadie, HA
Reuter, VE
Rosenberg, JE
Bajorin, DF
Bochner, BH
Solit, DB
Koppie, T
Robinson, B
Gordenin, DA
Fargo, D
Klimczak, LJ
Roberts, SA
Au, J
Laird, PW
Hinoue, T
Schultz, N
Ramirez, R
Hansel, D
Hoadley, KA
Kim, WY
Damrauer, JS
Baylin, SB
Mungall, AJ
Robertson, AG
Chu, A
Kwiatkowski, DJ
Sougnez, C
Cibulskis, K
Lichtenstein, L
Sivachenko, A
Stewart, C
Lawrence, MS
Getz, G
Lander, E
Gabriel, SB
Creighton, CJ
Donehower, L
Cherniack, AD
Kim, J
Carter, SL
Saksena, G
Schumacher, SE
Sougnez, C
Freeman, SS
Jung, J
Pedamallu, CS
Bhatt, AS
Pugh, T
Getz, G
Beroukhim, R
Gabriel, SB
Meyerson, M
Mungall, AJ
Robertson, AG
Chu, A
Ally, A
Balasundaram, M
Butterfield, YSN
Dhalla, N
Hirst, C
Holt, RA
Jones, SJM
Lee, D
Li, HYI
Marra, MA
Mayo, M
Moore, RA
Schein, JE
Sipahimalani, P
Tam, A
Thiessen, N
Wong, T
Wye, N
Bowlby, R
Chuah, E
Guin, R
Jones, SJM
Marra, MA
Hinoue, T
Shen, H
Bootwalla, MS
Triche, T
Lai, PH
Van den Berg, DJ
Weisenberger, DJ
Laird, PW
Hansel, D
Hoadley, KA
Balu, S
Bodenheimer, T
Damrauer, JS
Hoyle, AP
Jefferys, SR
Meng, SW
Mose, LE
Simons, JV
Soloway, MG
Wu, JY
Kim, WY
Parker, JS
Hayes, DN
Roach, J
Buda, E
Jones, CD
Mieczkowski, PA
Tan, DH
Veluvolu, U
Waring, S
Auman, JT
Perou, CM
Wilkerson, MD
Santoso, N
Parfenov, M
Ren, XJ
Pantazi, A
Hadjipanayis, A
Seidman, J
Kucherlapati, R
Lee, S
Yang, LX
Park, PJ
Baylin, SB
Xu, AW
Protopopov, A
Zhang, JH
Bristow, C
Mahadeshwar, HS
Seth, S
Song, XZ
Tang, JB
Zeng, D
Chin, LD
Guo, C
Weinstein, JN
Akbani, R
Broom, BM
McConkey, D
Casasent, TD
Liu, WB
Ju, ZL
Motter, T
Peng, B
Ryan, M
Wang, WY
Verhaak, RGW
Su, XP
Yang, JY
Lorenzi, PL
Yao, H
Zhang, NX
Zhang, JX
Mills, GB
Kim, J
Noble, MS
Cho, J
DiCara, D
Frazer, S
Gehlenborg, N
Heiman, DI
Lin, P
Liu, YC
Stojanov, P
Voet, D
Zhang, HL
Zou, LH
Chin, LD
Getz, G
Bernard, B
Kreisberg, D
Reynolds, S
Rovira, H
Shmulevich, I
Ramirez, R
Schultz, N
Gao, JJ
Jacobsen, A
Aksoy, BA
Antipin, Y
Ciriello, G
Dresdner, G
Gross, B
Lee, W
Reva, B
Shen, RL
Sinha, R
Sumer, SO
Weinhold, N
Ladanyi, M
Sander, C
Benz, C
Carlin, D
Haussler, D
Ng, S
Paull, EO
Stuart, J
Zhu, J
Liu, YX
Zhang, W
Taylor, BS
Lichtenberg, TM
Zmuda, E
Barr, T
Black, AD
George, M
Hanf, B
Helsel, C
McAllister, C
Ramirez, NC
Tabler, TR
Weaver, S
Wise, L
Bowen, J
Gastier-Foster, JM
Weinstein, JN
Lerner, S
Jian, WG
Tello, S
Ittman, M
Castro, P
McClenden, WD
Morgan, M
Gibbs, R
Liu, YC
Saller, C
Tarvin, K
DiPiero, JM
Owens, J
Bollag, R
Li, Q
Weinberger, P
Czerwinski, C
Huelsenbeck-Dill, L
Iacocca, M
Petrelli, N
Rabeno, B
Swanson, P
Shelton, T
Curley, E
Gardner, J
Mallery, D
Penny, R
Bang, NV
Hanh, PT
Kohl, B
Le, XV
Phu, BD
Thorp, R
Tien, NV
Vinh, LQ
Sandusky, G
Burks, E
Christ, K
Gee, J
Holway, A
Moinzadeh, A
Sorcini, A
Sullivan, T
Al-Ahmadie, HA
Bajorin, DF
Bochner, BH
Garcia-Grossman, IR
Regazzi, AM
Solit, DB
Rosenberg, JE
Reuter, VE
Koppie, T
Boice, L
Rathmell, WK
Thorne, L
Bastacky, S
Davies, B
Dhir, R
Gingrich, J
Hrebinko, R
Maranchie, J
Nelson, J
Parwani, A
Bshara, W
Gaudioso, C
Morrison, C
Alexopoulou, V
Bartlett, J
Engel, J
Kodeeswaran, S
Antic, T
O'Donnell, PH
Smith, ND
Steinberg, GD
Egea, S
Gomez-Fernandez, C
Herbert, L
Jorda, M
Soloway, M
Beaver, A
Carter, S
Kapur, P
Lewis, C
Lotan, Y
Robinson, B
Hansel, D
Guo, C
Bondaruk, J
Czerniak, B
Akbani, R
Broom, BM
Liu, YX
Zhang, W
Weinstein, JN
Lerner, S
Morgan, M
Kim, J
Cherniack, AD
Freeman, SS
Pedamallu, CS
Noble, MS
Kwiatkowski, DJ
Al-Ahmadie, HA
Bajorin, DF
Bochner, BH
Solit, DB
Rosenberg, JE
Reuter, VE
Koppie, T
Robinson, B
Skinner, E
Ramirez, R
Schultz, N
Hansel, D
Kim, WY
Guo, C
Bondaruk, J
Aldape, K
Czerniak, B
Jensen, MA
Kahn, AB
Pihl, TD
Pot, DA
Srinivasan, D
Wan, YH
Ferguson, ML
Zenklusen, JC
Davidsen, T
Demchok, JA
Shaw, KRM
Sheth, M
Tarnuzzer, R
Wang, ZN
Yang, LM
Hutter, C
Ozenberger, BA
Sofia, HJ
Eley, G
AF Weinstein, John N.
Akbani, Rehan
Broom, Bradley M.
Wang, Wenyi
Verhaak, Roeland G. W.
McConkey, David
Lerner, Seth
Morgan, Margaret
Creighton, Chad J.
Smith, Carolyn
Kwiatkowski, David J.
Cherniack, Andrew D.
Kim, Jaegil
Pedamallu, Chandra Sekhar
Noble, Michael S.
Al-Ahmadie, Hikmat A.
Reuter, Victor E.
Rosenberg, Jonathan E.
Bajorin, Dean F.
Bochner, Bernard H.
Solit, David B.
Koppie, Theresa
Robinson, Brian
Gordenin, Dmitry A.
Fargo, David
Klimczak, Leszek J.
Roberts, Steven A.
Au, Jessie
Laird, Peter W.
Hinoue, Toshinori
Schultz, Nikolaus
Ramirez, Ricardo
Hansel, Donna
Hoadley, Katherine A.
Kim, William Y.
Damrauer, Jeffrey S.
Baylin, Stephen B.
Mungall, Andrew J.
Robertson, A. Gordon
Chu, Andy
Kwiatkowski, David J.
Sougnez, Carrie
Cibulskis, Kristian
Lichtenstein, Lee
Sivachenko, Andrey
Stewart, Chip
Lawrence, Michael S.
Getz, Gad
Lander, Eric
Gabriel, Stacey B.
Creighton, Chad J.
Donehower, Lawrence
Cherniack, Andrew D.
Kim, Jaegil
Carter, Scott L.
Saksena, Gordon
Schumacher, Steven E.
Sougnez, Carrie
Freeman, Samuel S.
Jung, Joonil
Pedamallu, Chandra Sekhar
Bhatt, Ami S.
Pugh, Trevor
Getz, Gad
Beroukhim, Rameen
Gabriel, Stacey B.
Meyerson, Matthew
Mungall, Andrew J.
Robertson, A. Gordon
Chu, Andy
Ally, Adrian
Balasundaram, Miruna
Butterfield, Yaron S. N.
Dhalla, Noreen
Hirst, Carrie
Holt, Robert A.
Jones, Steven J. M.
Lee, Darlene
Li, Haiyan I.
Marra, Marco A.
Mayo, Michael
Moore, Richard A.
Schein, Jacqueline E.
Sipahimalani, Payal
Tam, Angela
Thiessen, Nina
Wong, Tina
Wye, Natasja
Bowlby, Reanne
Chuah, Eric
Guin, Ranabir
Jones, Steven J. M.
Marra, Marco A.
Hinoue, Toshinori
Shen, Hui
Bootwalla, Moiz S.
Triche, Timothy, Jr.
Lai, Phillip H.
Van den Berg, David J.
Weisenberger, Daniel J.
Laird, Peter W.
Hansel, Donna
Hoadley, Katherine A.
Balu, Saianand
Bodenheimer, Tom
Damrauer, Jeffrey S.
Hoyle, Alan P.
Jefferys, Stuart R.
Meng, Shaowu
Mose, Lisle E.
Simons, Janae V.
Soloway, Mathew G.
Wu, Junyuan
Kim, William Y.
Parker, Joel S.
Hayes, D. Neil
Roach, Jeffrey
Buda, Elizabeth
Jones, Corbin D.
Mieczkowski, Piotr A.
Tan, Donghui
Veluvolu, Umadevi
Waring, Scot
Auman, J. Todd
Perou, Charles M.
Wilkerson, Matthew D.
Santoso, Netty
Parfenov, Michael
Ren, Xiaojia
Pantazi, Angeliki
Hadjipanayis, Angela
Seidman, Jonathan
Kucherlapati, Raju
Lee, Semin
Yang, Lixing
Park, Peter J.
Baylin, Stephen B.
Xu, Andrew Wei
Protopopov, Alexei
Zhang, Jianhua
Bristow, Christopher
Mahadeshwar, Harshad S.
Seth, Sahil
Song, Xingzhi
Tang, Jiabin
Zeng, Dong
Chin, Lynda
Guo, Charles
Weinstein, John N.
Akbani, Rehan
Broom, Bradley M.
McConkey, David
Casasent, Tod D.
Liu, Wenbin
Ju, Zhenlin
Motter, Thomas
Peng, Bo
Ryan, Michael
Wang, Wenyi
Verhaak, Roeland G. W.
Su, Xiaoping
Yang, Ji-Yeon
Lorenzi, Philip L.
Yao, Hui
Zhang, Nianxiang
Zhang, Jiexin
Mills, Gordon B.
Kim, Jaegil
Noble, Michael S.
Cho, Juok
DiCara, Daniel
Frazer, Scott
Gehlenborg, Nils
Heiman, David I.
Lin, Pei
Liu, Yingchun
Stojanov, Petar
Voet, Doug
Zhang, Hailei
Zou, Lihua
Chin, Lynda
Getz, Gad
Bernard, Brady
Kreisberg, Dick
Reynolds, Sheila
Rovira, Hector
Shmulevich, Ilya
Ramirez, Ricardo
Schultz, Nikolaus
Gao, Jianjiong
Jacobsen, Anders
Aksoy, B. Arman
Antipin, Yevgeniy
Ciriello, Giovanni
Dresdner, Gideon
Gross, Benjamin
Lee, William
Reva, Boris
Shen, Ronglai
Sinha, Rileen
Sumer, S. Onur
Weinhold, Nils
Ladanyi, Marc
Sander, Chris
Benz, Christopher
Carlin, Daniel
Haussler, David
Ng, Sam
Paull, Evan O.
Stuart, Joshua
Zhu, Jing
Liu, Yuexin
Zhang, Wei
Taylor, Barry S.
Lichtenberg, Tara M.
Zmuda, Erik
Barr, Thomas
Black, Aaron D.
George, Myra
Hanf, Benjamin
Helsel, Carmen
McAllister, Cynthia
Ramirez, Nilsa C.
Tabler, Teresa R.
Weaver, Stephanie
Wise, Lisa
Bowen, Jay
Gastier-Foster, Julie M.
Weinstein, John N.
Lerner, Seth
Jian, Weiguo
Tello, Sebrina
Ittman, Michael
Castro, Patricia
McClenden, Whitney D.
Morgan, Margaret
Gibbs, Richard
Liu, Yingchun
Saller, Charles
Tarvin, Katherine
DiPiero, Jennifer M.
Owens, Jennifer
Bollag, Roni
Li, Qiang
Weinberger, Paul
Czerwinski, Christine
Huelsenbeck-Dill, Lori
Iacocca, Mary
Petrelli, Nicholas
Rabeno, Brenda
Swanson, Pat
Shelton, Troy
Curley, Erin
Gardner, Johanna
Mallery, David
Penny, Robert
Nguyen Van Bang
Phan Thi Hanh
Kohl, Bernard
Xuan Van Le
Bui Duc Phu
Thorp, Richard
Nguyen Viet Tien
Le Quang Vinh
Sandusky, George
Burks, Eric
Christ, Kimberly
Gee, Jason
Holway, Antonia
Moinzadeh, Alireza
Sorcini, Andrea
Sullivan, Travis
Al-Ahmadie, Hikmat A.
Bajorin, Dean F.
Bochner, Bernard H.
Garcia-Grossman, Ilana R.
Regazzi, Ashley M.
Solit, David B.
Rosenberg, Jonathan E.
Reuter, Victor E.
Koppie, Theresa
Boice, Lori
Rathmell, Wendy Kimryn
Thorne, Leigh
Bastacky, Sheldon
Davies, Benjamin
Dhir, Rajiv
Gingrich, Jeffrey
Hrebinko, Ronald
Maranchie, Jodi
Nelson, Joel
Parwani, Anil
Bshara, Wiam
Gaudioso, Carmelo
Morrison, Carl
Alexopoulou, Vina
Bartlett, John
Engel, Jay
Kodeeswaran, Sugy
Antic, Tatjana
O'Donnell, Peter H.
Smith, Norm D.
Steinberg, Gary D.
Egea, Sophie
Gomez-Fernandez, Carmen
Herbert, Lynn
Jorda, Merce
Soloway, Mark
Beaver, Allison
Carter, Suzie
Kapur, Payal
Lewis, Cheryl
Lotan, Yair
Robinson, Brian
Hansel, Donna
Guo, Charles
Bondaruk, Jolanta
Czerniak, Bogdan
Akbani, Rehan
Broom, Bradley M.
Liu, Yuexin
Zhang, Wei
Weinstein, John N.
Lerner, Seth
Morgan, Margaret
Kim, Jaegil
Cherniack, Andrew D.
Freeman, Samuel S.
Pedamallu, Chandra Sekhar
Noble, Michael S.
Kwiatkowski, David J.
Al-Ahmadie, Hikmat A.
Bajorin, Dean F.
Bochner, Bernard H.
Solit, David B.
Rosenberg, Jonathan E.
Reuter, Victor E.
Koppie, Theresa
Robinson, Brian
Skinner, Eila
Ramirez, Ricardo
Schultz, Nikolaus
Hansel, Donna
Kim, William Y.
Guo, Charles
Bondaruk, Jolanta
Aldape, Kenneth
Czerniak, Bogdan
Jensen, Mark A.
Kahn, Ari B.
Pihl, Todd D.
Pot, David A.
Srinivasan, Deepak
Wan, Yunhu
Ferguson, Martin L.
Zenklusen, Jean Claude
Davidsen, Tanja
Demchok, John A.
Shaw, Kenna R. Mills
Sheth, Margi
Tarnuzzer, Roy
Wang, Zhining
Yang, Liming
Hutter, Carolyn
Ozenberger, Bradley A.
Sofia, Heidi J.
Eley, Greg
CA Canc Genome Atlas Res Network
TI Comprehensive molecular characterization of urothelial bladder carcinoma
SO NATURE
LA English
DT Article
ID HUMAN CANCERS; GENE FUSIONS; TUMOR-GROWTH; MUTATIONS; GENOMES; KINASE;
FGFR
AB Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomasto provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.
C1 [Weinstein, John N.; Akbani, Rehan; Broom, Bradley M.; Wang, Wenyi; Verhaak, Roeland G. W.; Liu, Wenbin; Ju, Zhenlin; Motter, Thomas; Peng, Bo; Ryan, Michael; Su, Xiaoping; Yang, Ji-Yeon; Lorenzi, Philip L.; Yao, Hui; Zhang, Nianxiang; Zhang, Jiexin] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
[Liu, Wenbin; Ju, Zhenlin; Yang, Ji-Yeon; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
[McConkey, David; Shaw, Kenna R. Mills] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Lerner, Seth; Jian, Weiguo; Tello, Sebrina] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA.
[Morgan, Margaret; Jian, Weiguo; Tello, Sebrina; Ittman, Michael; Castro, Patricia; McClenden, Whitney D.; Gibbs, Richard] Baylor Coll Med, TCRB, Houston, TX 77030 USA.
[Gibbs, Richard] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Creighton, Chad J.; Donehower, Lawrence] Baylor Coll Med, Human Genome Sequencing Ctr, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Smith, Carolyn] Baylor Coll Med, Houston, TX 77030 USA.
[Kwiatkowski, David J.; Kwiatkowski, David J.; Cibulskis, Kristian; Lichtenstein, Lee; Sivachenko, Andrey; Stewart, Chip; Lawrence, Michael S.; Getz, Gad; Lander, Eric; Gabriel, Stacey B.; Carter, Scott L.; Saksena, Gordon; Schumacher, Steven E.; Freeman, Samuel S.; Jung, Joonil; Bhatt, Ami S.; Pugh, Trevor; Beroukhim, Rameen; Meyerson, Matthew; Chin, Lynda; Cho, Juok; DiCara, Daniel; Frazer, Scott; Gehlenborg, Nils; Heiman, David I.; Lin, Pei; Liu, Yingchun; Stojanov, Petar; Voet, Doug; Zhang, Hailei; Zou, Lihua] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA 02142 USA.
[Kwiatkowski, David J.; Casasent, Tod D.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Kwiatkowski, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Bhatt, Ami S.; Pugh, Trevor; Beroukhim, Rameen; Meyerson, Matthew; Stojanov, Petar] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Garcia-Grossman, Ilana R.; Regazzi, Ashley M.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Koppie, Theresa] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR 97239 USA.
Cornell Univ, Weill Med Coll, New York, NY 10065 USA.
[Gordenin, Dmitry A.; Fargo, David; Klimczak, Leszek J.; Roberts, Steven A.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Au, Jessie] OptimumTherapeutics LLC, San Diego, CA 92121 USA.
[Shen, Hui; Bootwalla, Moiz S.; Triche, Timothy, Jr.; Lai, Phillip H.; Van den Berg, David J.; Weisenberger, Daniel J.] Univ So Calif, Epigenome Ctr, Los Angeles, CA 90033 USA.
[Schultz, Nikolaus; Ramirez, Ricardo; Gao, Jianjiong; Jacobsen, Anders; Aksoy, B. Arman; Antipin, Yevgeniy; Ciriello, Giovanni; Dresdner, Gideon; Gross, Benjamin; Lee, William; Reva, Boris; Shen, Ronglai; Sinha, Rileen; Sumer, S. Onur; Weinhold, Nils; Ladanyi, Marc; Sander, Chris] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
[Hansel, Donna] UCSD Dept Pathol, La Jolla, CA 92093 USA.
[Hoadley, Katherine A.; Balu, Saianand; Bodenheimer, Tom; Hoyle, Alan P.; Jefferys, Stuart R.; Meng, Shaowu; Mose, Lisle E.; Simons, Janae V.; Soloway, Mathew G.; Wu, Junyuan; Parker, Joel S.; Hayes, D. Neil] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Parker, Joel S.; Perou, Charles M.; Wilkerson, Matthew D.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
[Baylin, Stephen B.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Canc Biol Div, Baltimore, MD 21231 USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Donehower, Lawrence] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
[Schumacher, Steven E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
[Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA.
[Mungall, Andrew J.; Chu, Andy; Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S. N.; Dhalla, Noreen; Hirst, Carrie; Holt, Robert A.; Jones, Steven J. M.; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Wong, Tina; Wye, Natasja; Bowlby, Reanne; Chuah, Eric; Guin, Ranabir] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada.
[Hayes, D. Neil] Univ N Carolina, Dept Internal Med, Div Med Oncol, Chapel Hill, NC 27599 USA.
[Roach, Jeffrey] Univ N Carolina, Res Comp Ctr, Chapel Hill, NC 27599 USA.
[Buda, Elizabeth; Jones, Corbin D.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Jones, Corbin D.; Mieczkowski, Piotr A.; Tan, Donghui; Veluvolu, Umadevi; Waring, Scot] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
[Auman, J. Todd] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
[Santoso, Netty; Parfenov, Michael; Ren, Xiaojia; Pantazi, Angeliki; Hadjipanayis, Angela; Seidman, Jonathan; Kucherlapati, Raju] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Hadjipanayis, Angela; Kucherlapati, Raju; Park, Peter J.; Xu, Andrew Wei] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
[Lee, Semin; Yang, Lixing; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
[Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA.
[Protopopov, Alexei; Zhang, Jianhua; Bristow, Christopher; Mahadeshwar, Harshad S.; Seth, Sahil; Song, Xingzhi; Tang, Jiabin; Zeng, Dong] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Inst Appl Canc Sci, Houston, TX 77030 USA.
[Guo, Charles; Bondaruk, Jolanta; Czerniak, Bogdan; Aldape, Kenneth] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Bernard, Brady; Kreisberg, Dick; Reynolds, Sheila; Rovira, Hector; Shmulevich, Ilya] Inst Syst Biol, Seattle, WA 98109 USA.
[Benz, Christopher] Buck Inst Res Aging, Novato, CA 94945 USA.
[Carlin, Daniel; Haussler, David; Ng, Sam; Paull, Evan O.; Stuart, Joshua; Zhu, Jing] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA.
[Liu, Yuexin; Zhang, Wei] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Taylor, Barry S.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA.
[Lichtenberg, Tara M.; Zmuda, Erik; Barr, Thomas; Black, Aaron D.; George, Myra; Hanf, Benjamin; Helsel, Carmen; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Weaver, Stephanie; Wise, Lisa; Bowen, Jay; Gastier-Foster, Julie M.] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.
[Ramirez, Nilsa C.; Gastier-Foster, Julie M.] Ohio State Univ, Columbus, OH 43210 USA.
[Ittman, Michael; Castro, Patricia] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA.
[Saller, Charles; Tarvin, Katherine] Analyt Biol Serv Inc, Wilmington, DE 19801 USA.
[DiPiero, Jennifer M.; Owens, Jennifer] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Bollag, Roni; Li, Qiang; Weinberger, Paul] Georgia Regents Univ, Canc Ctr, Augusta, GA 30912 USA.
[Czerwinski, Christine; Huelsenbeck-Dill, Lori; Iacocca, Mary; Petrelli, Nicholas; Rabeno, Brenda; Swanson, Pat] Christiana Care, Helen F Graham Canc Ctr, Newark, DE 19713 USA.
[Shelton, Troy; Curley, Erin; Gardner, Johanna; Mallery, David; Penny, Robert] Int Genom Consortium, Phoenix, AZ 85004 USA.
[Nguyen Van Bang; Phan Thi Hanh; Kohl, Bernard; Xuan Van Le; Bui Duc Phu; Thorp, Richard; Nguyen Viet Tien; Le Quang Vinh] ILSbio LLC, Chestertown, MD 21620 USA.
Hue Cent Hosp, Hue City, Vietnam.
[Sandusky, George] IU Sch Med, Indianapolis, IN 46202 USA.
[Burks, Eric; Christ, Kimberly; Gee, Jason; Holway, Antonia; Moinzadeh, Alireza; Sorcini, Andrea; Sullivan, Travis] Lahey Hosp & Med Ctr, Burlington, MA 01805 USA.
[Boice, Lori; Rathmell, Wendy Kimryn; Thorne, Leigh] Univ N Carolina, Lineberger Canc Ctr, Chapel Hill, NC 27599 USA.
[Bastacky, Sheldon; Davies, Benjamin; Dhir, Rajiv; Gingrich, Jeffrey; Hrebinko, Ronald; Maranchie, Jodi; Nelson, Joel; Parwani, Anil] Univ Pittsburgh, Pittsburgh, PA 15213 USA.
[Bshara, Wiam; Gaudioso, Carmelo; Morrison, Carl] Roswell Pk Canc Inst, Buffalo, NY 14063 USA.
[Alexopoulou, Vina; Bartlett, John; Engel, Jay; Kodeeswaran, Sugy] St Josephs Healthcare Hamilton, Ontario Tumour Bank, Hamilton, ON L8N 3Z5, Canada.
[Antic, Tatjana; O'Donnell, Peter H.; Smith, Norm D.; Steinberg, Gary D.] Univ Chicago, Chicago, IL 60637 USA.
[Egea, Sophie; Gomez-Fernandez, Carmen; Herbert, Lynn; Jorda, Merce; Soloway, Mark] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Beaver, Allison; Carter, Suzie; Kapur, Payal; Lewis, Cheryl; Lotan, Yair] UT Southwestern Med Ctr, Dallas, TX 75390 USA.
[Skinner, Eila] Stanford Univ, Dept Urol, Stanford, CA 94305 USA.
[Jensen, Mark A.; Kahn, Ari B.; Pihl, Todd D.; Pot, David A.; Srinivasan, Deepak; Wan, Yunhu] SRA Int, Fairfax, VA 22033 USA.
[Ferguson, Martin L.] MLF Consulting, Arlington, MA 02474 USA.
[Zenklusen, Jean Claude; Davidsen, Tanja; Demchok, John A.; Shaw, Kenna R. Mills; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming] NCI, Bethesda, MD 20892 USA.
[Hutter, Carolyn; Ozenberger, Bradley A.; Sofia, Heidi J.] NHGRI, Rockville, MD 20852 USA.
[Eley, Greg] Scimentis LLC, Atlanta, GA 30666 USA.
RP Weinstein, JN (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
EM jweinste@mdanderson.org; slerner@bcm.edu; dk@rics.bwh.harvard.edu
RI Laird, Peter/G-8683-2012; Jacobsen, Anders/K-1081-2013; Schein,
Jacquie/G-3674-2015; Weinberger, Paul/B-7007-2008; Jones,
Steven/C-3621-2009; Lee, Semin/S-2629-2016; Marra, Marco/B-5987-2008;
Holt, Robert/C-3303-2009;
OI Gordenin, Dmitry/0000-0002-8399-1836; Maranchie,
Jodi/0000-0002-8534-9468; Seth, Sahil/0000-0003-4579-3959; Pot,
David/0000-0002-1480-9826; Sinha, Rileen/0000-0001-5497-5055; Perou,
Charles/0000-0001-9827-2247; Gehlenborg, Nils/0000-0003-0327-8297;
Triche, Tim/0000-0001-5665-946X; Jacobsen, Anders/0000-0001-6847-4980;
Weinberger, Paul/0000-0002-5885-2631; Lee, Semin/0000-0002-9015-6046;
Kohl, Bernard/0000-0002-4610-0934; Schultz,
Nikolaus/0000-0002-0131-4904; Al-Ahmadie, Hikmat/0000-0002-2938-6627;
Rosenberg, Jonathan/0000-0003-2637-4249
FU United States National Institutes of Health [U54 HG003273, U54 HG003067,
U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843,
U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867,
U24 CA143882, U24 CA143883, U24 CA144025, P01 CA120964]
FX We are grateful to all of the patients and families who contributed to
this study, as well as C. Gunter and L. Chastain for scientific editing
and M. Sheth, J. Zhang and C. Ron Bouchard for administrative support.
This work was supported by the following grants from the United States
National Institutes of Health: U54 HG003273, U54 HG003067, U54 HG003079,
U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845,
U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882,
U24 CA143883, U24 CA144025 and P01 CA120964. Additional personnel and
funding sources are acknowledged in the Supplementary Information.
NR 39
TC 379
Z9 383
U1 14
U2 126
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 20
PY 2014
VL 507
IS 7492
BP 315
EP 322
DI 10.1038/nature12965
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1YG
UT WOS:000333029000025
ER
PT J
AU Gopal, S
Achenbach, CJ
Yanik, EL
Dittmer, DP
Eron, JJ
Engels, EA
AF Gopal, Satish
Achenbach, Chad J.
Yanik, Elizabeth L.
Dittmer, Dirk P.
Eron, Joseph J.
Engels, Eric A.
TI Moving Forward in HIV-Associated Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID HUMAN-IMMUNODEFICIENCY-VIRUS; NON-HODGKIN-LYMPHOMA; B-CELL LYMPHOMA;
HEPATITIS-C VIRUS; UNITED-STATES; HUMAN-PAPILLOMAVIRUS; CERVICAL-CANCER;
HEPATOCELLULAR-CARCINOMA; ANTIRETROVIRAL THERAPY; INFECTED PATIENTS
C1 [Gopal, Satish] Univ N Carolina, Chapel Hill, NC 27523 USA.
[Achenbach, Chad J.] Northwestern Univ, Chicago, IL 60611 USA.
[Yanik, Elizabeth L.; Engels, Eric A.] NCI, Bethesda, MD 20892 USA.
[Dittmer, Dirk P.; Eron, Joseph J.] Univ N Carolina, Chapel Hill, NC USA.
RP Gopal, S (reprint author), Univ N Carolina, Chapel Hill, NC 27523 USA.
EM gopal@med.unc.edu
OI Achenbach, Chad/0000-0003-4847-7249
FU FIC NIH HHS [K01 TW009488, R25 TW009340]; NCI NIH HHS [P30 CA016086, R01
CA163217, R21 CA180815, U01 CA121947]; NIAID NIH HHS [P30 AI050410, R24
AI067039]
NR 64
TC 14
Z9 15
U1 0
U2 4
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 20
PY 2014
VL 32
IS 9
BP 876
EP +
DI 10.1200/JCO.2013.53.1376
PG 6
WC Oncology
SC Oncology
GA AG0XA
UT WOS:000335137900012
PM 24550416
ER
PT J
AU Desmond, R
Townsley, DM
Dumitriu, B
Olnes, MJ
Scheinberg, P
Bevans, M
Parikh, AR
Broder, K
Calvo, KR
Wu, CO
Young, NS
Dunbar, CE
AF Desmond, Ronan
Townsley, Danielle M.
Dumitriu, Bogdan
Olnes, Matthew J.
Scheinberg, Phillip
Bevans, Margaret
Parikh, Ankur R.
Broder, Kinneret
Calvo, Katherine R.
Wu, Colin O.
Young, Neal S.
Dunbar, Cynthia E.
TI Eltrombopag restores trilineage hematopoiesis in refractory severe
aplastic anemia that can be sustained on discontinuation of drug
SO BLOOD
LA English
DT Article
ID COLONY-STIMULATING FACTOR; MYELODYSPLASTIC SYNDROMES; LONG-TERM;
IMMUNOSUPPRESSIVE THERAPY; ANTITHYMOCYTE GLOBULIN; C-MPL; CYTOGENETIC
ABNORMALITIES; PROGENITOR CELLS; MICE LACKING; STEM-CELLS
AB About a quarter of patients with severe aplastic anemia remain pancytopenic despite immunosuppressive therapy. We have previously demonstrated that eltrombopag has efficacy in this setting with 44%(11/25) of patients having clinically significant hematologic responses. We now report safety and efficacy data on a further 18 patients and long-term follow-up on the entire cohort of 43 patients. The overall response rate was 17 of 43 patients (40%) at 3 to 4 months, including tri- and bilineage responses. The majority of patients who remained on eltrombopag in an extension study (14/17) continued to show improvement, and 7 eventually had significant increases in neutrophil, red cell, and platelet lineages. Five patients with robust near-normalization of blood counts had drug discontinued at a median of 28.5 months after entry (range, 9-37 months), and all maintained stable counts a median of 13 months (range, 1-15 months) off eltrombopag. Eight patients, including 6 nonresponders and 2 responders, developed new cytogenetic abnormalities on eltrombopag, including 5 with chromosome 7 loss or partial deletion. None evolved to acute myeloid leukemia to date. Eltrombopag is efficacious in a subset of patients with aplastic anemia refractory to immunosuppressive therapy, with frequent multilineage responses and maintenance of normalized hematopoiesis off treatment. This study is registered at www.clinicaltrials.gov as #NCT00922883.
C1 [Desmond, Ronan; Townsley, Danielle M.; Dumitriu, Bogdan; Parikh, Ankur R.; Broder, Kinneret; Young, Neal S.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Olnes, Matthew J.] Alaska Native Tribal Hlth Consortium, Dept Hematol, Anchorage, AK USA.
[Scheinberg, Phillip] Hosp Beneficencia Portuguesa Sao Paulo, Hosp Sao Jose, Sao Paulo, Brazil.
[Bevans, Margaret] NIH, Bethesda, MD 20892 USA.
[Calvo, Katherine R.] NIH, Lab Med, Bethesda, MD 20892 USA.
[Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
RP Dunbar, CE (reprint author), NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bldg 10-CRC,Room 4E-5132,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dunbarc@nhlbi.nih.gov
OI Scheinberg, Phillip/0000-0002-9047-4538; Calvo,
Katherine/0000-0002-0771-4191
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda
FX This research was supported by the Intramural Research Program of the
National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda.
NR 49
TC 51
Z9 56
U1 0
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 20
PY 2014
VL 123
IS 12
BP 1818
EP 1825
DI 10.1182/blood-2013-10-534743
PG 8
WC Hematology
SC Hematology
GA AH0ZH
UT WOS:000335848800015
PM 24345753
ER
PT J
AU Paralkar, VR
Mishra, T
Luan, J
Yao, Y
Kossenkov, AV
Anderson, SM
Dunagin, M
Pimkin, M
Gore, M
Sun, D
Konuthula, N
Raj, A
An, XL
Mohandas, N
Bodine, DM
Hardison, RC
Weiss, MJ
AF Paralkar, Vikram R.
Mishra, Tejaswini
Luan, Jing
Yao, Yu
Kossenkov, Andrew V.
Anderson, Stacie M.
Dunagin, Margaret
Pimkin, Maxim
Gore, Meghneel
Sun, Diana
Konuthula, Neeraja
Raj, Arjun
An, Xiuli
Mohandas, Narla
Bodine, David M.
Hardison, Ross C.
Weiss, Mitchell J.
TI Lineage and species-specific long noncoding RNAs during
erythro-megakaryocytic development
SO BLOOD
LA English
DT Article
ID HUMAN GENOME; TRANSCRIPT EXPRESSION; DISTINCT STAGES; HUMAN-CELLS;
DIFFERENTIATION; REGULATORS; EVOLUTION; DATABASE; BIOLOGY; GENE
AB Mammals express thousands of long noncoding (lnc) RNAs, a few of which are known to function in tissue development. However, the entire repertoire of lncRNAs in most tissues and species is not defined. Indeed, most lncRNAs are not conserved, raising questions about function. We used RNA sequencing to identify 1109 polyadenylated lncRNAs expressed in erythroblasts, megakaryocytes, and megakaryocyte-erythroid precursors of mice, and 594 in erythroblasts of humans. More than half of these lncRNAs were un-annotated, emphasizing the opportunity for new discovery through studies of specialized cell types. Analysis of the mouse erythro-megakaryocytic polyadenylated lncRNA transcriptome indicates that similar to 75% arise from promoters and 25% from enhancers, many of which are regulated by key transcription factors including GATA1 and TAL1. Erythroid lncRNA expression is largely conserved among 8 different mouse strains, yet only 15% of mouse lncRNAs are expressed in humans and vice versa, reflecting dramatic species specificity. RNA interference assays of 21 abundant erythroid-specific murine lncRNAs in primary mouse erythroid precursors identified 7 whose knockdown inhibited terminal erythroid maturation. At least 6 of these 7 functional lncRNAs have no detectable expression in human erythroblasts, suggesting that lack of conservation between mammalian species does not predict lack of function.
C1 [Paralkar, Vikram R.] Univ Penn, Perelman Sch Med, Div Hematol Oncol, Philadelphia, PA 19104 USA.
[Mishra, Tejaswini; Hardison, Ross C.] Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
[Mishra, Tejaswini; Hardison, Ross C.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Luan, Jing; Yao, Yu; Pimkin, Maxim; Sun, Diana; Weiss, Mitchell J.] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA.
[Kossenkov, Andrew V.] Wistar Inst Anat & Biol, Ctr Syst & Computat Biol, Philadelphia, PA 19104 USA.
[Anderson, Stacie M.] NHGRI, Natl Human Genome Res Inst Flow Cytometry Core Fa, NIH, Bethesda, MD 20892 USA.
[Dunagin, Margaret; Raj, Arjun] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA.
[Gore, Meghneel] Salesforce, San Francisco, CA USA.
[Konuthula, Neeraja] Icahn Sch Med Mt Sinai, New York, NY USA.
[An, Xiuli] New York Blood Ctr, Lab Membrane Biol, New York, NY 10021 USA.
[Mohandas, Narla] New York Blood Ctr, Red Cell Physiol Lab, New York, NY 10021 USA.
[Bodine, David M.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Weiss, MJ (reprint author), Childrens Hosp Philadelphia, Div Hematol, Abramson Res Ctr 316B,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM weissmi@email.chop.edu
OI Raj, Arjun/0000-0002-2915-6960
FU American Society of Hematology (ASH); UPenn Measey Fellowship Award;
National Institutes of Health [1DP2OD008514]; Burroughs-Wellcome Fund
Career Award at the Scientific Interface; National Institutes of Health,
National Institute of Diabetes and Digestive and Kidney Diseases
[DK32094, DK065806, DK092318-01, P30DK090969]; National Institutes of
Health, National Human Genome Research Institute Intramural funds;
National Institutes of Health, National Human Genome Research Institute
[1RC2HG005573]; Roche Foundation for Anemia Research; National Science
Foundation [OCI-0821527]
FX This work was supported by the American Society of Hematology (ASH)
Research Training Award for Fellows (V. R. P.); ASH Scholar Award (V. R.
P.); UPenn Measey Fellowship Award (V. R. P.); National Institutes of
Health Common Fund, New Innovator (1DP2OD008514) (M. D., A. R.);
Burroughs-Wellcome Fund Career Award at the Scientific Interface (M. D.,
A. R.); National Institutes of Health, National Institute of Diabetes
and Digestive and Kidney Diseases (DK32094) (N.M.); National Institutes
of Health, National Human Genome Research Institute Intramural funds (D.
M. B.); National Institutes of Health, National Human Genome Research
Institute (1RC2HG005573) (R. C. H.); National Institutes of Health,
National Institute of Diabetes and Digestive and Kidney Diseases
(DK065806) (R. C. H.) and (DK092318-01 and P30DK090969) (M.J.W.); The
Roche Foundation for Anemia Research (M.J.W.); and the National Science
Foundation (OCI-0821527, for instrumentation).
NR 42
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U1 3
U2 18
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 20
PY 2014
VL 123
IS 12
BP 1927
EP 1937
DI 10.1182/blood-2013-12-544494
PG 11
WC Hematology
SC Hematology
GA AH0ZH
UT WOS:000335848800028
PM 24497530
ER
PT J
AU Gounden, V
Jonldaas, J
Soldin, SJ
AF Gounden, Verena
Jonldaas, Jacqueline
Soldin, Steven J.
TI A pilot study: Subclinical hypothyroidism and free thyroid hormone
measurement by immunoassay and mass spectrometry
SO CLINICA CHIMICA ACTA
LA English
DT Article
DE Mass spectrometry; Free thyroid hormone; Subclinical hypothyroidism
ID ANALYTE ASSAY FUNCTION; FREE-THYROXINE; ILLEGITIMATE TESTS; LEGITIMATE;
THERAPY; DISEASE
AB Background: The diagnosis of subclinical hypothyroidism is defined as the presence of an elevated thyroid stimulating hormone (TSH) with a normal free thyroxine (FT4) level. The commonly used direct analogue immunoassays for the measurement of FT4 have been shown to have poor performance at the upper and lower limits of the FT4 reference interval.
Purpose: The purpose of this pilot study was to investigate the percentage of individuals classified as having subclinical hypothyroidism with a standard immunoassay, that actually have low free thyroid hormone levels by mass spectrometry measurements.
Design: Outpatient samples with elevated TSH values and normal FT4 concentrations as per standard immunoassay methods were collected. FT4 and free triiodothyronine (FT3) analyses were performed on these samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Results: Sixty five percent (n = 26) of patients (n = 40) had (LC-MS/MS) FT4 or FT3 or both FT4 and FT3 values below mass spectrometry reference limits.
Conclusions: Our findings indicate that the direct analogue immunoassay method for FT4 measurement results in a significant proportion of patients being misclassified as having subclinical hypothyroidism. Published by Elsevier B.V.
C1 [Gounden, Verena; Soldin, Steven J.] NIH Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA.
[Jonldaas, Jacqueline; Soldin, Steven J.] Georgetown Univ, Med Ctr, Div Endocrinol, Washington, DC 20007 USA.
RP Soldin, SJ (reprint author), NIH Clin Ctr, Dept Lab Med, Bldg 10,Room 2C-249, Bethesda, MD 20892 USA.
EM Steven.soldin@nih.gov
FU National Center for Advancing Translational Sciences (NCATS), National
Institutes of Health (NIH), through the Clinical and Translational
Science Awards Program (CTSA) [UL1TR000101, UL1RR031975]; trademark of
DHHS, part of the Roadmap Initiative, "Re-Engineering the Clinical
Research Enterprise; Intramural Research Project of the NIH Clinical
Center
FX This project has been funded in whole or in part with Federal funds
(Grant # UL1TR000101 previously UL1RR031975) from the National Center
for Advancing Translational Sciences (NCATS), National Institutes of
Health (NIH), through the Clinical and Translational Science Awards
Program (CTSA), a trademark of DHHS, part of the Roadmap Initiative,
"Re-Engineering the Clinical Research Enterprise and supported (in part)
by the Intramural Research Project of the NIH Clinical Center.
NR 21
TC 8
Z9 8
U1 4
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0009-8981
EI 1873-3492
J9 CLIN CHIM ACTA
JI Clin. Chim. Acta
PD MAR 20
PY 2014
VL 430
BP 121
EP 124
DI 10.1016/j.cca.2013.12.034
PG 4
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA AG6RM
UT WOS:000335546100024
PM 24389098
ER
PT J
AU Escobar, VD
Kuo, YM
Orrison, BM
Giasson, BI
Nussbaum, RL
AF Escobar, Valerie Drews
Kuo, Yien-Ming
Orrison, Bonnie M.
Giasson, Benoit I.
Nussbaum, Robert L.
TI Transgenic mice expressing S129 phosphorylation mutations in
alpha-synuclein
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE alpha-synuclein; Parkinson's disease; Phosphorylation; Lewy bodies;
Transgenic
ID PARKINSONS-DISEASE; RAT MODEL; DROSOPHILA MODEL; SER-129; DYSFUNCTION;
SYSTEM
AB Aggregated alpha-synuclein is a predominant constituent of Lewy bodies, the intracellular protein aggregates seen in Parkinson's disease. While most alpha-synuclein in the nervous system is unphosphorylated, the majority of alpha-synuclein in Lewy bodies is phosphorylated at serine 129 (S129). We developed transgenic mice expressing human SNCA with either a phosphomimic (S129D) or a non-phosphorylatable (S129A) mutation, on a mouse Snca knockout background. Transgenic lines with each mutation expressing the human alpha-synuclein protein at levels ranging from 0.3 to 1.9 fold of endogenous mouse protein were chosen to avoid toxic overexpression effects. We previously demonstrated an altered distribution of presynaptic vesicles in Snca knockout mice, as well as enhanced interaction between presynaptic cytoskeletal proteins and alpha-synuclein when phosphorylated at S129 or carrying an S129D mutation. We therefore examined alpha-synuclein's synaptic localization and the distribution of presynaptic vesicles in these mutants. In addition, we evaluated the transgenic lines for reduced colonic motility, an early marker of alpha-synuclein pathology, and alpha-synuclein aggregates. No abnormalities were detected in mice expressing either phosphorylation mutant protein as their only alpha-synuclein protein. These results suggest the S129A and S129D mutations have no obvious effect on alpha-synuclein function. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Escobar, Valerie Drews; Kuo, Yien-Ming; Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Escobar, Valerie Drews; Kuo, Yien-Ming; Nussbaum, Robert L.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Orrison, Bonnie M.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Giasson, Benoit I.] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
RP Nussbaum, RL (reprint author), Univ Calif San Francisco, Box 0794,513 Parnassus Ave, San Francisco, CA 94143 USA.
EM nussbaumr@humgen.ucsf.edu
FU Division of Intramural Research, NHGRI; Michael J. Fox Foundation; UCSF
Department of Medicine; Institute of Human Genetics (RLN); NIH
[NS053488]
FX Supported by the Division of Intramural Research, NHGRI, the Michael J.
Fox Foundation, and the UCSF Department of Medicine and Institute of
Human Genetics (RLN), and NIH grant number NS053488 (BG). V.D.E.
participated in design of experiments, carried out the majority of
experiments, and was the primary author of the manuscript, B.M.O.
constructed the engineered PACs, Y.M.K. performed real time PCR and
colonic motility experiments, B.G. performed immunohistochemistry on the
brain tissue, and R.L.N. contributed to design of experiments, review of
data, and preparation of the manuscript.
NR 24
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U1 0
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD MAR 20
PY 2014
VL 563
BP 96
EP 100
DI 10.1016/j.neu1et.2014.01.033
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA AE5CR
UT WOS:000334005900020
PM 24486885
ER
PT J
AU Fruth, U
Broutet, N
Deal, C
Dodet, B
Meheus, A
AF Fruth, Uli
Broutet, Nathalie
Deal, Carolyn
Dodet, Betty
Meheus, Andre
TI Vaccines for sexually transmitted infections: Past, present and future
SO VACCINE
LA English
DT Editorial Material
C1 [Fruth, Uli; Broutet, Nathalie] World Hlth Org, Geneva, Switzerland.
[Deal, Carolyn] NIAID, Bethesda, MD 20892 USA.
[Dodet, Betty] Dodet Biosci, Caluire Et Cuire, France.
[Meheus, Andre] Univ Antwerp, NESI, B-2020 Antwerp, Belgium.
RP Fruth, U (reprint author), World Hlth Org, Geneva, Switzerland.
EM fruthu@who.int
FU World Health Organization [001]
NR 22
TC 1
Z9 1
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD MAR 20
PY 2014
VL 32
IS 14
SI SI
BP 1525
EP 1526
DI 10.1016/j.vaccine.2014.01.051
PG 2
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AE2HM
UT WOS:000333793900002
PM 24480028
ER
PT J
AU Knipe, DM
Corey, L
Cohen, JI
Deal, CD
AF Knipe, David M.
Corey, Lawrence
Cohen, Jeffrey I.
Deal, Carolyn D.
TI Summary and recommendations from a National Institute of Allergy and
Infectious Diseases (NIAID) workshop on "Next Generation Herpes Simplex
Virus Vaccines"
SO VACCINE
LA English
DT Editorial Material
C1 [Knipe, David M.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
[Corey, Lawrence] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Cohen, Jeffrey I.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
[Deal, Carolyn D.] NIAID, Div Microbiol & Infect Dis, Bethesda, MD 20892 USA.
RP Knipe, DM (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
EM david_knipe@hms.harvard.edu; CDeal@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000548-20]; NIAID NIH HHS [R01 AI057552]
NR 0
TC 11
Z9 11
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD MAR 20
PY 2014
VL 32
IS 14
SI SI
BP 1561
EP 1562
DI 10.1016/j.vaccine.2014.01.052
PG 2
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AE2HM
UT WOS:000333793900007
PM 24480025
ER
PT J
AU Broutet, N
Fruth, U
Deal, C
Gottlieb, SL
Rees, H
AF Broutet, Nathalie
Fruth, Uli
Deal, Carolyn
Gottlieb, Sami L.
Rees, Helen
CA 2013 STI Vaccine Tech Consultation
TI Vaccines against sexually transmitted infections: The way forward
SO VACCINE
LA English
DT Article
ID NEISSERIA-GONORRHOEAE; CHLAMYDIA-TRACHOMATIS; HERPES; METAANALYSIS;
PREVALENCE; AFRICA
C1 [Broutet, Nathalie; Fruth, Uli; Gottlieb, Sami L.] WHO, CH-1211 Geneva 27, Switzerland.
[Deal, Carolyn] NIAID, Bethesda, MD 20892 USA.
[Rees, Helen] Univ Witwatersrand, Wits Reprod Hlth & HIV Inst, Johannesburg, South Africa.
RP Broutet, N (reprint author), WHO, Dept Reprod Hlth & Res, Ave Appia 20, CH-1211 Geneva 27, Switzerland.
EM broutetn@who.int
OI Mabey, David/0000-0002-0031-8276; Hawkes, Sarah/0000-0003-1062-3538;
Ravel, Jacques/0000-0002-0851-2233
FU Prevent, a non-profit vaccine development enterprise; government of
Canada; US government; Canadian government; GSK; Merck Co.; Roche
Molecular Systems; Qiagen as a member of the Women's Health Advisory
Board; AiCuris GmbH; Agenus Inc; Genocea Biosciences; John Oishei
Foundation; Sanofi Pasteur; Agenus; Medimmune; Australian Government;
Queensland Government; Nobilon
FX R. BRUNHAM: His employer, the University of British Columbia, has filed
a patent application on chlamydia proteins discovered during government
funded research, and received research grants in the amount of
US$250,000 for chlamydia vaccine development work from Prevent, a
non-profit vaccine development enterprise funded by the government of
Canada.; C. CAMERON: Her employer, the University of Victoria, is in the
initial stages of filing a patent covering a recombinant T. pallidum
protein that shows promise as a syphilis vaccine candidate, and received
grants (in the total amount of US$1,500,000) from the US government and
Canadian government to support Dr Cameron's work to develop a syphilis
vaccine.; G. GARNETT: prior to 2011 received funding from GSK for his
work in HPV epidemiology, with no payment in the last 4 years.; P.
GRAVITT: Her employer (JHSPH) has received: (1) one grant from Merck &
Co. (in the amount of US$100,472 between 2012 and 2013) for HPV-related
epidemiological work; (2) a grant from Roche Molecular Systems (in the
amount of US$500,000 between 2005 and 2010). PG has received a grant
from Qiagen as a member of the Women's Health Advisory Board (= 3 mo preconception vs. Arm 2: 12-14 wk gestation vs. Arm 3: none.
192 (derived from 480) randomized mothers and living offspring in each arm in each of four research sites (Guatemala, India, Pakistan, Democratic Republic of the Congo). The intervention is a daily 20 g lipid-based (118 kcal) multi-micronutient (MMN) supplement. Women randomized to receive this intervention with body mass index (BMI) < 20 or whose gestational weight gain is low will receive an additional 300 kcal/d as a balanced energy-protein supplement. Researchers will visit homes biweekly to deliver intervention and monitor compliance, pregnancy status and morbidity; ensure prenatal and delivery care; and promote breast feeding. The primary outcome is birth length. Secondary outcomes include: fetal length at 12 and 34 wk; incidence of low birth weight (LBW); neonatal/infant anthropometry 0-6 mo of age; infectious disease morbidity; maternal, fetal, newborn, and infant epigenetics; maternal and infant nutritional status; maternal and infant microbiome; gut inflammatory biomarkers and bioactive and nutritive compounds in breast milk. The primary analysis will compare birth Length-for-Age Z-score (LAZ) among trial arms (independently for each site, estimated effect size: 0.35). Additional statistical analyses will examine the secondary outcomes and a pooled analysis of data from all sites.
Discussion: Positive results of this trial will support a paradigm shift in attention to nutrition of all females of child-bearing age.
C1 [Hambidge, K. Michael; Krebs, Nancy F.; Westcott, Jamie E.; Friedman, Jacob E.; Frank, Daniel N.] Univ Colorado Denver, Aurora, CO 80045 USA.
[Garces, Ana] Francisco Marroquin Univ, Guatemala City, Guatemala.
[Goudar, Shivaprasad S.; Kodkany, Balachandra S.] KLE Univ, Jawaharlal Nehru Med Coll, Belgaum, Karnataka, India.
[Pasha, Omrana] Aga Khan Univ, Karachi, Pakistan.
[Tshefu, Antoinette] Kinshasa Sch Publ Hlth, Kinshasa, Zaire.
[Bose, Carl L.] Univ N Carolina, Chapel Hill, NC USA.
[Figueroa, Lester] FANCAP, Guatemala City, Guatemala.
[Goldenberg, Robert L.] Columbia Univ, New York, NY USA.
[Derman, Richard J.] Christiana Care, Newark, DE USA.
[McClure, Elizabeth M.; Stolka, Kristen; Das, Abhik] RTI Int, Res Triangle Pk, NC USA.
[Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA.
[Sundberg, Shelly] Bill & Melinda Gates Fdn, Seattle, WA USA.
RP Hambidge, KM (reprint author), Univ Colorado Denver, Aurora, CO 80045 USA.
EM Michael.Hambidge@ucdenver.edu
OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053
FU Bill & Melinda Gates Foundation [OPP1055867]; Eunice Kennedy Shriver
National Institute of Child Health & Human Development; Office of
Dietary Supplements, NIH [U10 HD076474]
FX Supported by the Bill & Melinda Gates Foundation OPP1055867. Also
supported by The Eunice Kennedy Shriver National Institute of Child
Health & Human Development and the Office of Dietary Supplements, NIH #
U10 HD076474.
NR 37
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Z9 11
U1 5
U2 35
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2393
J9 BMC PREGNANCY CHILDB
JI BMC Pregnancy Childbirth
PD MAR 20
PY 2014
VL 14
AR 111
DI 10.1186/1471-2393-14-111
PG 16
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AE1AU
UT WOS:000333698400001
PM 24650219
ER
PT J
AU Wang, Y
Godec, J
Ben-Aissa, K
Cui, KR
Zhao, KJ
Pucsek, AB
Lee, YK
Weaver, CT
Yagi, R
Lazarevic, V
AF Wang, Yan
Godec, Jernej
Ben-Aissa, Khadija
Cui, Kairong
Zhao, Keji
Pucsek, Alexandra B.
Lee, Yun Kyung
Weaver, Casey T.
Yagi, Ryoji
Lazarevic, Vanja
TI The Transcription Factors T-bet and Runx Are Required for the Ontogeny
of Pathogenic Interferon-gamma-Producing T Helper 17 Cells
SO IMMUNITY
LA English
DT Article
ID IFNG GENE-EXPRESSION; HUMAN TH17 CELLS; ROR-GAMMA; T(H)17 CELLS;
LINEAGE; DIFFERENTIATION; PLASTICITY; CYTOKINE; FOXP3; ENCEPHALOMYELITIS
AB T helper 17 (Th17) cells can give rise to interleukin-17A (IL-17A)- and interferon (IFN)-gamma-double-producing cells that are implicated in development of autoimmune diseases. However, the molecular mechanisms that govern generation of IFN-gamma-producing Th17 cells are unclear. We found that coexpression of the Th1 and Th17 cell master transcription factors, T-bet and retinoid-related orphan receptor gamma-t (ROR gamma t), respectively, did not generate Th cells with robust IL-17 and IFN-gamma expression. Instead, development of IFN-gamma-producing Th17 cells required T-bet and Runx1 or Runx3. IL-12-stimulated Th17 cells upregulated Runx1, which bound to the Ifng locus in a T-bet-dependent manner. Reciprocally, T-bet or Runx1 deficiency or inhibition of Runx transcriptional activity impaired the development of IFN-gamma-producing Th17 cells during experimental autoimmune encephalomyelitis, which correlated with substantially ameliorated disease course. Thus, our studies identify a critical role for T-bet and Runx transcription factors in the generation of pathogenic IFN-gamma-producing Th17 cells.
C1 [Wang, Yan; Ben-Aissa, Khadija; Lazarevic, Vanja] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Godec, Jernej] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
[Godec, Jernej] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Cui, Kairong; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Pucsek, Alexandra B.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA.
[Lee, Yun Kyung; Weaver, Casey T.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Yagi, Ryoji] Chiba Univ, Grad Sch Med, Dept Immunol, Chiba 2608670, Japan.
RP Lazarevic, V (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM lazarevicv@mail.nih.gov
OI Weaver, Casey/0000-0002-2180-1793
FU Intramural NIH HHS [ZIA BC011431-02]; NCI NIH HHS [P30 CA013148]; NIAMS
NIH HHS [P30 AR048311]; NIDDK NIH HHS [P01 DK071176]
NR 39
TC 46
Z9 46
U1 2
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD MAR 20
PY 2014
VL 40
IS 3
BP 355
EP 366
DI 10.1016/j.immuni.2014.01.002
PG 12
WC Immunology
SC Immunology
GA AD7DQ
UT WOS:000333422300009
PM 24530058
ER
PT J
AU Yagi, RJ
Zhong, C
Northrup, DL
Yu, F
Bouladoux, N
Spencer, S
Hu, GQ
Barron, L
Sharma, S
Nakayama, T
Belkaid, Y
Zhao, KJ
Zhu, JF
AF Yagi, Ryoji
Zhong, Chao
Northrup, Daniel L.
Yu, Fang
Bouladoux, Nicolas
Spencer, Sean
Hu, Gangqing
Barron, Luke
Sharma, Suveena
Nakayama, Toshinori
Belkaid, Yasmine
Zhao, Keji
Zhu, Jinfang
TI The Transcription Factor GATA3 Is Critical for the Development of All
IL-7R alpha-Expressing Innate Lymphoid Cells
SO IMMUNITY
LA English
DT Article
ID ROR-GAMMA-T; TISSUE INDUCER CELLS; TYPE-2 IMMUNITY; RETINOIC-ACID;
EXPRESSION; DIFFERENTIATION; INFLAMMATION; GENERATION; LINEAGE; FETAL
AB Innate lymphoid cells (ILCs) are critical in innate immune responses to pathogens and lymphoid organ development. Similar to CD4(+) T helper (Th) cell subsets, ILC subsets positive for interleukin-7 receptor alpha (IL-7R alpha) produce distinct sets of effector cytokines. However, the molecular control of IL-7R alpha(+) ILC development and maintenance is unclear. Here, we report that GATA3 was indispensable for the development of all IL-7R alpha(+) ILC subsets and T cells but was not required for the development of classical natural killer cells. Conditionally Gata3-deficient mice had no lymph nodes and were susceptible to Citrobactor rodentium infection. After the ILCs had fully developed, GATA3 remained important for the maintenance and functions of ILC2s. Genome-wide gene expression analyses indicated that GATA3 regulated a similar set of cytokines and receptors in Th2 cells and ILC2s, but not in ILC3s. Thus, GATA3 plays parallel roles in regulating the development and functions of CD4(+) T cells and IL-7R alpha(+) ILCs.
C1 [Yagi, Ryoji; Zhong, Chao; Yu, Fang; Sharma, Suveena; Zhu, Jinfang] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Northrup, Daniel L.; Hu, Gangqing; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Bouladoux, Nicolas; Spencer, Sean; Barron, Luke; Belkaid, Yasmine] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Nakayama, Toshinori] Chiba Univ, Grad Sch Med, Dept Immunol, Chiba 2608670, Japan.
RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM jfzhu@niaid.nih.gov
RI HU, GANGQING/K-5849-2012; Zhu, Jinfang/B-7574-2012; Nakayama,
Toshinori/E-1067-2017
FU NIH NIAID Division of Intramural Research (DIR); NHLBI DIR
FX We thank Ronald Germain, Dragana Jankovic, William Paul, and John O'Shea
for their critical reading of our manuscript; Julie Edwards for her
excellent assistance in cell sorting; the NHLBI DNA Sequencing and
Computational Biology Core for sequencing the RNA-seq libraries; and
Naofumi Takemoto, Hidehiro Yamane, George Punkosdy, Michelle Crank,
Amina Metidji, Liying Guo, and Giuseppe Sciume for their helpful
discussions. The work was supported by the NIH NIAID Division of
Intramural Research (DIR) and NHLBI DIR.
NR 53
TC 87
Z9 90
U1 0
U2 17
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD MAR 20
PY 2014
VL 40
IS 3
BP 378
EP 388
DI 10.1016/j.immuni.2014.01.012
PG 11
WC Immunology
SC Immunology
GA AD7DQ
UT WOS:000333422300011
PM 24631153
ER
PT J
AU Bailey, AL
Lauck, M
Weiler, A
Sibley, SD
Dinis, JM
Bergman, Z
Nelson, CW
Correll, M
Gleicher, M
Hyeroba, D
Tumukunde, A
Weny, G
Chapman, C
Kuhn, JH
Hughes, AL
Friedrich, TC
Goldberg, TL
O'Connor, DH
AF Bailey, Adam L.
Lauck, Michael
Weiler, Andrea
Sibley, Samuel D.
Dinis, Jorge M.
Bergman, Zachary
Nelson, Chase W.
Correll, Michael
Gleicher, Michael
Hyeroba, David
Tumukunde, Alex
Weny, Geoffrey
Chapman, Colin
Kuhn, Jens H.
Hughes, Austin L.
Friedrich, Thomas C.
Goldberg, Tony L.
O'Connor, David H.
TI High Genetic Diversity and Adaptive Potential of Two Simian Hemorrhagic
Fever Viruses in a Wild Primate Population
SO PLOS ONE
LA English
DT Article
ID RESPIRATORY-SYNDROME-VIRUS; DEHYDROGENASE-ELEVATING VIRUS; EQUINE
ARTERITIS VIRUS; N-LINKED GLYCOSYLATION; NEUTRALIZATION EPITOPE;
ANTIBODY NEUTRALIZATION; IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN;
INFECTIOUS-DISEASES; MOLECULAR-BIOLOGY
AB Key biological properties such as high genetic diversity and high evolutionary rate enhance the potential of certain RNA viruses to adapt and emerge. Identifying viruses with these properties in their natural hosts could dramatically improve disease forecasting and surveillance. Recently, we discovered two novel members of the viral family Arteriviridae: simian hemorrhagic fever virus (SHFV)-krc1 and SHFV-krc2, infecting a single wild red colobus (Procolobus rufomitratus tephrosceles) in Kibale National Park, Uganda. Nearly nothing is known about the biological properties of SHFVs in nature, although the SHFV type strain, SHFV-LVR, has caused devastating outbreaks of viral hemorrhagic fever in captive macaques. Here we detected SHFV-krc1 and SHFV-krc2 in 40% and 47% of 60 wild red colobus tested, respectively. We found viral loads in excess of 10(6)-10(7) RNA copies per milliliter of blood plasma for each of these viruses. SHFV-krc1 and SHFV-krc2 also showed high genetic diversity at both the inter-and intra-host levels. Analyses of synonymous and non-synonymous nucleotide diversity across viral genomes revealed patterns suggestive of positive selection in SHFV open reading frames (ORF) 5 (SHFV-krc2 only) and 7 (SHFV-krc1 and SHFV-krc2). Thus, these viruses share several important properties with some of the most rapidly evolving, emergent RNA viruses.
C1 [Bailey, Adam L.; Lauck, Michael; O'Connor, David H.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA.
[Bailey, Adam L.; Lauck, Michael; Weiler, Andrea; Sibley, Samuel D.; Bergman, Zachary; Friedrich, Thomas C.; Goldberg, Tony L.; O'Connor, David H.] Wisconsin Natl Primate Res Ctr, Madison, WI USA.
[Weiler, Andrea; Sibley, Samuel D.; Dinis, Jorge M.; Bergman, Zachary; Friedrich, Thomas C.; Goldberg, Tony L.] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA.
[Nelson, Chase W.; Hughes, Austin L.] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA.
[Correll, Michael; Gleicher, Michael] Univ Wisconsin, Dept Comp Sci, Madison, WI 53706 USA.
[Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Chapman, Colin] Makerere Univ, Kampala, Uganda.
[Chapman, Colin] McGill Univ, Dept Anthropol, Montreal, PQ, Canada.
[Chapman, Colin] McGill Univ, Sch Environm, Montreal, PQ, Canada.
[Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA.
RP O'Connor, DH (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA.
EM dhoconno@wisc.edu
RI Kuhn, Jens H./B-7615-2011;
OI Kuhn, Jens H./0000-0002-7800-6045; o'connor, david/0000-0003-2139-470X;
Sibley, Samuel/0000-0002-6754-3187; Friedrich,
Thomas/0000-0001-9831-6895
FU US Department of Health and Human Services [HHSN272200700016I]
FX Jens H. Kuhn is employed by a commercial company, Tunnell Government
Services, Inc. Tunnell is a subcontractor to Battelle Memorial
Institute, which is the primary contractor to NIH to run the NIH
facility "Integrated Research Facility at Fort Detrick". As the authors
pointed out in the disclaimer, Tunnell's involvement with Battelle, and
Battelle's involvement with NIH is stipulated in US Department of Health
and Human Services contract HHSN272200700016I. All work performed by
Jens H. Kuhn (and all other Tunnell IRF employees) is property of the US
government under the contract. Jens H. Kuhn therefore has no competing
interests. The affiliation with Tunnell/Battelle does not alter Jens H.
Kuhn's adherence to all PLOS ONE policies on sharing data and materials.
To be completely clear, this does not alter the authors' adherence to
PLOS ONE policies on sharing data and materials. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 68
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U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 20
PY 2014
VL 9
IS 3
AR e90714
DI 10.1371/journal.pone.0090714
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6FV
UT WOS:000333352800021
PM 24651479
ER
PT J
AU Burk, D
Ingram, JN
Franklin, DW
Shadlen, MN
Wolpert, DM
AF Burk, Diana
Ingram, James N.
Franklin, David W.
Shadlen, Michael N.
Wolpert, Daniel M.
TI Motor Effort Alters Changes of Mind in Sensorimotor Decision Making
SO PLOS ONE
LA English
DT Article
ID DEVELOPING OCULOMOTOR COMMANDS; PERCEPTUAL DECISION; NEURAL BASIS;
DISCRIMINATION; REPRESENTATION; TIME
AB After committing to an action, a decision-maker can change their mind to revise the action. Such changes of mind can even occur when the stream of information that led to the action is curtailed at movement onset. This is explained by the time delays in sensory processing and motor planning which lead to a component at the end of the sensory stream that can only be processed after initiation. Such post-initiation processing can explain the pattern of changes of mind by asserting an accumulation of additional evidence to a criterion level, termed change-of-mind bound. Here we test the hypothesis that physical effort associated with the movement required to change one's mind affects the level of the change-of-mind bound and the time for post-initiation deliberation. We varied the effort required to change from one choice target to another in a reaching movement by varying the geometry of the choice targets or by applying a force field between the targets. We show that there is a reduction in the frequency of change of mind when the separation of the choice targets would require a larger excursion of the hand from the initial to the opposite choice. The reduction is best explained by an increase in the evidence required for changes of mind and a reduced time period of integration after the initial decision. Thus the criteria to revise an initial choice is sensitive to energetic costs.
C1 [Burk, Diana; Ingram, James N.; Franklin, David W.; Wolpert, Daniel M.] Univ Cambridge, Dept Engn, Computat & Biol Learning Lab, Cambridge CB2 1PZ, England.
[Burk, Diana] Howard Hughes Med Inst, Ashburn, VA USA.
[Burk, Diana] NIDA, Intramural Res Program, Baltimore, MD USA.
[Shadlen, Michael N.] Columbia Univ, Howard Hughes Med Inst, Kavli Inst, New York, NY 10032 USA.
[Shadlen, Michael N.] Columbia Univ, Zuckerman Mind Brain Behav Inst, Dept Neurosci, New York, NY USA.
RP Wolpert, DM (reprint author), Univ Cambridge, Dept Engn, Computat & Biol Learning Lab, Cambridge CB2 1PZ, England.
EM wolpert@eng.cam.ac.uk
RI Franklin, David/A-2371-2009
OI Franklin, David/0000-0001-9530-0820
FU Human Frontiers Science Program; Wellcome Trust; Howard Hughes Medical
Institute; NIH [R01EY11378]
FX This work was supported by the Human Frontiers Science Program, the
Wellcome Trust, Howard Hughes Medical Institute and the NIH
(R01EY11378). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 26
TC 11
Z9 11
U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 20
PY 2014
VL 9
IS 3
AR e92681
DI 10.1371/journal.pone.0092681
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6FV
UT WOS:000333352800141
PM 24651615
ER
PT J
AU Veselits, M
Tanaka, A
Lipkowitz, S
O'Neill, S
Sciammas, R
Finnegan, A
Zhang, J
Clark, MR
AF Veselits, Margaret
Tanaka, Azusa
Lipkowitz, Stanley
O'Neill, Shannon
Sciammas, Roger
Finnegan, Alison
Zhang, Jian
Clark, Marcus R.
TI Recruitment of Cbl-b to B Cell Antigen Receptor Couples Antigen
Recognition to Toll-Like Receptor 9 Activation in Late Endosomes
SO PLOS ONE
LA English
DT Article
ID MHC CLASS-II; LIGHT-CHAIN RECOMBINATION; UBIQUITIN LIGASE CBL; C-CBL;
NEGATIVE REGULATION; IG-BETA; COMPLEX; DEGRADATION; PROTEINS; CIN85
AB Casitas B-lineage lymphoma-b (Cbl-b) is a ubiquitin ligase (E3) that modulates signaling by tagging molecules for degradation. It is a complex protein with multiple domains and binding partners that are not involved in ubiquitinating substrates. Herein, we demonstrate that Cbl-b, but not c-Cbl, is recruited to the clustered B cell antigen receptor (BCR) and that Cbl-b is required for entry of endocytosed BCRs into late endosomes. The E3 activity of Cbl-b is not necessary for BCR endocytic trafficking. Rather, the ubiquitin associated (UBA) domain is required. Furthermore, the Cbl-b UBA domain is sufficient to confer the receptor trafficking functions of Cbl-b on c-Cbl. Cbl-b is also required for entry of the Toll-like receptor 9 (TLR9) into late endosomes and for the in vitro activation of TLR9 by BCR-captured ligands. These data indicate that Cbl-b acts as a scaffolding molecule to coordinate the delivery of the BCR and TLR9 into subcellular compartments required for productively delivering BCR-captured ligands to TLR9.
C1 [Veselits, Margaret; Tanaka, Azusa; Sciammas, Roger; Clark, Marcus R.] Univ Chicago, Dept Med, Rheumatol Sect, Chicago, IL 60637 USA.
[Veselits, Margaret; Tanaka, Azusa; Sciammas, Roger; Clark, Marcus R.] Univ Chicago, Knapp Ctr Lupus & Immunol Res, Chicago, IL 60637 USA.
[Lipkowitz, Stanley] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[O'Neill, Shannon] Natl Jewish Med & Res Ctr, Integrated Dept Immunol, Denver, CO USA.
[O'Neill, Shannon] Univ Colorado, Denver, CO 80202 USA.
[O'Neill, Shannon] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
[Finnegan, Alison] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA.
[Finnegan, Alison] Rush Univ, Med Ctr, Dept Internal Med, Rheumatol Sect, Chicago, IL 60612 USA.
[Zhang, Jian] Univ Chicago, Dept Med, Nephrol Sect, Chicago, IL 60637 USA.
RP Clark, MR (reprint author), Univ Chicago, Dept Med, Rheumatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM mclark@medicine.bsd.uchicago.edu
RI Zhang, Jian/A-2564-2008
FU National Institutes of Health [GM088847, GM101090, AI090901]; Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research
FX This study was supported by National Institutes of Health (MRC, GM088847
and GM101090 and JZ, AI090901). This research was supported in part by
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 50
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U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 20
PY 2014
VL 9
IS 3
AR e89792
DI 10.1371/journal.pone.0089792
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6FV
UT WOS:000333352800004
PM 24651487
ER
PT J
AU McCarty, CA
Huggins, W
Aiello, AE
Bilder, RM
Hariri, A
Jernigan, TL
Newman, E
Sanghera, DK
Strauman, TJ
Zeng, Y
Ramos, EM
Junkins, HA
AF McCarty, Catherine A.
Huggins, Wayne
Aiello, Allison E.
Bilder, Robert M.
Hariri, Ahmad
Jernigan, Terry L.
Newman, Erik
Sanghera, Dharambir K.
Strauman, Timothy J.
Zeng, Yi
Ramos, Erin M.
Junkins, Heather A.
CA PhenX RISING Network
TI PhenX RISING: real world implementation and sharing of PhenX measures
SO BMC MEDICAL GENOMICS
LA English
DT Article
DE PhenX; Phenotype; Epidemiology; Risk factors; Harmonization
ID PHENOTYPE STANDARDIZATION; COMMUNITY; DISORDER; DETROIT; PROJECT;
INJURY; SAMPLE
AB Background: The purpose of this manuscript is to describe the PhenX RISING network and the site experiences in the implementation of PhenX measures into ongoing population-based genomic studies.
Methods: Eighty PhenX measures were implemented across the seven PhenX RISING groups, thirty-three of which were used at more than two sites, allowing for cross-site collaboration. Each site used between four and 37 individual measures and five of the sites are validating the PhenX measures through comparison with other study measures. Self-administered and computer-based administration modes are being evaluated at several sites which required changes to the original PhenX Toolkit protocols. A network-wide data use agreement was developed to facilitate data sharing and collaboration.
Results: PhenX Toolkit measures have been collected for more than 17,000 participants across the PhenX RISING network. The process of implementation provided information that was used to improve the PhenX Toolkit. The Toolkit was revised to allow researchers to select self-or interviewer administration when creating the data collection worksheets and ranges of specimens necessary to run biological assays has been added to the Toolkit.
Conclusions: The PhenX RISING network has demonstrated that the PhenX Toolkit measures can be implemented successfully in ongoing genomic studies. The next step will be to conduct gene/environment studies.
C1 [McCarty, Catherine A.] Essentia Inst Rural Hlth, Duluth, MN 55805 USA.
[Huggins, Wayne] RTI Int, Durham, NC USA.
[Aiello, Allison E.] Univ N Carolina, Chapel Hill, NC USA.
[Bilder, Robert M.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Hariri, Ahmad; Strauman, Timothy J.; Zeng, Yi] Duke Univ, Durham, NC USA.
[Jernigan, Terry L.; Newman, Erik] Univ Calif San Diego, San Diego, CA 92103 USA.
[Sanghera, Dharambir K.] Univ Oklahoma, Coll Med, Oklahoma City, OK 73190 USA.
[Ramos, Erin M.; Junkins, Heather A.] NHGRI, Bethesda, MD 20892 USA.
RP McCarty, CA (reprint author), Essentia Inst Rural Hlth, Maildrop 6AV-2,502 East Second St, Duluth, MN 55805 USA.
EM cmccarty@eirh.org
RI Bilder, Robert/A-8894-2008
OI Bilder, Robert/0000-0001-5085-7852
FU National Human Genome Research Institute [U01HG004597, R01
DA022720-05S1, 3PL1 MH083271-05S1, 3RC2 DA029475-02S1, R01 HD61414, 3U01
HG006389-01S1, R01DK082766-03S1, 3R01 DA031579-02S1,
3R01AG023627-06A2S1]
FX PhenX is supported by award number U01HG004597 from the National Human
Genome Research Institute. PhenX RISING was supported by administrative
supplements from the National Human Genome Research Institute,
including: R01 DA022720-05S1 (PI: Aiello) 3PL1 MH083271-05S1 (PI:
Bilder), 3RC2 DA029475-02S1 and R01 HD61414 (PI: Jernigan), 3U01
HG006389-01S1 (PI: McCarty), R01DK082766-03S1 (PI: Sanghera), 3R01
DA031579-02S1 (PI: Strauman and Hariri), 3R01AG023627-06A2S1 (PI: Yi
Zeng).
NR 19
TC 8
Z9 8
U1 3
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD MAR 20
PY 2014
VL 7
AR 16
DI 10.1186/1755-8794-7-16
PG 18
WC Genetics & Heredity
SC Genetics & Heredity
GA AD6RY
UT WOS:000333389800002
PM 24650325
ER
PT J
AU Nussinov, R
Tsai, CJ
AF Nussinov, Ruth
Tsai, Chung-Jung
TI Free Energy Diagrams for Protein Function
SO CHEMISTRY & BIOLOGY
LA English
DT Review
ID FOLDING FUNNELS; CELL FATE; SCAFFOLD PROTEINS; BINDING CASCADES;
MAMMALIAN-CELLS; MAP KINASE; LANDSCAPES; ALLOSTERY; FRUSTRATION;
MECHANISMS
AB Simplified representations can be powerful. Two common examples are sequence logos and ribbon diagrams. Both have been extraordinarily successful in capturing complex static features of sequences and structures. Capturing function is challenging, since activation involves triggered dynamic shifts between ON and OFF states. Here, we show that simple funnel drawings can capture and usefully portray proteins by their cellular triggering mechanism. The funnel shape around the proteins' native states can describe mechanisms of upstream signal integration and downstream response. "Function diagrams" are important: they can combine diverse biochemical data to visually distinguish among activation (or recruitment) mechanisms and tag proteins in cellular networks, clarifying their mechanism at a glance. We create templates for function classification and suggest that they can extend signaling pathway maps. Of note, the diagrams describe free energy landscapes; thus, they can be quantified. We name our dynamic free-energy diagrams dFEDs.
C1 [Nussinov, Ruth; Tsai, Chung-Jung] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM nussinor@helix.nih.gov
FU National Cancer Institute [HHSN261200800001E]; National Cancer
Institute, Center for Cancer Research
FX We thank Professors Peter Wolynes and Jose Onuchic for insightful
discussions on how to quantify the different possible mechanisms of
input integration. This project has been funded in whole or in part by
federal funds from the National Cancer Institute under contract number
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
National Cancer Institute, Center for Cancer Research.
NR 38
TC 10
Z9 10
U1 2
U2 38
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
EI 1879-1301
J9 CHEM BIOL
JI Chem. Biol.
PD MAR 20
PY 2014
VL 21
IS 3
BP 311
EP 318
DI 10.1016/j.chembiol.2013.12.015
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD6YH
UT WOS:000333407000003
PM 24508196
ER
PT J
AU Freed, EO
Gale, M
AF Freed, Eric O.
Gale, Michael, Jr.
TI Antiviral Innate Immunity: Editorial Overview
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Editorial Material
ID HOST RESTRICTION FACTOR; MECHANISMS; INFECTION
C1 [Freed, Eric O.] NCI, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Gale, Michael, Jr.] Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
[Gale, Michael, Jr.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Ctr Canc Res, Bg 535,Rm 110,1050 Boyles St, Frederick, MD 21702 USA.
EM efreed@mail.nih.gov
OI Gale, Michael/0000-0002-6332-7436
NR 28
TC 2
Z9 3
U1 1
U2 10
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD MAR 20
PY 2014
VL 426
IS 6
SI SI
BP 1129
EP 1132
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD7ZZ
UT WOS:000333487600001
PM 24462565
ER
PT J
AU Desimmie, BA
Delviks-Frankenberrry, KA
Burdick, RC
Qi, DF
Izumi, T
Pathak, VK
AF Desimmie, Belete A.
Delviks-Frankenberrry, Krista A.
Burdick, Ryan C.
Qi, DongFei
Izumi, Taisuke
Pathak, Vinay K.
TI Multiple APOBEC3 Restriction Factors for HIV-1 and One Vif to Rule Them
All
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Review
DE APOBEC3G; APOBEC3F; APOBEC3H; Vif; restriction factor
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SINGLE-STRANDED-DNA; CD4(+) T-CELLS;
RNA-EDITING ENZYME; ACTIVATION-INDUCED DEAMINASE; VIRAL INFECTIVITY
FACTOR; BINDING-FACTOR-BETA; APOBEC3G-CATALYZED PROCESSIVE DEAMINATION;
ANTIVIRAL PROTEIN APOBEC3G; INDUCED CYTIDINE DEAMINASE
AB Several members of the APOBEC3 family of cellular restriction factors provide intrinsic immunity to the host against viral infection. Specifically, APOBEC3DE, APOBEC3F, APOBEC3G, and APOBEC3H haplotypes II, V, and VII provide protection against HIV-1 Delta vif through hypermutation of the viral genome, inhibition of reverse transcription, and inhibition of viral DNA integration into the host genome. HIV-1 counteracts APOBEC3 proteins by encoding the viral protein Vif, which contains distinct domains that specifically interact with these APOBEC3 proteins to ensure their proteasomal degradation, allowing virus replication to proceed. Here, we review our current understanding of APOBEC3 structure, editing and non-editing mechanisms of APOBEC3-mediated restriction, Vif-APOBEC3 interactions that trigger APOBEC3 degradation, and the contribution of APOBEC3 proteins to restriction and control of HIV-1 replication in infected patients. Published by Elsevier Ltd.
C1 [Desimmie, Belete A.; Delviks-Frankenberrry, Krista A.; Burdick, Ryan C.; Qi, DongFei; Izumi, Taisuke; Pathak, Vinay K.] NCI, Viral Mutat Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Pathak, VK (reprint author), NCI, Viral Mutat Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM vinay.pathak@nih.gov
RI Izumi, Taisuke/J-5607-2014; Qi, Dongfei/L-9548-2015; Qi,
Dongfei/M-1050-2015
OI Izumi, Taisuke/0000-0002-9694-1459; Qi, Dongfei/0000-0001-9104-978X; Qi,
Dongfei/0000-0001-9104-978X
FU Intramural NIH HHS [ZIA BC011435-02, ZIA BC010595-10]
NR 277
TC 66
Z9 66
U1 3
U2 22
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD MAR 20
PY 2014
VL 426
IS 6
SI SI
BP 1220
EP 1245
DI 10.1016/j.jmb.2013.10.033
PG 26
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD7ZZ
UT WOS:000333487600008
PM 24189052
ER
PT J
AU Tamiru, A
Tsegay, G
Wubie, M
Gedefaw, M
Tomczyk, S
Tekola-Ayele, F
AF Tamiru, Abreham
Tsegay, Girmay
Wubie, Moges
Gedefaw, Molla
Tomczyk, Sara
Tekola-Ayele, Fasil
TI Podoconiosis patients' willingness to pay for treatment services in
Northwest Ethiopia: potential for cost recovery
SO BMC PUBLIC HEALTH
LA English
DT Article
DE Willingness to pay (WTP); Podoconiosis; Neglected tropical disease;
Health policy; Global health; Treatment; Contingent valuation method;
Ethiopia
ID NON-FILARIAL ELEPHANTIASIS; SOUTHERN ETHIOPIA; NORTHERN ETHIOPIA; WEST
ETHIOPIA; DISTRICT; STIGMA; WOREDA; GOJAM; EAST
AB Background: Podoconiosis is non-filarial elephantiasis of the lower legs. It is more commonly found in tropical Africa, Central and South America, and northwest India. In Ethiopia, a few non-governmental organizations provide free treatment to podoconiosis patients, but sustainability of free treatment and scale-up of services to reach the huge unmet need is challenged by resource limitations. We aimed to determine podoconiosis patient's willingness to pay (WTP) for a treatment package (composed of deep cleaning of limbs with diluted antiseptic solution, soap, and water, bandaging, application of emollient on the skin, and provision of shoes), and factors associated with WTP in northwestern Ethiopia.
Methods: A cross-sectional study was conducted among randomly selected untreated podoconiosis patients (n = 393) in Baso Liben woreda, northwestern Ethiopia. The contingent valuation method was used with a pre-tested interviewer-administered questionnaire.
Results: The majority of podoconiosis patients (72.8%) were willing to pay for treatment services. The median WTP amount was 64 Birr (USS 3.28) per person per year. More than one-third of patients (36.7%) were willing to pay at least half of the full treatment cost and 76.2% were willing to pay at least half of the cost of shoes. A multivariate analysis showed that having a higher monthly income, being a woman, older age, being aware of the role of shoes to prevent podoconiosis, and possession of a functional radio were significantly associated with higher odds of WTP.
Conclusions: The considerable WTP estimates showed that podoconiosis treatment could improve sustainability and service utilization. A subsidized cost recovery scheme could reduce treatment costs and more feasibility integrate podoconiosis treatment service with other NTDs and the government's primary health care system.
C1 [Tamiru, Abreham; Tsegay, Girmay; Wubie, Moges] Debre Markos Univ, Coll Med & Hlth Sci, Sch Publ Hlth, Debre Markos, Ethiopia.
[Gedefaw, Molla] GAMBY Med Sci Coll, Bahir Dar, Ethiopia.
[Tomczyk, Sara] Inst Trop Med, B-2000 Antwerp, Belgium.
[Tekola-Ayele, Fasil] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
RP Tamiru, A (reprint author), Debre Markos Univ, Coll Med & Hlth Sci, Sch Publ Hlth, POB 269, Debre Markos, Ethiopia.
EM abrish80@gmail.com
OI Tekola-Ayele, Fasil/0000-0003-4194-9370
FU Welcome Trust grant [095956]
FX We thank the staff of the International Orthodox Christian Charities
Podoconiosis Project in Ethiopia for coordinating the study and
Professor Gail Davey for the financial support of the fieldwork through
the Welcome Trust grant (grant number 095956).
NR 26
TC 3
Z9 3
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD MAR 19
PY 2014
VL 14
AR 259
DI 10.1186/1471-2458-14-259
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AG4PN
UT WOS:000335402700001
PM 24642085
ER
PT J
AU Das, D
Murzin, AG
Rawlings, ND
Finn, RD
Coggill, P
Bateman, A
Godzik, A
Aravind, L
AF Das, Debanu
Murzin, Alexey G.
Rawlings, Neil D.
Finn, Robert D.
Coggill, Penelope
Bateman, Alex
Godzik, Adam
Aravind, L.
TI Structure and computational analysis of a novel protein with
metallopeptidase-like and circularly permuted winged-helix-turn-helix
domains reveals a possible role in modified polysaccharide biosynthesis
SO BMC BIOINFORMATICS
LA English
DT Article
DE CA_C2195; Peptidase; DUF4910; DUF2172; HTH_47; Structural genomics
ID CRYSTAL-STRUCTURE; MACROMOLECULAR CRYSTALLOGRAPHY; UNKNOWN FUNCTION; WEB
SERVER; PSI-BLAST; DATABASE; GENOMICS; ENZYME; SEQUENCE; INHIBITORS
AB Background: CA_C2195 from Clostridium acetobutylicum is a protein of unknown function. Sequence analysis predicted that part of the protein contained a metallopeptidase-related domain. There are over 200 homologs of similar size in large sequence databases such as UniProt, with pairwise sequence identities in the range of similar to 40-60%. CA_C2195 was chosen for crystal structure determination for structure-based function annotation of novel protein sequence space.
Results: The structure confirmed that CA_C2195 contained an N-terminal metallopeptidase-like domain. The structure revealed two extra domains: an alpha+beta domain inserted in the metallopeptidase-like domain and a C-terminal circularly permuted winged-helix-turn-helix domain.
Conclusions: Based on our sequence and structural analyses using the crystal structure of CA_C2195 we provide a view into the possible functions of the protein. From contextual information from gene-neighborhood analysis, we propose that rather than being a peptidase, CA_C2195 and its homologs might play a role in biosynthesis of a modified cell-surface carbohydrate in conjunction with several sugar-modification enzymes. These results provide the groundwork for the experimental verification of the function.
C1 [Das, Debanu] Joint Ctr Struct Genom, La Jolla, CA 92037 USA.
[Das, Debanu] SLAC Natl Accelerator Lab, Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA USA.
[Murzin, Alexey G.] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
[Rawlings, Neil D.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England.
[Rawlings, Neil D.; Coggill, Penelope; Bateman, Alex] European Bioinformat Inst, European Mol Biol Lab, Hinxton CB10 1SD, Cambs, England.
[Finn, Robert D.] Howard Hughes Med Inst, Ashburn, VA USA.
[Godzik, Adam] Sanford Burnham Med Res Inst, Program Bioinformat & Syst Biol, La Jolla, CA USA.
[Aravind, L.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Das, D (reprint author), Joint Ctr Struct Genom, La Jolla, CA 92037 USA.
EM debanu@slac.stanford.edu; aravind@ncbi.nlm.nih.gov
RI Godzik, Adam/A-7279-2009; Rawlings, Neil/M-5566-2013;
OI Godzik, Adam/0000-0002-2425-852X; Rawlings, Neil/0000-0001-5557-7665;
Finn, Robert/0000-0001-8626-2148; Bateman, Alex/0000-0002-6982-4660
FU National Institutes of Health, USA [U54 GM094586]; NIGMS Protein
Structure Initiative; National Science Foundation; UK Medical Research
Council [MC_U105192716]; National Library of Medicine, USA; NIH
[R01GM101457]; Howard Hughes Medical Institute; Wellcome Trust
[WT077044/Z/05/Z]; DOE Office of Biological and Environmental Research;
National Institutes of Health; National Institute of General Medical
Sciences [P41GM103393]; [IIS-0646708]; [IIS-1153617]
FX We are grateful to the Sanford Burnham Medical Research Institute and
University of California, San Diego, for hosting the DUF Annotation
Jamboree in June 2013, which allowed the authors to collaborate on this
work. We would like to thank all the other participants of this workshop
for their intellectual contributions to this work: Herbert Axelrod,
Yuanyuan Chang, Ruth Y. Eberhardt, William Hwang, Lukasz Jaroszewski,
Padmaja Natarajan, Marco Punta, Daniel Rigden, Mayya Sedova, Anna
Sheydina and John Wooley. We would like to thank Mayya Sedova for
assistance in preparing some of the figures. We thank members of the
JCSG High-Throughput Structural Biology pipeline for their contribution
to this work. This work was supported in part by National Institutes of
Health, USA, grant U54 GM094586 from the NIGMS Protein Structure
Initiative to JCSG; National Science Foundation grants IIS-0646708 and
IIS-1153617; UK Medical Research Council grant MC_U105192716 to AGM;
intramural funds of the National Library of Medicine, USA, to LA; NIH
grant R01GM101457 to AG; Howard Hughes Medical Institute to RDF; and
Wellcome Trust grant WT077044/Z/05/Z for funding for open access
charges. Portions of this research were carried out at the Stanford
Synchrotron Radiation Lightsource, a Directorate of SLAC National
Accelerator Laboratory and an Office of Science User Facility operated
for the U. S. Department of Energy Office of Science by Stanford
University. The SSRL Structural Molecular Biology Program is supported
by the DOE Office of Biological and Environmental Research, and by the
National Institutes of Health, National Institute of General Medical
Sciences (including P41GM103393). The contents of this publication are
solely the responsibility of the authors and do not necessarily
represent the official views of DOE, NSF, NIGMS or NIH.
NR 49
TC 1
Z9 1
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD MAR 19
PY 2014
VL 15
AR 75
DI 10.1186/1471-2105-15-75
PG 12
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA AF2LZ
UT WOS:000334544900001
PM 24646163
ER
PT J
AU Bai, HH
Yang, XK
Temuribagen
Guilan
Suyalatu
Narisu, N
Wu, HG
Chen, YJ
Liu, YJ
Wu, QZ
AF Bai, Haihua
Yang, Xukui
Temuribagen
Guilan
Suyalatu
Narisu, Narisu
Wu, Huiguang
Chen, Yujie
Liu, Yangjian
Wu, Qizhu
TI A rare novel mutation in TECTA causes autosomal dominant nonsyndromic
hearing loss in a Mongolian family
SO BMC MEDICAL GENETICS
LA English
DT Article
DE TECTA gene; Mongolian family; Autosomal dominant nonsyndromic hearing
loss
ID GENOTYPE-PHENOTYPE CORRELATION; TECTORIAL MEMBRANE; DEAFNESS;
IMPAIRMENT; DOMAIN
AB Background: The genetic basis of autosomal dominant nonsyndromic hearing loss is complex. Genetic factors are responsible for approximately 50% of cases with congenital hearing loss. However, no previous studies have documented the clinical phenotype and genetic basis of autosomal dominant nonsyndromic hearing loss in Mongolians.
Methods: In this study, we performed exon capture sequencing of a Mongolian family with hereditary hearing loss and identified a novel mutation in TECTA gene, which encodes alpha - tectorin, a major component of the inner ear extracellular matrix that contacts the specialized sensory hair cells.
Results: The novel G -> T missense mutation at nucleotide 6016 results in a substitution of amino acid aspartate at 2006 with tyrosine (Asp2006Tyr) in a highly conserved zona pellucida (ZP) domain of alpha tectorin. The mutation is not found in control subjects from the same family with normal hearing and a genotype-phenotype correlation is observed.
Conclusion: A novel missense mutation c.6016 G > T ( p.Asp2006Tyr) of TECTA gene is a characteristic TECTA-related mutation which causes autosomal dominant nonsyndromic hearing loss. Our result indicated that mutation in TECTA gene is responsible for the hearing loss in this Mongolian family.
C1 [Bai, Haihua; Temuribagen; Guilan; Suyalatu; Wu, Huiguang; Chen, Yujie] Inner Mongolia Univ Nationalities, Tongliao 028000, Inner, Mongol Peo Rep.
[Yang, Xukui; Wu, Qizhu] BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China.
[Narisu, Narisu] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Yangjian] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
RP Bai, HH (reprint author), Inner Mongolia Univ Nationalities, Tongliao 028000, Inner, Mongol Peo Rep.
EM hhbai2010@gmail.com; qizhu_wu@sohu.com
FU National Natural Science Foundation of China [81160101, 81060098]
FX We thank each member of the family for their generous participation in
this study. This study was supported by the National Natural Science
Foundation of China (81160101,81060098).
NR 19
TC 2
Z9 2
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD MAR 19
PY 2014
VL 15
AR 34
DI 10.1186/1471-2350-15-34
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA AF2JH
UT WOS:000334537900001
PM 25008054
ER
PT J
AU Holt, DJ
Cassidy, BS
Yue, XM
Rauch, SL
Boeke, EA
Nasr, S
Tootell, RBH
Coombs, G
AF Holt, Daphne J.
Cassidy, Brittany S.
Yue, Xiaomin
Rauch, Scott L.
Boeke, Emily A.
Nasr, Shahin
Tootell, Roger B. H.
Coombs, Garth, III
TI Neural Correlates of Personal Space Intrusion
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE connectivity; fMRI; intraparietal sulcus; personal space; premotor
cortex; social behavior
ID VENTRAL INTRAPARIETAL AREA; INTRINSIC FUNCTIONAL CONNECTIVITY; HUMAN
CEREBRAL-CORTEX; SOCIAL NETWORK SIZE; PREMOTOR CORTEX; INTERPERSONAL
DISTANCE; DEPENDENT PLASTICITY; RESPONSE PROPERTIES; PERIPERSONAL SPACE;
HUMAN BRAIN
AB A parietal-frontal network in primates is thought to support many behaviors occurring in the space around the body, including interpersonal interactions and maintenance of a particular "comfort zone" or distance from other people ("personal space"). To better understand this network in humans, we used functionalMRIto measure the responses to moving objects (faces, cars, simple spheres) and the functional connectivity of two regions in this network, the dorsal intraparietal sulcus (DIPS) and the ventral premotor cortex (PMv). We found that both areas responded more strongly to faces that were moving toward (vs away from) subjects, but did not show this bias in response to comparable motion in control stimuli (cars or spheres). Moreover, these two regions were functionally interconnected. Tests of activity-behavior associations revealed that the strength of DIPS-PMv connectivity was correlated with the preferred distance that subjects chose to stand from an unfamiliar person (personal space size). In addition, the magnitude of DIPS and PMv responses was correlated with the preferred level of social activity. Together, these findings suggest that this parietal-frontal network plays a role in everyday interactions with others.
C1 [Holt, Daphne J.; Boeke, Emily A.; Coombs, Garth, III] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Holt, Daphne J.; Rauch, Scott L.; Tootell, Roger B. H.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Holt, Daphne J.; Boeke, Emily A.; Nasr, Shahin; Tootell, Roger B. H.; Coombs, Garth, III] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Cassidy, Brittany S.] Brandeis Univ, Dept Psychol, Waltham, MA 02453 USA.
[Yue, Xiaomin] NIMH, Bethesda, MD 20892 USA.
[Rauch, Scott L.] McLean Hosp, Belmont, MA 02478 USA.
[Nasr, Shahin; Tootell, Roger B. H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Holt, DJ (reprint author), 149 13th St, Charlestown, MA 02129 USA.
EM dholt@partners.org
FU National Institute of Mental Health [K23MH076054]
FX This study was supported by the National Institute of Mental Health
K23MH076054 (DH).
NR 50
TC 15
Z9 15
U1 3
U2 17
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 19
PY 2014
VL 34
IS 12
BP 4123
EP 4134
DI 10.1523/JNEUROSCI.0686-13.2014
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA AD4WX
UT WOS:000333253300002
PM 24647934
ER
PT J
AU Li, Q
Hill, Z
He, BYJ
AF Li, Qi
Hill, Zachary
He, Biyu J.
TI Spatiotemporal Dissociation of Brain Activity Underlying Subjective
Awareness, Objective Performance and Confidence
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE conscious perception; MEG; metacognition; slow cortical potential;
subjective awareness; visual perception
ID SHORT-TERM-MEMORY; VISUAL AWARENESS; PREFRONTAL CORTEX; CEREBRAL-CORTEX;
WORKING-MEMORY; INDIVIDUAL-DIFFERENCES; PERCEPTUAL AWARENESS; CONSCIOUS
PERCEPTION; ACTIVITY PREDICTS; NORMAL OBSERVERS
AB Despite intense recent research, the neural correlates of conscious visual perception remain elusive. The most established paradigm for studying brain mechanisms underlying conscious perception is to keep the physical sensory inputs constant and identify brain activities that correlate with the changing content of conscious awareness. However, such a contrast based on conscious content alone would not only reveal brain activities directly contributing to conscious perception, but also include brain activities that precede or follow it. To address this issue, we devised a paradigm whereby we collected, trial-by-trial, measures of objective performance, subjective awareness, and the confidence level of subjective awareness. Using magnetoencephalography recordings in healthy human volunteers, we dissociated brain activities underlying these different cognitive phenomena. Our results provide strong evidence that widely distributed slow cortical potentials (SCPs) correlate with subjective awareness, even after the effects of objective performance and confidence were both removed. The SCP correlate of conscious perception manifests strongly in its waveform, phase, and power. In contrast, objective performance and confidence were both contributed by relatively transient brain activity. These results shed new light on the brain mechanisms of conscious, unconscious, and metacognitive processing.
C1 [Li, Qi; Hill, Zachary; He, Biyu J.] NINDS, NIH, Bethesda, MD 20892 USA.
RP He, BYJ (reprint author), 10 Ctr Dr,Bldg 10,Room B1D728, Bethesda, MD 20892 USA.
EM biyu.he@nih.gov
OI He, Biyu/0000-0003-1549-1351
FU Intramural Research Program of the National Institutes of
Health/National Institute of Neurological Disorders and Stroke
FX This research was supported by the Intramural Research Program of the
National Institutes of Health/National Institute of Neurological
Disorders and Stroke. We thank Tom Holroyd, Ziad Saad, Gang Chen, John
Ostuni, Ole Jensen, and Stanislas Dehaene for helpful discussions.
NR 76
TC 10
Z9 11
U1 0
U2 8
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 19
PY 2014
VL 34
IS 12
BP 4382
EP 4395
DI 10.1523/JNEUROSCI.1820-13.2014
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA AD4WX
UT WOS:000333253300026
PM 24647958
ER
PT J
AU Yates, NL
Liao, HX
Fong, YI
deCamp, A
Vandergrift, NA
Williams, WT
Alam, SM
Ferrari, G
Yang, ZY
Seaton, KE
Berman, PW
Alpert, MD
Evans, DT
O'Connell, RJ
Francis, D
Sinangil, F
Lee, C
Nitayaphan, S
Rerks-Ngarm, S
Kaewkungwal, J
Pitisuttithum, P
Tartaglia, J
Pinter, A
Zolla-Pazner, S
Gilbert, PB
Nabel, GJ
Michael, NL
Kim, JH
Montefiori, DC
Haynes, BF
Tomaras, GD
AF Yates, Nicole L.
Liao, Hua-Xin
Fong, Youyi
deCamp, Allan
Vandergrift, Nathan A.
Williams, William T.
Alam, S. Munir
Ferrari, Guido
Yang, Zhi-yong
Seaton, Kelly E.
Berman, Phillip W.
Alpert, Michael D.
Evans, David T.
O'Connell, Robert J.
Francis, Donald
Sinangil, Faruk
Lee, Carter
Nitayaphan, Sorachai
Rerks-Ngarm, Supachai
Kaewkungwal, Jaranit
Pitisuttithum, Punnee
Tartaglia, James
Pinter, Abraham
Zolla-Pazner, Susan
Gilbert, Peter B.
Nabel, Gary J.
Michael, Nelson L.
Kim, Jerome H.
Montefiori, David C.
Haynes, Barton F.
Tomaras, Georgia D.
TI Vaccine-Induced Env V1-V2 IgG3 Correlates with Lower HIV-1 Infection
Risk and Declines Soon After Vaccination
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CONSENSUS ENVELOPE GLYCOPROTEIN; B-CELL
RESPONSES; EFFICACY TRIAL; ANTIBODY-RESPONSES; IMMUNOGLOBULIN G3; RV144;
GP120; IMMUNOGENICITY; ANTIGENICITY
AB HIV-1-specific immunoglobulin G (IgG) subclass antibodies bind to distinct cellular Fc receptors. Antibodies of the same epitope specificity but of a different subclass therefore can have different antibody effector functions. The study of IgG subclass profiles between different vaccine regimens used in clinical trials with divergent efficacy outcomes can provide information on the quality of the vaccine-induced B cell response. We show that HIV-1-specific IgG3 distinguished two HIV-1 vaccine efficacy studies (RV144 and VAX003 clinical trials) and correlated with decreased risk of HIV-1 infection in a blinded follow-up case-control study with the RV144 vaccine. HIV-1-specific IgG3 responses were not long-lived, which was consistent with the waning efficacy of the RV144 vaccine. These data suggest that specific vaccine-induced HIV-1 IgG3 should be tested in future studies of immune correlates in HIV-1 vaccine efficacy trials.
C1 [Yates, Nicole L.; Liao, Hua-Xin; Vandergrift, Nathan A.; Williams, William T.; Alam, S. Munir; Ferrari, Guido; Seaton, Kelly E.; Montefiori, David C.; Haynes, Barton F.; Tomaras, Georgia D.] Duke Human Vaccine Inst, Durham, NC 27710 USA.
[Yates, Nicole L.; Liao, Hua-Xin; Vandergrift, Nathan A.; Williams, William T.; Alam, S. Munir; Ferrari, Guido; Seaton, Kelly E.; Haynes, Barton F.] Duke Univ, Dept Med, Durham, NC 27710 USA.
[Fong, Youyi; deCamp, Allan; Gilbert, Peter B.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
[Yang, Zhi-yong; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Berman, Phillip W.] Univ Calif Santa Cruz, Baskin Sch Engn, Santa Cruz, CA 95064 USA.
[Alpert, Michael D.; Evans, David T.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA.
[O'Connell, Robert J.] Armed Forces Res Inst Med Sci US Component, Bangkok, Thailand.
[Francis, Donald; Sinangil, Faruk; Lee, Carter] Global Solut Infect Dis, San Francisco, CA 94080 USA.
[Nitayaphan, Sorachai] Armed Forces Res Inst Med Sci Royal Thai Army Com, Bangkok, Thailand.
[Rerks-Ngarm, Supachai] Minist Publ Hlth, Dept Dis Control, Nonthaburi, Thailand.
[Kaewkungwal, Jaranit] Mahidol Univ, Fac Trop Med, Ctr Excellence Biomed & Publ Hlth Informat BIOPH, Bangkok, Thailand.
[Pitisuttithum, Punnee] Mahidol Univ, Bangkok 10700, Thailand.
[Tartaglia, James] Sanofi Pasteur, Swiftwater, PA 18370 USA.
[Pinter, Abraham] Rutgers State Univ, New Jersey Med Sch, Newark, NJ 07103 USA.
[Zolla-Pazner, Susan] Vet Affairs Med Ctr, New York, NY 10010 USA.
[Zolla-Pazner, Susan] NYU, Sch Med, New York, NY 10010 USA.
[Michael, Nelson L.; Kim, Jerome H.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA.
[Montefiori, David C.; Tomaras, Georgia D.] Duke Univ, Dept Surg, Durham, NC 27710 USA.
[Haynes, Barton F.; Tomaras, Georgia D.] Duke Univ, Dept Immunol, Durham, NC 27710 USA.
[Tomaras, Georgia D.] Duke Univ, Durham, NC 27710 USA.
RP Tomaras, GD (reprint author), Duke Human Vaccine Inst, Durham, NC 27710 USA.
EM gdt@duke.edu
RI Ferrari, Guido/A-6088-2015; Tomaras, Georgia/J-5041-2016
FU Bill and Melinda Gates Foundation grants; Collaboration for AIDS Vaccine
Discovery [CAVIMC OPP1032144, 38619, OPP 1033098]; NIH/NIAID/Division of
Acquired Immunodeficiency Syndrome: Center for HIV/AIDS Vaccine
Immunology Grant [U01 AI067854]; HIV-1 Vaccine Trials Network (HVTN)
[5U01 AI46725-05]; Duke University Center for AIDS Research (CFAR) [P30
AI 64518]; intramural program of NIH (Vaccine Research Center, NIAID);
Interagency Agreement [Y1-AI-2642-12, Y1-AI-2642-16]; NIAID
[W81XWH-11-2-0174, W81XWH-07-2-0067]; U.S. Department of Defense
[694251]; U.S. Army Medical Research and Material Command; Henry M.
Jackson Foundation for the Advancement of Military Medicine Inc.
FX This work was supported by the Bill and Melinda Gates Foundation grants,
Collaboration for AIDS Vaccine Discovery (CAVIMC OPP1032144, 38619)
(N.L.Y., W.T.W., S.M.A., G.F., D.C.M., and G.D.T.), OPP 1033098 (N.L.Y.,
W.T.W., G.F., B.F.H., and G.D.T.), and NIH/NIAID/Division of Acquired
Immunodeficiency Syndrome: Center for HIV/AIDS Vaccine Immunology Grant
(U01 AI067854) (N.L.Y., H.-X.L., N.A.V., B.F.H., and G.D.T.). In
addition, funding was provided by HIV-1 Vaccine Trials Network (HVTN)
(5U01 AI46725-05) (N.L.Y., W.T.W., K.E.S., and G.D.T.) and the Duke
University Center for AIDS Research (CFAR) Grant (P30 AI 64518)
(G.D.T.). The work was also supported in part by the intramural program
of NIH (Vaccine Research Center, NIAID) (G.J.N. and Z.-y.Y.) and an
Interagency Agreement (Y1-AI-2642-12 and Y1-AI-2642-16) between the U.S.
Army Medical Research and Material Command and the NIAID and by a
cooperative agreement (W81XWH-11-2-0174 and W81XWH-07-2-0067) between
the Henry M. Jackson Foundation for the Advancement of Military Medicine
Inc. and the U.S. Department of Defense (M.D.A., D.T.E., R.J.O., N.L.M.,
J.H.K., B.F.H., and G.D.T.) and including contract #694251 (Y.F.,
A.d.C., and P.B.G.).
NR 43
TC 34
Z9 34
U1 0
U2 8
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 19
PY 2014
VL 6
IS 228
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AD4XV
UT WOS:000333256000009
ER
PT J
AU Beaudry, JT
Krause, MA
Diakite, SAS
Fay, MP
Joshi, G
Diakite, M
White, NJ
Fairhurst, RM
AF Beaudry, Jeanette T.
Krause, Michael A.
Diakite, Seidina A. S.
Fay, Michael P.
Joshi, Gyan
Diakite, Mahamadou
White, Nicholas J.
Fairhurst, Rick M.
TI Ex-Vivo Cytoadherence Phenotypes of Plasmodium falciparum Strains from
Malian Children with Hemoglobins A, S, and C
SO PLOS ONE
LA English
DT Article
ID INFECTED ERYTHROCYTES; SEVERE MALARIA; VAR GENES; PROTECTION; DISEASE;
POPULATION; EXPRESSION; VARIANTS; IMMUNITY; DISPLAY
AB Sickle hemoglobin (Hb) S and HbC may protect against malaria by reducing the expression of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) on the surface of parasitized red blood cells (RBCs), thereby weakening their cytoadherence to microvascular endothelial cells (MVECs) and impairing their activation of MVECs to produce pathological responses. Therefore, we hypothesized that parasites causing malaria in HbAS or HbAC heterozygotes have overcome this protective mechanism by expressing PfEMP1 variants which mediate relatively strong binding to MVECs. To test this hypothesis, we performed 31 cytoadherence comparisons between parasites from HbAA and HbAS (or HbAC) Malian children with malaria. Ring-stage parasites from HbAA and HbAS (or HbAC) children were cultivated to trophozoites, purified, and then inoculated in parallel into the same wildtype uninfected RBCs. After one cycle of invasion and maturation to the trophozoite stage expressing PfEMP1, parasite strains were compared for binding to MVECs. In this assay, there were no significant differences in the binding of parasites from HbAS and HbAC children to MVECs compared to those from HbAA children (HbAS, fold-change = 1.46, 95% CI 0.97-2.19, p = 0.07; HbAC, fold-change = 1.19, 95% CI 0.77-1.84, p = 0.43). These data suggest that in-vitro reductions in cytoadherence by HbS and HbC may not be selecting for expression of high-avidity PfEMP1 variants in vivo. Future studies that identify PfEMP1 domains or amino-acid motifs which are selectively expressed in parasites from HbAS children may provide further insights into the mechanism of malaria protection by the sickle-cell trait.
C1 [Beaudry, Jeanette T.; Krause, Michael A.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Beaudry, Jeanette T.] Univ Oxford, Nuffield Dept Clin Med, Oxford, England.
[Diakite, Seidina A. S.; Diakite, Mahamadou] Univ Bamako, Fac Med Pharm & Odontostomatol, Malaria Res & Training Ctr, Bamako, Mali.
[Fay, Michael P.; Joshi, Gyan] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[White, Nicholas J.] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Dis Res Unit, Bangkok, Thailand.
RP Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rfairhurst@niaid.nih.gov
OI Fay, Michael P./0000-0002-8643-9625
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This study was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, 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 31
TC 1
Z9 2
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 19
PY 2014
VL 9
IS 3
AR e92185
DI 10.1371/journal.pone.0092185
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6ER
UT WOS:000333348500096
PM 24647281
ER
PT J
AU Bortner, CD
Cidlowski, JA
AF Bortner, Carl D.
Cidlowski, John A.
TI Ion channels and apoptosis in cancer
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Review
DE apoptosis; ion channels; cancer; cell death
ID CELL-VOLUME REGULATION; TUMOR-NECROSIS-FACTOR; MITOCHONDRIAL POTASSIUM
CHANNEL; K+ CHANNELS; CHLORIDE CHANNELS; DEATH RECEPTORS; TARGETING
DEATH; KV1.3 CHANNELS; LEUKEMIA-CELLS; OVARIAN-CANCER
AB Humans maintain a constant cell number throughout their lifespan. This equilibrium of cell number is accomplished when cell proliferation and cell death are kept balanced, achieving a steady-state cell number. Abnormalities in cell growth or cell death can lead to an overabundance of cells known as neoplasm or tumours. While the perception of cancer is often that of an uncontrollable rate of cell growth or increased proliferation, a decrease in cell death can also lead to tumour formation. Most cells when detached from their normal tissue die. However, cancer cells evade cell death, tipping the balance to an overabundance of cell number. Therefore, overcoming this resistance to cell death is a decisive factor in the treatment of cancer. Ion channels play a critical role in cancer in regards to cell proliferation, malignant angiogenesis, migration and metastasis. Additionally, ion channels are also known to be critical components of apoptosis. In this review, we discuss the modes of cell death focusing on the ability of cancer cells to evade apoptosis. Specifically, we focus on the role ion channels play in controlling and regulating life/death decisions and how they can be used to overcome resistance to apoptosis in the treatment of cancer.
C1 [Bortner, Carl D.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA.
RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM cidlowski@niehs.nih.gov
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences.
NR 120
TC 16
Z9 16
U1 4
U2 22
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
EI 1471-2970
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD MAR 19
PY 2014
VL 369
IS 1638
SI SI
AR 20130104
DI 10.1098/rstb.2013.0104
PG 9
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AC4BU
UT WOS:000332466400012
PM 24493752
ER
PT J
AU Stein-Streilein, J
Caspi, RR
AF Stein-Streilein, Joan
Caspi, Rachel R.
TI Immune privilege and the philosophy of immunology
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Editorial Material
DE immune privilege; tolerance; immune suppression; eye; regulatory cells
C1 [Stein-Streilein, Joan] Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol,Mass Eye & Ear, Boston, MA 02115 USA.
[Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Stein-Streilein, J (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol,Mass Eye & Ear, Boston, MA 02115 USA.
EM joan.stein@schepens.harvard.edu; rcaspi@helix.nih.gov
OI Caspi, Rachel/0000-0002-7140-7671
NR 9
TC 8
Z9 8
U1 0
U2 2
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PD MAR 19
PY 2014
VL 5
AR 110
DI 10.3389/fimmu.2014.00110
PG 2
WC Immunology
SC Immunology
GA CH5GE
UT WOS:000354062600001
PM 24678312
ER
PT J
AU Pearl, PL
Schreiber, J
Theodore, WH
McCarter, R
Barrios, ES
Yu, J
Wiggs, E
He, JP
Gibson, KM
AF Pearl, Phillip L.
Schreiber, John
Theodore, William H.
McCarter, Robert
Barrios, Emily S.
Yu, Joe
Wiggs, Edythe
He, Jianping
Gibson, K. Michael
TI Taurine trial in succinic semialdehyde dehydrogenase deficiency and
elevated CNS GABA
SO NEUROLOGY
LA English
DT Article
ID EPILEPSY; MICE; METABOLISM; DISORDER
AB Objectives:The objective of this open-label study was primarily to assess the effect of taurine on adaptive behavior and secondarily to collect safety and tolerability data in patients with succinic semialdehyde dehydrogenase deficiency.Methods:In the current study, subjects were titrated weekly from a starting dose of 50 mg/kg/d to a target 200 mg/kg/d, and assessed for safety, tolerability, and adaptive functioning using age-normalized Adaptive Behavior Assessment Scales.Results:Eighteen patients (8 males/10 females, aged 0.5-28 years, mean 12 years) were recruited. Three subjects withdrew because of perceived lack of efficacy. One serious adverse event occurred (hospitalization for hypersomnia) on 16 g/d (200 mg/kg/d), leading to a dose-lowering paradigm with a maximum dose of 10 g/d. Results did not show clinically meaningful improvement in the adaptive domains after taurine therapy. Pre- and posttherapy adaptive scores also demonstrated no statistically significant difference (p > 0.18).Conclusions:Adaptive behavior did not improve significantly with taurine intervention. Further therapeutic clinical trials including an on-off paradigm using biomarkers are planned.Classification of evidence:This study provides Class IV evidence that for patients with succinic semialdehyde dehydrogenase deficiency, taurine does not significantly improve adaptive behavior. The study is rated Class IV because of the absence of a control group.
C1 [Pearl, Phillip L.; Schreiber, John; Barrios, Emily S.; Yu, Joe] Childrens Natl Med Ctr, Dept Child Neurol, Washington, DC 20010 USA.
[McCarter, Robert; He, Jianping] Childrens Natl Med Ctr, Dept Biostat Epidemiol, Washington, DC 20010 USA.
[Schreiber, John; Theodore, William H.; Wiggs, Edythe] NINDS, Clin Epilepsy Branch, NIH, Bethesda, MD 20892 USA.
[Gibson, K. Michael] Washington State Univ, Spokane, WA USA.
RP Pearl, PL (reprint author), Childrens Natl Med Ctr, Dept Child Neurol, Washington, DC 20010 USA.
EM Phillip.Pearl@childrens.harvard.edu
FU NIH/NICHD [R01 HD58553]
FX The trial was funded by NIH/NICHD R01 HD58553.
NR 21
TC 7
Z9 7
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAR 18
PY 2014
VL 82
IS 11
BP 940
EP 944
DI 10.1212/WNL.0000000000000210
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH6TB
UT WOS:000336262500011
PM 24523482
ER
PT J
AU Oh, J
Saidha, S
Cortese, I
Ohayon, J
Bielekova, B
Calabresi, PA
Newsome, SD
AF Oh, Jiwon
Saidha, Shiv
Cortese, Irene
Ohayon, Joan
Bielekova, Bibiana
Calabresi, Peter A.
Newsome, Scott D.
TI Daclizumab-induced adverse events in multiple organ systems in multiple
sclerosis
SO NEUROLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; ACTIVATION; THERAPY
AB Objective:To report 3 patients with multiple sclerosis (MS) who presented with daclizumab-related adverse events (AEs) in multiple organ systems.Methods:A retrospective chart review was performed of patients with MS who had clinical and histopathologic findings suggestive of daclizumab-induced AEs between 2004 and 2010 at the Johns Hopkins MS Clinic. This study met criteria for exemption from review from the institutional review board.Results:Of 20 total patients with MS who had been treated with daclizumab, 3 patients with clinical and histopathologic findings suggestive of daclizumab-induced AEs were identified. All patients were treated with Zenapax (1 mg/kg monthly IV infusions) outside of a clinical trial setting. Clinical manifestations after a mean treatment duration of 20 months consisted of diffuse rash and alopecia, diffuse lymphadenopathy, and breast nodules. Tissue histopathology demonstrated lymphocytic infiltrates with CD56-expressing cells in 2 patients (lymph node, breast nodule). On daclizumab discontinuation, the rash/alopecia and diffuse lymphadenopathy resolved, while the breast nodules stabilized.Conclusions:Daclizumab-induced AEs can occur in various organ systems after a relatively prolonged duration of exposure and require clinician awareness. Future studies are needed to better understand the relationship between natural killer cells and daclizumab-related AEs.
C1 [Oh, Jiwon; Saidha, Shiv; Calabresi, Peter A.; Newsome, Scott D.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Cortese, Irene; Ohayon, Joan; Bielekova, Bibiana] NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA.
RP Newsome, SD (reprint author), Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
EM snewsom2@jhmi.edu
FU Multiple Sclerosis Society of Canada Decker Family Transitional Career
Development Award
FX Supported by a Multiple Sclerosis Society of Canada Decker Family
Transitional Career Development Award (to J. Oh).
NR 10
TC 8
Z9 8
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAR 18
PY 2014
VL 82
IS 11
BP 984
EP 988
DI 10.1212/WNL.0000000000000222
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH6TB
UT WOS:000336262500017
PM 24532277
ER
PT J
AU Zhao, HY
Mayer, ML
Schuck, P
AF Zhao, Huaying
Mayer, Mark L.
Schuck, Peter
TI Analysis of Protein Interactions with Picomolar Binding Affinity by
Fluorescence-Detected Sedimentation Velocity
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID CROSS-CORRELATION SPECTROSCOPY; SURFACE-PLASMON RESONANCE;
MOBILITY-SHIFT ASSAY; ANALYTICAL ULTRACENTRIFUGATION; DNA-BINDING;
COMPLEXES; SYSTEMS; SIZE; ELECTROPHORESIS; MACROMOLECULES
AB The study of high-affinity protein interactions with equilibrium dissociation constants (K-D) in the picomolar range is of significant interest in many fields, but the characterization of stoichiometry and free energy of such high-affinity binding can be far from trivial. Analytical ultracentrifugation has long been considered a gold standard in the study of protein interactions but is typically applied to systems with micromolar K-D. Here we present a new approach for the study of high-affinity interactions using fluorescence detected sedimentation velocity analytical ultracentrifugation (FDS-SV). Taking full advantage of the large data sets in FDS-SV by direct boundary modeling with sedimentation coefficient distributions c(s), we demonstrate detection and hydrodynamic resolution of protein complexes at low picomolar concentrations. We show how this permits the characterization of the antibody antigen interactions with low picomolar binding constants, 2 orders of magnitude lower than previously achieved. The strongly size-dependent separation and quantitation by concentration, size, and shape of free and complex species in free solution by FDS-SV has significant potential for studying high-affinity multistep and multicomponent protein assemblies.
C1 [Zhao, Huaying; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
[Mayer, Mark L.] NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Schuck, P (reprint author), Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
EM Peter.Schuck@nih.gov
OI Schuck, Peter/0000-0002-8859-6966
FU National Institute of Biomedical Imaging and Bioengineering; National
Institute of Child Health and Human Development, National Institutes of
Health
FX We thank Dr. George H. Patterson for a supply of EGFP and for helpful
discussions. This work was supported by the Intramural Research Programs
of the National Institute of Biomedical Imaging and Bioengineering and
the National Institute of Child Health and Human Development, National
Institutes of Health.
NR 61
TC 10
Z9 10
U1 0
U2 22
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
EI 1520-6882
J9 ANAL CHEM
JI Anal. Chem.
PD MAR 18
PY 2014
VL 86
IS 6
BP 3181
EP 3187
DI 10.1021/ac500093m
PG 7
WC Chemistry, Analytical
SC Chemistry
GA AD4QN
UT WOS:000333235700050
PM 24552356
ER
PT J
AU Wattenberg, MM
Kwilas, AR
Gameiro, SR
Dicker, AP
Hodge, JW
AF Wattenberg, M. M.
Kwilas, A. R.
Gameiro, S. R.
Dicker, A. P.
Hodge, J. W.
TI Expanding the use of monoclonal antibody therapy of cancer by using
ionising radiation to upregulate antibody targets
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE radiation; immunotherapy; monoclonal antibody; trastuzumab
ID SQUAMOUS-CELL CARCINOMA; BREAST-CANCER; TUMOR-CELLS; STEM-CELLS;
INITIATING CELLS; TRASTUZUMAB; RESISTANCE; IMMUNOTHERAPY; EXPRESSION;
IRRADIATION
AB Background: Monoclonal antibody (mAb) therapy for the treatment of solid and haematologic malignancies has shown poor response rates as a monotherapy. Furthermore, its use is limited to tumours expressing certain molecular targets. It has been shown that single-dose radiation can induce immunogenic modulation that is characterised by cell-surface phenotypic changes leading to augmented tumour cell/cytotoxic T-cell interaction.
Methods: We examined radiation's ability to upregulate mAb therapy targets. We also used radiation to sensitise tumour cells to antibody-dependent cell-mediated cytotoxicity (ADCC).
Results: Radiation significantly increased cell-surface and total protein expression of mAb targets HER2, EGFR, and CD20. Focusing on HER2, targeted by trastuzumab, we observed significant upregulation of HER2 following radiation of 3 out of 3 breast cancer cell lines, one of which was triple negative, as well as in residential stem-cell populations. HER2 upregulation was sustained up to 96 h following radiation exposure and was largely dependent on intracellular reactive oxygen species. Improved ADCC and sensitisation to the antiproliferative effects of trastuzumab demonstrated the functional significance of radiation-induced HER2 upregulation.
Conclusions: We show that single-dose radiation enhances mAb therapy. These findings highlight a mechanism for combining radiation with immunotherapy and expand the patient population that can be treated with targeted therapy.
C1 [Wattenberg, M. M.; Kwilas, A. R.; Gameiro, S. R.; Hodge, J. W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Dicker, A. P.] Thomas Jefferson Univ, Dept Radiat Oncol, Philadelphia, PA 19107 USA.
RP Hodge, JW (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B13, Bethesda, MD 20892 USA.
EM jh241d@nih.gov
RI Hodge, James/D-5518-2015;
OI Hodge, James/0000-0001-5282-3154; Dicker, Adam/0000-0003-0733-3337
FU Intramural Research Program of the Center for Cancer Research; National
Cancer Institute; National Institutes of Health; NIH Medical Research
Scholars Program; NIH from Pfizer Inc.; Leona M and Harry B Helmsley
Charitable Trust; Howard Hughes Medical Institute
FX We thank Dr Jeffrey Schlom for helpful suggestions, Marion Taylor for
excellent technical assistance, and Bonnie L Casey for editorial
assistance in the preparation of this manuscript. This research was
supported by the Intramural Research Program of the Center for Cancer
Research, National Cancer Institute, and National Institutes of Health.
Further support was provided by the NIH Medical Research Scholars
Program, a public-private partnership supported by the NIH along with
generous contributions to the Foundation for the NIH from Pfizer Inc.,
The Leona M and Harry B Helmsley Charitable Trust, the Howard Hughes
Medical Institute, and other private donors. For a complete list of
donors, see the Foundation website at
http://www.fnih.org/work/programs-development/medical-research-scholars-
program.
NR 41
TC 9
Z9 9
U1 3
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAR 18
PY 2014
VL 110
IS 6
BP 1472
EP 1480
DI 10.1038/bjc.2014.79
PG 9
WC Oncology
SC Oncology
GA AD4DB
UT WOS:000333195800010
PM 24556625
ER
PT J
AU Akrawinthawong, K
Park, JW
Piknova, B
Sibmooh, N
Fucharoen, S
Schechter, AN
AF Akrawinthawong, Krittapoom
Park, Ji Won
Piknova, Barbora
Sibmooh, Nathawut
Fucharoen, Suthat
Schechter, Alan N.
TI A Flow Cytometric Analysis of the Inhibition of Platelet Reactivity Due
to Nitrite Reduction by Deoxygenated Erythrocytes
SO PLOS ONE
LA English
DT Article
ID VENOUS THROMBOEMBOLISM; HYPOXIC CONDITIONS; DIETARY NITRATE; RELAXING
FACTOR; OXIDE; ENDOTHELIUM; AGGREGATION; ACTIVATION; ASPIRIN; HUMANS
AB Nitric oxide (NO), a small gas molecule, has long been known to be a potent inhibitor of platelet function but the physiological and pathological implications of platelet inhibition by NO have not been well clarified. We recently showed that the addition of nitrite to platelet-rich plasma in the presence of erythrocytes could inhibit platelet aggregation and this inhibitory effect of nitrite + erythrocytes was enhanced by deoxygenation of erythrocytes as measured by P-selectin expression and cGMP production. In order to study the nitrite effect on platelets at different oxygen levels, we used the flow cytometric assays to detect platelet membrane surface markers upon activation. The P-selectin and activated gpIIb/IIIa expression on platelet membranes in response to ADP, collagen and thrombin stimulation was measured at various hematocrit and oxygen levels. Nitrite (0.1 to 1.0 mu M) significantly decreased the percentage of these surface markers on the platelet membrane at the hematocrit values above 23% and oxygen levels lower than 49 mmHg. The inhibitory effect of nitrite was augmented by increasing hematocrit values and decreasing oxygen saturation. C-PTIO (an NO scavenger) prevented the platelet inhibition by nitrite + erythrocytes whereas the inhibitors of NO synthase and xanthine oxidoreductase had no effect. These results support the proposal that circulating nitrite decreases platelet reactivity in the presence of partially deoxygenated erythrocytes through its reduction to NO, which may also explain certain differences between arterial and venous thrombosis and support directly the role of deoxyhemoglobin in this process. We believe that our flow cytometric assays offer a possibility to identify the individual molecular process involved in these effects.
C1 [Akrawinthawong, Krittapoom; Park, Ji Won; Piknova, Barbora; Schechter, Alan N.] Natl Inst Diabet & Digest & Kidney Dis, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
[Sibmooh, Nathawut] Mahidol Univ, Fac Sci, Dept Pharmacol, Bangkok 10400, Thailand.
[Akrawinthawong, Krittapoom] Mahidol Univ, Dept Biochem, Fac Med, Siriraj Hosp, Bangkok 10700, Thailand.
[Fucharoen, Suthat] Mahidol Univ, Thalassemia Res Ctr, Inst Sci & Technol Res & Dev, Nakhon Pathom, Thailand.
RP Schechter, AN (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
EM alans@intra.niddk.nih.gov
OI Schechter, Alan N/0000-0002-5235-9408
FU intramural program of the National Institute of Diabetes and Digestive
and Kidney Diseases
FX This research was supported by grants from the intramural program of the
National Institute of Diabetes and Digestive and Kidney Diseases. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 32
TC 11
Z9 11
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 18
PY 2014
VL 9
IS 3
AR e92435
DI 10.1371/journal.pone.0092435
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD4ZE
UT WOS:000333259900139
PM 24642865
ER
PT J
AU Homolya, L
Fu, D
Sengupta, P
Jarnik, M
Gillet, JP
Vitale-Cross, L
Gutkind, JS
Lippincott-Schwartz, J
Arias, IM
AF Homolya, Laszlo
Fu, Dong
Sengupta, Prabuddha
Jarnik, Michal
Gillet, Jean-Pierre
Vitale-Cross, Lynn
Gutkind, J. Silvio
Lippincott-Schwartz, Jennifer
Arias, Irwin M.
TI LKB1/AMPK and PKA Control ABCB11 Trafficking and Polarization in
Hepatocytes
SO PLOS ONE
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; SALT EXPORT PUMP; BINDING CASSETTE
TRANSPORTERS; BILE-ACID TRANSPORT; CANALICULAR MEMBRANE;
EXTRACELLULAR-MATRIX; LKB1; LIVER; AMPK; EXPRESSION
AB Polarization of hepatocytes is manifested by bile canalicular network formation and activation of LKB1 and AMPK, which control cellular energy metabolism. The bile acid, taurocholate, also regulates development of the canalicular network through activation of AMPK. In the present study, we used collagen sandwich hepatocyte cultures from control and liver-specific LKB1 knockout mice to examine the role of LKB1 in trafficking of ABCB11, the canalicular bile acid transporter. In polarized hepatocytes, ABCB11 traffics from Golgi to the apical plasma membrane and endogenously cycles through the rab 11a-myosin Vb recycling endosomal system. LKB1 knockout mice were jaundiced, lost weight and manifested impaired bile canalicular formation and intracellular trafficking of ABCB11, and died within three weeks. Using live cell imaging, fluorescence recovery after photobleaching (FRAP), particle tracking, and biochemistry, we found that LKB1 activity is required for microtubule-dependent trafficking of ABCB11 to the canalicular membrane. In control hepatocytes, ABCB11 trafficking was accelerated by taurocholate and cAMP; however, in LKB1 knockout hepatocytes, ABCB11 trafficking to the apical membrane was greatly reduced and restored only by cAMP, but not taurocholate. cAMP acted through a PKA-mediated pathway which did not activate AMPK. Our studies establish a regulatory role for LKB1 in ABCB11 trafficking to the canalicular membrane, hepatocyte polarization, and canalicular network formation.
C1 [Homolya, Laszlo; Fu, Dong; Sengupta, Prabuddha; Jarnik, Michal; Lippincott-Schwartz, Jennifer; Arias, Irwin M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Homolya, Laszlo] Hungarian Acad Sci, Mol Cell Biol Lab, Inst Mol Pharmacol, Res Ctr Nat Sci, Budapest, Hungary.
[Fu, Dong] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia.
[Gillet, Jean-Pierre] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Gillet, Jean-Pierre] Belgium Univ Namur, Univ Namur, Fac Med, Lab Mol Canc Biol,Mol Physiol Res Unit URPhyM,Nam, Namur, Belgium.
[Vitale-Cross, Lynn; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RP Homolya, L (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM homolya.laszlo@ttk.mta.hu
RI Homolya, Laszlo/N-1154-2016;
OI Sengupta, Prabuddha/0000-0001-7094-6967
FU Hungarian-American Enterprise Scholarship Fund (HAESF); Momentum Program
of the Hungarian Academy of Sciences [LP2012-025]; Ministry of National
Development/National Development Agency/Hungarian Scientific Research
Fund [KTIA_OTKA_CK80283, KTIA_AIK_12-1-2012-0025]
FX This work has been supported by a scholarship from the
Hungarian-American Enterprise Scholarship Fund (HAESF), grants from the
Momentum Program of the Hungarian Academy of Sciences (LP2012-025), and
Ministry of National Development/National Development Agency/Hungarian
Scientific Research Fund (KTIA_OTKA_CK80283 and
KTIA_AIK_12-1-2012-0025). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 29
TC 12
Z9 13
U1 3
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 18
PY 2014
VL 9
IS 3
AR e91921
DI 10.1371/journal.pone.0091921
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD4ZE
UT WOS:000333259900048
PM 24643070
ER
PT J
AU Rao, RP
Scheffer, L
Srideshikan, SM
Parthibane, V
Kosakowska-Cholody, T
Masood, MA
Nagashima, K
Gudla, P
Lockett, S
Acharya, U
Acharya, JK
AF Rao, Raghavendra Pralhada
Scheffer, Luana
Srideshikan, Sargur M.
Parthibane, Velayoudame
Kosakowska-Cholody, Teresa
Masood, M. Athar
Nagashima, Kunio
Gudla, Prabhakar
Lockett, Stephen
Acharya, Usha
Acharya, Jairaj K.
TI Ceramide Transfer Protein Deficiency Compromises Organelle Function and
Leads to Senescence in Primary Cells
SO PLOS ONE
LA English
DT Article
ID ENDOPLASMIC-RETICULUM; STRUCTURAL BASIS; RAT-LIVER; LIFE-SPAN; GOLGI;
TRAFFICKING; CERT; GLUCOSYLCERAMIDE; APOPTOSIS; TRANSPORT
AB Ceramide transfer protein (CERT) transfers ceramide from the endoplasmic reticulum (ER) to the Golgi complex. Its deficiency in mouse leads to embryonic death at E11.5. CERT deficient embryos die from cardiac failure due to defective organogenesis, but not due to ceramide induced apoptotic or necrotic cell death. In the current study we examined the effect of CERT deficiency in a primary cell line, namely, mouse embryonic fibroblasts (MEFs). We show that in MEFs, unlike in mutant embryos, lack of CERT does not lead to increased ceramide but causes an accumulation of hexosylceramides. Nevertheless, the defects due to defective sphingolipid metabolism that ensue, when ceramide fails to be trafficked from ER to the Golgi complex, compromise the viability of the cell. Therefore, MEFs display an incipient ER stress. While we observe that ceramide trafficking from ER to the Golgi complex is compromised, the forward transport of VSVG-GFP protein is unhindered from ER to Golgi complex to the plasma membrane. However, retrograde trafficking of the plasma membrane-associated cholera toxin B to the Golgi complex is reduced. The dysregulated sphingolipid metabolism also leads to increased mitochondrial hexosylceramide. The mitochondrial functions are also compromised in mutant MEFs since they have reduced ATP levels, have increased reactive oxygen species, and show increased glutathione reductase activity. Live-cell imaging shows that the mutant mitochondria exhibit reduced fission and fusion events. The mitochondrial dysfunction leads to an increased mitophagy in the CERT mutant MEFs. The compromised organelle function compromise cell viability and results in premature senescence of these MEFs.
C1 [Rao, Raghavendra Pralhada; Scheffer, Luana; Srideshikan, Sargur M.; Parthibane, Velayoudame; Kosakowska-Cholody, Teresa; Acharya, Jairaj K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21701 USA.
[Masood, M. Athar] Frederick Natl Lab Canc Res, Lab Prote & Analyt Technol, Frederick, MD USA.
[Nagashima, Kunio] Frederick Natl Lab Canc Res, Electron Microscopy Lab, Frederick, MD USA.
[Gudla, Prabhakar; Lockett, Stephen] Frederick Natl Lab Canc Res, Opt Microscopy & Anal Lab, Frederick, MD USA.
[Acharya, Usha] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA USA.
RP Acharya, JK (reprint author), NCI, Lab Cell & Dev Signaling, Frederick, MD 21701 USA.
EM acharyaj@mail.nih.gov
FU intramural division of the National Cancer Institute, National
Institutes of Health, Department of Health and Human Resources
FX This project has been funded in whole by the intramural division of the
National Cancer Institute, National Institutes of Health, Department of
Health and Human Resources. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 36
TC 10
Z9 11
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 18
PY 2014
VL 9
IS 3
AR e92142
DI 10.1371/journal.pone.0092142
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD4ZE
UT WOS:000333259900093
PM 24642596
ER
PT J
AU Patel, K
Wang, JJ
Jacobson, DL
Lipshultz, SE
Landy, DC
Geffner, ME
DiMeglio, LA
Seage, GR
Williams, PL
Van Dyke, RB
Siberry, GK
Shearer, WT
Young, L
Scott, GB
Wilkinson, JD
Fisher, SD
Starc, TJ
Miller, TL
AF Patel, Kunjal
Wang, Jiajia
Jacobson, Denise L.
Lipshultz, Steven E.
Landy, David C.
Geffner, Mitchell E.
DiMeglio, Linda A.
Seage, George R., III
Williams, Paige L.
Van Dyke, Russell B.
Siberry, George K.
Shearer, William T.
Young, Luciana
Scott, Gwendolyn B.
Wilkinson, James D.
Fisher, Stacy D.
Starc, Thomas J.
Miller, Tracie L.
CA PHACS
TI Aggregate Risk of Cardiovascular Disease Among Adolescents Perinatally
Infected With the Human Immunodeficiency Virus
SO CIRCULATION
LA English
DT Article
DE adolescence; atherosclerosis; HIV; risk factors
ID ACTIVE ANTIRETROVIRAL THERAPY; PEDIATRIC HIV/AIDS COHORT; ANTI-HIV
DRUGS; YOUNG-ADULTS; MYOCARDIAL-INFARCTION; PROTEASE INHIBITORS;
DATA-COLLECTION; CHILDREN; ATHEROSCLEROSIS; ASSOCIATION
AB Background Perinatally HIV-infected adolescents may be susceptible to aggregate atherosclerotic cardiovascular disease risk, as measured by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries and abdominal aorta risk scores, as a result of prolonged exposure to HIV and antiretroviral therapy.
Methods and Results Coronary arteries and abdominal aorta PDAY scores were calculated for 165 perinatally HIV-infected adolescents, using a weighted combination of modifiable risk factors: dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. Demographic and HIV-specific predictors of scores 1 were identified, and trends in scores over time were assessed. Forty-eight percent and 24% of the perinatally HIV-infected adolescents had coronary arteries and abdominal aorta scores 1, representing increased cardiovascular disease risk factor burden. Significant predictors of coronary arteries scores 1 included male sex, history of an AIDS-defining condition, longer duration of use of a ritonavir-boosted protease inhibitor, and no prior use of tenofovir. Significant predictors of abdominal aorta scores 1 included suppressed viral load, history of an AIDS-defining condition, and longer duration of boosted protease inhibitor use. No significant changes in coronary arteries and abdominal aorta risk scores were observed over the 4-year study period.
Conclusions A substantial proportion of perinatally HIV-infected youth have high PDAY scores, reflecting increased aggregate atherosclerotic cardiovascular disease risk factor burden. High scores were predicted by HIV disease severity and boosted protease inhibitor use. PDAY scores may be useful in identifying high-risk youth who may benefit from early lifestyle or clinical interventions.
C1 [Patel, Kunjal; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Patel, Kunjal; Wang, Jiajia; Jacobson, Denise L.; Seage, George R., III; Williams, Paige L.] Ctr Biostat AIDS Res, Boston, MA USA.
[Lipshultz, Steven E.] Wayne State Univ, Sch Med, Dept Pediat, Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Landy, David C.; Scott, Gwendolyn B.; Wilkinson, James D.; Miller, Tracie L.] Univ Miami, Miller Sch Med, Div Pediat Clin Res, Dept Pediat, Miami, FL 33136 USA.
[Landy, David C.; Scott, Gwendolyn B.; Wilkinson, James D.; Miller, Tracie L.] Univ Miami, Miller Sch Med, Div Pediat Infect Dis & Immunol, Dept Pediat, Miami, FL 33136 USA.
[Geffner, Mitchell E.] USC, Keck Sch Med, Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA USA.
[DiMeglio, Linda A.] Indiana Univ Sch Med, Dept Pediat, Sect Pediat Endocrinol & Diabetol, Indianapolis, IN 46202 USA.
[Van Dyke, Russell B.] Tulane Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA 70118 USA.
[Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, Bethesda, MD USA.
[Shearer, William T.] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Young, Luciana] Northwestern Univ, Childrens Mem Hosp, Dept Pediat, Feinberg Sch Med, Chicago, IL 60614 USA.
[Fisher, Stacy D.] Univ Maryland, Sch Med, Div Cardiol, Baltimore, MD 21201 USA.
[Starc, Thomas J.] Columbia Univ Coll Phys & Surg, Dept Pediat, Div Pediat Cardiol, Presbyterian Hosp, New York, NY 10032 USA.
RP Patel, K (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM kpatel@hsph.harvard.edu
OI DiMeglio, Linda/0000-0002-8033-6078
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute on Drug Abuse; National Institute of
Allergy and Infectious Diseases; Office of AIDS Research; National
Institute of Mental Health; National Institute of Neurological Disorders
and Stroke; National Institute on Deafness and Other Communication
Disorders; National Heart, Lung, and Blood Institute; National Institute
of Dental and Craniofacial Research; National Institute on Alcohol Abuse
and Alcoholism; Harvard University School of Public Health [HD052102, 3
U01 HD052102-05S1, 3 U01 HD052102-06S3]; Tulane University School of
Medicine [HD052104, 3U01 HD052104-06S1]
FX PHACS was supported by the Eunice Kennedy Shriver National Institute of
Child Health and Human Development with cofunding from the National
Institute on Drug Abuse; the National Institute of Allergy and
Infectious Diseases; the Office of AIDS Research; the National Institute
of Mental Health; the National Institute of Neurological Disorders and
Stroke; the National Institute on Deafness and Other Communication
Disorders; the National Heart, Lung, and Blood Institute; the National
Institute of Dental and Craniofacial Research; and the National
Institute on Alcohol Abuse and Alcoholism, through cooperative
agreements with the Harvard University School of Public Health
(HD052102, 3 U01 -HD052102-05S1, 3 U01 HD052102-06S3; principal
investigator, George Seage; project director: Julie Alperen) and the
Tulane University School of Medicine (HD052104, 3U01 HD052104-06S1;
principal investigator, Russell Van Dyke; co-principal investigator,
Kenneth Rich; project director, Patrick Davis). The conclusions and
opinions expressed in this article are those of the authors and do not
necessarily reflect those of the National Institutes of Health or US
Department of Health and Human Services.
NR 42
TC 10
Z9 10
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 18
PY 2014
VL 129
IS 11
BP 1204
EP 1212
DI 10.1161/CIRCULATIONAHA.113.001978
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AD3MN
UT WOS:000333145200010
PM 24366631
ER
PT J
AU Soekadar, SR
Witkowski, M
Cossio, EG
Birbaumer, N
Cohen, LG
AF Soekadar, Surjo R.
Witkowski, Matthias
Cossio, Eliana G.
Birbaumer, Niels
Cohen, Leonardo G.
TI Learned EEG-based brain self-regulation of motor-related oscillations
during application of transcranial electric brain stimulation:
feasibility and limitations
SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE
LA English
DT Article
DE brain-machine interface (BMI) control; motor imagery; EEG; transcranial
electric stimulation (TES); stimulation artifacts
ID INTERFACE BCI SYSTEM; COMPUTER INTERFACE; SKILL ACQUISITION; CHRONIC
STROKE; MODULATION; CORTEX; EXCITABILITY; PERFORMANCE; PLASTICITY;
MOVEMENT
AB Objective: Transcranial direct current stimulation (tDCS) improves motor learning and can affect emotional processing and attention. However, it is unclear whether learned electroencephalography (EEG)-based brain-machine interface (BMI) control during tDCS is feasible, how application of transcranial electric currents during BMI control would interfere with feature-extraction of physiological brain signals and how it affects brain control performance. Here we tested this combination and evaluated stimulation-dependent artifacts across different EEG frequencies and stability of motor imagery-based BMI control.
Approach: Ten healthy volunteers were invited to two BMI-sessions, each comprising two 60-trial blocks. During the trials, learned desynchronization of mu-rhythms (8-15 Hz) associated with motor imagery (MI) recorded over C4 was translated into online cursor movements on a computer screen. During block 2, either sham (session A) or anodal tDCS (session B) was applied at 1 mA with the stimulation electrode placed 1 cm anterior of C4.
Main results: tDCS was associated with a significant signal power increase in the lower frequencies most evident in the signal spectrum of the EEG channel closest to the stimulation electrode. Stimulation-dependent signal power increase exhibited a decay of 12 dB per decade, leaving frequencies above 9 Hz unaffected. Analysis of BMI control performance did not indicate a difference between blocks and tDCS conditions.
Conclusion: Application of tDCS during learned EEG-based self-regulation of brain oscillations above 9 Hz is feasible and safe, and might improve applicability of BMI systems.
C1 [Soekadar, Surjo R.; Witkowski, Matthias; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
[Soekadar, Surjo R.; Witkowski, Matthias; Cossio, Eliana G.] Univ Tubingen Hosp, Dept Psychiat & Psychotherapy, Appl Neurotechnol Lab, D-72076 Tubingen, Germany.
[Soekadar, Surjo R.; Witkowski, Matthias; Cossio, Eliana G.; Birbaumer, Niels] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany.
[Birbaumer, Niels] Osped San Camillo, IRCCS, Venice, Italy.
RP Soekadar, SR (reprint author), Univ Tubingen Hosp, Dept Psychiat & Psychotherapy, Appl Neurotechnol Lab, Calwerstr 14, D-72076 Tubingen, Germany.
EM surjo.soekadar@uni-tuebingen.de
FU National Institute of Neurological Disorders and Stroke (NINDS), USA;
Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed
Services University of Health Sciences, USA; Advanced Convergence
Research Center at the Daegu Gyeongbuk Institute of Science and
Technology, Korea; German Federal Ministry of Education and Research
(BMBF) [01GQ0831, 165V5838K]; Deutsche Forschungsgemeinschaft (DFG)
[SO932-1]; European Commission under the project WAY [288551];
Volkswagenstiftung; Baden-Wurttemberg Stiftung, Germany
FX This work was supported by the Intramural Research Program (IRP) of the
National Institute of Neurological Disorders and Stroke (NINDS), USA;
the Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed
Services University of Health Sciences, USA; the Advanced Convergence
Research Center at the Daegu Gyeongbuk Institute of Science and
Technology, Korea; the German Federal Ministry of Education and Research
(BMBF, grant number 01GQ0831, 165V5838K to Surjo R. Soekadar and Niels
Birbaumer); the Deutsche Forschungsgemeinschaft (DFG, grant number
SO932-1 to Surjo R. Soekadar and Reinhart Koselleck Project support to
Niels Birbaumer); the European Commission under the project WAY (grant
number 288551 to Surjo R. Soekadar and Niels Birbaumer); the
Volkswagenstiftung and the Baden-Wurttemberg Stiftung, Germany. We thank
Sook-Lei Liew and Birgit Teufel for their assistance in preparing the
manuscript.
NR 34
TC 14
Z9 15
U1 0
U2 25
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5153
J9 FRONT BEHAV NEUROSCI
JI Front. Behav. Neurosci.
PD MAR 18
PY 2014
VL 8
AR 93
DI 10.3389/fnbeh.2014.00093
PG 8
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA AD0NK
UT WOS:000332930900002
PM 24672456
ER
PT J
AU Liao, JL
Wu, CX
Burlak, C
Zhang, S
Sahm, H
Wang, M
Zhang, ZY
Vogel, KW
Federici, M
Riddle, SM
Nichols, RJ
Liu, DL
Cookson, MR
Stone, TA
Hoang, QQ
AF Liao, Jingling
Wu, Chun-Xiang
Burlak, Christopher
Zhang, Sheng
Sahm, Heather
Wang, Mu
Zhang, Zhong-Yin
Vogel, Kurt W.
Federici, Mark
Riddle, Steve M.
Nichols, R. Jeremy
Liu, Dali
Cookson, Mark R.
Stone, Todd A.
Hoang, Quyen Q.
TI Parkinson disease-associated mutation R1441H in LRRK2 prolongs the
"active state" of its GTPase domain
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE neurodegenerative disease; dimer; monomer; oligomeric states
ID KINASE-ACTIVITY; CRYSTAL-STRUCTURE; PROTEIN; GENE; BINDING; DYNAMIN
AB Mutation in leucine-rich-repeat kinase 2 (LRRK2) is a common cause of Parkinson disease (PD). A disease-causing point mutation R1441H/G/C in the GTPase domain of LRRK2 leads to overactivation of its kinase domain. However, the mechanism by which this mutation alters the normal function of its GTPase domain [Ras of complex proteins (Roc)] remains unclear. Here, we report the effects of R1441H mutation (Roc(R1441H)) on the structure and activity of Roc. We show that Roc forms a stable monomeric conformation in solution that is catalytically active, thus demonstrating that LRRK2 is a bona fide self-contained GTPase. We further show that the R1441H mutation causes a twofold reduction in GTPase activity without affecting the structure, thermal stability, and GDP-binding affinity of Roc. However, the mutation causes a twofold increase in GTP-binding affinity of Roc, thus suggesting that the PD-causing mutation R1441H traps Roc in a more persistently activated state by increasing its affinity for GTP and, at the same time, compromising its GTP hydrolysis.
C1 [Liao, Jingling; Wu, Chun-Xiang; Zhang, Sheng; Sahm, Heather; Wang, Mu; Zhang, Zhong-Yin; Hoang, Quyen Q.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
[Liao, Jingling; Wu, Chun-Xiang; Hoang, Quyen Q.] Indiana Univ Sch Med, Stark Neurosci Inst, Indianapolis, IN 46202 USA.
[Burlak, Christopher] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA.
[Vogel, Kurt W.; Federici, Mark; Riddle, Steve M.] Thermo Fisher Sci, Madison, WI 53719 USA.
[Nichols, R. Jeremy] Parkinsons Inst & Clin Ctr, Sunnyvale, CA 94085 USA.
[Liu, Dali] Loyola Univ, Chicago, IL 60626 USA.
[Cookson, Mark R.] NIH, Lab Neurogenet, Bethesda, MD 20892 USA.
[Stone, Todd A.] Indiana Univ, Dept Mol & Cellular Biochem, Bloomington, IN 47405 USA.
RP Hoang, QQ (reprint author), Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
EM qqhoang@iu.edu
FU Michael J. Fox Foundation Community Fast Track grant; Indiana University
School of Medicine's Biomedical Research grant; Showalter Research Trust
grant; Intramural Research Program of the National Institutes of Health,
National Institute on Aging; Brin/Wojcicki Foundation; [RO1 CA69202]
FX We thank Clark Wells and Yuro Takagi for helpful discussions. Q. Q. H.
acknowledges support from a Michael J. Fox Foundation Community Fast
Track grant. Q. Q. H. acknowledges additional support from the Indiana
University School of Medicine's Biomedical Research grant and the
Showalter Research Trust grant. This research was supported, in part, by
the Intramural Research Program of the National Institutes of Health,
National Institute on Aging (M. R. C.). R.J.N. acknowledges the
Brin/Wojcicki Foundation for support. S.Z. and Z.-Y.Z. were supported in
part by Grant RO1 CA69202.
NR 26
TC 36
Z9 37
U1 4
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 18
PY 2014
VL 111
IS 11
BP 4055
EP 4060
DI 10.1073/pnas.1323285111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1XV
UT WOS:000333027900046
PM 24591621
ER
PT J
AU Wang, XH
Wang, HK
Li, Y
Hafner, M
Banerjee, NS
Tang, S
Briskin, D
Meyers, C
Chow, LT
Xie, X
Tuschl, T
Zheng, ZM
AF Wang, Xiaohong
Wang, Hsu-Kun
Li, Yang
Hafner, Markus
Banerjee, Nilam Sanjib
Tang, Shuang
Briskin, Daniel
Meyers, Craig
Chow, Louise T.
Xie, Xing
Tuschl, Thomas
Zheng, Zhi-Ming
TI microRNAs are biomarkers of oncogenic human papillomavirus infections
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE oncogenes E6 and E7; noncoding RNAs; regulatory RNAs; virol oncogenesis;
DNA tumor viruses
ID B-CELL LYMPHOMAS; CERVICAL-CANCER; C-MYC; EPITHELIAL DIFFERENTIATION;
EXPRESSION PROFILES; MIRNA EXPRESSION; TARGET GENES; E6; PROLIFERATION;
CLUSTER
AB Cellular and viral microRNAs (miRNAs) are the transcriptional products of RNA polymerase II and are regulated by transcriptional factors for their differential expression. The altered expression of miRNAs in many cancer types has been explored as a marker for possible diagnosis and therapy. We report in this study that oncogenic human papillomaviruses (HPVs) induce aberrant expression of many cellular miRNAs and that HPV18 infection produces no detectable viral miRNA. Thirteen abundant host miRNAs were specifically regulated by HPV16 and HPV18 in organotypic raft cultures of foreskin and vaginal keratinocytes as determined by miRNA array in combination with small RNA sequencing. The increase of miR-16, miR-25, miR-92a, and miR-378 and the decrease of miR-22, miR-27a, miR-29a, and miR-100 could be attributed to viral oncoprotein E6, E7, or both, all of which are known to target many cellular transcription factors. The examination of 158 cervical specimens, including 38 normal, 52 cervical intraepithelial neoplasia (CIN), and 68 cervical cancer (CC) tissues, for the expression of these eight miRNAs showed a remarkable increase of miR-25, miR-92a, and miR-378 with lesion progression but no obvious change of miR-22, miR-29a, and miR-100 among the HPV-infected tissues. Further analyses indicate that an expression ratio >= 1.5 of miR-25/92a group over miR-22/29a group could serve as a cutoff value to distinguish normal cervix from CIN and from CIN to CC.
C1 [Wang, Xiaohong; Li, Yang; Tang, Shuang; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Wang, Hsu-Kun; Banerjee, Nilam Sanjib; Chow, Louise T.] Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA.
[Li, Yang; Xie, Xing] Zhejiang Univ Sch Med, Womens Hosp, Dept Gynecol Oncol, Hangzhou 310006, Peoples R China.
[Hafner, Markus; Briskin, Daniel; Tuschl, Thomas] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
[Hafner, Markus; Briskin, Daniel; Tuschl, Thomas] Rockefeller Univ, Lab RNA Mol Biol, New York, NY 10065 USA.
[Meyers, Craig] Penn State Univ Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA.
RP Chow, LT (reprint author), Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA.
EM ltchow@uab.edu; zhengt@mail.nih.gov
RI Tang, Shuang/F-9115-2014;
OI Tang, Shuang/0000-0002-3084-0903; Hafner, Markus/0000-0002-4336-6518
FU National Cancer Institute, Center for Cancer Research; National
Institutes of Health [R01 CA83679, R01 AI57988]; Natural Science
Foundation of China [NSFC 81172475]; Natural Science Foundation of
Zhejiang Province of China [LQ13H160003]
FX We thank Jeffrey Strathern for his support and critical reading of our
manuscript. This study was supported by the Intramural Research Programs
of the National Cancer Institute, Center for Cancer Research and
National Institutes of Health Grants R01 CA83679 (to L. T. C.) and R01
AI57988 (to C. M.), Natural Science Foundation of China Grant NSFC
81172475 (to X. X.), and Natural Science Foundation of Zhejiang Province
of China Grant LQ13H160003 (to Y.L.).
NR 60
TC 46
Z9 51
U1 1
U2 29
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 18
PY 2014
VL 111
IS 11
BP 4262
EP 4267
DI 10.1073/pnas.1401430111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1XV
UT WOS:000333027900081
PM 24591631
ER
PT J
AU Ippolito, GC
Dekker, JD
Wang, YH
Lee, BK
Shaffer, AL
Lin, J
Wall, JK
Lee, BS
Staudt, LM
Liu, YJ
Iyer, VR
Tucker, HO
AF Ippolito, Gregory C.
Dekker, Joseph D.
Wang, Yui-Hsi
Lee, Bum-Kyu
Shaffer, Arthur L., III
Lin, Jian
Wall, Jason K.
Lee, Baeck-Seung
Staudt, Louis M.
Liu, Yong-Jun
Iyer, Vishwanath R.
Tucker, Haley O.
TI Dendritic cell fate is determined by BCL11A
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID TRANSCRIPTION FACTOR E2-2; HEMATOPOIETIC STEM-CELLS; GENE-EXPRESSION;
T-CELLS; LYMPHOID DEVELOPMENT; PROTEIN; ID3; E2A; LINEAGE; ORIGIN
AB The plasmacytoid dendritic cell (pDC) is vital to the coordinated action of innate and adaptive immunity. pDC development has not been unequivocally traced, nor has its transcriptional regulatory network been fully clarified. Here we confirm an essential requirement for the BCL11A transcription factor in fetal pDC development, and demonstrate this lineage-specific requirement in the adult organism. Furthermore, we identify BCL11A gene targets and provide a molecular mechanism for its action in pDC commitment. Embryonic germ-line deletion of Bcl11a revealed an absolute cellular, molecular, and functional absence of pDCs in fetal mice. In adults, deletion of Bcl11a in hematopoietic stem cells resulted in perturbed yet continued generation of progenitors, loss of downstream pDC and B-cell lineages, and persisting myeloid, conventional dendritic, and T-cell lineages. Challenge with virus resulted in a marked reduction of antiviral response in conditionally deleted adults. Genome-wide analyses of BCL11A DNA binding and expression revealed that BCL11A regulates transcription of E2-2 and other pDC differentiation modulators, including ID2 and MTG16. Our results identify BCL11A as an essential, lineage-specific factor that regulates pDC development, supporting a model wherein differentiation into pDCs represents a primed "default" pathway for common dendritic cell progenitors.
C1 [Ippolito, Gregory C.; Dekker, Joseph D.; Lee, Bum-Kyu; Lin, Jian; Wall, Jason K.; Lee, Baeck-Seung; Iyer, Vishwanath R.; Tucker, Haley O.] Univ Texas Austin, Inst Cellular & Mol Biol, Dept Mol Biosci, Austin, TX 78712 USA.
[Wang, Yui-Hsi] Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 44229 USA.
[Shaffer, Arthur L., III; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Liu, Yong-Jun] Baylor Inst Immunol Res, Dallas, TX 75204 USA.
RP Tucker, HO (reprint author), Univ Texas Austin, Inst Cellular & Mol Biol, Dept Mol Biosci, Austin, TX 78712 USA.
EM haleytucker@austin.utexas.edu
RI Dekker, Joseph/G-4924-2013
OI Dekker, Joseph/0000-0002-2068-3529
FU Intramural Research Program of the National Institutes of Health (NIH)
National Cancer Institute, Centre for Cancer Research; NIH [F32CA110624,
R01CA31534]; Cancer Prevention Research Institute of Texas (CPRIT)
[RP100612, RP120348]; Marie Betzner Morrow Centennial Endowment
FX We thank June V. Harriss, Deborah Surman, and the late Shanna D. Maika
for expert assistance in the generation of Bcl11a conditional knockout
mice, and Chhaya Das and Maya Ghosh for help in ChIP analysis and cell
culture. The CAL-1 cell line was kindly provided by Dr. Takahiro Maeda
and Dr. Boris Reizis. Conventional Bcl11a knockout mice were provided by
Dr. Pentao Liu. Support for this work was provided by the Intramural
Research Program of the National Institutes of Health (NIH) National
Cancer Institute, Center for Cancer Research (to L.M.S. and A.L.S.); NIH
Grants F32CA110624 (to G.C.I.) and R01CA31534 (to H.O.T.); Cancer
Prevention Research Institute of Texas (CPRIT) Grants RP100612,
RP120348; and the Marie Betzner Morrow Centennial Endowment (H.O.T).
NR 58
TC 19
Z9 19
U1 0
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 18
PY 2014
VL 111
IS 11
BP E998
EP E1006
DI 10.1073/pnas.1319228111
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1XV
UT WOS:000333027900009
PM 24591644
ER
PT J
AU Zhi, N
Hu, GQ
Wong, S
Zhao, KJ
Mao, Q
Young, NS
AF Zhi, Ning
Hu, Gangqing
Wong, Susan
Zhao, Keji
Mao, Qing
Young, Neal S.
TI Reply to Naccache et al: Viral sequences of NIH-CQV virus, a
contamination of DNA extraction method
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Letter
C1 [Zhi, Ning; Wong, Susan; Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Hu, Gangqing; Zhao, Keji] NHLBI, Syst Biol Ctr, Bethesda, MD 20892 USA.
[Mao, Qing] Third Mil Med Univ, Inst Infect Dis, Southwest Hosp, Chongqing 400038, Peoples R China.
RP Zhi, N (reprint author), NHLBI, Hematol Branch, Bldg 10, Bethesda, MD 20892 USA.
EM zhin@nhlbi.nih.gov
RI HU, GANGQING/K-5849-2012
NR 6
TC 6
Z9 6
U1 2
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 18
PY 2014
VL 111
IS 11
BP E977
EP E977
DI 10.1073/pnas.1318965111
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1XV
UT WOS:000333027900006
PM 24829942
ER
PT J
AU Paoloni, M
Webb, C
Mazcko, C
Cherba, D
Hendricks, W
Lana, S
Ehrhart, EJ
Charles, B
Fehling, H
Kumar, L
Vail, D
Henson, M
Childress, M
Kitchell, B
Kingsley, C
Kim, S
Neff, M
Davis, B
Chand, K
Trent, J
AF Paoloni, Melissa
Webb, Craig
Mazcko, Christina
Cherba, David
Hendricks, William
Lana, Susan
Ehrhart, E. J.
Charles, Brad
Fehling, Heather
Kumar, Leena
Vail, David
Henson, Michael
Childress, Michael
Kitchell, Barbara
Kingsley, Christopher
Kim, Seungchan
Neff, Mark
Davis, Barbara
Khanna, Chand
Trent, Jeffrey
TI Prospective Molecular Profiling of Canine Cancers Provides a Clinically
Relevant Comparative Model for Evaluating Personalized Medicine (PMed)
Trials
SO PLOS ONE
LA English
DT Article
ID TARGETS; GENOME; CHEMOSENSITIVITY; OSTEOSARCOMA; DISEASE; TUMORS; GENES;
DOG
AB Background: Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting.
Methodology: A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type.
Conclusions: Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (<1 week). Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of dogs with cancer into the preclinical modeling of personalized medicine. Future comparative oncology studies optimizing the delivery of PMed strategies may aid cancer drug development.
C1 [Paoloni, Melissa; Mazcko, Christina; Khanna, Chand] NCI, Comparat Oncol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
[Webb, Craig; Cherba, David; Neff, Mark; Trent, Jeffrey] Van Andel Res Inst, Grand Rapids, MI USA.
[Hendricks, William; Kingsley, Christopher; Kim, Seungchan; Davis, Barbara; Trent, Jeffrey] Translat Genom Res Inst TGen, Phoenix, AZ USA.
[Lana, Susan; Ehrhart, E. J.; Charles, Brad] Colorado State Univ, Coll Vet Med, Ft Collins, CO 80523 USA.
[Fehling, Heather; Kumar, Leena] Clin Reference Lab, Lenexa, KS USA.
[Vail, David] Univ Wisconsin, Sch Vet Med, Madison, WI 53706 USA.
[Henson, Michael] Univ Minnesota, Coll Vet Med, St Paul, MN 55108 USA.
[Childress, Michael] Purdue Univ, Sch Vet Med, W Lafayette, IN 47907 USA.
[Kitchell, Barbara] Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA.
RP Chand, K (reprint author), NCI, Comparat Oncol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
EM khannac@mail.nih.gov; jtrent@tgen.org
OI , William/0000-0001-7192-8699; Childress, Michael/0000-0001-6127-4679
FU National Institutes of Health [UC2 CA148149]
FX Grant support: National Institutes of Health UC2 CA148149. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 38
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U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 17
PY 2014
VL 9
IS 3
AR e90028
DI 10.1371/journal.pone.0090028
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD4XD
UT WOS:000333254100002
PM 24637659
ER
PT J
AU Stephen, AG
Esposito, D
Bagni, RK
McCormick, F
AF Stephen, Andrew G.
Esposito, Dominic
Bagni, Rachel K.
McCormick, Frank
TI Dragging Ras Back in the Ring
SO CANCER CELL
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; BLADDER-CARCINOMA ONCOGENE; CELL
LUNG-CARCINOMA; AMINO-ACID 12; K-RAS; IN-VITRO; N-RAS; EFFECTOR
INTERACTIONS; TRANSFORMING GENES; COLORECTAL-CANCER
AB Ras proteins play a major role in human cancers but have not yielded to therapeutic attack. Ras-driven cancers are among the most difficult to treat and often excluded from therapies. The Ras proteins have been termed "undruggable," based on failures from an era in which understanding of signaling transduction, feedback loops, redundancy, tumor heterogeneity, and Ras' oncogenic role was poor. Structures of Ras onco-proteins bound to their effectors or regulators are unsolved, and it is unknown precisely how Ras proteins activate their downstream targets. These knowledge gaps have impaired development of therapeutic strategies. A better understanding of Ras biology and biochemistry, coupled with new ways of targeting undruggable proteins, is likely to lead to new ways of defeating Ras-driven cancers.
C1 [Stephen, Andrew G.; Esposito, Dominic; Bagni, Rachel K.; McCormick, Frank] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[McCormick, Frank] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA.
RP McCormick, F (reprint author), Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, POB B, Frederick, MD 21702 USA.
EM mccormic@cc.ucsf.edu
FU Children's Tumor Foundation; Pancreatic Cancer Action Network,
Wellspring; Lustgarten Foundation; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]
FX Thanks to Sarangan Ravichandran (Frederick National Laboratory for
Cancer Research) for help with Figure 2. F.M. wishes to thank his
friends and colleagues in the Ras community, past and present members of
his lab at UCSF and at Frederick National Lab for Cancer Research for
discussions, data, and friendship, and for the NCI, Daiichi Sankyo, The
Children's Tumor Foundation, the Pancreatic Cancer Action Network,
Wellspring, and the Lustgarten Foundation for support. This work 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.
NR 86
TC 171
Z9 173
U1 9
U2 52
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD MAR 17
PY 2014
VL 25
IS 3
BP 272
EP 281
DI 10.1016/j.ccr.2014.02.017
PG 10
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AD4PQ
UT WOS:000333233400007
PM 24651010
ER
PT J
AU Dupont, N
Chauhan, S
Arko-Mensah, J
Castillo, EF
Masedunskas, A
Weigert, R
Robenek, H
Proikas-Cezanne, T
Deretic, V
AF Dupont, Nicolas
Chauhan, Santosh
Arko-Mensah, John
Castillo, Eliseo F.
Masedunskas, Andrius
Weigert, Roberto
Robenek, Horst
Proikas-Cezanne, Tassula
Deretic, Vojo
TI Neutral Lipid Stores and Lipase PNPLA5 Contribute to Autophagosome
Biogenesis
SO CURRENT BIOLOGY
LA English
DT Article
ID ADIPOSE TRIGLYCERIDE LIPASE; ENDOPLASMIC-RETICULUM;
SACCHAROMYCES-CEREVISIAE; MAMMALIAN AUTOPHAGY; MEMBRANE; DROPLETS;
COMPLEX; FAT; PHOSPHATIDYLCHOLINE; MACROAUTOPHAGY
AB Background: Autophagy is a fundamental cell biological process whereby eukaryotic cells form membranes in the cytoplasm to sequester diverse intracellular targets. Although significant progress has been made in understanding the origins of autophagosomal organelles, the source of lipids that support autophagic membrane formation remain an important open question.
Results: Here we show that lipid droplets as cellular stores of neutral lipids including triglycerides contribute to autophagic initiation. Lipid droplets, as previously shown, were consumed upon induction of autophagy by starvation. However, inhibition of autophagic maturation by blocking acidification or using dominant negative Atg4(C74A) that prohibits autophagosomal closure did not prevent disappearance of lipid droplets. Thus, lipid droplets continued to be utilized upon induction of autophagy, but not as autophagic substrates in a process referred to as lipophagy. We considered an alternative model whereby lipid droplets were consumed not as a part of lipophagy, but as a potential contributing source to the biogenesis of lipid precursors for nascent autophagosomes. We carried out a screen for a potential link between triglyceride mobilization and autophagy and identified a neutral lipase, PNPLA5, as being required for efficient autophagy. PNPLA5, which localized to lipid droplets, was needed for optimal initiation of autophagy. PNPLA5 was required for autophagy of diverse substrates, including degradation of autophagic adaptors, bulk proteolysis, mitochondrial quantity control, and microbial clearance.
Conclusions: Lipid droplets contribute to autophagic capacity by enhancing it in a process dependent on PNPLA5. Thus, neutral lipid stores are mobilized during autophagy to support autophagic membrane formation.
C1 [Dupont, Nicolas; Chauhan, Santosh; Arko-Mensah, John; Castillo, Eliseo F.; Deretic, Vojo] Univ New Mexico Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA.
[Dupont, Nicolas] Univ Paris 05, Sorbonne Paris Cite, INEM, INSERM U1151,CNRS UMR8253, F-75014 Paris, France.
[Masedunskas, Andrius; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Robenek, Horst] Univ Munster, Leibniz Inst Arteriosclerosis Res, D-48149 Munster, Germany.
[Proikas-Cezanne, Tassula] Univ Tubingen, Dept Mol Biol, Autophagy Lab, D-72076 Tubingen, Germany.
RP Deretic, V (reprint author), Univ New Mexico Hlth Sci Ctr, Dept Mol Genet & Microbiol, 915 Camino Salud NE, Albuquerque, NM 87131 USA.
EM vderetic@salud.unm.edu
OI Masedunskas, Andrius/0000-0002-4533-5467; Deretic,
Vojo/0000-0002-3624-5208
FU FRM; INSERM; University Paris-Descartes; ANR; INCa; DFG [SFB773/TP A03];
National Institutes of Health [R01 AI042999, R01 AI111935];
[AI042999-13S1]
FX We thank Patrice Codogno for his generous support of N.D. and Chantal
Bauvy for experimental help. We acknowledge W. Ornatowski, D.
Bhattacharya, and M. Mudd for assistance. We are grateful to N.
Mizushima for GFP-LC3 transgenic mice, T. Yoshimori for NIH3T3 cells
stably expressing Atg4B or mStrawberry-Atg4BC74A, N. Ktistakis for
HEK-293 stably expressing GFP-DFCP1, D. Rubinsztein for mRFP-GFP-LC3 He
La cells, S. Tooze for spontaneously immortalized ULK1/ ULK2
double-knockout MEFs, and X. M. Yin and T. Balla for plasmids
expressing, respectively, GFP-Atg16L1 and NES-GFP-DAG. N.D. acknowledges
facilities support by Conseil de la Region Ile-de-France (program Sesame
2007, project Imagopole, S. Shorte) and from the Fondation Francaise
pour la Recherche Medicate (FRM, Programme Grands Equipements) to N.
Aulner, the Necker Institute Imaging Facility, and the Fondation Imagine
and the Imagopole-PFID France-BioImaging infrastructure supported by the
French National Research Agency (ANR-10-INSB-04-01, "Investments for the
future") for advice and access to the Opera system. N.D. is a recipient
of a FRM fellowship. Studies in Patrice Codogno's laboratory are
supported by institutional funding from INSERM, University
Paris-Descartes, and grants from ANR and INCa. T.P.-C. acknowledges
support from DFG SFB773/TP A03. E.F.C. was supported by minority
supplement grant AI042999-13S1. This work was supported by grant R01
AI042999 and R01 AI111935 from the National Institutes of Health to V.D.
NR 40
TC 47
Z9 48
U1 3
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
EI 1879-0445
J9 CURR BIOL
JI Curr. Biol.
PD MAR 17
PY 2014
VL 24
IS 6
BP 609
EP 620
DI 10.1016/j.cub.2014.02.008
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AD4PP
UT WOS:000333233300020
PM 24613307
ER
PT J
AU Wu, XF
Hammer, JA
AF Wu, Xufeng
Hammer, John A.
TI Organelle Interactions: Melanosomes and Mitochondria Get Cozy
SO CURRENT BIOLOGY
LA English
DT Editorial Material
ID MELANOCYTES; DYNAMICS; MFN2
C1 [Wu, Xufeng; Hammer, John A.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
RP Wu, XF (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM hammerj@nhlbi.nih.gov
NR 15
TC 1
Z9 1
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
EI 1879-0445
J9 CURR BIOL
JI Curr. Biol.
PD MAR 17
PY 2014
VL 24
IS 6
BP R240
EP R242
DI 10.1016/j.cub.2014.02.014
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AD4PP
UT WOS:000333233300015
PM 24650913
ER
PT J
AU Ingaramo, M
York, AG
Hoogendoorn, E
Postma, M
Shroff, H
Patterson, GH
AF Ingaramo, Maria
York, Andrew G.
Hoogendoorn, Eelco
Postma, Marten
Shroff, Hari
Patterson, George H.
TI Richardson-Lucy Deconvolution as a General Tool for Combining Images
with Complementary Strengths
SO CHEMPHYSCHEM
LA English
DT Article
DE deconvolution; fluorescence microscopy; Richardson-Lucy;
superresolution; Toeplitz matrix
ID STRUCTURED ILLUMINATION MICROSCOPY; FLUORESCENCE MICROSCOPY; RESOLUTION;
RESTORATION
AB We use Richardson-Lucy (RL) deconvolution to combine multiple images of a simulated object into a single image in the context of modern fluorescence microscopy techniques. RL deconvolution can merge images with very different point-spread functions, such as in multiview light-sheet microscopes,1,2 while preserving the best resolution information present in each image. We show that RL deconvolution is also easily applied to merge high-resolution, high-noise images with low-resolution, low-noise images, relevant when complementing conventional microscopy with localization microscopy. We also use RL deconvolution to merge images produced by different simulated illumination patterns, relevant to structured illumination microscopy (SIM)3,4 and image scanning microscopy (ISM). The quality of our ISM reconstructions is at least as good as reconstructions using standard inversion algorithms for ISM data, but our method follows a simpler recipe that requires no mathematical insight. Finally, we apply RL deconvolution to merge a series of ten images with varying signal and resolution levels. This combination is relevant to gated stimulated-emission depletion (STED) microscopy, and shows that merges of high-quality images are possible even in cases for which a non-iterative inversion algorithm is unknown.
C1 [Ingaramo, Maria; Patterson, George H.] Natl Inst Biomed Imaging & Bioengn, Sect Biophoton, NIH, Bethesda, MD 20892 USA.
[York, Andrew G.; Shroff, Hari] Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD 20892 USA.
[Hoogendoorn, Eelco; Postma, Marten] Univ Amsterdam, Swammerdam Inst Life Sci, NL-1098 XH Amsterdam, Netherlands.
RP Patterson, GH (reprint author), Natl Inst Biomed Imaging & Bioengn, Sect Biophoton, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pattersg@mail.nih.gov
RI Shroff, Hari/E-7247-2016
OI Shroff, Hari/0000-0003-3613-8215
FU National Institutes of Health (NIH); National Institute of Biomedical
Imaging and Bioengineering
FX We thank Michael Broxton for valuable discussions and critical
evaluation of this manuscript. This work was supported by the Intramural
Research Program of the National Institutes of Health (NIH) including
the National Institute of Biomedical Imaging and Bioengineering.
NR 20
TC 16
Z9 16
U1 1
U2 24
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1439-4235
EI 1439-7641
J9 CHEMPHYSCHEM
JI ChemPhysChem
PD MAR 17
PY 2014
VL 15
IS 4
SI SI
BP 794
EP 800
DI 10.1002/cphc.201300831
PG 7
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA AC7XL
UT WOS:000332747500030
PM 24436314
ER
PT J
AU Addlagatta, A
Gumpena, R
Marapaka, A
Allanki, AD
Jun, JH
Sijwali, PS
Malhotra, SV
AF Addlagatta, Anthony
Gumpena, Rajesh
Marapaka, Anil
Allanki, Aparna Devi
Jun, Jung Ho
Sijwali, Puran Singh
Malhotra, Sanjay V.
TI Study of quinoxaline-based new compounds against aminopeptidase N, and
Plasmodium falciparum malarial parasite
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Addlagatta, Anthony; Gumpena, Rajesh; Marapaka, Anil; Allanki, Aparna Devi] Indian Inst Chem Technol, Ctr Chem Biol, Hyderabad 500007, Andhra Pradesh, India.
[Sijwali, Puran Singh] Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India.
[Jun, Jung Ho; Malhotra, Sanjay V.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Lab Synthet Chem, Frederick, MD 21702 USA.
EM anthony@iict.res.in; malhotrasa@mail.nih.gov
RI Addlagatta, Anthony/B-1101-2010
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 65-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602236
ER
PT J
AU Anfinrud, P
Schotte, F
Cho, HS
Kyndt, J
Kamikubo, H
Kataoka, M
AF Anfinrud, Philip
Schotte, Friedrich
Cho, Hyun Sun
Kyndt, John
Kamikubo, Hironari
Kataoka, Mikio
TI Picosecond photobiology: Watching a signaling protein function in real
time via 150 picosecond time-resolved X-ray diffraction and solution
scattering
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Anfinrud, Philip; Schotte, Friedrich; Cho, Hyun Sun] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Kyndt, John] Bellevue Univ, Coll Sci & Technol, Bellevue, NE 68005 USA.
[Kamikubo, Hironari; Kataoka, Mikio] NAIST, Grad Sch Mat Sci, Nara, Japan.
EM anfinrud@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 28-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457603435
ER
PT J
AU Appella, DH
AF Appella, Daniel H.
TI Versatile multivalent display system to investigate membrane receptor
interactions
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM appellad@niddk.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 342-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457603055
ER
PT J
AU Appella, DH
AF Appella, Daniel H.
TI Controlling conformation in peptide nucleic acids for nucleic acid
detection
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM appellad@niddik.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 233-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602832
ER
PT J
AU Arnold, LA
Nandhikonda, P
Maloney, DJ
Schoenen, FJ
AF Arnold, Leggy A.
Nandhikonda, Premchendar
Maloney, David J.
Schoenen, Frank J.
TI Discovery of transcriptional modulators that target the vitamin D
receptor
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Arnold, Leggy A.; Nandhikonda, Premchendar] Univ Wisconsin, Dept Chem & Biochem, Milwaukee, WI 53211 USA.
[Maloney, David J.] Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Schoenen, Frank J.] Univ Kansas, Specialized Chem Ctr, Lawrence, KS 66047 USA.
EM arnold2@uwm.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 14-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602190
ER
PT J
AU Beck, DE
Agama, K
Marchand, C
Pommier, Y
Cushman, M
AF Beck, Daniel E.
Agama, Keli
Marchand, Christophe
Pommier, Yves
Cushman, Mark
TI Synthesis and biological evaluation of new carbohydrate-substituted
indenoisoquinoline Topoisomerase I inhibitors and improved syntheses of
the experimental anticancer agents indotecan (LMP400) and indimitecan
(LMP776)
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Beck, Daniel E.; Cushman, Mark] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA.
[Beck, Daniel E.; Cushman, Mark] Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA.
[Agama, Keli; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM debeck@purdue.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 333-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602487
ER
PT J
AU Horkay, F
Basser, PJ
Hecht, AM
Geissler, E
AF Horkay, Ferenc
Basser, Peter J.
Hecht, Anne-Marie
Geissler, Erik
TI Cartilage biopolymers and their assemblies
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Horkay, Ferenc; Basser, Peter J.] NICHD, NIH, Bethesda, MD 20892 USA.
[Hecht, Anne-Marie; Geissler, Erik] Univ Grenoble, Lab Interdisciplinaire Phys, St Martin Dheres, France.
EM horkayf@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 567-POLY
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457605103
ER
PT J
AU Jun, JH
Duscharla, D
Ummanni, R
Hanson, PH
Malhotra, SV
AF Jun, Jung Ho
Duscharla, Divya
Ummanni, Ramesh
Hanson, Paul H.
Malhotra, Sanjay V.
TI Synthesis and antitumor activity of piperidinyl sulfamides
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Jun, Jung Ho; Malhotra, Sanjay V.] Leidos Biomed Res Inc, Lab Synthet Chem, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Duscharla, Divya; Ummanni, Ramesh] Indian Inst Chem Technol, Ctr Chem Biol, Hyderabad 500607, Andhra Pradesh, India.
[Jun, Jung Ho; Hanson, Paul H.] Univ Kansas, Dept Chem, Lawrence, KS 66045 USA.
EM phanson@ku.edu; phanson@ku.edu; malhotras@gmail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 108-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602277
ER
PT J
AU Kim, YS
Schneekloth, J
AF Kim, Yeong Sang
Schneekloth, John, Jr.
TI Identification and mechanism of action studies of novel sumoylation
inhibitors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Kim, Yeong Sang; Schneekloth, John, Jr.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
EM kimye@mail.nih.gov
NR 0
TC 0
Z9 0
U1 3
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 125-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602293
ER
PT J
AU Kiselev, E
Barrett, MO
Paoletta, S
Ball, CB
Zhao, Q
Stevens, RC
Katritch, V
Harden, K
Jacobson, KA
AF Kiselev, Evgeny
Barrett, Matthew O.
Paoletta, Silvia
Ball, Christopher B.
Zhao, Qiang
Stevens, Raymond C.
Katritch, Vsevolod
Harden, Kendall
Jacobson, Kenneth A.
TI Exploring a 2-naphthoic acid template for the design of P2Y(14) receptor
antagonist molecular probes
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Kiselev, Evgeny; Paoletta, Silvia; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Barrett, Matthew O.; Ball, Christopher B.; Jacobson, Kenneth A.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Zhao, Qiang] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 200031, Peoples R China.
[Stevens, Raymond C.; Katritch, Vsevolod] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
EM ekiselev82@gmail.com
RI Katritch, Vsevolod/Q-8357-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 73-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602243
ER
PT J
AU Laughon, BE
Boyce, JP
AF Laughon, Barbara E.
Boyce, Jim P.
TI Therapeutics resources for TB R&D: US National Institute of Allergy and
Infectious Diseases
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Laughon, Barbara E.; Boyce, Jim P.] NIAID, Div Microbiol & Infect Dis, Bethesda, MD 20892 USA.
EM BLaughon@niaid.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 149-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602316
ER
PT J
AU Li, K
Lv, ZL
Li, QS
AF Li, Ke
Lv, Zhiliang
Li, Qisheng
TI In vitro and in vivo anti-hepatitis B virus activities of novel
2-pyridone derivatives
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Li, Ke; Lv, Zhiliang] Second Mil Med Univ, Sch Pharm, Dept Med Chem, Shanghai, Peoples R China.
[Li, Qisheng] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
EM proflike@hotmail.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 349-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602501
ER
PT J
AU Lu, SY
Zhang, Y
Kalin, J
Cai, LS
Kozikowski, AP
Pike, VW
AF Lu, Shuiyu
Zhang, Yi
Kalin, Jay
Cai, Lisheng
Kozikowski, Alan P.
Pike, Victor W.
TI Labeling of tubastatin A in the hydroxamic acid functional group with
carbon-11
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Lu, Shuiyu; Zhang, Yi; Cai, Lisheng; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Kalin, Jay; Kozikowski, Alan P.] Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA.
EM shuiyu.lu@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 332-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602486
ER
PT J
AU Ocola, EJ
Shin, HW
Kim, S
Laane, J
AF Ocola, Esther J.
Shin, Hee-Won
Kim, Sunghwan
Laane, Jaan
TI Spectroscopic and theoretical studies of the structures and vibrations
of benzocyclobutane and related molecules in their ground state and
excited electronic states
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Ocola, Esther J.; Shin, Hee-Won; Laane, Jaan] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA.
[Kim, Sunghwan] Natl Lib Med, Dept Hlth & Human Serv, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM eocola@mail.chem.tamu.edu
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 345-PHYS
PG 2
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457603732
ER
PT J
AU Paoletta, S
Tosh, DK
Salvemini, D
Jacobson, KA
AF Paoletta, Silvia
Tosh, Dilip K.
Salvemini, Daniela
Jacobson, Kenneth A.
TI Structural probing of off-target receptor activities within a series of
adenosine/adenine congeners
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Paoletta, Silvia; Tosh, Dilip K.; Jacobson, Kenneth A.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Salvemini, Daniela] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA.
EM paolettas@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 247-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602411
ER
PT J
AU Ranade, A
Glaser, N
Sasse, F
Hofle, G
Hamel, E
Bai, RL
Higgins, L
Georg, GI
AF Ranade, Adwait
Glaser, Nicole
Sasse, Florenz
Hoefle, Gerhard
Hamel, Ernest
Bai, Ruoli
Higgins, LeeAnn
Georg, Gunda I.
TI Elucidating the binding site of epothilones on beta-tubulin with
epothilone photoaffinity probes
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Ranade, Adwait; Georg, Gunda I.] Univ Minnesota, ITDD, Minneapolis, MN 55414 USA.
[Glaser, Nicole; Sasse, Florenz; Hoefle, Gerhard] Helmholtz Ctr Infect Res, Braunschweig, Germany.
[Hamel, Ernest; Bai, Ruoli] NCI, Screening Technol Branch, DTP, DCTD, Frederick, MD 21702 USA.
[Higgins, LeeAnn] Univ Minnesota, Dept Biochem Mol Biol & Biophys, St Paul, MN 55108 USA.
EM ranad005@umn.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 145-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602312
ER
PT J
AU Sharma, GVM
Sureshkumar, K
Reddy, SV
Nagalingam, A
Ummanni, R
Hugel, H
Sharma, D
Malhotra, SV
AF Sharma, Gangavaram V. M.
Sureshkumar, Kandikonda
Reddy, Sheri Venkata
Nagalingam, Arumugam
Ummanni, Ramesh
Hugel, Helmut
Sharma, Dipali
Malhotra, Sanjay V.
TI Synthesis of triazole-vanillin molecular hybrids and their cytotoxic
studies
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Sharma, Gangavaram V. M.; Sureshkumar, Kandikonda; Reddy, Sheri Venkata; Ummanni, Ramesh] CSIR Indian Inst Chem Technol, Organ & Biomol Chem Div, Hyderabad 500007, Andhra Pradesh, India.
[Nagalingam, Arumugam; Sharma, Dipali] Johns Hopkins Univ, Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA.
[Hugel, Helmut] RMIT Univ, Sch Appl Sci, Melbourne, Vic 3001, Australia.
[Malhotra, Sanjay V.] Leidos Biomed Res Inc, Lab Synthet Chem, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM esmvee@iict.res.in; malhotrasa@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 331-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602485
ER
PT J
AU Tomaszewski, JE
Malhotra, SV
AF Tomaszewski, Joseph E.
Malhotra, Sanjay V.
TI NCI's drug discovery and development programs, CBC and NExT
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Tomaszewski, Joseph E.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Malhotra, Sanjay V.] Leidos Biomed Res Inc, Lab Synthet Chem, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM tomaszewsk@dtpepn.nci.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 8-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602184
ER
PT J
AU Tosh, DK
Paoletta, S
Ford, A
Janes, K
Salvemini, D
Jacobson, KA
AF Tosh, Dilip K.
Paoletta, Silvia
Ford, Amanda
Janes, Kali
Salvemini, Daniela
Jacobson, Kenneth A.
TI Discovery of next generation A(3) adenosine receptor selective agonists
for treatment of chronic neuropathic pain
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Tosh, Dilip K.; Paoletta, Silvia; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Ford, Amanda; Janes, Kali; Salvemini, Daniela] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA.
EM toshd@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 71-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602241
ER
PT J
AU Bao, X
Rijal, K
Jiang, J
Rodgers, MT
Chow, CS
AF Bao, Xun
Rijal, Keshab
Jiang, Jun
Rodgers, M. T.
Chow, Christine S.
TI Synthesis, characterization, and RNA reactivity of cisplatin analogs
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Bao, Xun; Jiang, Jun; Rodgers, M. T.; Chow, Christine S.] Wayne State Univ, Dept Chem, Detroit, MI 48202 USA.
[Rijal, Keshab] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
EM xunbao@chem.wayne.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 114-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455200439
ER
PT J
AU Bolton, E
AF Bolton, Evan
TI PubChem: A platform to archive and share scientific information
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Bolton, Evan] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM bolton@ncbi.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 39-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455203631
ER
PT J
AU Bolton, E
AF Bolton, Evan
TI PubChem: Data access, navigation, and integration by means of
classifiers and ontologies
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Bolton, Evan] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM bolton@ncbi.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 16-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455203610
ER
PT J
AU Bolton, E
AF Bolton, Evan
TI How can PubChem be leveraged for neglected and rare disease drug
discovery?
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Bolton, Evan] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM bolton@ncbi.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 28-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455203622
ER
PT J
AU Gindulyte, A
Han, LY
Thiessen, P
Yu, B
Geer, L
Bolton, E
AF Gindulyte, Asta
Han, Lianyi
Thiessen, Paul
Yu, Bo
Geer, Lewis
Bolton, Evan
TI New approaches to search interfaces in PubChem
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Gindulyte, Asta; Han, Lianyi; Thiessen, Paul; Yu, Bo; Geer, Lewis; Bolton, Evan] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM bolton@ncbi.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 66-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455203657
ER
PT J
AU Guasch, L
Nicklaus, MC
AF Guasch, Laura
Nicklaus, Marc C.
TI Analysis of prototropic and ring-chain tautomerism to predict favorable
tautomers in drug-like molecules
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Guasch, Laura; Nicklaus, Marc C.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
EM lguasch@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 31-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455204602
ER
PT J
AU Hao, M
Wang, YL
Bryant, SH
AF Hao, Ming
Wang, Yanli
Bryant, Stephen H.
TI Classification of imbalanced PubChem BioAssay data using an efficient
algorithm coupled with synthetic minority over-sampling technique
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Hao, Ming; Wang, Yanli; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM haom@ncbi.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 216-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455204771
ER
PT J
AU Horkay, F
Horkayne-Szakaly, I
Dimitriadis, EK
Basser, PJ
AF Horkay, Ferenc
Horkayne-Szakaly, Iren
Dimitriadis, Emilios K.
Basser, Peter J.
TI Cartilage extracellular matrix: Scattering and osmotic behavior
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Horkay, Ferenc; Horkayne-Szakaly, Iren; Basser, Peter J.] NICHD, NIH, Bethesda, MD 20892 USA.
[Dimitriadis, Emilios K.] NIBIB, NIH, Bethesda, MD 20892 USA.
EM horkayf@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 142-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455200465
ER
PT J
AU Konig, G
Pickard, FC
Mei, Y
Brooks, BR
AF Koenig, Gerhard
Pickard, Frank C.
Mei, Ye
Brooks, Bernard R.
TI First tests of a hybrid quantum-chemical approach for free energy
calculations
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Koenig, Gerhard; Pickard, Frank C.; Mei, Ye; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
EM gerhard.koenig@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 338-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455205002
ER
PT J
AU Koenig, G
Hudson, P
Boresch, S
Woodcock, HL
AF Koenig, Gerhard
Hudson, Phillip
Boresch, Stefan
Woodcock, Henry L.
TI High-level QM/MM free energy calculations at affordable computational
cost
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Hudson, Phillip; Woodcock, Henry L.] Univ S Florida, Dept Chem, Tampa, FL 33620 USA.
[Koenig, Gerhard] NHLBI, NIH, Bethesda, MD 20892 USA.
[Boresch, Stefan] Univ Vienna, Dept Computat Biol Chem, A-1090 Vienna, Austria.
EM hlw@mail.usf.edu
RI Boresch, Stefan/F-3467-2014
OI Boresch, Stefan/0000-0002-2793-6656
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 104-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455204672
ER
PT J
AU Miller, BT
Damjanovic, A
Smith, DB
Brooks, BR
AF Miller, Benjamin T.
Damjanovic, Ana
Smith, Daniel B.
Brooks, Bernard R.
TI Advances in reservoir replica exchange methodology
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Miller, Benjamin T.; Damjanovic, Ana; Smith, Daniel B.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, Bethesda, MD 20892 USA.
[Damjanovic, Ana] Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21218 USA.
EM btmiller@nhlbi.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 332-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455204874
ER
PT J
AU Pan, YM
Wang, YL
Bryant, S
AF Pan, Yongmei
Wang, Yanli
Bryant, Stephen
TI Ligand- and structure-based characterization of protein-ligand
interaction associated with Cdc2-like kinase 4 (Clk4) and dual
specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A)
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Pan, Yongmei; Wang, Yanli; Bryant, Stephen] NIH, NLM NCBI, Bethesda, MD 20894 USA.
EM yongmei.pan@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 222-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455204775
ER
PT J
AU Pevzner, Y
Schalk, V
Miller, BT
Woodcock, HL
AF Pevzner, Yuri
Schalk, Vinushka
Miller, Benjamin T.
Woodcock, Henry L.
TI Development of the CHARMM inteface and graphics Web User Interface as a
platform for comptuer aided drug design
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Pevzner, Yuri; Schalk, Vinushka; Woodcock, Henry L.] Univ S Florida, Dept Chem, Tampa, FL 33620 USA.
[Miller, Benjamin T.] NHLBI, NIH, Bethesda, MD 20892 USA.
EM hlw@mail.usf.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 291-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HD
UT WOS:000348455204835
ER
EF